10. CARDIOVASCULAR DRUGS                                                                                 

10.1.Anti Anginal Drugs:

 

                                                        ISOSORBIDE DINITRATE

 

General information

 

Drug Code                  Preparation                                        Strength

       86                         Tab. Isosorbide Dinitrate                      5 mg.

                                             

Description of the Drug:

            Isosorbide dinitrate is an organic nitrate used as a anti anginal agent.

 

Mode of Action

In the tissues , isosorbide dinitrate is denitrated and nitrous oxide (NO) is released. It acts on vascular smooth muscle and is a potent vasodilator . Venous smooth muscle is more sensitive than arterial smooth muscle. This results in a peripheral pooling of blood, decreased venous return in the hear and also a decrease in the peripheral arterial resistance (reduces preload and after load ). Coronary vasodilatation is also produced. All these effects results in decreased myocardial oxygen demand and relief of anginal  symptoms. In congestive cardiac failure, its reduces preload and ventricular filling pressures, hence reducing symptoms and increasing exercise capacity in congestive cardiac failure patients. It also decreases platelet aggregation.

 

Pharmacokinetics:

It is absorbed from the GIT but due to extensive first passmetabolism, bioavailability is as low as 10 % . Hence usually it is administered sublingually, which bypasses the first  pass effect and bioavailability increases by 50 % . Onset of action is few minutes after administration. Duration of effect is 15 –30 minutes. When longer duration of action is needed, transferal or buccal routes do administration or slow release preparations can be used. It is excreted as glucuronide conjugates in the urine.

 

Clinical Information

 

Indication

·    Angina pectoris – management of acute attack. Extended release preparation can be used in the chronic management of angina.

·    Prophylaxis of angina – prevention of attack by taking before performing activities, which can precipitate angina.

·    Congestive cardiac failure – for decreasing preload and ventricular filling pressures and symptom relief.

·    In cardiomyopathies – improves ventricular function by increasing coronary blood flow and relief of ischaemic symptoms.

 

Dosage

·    In acute angina : 2.5 – 10 mg sublingually.

·    In congestive cardiac failure 5 –15 mg sublingually every 2 –3 hours.

·    Angina pectoris orally: 30 – 120 mg/day in divided doses.

·    In unstable angina or unresponsive left ventricular failure 2 –12 mg/hours.

 

Routes of Administration      Sublingual, Oral.

 

Contraindications

·    Should not be used in patients with severe hypotension (systolic BP <90 mm Hg), hypovolemia, marked anemia constrictive pericaditis and  increased intracranial pressure. Venous dilation and reduction of per load may impair cardiac. Output.

·    Hepatic and renal failure.

·    Patients with electrolyte disturbances.

·    Recent incidence of hypothermia.

·    Closed angle glaucoma.

·    Head trauma, cerebral haemorrhage.

 

Precaution / Practice Points

·    With continuous exposure the effect of the drug decreases and tolerance occurs (tachyphylaxis ) – dosage adjustments to be done so that an appropriate nitrate free interval is given for effective action of next administered dose.

·    Nitrate therapy may aggravate angina caused by outflow obstruction states like hypertrophic obstruction cardiomyopathy, by excessively reducing venous return to the heart.

·    Instruct patients that headache appearing after nitrate therapy is actually a marker of the activity of the drug and aspirin, paracetamol can be used for relief without affecting the antianginal activity of the drug.

·    Relation to alcohol – peripheral vasodilatory effects are increased and patients may experience giddiness on assuming standing posture. It may even progress to syncope and loss of consciousness . Hence, patients should be advised to abstain from alcohol.

·    Administration Instruction;

-  It can be chewed and swallowed.

 

Drug Interactions

Non fatal:

Effectiveness isosorbide dinitrate may be reduced if given along with anticholinergics, or drugs with anticholinergic effects due to decreased oral secretions.

 

Adverse Effects

            Dose related.

Common effects:

·    Headache – throbbing type due to cerebral vasodilatation.

·    Postural hypotension – light-headedness and giddiness on standing.

·    Reflex tachycardia experienced as palpitations by the patient.

Rare effects:

·    Syncope can occur.

·    Hypersensitivity.

·    Drug rashes may occur.

 

Drug Toxicity

·    Increased intracranial pressure – severe headache, vertigo, confusion, diaphoresis, followed by ear block or bradycardia. In severe poisoning (> 1 mg/kg ) methaemoglobinemia can occur because nitrate ions from isosorbide dinitrate, reduce  Hb to methaemoglobin. Clinically, in pressure of normal PO2 in blood gas analysis, patient exhibits signs of impaired oxygen delivery.

 

Treatment of Toxicity

·    The effects are due to arterial hypovolemia. Hence, measures to increases control fluid volume – I.V. fluids, elevation of extremities is advocated vasopressors are not recommended.

·    Treatment of methaemoglobinemia – I.V. methylene blue (1 – 2 mg/kg.).

 

Storage

Store in airtight containers at a temperature not exceeding 15oC away from light.

 

Shelf Life                     33     months.

 

 

DILTIAZEM

 

General information

 

Drug Code                     Preparation                               Strength

       98                            Tab. Diltiazem                                        30 mg.

 

Description of the Drug

Diltiazem is calcium channel blocker belonging to the pondihydropyridine group.

 

Mode of Action

It inhibits influx of calcium in vascular and cardiac smooth muscle. Hence, it produces relaxation of vascular smooth muscle and a decrease in the peripheral arterial resistance and tone. On the heart, it relieves coronary artery spasm, acts as a coronary vasodilator and increases coronary blood flow. It also decreases myocardial oxygen demand by means of decreasing heart rate and myocardial contractility.

 

Pharmacokinetics

It is rapidly and completely absorbed from the GIT . It undergoes extensive first pass hepatic metabolism. It is excreted in the urine and bile. Onset of action is 30 minutes after administration and plasma half-life is 6 hours.  It is secreted in the breast milk.

 

Clinical Information

 

Indications

·    Hypertension – either alone or in conjunction with other drugs.

·    Angina – chronic stable angina, as well as variant angina and unstable angina.

 

Dosage

For angina:

60 – 3 times daily gradually increased are 1 –2 day intervals, in increments of 30 mg. Dosage requirement vary considerably, some requiring 360 mg/daily while others need 480 mg.day.

As an anti hypertensive :

60 –120 mg twice daily, increased at 14 days intervals to a maximum of 360 mg. The dose should not be increased if heart rate drops below 50 beats/minute.

 

Route of Administration      Oral:

 

Contraindications

·    Sick sinus syndrome, pre-existing second or third degree atrio ventricular block.

·    Hypotension or cardiogenic shock.

·    Patients with acute myocardial infraction and left ventricular dysfunction.

·    Know hypersensitivity to the drug.

·    Congestive cardiac failure.

·    Pregnancy and lactation.

 

Precaution / Practice Points

·    Reduction of dosage is advised in impaired liver function.

·    Adjust the dose if administrated along with drugs which inhibit or induce the hepatic microsomal enzyme system.

