Cardiovascular Drugs

Protocols

Nifedipine:

Brand name; Nidipine SR(Square)

Nifin(ACME),Nificap(drug int)

Indications

Nifedipine is indicated in the management of all types of essential & renal hypertension. Also indicated in the management of hypertension during pregnancy & during coronary by pass surgery.

Nifedipine is also used for prophylaxis and the treatment of unstable & variant angina, myocardial infarction, and silent myocardial ischaemia. Moreover Nifedipine is also used in Raynaud's phenomenon & heart failure.

Pharmacology

Nifedipine is an inhibitor of Calcium Channel Blocker that blocks the transmembrane influx of Calcium ions into muscle cells. Nifedipine has selective effects as a dilator of arterial vessels. Nifedipine dilates main coronary and systemic arteries. As a result blood pressure falls and this elicits a sympathetic reflex response causing tachycardia and an increased cardiac output. Pulmonary arterial pressure also falls. Nifedipine has direct negative inotropic effects on cardiac muscles and these effects are seen at higher doses than dose which causes arterial vasodilatation.

Dosage & Administration

Nifedipine 10 mg:

  • Angina: Initially 10 mg 3 times daily with food increased to 20 mg 3 times daily if necessary, in elderly patients, initially 5 mg 3 times daily.
  • Raynaud's Phenomenon: 10 mg 3 times daily; maximum 60 mg daily. In urgent cases, the tablet should be dissolved under the tongue like a sublingual tablet. The effect occurs within some minutes.

Nifedipine 20 mg: The starting dose for patients, not previously prescribed Nifedipine products is one tablet once daily. The recommended dose in hypertension and angina prophylaxis is 20 mg twice daily during or after food. Dosage may be adjusted within the range 10 mg twice daily to 40 mg twice daily.

Patients with liver dysfunction should commence therapy with 10 mg twice daily with careful monitoring.

Patients with renal impairment do not require adjustment of dosage.

 

Interaction

  • ACE inhibitors: Enhanced hypotensive effect.
  • Anti-arrythmics: Plasma concentration of quinidine is reduced.
  • Anti-bacterials: Rifampicin possibly increases metabolism of Nifedipine.
  • Anti-epileptics: Plasma concentration of phenytoin increases.
  • Antipsychotics: Enhanced hypotensive effect.
  • β-blockers: Occasionally severe hypotension and heart failure may occur.
  • Cyclosporin: Plasma concentration of Nifedipine possibly increases.
  • Muscle relaxants: Effect of muscle relaxants e.g. tubocurarine increases.
  • Ulcer healing drugs: Metabolism of Nifedipine increases.

Contraindications

Cardiogenic shock, advanced aortic stenosis, nursing mothers, GI obstruction, inflammatory bowel disease, hypotension.

Side Effects

Headache, flushing, lethargy, gravitational oedema rash, nausea, increased frequency of micturation, eye pain, gum hyperplasia, depression, tremor, photosensitivity and few cases of jaundice have been reported. These reactions may regress on discontinuation of therapy. Its introduction may induce attacks of ischaemic pain in some patients with angina pectoris.

Pregnancy & Lactation

There are no adequate and well controlled studies in pregnant women. It should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Precautions & Warnings

Tablets should be swallowed whole and should not be bitten, chewed or broken up. It should be used with caution in patient whose cardiac reserve is poor. Should be withdrawn if ischaemic pain occurs or existing pain worsens shortly after initiating treatment. Use in diabetic patients requires adjustment of their control. Since the absorption of the drug could be modified by renal disease, caution should be exercised in treating such patients.

Therapeutic Class

Calcium-channel blockers

 

Aspirin :

Brand name:Carva(square),ecosprin(ACME)

Disprin(reckitt)


Indications

Aspirin is indicated in the following indications-

  • Prophylaxis against arterial occlusive events: Myocardial infarction, myocardial re-infarction, after bypass surgery, acute ischaemic stroke/TIA.
  • Mild to moderate pain: Headache, muscle pain, dysmenorrhoea and toothache etc.
  • Chronic disease accompanied by pain and inflammation: Osteoarthritis.
  • Antipyretic: Cold fever and influenzae.

Pharmacology

By decreasing platelet aggregation, Aspirin inhibits thrombus formation on the arterial side of the circulation, where thrombi are formed by platelet aggregation and anticoagulants have little effect. Aspirin is the analgesic of choice for headache, transient musculoskeletal pain and dysmenorrhoea. It has anti-inflammatory and antipyretic properties, which may be useful. Enteric-coated Aspirin reduces intestinal disturbance and gastrointestinal ulceration due to aspirin.

Dosage & Administration

Pain, inflammatory diseases and as antipyretic: Aspirin 300 mg 1-3 tablets 6 hourly with a maximum daily dose of 4 gm.

Suspected acute coronary syndrome: 150 mg-300 mg immediately unless there are clear contraindications.

After myocardial infarction: Aspirin 150 mg daily for 1 month. Long-term use of aspirin in a dose of 75 mg daily is recommended thereafter.

Acute ischaemic stroke/Transient ischaemic stroke (TIA): The starting dose is 150 mg-300 mg daily and Aspirin 75 mg daily thereafter.

Following bypass surgery: 75 mg-300 mg daily starting 6 hours post-procedure.

 

Interaction

Salicylates may enhance the effect of anticoagulants, oral hypoglycaemic agents, phenytoin and sodium valporate. They inhibit the uricosuric effect of probenecid and may increase the toxicity of sulphonamides. They may also precipitate bronchospasm or induce attacks of asthma in susceptible subjects.

Contraindications

Aspirin is contraindicated to the children (Reye's syndrome) less than 12 years, in breast-feeding and active peptic ulcer. It is also contraindicated in bleeding due to haemophilia, intracranial haemorrhage and other ulceration.

Side Effects

Side effects for the usual dosage of Aspirin are mild including nausea, dyspepsia, gastrointestinal ulceration and bronchospasm etc.

Pregnancy & Lactation

It is especially important not to use aspirin during the last 3 months of pregnancy unless specifically directed to do so by a doctor because it may cause problems in the unborn child or complications during delivery. Aspirin penetrates into breast milk. So, it should be administered with caution to lactating mothers.

Precautions & Warnings

It should be administered cautiously in asthma, uncontrolled blood pressure, and pregnant women. It should be administered with caution to patients with a nasal polyp and nasal allergy.

Overdose Effects

Overdosage produces dizziness, tinnitus, sweating, nausea and vomiting, confusion and hyperventilation. Gross overdosage may lead to CNS depression with coma, cardiovascular collapse and respiratory depression. If the overdosage is suspected, the patient should be kept under observation for at least 24 hours, as symptoms and salicylate blood levels may not become apparent for several hours. Treatment of overdosage consists of gastric lavage and forced alkaline diuresis. Haemodialysis may be necessary in severe cases.

Therapeutic Class

Anti-platelet drugs

Storage Conditions

Keep all medicines out of reach of children. Store in a cool and dry place, protected from light.

Price : 1 tab-1 tk

Clopidogrel :

Brand: Clopid(drug int),lopirel(incepta),anclog(square)

Indications

Acute Coronary Syndrome (ACS): It is indicated to reduce the rate of myocardial infarction (MI) and stroke in patients with non-ST-segment elevation ACS [unstable angina (UA)/non-ST-elevation myocardial infarction (NSTEMI)]. It is indicated to reduce the rate of myocardial infarction and stroke in patients with acute ST-elevation myocardial infarction (STEMI).

Recent MI, recent Stroke, or established Peripheral Arterial Disease: In patients with established peripheral arterial disease or with a history of recent myocardial infarction (MI) or recent stroke it is indicated to reduce the rate of MI and stroke.

Pharmacology

Clopidogrel is a prodrug. It inhibits platelet activation and aggregation through the irreversible binding of its active metabolite to the P2Y12 class of ADP receptors on platelets. Dose-dependent inhibition of platelet aggregation can be seen 2 hours after single oral doses. Repeated doses of 75 mg per day inhibit ADP-induced platelet aggregation on the first day, and inhibition reaches steady state between Day 3 and Day 7.

Dosage & Administration

Acute Coronary Syndrome: In patients who need an antiplatelet effect within hours, initiate clopidogrel with a single 300 mg (4 tablets) oral loading dose and then continue at 75 mg once daily. Initiating it without a loading dose will delay establishment of an antiplatelet effect by several days.

Recent MI, Recent Stroke, or Established Peripheral Arterial Disease: 75 mg once daily orally without a loading dose.

It is given orally with or without food.

Interaction

  • NSAIDs, warfarin, selective serotonin and serotonin norepinephrine reuptake inhibitors (SSRIs, SNRIs): Increases risk of bleeding
  • CYP2C19 inhibitors (omeprazole or esomeprazole): Avoid concomitant use of omeprazole or esomeprazole
  • Repaglinide (CYP2C8 substrates): Avoid concomitant use of Clopidogrel with Repaglinide as it increases plasma concentrations of Repaglinide

Contraindications

Clopidogrel is contraindicated in the following conditions: Hypersensitivity to the drug substance or any component of the product. Active pathological bleeding such as peptic ulcer or intracranial hemorrhage.

Side Effects

Clopidogrel is generally well tolerated drug.

  • Common side effects: Bleeding, Diarrhoea, gastrointestinal discomfort, haemorrhage, Skin reactions.
  • Rare side effects: Acquired haemophilia, anaemia, angioedema, arthralgia, arthritis, bone marrow disorders.

Pregnancy & Lactation

There are no adequate and well-controlled studies in pregnant women. It should be used during pregnancy only if clearly needed. It is unknown whether clopidogrel is excreted in human breast milk. A decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Precautions & Warnings

  • As it is a prodrug, so metabolism to its active metabolite is impaired by genetic variations in CYP2C19 (poor metabolizer) and by the drugs that inhibit CYP2C19 such as Omeprazole and Esomeprazole. Concomitant use with these drugs and in CYP2C19 poor metaboliser may reduce the antiplatelet activity of Clopidogrel.
  • As it inhibits platelet aggregation for the lifetime of the platelet (7-10 days), risk of bleeding may increase. To restore hemostasis, platelet transfusions within 4 hours of the loading dose or 2 hours of the maintenance dose may be less effective.
  • Discontinuation of Clopidogrel increases the risk of cardiovascular events. Discontinue 5 days prior to elective surgery that has a major risk of bleeding. Resume Clopidogrel as soon as hemostasis is achieved.
  • Thrombotic Thrombocytopenic Purpura (TTP) has been reported that requires urgent treatment including plasmapheresis (plasma exchange).
  • Hypersensitivity including rash, angioedema or hematologic reaction has been reported in patients receiving clopidogrel or history of hypersensitivity to other thienopyridines.

Use in Special Populations

Safety and effectiveness in pediatric populations have not been established. No dosage adjustment is necessary in elderly patients.

Overdose Effects

Overdose following clopidogrel administration may lead to bleeding complications. Based on biological plausibility, platelet transfusion may restore clotting ability.

Therapeutic Class

Anti-platelet drugs

 

Nitroglycerin:

Brand:GTN(SKF),ANRIL(square),nitrosol(beximco)

Indications

Nitroglycerin sublingual spray is indicated for acute relief of an attack or prophylaxis of angina pectoris due to coronary artery disease.

Description

Nitroglycerin, an organic nitrate, is a vasodilator which has effects on both arteries and veins. This is a metered dose spray containing nitroglycerin. This product delivers nitroglycerin (400 mcg per spray, 200 metered sprays) in the form of spray droplets under the tongue.

Pharmacology

The principal pharmacological action of nitroglycerin is relaxation of vascular smooth muscle, producing a vasodilator effect on both peripheral arteries and veins with more prominent effects on the latter. Dilation of the post-capillary vessels, including large veins, promotes peripheral pooling of blood and decreases venous return to the heart, thereby reducing left ventricular enddiastolic pressure (pre-load). Arteriolar relaxation reduces systemic vascular resistance and arterial pressure (after-load).

Dosage & Administration

At the onset of an attack, 1 or 2 metered sprays should be administered under the tongue. No more than 3 metered sprays are recommended within a 15 minute period. If the chest pain persists, prompt medical attention is recommended. Nitroglycerin spray may be used prophylactically 5 to 10 minutes prior to engaging in activities which might precipitate an acute attack.

 

Interaction

Use of alcohol with Nitroglycerin may produce severe hypotension and collapse. Oral Nitroglycerin may enhance the bioavailability of dihydroergotamine. Orthostatic hypotension may occur with the combined use of calcium channel blocker, phenothiazines and tricyclic antidepressants.

Contraindications

Hypersensitivity to nitrates or any constituents of the formulation. Hypotension, hypovolaemia, severe anaemia, cerebral haemorrhage and brain trauma, mitral stenosis and angina caused by hypertrophic obstructive cardiomyopathy. Concomitant administration of phosphodiesterase inhibitors used for the treatment of erectile dysfunction.

Side Effects

A number of nitrate related adverse effects may occur including headache, facial flushing, dizziness, nausea, vomiting, feelings of weakness, postural hypotension and reflex tachycardia .

