CHLORPROMAZINE

General Information 

Drug code                   Preparation                                         Strength

       185                       Tab. Chlorpromazine HCI                    25 mg              

      187                        Tab. Chlorpromazine HCI                    100 mg               

Description of the Drug

Chlorpromazine is a neuroleptic agent, a phenothiazine derivative with sedative, anti emetic, antiadrenergic, and slight antihistaminic and anti serotonin activity. 

Mode of Action

Chlorpromazine acts on various receptors at all levels of the CNS – adrenergic, dopaminergic and serotonergic receptors. It blocks alpha one and serotonin receptors more avidly than D2 and D1 receptors. 

Pharmacokinetics:

It is absorbed from the GIT and metabolized in the liver and excreted in the urine and bile. It has a biphasic mode of elimination – initial fast phase (2 hours) followed by a longer second phase (30 hours). 

Clinical Information 

Indications

·    It is a neuroleptic used in psychotic conditions -acute and chronic schizophrenic patients, to control severely disturbed, agitated or violent behavior.

·    Behavioral problems in children, with psychomotor agitation and hyperkinetic behavior and in  Gille de la Tourette’s syndrome.

·    Post – operative nausea, vomiting.

·    As an adjunct in the treatment of tentanus.

·    Alleviation of intractable hiccough.

·    As a part of lytic coktril (menon’s regimen in) control of eclampsia.

 Dosage

            Usual dose:

Adult:

Oral – 25 –30 mg. Three times daily  and increased as necessary upto 300 mg.

            Maintenance dose – 25 – 100 mg three times daily.

Children:

·    500 microgram /kg body weight, every 4 – 6 hours.

·    Daily doses should not normally exceed 40 mg for children 1 – 5 years and 75 mg for children
over 5 years.

·    For nausea and vomiting – 10 –25 mg every 6 hours. 

Route of Administration   Oral

Contraindication

·    Pregnant and nursing mothers.

·    In patients with pre-existing CNS depression or coma.

·    Bone  marrow suppression.

·    Closed angle glaucoma.

·    Parkinsonism.

·    Diabetes mellitus.

·    Hypothyroidism.

·    Myasthenia gravis.

·    Prostatic hypertrophy.

·    Untreated epileptics – lowers seizure threshold and may precipitate fits.

Precaution / Practice points

·    Patients should remain supine for atleast 30 minutes after the first dose and blood do pressure to be monitored, due to its hypotensive effects.

·    Use with caution in cardiovascular disease, liver disorders renal diseases and respiratory
diseases with decreased respiratory reserve.

·    Monitor hematological parameters, ocular examination abnormal movements when on chronic therapy. Frequent ophthalmologic examinations and continuous monitoring for abnormal movements should be done.

·    Avoid abrupt withdrawal of therapy.

·    Reduce dose in elderly (risk of side effects).

·    Instruct patients to abstain from alcohol.

·    Administration instructions:

-  Do not crush tablets; avoid direct contact bare skin due to risk of contact sensitization.

-  Do not give antacids for 1 hour after the drug is ingested. 

Drug Interactions

Potentially fatal:

      ·    CNS depression may be enhanced by concomitant administration of other drugs with CNS- depressant properties like alcohol general anesthetics, hypnotics and sedatives, opioid analgesics.

      ·    Propranolol when given along with chlorpromazine increases levels of both drugs and may cause                  toxicity.           

      ·    Lithium may increase risk of extra pyramidal side effects and chlorpromazine increases the
      neurotoxic effects of lithium.

Non fatal

·    Potentiate the antimuscarininc effects of other anti cholinergics, tricyclic antidepressants and MAO inhibitors.

·    May antagonise – orthostatic hypotension due to alpha-blockers especially in elderly.

·    Metaclopramide increases the risk of neuroleptic induced extra pyramidal effects.

·    Increased doses of antiepileptics may be necessary-lowers the seizure threshold. 

Adverse Effects

Common effects:

·    Extrapyamidal symptoms – acute dystonias, parkinsonism like  syndrome, akathesia, perioral tremor. Tardive dyskinesia irreversible, involuntary, dyskinetic movements of face, choreoathtoid
movement of  limbs tongue, mouth, jaw. Elderly  women are especially susceptible.

·    Antimuscarnic dry mouth, difficulty in micturition, and defecation, loss of accommodation, postural hypotenson.