·    When administered for a long period of time – hepatic parameters to be monitored – SGOT, SGPT, LDH etc., since hepatic damage has been reported with prolonged use.

·    Not advised in lactating mothers , because it is secreted in breast milk.

·    With caution in impaired left venricular function.

·    Administration Instruction:

-     Administer by schedule. Do not abruptly change dosing intervals or time of administration.

 

Drug Interactions

Potentially fatal:

·    With beta-blockers, increased serum levels and effects of beta-blockers are seen, excessive myocardial depression may occur.

·    With digitalis, diltiazem increases serum levels and toxicity of digoxin. Hence, adjustment of dose should be done depending on clinical response.

·    Enhances myocardial depressent effect of amiodarone, antiarrythmics, other calcium channel blockers and may cause bradyarrythmias , AV block etc.

·    Plasma concentration and toxicity of phenytoin and carbamazepine may be increased.

·    Increased the toxicity of theophylline and may precipitate convulsions.

·    Increase plasma levels and toxicity of cyclosporine.

·    Increase neurotoxicity of lithium.

Non fatal:

·    Enhances the effects of alcohol, other antihypertensives, antipsychotics, diuretics and volatile anaesthetics.

·    Rifampicin increased the clearance of diltiazem and may reduce therapeutic efficacy.

·    Increase the serum levels of tricyclic antidepressants like imipramine.

·    Enhances neuromuscular blocking effects of nondepolarishing muscle relaxants and may prolong recovery from their effects.

 

Adverse Effects

Common effects:

·    GI disturbances – nausea, anorexia, abdominal pain etc.,

·    Headache, dizziness, asthenia.

·    First-degree atrio ventricular block and bradycardia.

·    Flushing , edema of ankle.

 

Rare Effects :

·    Arrhythmiss – bradyarrhymiss, complete heart block.

·    Hepatic damage – elevation of enzymes like SGOT, SGPT and alkaline phosphatase, especially when drug is used for long periods of time.

·    Skin reaction – photosensitivity, exfoliative dermatitis, erythema multiforme etc.,

·    CNS effects – depression.

 

Drug Toxicity

Results in excessive hypotension, heart block, cardic, arrest and cardiac failure.

 

Treatment of Toxicity

·    Atropine can be used to treat bradycardia.

·    Fluids and vasopressors to maintain B.P.

·    Inotropic agents can be used to reverse cardiac depressant effects.

·    Temporary pacing can be employed.

 

Storage

            Store in airtight containers, protect from light.

 

Shelf Life                          3    years.

 

 

 

NIFEDIPINE

 

General information

 

Drug Code                  Preparation                                     Strength

     109                         Tab. Nifedipine                     10 mg.

     261                         Cap. Nifedipine                                5 mg.

 

Description of the drug

Nifedipine is a calcium channel blocker belonging to the dihydropyridine group.

 

Mode of action

Nifedipine inhibits transmembrane influx of calcium ions into cardiac and vascular smooth muscle. It causes coronary  vasodilation, relieves coronary artery spasm, induces peripheral vasodilatation and decreases myocardial oxygen consumption by decreasing the after load. However, these actions elicit a reflex sympathetic response and reflex tachycardia can occur . It does not have clinically significant effects on atrio ventricular conduction. It also is a potent inhibitor of platelet aggregation.

 

Pharmacokinetics

It is rapidly and completely absorbed from the GIT and undergoes extensive hepatic first – pass metabolism. Bioavailability increases on sublingual administration. Execreted in the urine almost entirely as inactive metabolites. Onset of action is 5 –20 minutes after oral ingestion, earlier effects if bitten and swallowed or sublingually administered. Half-life is 2 hours.

 

Clinical Information

 

Indications

·    Angina – chronic stable angina , vasopastic angina.

·    Hypertension – chronic therapy, as well as in the management of hypertensive emergencies.

·    Peripheral vascular diseases (Raynaud’s disease).

·    Primary pulmonary hypertension.

 

Dosage

            Therapy should be inividualized for each patient.

Initial dose – 10 mg t.d.s.gradually increased till relief of anginal symptoms occur.

 

Route of Administration       Oral, sublingual.

 

Contraindications

·    Recent myocardial infraction (within one week of an infract).

·    Increasing anginal symptoms in the setting of imminent myocardial infraction.

·    Sick sinus syndrome, second or third degree AV block.

·    Hypersensitivity.

 

Precautions / Practice Points

·    The dose should be reduced in patients with hepatic impairment.

·    When therapy is being initiated, dose adjustments should be made under medical supervision, depending on clinical response.

·    Use with caution inpatients with outflow obstruction, congestive failure, severe left ventricular dysfunction.

·    Some patients may experience paradoxical  increase in anginal symptoms, and even may proceed to myocardial infraction. Discontinue immediately if symptoms worsen.

·    Use with caution in diabetes mellitus – may impair glucose tolerance.

·    Instruct patients to abstain from alcohol (enhanced hypotensive effects).

·    Administration Instruction:

-     Can be placed under the tongue or bitten to release the liquid contents and then swallowed.

 

Drug Interaction

Potentially fatal:

·    Plasma levels of digoxin are increased by nifedipine (toxicity may occur.)

·    Cardiac depression may be excessive. Hypotension and heart failure may be precipitated when concomitantly administered with beta-blockers.

·    Plasma levels of phenytoin and theophyline are increased (toxicity may occur).

·    Quinidine may increase nifedipine levels and toxicity.

Non fatal :

·    Rifamption carbamazepine, barbiturates increase clearance of nifedipine.

·    Cyclosporine may increase levels of nifedipine.

·    Nifedipine enhances the action of nondepolarising nevromuscular blocking agents.

·    Isoflurane and other volatile anaesthetic, diuretics, other anti hypertensive agents and alcohol enhance the hypotensive effect of nifedipine.

 

Adverse Effects:

Common effects:

·    Headache, giddiness, light headache ness (due to decrease in B.P).

·    Peripheral edema, palpitations (due to reflex tachycardia ) and postural hypotension.

·    Nausea, heat burn.

Rare effect:

·    Syncopal episodes, precipitaion of congestive cardiac failure, myocardial, infraction, worsening of angina.

·    Hypersensitivity reactions – skin eruptions, exfoliative dermatitis and angioedema.

·    Increased frequency of micturition.

·    Gum hyperplasia.

·    Parasphisias, myalgia, tremors.

·    Constipation and abdominal pain.

·    Nervousness, mood changes, somnolence.

 

Drug Toxicity

Severe hypotension, bradycardia, second or third degree heart block, confusion , stupor, nausea, vomiting, metabolic acidosis and cardiovascular collapse may occur.

 

Treatment of Toxicity

·    Gastric lavage and emesis.

·    Continuous monitoring of ECG, CVS status, use of I.V. fluids and vasopressors to maintain B.P., elevation of extremities and head down position.

·    I.V. calcium can be tried, judiciously.

 

Storage

            Store in airtight containers. Protect from light.

 

Shelf    Life          2    years.