Pregnancy & Lactation

Pregnancy Category C. There are no adequate and well controlled studies in pregnant women. Nitroglycerin should be given to pregnant women only if clearly needed. It is not known whether nitroglycerin is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Nitroglycerin spray is administered to a nursing woman.

Precautions & Warnings

The use of Nitroglycerin during the early days of acute myocardial infarction requires particular attention to monitoring hemodynamics and clinical status. Nitroglycerin should be used with caution in patients with severely impaired renal or hepatic function, hypothyroidism, malnutrition or hypothermia.

Use in Special Populations

Safety and effectiveness of nitroglycerin in pediatric patients have not been established.

Overdose Effects

Nitrate overdosage may result in: severe hypotension, persistent throbbing headache, vertigo, palpitation, visual disturbance, flushing and perspiring skin (later becoming cold and cyanotic), nausea and vomiting (possibly with colic and even bloody diarrhea), syncope (especially in the upright posture), methemoglobinemia with cyanosis and anorexia, initial hyperpnea, dyspnea and slow breathing, slow pulse, heart block, increased intracranial pressure with cerebral symptoms of confusion and moderate fever, paralysis and coma followed by clonic convulsions and possibly death due to circulatory collapse.

Methemoglobinemia: Case reports of clinically significant methemoglobinemia are rare at conventional doses of organic nitrates. The formation of methemoglobin is dose-related and in the case of genetic abnormalities of hemoglobin that favor methemoglobin formation, even conventional doses of organic nitrates could produce harmful concentrations of methemoglobin.

Treatment of Overdosage: Keep the patient recumbent in a shock position and comfortably warm. Passive movement of the extremities may aid venous return. Administer oxygen and artificial ventilation, if necessary. If methemoglobinemia is present, administration of methylene blue (1% solution), 1-2 mg per kilogram of body weight intravenously, may be required. If an excessive quantity of Nitroglycerin spray has been recently swallowed, gastric lavage may be of use.

Therapeutic Class

Nitrates: Coronary vasodilators

Price : spray_ 270tk ,tab

Morphine:

Indications

This medication is used to help relieve moderate to severe pain. Morphine belongs to a class of drugs known as opioid (narcotic) analgesics. It works in the brain to change how your body feels and responds to pain.

Pharmacology

Morphine is a phenanthrene derivative which acts mainly on the CNS and smooth muscles. It binds to opiate receptors in the CNS altering pain perception and response. Analgesia, euphoria and dependence are thought to be due to its action at the mu-1 receptors while resp depression and inhibition of intestinal movements are due to action at the mu-2 receptors. Spinal analgesia is mediated by morphine agonist action at the K receptor.

Dosage

Oral- Moderate to severe pain: 5-20 mg 4 hrly. Extended-release: 5-20 mg 12 hrly. Dosage is dependent on the severity of pain.

Intraspinal- 
Moderate to severe pain: Initially, 5 mg epidural inj; after 1 hr, additional doses of 1-2 mg may be given up to a total dose of 10 mg/24 hr if pain relief is unsatisfactory. A dose of 20-30 mg daily may be required in some patients. Liposomal inj: 10-20 mg depending on the type of surgery.

Intrathecal- 
Moderate to severe pain: 0.2-1 mg once daily or 1-10 mg daily for patients with opioid tolerance. Some patients may require a dose of up to 20 mg daily.

Intravenous- 
Acute pulmonary oedema:

  • Adult: 5-10 mg via slow inj at 2 mg/min.
  • Elderly: Half of the usual adult dose.

Intravenous- Pain associated with myocardial infarction:

  • Adult: 5-10 mg at 1-2 mg/min followed by a further 5-10 mg as necessary.
  • Elderly: Half of the usual adult dose.

Parenteral- 

  • Moderate to severe pain: 5-20 mg; 2.5-10 mg via slow IV inj over 4-5 min with patient in recumbent position or a starting dose of 1-2 mg/hr via continuous IV infusion (max: 100 mg/day; 4 g/day in cancer patients). Doses may be adjusted according to severity of pain and patient's response.
  • Premedication in surgery: Up to 10 mg, given 60-90 min before operation.

 

Administration

May be taken with or without food. May be taken with meals to reduce GI discomfort.

 

Interaction

Additive depressant effects with other CNS depressants (e.g. sedatives, hypnotics, general anaesth, phenothiazines, other tranquilisers). May enhance the neuromuscular blocking action of skeletal muscle relaxants. Reduced analgesic effect with mixed agonist/antagonist opioid analgesics (e.g. pentazocine, nalbuphine, buprenorphine). Increased plasma concentrations with cimetidine. May reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. May delay the absorption of mexiletine. May antagonise the GI effect of cisapride, domperidone and metoclopramide. May produce hyperpyrexia and CNS toxicity with dopaminergics.

Contraindications

Resp depression, obstructive airway disease, delayed gastric emptying, acute abdomen, heart failure secondary to chronic lung disease, known or suspected paralytic ileus, phaeochromocytoma. Concurrent admin with MAOIs or within 2 wk after treatment.

Side Effects

Nausea, vomiting, constipation, abdominal pain, dry mouth, anorexia, taste disturbance, dyspepsia, resp depression, sedation, dizziness, confusion, insomnia, headache, somnolence, involuntary muscle contractions, hyperhidrosis, rash, pruritus, asthenic conditions, HTN, bronchospasm, seizures, amenorrhoea, rhabdomyolysis, nystagmus.

Pregnancy & Lactation

Parenteral or oral: C, D (if prolonged use/high doses at term)

Precautions & Warnings

Patient with impaired resp function, severe bronchial asthma, convulsive disorders, acute alcoholism, delirium tremens, raised intracranial pressure, hypotension with hypovolaemia, cardiac arrhythmias, severe cor pulmonale, history of substance abuse, diseases of the biliary tract, pancreatitis, inflammatory bowel disorders, prostatic hypertrophy, adrenocortical insufficiency, toxic psychoses. Opioid dependent patients. Renal and hepatic impairment. Pregnancy and lactation.

Use in Special Populations

Renal Impairment: Dosage may need to be reduced.
Hepatic Impairment: Dosage may need to be reduced.

Overdose Effects

Symptoms: Resp depression, pinpoint pupils, extreme somnolence progressing to stupor and coma, skeletal muscle flaccidity, cold and clammy skin and sometimes bradycardia and hypotension. Apnoea, circulatory collapse, and cardiac arrest may occur in severe cases.

Management: Re-establish adequate resp exchange through provision of a patent airway and institution of assisted or controlled ventilation. Oxygen, IV fluid, vasopressors and other supportive measures may be employed as necessary. Naloxone may be given as antidote.

Therapeutic Class

Opioid analgesics

 

Atorvastatin :

brand:atova(beximco)tiginor(incepta),ATV(delta)

Indications

Atorvastatin is indicated as an adjunct to diet to reduce elevated total cholesterol, LDL cholesterol, apolipoprotein B (Apo-B) and triglycerides levels in following diseases when response to diet and other non-pharmacological measures is inadequate.

  • To reduce total cholesterol and LDL cholesterol in patients with heterozygous and homozygous familial hypercholesterolaemia.
  • To reduce elevated cholesterol and triglycerides in patient with mixed dyslipidemia (Fredrickson Type Ia and Ib).
  • For the treatment of patients with elevated serum triglyceride levels in hypertriglyceridaemia (Fredrickson Type IV).
  • For the treatment of patients with dysbetalipoproteinaemia (Fredrickson Type III).
  • To reduce cardiac ischaemic events in patients with asymptomatic or mild to moderate symptomatic coronary artery disease with elevated LDL-cholesterol level.
  • To reduce total and LDL-cholesterol concentrations patients with hypercholesterolemia associated with or exacerbated by diabetes mellitus or renal transplantation.

Pharmacology

Atorvastatin is a selective inhibitor of HMG-CoA reductase. This enzyme is the rate-limiting enzyme responsible for the conversion of HMG-CoA to mevalonate, a precursor of sterols, including cholesterol. Atorvastatin lowers plasma cholesterol and lipoprotein levels by inhibiting HMG-CoA reductase and cholesterol synthesis in the liver and increases the number of hepatic LDL receptors on the cell surface for enhanced uptake and catabolism of LDL.

Dosage & Administration

Primary hypercholesterolaemia and combined hyperlipidaemia-

  • Adults: Usually 10 mg once daily; if necessary, may be increased at intervals of at least 4 weeks to max. 80 mg once daily.
  • Child (10-18 years): Initially 10 mg once daily, increased if necessary at intervals of at least 4 weeks to usual max. 20 mg once daily.

Familial hypercholesterolaemia-

  • Adults: Initially 10 mg daily, increased at intervals of at least 4 weeks to 40 mg once daily; if necessary, further increased to max. 80 mg once daily (or 40 mg once daily combined with anion-exchange resin in heterozygous familial hypercholesterolaemia).
  • Child (10-18 years): Initially 10 mg once daily, increased if necessary at intervals of at least 4 weeks to usual max. 80 mg once daily.

Prevention of cardiovascular events-

  • Adults: Initially 10 mg once daily adjusted according to response.

 

Interaction

The risk of myopathy during treatment with Atorvastatin is increased with concurrent administration of cyclosporin, fibric acid derivatives, erythromycin, azole antifungals and niacin. No clinically significant interactions were seen when Atorvastatin was administered with antihypertensives or hypoglycemic agents. Patients should be closely monitored if Atorvastatin is added to digoxin, erythromycin, oral contraceptives, colestipol, antacid and warfarin.

Contraindications

Atorvastatin should not be used in patient with hypersensitivity to any component of this medication. Atorvastatin is contraindicated in active liver disease or unexplained persistent elevations of serum transaminases. It is also contraindicated in patient with history of serious adverse reaction to prior administration of HMG-CoA reductase inhibitors.

Side Effects

Atorvastatin is generally well-tolerated. The most frequent side effects related to Atorvastatin are constipation, flatulence, dyspepsia, abdominal pain. Other side effects includes infection, headache, back pain, rash, asthenia, arthralgia, myalgia.

Pregnancy & Lactation

Pregnancy: Atorvastatin is contraindicated during pregnancy. Safety in pregnant women has not been established. No controlled clinical trials with atorvastatin have been conducted in pregnant women. Rare reports of congenital anomalies following intrauterine exposure to HMG-CoA reductase inhibitors have been received. Animal studies have shown toxicity to reproduction. Maternal treatment with atorvastatin may reduce the fetal levels of mevalonate which is a precursor of cholesterol biosynthesis. Atorvastatin should not be used in women who are pregnant, trying to become pregnant or suspect they are pregnant. Treatment with atorvastatin should be suspended for the duration of pregnancy or until it has been determined that the woman is not pregnant

Lactation: It is not known whether atorvastatin or its metabolites are excreted in human milk. In rats, plasma concentrations of atorvastatin and its active metabolites are similar to those in milk. Because of the potential for serious adverse reactions, women taking atorvastatin should not breastfeed their infants. Atorvastatin is contraindicated during breastfeeding.

Precautions & Warnings

Liver effects: Liver function tests should be performed before the initiation of treatment and periodically thereafter. Atorvastatin should be used with caution in patients who consume substantial quantities of alcohol or have a history of liver disease. Atorvastatin therapy should be discontinued if markedly elevated CPK levels occur or myopathy is diagnosed or suspected.

Use in Special Populations

Hepatic impairment: Atorvastatin should be used with caution in patients with hepatic impairment.

Pediatric use: For patients aged 10 years and above, the recommended starting dose of atorvastatin is 10 mg per day with titration up to 20 mg per day. Atorvastatin is not indicated in the treatment of patients below the age of 10 years.

Overdose Effects

Specific treatment is not available for atorvastatin overdose. The patient should be treated symptomatically and supportive measures instituted, as required. Liver function tests should be performed and serum CK levels should be monitored. Due to extensive atorvastatin binding to plasma proteins, hemodialysis is not expected to significantly enhance atorvastatin clearance.

Therapeutic Class

Other Anti-anginal & Anti-ischaemic drugs, Statins

Price: 12-20tk unit price

Trimetazidine:

brand:metacardMR(Aristopharma),MetazidineMR(Beximco)


Indications

Trimetazidine Dihydrochloride is indicated in adults as add-on therapy for the symptomatic treatment of patients with stable angina pectoris who are inadequately controlled by or intolerant to first-line antianginal therapies.

Pharmacology

Trimetazidine Dihydrochloride is the first 3- keto acyl CoA thiolase inhibitor (KAT), a metabolic anti-ischemic agent with proven benefits for all coronary patients. Trimetazidine Dihydrochloride inhibits fatty acid pathway by inhibiting 3-keto acyl CoA thiolase enzyme and transfers oxygen to glucose pathway. Since glucose pathway is more efficient in producing energy, the same oxygen produces more energy and makes the heart more active. Moreover, the aerobic oxidation of glucose stops production of lactic acid, which prevents angina pectoris.