Rare effects

·    Malignant neuroleptic syndrome – characterized by hyperpyrexia, rigidity, altered mental
status and autonomic instability, (believed to be due to excessively rapid block of postsynaptic dopamine receptors).

·    Endocrine and metabolic disturbances, amenorrhoea, galactorrhoea, gynaecomastia, weight gain, hyperglycemic and altered glucose tolerance.

·    Pigment deposition in skin, eyes (cornea and lens).

·    Allergic reactions – skin eruptions, agranulocytosis , hepatitis and cholestatic jaundice. 

Drug Toxicity

Symptoms of CNS depression like somnolence, stupor, coma, hypotension, hypothermia and extra pyramidal symptoms. 

Treatment of Toxicity

·    Gastric lavage, EMESIS IS CONTRAINDICATED.

·    Maintain airway, supportive ventilation.

·    Monitor pulse, B.P. if hypotension develops, treat with I.V. fluids vasopressors, trendlenburg’s
position.

·    If extrapyramidal side effects develop, treat with procyclidine 5 –10 mg I.M or I.V or orphenadrine 2-40 mg IV. Or I.M. (anti cholinergics like benzhexol or barbiturates or benadryl.)

·    If seizures occur diazepam or phenytoin can be given. 

Storage

            Protect from light. 

Shelf life          1  year. 

IMIPRAMINE

General Information 

Drug code                   Preparation                        Strength

      188                        Tab. Imipramine                      25 mg                

Description of the Drug

Imipramine is a dibenzazepine derivative, a commonly employed tricyclic antidepressant drug. 

Mode of Action

It inhibits the uptake of norepinebhrine at nerve endings and causes a localized increase in
norepinephrine in the synapse. It also has antichlonergic and antiserotonin activity. 

Pharmacokinetics

It is well absorbed, widely distributed and is extensively bound to plasma and tissue proteins.
It is metabolized in the liver and its metabolite desimipramine is also active. It is excreted in urine. It crosses the placental barrier and blood brain barrier and secretedin breast milk. Therapeutic
effects are seen only after 1 –3 weeks of imitating therapy. 

Clinical Information 

Indications

·    Treatment of depression, particularly endogenous depression.

·    In selected cases for the treatment of nocturnal enuresis.

·    Anxiety and panic disorders.

·    Sleep disorders – catalepsy and sleep paralysis.

·    Obsessive-compulsive disorder, school phobia.

·    Can also be used in treatment of chronic naturopathic pain 

Dosage

Adult:

-  75 mg o.d. can be increased to 150 –200 mg. Maintenance dose 75 –150 mg/day.

Children :

-  Give lower doses (25 –50 mg.) 

Route of Administration   Oral

 Contraindications

·    Patients on MAO inhibitors and 14 days of stopping it.

·    Patients with recent myocardial infarction, other C.V.S disorders - heart block and cardiac arrhythmias.

·    Known hypersensitivity.

·    Severe hepatic impairment.

·    Narrow angle glaucoma.

·    Pregnant and nursing mothers. 

Precaution / Practice points :

·    Used with caution in patients with urinary retention, prostatic hypertrophy or constipation and
epileptic patients due to its antimuscarinic effects.

·    Use with caution in hyperthyroid patients as it Amay precipitate cardiac disorders.

·    Blood sugar concentrations may be altered in diabetic patients and glycemic control may be difficult.

·    Drowsiness is the common side effect; the patients should not drive or operate machinery. Instruct patients to abstain  from alcohol.

·    Dosage to be reduced in elderly and young children.

·    Clinical effect is seen only 2 –3 weeks after initiating  therapy.

·    Instruct patients to avoid sudden position changes, like sitting up from supine position because
orthostatic hypotension being a common side effect and dizziness may occur.

·    Administration instructions:

-  Usually given at bedtime. Don’t  crush or chew the tablets. 

Drug Interactions

Potentially fatal:

·    Risk of arrhythmias are enhanced by imipramine when volatile anesthetics, amiodarone, quinidine, disopyramide, astemizole, terfenadine and pimoxide.

·    Diltiazem and verapamil increases serum levels and toxicity of imipramine.

·    CNS depressants – alcohol, sedative hypnotics opioid analgesics causes excessive CNS depression.