 

 

 

10.2.                      Anti Dysarrhythmic Drugs

 

VERAPAMIL HCI

General information

 

Drug Code                              Preparation                             Strength

       101                                   Tab.Verapamil              40 mg.

 

Description of the Drug

It is a synthetic derivative of palavering. It is a calcium channel blocker and belongs to class IV of antiarrhythmic drugs.

 

Mode of Action

Verapamil binds to the calcium influx channels and decreases the entry of calcium into the cells. Vascular smooth muscle and cardiac cells are more sensitive to this effect. Hence, clinically, the following effects are seen -

·    Peripheral vasodilation – decrease in arterial tone, blood pressure.

·    Reduction in myocardial contractility (and hence myocardial oxygen demand).

·    Slowing of heart rate and conduction velocity at the AV mode.

·    Coronary vasodilatation and relief of coronary artery spasm. Varapamil also possesses a non specific anti adrenergic effect and hence does not produce reflex tachyardia.

 

Pharmacokinetics

90 % absorbed from the GIT but undergoes first pass metabolism in liver. Hence, bioavailability is only 20 – 35 %. Onset of action is 30 minutes after oral ingestion . Half-life is 6 hours. It is metabolized in the liver and excreted in the urine and some amount in the faeces. Secreted in the breast milk.

 

Clinical Information:

 

Indications

·    Arrhythmias :

-     Used to slow the  ventricular rate in supraventricular tachyarrhythmias like artrial flutter, atrial fibrillation.

-     Paroxysmal surraventricular tachycardia – to reduce frequency of episodes.

·    Hypertension.

·    Angia :

-     It can be used in effort angina, unstable (crescendo angina ) as well as variant angina (vasospastic).

 

Dosage

·    Angina : 80 – 120 mg t.d.s

·    Arrhymias : 40 – 120  mg t.d.s

·    Hypertension  : initial dose is 80 mg t.d.s (individualize the maintenance dose depending on clinical response), upto a maximum of 240 – 360 mg/day in 3 divided doses.

 

Route of Administration          Oral

 

Contraindications

·    Left ventricular dysfunction and history of cardiac failure can precipiate pulmonary edema and congestive cardiac failure.

·    Hypotension and cardiogenic shock.

·    Bradycardia, sick sinus syndrome, II or III degree AV blocks, patients with Wolff – Parkinson – white syndrome or Lawn – ganong – Levine syndrome can produce complete heart block or cardiac arrest door due to its cardiac depressant action.

·    Patients with known hypersensitivity.

·    Porphyria.

 

Precautions / Practice Point

·    Reduction of dosage is advised in patients with impaired liver function and renal function.

·    Use with caution in conditions with outflow tract obstruction. As in HOCM, cardiac output may be decreased and CCF precipitated.

·    Muscular dystrophies like Duchenne’s muscular dystrophy. Verapmil can decrease neural muscular transmission. In cardiomyopathies, left ventricycular failure may occur.

·    Use with Caution in pregnancy, lactation and children.

·    Avoid in the acute phase of myocardial infarction.

·    Do not administer beta-blockers and verapamil together unless absolutely essential.

·    Administration Instruction:

- Take with or after food.

 

Drug Interactions

Potentially fatal:

·    Concomitant therapy with beat blockers and other antihypertensives can lead to additive depressant effect on the heart rate, conduction and contractility.

·    Digoxin effects are increased with verapamil . Hence, patients should be monitored for digitals toxicity and dose adjustments to be done.

·    Increase the cardiac effects of amiodarone, disopyramide and flecanamide (Hence, risk of AV blocks, excessive, bradycardia and myocardial depression) and quinidine ( Increases serum levels and toxicity).

·    Increases serum levels and toxicity of theophyline.

·    Increases serum levels and toxicity of cycloporin.

Non fatal:

·    Alcohol , volatile anaesthetic, diuretics and other antihypertensives enhances hypotensive effects.

·    Alfampicin increases the metabolism of verapamil.

·    Increases serum levels of imipramine.

·    Effects of antiepileptics like carbamazepine are enhanced.

·    Prolongs action of nondepolarising muscle relaxants.

 

Adverse Effects

Common effects:

·    Constipation.

·    Bradycardia.

·    Nausea, vomiting.

·    Dizziness, lightheadedness, fatigue, malaise, headache,

·    Flushing and edema.

Rare effects:

·    Elevation of liver enzymes.

·    Allergic manifestations – dermatitis, urticaria, steven Johnson’s syndrome.

·    Myalgia,  arthralgia and parasthesias.

·    Gingival hyperplasia.

·    Gynaecomastia.

 

Drug Toxicity

·    Severe braducardia, complete heart block, cardiac arrest, profound hypotension, loss of peripheral pulse can occur.

·    Non cardiac symptoms – confusion , stupor, severe nausea and vomiting.

 

Treatment of Toxicity

·    Continuous ECG monitoring.

·    Beta adrenergic stimulation with IV norepinephrine or atropine to reverse cardia depression.

·    IV calcium salts – infusion of calcium gluconate 10 –20 ml of 10 % solution may increase calcium influx across membrane.

·    Treat hypotension with vasopressors like metaraminol, dopmine etc.,

·    Temporary cardiac pacing for arrhythmias  and heart blocks.

 

Storage

             Store in airtight containers, Protected from light.

 

Shelf Life             2   years.

 

 

ATENOLOL

 

General information

 

Drug Code                              Preparation                             Strength

      104                                    Tab.Tenolol                              50 mg.

 

Description of the Drug

            Atenolol is a beta 1 selective (cardioselective ) blocking agent.

 

Mode of Action

It is a competitive inhibitor of the effects of catecholamines at beta 1 adrenergic receptor sites. It has no membrane stabilizing effect. It produces a decrease raty cardiac output with a reduction in blood pressure.

 

Pharmacokinetics

It is incompletely absorbed from the GIT (bioavailability is only 50 % ). Peak plasma concentration is reached within 2 –4 hours. Plasma half-life is 6 –7 hours, but effective for 24 hours . Full therapeutic effect is seen 1 –2 weeks after initiation of therapy. It is excreted by the kidney.

 

Clincial Inforamtion:

 

Indications

·    In treatment of hypertension – alone or in combination with other drugs.

·    In treatment of angina pectoris.

 

Dosage

            Hypertension : 50 to 100 mg/day.

            Angina pectoris : up to 200 mg/day.

 

Route of Administration     Oral:

 

Contraindications

·    Patients with congestive cardiac failure, caediogenci shock, left ventricular dysfunction.

·    Sinus bradycardia, heart blocks – II and III degrees.

·    Pregnant and nursing mothers.

 

Precautions / Practice Points

·    In patients with history of congestive cardiac failure, which has been controlled by medication, beta-blockers may precipitate congestive cardiac failure.

·    Abrupt withdrawal of beta-blockers can result in angina myocardial infraction, ventricular arrhythmias and death.

·    Atenolol in high does can block beta 2 receptors also. Hence, when used in asthmatics or patients with COPD, lowest possible dose must be employed.

·    In diabetics, it may mask symptoms and sings of hypoglycemia  and subsequent glucagons response.