Dosage & Administration

The recommended dose of Trimetazidine is 35 mg twice daily or 20 mg tablet thrice daily during meals. The benefit of the treatment should be assessed after three months and Trimetazidine should be discontinued if there is no treatment response.

 

Interaction

No drug interaction so far has been reported. In particular, no interaction has been reported with beta-blockers, calcium antagonists, nitrates, heparin, hypolipidemic agents or digitalis preparation.

Contraindications

Trimetazidine is contraindicated in patients who have hypersensitivity to the active substance or to any of the excipients. It is also is contraindicated in patients with Parkinson’s disease, parkinsonian symptoms, tremors, restless legs movement disorders, severe renal impairment.

Side Effects

Trimetazidine is safe and well tolerated. The Common side effects associated with Trimetazidine are dizziness, headache, abdominal pain, diarrhoea, dyspepsia, nausea, vomiting, rash, pruritus, urticaria and asthenia

Pregnancy & Lactation

There is no data on the use of Trimetazidine in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity. As a precautionary measure, it is preferable to avoid the use of Trimetazidine during pregnancy. It is unknown whether Trimetazidine is excreted in human milk. A risk to the newborns/infants cannot be excluded. Trimetazidine should not be used during breast-feeding.

Precautions & Warnings

Trimetazidine is not a curative treatment for angina attacks, nor an initial treatment for unstable angina pectoris. It is also not a treatment for myocardial infarction.

Therapeutic Class

Other Anti-anginal & Anti-ischaemic drugs

Price : 6-10 tk unit price

Indications

Acute Coronary Syndrome (ACS): It is indicated to reduce the rate of Myocardial Infarction (MI) and Stroke in patients with non-ST-segment elevation ACS [unstable angina (UA)/non-ST-elevation Myocardial Infarction (NSTEMI)] and acute ST-segment elevation ACS [ST-elevation Myocardial Infarction (STEMI)].

Recent MI, recent Stroke, or established Peripheral Arterial Disease: In patients with established peripheral arterial disease or with a history of recent Myocardial Infarction (MI) or recent Stroke it is indicated to reduce the rate of MI and Stroke.

Pharmacology

Clopidogrel is a prodrug. It inhibits platelet activation and aggregation through the irreversible binding of its active metabolite to the P2Y12 class of ADP receptors on platelets. Dose-dependent inhibition of platelet aggregation can be seen at 2 hours after single oral doses. Repeated doses of 75 mg per day inhibit ADP-induced platelet aggregation on the first day, and inhibition reaches steady state between Day 3 and Day 7.

Aspirin inhibits platelet aggregation by irreversible inhibition of platelet cyclooxygenase and thus inhibiting the generation of thromboxane A2 a powerful inducer of platelet aggregation and vasoconstriction.

Dosage & Administration

The recommended oral dose is one tablet daily.

 

Interaction

Oral anticoagulants, NSAIDs, Metamizole, SSRIs, CYP2C19 inhibitors increase the risk of bleeding. It shows interaction with Tonofovir, Valproic acid, Varicella vaccine, Acetazolamide and Nicorandil.

Contraindications

This combination is contraindicated in the following conditions: Hypersensitivity to the drug substance or any component of the product. Active pathological bleeding such as peptic ulcer or intracranial hemorrhage.

Side Effects

This combination is generally well tolerated.

Pregnancy & Lactation

There are no adequate and well-controlled studies in pregnant women. It should be used during first and second trimesters of pregnancy only if clearly needed. It is contraindicated during the third trimester of pregnancy. It is unknown whether Clopidogrel is excreted in human breast milk but Aspirin is known to be excreted in human milk. This Drug should be discontinued during the breast feeding.

Precautions & Warnings

  • This combination may prolongs the bleeding time.
  • Thrombotic thrombocytopenic purpura (TTP): TTP has been reported rarely following use of this combination.
  • Reye's syndrome: Reye's syndrome may develop in individuals who have chicken pox, influenza or flu symptoms. Hypersensitivity including rash, angioedema or hematologic reaction has been reported in patients receiving this combination or history of hypersensitivity to other thienopyridines

Use in Special Populations

It should not be given to children, particularly those under 12 years, unless the expected benefits outweight the possible risks. Aspirin may be a contributory factor in the causation of Reye’s syndrome in some children.

Overdose Effects

Clopidogrel overdose may lead to bleeding complications. Based on biological plausibility, platelet transfusion may restore clotting ability. In moderate aspirin intoxication dizziness, headache, tinnitus, confusion, and gastrointestinal symptoms may occur which can be treated by inducing vomiting followed by gastric lavage if needed. In severe Aspirin intoxication respiratory alkalosis respiratory acidosis, metabolic acidosis, hyperthermia, perspiration, dehydration can occur. It can be treated with haemodialysis and other symptomatic treatment.

Therapeutic Class

Anti-platelet drugs

 

Digoxin :

Brand:Agoxin(aristopharma),Centoxin(opsonin)

Indications

Digoxin is indicated in:

  • Heart failure.
  • Atrial fibrillation with an uncontrolled ventricular rate.
  • Acute left ventricular failure.
  • Chronic left ventricular failure and conjestive heart failure,especially when caused by hypertensive valvular (especially mitral valvular) disease or ischaemic heart disease.

Pharmacology

Digoxin is a cardiac glycoside used in the management of particularly atrial fibrillation and in heart failure.The principal actions of digoxin are an increase in the force of myocardial contraction (positive inotropic activity and a reduction in the conductivity of the heart particularly in conduction through the atrioventricular node. Digoxin also has a direct action on vascular smooth muscle and indirect effects mediated primarily by the autonomic nervous system and particularly by an increase in vagal activity.

Dosage & Administration

By oral administration:

  • Rapid digitalization: 1-1.5 mg in divided doses over 24 hours
  • Less urgent digitalization: 250-500 micrograms daily (higher dose may be divided)
  • Maintenance: 62.5-500 micrograms daily (higher dose may be divided) according to renal function and in atrial fibrillation on heart rate response.
  • Usual range: 125-250 micrograms daily (lower dose may be divided) according to renal function and in atrial fibrilation on heart rate response.
  • Usual range: 125-250 micrograms daily (lower dose may be appropriate in the elderly).

 

Interaction

Potassium-depleting diuretics increase the effects of digitalis. Calcium particularly if administered rapidly by the intravenous route, may produce serious arrhythmia in digitalized patients. Quinidine, verapamil, amiodarone, propafenone, indomethacin, itraconazole, alprazolam, spironolactone, erythromycin, clarithromycin (and possibly other macrolide antibiotics) and tetracycline increase digoxin serum level. Besides antacids, kaolinpectin, sulfasalazine, neomycin, penicillamine, calestipol, metoclopramide, rifampin may interfere with intestinal absorption of digoxin resulting low serum concentrations of the drug.

Contraindications

  • Ventricular fibrillation.
  • Hypersensitivity to digoxin or other digitalis preparation.

Side Effects

Usually associated with excessive dosage include anorexia, nausea, vomiting, diarrhoea, abdominal pain, visual disturbance, headache, fatigue, drowsiness, confusion, delirium, hallucination, depression, arrhythmia, heart block, intestinal ischaemia, gynaecomastia on long term use, thrombocytopenia reported. Digoxin can be safely used in pregnancy

Pregnancy & Lactation

Digoxin is excreted in breast milk but in concentration below those found in plasma and therefore poses no hazard to the breast-fed infant.

Use in Special Populations

Neonates: Digoxin can be used in neonates.

Children: Digoxin can be used in children.

The elderly: Partly because of reduced renal function and partly because their tissues are more sensitive to the effects of digitalis, the elderly require a lower maintenance dose of digoxin than younger adults.

Therapeutic Class

Positive Inotropic drugs

Price: 1 unit 1-3tk

 

Ramipril:

Brand: Ramoril(incepta),Ramil(popular)

Indications

Ramipril indicated in the following cases:

  • Hypertension; to lower blood pressure, as single-drug therapy or in combination with other antihypertensive agents.
  • Congestive heart failure; also in combination with diuretics.
  • Treatment of patients who- within the first few days after an acute myocardial infarction- have demonstrated clinical signs of congestive heart failure.
  • Treatment of non-diabetic or diabetic overt glomerular or incipient nephropathy.
  • Reduction in the risk of myocardial infarction, stroke, or cardiovascular death in patients with an increased cardiovascular risk, such as manifest coronary heart disease (with or without a history of myocardial infarction), a history of stroke, a history of peripheral vascular disease, or diabetes mellitus that is accompanied by at least one other cardiovascular risk factor (microalbuminuria, hypertension, elevated total cholesterol levels, low high-density lipoprotein cholesterol levels, smoking).

Pharmacology

Ramipril is an angiotensin converting enzyme (ACE) inhibitor, which after hydrolysis to ramiprilat, blocks the conversion of angiotensin I to the vasoconstrictor substance, angiotensin II. So, inhibition of ACE by ramipril results in decreased plasma angiotensin II, which leads to decreased vasopressor activity and decreased aldosterone secretion. Thus ramipril exerts its antihypertensive activity. It is also effective in the management of heart failure and reduction of the risk of stroke, myocardial infarction and death from cardiovascular events. It is long acting and well tolerated; so, can be used in long term therapy.

Dosage

Dosage of Ramipril must be adjusted according to the patient tolerance and response.

Hypertension: For the management of hypertension in adults not receiving a diuretic, the usual initial dose of Ramipril is 1.25-2.5 mg once daily. Dosage generally is adjusted no more rapidly than at 2 week intervals. The usual maintenance dosage in adults is 2.5-20 mg daily given as a single dose or in 2 divided doses daily. If BP is not controlled with Ramipril alone, a diuretic may be added.

Congestive heart failure after myocardial infarction: In this case, Ramipril therapy may be initiated as early as 2 days after myocardial infarction. An initial dose of 2.5 mg twice daily is recommended, but if hypotension occurs, dose should be reduced to 1.25 mg twice daily. Therapy is then titrated to a target daily dose of 5 mg twice daily.

Prevention of major cardiovascular events: In this case, the recommended dose is 2.5 mg once daily for the first week of therapy and 5 mg once daily for the following 3 weeks; dosage then may be increased, as tolerated, to a maintenance dosage of 10 mg once daily.

Dosage in renal impairment:

  • For patients with hypertension and renal impairment: The recommended initial dose is 1.25 mg Ramipril once daily. Subsequent dosage should be titrated according to individual tolerance and BP response, up to a maximum of 5 mg daily.
  • For patients with heart failure and renal impairment: The recommended dose is 1.25 mg once daily. The dose may be increased to 1.25 mg twice daily and up to a maximum dose of 2.5 mg twice daily depending upon clinical response and tolerability.

 

Administration

Ramipril tablets have to be swallowed with sufficient amounts of liquid. The tablets must not be chewed or crushed. Absorption of Ramipril is not significantly affected by food. Ramipril may, therefore, be taken before, during or after a meal.

 

Interaction

Concomitant administration with diuretics may lead to serious hypotension and in addition dangerous hyperkalemia with potassium sparing diuretics. Concomitant therapy with lithium may increase the serum lithium concentration. Reduction in BP may affect the ability to drive and operate machinery and this may be exacerbated by alcohol. NSAIDs may reduce the antihypertensive effect of Ramipril and cause deterioration of renal function.

Contraindications

Ramipril must not be used

  • in patients with hypersensitivity to ramipril, to any other ACE inhibitor, or any of the excipients of Ramipril.
  • in patients with a history of angioedema.
  • concomitantly with sacubitril/valsartan therapy. Do not initiate Ramipril until sacubitril/valsartan is eliminated from the body. In case of switch from Ramipril to sacubitril/valsartan, do not start sacubitril/valsartan until Ramipril is eliminated from the body.
  • in patients with haemodynamically relevant renal artery stenosis, bilateral or unilateral in the single kidney.
  • in patients with hypotensive or haemodynamically unstable states.
  • with aliskiren-containing medicines in patients with diabetes or with moderate to severe renal impairment (creatinine clearance <60 ml/min).
  • with angiotensin II receptor antagonists (AIIRAs) in patients with diabetic nephropathy.
  • during pregnancy.

Concomitant use of ACE inhibitors and extracorporeal treatments leading to contact of blood with negatively charged surfaces must be avoided, since such use may lead to severe anaphylactoid reactions. Such extracorporeal treatments include dialysis or haemofiltration with certain high-fux (e.g. polyacrylonitril) membranes and low-density lipoprotein apheresis with dextran sulfate.

Side Effects

Ramipril is generally well tolerated. Dizziness, headache, fatigue and asthenia are commonly reported side effects. Other side effects occurring less frequently include symptomatic hypotension, cough, nausea, vomiting, diarrhoea, rash, urticaria, oliguria, anxiety, amnesia etc. Angioneurotic oedema, anaphylactic reactions and hyperkalaemia have also been reported rarely.

Pregnancy & Lactation

Ramipril must not be taken during pregnancy. Therefore, pregnancy must be excluded before starting treatment. Pregnancy must be avoided in cases where treatment with ACE inhibitors is indispensable. If the patient intends to become pregnant, treatment with ACE inhibitors must be discontinued, i.e. replaced by another form of treatment. If the patient becomes pregnant during treatment, medication with Ramipril must be replaced as soon as possible by a treatment regimen without ACE inhibitors. Otherwise, there is a risk of harm to the fetus. Ramipril is not recommended during breastfeeding.