·    With MAO inhibitors hypertensive crisis with convulsions  may occur.

·    Thyroxine, sympathomimetics, adrenaline and noradrenaline may cause hypertensive crisis. 

Non fatal:

·    Neuroleptics, antihistamines  and anticholinergics potentiate  the  antimuscarinic side effects.

·    Imipramine decreases the effects of antiepilieptic drugs.

·    Diuretics enhance the side effects of postural hypotension. 

Adverse Effects

Common effects:

·    Antimuscarinic effects – dry  - mouth, constipation occasionally leading to paralytic ileus, urinary retention, blurred vision, disturbances in accommodation, increased intraocular pressure and hyperpyrexia.

·    CNS – peripheral neuropathy, ataxia, extrapyramidal symptoms.

·    CVS – orthostatic hypotension, tachycardia, intraventricular conduction defects, painful vasospastic episodes and acrocyanosis.

Rare effects

·    Allergic hypersensitivity skin reactions – urticaria, photosensitation, and pigmentation.

·    Weight gain and edema.

·    Endocrine abnormalities. 

Drug Toxicity

Most significant is CVS adverse effects – arrhythmias, hypotension, heart block etc. antimuscarinic effects, myoclonic twitching, convulsions, hypothermia, coma and death may occur. 

Treatment of Toxicity

·    Gastric lavage, emesis or activated charcoal, if recently ingested.

·    Continuous ECG monitoring – if arrhythamias occur, use lidocaine, or bretylium or phenytoin.

·    Maintain ph from 7.45 – 7.55 by infusion of sodium bicarbonate.

·    Treat convulsions by giving I.V. diazepam.

·    Supportive and symptomatic line of management.

·    Physostigmine can be used to reverse antimuscarinic effects. 

Storage

            Protect from light. 

Shelf life         2   years.  

AMITRIPTYLINE

General Information 

Drug code                   Preparation                                         Strength

       189                       Tab. Amitriptyline                                 25 mg.           

Description of the Drug

            Amitriptyline is a tricyclic antidepressant, with sedative effects. 

Mode of Action

It inhibits the reuptake of norepinephrine and serotonin in neurons thereby promoting prolonged action of neurotransmitters in the synapse. It also has anti cholnergic properties. 

Pharmacokinetics:

It is readily absorbed from gastro – intestinal tract, under goes extensive first pass metabolism, and
it excreted in the urine. Widely distributed throughout the body and are extensively bound to plasma and tissue proteins. It crosses the placental barrier and in secreted in breast milk. Plasma half-life is 15 hours and onset of therapeutic effect occurs only after 7 –21 days after imitation of therapy. 

Clinical Information 

Indications

·    Treatment of depression, particularly endogenous depression.

·    Anxiety and panic disorders.

·    Obsessive compulsive disorders, school phobia.

·    Can also be used for prophylaxis against migraine and treatment of chronic pain syndromes.

·    Selected cases of nocturnal enuresis and urinary incontinence. 

Dosage

Oral – 75 mg initially , gradually increased to 150 mg daily in a single or divided daily doses, normally given at bed time.

Maintenance doses 50 –100 mg daily continued for atleast 3 months before being gradually withdrawn.

Maximum – upto 300 mg daily can be given in severely depressed patients. 

Elderly – 10 –50  mg/day.

Children (nocturnal enuresis).

            10 –20 mg at bed time – 6 –10 years.

            25 – 50 mg over 11 years.

            Treatment should not continue for longer than 3 months. 

Route of Administration     Oral 

Contraindications

·    Patients with CVS disorders heart block, cardiac arrhymias and immediate recovery period after myocardial infarction.

·    Severe hepatic impairment.

·    Pregnancy and nursing mothers.

·    Acute angle glaucoma.

·    Patients receiving MAO inhibitors or within 14 days of stopping them. 

Precaution  / Practice points:

·    Use with caution in elderly patients with urinary retention, prostatic hypertrophy or constipation, because of its antimucarinic effects.

·    Use with caution in patients having cardiovascular disorders, hyperthyroidism.

·    Blood sugar concentrations may be altered in diabeticpatients.

·    Maximum clinical response is seen only after 3 –4 weeks of initating therapy. Hence dose adjustments should be made only after appropriate intervals.

·    Instruct patients to avoid driving and operating machinery and to abstain from alcohol.