·    When used in thyrotoxicosis – abrupt withdrawal may precipitate  a thyroid storm, hence withdraw gradually.

·    The dose has to be reduced in patients with hepatic or renal dysfunction.

 

Drug Interaction

Potentially fatal:

·    When combined with calcium channel blockers like verapamil dilitiazem or amiodarone, disopyramide – excessive depressent action leading to bradycardia or complete heart block can occur.

·    When used with catecholamine depleting drugs like reserpine, excessive therapeutic effect can occur, due to a decrease in basal sympathetic tone.

·    Increased risk of lignocaine, bupivacaine toxicity.

·    Risk of arryhythmias increased with astemizole, terfenadine.

·    Risk of excessive digoxin effects and toxicity.

·    Antagonism of the therapeutic effects of theophyline.

 

Non-fatal;

·    Barbiturates, phenytoin, benzodiazepines reduce the effects of atenolol.

·    Enhanced hypotensive effects with alcohol, ACE inhibitors, diurtics, anesthetics, clonidine and other antihypertensives.

·    Rifampion increase the clearance of atenolol.

·    Enhances effects of muscle relaxants.

·    Oral Contraceptives and steroids antagonize hypotensive effects of atenolol.

 

Adverse Effects

Common effects:

·    Bradycardia

·    Coldness of extremities, postural hypotension.

·    Nausea, vomiting , diarrhoea or constipation, abdominal cramps.

Rare effects:

·    CNS effects dizziness, fatigue, vertigo, light headedness, insomnia etc.,

 

Drug Toxicity

Lethargy, respiratory distress, wheezing, bradycardia, conduction defects, cardiac arrest, congestive cardiac failure, hypotension and hypoglycemia may occur.

 

Treatment of Toxicity

·    Emesis, gastric lavage or activated charcoal for gastro intestinal decontamination.

·    Atropine for bradycardia, vasopressors for hypotension, aminophyline for bronochospasm, IV glucose for hypoglycemia to be given if need arises.

 

Storage

            Store in a cool, dark place.

 

Shelf Life         2   years.

 

 

PROPRANOLOL

           

General information

 

Drug Code                              Preparation                             Strength

       110                                   Tab.Propranolol                       40 mg.

 

Description of the Drug

             Asynthetic, nonselective beta-blockers.

 

Mode of Action

Competitive blockade of beta-receptors therapy, blocking chronotropic and inotropic responses to beta-adrenergic stimulation. It therapy reduces myocardial oxygen demand (cardiac depressant action) and cardiac output. It has a membrane stabilizing action and also inhibits renin release.

 

Pharmacokinetics

It is almost completely absorbed from the GIT but subjected to first pass metabolism and considerable hepatic tissue binding. Onset of action is 1 – 1.5 hours after ingestion and the effects lasting for 4 hours. It is metabolized in the liver and the metabolites are excreted in the urine together with only a small proportion of the unchanged drug.

 

Clinical Information

 

Indications

·    Management of hypertension.

·    Long-term management of angina pectoris.

·    As an antiarrhythmic in

-     supra ventricular tachyarrhythmias.

-     Paroxysmal atrial tachycardia, especially if associated with digitalis toxicity. 

-     Tachycardia sinus tachycardia.

-     Trachycardia and arrhythmias due to thyrotoxicosis.

-     Atrial flutter,  atrial fibrillation when digitalis is contraindicated.

-     Ventricular tachycardias especially if associated with digitalis or catecholamine excess and persistent premature ventricular extrasystoles.

·    To reduced  mortality in myocardial infarction – in patients who have survived the acute phase.

·    Migraine – prophylaxis of attacks.

·    Essential tremors – benign or familial variety.

·    Hypertrophic sub aortic stenosis.

·    Pheochromocytoma – as an adjunct to alpha blockade.

 

Dosage

Adult:

·    Hypertension: 40 – 80 mg twice daily.

·    Angina: (individualize the dose) 80 – 320 mg in 2 –3 divided doses.

·    Arrhythmias : 10 – 30 mg, 3 –4 times a day.

·    For temporary suppression of thyrotoxicosis : 10 –40 mg. 3 times daily.

·    Post myocardial infarction: 180 – 240 mg – 2 –3 times a day.

·    Migraine : (individualize the dose )  160 – 240 mg /day.

Children:

1 mg/kg/day.

 

Route of Administration       Oral:

 

Contraindications

·    Cardiogenic shock.

·    Sinus bradycardia.

·    Congestive cardiac failure.

·    Bronchial asthma.

·    Relative Contraindications:

-     Diabetics.

-     Patients with peripheral vascular disease.

-     Pregnant and nursing mothers.

 

Precaution / Practice Points

·    Use with caution in patients with compromised circulatory function as it can precipitate congestive cardiac failure.

·    In diabetic patients, symptoms and signs of hypoglycemia may be suppressed by beta-blockers and also delay in recovery of normal blood glucose levels occurs.

·    In thyrotoxicosis and patients with angina, who are receiving beta-blockers, withdrawal should be very gradual for the fear of precipitating symptoms.

·    Use with caution in hepatic and renal dysfunction.

 

Drug Interactions

Potentially fatal:

·    Concomitant administration with calcium channel blockers, amiodaraone, disopyramide, quinidine any excessively depress myocardial contractility and conduction.

·    Catecholamine depleting drugs like reserpine may reduce the resting  sympathetic tone of the body, resulting in marked bradycardia, syncope, etc.,

·    Increase risk of lignocaine, bupivacaine toxicity.

·    Risk of  arrhythmias increased with astemizole and terfenadine.

·    Digoxin effects and toxicity are increased by  propranolol.

·    Antagonism of the therapeutic effects of theophyline.

Non fatal:

·    Barbiturates, phonytion and benzodiazepines reduce the effects of propranolol.

·    Chlorpromazine increases plasma propranolol levels.

·    Enhanced hypotensive effects with alcohol, ACE inhibitors, diuretics, anaesthetics, clonidine and other anthihypertensives.

·    Rifampicin increases clearance of proponolol.

·    Enhances effects of muscle relaxants.

·    Oral contraceptives and steroids antagonize hypotensive effects.

 

Adverse Effects

Common effects:

·    Coldness of extremities, fatigue, malaise etc.,

·    Nausea, vomiting, diarrhoea, abdominal cramps etc.,

Rare effects:

·    Heart failure, bradycardia, atrio ventricular block, hypotension.

·    CNS effects include depression, insomnia, lassitude, fatigue, disorientation, and dizziness.

 

Drug Toxicity

·    CVS effects – bradycardia, heart block , hypotension, cardiac failure.

·    Gastric lavage or emesis if recently ingested.

·    Symptomatic therapy:

      For bradycardia – stropine 0.25 – 1 mg.

For failure  - digitalis and diuretics.

For hypotension – isoproterenol , epinephrine.

For hronchospasm – aminophyline.

           

Storage

            Store in a cool, dark place.

 

Shelf Life                     3    years.