Precautions & Warnings

Ramipril should be used with caution in patients with impaired renal function, hyperkalaemia, hypotension, and impaired hepatic function.

Use in Special Populations

Elderly: A reduced initial dose of 1.25 mg Ramipril daily must be considered.

Hepatic impairment: Treatment in these patients must therefore be initiated only under close medical supervision. The maximum permitted daily dose in such cases is 2.5 mg Ramipril.

Renal impairment: With a creatinine clearance between 50 and 20 ml/min per 1.73 m2 body surface area, the initial daily dose is generally 1.25 mg Ramipril. The maximum permitted daily dose, in this case, is 5 mg Ramipril. Patients with incompletely corrected fuid or salt depletion, in patients with severe hypertension, as well as in patients in whom a hypotensive reaction would constitute a particular risk, (e.g., with relevant stenoses of the coronary vessels or those supplying the brain) A reduced initial dose of 1.25 mg Ramipril daily must be considered.

Patients pretreated with a diuretic: Consideration must be given to discontinuing the diuretic for at least 2 to 3 days or- depending on the duration of action of the diuretic- longer before starting treatment with Ramipril, or at least to reducing the diuretic dose. The initial daily dose in patients previously treated with a diuretic is generally 1.25 mg Ramipril.

Overdose Effects

Sign and symptom: Overdosage may cause excessive peripheral vasodilatation (with marked hypotension, shock), bradycardia, electrolyte disturbances, and renal failure.

Management: Primary detoxifcation by, for example, gastric lavage, administration of adsorbents, sodium sulfate; (if possible during the frst 30 minutes). In the event of hypotension administration of α1-adrenergic agonists (e.g. norepinephrine, dopamine) or angiotensin II (angiotensinamide), which is usually available only in scattered research laboratories, must be considered in addition to volume and salt substitution.

Therapeutic Class

Angiotensin-converting enzyme (ACE) inhibitors

 

Atenolol :

Brand:Tenoloc(ACME),Betaloc(ACI)

Indications

Atenolol is indicated-

  • In the management of hypertension. It may be used alone or concomitantly with other antihypertensive agents, particularly with a thiazide-type diuretic.
  • For the long-term management of patients with angina pectoris.
  • In the management of hemodynamically stable patients with defnite or suspected acute myocardial infarction to reduce cardiovascular mortality.

Pharmacology

The synthesis of atenolol resulted from attempts to produce a β-adrenoceptor antagonist that would competitively block β1 (cardiac) receptors but have no effect on β2-receptors. It is classified as a β1 selective (cardioselective) β-adrenergic receptor antagonist with no membranestability activity and no partial agonist activity. It is markedly the most hydrophilic of the currently available β- blockers and thus penetrates the lipid of cell membranes poorly

Dosage & Administration

Hypertension: The initial dose of Atenolol is 50 mg given as one tablet a day either alone or added to diuretic therapy. The full effect of this dose will usually be seen within one to two weeks. If an optimal response is not achieved, the dosage should be increased to Atenolol 100 mg given as one tablet a day. Increasing the dosage beyond 100 mg a day is unlikely to produce any further benefit.

Angina Pectoris: The initial dose of Atenolol is 50 mg given as one tablet a day. If an optimal response is not achieved within one week, the dosage should be increased to Atenolol 100 mg given as one tablet a day. Some patients may require a dosage of 200 mg once a day for optimal effect. Twenty-four hour control with once daily dosing is achieved by giving doses larger than necessary to achieve an immediate maximum effect. The maximum early effect on exercise tolerance occurs with doses of 50 to 100 mg, but at these doses the effect at 24 hours is attenuated, averaging about 50% to 75% of that observed with once a day oral doses of 200 mg.

Acute Myocardial Infarction: In patients with definite or suspected acute myocardial infarction, treatment with Atenolol I.V. Injection should be initiated as soon as possible after the patient's arrival in the hospital and after eligibility is established. Treatment should begin with the intravenous administration of 5 mg Atenolol over 5 minutes followed by another 5 mg intravenous injection 10 minutes later. In patients who tolerate the full intravenous dose (10 mg), Atenolol Tablets 50 mg should be initiated 10 minutes after the last intravenous dose followed by another 50 mg oral dose 12 hours later. Thereafter, Atenolol can be given orally either 100 mg once daily or 50 mg twice a day for a further 6-9 days or until discharge from the hospital. If bradycardia or hypotension requiring treatment or any other untoward effects occur, Atenolol should be discontinued.

 

Interaction

  • Catecholamine-depleting drugs (eg, reserpine) may have an additive effect when given with beta-blocking agents. Patients treated with Atenolol plus a catecholamine depletor should therefore be closely observed for evidence of hypotension and/or marked bradycardia which may produce vertigo, syncope, or postural hypotension.
  • Calcium channel blockers may also have an additive effect when given with Atenolol.
  • Disopyramide is a Type I antiarrhythmic drug with potent negative inotropic and chronotropic effects. Disopyramide has been associated with severe bradycardia, asystole and heart failure when administered with beta blockers.
  • Amiodarone is an antiarrhythmic agent with negative chronotropic properties that may be additive to those seen with beta blockers.
  • Beta blockers may exacerbate the rebound hypertension which can follow the withdrawal of clonidine. If the two drugs are coadministered, the beta blocker should be withdrawn several days before the gradual withdrawal of clonidine. If replacing clonidine by beta-blocker therapy, the introduction of beta blockers should be delayed for several days after clonidine administration has stopped.
  • Concomitant use of prostaglandin synthase inhibiting drugs, eg, indomethacin, may decrease the hypotensive effects of beta blockers.
  • While taking beta blockers, patients with a history of anaphylactic reaction to a variety of allergens may have a more severe reaction on repeated challenge, either accidental, diagnostic or therapeutic. Such patients may be unresponsive to the usual doses of epinephrine used to treat the allergic reaction.
  • Both digitalis glycosides and beta-blockers slow atrioventricular conduction and decrease heart rate. Concomitant use can increase the risk of bradycardia.

Contraindications

Atenolol is contraindicated in-

  • Sinus bradycardia, heart block greater than first degree, cardiogenic shock, and overt cardiac failure.
  • Those patients with a history of hypersensitivity to the atenolol or any of the drug product’s components.

Side Effects

In a series of investigations in the treatment of acute myocardial infarction, bradycardia and hypotension occurred more commonly, as expected for any beta blocker. In addition, a variety of adverse efects has been reported with other beta-adrenergic blocking agents, and may be considered potential adverse efects of Atenolol.

  • Hematologic: Agranulocytosis.
  • Allergic: Fever, combined with aching and sore throat, laryngospasm, and respiratory distress.
  • Central Nervous System: Reversible mental depression progressing to catatonia; an acute reversible syndrome characterized by disorientation of time and place; short term memory loss; emotional lability with slightly clouded sensorium; and, decreased performance on neuropsychometrics.
  • Gastrointestinal: Mesenteric arterial thrombosis, ischemic colitis.
  • Miscellaneous: There have been reports of skin rashes and/or dry eyes associated with the use of beta-adrenergic blocking drugs. Discontinuance of the drug should be considered if any such reaction is not otherwise explicable. Patients should be closely monitored following cessation of therapy.
  • Other: Erythematous rash

Pregnancy & Lactation

Pregnancy Category D. Caution should be exercised when Atenolol is administered to a nursing woman. Clinically significant bradycardia has been reported in breast-fed infants. Premature infants, or infants with impaired renal function, may be more likely to develop adverse effects.

Precautions & Warnings

General: Patients already on a beta blocker must be evaluated carefully before Atenolol is administered. Initial and subsequent Atenolol dosages can be adjusted downward depending on clinical observations including pulse and blood pressure. Atenolol may aggravate peripheral arterial circulatory disorders.

Impaired Renal Function: The drug should be used with caution in patients with impaired renal function.

Geriatric Use:

  • Hypertension and Angina Pectoris: Due to Coronary Atherosclerosis: Dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
  • Acute Myocardial Infarction: Dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. Evaluation of patients with hypertension or myocardial infarction should always include assessment of renal function.

Use in Special Populations

Elderly Patients or Patients with Renal Impairment: Atenolol is excreted by the kidneys; consequently dosage should be adjusted in cases of severe impairment of renal function. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, refecting greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. The following maximum oral dosages are recommended for elderly, renal impaired patients and for patients with renal impairment due to other causes:

  • Creatinine clearance 15-35 ml/min/1.73 m2: Maximum dosage 50 mg daily
  • Creatinine clearance <15 mL/min/1.73 m2: Maximum dosage 25 mg daily

Some renal impaired or elderly patients being treated for hypertension may require a lower starting dose of Atenolol: 25 mg given as one tablet a day. Patients on hemodialysis should be given 25 mg or 50 mg after each dialysis; this should be done under hospital supervision as marked falls in blood pressure can occur.

Overdose Effects

Overdosage with Atenolol has been reported with patients surviving acute doses as high as 5 g. One death was reported in a man who may have taken as much as 10 g acutely. The predominant symptoms reported following Atenolol overdose are lethargy, disorder of respiratory drive, wheezing, sinus pause and bradycardia. Additionally, common efects associated with overdosage of any beta-adrenergic blocking agent and which might also be expected in Atenolol overdose are congestive heart failure, hypotension, bronchospasm and/or hypoglycemia. Treatment of overdose should be directed to the removal of any unabsorbed drug by induced emesis, gastric lavage, or administration of activated charcoal. Atenolol can be removed from the general circulation by hemodialysis. Based on the severity of symptoms, management may require intensive support care and facilities for applying cardiac and respiratory support.

Therapeutic Class

Beta-adrenoceptor blocking drugs, Beta-blockers

 

Metoprolol:

Brand: Betaloc(drug int),Metaloc(renata)

Indications

ln the management of hypertension and angina pectoris. Cardiac arrhythmias, especially supraventricular tachyarrhythmias. Adjunct to the treatment of hyperthyroidism. Early intervention with Metoprolol in acute myocardial infarction reduces infarct size and the incidence of ventricular fibrillation. Pain relief may also decrease the need for opiate analgesics. Metoprolol has been shown to reduce mortality when administered to patients with acute myocardial infarction.

Pharmacology

Metoprolol is a selective beta1-blocker. Metoprolol reduces or inhibits the agonistic effect on the heart of catecholamines (which are released during physical and mental stress). This means that the usual increase in heart rate, cardiac output, cardiac contractility and blood pressure, produced by the acute increase in catecholamines, is reduced by Metoprolol. Metoprolol interferes less with Insulin release and carbohydrate metabolism than do non-selective beta-blockers. Metoprolol interferes much less with the cardiovascular response to hypoglycaemia than do non-selective beta-blockers.

Dosage & Administration

Film-coated tablet-

  • Hypertension: Total daily dosage Metoprolol 100-400 mg to be given as a single or twice-daily dose. The starting dose is 100 mg (two Metoprolol-50 tablets) per day. This may be increased by 100 mg per day at weekly intervals. lf full control is not achieved using a single daily dose, a b.i.d. regimen should be initiated. Combination therapy with a diuretic or other antihypertensive agents may also be considered.
  • Angina: Usually Metoprolol 50 mg (one Metoprolol-50 tablet) to 100 mg (two Metoprolol-50 tablets) twice or three times daily.
  • Cardiac arrhythmias: Metoprolol 50 mg (one Metoprolol-50 tablet) b.i.d or t.i.d should usually control the condition. It is necessary the dose can be increased up to 300 mg per day in divided doses. Following the treatment of an acute arrhythmia with Metoprolol injection, continuation therapy with Metoprolol tablets should be initiated 4-6 hours later. The initial oral dose should not exceed 50 mg t.i.d.
  • Hyperthyroidism: Metoprolol 50 mg (one Metoprolol-50 tablet) four times a day. The dose should be reduced as the euthyroid state is achieved.
  • Myocardial infarction: Orally, therapy should commence 15 minutes after the last injection with 50 mg every 6 hours for 48 hours. Patients who fail to tolerate the full intravenous dose should be given half the suggested oral dose. Maintenance- The usual maintenance dose is 200 mg daily given in divided doses. Elderly’ There are no special dosage requirements in otherwise healthy elderly patients. Significant hepatic dysfunction: A reduction in dosage may be necessary.

Extended-release tablet-

  • Hypertension: The usual initial dosage is 25 to 100 mg daily in a single dose, whether used alone or added to a diuretic.
  • Angina Pectoris: The dosage of extended-release Metoprolol Succinate should be individualized. The usual initial dosage is 100 mg daily, in a single dose.
  • Heart Failure: The recommended starting dose of sustained-release Metoprolol Succinate is 25 mg once daily for two weeks in patients with NYHA class II heart failure and 12.5 mg once daily in patients with more severe heart failure. The dosage may be increased at weekly (or longer) intervals until optimum blood pressure reduction is achieved. If treatment is to be discontinued, the dosage should be reduced gradually over a period of 1-2 weeks.