·    Do not withdraw abruptly.

·    Use with caution in hepatic dysfunction.

·    Administration instructions:

- Usually administered as a single dose at bedtime. 

Drug Interactions

Potentially fatal:

·    Excessive CNS depressant effects may occur with alcohol barbiturates, sedative hypnotics, opioids etc.,

·    MAO inhibitors – severe hypertensive, hyperpyrexia crisis convulsions and fatalities.

·    Risk of arrhythmias are increased with anesthetic agents, amiodarone, disopyramide, procainamide, quinidine, pimozide, sotolol.

Non fatal

·    Neuroleptics, anticholinergic and antihistamines potentiate the antimuscarinic effects of amitripytline.

·    Oral contraceptive pills, verapamil, diltiazem, increase the side effects due to increase in serum levels of amitriptyline.

·    Drugs decreasing serum level of amitriptyline – phenytoin, barbiturates and rifampicin.

·    Amitriptyline decreases the action of antiepileptic agents.

·    Diuretics may enhance postural hypotension due to amitriptyline. 

Adverse Effects

Common effects:

·    Antimuscarinic effects –dry mouth, mydriasis, constipation, urninary retention, blurred vision, disturbances in accommodation, increased intra – ocular pressure and hyperpyrexia.

·    CNS – drowsiness, peripheral neuropathy, ataxia, extra pyramidal symptoms.

·    Psychiatric confusion, hallucination, disorientation, delusion.

·    CVS – (due to anticholinergic effects and enhancement of nor adrenaline activity) orthostatic hypotension, tachycardia, intraventricular conduction defects, painful vasospastic episodes and
acrocyanosis may occur.

Rare effects

·    Allergic hypersensitivity skin reactions – urticaria, photosensitization, pigmentation.

·    Haematotoxicity – bone marrow depression, thrombocytopenia, lecopenia, agranulocytosis,
neutropenia.

·    Weight gain, fluid retention, alopecia, galactorrhoea. 

Drug Toxicity

Dilated pupils, agitation, hyperactive reflexes, antimuscarinic effects, respiratory depression and apnoea, hyperpyrexia, cardio toxicity, hypotension, myoclonic twitching, convulsions, hypothermia, coma, and death may occur. 

Treatment of Toxicity

·    Gastric lavage. Emesis is contraindicated.

·    Continuous ECG monitoring , observation for CNS , respiratory depression.

·    Infusion of sodium bicarbonate to nullify  the cardiac toxicity lidocaine and phenytoin for arrhythmias.

·    Convulsions treated by giving diazepam I.V.

·    Manage electrolyte balance and ph.

·    Physotigmine can be used to reverse antimuscarinic effects. 

Storage

            Protect from light. 

Shelf life          2  years. 

HALOPERIDOL

General Information 

Drug code                   Preparation                                         Strength

      190                        Tab. Haloperidol                                  1.5 mg

      191                        Tab. Haloperidol                                  5 mg           

Description of the Drug

            Haloperidol  is a butyrophenone-tranquilizing agent. 

Mode of Action

Haloperidol has potent dopamine D2 receptors blocking action, especially in the temporal and prefrontal areas. It also blocks D1 and D4, alpha and serotonin receptors, but with less potency. 

Pharmacokinetics:

Readily absorbed from the gastro intestinal tract. Metabolized in liver and excreted inurine. It
undergoes first pass metabolism in the liver and bioavailability is 65 % plasma half-life is about 24 hours. 

Clinical Information 

Indications

·    Schizophrenia.

·    Mania and other psychoses.

·    For the control of severely disturbed or agitated and violently dangerous behavior.

·    Management of Gille de la Tourette’s syndrome.

·    Severe behavioral problems in children.

·    Short-term treatment of hyperactive children with excessive motor activity.

·    Intractable hiccup. 

Dosage

Adults and children more than 40 mg.

Initially 0.5 – 2 mg, twice or three times daily, gradual increased to 5 – 10 mg, or as clinical response dictates.

Dose to be individualized to each patient.

Children less than 40 kg.

            0.05- 0.15 mg.kg/day. 

Route of Administrations    oral 

Contraindications

·    Severe CNS depression or comatose states from any cause.

·    Parkinsonism.

·    Hypersensitivity to the drug.

·    Narrow angle glaucoma.

·    Bone marrow depression.