 

 

10.3.          Anti Hypertensive Drugs

 

AMLODIPINE

 

General information

 

Drug Code                              Preparation                             Strength

      489                                    Tab.Amlodipine                        5 mg.

 

Description of the Drug:

            Amlodipine is a dihydropyridine calcium channel blockers.

 

Mode of Action

Amlodipine inhibits the transmembrane calcium influx with greater effects on vascular smooth muscle than on cardiac muscle. Its main action is to cause peripheral arterial vasodilatation and therapy a reduction in after load and blood pressure. Hence, it reduces  myocardial oxygen demand more by an indirect effect than direct on cardiac muscle. Reflex tachycarida does not occur due to slow onset of action.

 

Pharmacokinetics

Well-absorbed following oral administration. It is extensively metabolized and metabolites are excreted in the urine. Onset of drug action is gradual. It is a long acting drug with half-life of about 30 – 50 hours. Steady plasma levels are reached, 1 week after imitation of treatment. Thereafter effects of   a single dose lasts for about 24 hours (hence, once a day dosing is sufficient.).

 

Clinical Information

 

 

Indication

·    Hypertension:

Long-term management of hypertension. May be used alone to in combination with other drugs.

·    Management of chronic stable angina.

 

Dosage

            Hypertension and angina: 5 mg daily (single dose).

            The dose may be increased to 10 mg daily if necessary.

 

Route of Administration    Oral.

 

Contraindications

·    Known hypersensitivity.

·    Cardiogenic shock.

·    Unstable angina.

·    Significant aortic stenosis

·    Pregnancy and  lactation.

 

Precautions / Practice Points

·    Redcution of dosage is advised in hepatic failure.

·    Some patients with severe conronary obstruction may experience a paradoxical increase in anginal  symptoms. Hence discountinue the drug if symptoms are increasing.

·    Use with caution in left ventricular dysfunction, sick sinua syndrome, cardiomyoptheies.

·    Withdraw gradually to prevent a rebound increase in angina and other symptoms.

·    Use with caution in the elderly risk of side effects are more.

·    Administer with beta-blockers and digoxin only if absolutely necessary.

·    Administration Instruction:

-     Once daily doses are sufficient. Do not alter time of administration or dosing intervals abruptly.

 

Drug Interactions

Potentially fatal:

·    With digoxin, beta-blocker may cause excessive myocardial depression. Hypotension, heart block and cardiac arrest may occur.

·    Plasma levels of theophyline are increased and may cause toxicity.

·    Cyclosporin levels and toxicity are increased.

Non fatal:

·    Enhanced hypotensive effects with anaesthetics, other  antihypertensives, alcohol and diuretics.

·    Rifampicin  increase clearance of amilodipine.

·    Plasma phenytoin levels are increased.

·    Effects of amilodipine may be decreased by barbiturates and carbamazepine.

 

Adverse Effects

Common effects:

Usually well tolerated. Adverse effects which may be seen are

·    Flushing, palpitations and peripheral edema.

·    Dizziness, headache, hypotension.

Rare effects:

·    Prutins, rashes, urtocardia.

·    Nausea, abdominal pain.

·    Muscle pain, weakness, paraesthesias etc.

·    Gum hyperplasic.

·    Importance

·    E, increased urinary frequency.

·    Altered  Liver functions elevate

·    Ion of serum liver

·    Enzymes jaundice.

·    Gynaecomastia.

 

Drug Toxicity

            Myocardial depression, heart blocks and cardiac arrest may occur.

 

Treatment of Toxicity

·    Gastric lavage, emesis.

·    Continuous CVS monitoring, presser agents and IV fluids to combat hypotension. IV calcium can be tried in refractory cases.

·    Symptomatic treatment.

 

Storage

            Store in airtight containers. Protect from light.

 

Shelf Life                       2    years.

 

METHYLDOPA

 

General information

 

Drug Code                              Preparation                             Strength

       107                                   Tab. Methyldopa                      250 mg.

 

Description of the Drug

Methyldopa is a centrally acting alpha – 2 adrenergic agonist that reduce sympathetic tone and produces a fall in blood pressure.

 

Mode of Action

It is decarboxylated in the  CNS to  alpha – methyladrenaline ( a false neuro transmitter replacing norepinephrine) which is thought to stimulate alpha –2 adenoreceptors, resulting in a reduction in the sympathetic tone and fall in the B.P.  It has an inhibitors action on plasma renin activity. It reduces the tissue concentration of adernaline, noradrenaline, dopamine and serotonin.

 

Pharmacokinetics

It is incompletely absorbed from the GIT and biaovailability is only 25 %> Hence large doses are necessary. Onset of action 2 – 4 hours after ingestion and lasts for 24 hours. It is extensively metabolized and excreted in the urine. It crosses the blood brain barrier and is decarboxylated in the CNS to its active metabolites. It crosses the placenta and small amount are secreted in breast milk.

 

Clinical Information

 

Indications

            Mild to moderate hypertension in pregnancy.

 

Dosage

Adult  - Initial dose: 250 mg 2 – 3 times daily for 2 years to a  maximum dose of  3

              gram daily.

              Maintenance dose – 0.5 – 2 gram/daily depending on response.

Children – 10 mg/kg/day.

 

Route of Administration   Oral:

 

Contraindications

Absolute

·    Active hepatic disease, cirrhosis.

Relative

·    Renal failure – patients are more sensitive to the antihypertensive effects of methyldopa.

·    Hypersensitivity.

·    Co – administration with MAOIs.

 

Precautions / Practice Points

·    Use with caution in patients with impaired kidney or liver function, with a history of haemolytic anaemia and parkinsonism.

·    Periodic blood counts and liver function to be tested at intervals during the first 6 – 12 weeks of therapy.

·    It may cause sedation. Instruct the patient not to drive or operative machinery and to obtain from alcohol.

·    Can be given with other antihypertensives and diuretics but limit to 500 mg/day.

·    Administration Instructions:

-     Give at the same time every day and administer round  the clock to prevent variations in serum levels and response.

 

Drug Interactions

Potentially fatal:

·    Lithium toxicity may be precipitated.

Non fatal:

·    Diuretics, other antihypertensives, anaesthetics, anxiolytics, L-dopa, muscle relaxants – hypotensive effects are enhanced.

·    Tricyclic antidepressant, analgesics, steroids, estrogen and progesterone  antagonize the effects of methyldopa.

·    Neurolpetics – haloperidol increases the CNS side effects .

 

Adverse Effects

Common effects:

·    CNS – drowsiness and sedation are the most important adverse effects. Other effects are dizziness, headache, weakness, fatigue, impaired concentration, memory depression and disturbed sleep. Very rarely choreoathetotic movements, paraesthesias, parkinsonism have also been reported.

·    Blood – haemolytic anaemia, positive coombs test.

·    Endocrine – hypeprolactiemia, gynaecomastia, breast enlargement, galactorrhoea, and  amenorrhoea due to central dopaminergic inhibition.

·    Hypersensitivity – drug fever, (IV like syndrome, eosinophilia, diaturbance of liver function, hepatic necrosis, skin rashes.