IV Injection-

  • Arrhythmias: By intravenous injection, up to 5 mg at a rate of 1-2 mg/minute, repeated after 5 minutes if necessary, total dose 10-15 mg.
  • In surgery: By slow intravenous injection 2-4 mg at induction or to control arrhythmias developing during anaesthesia; 2 mg doses may be repeated to a maximum of 10 mg.
  • Myocardial Infarction: Early intervention within 12 hours of infarction, by intravenous injection 5 mg every 2 minutes to a maximum of 15 mg, followed after 15 minutes by 50 mg by mouth every 6 hours for 48 hours; maintenance 200 mg daily in divided doses.

 

Interaction

Catecholaminedepleting drugs (e.g. Reserpine, Monoamine Oxidase (MAO) inhibitors) may have an additive effect when given with betablocking agents. Drugs that inhibit CYP2D6 such as quinidine, fluoxetine, paroxetine and propafenone are likely to increase Metoprolol concentration. These increases in plasma concentration would decrease the cardioselectivity of Metoprolol. Concomitant use of digitalis glycosides and betablockers can increase the risk of bradycardia. Betablockers may exacerbate the rebound hypertension which can follow the withdrawal of clonidine.

Contraindications

AV block, Uncontrolled heart failure, severe bradycardia, sick-sinus syndrome, cardiogenic shock and severe peripheral arterial disease. Known hypersensitivity to Metoprolol or other B-blockers. Metoprolol is also contra-indicated when myocardial infarction is complicated by significant bradycardia, first-degree heart block, systolic hypotension (<100mmHg) and/or severe heart failure.

Side Effects

Tiredness, dizziness, depression, diarrhea, itching or rash, shortness of breath, slow heart rate, mental confusion, headache, somnolence, nightmares, insomnia, dyspnea, Nausea, dry mouth, gastric pain, constipation, flatulence, digestive tract disorders, heartburn, pruritus, musculoskeletal pain, blurred vision, decreased libido, and tinnitus have also been reported, intensification of AV block.

Pregnancy & Lactation

Pregnancy Category C. There are no adequate and wellcontrolled studies in pregnant women. This drug should be used during pregnancy only if clearly needed. Metoprolol is excreted in breast milk in very small quantities. Caution should be exercised when Metoprolol is administered to a nursing woman.

Precautions & Warnings

Bronchospastic Diseases: Because of its relative beta 1 selectivity, however, Metoprolol may be used with caution in patients with bronchospastic disease who do not respond to, or cannot tolerate other antihypertensive treatment.

Major Surgery: The necessity or desirability of withdrawing betablocking therapy prior to major surgery is controversial; the impaired ability of the heart to respond to reflex adrenergic stimuli may augment the risks of general anesthesia and surgical procedures.

Diabetes and Hypoglycemia: Betablockers may mask tachycardia occurring with hypoglycemia, but other manifestations such as dizziness and sweating may not be significantly affected. Peripheral Vascular Disease: Betablockers can precipitate or aggravate symptoms of arterial insufficiency in patients with peripheral vascular disease. Calcium Channel Blockers: Because of significant inotropic and chronotropic effects in patients, caution should be exercised in patients treated with these agents concomitantly.

Use in Special Populations

Hepatic impaired patient: Metoprolol should be used with caution in patients with impaired hepatic function.

Pediatric Use: No clinically relevant differences in the adverse event profile were observed for pediatric patients aged 6 to 16 years as compared with adult patients. Safety and effectiveness of Metoprolol have not been established in patients <6 years of age.

Geriatric Use: There were no notable differences in efficacy or the rate of adverse events between older and younger patients.

Overdose Effects

Poisoning due to an overdose of metoprolol may lead to severe hypotension, sinus bradycardia, atrioventricular block, heart failure, cardiogenic shock, cardiac arrest, bronchospasm, impairment of consciousness, coma, nausea, vomiting, cyanosis, hypoglycaemia and, occasionally, hyperkalaemia. The first manifestations usually appear 20 minutes to 2 hours after drug ingestion. Treatment: Treatment should include close monitoring of cardiovascular, respiratory and renal function, and blood glucose and electrolytes. Further absorption may be prevented by induction of vomiting, gastric lavage or administration of activated-charcoal if ingestion is recent. Cardiovascular complications should be treated symptomatically, which may require the use of sympathomimetic agents (e.g. noradrenaline, metaramionl), atropine or inotropic agents (e.g. dopamine, dobutamine). Temporary pacing may be required for AV block. Glucagon can reverse the effects of excessive B-blockade, given in a dose of 1-10 mg intravenously. Intravenous B2-stimulants e.g. terbutaline may be required to relieve bronchospasm. Metoprolol cannot be effectively removed by haemodialysis.

Storage Conditions

Store in a cool and dry place, protected from light.

 

Losartan:

Brand : Angilock(square),osartil(incepta),Losart(acme)

Prosan(beximco)

Indications

Hypertension: Losartan Potassium is indicated for the treatment of hypertension. It may be used alone or in combination with other antihypertensive agents (eg. thiazide diuretics).

Renal Protection in Type-2 Diabetic Patients with Proteinuria: Losartan Potassium is indicated to delay the progression of renal disease in hypertensive type-2 diabetics with proteinuria, defined as urinary albumin to creatinine ratio >300 mg/g.

Pharmacology

Losartan Potassium is the first non-peptide orally active angiotensin II receptor blocker. It binds to the AT1 receptor found in many tissues (e.g. vascular smooth muscle, adrenal gland, kidneys and the heart) and reduces several important biological actions including vasoconstriction and the release of aldosterone responsible for hypertension.

Dosage & Administration

The usual starting and maintenance dose is 50 mg once daily for most patients. If the antihypertensive effect using 50 mg once daily is inadequate, 25 mg twice daily is recommended prior to increasing the dose. For patients with intravascular volume-depletion (e.g., those treated with high-dose diuretics), a starting dose of 25 mg once daily should be considered. Losartan Potassium can be administered once or twice daily. The total daily dose ranges from 25 mg to 100 mg.

 

Interaction

Rifampicin and fluconazole reduce levels of active metabolite of Losartan Potassium. Concomitant use of Losartan Potassium and hydrochlorothiazide may lead to potentiation of the antihypertensive effects. Concomitant use of potassium-sparing diuretics (eg, spironolactone, triamterene, amiloride), potassium supplements or salt substitutes containing potassium may lead to increases in serum potassium. The antihypertensive effect of losartan may be attenuated by the non-steroidal anti-inflammatory drug indomethacin. The use of ACE-inhibitor, angiotensin receptor antagonist, an anti-inflammatory drug and a thiazide diuretic at the same time increases the risk of renal impairment.

Contraindications

Losartan Potassium is contraindicated in pregnant women and in patients who are hypersensitive to any component of this product. Losartan Potassium should not be administered with Aliskiren in patients with diabetes.

Side Effects

The side effects with the use of Losartan Potassium are mild and transient in nature. The most common side effects are dizziness, diarrhea, nasal congestion, cough, upper respiratory infection. Other side effects are fatigue, oedema, abdominal pain, chest pain, nausea, headache & pharyngitis.

Pregnancy & Lactation

Pregnancy Category D. The risk to the fetus increases if Losartan Potassium is administered during the second or third trimesters of pregnancy. It is not known whether Losartan Potassium is excreted in human milk, as many drugs are excreted in human milk and because of the potential for adverse effects on the nursing infant, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.

Precautions & Warnings

Use of Losartan Potassium during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death. In patients who are intravascularly volume-depleted (e.g., those treated with high-dose diuretics), symptomatic hypotension may occur. Plasma concentration of Losartan Potassium is significantly increased in cirrhotic patients. Changes in renal function including renal failure have been reported in renal impaired patient.

Therapeutic Class

Angiotensin-ll receptor blocker

Storage Conditions

keep in a dry place away from light and heat. Keep out of the reach of children.

Price: 25mg-6tk,50mg-10tk,100mg-12tk

Amlodipine:

Brand: Amdocal(beximco)camlpdin(square)

Indications

Essential hypertension: Amlodipine is efficacious as monotherapy in the treatment of hypertension. It may be used in combination with other antihypertensive agents.

Angina pectoris: Amlodipine is indicated for the treatment of chronic stable angina pectoris and is efficacious as monotherapy. It may be used in combination with other antianginal agents.

Vasospastic angina: Amlodipine is indicated for the treatment of confirmed or suspected vasospastic angina. It may be used as monotherapy or in combination with other antianginal drugs.

Pharmacology

Amlodipine is a dihydropyridine calcium-channel blocker, with a long duration of action, used for the treatment of hypertension and angina pectoris. Amlodipine influences the myocardial cells, the cells within the specialized conducting system of the heart, and the cells of vascular smooth muscle. Administration of Amlodipine results primarily in vasodilation, with reduced peripheral resistance, blood pressure and afterload, increased coronary blood flow and a reflex increase in coronary heart rate. This in turn results in an increase in myocardial oxygen supply and cardiac output.

Dosage & Administration

Hypertension: Usual dose is 5 mg once daily. The maximum dose is 10 mg once daily. Elderly patients with hepatic insufficiency may be started on 2.5 mg once daily; this dose may also be used when adding Amlodipine to other antihypertensive therapy.

Angina (Chronic stable or Vasospastic): 5 to 10 mg, using the lower dose for elderly and in patients with hepatic insufficiency. Most patients require 10 mg.

Administrations: May be taken without regard to meals.

 

Interaction

Drug Interactions-

  • Potentially hazardous interactions: Little or no data are available in patients with markedly impaired cardiac left ventricular function; however, as with other calcium antagonist drugs, the combination of Amlodipine and p-blockers should be avoided in such patients.

Other Significant Interactions-

  • Digoxin: Absence of any interaction between Amlodipine and Digoxin in healthy volunteers has been documented in a controlled clinical study.
  • Cimetidine: An unpublished clinical study indicated no interaction between, Amlodipine and Cimetidine in healthy volunteers.
  • Warfarin: An unpublished clinical study in healthy volunteers indicates that Amlodipine did not significantly alter the effect of Warfarin on prothrombin time.
  • Food: Food does not alter the rate or extent of absorption of Amlodipine.

Contraindications

Hypersensitivity to dihydropyridine derivatives. Pregnant woman.

Side Effects

The most common adverse effects of amlodipine are associated with vasodilatory action, such as dizziness, flushing, headache, hypotension and peripheral edema. Gastrointestinal disturbances, increased micturition frequency, lethargy, eye pain and mental depression may also occur. A paradoxical increase in ischaemic chest pain may occur at the start of the treatment and in a few patients excessive fall in blood pressure has led to cerebral or myocardial ischaemia or transient blindness. Rashes, fever and abnormalities in liver function due to hypersensitivity reaction of Amlodipine may occur.

Pregnancy & Lactation

Pregnancy Category C. There are no adequate and well-controlled studies of Amlodipine in pregnant women. Amlodipine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. It is not known whether Amlodipine is excreted in human milk. In the absence of this information, it is recommended that nursing be discontinued while Amlodipine is administered.

Precautions & Warnings

Precaution should be taken in patients with hepatic impairment and during pregnancy and breast feeding.

Use in Special Populations

Children with hypertension from 6 years to 17 years of age: 2.5 mg once daily as a starting dose, up-titrated to 5 mg once daily if blood pressure goal is not achieved after 4 weeks. Doses in excess of 5 mg daily have not been studied in pediatric patients.

Children under 6 years old:  The effect of amlodipine on blood pressure in patients less than 6 years of age is not known.

Elderly: Amlodipine used at similar doses in elderly or younger patients is equally well tolerated. Normal dosage regimens are recommended in the elderly, but increase of the dosage should take place with care.

Renal impairment: Changes in amlodipine plasma concentrations are not correlated with degree of renal impairment, therefore the normal dosage is recommended. Amlodipine is not dialysable.

Hepatic impairment: Dosage recommendations have not been established in patients with mild to moderate hepatic impairment; therefore dose selection should be cautions and should start at the lower end of the dosing range. The pharmacokinetics of Amlodipine have not been studied in severe hepatic impairment. Amlodipine should be initiated at the lowest dose (2.5 mg once daily) and titrated slowly in patients with severe hepatic impairment.

Overdose Effects

Symptoms: Available data suggest that large overdosage could result in excessive peripheral vasodilatation and possibly reflex tachycardia. Marked and probably prolonged systemic hypotension up to and including shock with fatal outcome have been reported.

Management: Clinically significant hypotension due to amlodipine overdosage calls for active cardiovascular support including frequent monitoring of cardiac and respiratory function, elevation of extremities, and attention to circulating fluid volume and urine output. 

A vasoconstrictor may be helpful in restoring vascular tone and blood pressure, provided that there is no contraindication to its use. Intravenous calcium gluconate may be beneficial in reversing the effects of calcium channel blockade. Gastric lavage may be worthwhile in some cases. In healthy volunteers the use of charcoal up to 2 hours after administration of amlodipine 10 mg has been shown to reduce the absorption rate of amlodipine. Since amlodipine is highly protein-bound, dialysis is not likely to be of benefit.