·    Severe liver or cardiac disease. 

Precaution/ practice points.

·    May cause severe neurtoxic reactions in patients with hyperthyroidsm.

·    Use with caution in patients with CVS disorders – if hypotension occurs epinephrine cannot be used as vasopressor because halopeidol blocks its effect.

·    Instruct patients to abstain from alcohol; not to operate machinery or drive.

·    Monitor B.P> (3 –5 days after initiation of therapy) and for signs of extra pyramidal side effects.

·    Administration Instructions:

-  Take with food. 

Drug Interactions

Potentially fatal:

·    CNS depression may be enhanced by concomitant administration of other drugs with CNS depressant properties like alcohol, general anesthetics, hypnotics and sedatives, opioid  analgesics.

·    In patients receiving lithium, haloperidol may precipitate a syndrome characterized by weakness, lethargy, fever, confusion, and extra pyramidal side effects.

·    Propranolol when given along with haloperidol , increases levels of both drugs and toxicity may occur.

Non fatal

·    Potentiate the adverse effects of other anti muscarinics and alpha-blockers and the antimuscarinic side effects of drugs like MAO inhibitors and tricyclic antidepressants.

·    Metaclopramide increases  the risk of neuroleptic induced extra pyramideal effects.

·    Increased doses of antiepileptics may be necessary due to lowering of seizure threshold.

·    Carbamazepine and barbiturates may decrease effects of haloperidol. 

Adverse Effects

Common effects:

·    Tardive dyskinesia – irreversible, involuntary, dyskinetic movements of face, tongue, mouth, jaw especially in elderly women. Occurs due to hypersensitivity of dopamine receptors, secondary to receptor blockade by haloperidol.

·    Extrapyramidal side effects – akathesia, motor restlessness, oculo-gyric crisis , parkinsonism, ECG changes.

·    Others – dry mouth , constipation, difficulty with micturition blurred vision and mydriasis.

Rare effects :

·    Malignant neuroleptic syndrome – hyperpyrexia, rigidity, altered mental status, autonomic instability.

·    Others CNS side effects   -insomnia, restlessness, euphoria, vertigo, confusion, hallucinations, seizures, catatonia like state.

·    Endocrine – galactorrhoea, menstrual irregularities, gynaecomastia, weight gain.

·    Allergic reactions pruritis, skin, rash, photosensitivity, contact dermatitis.

·    Retinal pigmentation.

·    Agranulcoutosis, leucopenia. 

Drug Toxicity

Extrapyramidal reactions, dystonias, muscular weakness rigidity tremors,

hypotension, somnolence, sedation respiratory depression, arrhythmias and CVS collapse can
            occur. 

Treatment of Toxicity

·    Gastric lavage, emesis is contraindicated.

·    Maintain airway and supportive ventilation.

·    Treat hypotension with metaraminol , phenylephrine, IV fluids and trendlenburg position.

·    Treat extrapyramidal side effects with benzhexol and diphenhydramine.

 Storage

            Protect from light. 

Shelf life          2– 3 years. 

LITHIUM CARBONATE

General Information 

Drug code                   Preparation                            Strength

      286                        Tab. Lithium carbonate             300 mg 

Description of the Drug

            Lithium is small monovalent cation. It is administered its carbonate salt. 

Mode of Action

It alters the sodium  transport in nerve and muscle cells. It also causes depletion of messenger
enzymes in muscarinic and adrenergic neurotransmission, producing antimaniac effects. 

Pharmacokinetics

Well absorbed and widely distributed throughout the body, mainly excreted in the urine, the renal clearance being proportional to its plasma concentration. Effects of the drug of produced gradually and dosages must be adjusted to provide a steady concentration of lithium in the plasma. 

Clinical Information 

Indications

·    Prophylaxis and treatment of mania or hypomania, manic-depressive disorder.

·    Maintenance therapy in bipolar maniac depressive disorders.

·    Aggressive or self-initiating behavior. 

Dosage

·    300 –1200 mg orally daily in divided doses.

·    Dose can be adjusted after 2 – 7 days according to serum. Lithium concentrations. Recommended range 0.6 – 1.2 meq/litre. 

Route of Administration  oral 

Contraindications :

·    Severe renal impairment.

·    Patients on  ACE inhibitors.

·    Debilitated and dehydrated patients.