Rare effects:

·    CVS – angina and bradycardia may occur.

·    GIT  - nausea, vomiting and diarrhoea.

 

Drug Toxicity

A dose of 2.5 grams produces acute hypotentison sedation, constipation, nausea, vomiting and bradycardia.

 

Treatment of Toxicity

·    Gastric lavage or emesis.

·    Symptomatic – I.V. infusion of vasopresors to combat hypotension.

·    Place the patient in the supine position with the foot rasised.

·    Monitor B.P.  Electrolytes, CVS status continuously.

 

Storage

            Protect from light.

 

Shelf  Life           18   months.

 

 

ENALAPRIL

 

General information

 

Drug Code                              Preparation                             Strength

      259                                    Tab. Enalapril                           2.5 mg.

 

Description of the Drug

Enalapril is a prodrug and it’s metabolite – enalaprilat is an angiotensin converting enzyme inhibitor.

 

Mode of Action

Enalapril inhibits the angiotension converting enzyme and prevents conversion of angiotensin I to angiotensin II. It  therapy suppresses the renin – angiotensin – aldosterone system because of decreased production of angiotensin II. There is a resulting decrease in vasopressor activity and decreased aldosterone secretion . It also reduces degradation of bradykinin resulting in lowering of B.P. due to bradykinin induced vasodilation.

 

Pharmacokinetics

On oral administration, it is absorbed and converted to enalaprilat (its active form). It’s absorption is unaffected by food. Onset of antihypertensive action is 1 hour after administration and lasts for about 24 hours (effects may decrease at end of the day). Excreted in the urine and faeces. It crosses the placental barrier.

 

Clinical Information

 

Indications

·    Mild to moderate hypertension.

·    Congestive heart failure – in enalapril treated patients. There occurs an increase in cardiac output (with no increase I heart rate) and a decrease in peripheral vascular resistance and blood pressure. There is also an increase in renal blood flow. Can now used in conjunction with diuretics and digitalis.

·    Left ventricular dysfunction.

·          Patients with diabetic nephropathy – it diminishes proteinuria and stabilizes renal

Dosage

·    Initial dose is 5 mg o.d. can be increased gradually to 10 – 20 mg/day (maintenance dose.)

·    For patients on diuretics, mild renal dysfunction, elderly patients – start with 2.5 mg and then individualize the dose depending on clinical response.

 

Route of Administration    Oral.

 

Contraindications

·    Pregnancy, especially in II and III trimesters may cause fetal hypotension and renal failure leading to oligohydramnios.

·    Hypersensitivity or development of angioedema when exposed to the durg.

 

Precaution / Practice Points

·    Patients with impaired renal function or whose renal function depends on the rennin – angiotensin system (eg. Renal artery stenosias, congestive heart failure and  other high  renin states), when treated with enalapril, due to suppression of renin – angiotensin – aldosterone system may go in for acute renal shutdown, with oliguria and increasing blood urea nitrogen and creatinine. Caution is advised in such patients.

·    Hypotension can occur after the first dose (especially in valued depleted individuals) . Hence initiate treatment under medical supervision and ask patient to report immediately if states of fluid loss like vomiting, diarrhoea and excess perspiration occurs.

·    Effects of enalapril may  wear off at the end of dosing interval Hence, individualize  the dose and once to twice daily administration schedules to be adopted depending on the patients.

 

Drug Interaction

Potentially fatal:

·    Enalapril may cause an increase in serum potassium due to aldosterone suppression. Hence , it should not be used with potassium sparing diuretics (like spirinolactone ) or oral potassium supplements.

·    Enalapril should never be combined with NSAIDs.

·    Risk of hypoglycemic episodes may be increased with oral hypoglycemic agents.

·    Lithium excretion may be decreased. Toxicity may be precipitated.       

·    With potassium salts – risk of hyperkalemia.

Non fatal:

·    Enhanced hypotensive effects with alcohol, antidepressant, other anti hypertensives, antipsychotics, diuretics, L-dopa and muscle relaxants.

·    Antagonism of hypotensive effects of enalapril by steroids, sotrogen and progesterone.

·    Antacids decrease absorption of enalapril.

 

Adverse Effects

Common effects:

·    Dry cough, altered sense of taste.

Rare effects:

·    Anaphylactoid reactions may occur during use of enalapril, (possibly due to increased endogenous bradykinin) and may be manifested as angioedema – swelling of face, tongue, lipa dyspnoea etc.

·    Bone marrow suppression – neutropenia, agranulcytosis.

·    Hypersensitivity – angioedema, branchospasm, respiratory distress; skin manifestation like exfoliate dermatitis, erythematous rash, drug fever etc.,

 

Drug Toxicity

Occurs are more than 1000 mg/kg. Severe hypotension with C.V.S. collapse occurs.

 

Treatment of Toxicity

·    Continuous monitoring of CVS status – D.P. pulse rate, ECG etc.,

·    Volume expansion with an I.V. fluids.

·    Haemodialysis may help to remove systemically absorbed  poison.

 

Storage                       Store in airtight containers.

 

Shelf Life                    2  years.

 

 

10.4.                                 Cardiac glycosides

 

DIGOXIN

           

General information

 

 

Drug Code                              Preparation                             Strength

       95                                     Tab. Dogoxin                           0.25 mg.

 

Description of the Drug

            It is a cardiac glycoside extracted from the plant digitalis lanata.

Mode of Action

The basic action of digoxin is inhibition of sodium-  potassium ATP use pump in the cardiac tissue. It has a direct action on the myocardium (increase the force of contractility , a positive inotropic action ) and  indirect vagomimetic effect on conduction system (slows the heart rate; a negative chronotropic effect and decreases conduction velocity in the AV node; negative dromotropic effect.

 

Pharmacokinetics:

Absorbed slowly from the GIT, with biovailability of 40-60 %. Pharmacological effects depend of levels of digoxin in the tissues. Adequate concentrations in the tissues are attained in 3 – 5 days after initiation of therapy. This process  of digitalizing the patient can be speeded up to 6 – 24 hours with an initial high loading dose. Does not undergo  extensive metabolism and is mostly excreted unchanged in the urine.

 

Clinical Information

 

Indication

·    Cardiac failure – more effective in low output failure states.

·    Atrial fibriliation and flutter – for stabilization of ventricular rate.

·    Paroxysmal supraventricular tachcardia – may convert it into  normal sinus rhythm.

 

Dosage

Adult

Loading dose – 0.25 – 1.5 mg/day according to desired speed of digitalization.

Maintenance dose – 0.0625 – 0.75 mg/day.

 

Children                      Digitalising Dose                   Maintenance dose

2-5 years                      25 – 35 mc/kg                          25 –35 % of loading dose

5-10 years                    15 –30 mcg/kg                         25 –35% of loading dose

> 10 years                    8 –12 mcg/kg                           25 –35% of loading dose

 

Route of Administration     Oral :

 

Contraindications

·    Ventricular tachycardia, ventricular fibriliation.

·    AV block, WPW syndrome.

·    HOCM, constrictive pericarditis.

·    Hypersensitivity.