Therapeutic Class

Calcium-channel blockers

Storage Conditions

Keep all medicines out of reach of children. Store in a cool & dry place, protected from light.

 price: 8-10tk

Amlodipine Besilate + Olmesartan Medoxomil:

brand:bizoran(beximco),ABecap(aci)

Camlosart(square)

Indications

Indicated for the treatment of hypertension alone or with other antihypertensive agents, to lower blood pressure. This combination drug is indicated as initial therapy in patients likely to need multiple antihypertensive agents to achieve their blood pressure goals. The decision to use a combination as initial therapy should be individualized and shaped by considerations such as baseline blood pressure, the target goal, and the incremental likelihood of achieving goal with a combination compared to monotherapy. Individual blood pressure goals may vary based upon the patient’s risk.

 

Pharmacology

Amlodipine is a dihydropyridine calcium channel blocker that inhibits the transmembrane influx of calcium ions into vascular smooth muscle and cardiac muscle. Amlodipine has a greater effect on vascular smooth muscle cells than on cardiac muscle cells. Amlodipine is a peripheral arterial vasodilator that acts directly on vascular smooth muscle to cause a reduction in peripheral vascular resistance and reduction in blood pressure.

Angiotensin II formed from angiotensin I in a reaction catalyzed by angiotensin-converting enzyme (ACE), is a potent vasoconstrictor, the primary vasoactive hormone of the Renin-angiotensin system and an important component in the pathophysiology of hypertension. It also stimulates aldosterone secretion by the adrenal cortex.

Olmesartan Medoxomil blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selectively blocking the binding of angiotensin II to the AT1 receptor found in many tissues, (e.g. vascular smooth muscle, adrenal gland). In vitro binding studies indicate that Olmesartan Medoxomil is a reversible, competitive inhibitor of the AT1 receptor. Olmesartan Medoxomil does not inhibit ACE (kinase II, the enzyme that converts angiotensin I to angiotensin II and degrades bradykinin).

Dosage & Administration

Substitute individually titrated components for patients on Amlodipine and Olmesartan Medoxomil. This combination may also be given with increased amounts of Amlodipine, Olmesartan Medoxomil, or both, as needed.

Initial therapy: Initiate with 5/20 mg once daily for 1 to 2 weeks and titrate as needed up to a maximum of 10/40 mg once daily. Due to decreased clearance of Amlodipine among elderly patients the recommended starting dose of Amlodipine is 2.5 mg in patients 75 years. The lowest dose of the combination is 5/20 mg; therefore, initial therapy with this combination drug is not recommended in patients >75 years old.

 

Interaction

The antihypertensive effect of angiotensin II receptor antagonists, including Olmesartan Medoxomil may be attenuated by NSAIDs including selective COX-2 inhibitors. Blood pressure, renal function and electrolytes should be closely monitored in patients on combination therapy and other agents that affect the RAS.

Contraindications

Cannot be co-administered with Aliskiren in patients with diabetes.

Side Effects

The most common side effects include peripheral edema, headache, flushing, and dizziness. It can also cause Intestinal problems known a sprue-like enteropathy.

Pregnancy & Lactation

Pregnancy Category D. Amlodipine and Olmesartan Medoxomil combination should not be used in 2nd and 3rd trimester because it can cause fetal death. When pregnancy is detected this combination should be discontinued as soon as possible. It is not known whether Olmesartan and Amlodipine are excreted in human milk. Because of the potential for adverse effects on the nursing infant, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.

Precautions & Warnings

Amlodipine and Olmesartan Medoxomil combination should be used with caution because there is a risk for-

  • Hypotension in volume- or salt depleted patients.
  • Vasodilation in patients with severe aortic stenosis.
  • Increased frequency, duration or severity of angina or acute Ml in patients with severe obstructive coronary artery disease.

Use in Special Populations

Pediatric use: The safety and effectiveness have not been established in pediatric patients.
Geriatric use: No overall differences in safety or effectiveness were observed between subjects 65 years of age or older and younger subjects.
Renal impairment: There are no studies in patients with renal impairment.
Hepatic impairment: Initial therapy is not recommended in hepatically impaired patients.

Overdose Effects

There is no information on over dosage in humans.

Therapeutic Class

Combined antihypertensive preparations

Storage Conditions

Do not store above 30°C. Keep away from light and out of the reach of children.

 price-12-20tk

Losartan Potassium + Hydrochlorothiazide:

Brand: Angilock plus(square),osartil plus(incepta)

Indications

This is indicated for the treatment of hypertension. It is also indicated to reduce the risk of stroke in patients with hypertension and left ventricular hypertrophy.

Pharmacology

Angiotensin II formed from angiotensin I in a reaction catalyzed by angiotensin converting enzyme (ACE), is a potent vasoconstrictor, the primary vasoactive hormone of the renin-angiotensin system and an important component in the pathophysiology of hypertension. It also stimulates aldosterone secretion by the adrenal cortex. Losartan and its principal active metabolite block the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selectively blocking the binding of angiotensin II to the ATreceptor found in many tissues, (e.g. vascular smooth muscle, adrenal gland). In vitro binding studies indicate that losartan is a reversible, competitive inhibitor of the ATreceptor. Neither Losartan nor its active metabolite inhibits ACE (kinase II, the enzyme that converts angiotensin I to angiotensin II and degrades bradykinin); nor do they bind to or block other hormone receptors or ion channels known to be important in cardiovascular regulation.

Hydrochlorothiazide is a thiazide diuretic. Thiazides affect the renal tubular mechanisms of electrolyte reabsorption, directly increasing excretion of Sodium and Chloride in approximately equivalent amounts. Indirectly, the diuretic action of Hydrochlorothiazide reduces plasma volume, with consequent increases in plasma renin activity, increases in Aldosterone secretion, increases in urinary Potassium loss, and decreases in serum Potassium. The renin-aldosterone link is mediated by angiotensin II, so co-administration of an angiotensin II receptor antagonist tends to reverse the Potassium loss associated with these diuretics.

Dosage

Hypertension-

  • The usual starting dose of 50/12.5 is one tablet once daily.
  • For patients who do not respond adequately to one tablet the dosage may be increased to 100/25 once daily.
  • A patient whose blood pressure is not adequately controlled with Losartan 100 mg monotherapy may be switched to this combination 100/12.5 once daily.
  • In hypertensive patients with left ventricular hypertrophy initial dose is 50/12.5, if additional blood pressure reduction is needed, 100/12.5 may be given, followed by 100/25 if required. The maximum dose is 100/25 once daily.
  • In general, the antihypertensive effect is attained within three weeks after initiation of therapy.
  • No initial dosage adjustment of 50/12.5 is necessary for elderly patients. But maximum dose of 100/25 once daily dose should not be used as initial therapy in elderly patients.

Severe Hypertension:

  • The starting dose for initial treatment of severe hypertension is one tablet of 50/12.5 once daily.
  • For patients who do not respond adequately to this dose after 2 to 4 weeks of therapy, the dosage may be increased to 100/25 once daily. The maximum dose is one tablet of 100/25 once daily.

 

Administration

This preparation may be administered with other antihypertensive agents. This may be administered with or without food.

 

Interaction

Losartan Potassium: No significant drug-drug pharmacokinetic interactions have been found in interaction studies with Hydrochlorothiazide, Digoxin, Warfarin, Cimetidine and Phenobarbital. As with other drugs that block angiotensin II or its effects, concomitant use of potassium-sparing diuretics (e.g. Spironolactone, Triamterene, Amiloride), potassium supplements, or salt substitutes containing potassium may lead to increase in serum potassium. As with other antihypertensive agents, the antihypertensive effect of Losartan may be blunted by the non-steroidal anti-inflammatory drug Indomethacin.

Hydrochlorothiazide: When administered concurrently, the following drugs may interact with Thiazide diuretics: alcohol, barbiturates, or narcotics-potentiation of orthostatic hypotension may occur.

Antidiabetic drugs (oral agents and Insulin): dosage adjustment of the antidiabetic drug may be required.

Other antihypertensive drugs: additive effect or potentiation.

Cholestyramine and colestipol resins: absorption of Hydrochlorothiazide is impaired in the presence of anionic exchange resins

Contraindications

The combination of Losartan and Hydrochlorothiazide is contraindicated in patients who are hypersensitive to any component of this product. Because of the Hydrochlorothiazide component, this product is contraindicated in patients with anuria or hypersensitivity to other sulfonamide-derived drugs.

Side Effects

Side-effects are usually mild. Symptomatic hypotension including dizziness may occur, particularly in patients with intravascular volume depletion (e.g. those taking high-dose diuretics). Hyperkalaemia occurs occasionally; angioedema has also been reported with some angiotensin-II receptor antagonists. Vertigo; less commonly gastro-intestinal disturbances, angina, palpitation, oedema, dyspnoea, headache, sleep disorders, malaise, urticaria, pruritus, rash; rarely hepatitis, atrial fibrillation, cerebrovascular accident, syncope, paraesthesia; also reported pancreatitis, anaphylaxis, cough, depression, erectile dysfunction, anaemia, thrombocytopenia, hyponatraemia, arthralgia, myalgia, renal impairment, rhabdomyolysis, tinnitus, photosensitivity, and vasculitis (including Henoch-Schonlein purpura)

Pregnancy & Lactation

Angiotensin-II receptor antagonists should be avoided in pregnancy unless essential. They may adversely affect fetal and neonatal blood pressure control and renal function; skull defects and oligohy dramnios have also been reported. Information on the use of angiotensin-II receptor antagonists in breastfeeding is limited. They are not recommended in breastfeeding and alternative treatment options, with better-established safety information during breastfeeding, are available.

Precautions & Warnings

  • Hypersensitivity: Angiooedema
  • Periodic determination of serum electrolytes to detect possible electrolyte imbalance should be performed at appropriate intervals
  • Hypokalemia may rarely develop, especially with brisk diuresis, when severe cirrhosis is present, or after prolonged therapy
  • Impaired renal function and
  • Symptomatic hypotension

Use in Special Populations

Use in Patients with Renal Impairment: The usual regimens of therapy with 50/12.5 may be followed as long as the patient's creatinine clearance is >30 ml/min. In patients with more severe renal impairment, loop diuretics are preferred to thiazides. In that case, hydrochlorothiazide is not recommended.

Use in Patients with Hepatic Impairment: The combination of Losartan and Hydrochlorothiazide is not recommended for titration in patients with hepatic impairment because the appropriate 25 mg starting dose of Losartan cannot be given.

Use in pediatric patients: The safety and effectiveness in pediatric patients have not been established.

Overdose Effects

Losartan Potassium: Limited data are available in regard to overdosage in humans. The most likely manifestation of overdosage would be hypotension and tachycardia; bradycardia could occur from parasympathetic (vagal) stimulation. If symptomatic hypotension should occur, supportive treatment should be instituted. Neither losartan nor its metabolite can be removed by hemodialysis.

Hydrochlorothiazide: The most common signs and symptoms observed are those caused by electrolyte depletion (hypokalemia, hypochloremia, and dehydration resulting from excessive diuresis. If digitalis has also been administered, hypokalemia, may accentuate cardiac arrhythmias. The degree to which Hydrochlorothiazide is removed by hemodialysis has not been established.

Therapeutic Class

Combined antihypertensive preparations

Price: 8-12tk

Prazosin:

Brand: Alphapress(Renata),Prazopress(unimed)

Prazolok(square)

Indications

Hypertension: Prazosin is indicated in the treatment of all grades of essential (primary) hypertension and of all grades of secondary hypertension of variec etiology. It can be used as the initial and sole agent or it may be employed in a treatment program in combination with a diuretic and/or other antihypertensive drugs as needed for proper patient response. Renal blood flow and glomerular filtration rate are not impaired by long-term oral administration and thus Prazosin can be used with safety in hypertensive patients with impaired renal function.

Left Ventricular Failure: Prazosin is indicated in the treatment of left ventricular failure. Prazosin may be added to the therapeutic regimen in those patients who have not shown a satisfactory response or who have become refractory to conventional therapy with diuretics, with or without cardiac glycosides.

Raynaud's Phenomenon And Raynaud's Disease: Prazosin indicated in the treatment of Raynaud's phenomenon and Raynaud's disease.

Benign Prostatic Hyperplasia: Prazosin is indicated as an adjunct in the symptomatic treatment of urinary obstruction caused by benign prostatic hyperplasia. It is also of value in patients awaiting prostatic surgery.

Pharmacology

Prazosin causes a decrease in total peripheral vascular resistance through selective inhibition of postsynaptic alpha-1-adrenoreceptors in vascular smooth muscle. In hypertensive patients, blood pressure is lowered in both the supine and standing positions; this effect is more pronounced on the diastolic blood pressure. Rebound elevation of blood pressure does not occur following abrupt cessation of Prazosin therapy.

The therapeutic efficacy of Prazosin in patients with congestive heart failure is ascribed to a reduction in left ventricular filling pressure, reduction in cardiac impedance and an augmentation of cardiac output. The use of Prazosin in congestive heart failure does not provoke a reflex tachycardia and blood pressure reduction is minimal in normotensive patients. Prazosin reduce the severity of the signs, symptoms, frequency and duration of attacks, in patients with Raynaud's disease. In low dosage, antagonism of alpha-1-receptors on prostatic and urethral smooth muscle has been shown to improve the urinary pressure profile in men and to improve symptoms of benign prostatic hyperplasia. Clinical studies have shown that Prazosin therapy is not associated with adverse changes in the serum lipid profile.

Dosage & Administration

Prazosin Tablet: There is evidence that toleration is best when therapy is initiated with a low starting dose. During the first week, the dosage of Prazosin should be adjusted according to the patient's individual toleration. Thereafter the daily dosage is to be adjusted on the basis of the patient's response. The response is usually seen within one to 14 days if it is to occur at any particular dose. When a response is seen, therapy should be continued at that dosage until the degree of response has reached optimum before the next dose increment is added.

  • Hypertension: For maximum benefit, small increases should be continued until the desired effect is achieved or a total daily dosage of 20 mg is reached. A diuretic or adrenergic beta-blocking agent may be added to enhance efficacy. The maintenance dosage of Prazosin may be given as a twice or three times daily regimen.
  • Patients Receiving No Antihypertensive Therapy. It is recommended that therapy be initiated with 0.5 mg given in the evening at bedtime then 0.5 mg b.i.d. or t.i.d for three to seven days. Unless poor toleration suggests the patient is unusually sensitive, this dosage should be increased to 1 mg given b.i.d. or t.i.d. for a further three to seven days. Thereafter, as determined by the patient's response to the blood pressure lowering effect, the dosage should be increased gradually to a total daily dosage of 20 mg given in divided doses.
  • Patients Receiving Diuretic Therapy With inadequate Control of Blood Pressure. The diuretic should be reduced to a maintenance dosage level for the particular agent and Prazosin initiated with 0.5 mg h.s then proceeding to 0.5 mg b.i.d or t.i.d. After the initial period of observation, the dosage of Prazosin should be gradually increased as determined by the patient's response.
  • Patients Receiving Other Antihypertensives But With Inadequate Control. Because some additive effect is anticipated, the other agent dosage level (e.g. beta-adrenergic blocking agents, methyldopa. reserpine, lsnidine etc.) should be reduced and Prazosin initiated at 0.5 mg h.s. then proceeding to 0.5 mg b.i.d, or t.i.d. Subsequent dosage increase should be made depending upon the patient's response. There is evidence that adding Prazosin to beta-adrenergic blocking agents, calcium antagonists or ACE inhibitors may bring about a substantial reduction in blood pressure. Thus, to low initial dosage regimen is strong, recommended.
  • Patients With Moderate to Severe Grades of Renal Impairment Evidence to date shows that Prazosin does not further compromise renal function when used in patients with renal impairment. Because some patients in this category have responded to small doses of Prazosin , it is recommended that therapy be initiated at 0.5 mg daily and that dosage increases be instituted cautiously.

Left Ventricular Failure: The recommended starting dose is 0.5 mg two, three or four times a day, Dosage should be titrated according to the patent's clinical response, based on careful monitoring of cardiopulmonary signs and symptoms, and when indicated, hemodynamic studies. Dosage titration steps may be performed as often as every two or three days in patients under close medical supervision. In severely ill, decompensated patients, rapid dosage titiration over one to two days may be indicated and is best done when hemodynamic- monitoring is available In dininai studies, the therapeutic dosages ranged from 4 mg to 20mg daily in divided doses. Adjustment of dosage may be required in the course of Prazosin therapy in some patients to maintain optimal clinical improvement.

Suggested Starting Dosage: 0.5 mg b.i.d., t.i.d. or q.i.d. increasing to 4 mg in divided doses.

Use Daily Maintenance Dosage: 4 mg once daily to 20 mg in divided doses.

Raynaud's Phenomenon And Raynaud's Disease: The recommended starting dosage is 0.5 mg b.i.d. given for a period of three to seven days. Dosage should be adjusted according to the patient's clinical response.

Suggested Starting Dosage: 0.5mg b.i.d.

Usual Daily Maintenance Dosage: 1mg or 2 mg b.i.d Doses up to 2 mg t.i.d. may be required for some patients.

Benign Prostatic Hyperplasia: The recommended starting dose is 0.5 mg twice daily given for a period of 3 to 7 days and should then be adjusted according to the patient's clinical responses. The usual maintenance dose is 2 mg twice daily. The safety and efficacy of a total daily dosage greater than 4 mg have not been established. Therefore, total daily dosages greater than 4mg should be used with caution.

Prazosin XR Tablet: Prazosin XR Extended-Release Tablets must be swallowed whole and should not be bitten or divided. Therapy for hypertension with Prazosin XR must be initiated at 2.5 mg once daily. The 5 mg dosage form of Prazosin XR is not for initial dosing. Dosage may be increased slowly, in general over a 7 to 14-day period, depending on the response to each dose level. Doses above 20 mg once daily have not been studied.

Maintenance Dose: Dosage may be increased as clinically indicated to 20 mg given in once-daily doses.

Hypertensive patients controlled on Prazosin Tablets alone or in combination with other antihypertensive medications may be switched to Prazosin XR Extended Release Tablets at the equivalent or nearest higher total daily dose, e.g. Prazosin Tablets 4 mg daily equivalent to Prazosin XR Extended Release Tablets 5 mg once daily. Blood pressure measurements should be taken at the end of the dosing interval to assure adequate blood pressure control is maintained throughout the 24-hour period. Further titration may be necessary in some patients.

The addition of a diuretic or other antihypertensive agent to prazosin has been shown to cause an additive hypotensive effect.

 

Interaction

Prazosin XR has been administered without any adverse drug interaction in clinical experience to date with the following:

  • Cardiac-glycosides-digitalis and digoxin;
  • Hypoglycemic agents-insulin, chlorpropamide, phenformin, tolazamide, and tolbutamide;
  • tranquilizers and sedatives-chlordiazepoxide, diazepam and phenobarbital;
  • antiarrhythmic agents-procainamide, propranolol and quinidine; and
  • analgesic, antipyretic and anti-inflammatory agents-propxyphene, aspirin, indomethacin and phenylbutazone type.

Contraindications

Prazosin is contraindicated in patients with a known sensitivity to quinazolines.

Side Effects

The most common reactions associated with Prazosin therapy are dizziness, headache, drowsiness, lack of energy, weakness, palpitations and nausea. In most instances, side effects have disappeared with continued therapy or have been tolerated with no decrease in the dosage of the drug. In addition, the following reactions have been associated with Prazosin therapy; vomiting diarrhea, constipation, abdominal discomfort and/or pain, liver function abnormalities, pancreatitis, edema, orthostatic hypotension, dyspnea, faintness, tachycardia, nervousness, vertigo, hallucinations, depression, paresthesia, rash, pruritus alopecia, lichen planus, urinary frequency, impotence, incontinence, priapism, blurred vision, reddened solera, epistaxis, tinnitus, dry mouth, nasal congestion, diaphoresis, fever, positive ANA liter, and arthralgia. Some of these reactions have occurred rarely, and in many instances, the exact causal relationships have not been established. Literature reports exist associating Prazosin, therapy with a worsening of pre-existing narcolepsy. A causal relationship is uncertain in these cases. The following have been observed in parents being managed for left ventricular failure with Prazosin when used in conjunction with cardiac glycosides and diuretics; drowsiness, dizziness, postural hypotension, blurred vision, edema, dry mouth, palpitations, nausea, diarrhea, impotence, headache, and nasal congestion. In most instances, these occurrences have been mild to moderate in severity and have resolved with continued therapy or have been tolerated with no decrease in drug dosage. The most commonly although infrequently reported side effect in the treatment of Raynaud's Phenomenon/Disease was mild dizziness.

Pregnancy & Lactation

Although no teratogenic effects were seen in animal testing; the safety of Prazosin use during. pregnancy has not yet been established. The use of prazosin and a beta-blocker for the control of sever hypertension of 44 pregnant women revealed no drug-related fetal adnormalities or adverse effects. Therapy with prazosin was continued for as long as 14 weeks. Prazosin has also been used alone or in combination with other hypotensive agents in severe hypertension or pregnancy. No fetal or neonatal abnormalities have been reported with the use of Prazosin. There are no adequate and well controlled studies that establish the safety of Prazosin in pregnant women. Prazosin should be used during pregnancy only if in the opinion of the physician the potential benefit justifies the potential risk to the mother and fetus. Prazosin has been shown to be excreted in small amounts in human milk. Caution shold be exercised when Prazosin is adminsitered to nursing mothers.

Precautions & Warnings

Hypertension: A very small percentage of patients have responded in an abrupt and exaggerated manner to the initial dose of Prazosin. Postural hypotension evidenced by dizziness and weakness, or rarely loss of consciousness, has been reported, particularly with the commencement of therapy, but this effect is readily avoided by initiating treatment with a low dose of Prazosin XR and with small increases in dosage during the first one to two weeks of therapy. The effect when observed is not related to the severity of hypertension is self-limiting and in most patients does not recur after the initial period of therapy or during subsequent dose titration steps. When instituting therapy with any effective antihypertensive agent, the patient should be advised how to avoid symptoms resulting from postural hypotension and what measures to take should they develop. The patient should be cautioned to avoid situations where injury could result should dizziness or weakness occur during the initiation of Prazosin therapy.

Left Ventricular Failure: When prazosin is initially administered to patients with left ventricular failure who have undergone vigorous diuretic or other vasodilator treatment, particularly in higher than the recommended starting dose, the resultant decrease in left ventricular filling pressure may be associated with a significant fall in cardiac output and systemic blood pressure. In such patients, observance of the recommended starting dose of prazosin followed by gradual titration is particularly important. (See dosage and administration). In occasional patients with left ventricular failure, the clinical efficacy of Prazosin has been reported to diminish after several months of treatment. In these patients, there is usually evidence of weight gain or peripheral edema indicating fluid retention. Since spontaneous deterioration may occur in such severely ill patients a causal relationship to prazosin therapy has not been established. Thus, as with all patients with left ventricular failure, careful adjustment of diuretic dosage according to the patient's clinical condition is required to prevent excessive fluid retention and consequent relief of symptoms. In those patients without evidence of fluid retention, when clinical improvement has diminished; an increase in the dosage, of Prazosin will usually restore clinical efficacy.

Raynaud's Phenomenon and Raynaud's Disease: Because Prazosin decreases peripheral vascular resistance, careful monitoring of blood pressure during initial administration and titration of Prazosin is suggested. Close observation is especially recommended for patients already taking medication that are known the lower blood pressure.

Benign Prostatic Hyperplasia: Prazosin decreases peripheral vasular resistance and since many patients with this disorder are elderly, careful monitoring of blood pressure during initial administration and during adjustment of the dose of Prazosin is suggested. Close observation is especially recommended for patients taking medications that are known to lower blood pressure.

Use in Special Populations

Children: Prazosin is not recommended for the treatment of children under the age of 12 years since safe conditions for its use have not been established.

Left Ventricular Failure: Prazosin is not recommended in the treatment of left ventricular failure due to mechanical obstrcution such as aortic valve stenosis, mitral valve stenosis, pulmonary embolism and restrictive pericardial disease. Adequate data are not yet available to establish efficacy in patients with left ventricular failure due to a recent myocardial infarction.

Overdose Effects

Accidental ingestion of at least 50 mg of Prazosin in a two-year child resulted in profound drowsiness and depressed reflexes, No decrease in blood pressure was noted. Recovery was uneventful. Should overdosage lead to hypotension, support of the cardiovascular system is of first importance. Restoration of blood pressure and normalization of heart rate may be accomplished by keeping the patient in the supine position. If this measure is inadequate, shock should first be treated with volume expanders. If necessary, vasopressors should then be used. Renal function should be monitored and supported as needed. Laboratory data indicate Prazosin is not dialyzable because it is protein bound.

Therapeutic Class

Alpha adrenoceptor blocking drugs

Price: 1mg-4tk ,2mg-6tk

 Hydrochlorothiazide:

Brand: Htz(unimed),Acuren(incepta),

Preparation: 25& 50 mg tab

Indications

Edema associated with congestive heart failure, hepatic cirrhosis, premenstrual tension and oedema due to various forms of renal dysfunction (i.e. nephrotic syndrome, acute glomerulonephritis, chronic renal failure). Hypertension, either alone or as an adjunct to other antihypertensive drugs.

Pharmacology

Thiazides such as hydrochlorothiazide promote water loss from the body (diuretics). They inhibit Na+/Cl- reabsorption from the distal convoluted tubules in the kidneys. Thiazides also cause loss of potassium and an increase in serum uric acid. Thiazides are often used to treat hypertension, but their hypotensive effects are not necessarily due to their diuretic activity. Thiazides have been shown to prevent hypertension-related morbidity and mortality although the mechanism is not fully understood. Thiazides cause vasodilation by activating calcium-activated potassium channels (large conductance) in vascular smooth muscles and inhibiting various carbonic anhydrases in vascular tissue.