 

Precaution / Practice Points

·    The risk of arrhythmias is also increased in  patients with cor pulmonale, acute  myocarditis and dilated cardiomypathies.

·    Reduction of dosage is advised in renal impairment.

·    Individulization of the dose of digoxin to ech patient is necessary, because some patients may harbour certain colonic bateria (eg. Enbacterium lentum ) which degrades digoxin and  these patients need higher than usual doses.

·    Potassium competitively binds with digoxin are the same site. Hence hypokalemia increases digoxin toxicity. Hence, carefully monitor patients on diuretics, steroid therapy , dialysis, patients with loss of fluid from the GIT (vomiting, diarrhoea , mechanical nasogastric suction) and malnourished patients for signs of digitalis toxicity and frequently monitor serum potassium levels.

·    Hypercalcemia of any cause predisposes to digoxin toxicity. So calcium levels are also to be monitored and IV calcium should never be given to digitalized patients.

·    Use with caution in patients with arrhythmias as digoxin aggravates arrhythmias like WPW syndrome by increasing conduction through aberrant pathways. It may worsen AV blocks and convert a partial block to complete block. Digoxin may worsen outflow instruction in HOCM and constrictive pericarditis.

·    Can be administered for 5 – 6 days of a week with one-day intermission to prevent cumulative toxicity.

 

Drug Interactions

Potentially fatal:

·    Drugs causing hypokalemia (and increase risk of digoxin toxicity) diuretics, steroids and amphotericin B.

·    Drugs increasing digoxin levels and hence causing toxicity  Antibiotics – erythromycin, clarithromycin, tetrachclines. Others – indomethacin, alprazolam, anti malarial – quinine, chloroquine.

·    Sympathomimetics and succinycholine (by increasing astrl cellular potassium levels) may increase the risk of arrhythmias.

·    Beta-blockers and calcium channel blockers decrease AV conduction and aggravate heart block.

Non fatal:

·    Drugs decreasing  absorption of digoxin – antacids, metaclopramide , cholestyramine, sulphasalazine.

 

Adverse Effects

            Dose related.

Common effects:

·    GIT – nausea, vomiting, anorexia, abdominal pain, diarrhoea.

·    CVS  - pulses bigeminus , ventricular extrasytole, ventricular tachycardia, partial or complete AV block.

Rare effects :

·    Headache, fatigue, dizziness, malaise, apathy.

·    Gynecomastia.

·    Visual disturbance, confusion, hallucination.

 

Drug Toxicity

            Toxic dose is more than 10 mg in adults; more than 4 mg in children.

·    Cardiac arrhythmias – ventricular tachycardia or ventricular fibrillation or bradyarrhythmias like sinus bradycardia , II, III degree heart block and cardiac arrest. In massive over dosage, hyperkalemia can occur.

 

Treatment of Toxicity

·    Acute poisoning

-     emesis, gastric lavage and activatd charcoal.

-     Continuous ECG and electrolyte (especially potassium monitoring).

·    Intravenous potassium to reduce arrhythmic activity.

-     Treatment of arrhythmias by phenytoin , lignocaine, propranolol. If bradyarrhythmias, atropine or temporary pacing can be used.

-     Digoxin antibodies – DIGIBIND  can be used.

 

Storage

            Store in airtight containers. Protect from light and heat.

 

Shelf    Life       2    years.

 

 

10.4          Drugs used in Vascular shock

 

DOPAMINE HYDROCHLORIDE

 

General information

 

Drug Code                  Preparation                                               Strength

      94                          Inj. Dopamine Hydrochloride                  40 mg/ml.

 

Description of the Drug

           Dopamine is both a direct and indirect acting sympathominetic agent.

 

Mode of Action

It acts on dopamine 1, dopamine 2, alpha and beta-receptors, but not on beta 2 or extravascular adrenergic receptors. On the heart it has an inotropic effect and increases the systolic B.P. At doses infused, it acts on dopamine 1 and dopamine 2 receptors and dilates the renal and mesenteric blood vessels and increases the urine output.  At high doses it causes vaso constriction due to action on alpha-receptors.

 

Pharmacokinetics

Dopamine is inactive when given by mouth because of enzymatic degradation in the gut and first pass metabolism in the liver. When injected into the body, it is rapidly inactivated by enzymatic degradation in the liver and body tissues and uptake into adrenergic neurons. Half-life is 2 minutes.

Large portions of dopamine is directly metabolized into dopamine related metabolic products and a proportion is excreted as metabolites of noradrenaline.

 

Clinical Information

 

Indications

·    It is used in inotropic support for cardiogenic and septic shock.

·    Severe congestive cardiac failure.

·    Myocardial infarction going in for cardiogenic shock.

·    Renal failure – to increase GFR.

 

Dosage

0.2 –1 microgram/min as infusion in 5 % dextrose or normal saline. Adjust according to patient’s  blood pressure , cardiac output and urine output.

Children  : 10 microgram/kg/minute.

 

Route of Administration

           I.V. infusion as a dilute solution in 5 % glucose, 0.9 % Normal Saline

 

Contraindications

·    In hypertensive, hyperthyroid patients.

·    It should not be given during anaesthesia with halothane.

·    In patients receiving MAO inhibitors currently or within 14 days of termination of treatment.

·    Pheochromocytoma and ventricular arrhythmias (untreated).

 

Precautions / Practice Points

·    Great care is needed in patients with cardiovascular diseases such as ischaemic heart diseases, arrhythmias, tachycardias, and occlusive vascular disorders like arteriosclerosis, hypertension and aneurysm.

·    Correct hypovolemia before administration.

·    Administration Instructions:

-     Dopamine Iv line must be kept free from administration of other IV injections.

-     It can be mixed with any IV fluids except soda bicarbonate.

 

Drug Interactions

Potential fatal:

·    Risk of ventricular fibrillation in patients undergoing anesthesia with halothane or other halogenated anaesthetics and patients on MAO inhibitors.

Non fatal:

·    Beta-blockers antagonize effects of dopamine (pharmacological antagonism).

 

Adverse Effects

Common effects:

·    Nausea, vomiting.

Rare effects:

·    Occurs in very large doses, where its action becomes similar to adrenaline.

·    CNS – Headache, fear, anxiety, restlessness; insomnia and irritability.

·    CVS – Alpha-adrenergic stimulation (only in very large doses) causing hypertension, cerebral haemorrhage, pulmonary edema, reflex bradycardia.

-     Beta-adrenergic stimulation causing tachycardia, cardiac arrhythmias, anginal pain, palpitations.

·    Extravasations results in tissue necrosis and sloughing.

·    Hypotension, dizziness, fainting and flushing.

 

Drug of Toxicity

Excessive doses may result in CVS toxicity – tachycardia, acute hypertension, causing cerebral haemorrhage, marked pallor, pulselessness and circulatory collapse.

 

Treatment of Toxicity

As dopamine is rapidly metabolized, administer supportive treatment till it is cleared from the body. Continuous ECG monitoring, beta-blockers like propranolol and vasodilators like glyceryl trinitrate can be used.