Dosage & Administration

Edema: initially 25 to 50 mg daily, reduced for maintenance if possible; maximum 100 mg daily.

Hypertension: 25 mg daily, increased to 50 mg daily if necessary.

Elderly: in some patients, especially the elderly an initial dose of 12.5 mg daily may be sufficient.

Children: An initial dose for children has been 1 to 2 mg per kg body-weight in 2 divided doses. Infants under 6 months may need doses up to 3 mg per kg daily.

 

Interaction

Alcohol, barbiturates or narcotics: Co-administration may potentiate orthostatic hypotension. Oral and parenteral antidiabetic drugs may require adjustment of dosage with concurrent use. Other antihypertensive drugs may have an additive effect. Discontinuation of diuretic therapy 2-3 days before the initiation of treatment with an ACE inhibitor may reduce the likelihood of first-dose hypotension. The antihypertensive effect of the drug may be enhanced in the post-sympathectomy patient.

Cholestyramine and colestipol resin: Absorption of hydrochlorothiazide is impaired in the presence of anionic exchange resin. Single doses of either cholestyramine or colestipol resins bind the hydrochlorothiazide and reduce its absorption from the gastrointestinal tract by up to 85% and 43%, respectively. Corticosteroids or ACTH may intensify any Thiazide-induced electrolyte depletion, particularly hypokalaemia. Pressor amines such as adrenaline may show decreased arterial responsiveness when used with hydrochlorothiazide, but this reaction is not enough to preclude their therapeutic usefulness. Non-depolarising muscle relaxants such as tubocurarine may possibly interact with Hydrochlorothiazide to increase muscle relaxation. Non-steroidal anti-inflammatory drugs may attenuate the diuretic and antihypertensive effects of diuretics.

Drug/laboratory tests: Because thiazides may affect calcium metabolism, Hydrochlorothiazide may interfere with tests for parathyroid function.

Contraindications

Anuria, hypersensitivity to Hydrochlorothiazide or to other sulphonamide-derived drugs, severe renal or hepatic failure, Addison’s disease, hypercalcemia, concurrent lithium therapy.

Side Effects

Gastro-intestinal system: Anorexia, gastric irritation, nausea, vomiting, cramps, diarrhoea, constipation, jaundice (intrahepatic cholestatic jaundice), pancreatitis, salivary gland inflammation.

Central nervous system: Dizziness, vertigo, paraesthesiae, headache, yellow vision.

Heamatological: Leucopenia, agranulocytosis, thrombocytopenia, aplastic anaemia, haemolytic anaemia.

Cardiovascular: Hypotension, including orthostatic hypotension.

Hypersensitivity: Purpura, photosensitivity, rash, urticaria, necrotising angiitis (vasculitis, cutaneous vasculitis), fever, respiratiory distress including pneumonitis and pulmonary oedema, anaphylactic reactions, toxic epidermal necrolysis.

Metabolic: Hyperglycaemia, glycosuria, hyperuricaema, electrolyte imbalance including hyponatraemia and hypokalaemia.

Renal: Renal dysfunction, interstitial nephritis, renal failure.

Other: Muscle spasm, weakness, restlessness, transient blurred vision, impotence. Whenever side-effects are moderate to severe, thiazide dosage should be reduced or therapy was withdrawn.

Pregnancy & Lactation

Use in pregnancy: Thiazides cross the placental barrier and appear in cord blood. The use of Hydrochlorothiazide when pregnancy is present or suspected requires, therefore, that the benefits of the drug be weighed against possible hazards to the fetus. These hazards include fetal or neonatal jaundice, thrombocytopenia, and possibly other adverse reactions, which have occurred in the adult. The routine use of diuretics in otherwise healthy pregnant women with or without mild oedema is not recommended, because their use may be associated with hypovolaemia, increased blood viscosity and decreased placental perfusion.

Use in breastfeeding mothers: Thiazides appear in breast milk. If use of the drug is deemed essential, the patient should stop breast-feeding.

Precautions & Warnings

Patients should be carefully monitored for signs of fluid and electrolyte imbalance (hyponatraemia, hypochloraemic alkalosis, hypokalaemia and hypomagnesaemia). It is particularly important to make serum and urine electrolyte determinations when the patient is vomiting excessively or receiving parenteral fluids. Warning signs or symptoms of fluid and electrolyte imbalance include: dryness of mouth, thirst, weakness, lethargy, drowsiness, restlessness, seizures, confusion, muscle pains or cramps, muscle fatigue, hypotension, oliguria, tachycardia, and gastro-intestinal disturbances such as nausea and vomiting. Hypokalaemia may develop, especially with brisk diuresis, when severe cirrhosis is present, or after prolonged therapy. Hypokalaemia can sensitise or exaggerate the response of the heart to the toxic effects of digitalis (e.g. increased ventricular irritability). Sensitivity reactions may occur in patients with or without history of allergy or bronchial asthma. Hypokalaemia may be avoided or treated in the adult by concurrent use of amiloride hydrochloride, a potassium conserving agent. It may also be avoided by giving potassium chloride or foods with a high potassium content. Diuretic-induced hyponatraemia is usually mild and asymptomatic. Dilutional hyponatraemia may occur in oedematous patients in hot weather; and, except in rare instances when hyponatraemia is life-threatening, appropriate therapy is water restriction rather than administration of salt. Thiazides may decrease serum protein bound iodine levels without signs of thyroid disturbances. Thiazides may decrease urinary calcium excretion, and may also cause intermittent and slight elevation of serum calcium in the absence of known disorders of calcium metabolism. Thiazides should be discontinued before carrying out tests for parathyroid function. When creatinine clearance falls below 30ml/min, thiazide diuretics become ineffective. Uraemia may be precipitated or increased by chlorothiazide. Cumulative effects of the drug may develop in patients with impaired renal function. If increasing uraemia and oliguria occur during treatment of renal disease, Hydrochlorothiazide should be discontinued. Thiazides should be used with caution in patients with impaired hepatic function or progressive liver disease, since minor alterations of fluid and electrolyte balance may precipitate hepatic coma. Hyperuricaemia may occur, or gout may be precipitated, in certain patients receiving thiazide therapy. Thaizide therapy may impair glucose tolerance. Increases in cholesterol and triglyceride levels may be associated with thiazide diuretic therapy. The possibility of exacerbation or activation of systemic lupus erythematosus has been reported. Latent diabetes may become manifest during thiazide administration.

Overdose Effects

The most common signs and symptoms observed are those caused by electrolyte depletion (hypokalaemia, hypochloraemia, hyponatraemia) and dehydration resulting from excessive diuresis. If digitalis has also been administered, hypokalaemia may accentuate cardiac arrhythmias. In the event of overdosage, symptomatic and supportive measures should be employed. If ingestion is recent, emesis should be induced or gastric lavage performed. Dehydration, electrolyte imbalance, hepatic coma and hypotension should be corrected by established methods. If required, give oxygen or artificial respiration for respiratory impairment.

Therapeutic Class

Thiazide diuretics & related drugs

Price: unit price-1tk

Indapamide:

Brand: Indap-SR(ubimed),Hypen SR(opsonin)

Indications

Indapamide is indicated in the treatment of essential hypertension . It is effective in treating hypertension in patients with renal function impairment, although its diuretic effect is reduced. Indapamide is also indicated for the treatment of salt and fluid retention associated with congestive heart failure.

Pharmacology

Indapamide is a diuretic antihypertensive. It appears to cause vasodilation, probably by inhibiting the passage of calcium and other ions (sodium, potassium) across membranes. It has an extra-renal antihypertensive action resulting in a decrease in vascular hyperreactivity and a reduction in total peripheral and arteriolar resistance.

Dosage & Administration

One tablet daily preferably in the morning. In more sever case Indapamide can be combine with other categories of anti-hypertensive agent. The safety and effectiveness in pediatric patients have not been established

 

Interaction

Other antihypertensive: Indapamide may add to or potentiate the action of other antihypertensive drugs.

Norepinephrine: Indapamide like thiazides, may decrease arterial responsiveness to norepinephrine.

Lithium: In general, diuretics should not be given concomitantly with lithium because they reduce its renal clearance and add a high risk of lithium toxicity.

Contraindications

This drug must not be taken in the following conditions:

  • Hypersensitivity to sulfonamides
  • Severe renal failure
  • Hepatic encephalopathy or severe hepatic failure
  • Hypokalaemia

Side Effects

Side effects of Indapamide include headache, anorexia, gastric irritation,nausea, vomiting, constipation, diarrhoea etc.

Pregnancy & Lactation

There are no adequate and well-controlled studies in pregnant women and so Indapamide is not recommended. Mothers taking Indapamide should not breast feed.

Precautions & Warnings

Monitoring of potassium and uric acid serum levels is recommended, especially in subjects with a predisposition or sensitivity to hypokalemia and in patients with gout. Although no allergic manifestations have been reported during clinical trials, patients with a history of allergy to sulfonamide derivatives should be closely monitored.

Overdose Effects

Symptoms: These could include: allergies, skin rashes, epigastric pain, nausea, photosensitivity, dizziness, weakness and paraesthesia.

Treatment: Treatment is supportive and symptomatic, directed at correcting the electrolyte abnormalities.

Therapeutic Class

Thiazide diuretics & related drugs

Price: unit price-6-9tk

Rosuvastatin:

Brand: Rosu(popular)Rosuva(square)

Indications

Rosuvastatin is indicated in-

  • Heterozygous Hypercholesterolemia (Familial and Non familial)
  • Homozygous Hypercholesterolemia (Familial)
  • Mixed Dyslipidemia (Fredrickson Type IIa and IIb)
  • Primary prevention of cardiovascular disease

Pharmacology

Rosuvastatin is a selective and competitive inhibitor of HMG-CoA reductase, the rate-limiting enzyme that converts 3-hydroxy-3-methyl glutaryl coenzyme A to mevalonate, a precursor of cholesterol. Rosuvastatin produces its lipid-modifying effects in two ways. First, it increases the number of hepatic LDL receptors on the cell surface to enhance uptake and catabolism of LDL. Second, Rosuvastatin inhibits hepatic synthesis of VLDL, which reduces the total number of VLDL and LDL particles.

Dosage

Dose range: 5-40 mg once daily. Use 40 mg dose only for patients not reaching LDL-C goal with 20 mg

HoFH: Starting dose 20 mg/day.

Pediatric patients with HeFH: 5-10 mg/day for patients 8 to less than 10 years age, and 5-20 mg/day for patients 10 to 17 years of age.

Pediatric patients with HoFH: 20 mg/day for patients 7 to 17 years of age.

 

Administration

Rosuvastatin can be taken with or without food, at any time of day.

 

Interaction

Remarkable drug interactions of Rosuvastatin are-

  • Cyclosporine: Combination increases Rosuvastatin exposure. Rosuvastatin dose should be limited to 5 mg once daily.
  • Gemfibrosil: Combination should be avoided. If used together, Rosuvastatin dose should be limited to 10 mg once daily.
  • Lopinavir/Ritonavir or atazanavir/ritonavir: Combination increases Rosuvastatin exposure. Rosuvastatin dose should be to 10 mg once daily.
  • Coumarin anticoagulants: Combination prolongs international normalized ratio (INR). Stable INR should be achieved prior to starting Rosuvastatin. INR should be monitored frequently until stable upon initiation or alteration of Rosuvastatin therapy.
  • Concomitant lipid-lowering therapies: Use with fibrates and niacin products may increase the risk of skeletal muscle effects.

Contraindications

Rosuvastatin is contraindicated if-

  • Known hypersensitivity to product components
  • Liver disease, which may include unexplained persistent elevations in hepatic transaminase levels
  • Pregnant women and women who may become pregnant
  • Nursing mothers

Side Effects

Rosuvastatin is generally well tolerated. The most frequent adverse events thought to be related to Rosuvastatin were headache, myalgia, constipation, asthenia, abdominal pain and nausea.

Pregnancy & Lactation

The safety in pregnant women has not been established. It is not known whether Rosuvastatin is excreted in human milk or not.

Precautions & Warnings

Skeletal muscle effects (e.g., myopathy and rhabdomyolysis): Risks increase with use of 40 mg dose, advanced age (>65 year), hypothyroidism, renal impairment and combination use with cyclosporine, lopinavir/ritonavir, atazanavir/ritonavir or certain other lipid-lowering drugs. Patients should be advised to promptly report unexplained muscle pain, tenderness or weakness. Rosuvastatin can be discontinued if signs or symptoms appear.

Liver enzyme abnormalities and monitoring: Persistent elevations in hepatic transaminases can occur.

Liver enzymes should be monitored before and during treatment

Use in Special Populations

Use in children: The safety and effectiveness in pediatric patients have not been established.

Therapeutic Class

Other Anti-anginal & Anti-ischaemic drugs, Statins

 Price: 5 mg-10tk ,10mg-20tk