 

Storage

            Protect from light.

 

Shelf life                     2    years.

 

 

DOBUTAMINE

 

General information

 

Drug Code                              Preparation                             Strength

      372                                    Injection Dobutamine                250 mg/5ml.

 

Description of the Drug

A derivative of isoprenaline acting on beta 1, beta 2 and alpha receptors, which is a directly acting sympathomimetic with positive inotropic effects with milder hypertensive, chronotropic, vasodilative effects.

 

Mode of Action

It is a directly acting sympathomimetic agent. It predominantly acts on beta 1 adrenergic receptors, with positive inotropic effect on the heart. Its advantage is that unlike other sympathomimetics, it does not increase the B.P. or heart rate, but only increases the strength of contraction to increase the cardiac output.

 

Pharmacokinetics

Dobutamine is inactive when given by mouth . Rapid action occurs following intramuscular and subcutaneous injections. Rapidly taken up by neurons and undergoes enzymatic degradation in liver and body tissues. Half-life is 2 minutes.

 

Clinical Information

 

Indications

·    Intropic agent to increase cardiac output due to cardiac failure from myocardial infarction, cardiac surgery or organic heart disease.

·    Short-term management of severe congestive cardiac failure.

 

Dosage

            Dose: 2.5 – 15 microgram/kg/min.

 

Route of Administration    IV  infusion

 

Contraindications

·    States in which obstruction of the outflow tract exist aortic stenos is, mitral stenosis, cardiac tamponade, hypertrophic obstructive cardiomyopathy where dobutamine cannot increase cardiac  output due to the obstruction.

·    Cardiac arrhythmias, hyperthyroidism

·    Patients on MAO inhibitors.

·    Pheochromocoytoma.

 

Precautions / Practice Points

·    Continuous ECG and B.P> monitoring should be done.  Hypovolemia if present should be corrected before infusion.

·    It may exacerbate pre existing tachycardia and ectopic rhythms.

·    Patients with atrial fibrillation should be given a cardiac glycoside before dobutamine treatment to reduce the risk of enhanced atrioventriuclar conduction leading to ventricular fibrillation.

·    Administration Instruction:

-     Dobutamine infusions can be given in any standard glucose or electrolytes solution like normal saline, 5 % dextrose, or Ringer lactate.

-     Alkaline solutions should not be used.

 

Drug Interactions

Potentially fatal;

·    Risk of ventricular fibrillation in patients undergoing anaesthesia with halothane or other halogenated anesthetics and in patients on MAO inhibitors.

Non fatal:

·    Inotropic effects of dobutamine on heart are reversed by concomitant administration of
beta-blockers.

 

Adverse Effects

            Are dose related.

Increase in heart rate, systolic blood pressure, ectopic heartbeats, precipitation of arrhythmias are felt by the patient as palpitations may occur.

 

Drug of Toxicity

Symptoms are anorexia, tremor, fear, anxiety, nausea, vomiting, headache, palpitation, chest pain and dypnoea. Fibrillation, tachyarrhythmias, angina and myocardial ischemia can also occur.

 

Treatment of Toxicity

Since half-life of dobutamine is only 2 minutes discontinuing rate of infusion reduces the toxic effects. Continuous ECG monitor to pick up arrhythmias and prompt treatment is necessary. Monitor vital signs.

 

Storage

            Store are 2- 8o C in airtight containers.

 

Shelf    Life                 18   months.

 

 

 

10.6.                     Anti thrombotic Drugs

 

STREPTOKINASE

           

General information

 

Drug Code                   Preparation                             Strength

       85                                     Streptokinase                           7.5 lacs IU

 

Description of the Drug

Streptokinase is a fibrinolytic agent, derived from group C beta haemolytic streptococci.

 

Mode of Action

It combines with plasminogen and activates it to the proteolytic enzyme, which has fibrinolytic effects and can dissolve intravascular clots.

 

Pharmacokinetics

It is rapidly cleared from circulation following I.V. administration. Half-life is 30 – 80 minutes. It causes a decrease in plasma fibrin levels and decreased RBC aggregation. Effects lasts for 24 hours.

 

Clinical Information

 

Indications

·    Acute myocardial infarction.

·    Thromboembolic disorders such as pulmonary embolism, deepvein thrombosis and arterial occlusion.

·    To clear occlusion of arterio venous cannulae.

 

Dosage

Thromboembolic disorders

Adults – initial loading dose of 2.5  lakhs followed by 1 lakh per hour for 24 hours.

 

Acute myocardial Infarction  7.5 – 15  lakh I.V – I.V. over 1 hour.

 

Routes of Administration       I.V. infusion, intracoronary.

 

Contraindications

·    Menstruation.

·    In patients with active internal bleeding, recent history of peptic ulcer, oesophageal varies, bleeding gastro – intestinal lesions.

·    Bleeding disorders.

·    Recent surgery, trauma, delivery.

·    Severe hypertension, aneurysms, aortic dissection.

·    Allergic reaction to streptokinase.

 

Precautions / Practice Points

·    Treatment with streptokinase should not be repeated within 12 month of previous course. Antibodies formed renders it inactive. (therapeutic resistance.)

·    Monitor the clotting time, PT, APTT, BP and for signs of bleeding.

·    IV injections should be given in upper limbs where they are easily accessible to compression measures if bleeding occurs due to the procedures.

·    With caution in bacterial endocarditis, pregnancy, age more than 75 years, diabetic retinopathy, cerebrovasscular accident.

·    Administration Instruction:

- Continuous monitoring of ECG and CVS status , because thrombolysis and reperfusion may precipitate arrhythmias.

            - Do not administer IM. Diluent to be used is 5 % dextrose.

 

 

 

Drug Interactions

Potentially fatal:

·    Oral anticoagulants can increase the risk of bleeding.

Non fatal:

·    Aspirin can be concomitantly used in treatment of M.I. The benefits outweigh risk of bleeding.

 

Adverse Effects

Common effects:

·    Bleeding – minor (from venipuncture sites etc) or major internal  haemorrhage can occur. Treat by immediately stopping the infusion and measures to stop bleeding like compression etc.,

·    Fall in arterial tone – hypotension on I.V. administration.

Rare effects:

·    Arrhythmias due to thrombolysis.

·    On subsequent exposure.

-     Therapeutic resistance due to antistreptococcal antibodies derived from

 prior exposure, the effect of streptokinase may be agent.

-     Allergic reactions  - fever , shivering, bronchospasm, angioneurotic

edema, urticaria, itching, flushing can occur.

Treat with adrenaline, antihistamine , steroids.

 

Drug Toxicity:

Internal bleeding reactions anti histamines, cortiscosteroids, and adrenaline can be given.

 

Treatment of Toxicity

·    For allergic reactions anti histamines, corticosterodis, adrenaline can be given.

·    Severe haemorrhage :

-     local pressure.

-     Tranekamic acid, aminocaproic acid or aprotinics.

-     Replacement therapy with packed RBCs.

 

Storage

            Store in a cool dark place.

 

Shelf    Life        33      months.