·    Addison’s disease.

·    Sodium depletion states.

·    Pregnancy and nursing mother.

·    Hypersensitivity reactions.

·    Sick sinus syndrome. 

Precaution / Practice points :

·    Serum lithium concentration should be monitored regularly (every 3 months, once patient is stabilized) because theraupetic index of lithium is low, and even slight increase in concentration
produces toxic effects.

·    Renal function test (S.G. volume and complete chemical analysis of urine, serum creatinine and
creatinine clearance) should be done before starting the drug.

·    Thyroid function should be monitored and dose adjusted in hypothyroidism.

·    Dose should be reduced in elderly persons.

·    Diuretics should never be combined with lithium they decrease lithium excretion and produce toxicity.

·    Withdrawal must be done gradually.

·    Use with caution in surgery and myasthenia gravis.

·    Maintain adequate salt and water intake, lithium, metabolism may be altered in states of vomiting, diarrhoea, intercurrent infections.

·    Adminstration Instructions :

- Patients should also be instructed to take their medications at exactly the stipulated time and not to compensate for an omitted dose by subsequently taking a double dose.

Drug Interactions

Potentially fatal :

Potentiates the Toxicity of Lithium Carbonate:

·    Anti epileptics – phenytoin, phenobarbitone, carbamazepine.

·    Antidepressants – amitriptyline and alpha selective serotoein.

·    Anti hypertensive  – enalaml, methyldopa, spectinomycin and tetracycline antibacterial agent.

·    Calcium channel blockers – verapamil, dilitiazem, increase neurotoxic side effects.

·    Diuretics and ACE inhibitors – decrease lithium excretion.

·    NSAID – ibuprofen, indomethacin, naproxen and piroxicam aspirin and phenylbutazone.

·    Neuroleptics like haloperidol, thioridazine and phenothiazines with lithium can cause
malignant neuroleptic syndrome.

Non-fatal:

·    Mannitol and aminophylline increase lithium excretion.

·    Antacids reduce lithium absorption.

·    Lithium impairs glucose tolerance.

·    Risk of hypothyroidism increased with amiodarone. 

Adverse effects:

·    Are dose dependent. Most commonly tremors appear first.

·    Toxicity occurs at serum levels of 1.5  – 2.5 meq./lit.

Common effects:

·      GIT – nausea, anorexia constipation or diarrhoea, epigastric discomfort, metallic taste.

·    Weight – gain, edema.

·    Renal - lithium induced nephrogenic diabetes insipidus like syndrome, edema.

Rare effects:

·    CNS – vertigo, abnormal involuntary movements like chorea, athetosis, muscle weakness,
somnolence, lethargy, mild cognitive and memory impairment, anxiety, depression, restlessness
and easy fatigue.

·    CVS – cardiac arrhythmias, bradycardia, premature ventricular contraction, atrioventricular block. T wave depression.

·    Epileptogenic – seizures are common in lithium toxicity.

·    Endocrine  - hyperthyroidism, goitre, rarely hyper thyroidism, hyperparathyroidism and diabetes mellitus, impotence. 

Drug Toxicity

·    Serum concentration exceeding 1.5 meq/litre.

·    Acute poisoning is due to suicidal intention or accidental ingestion.

·    Symptoms are abdominal pain, anorexia, nausea, vomiting, diarrhoea, giddiness , tremor, ataxia, myclonus, twitching, hyperreflexia, depression. Coma and convulsion with first-degree heart block, hypokalemia, hypothyrodism, ECG changes acute renal failure, oliguria and death. 

Treatment of Toxicity

·    Gastric lavage or emesis, if ingestion is acute.

·    Forced diuresis.

·    Hemodialysis.

·    Fluid and electrolyte balance maintenance.

·    Other supportive line of management. 

Storage

            Store in airtight containers. 

Shelf life               3 years. 

TRIFLUOPERAZINE HYDROCHLORIDE 

General Information 

Drug code                   Preparation                                         Strength

      288                        Tab. Trifluoperazine                              5 mg. 

Description of the Drug

It is a phenothiazine derivative, blocking to the piperazine group, used as an anti psychotic agent. 

Mode of Action

It acts by belonging dopamine, serotonin, alpha 1 and muscarinic receptors. However it is more potent with less sedative, hypotensive and antimuscarinic effects than chlorpromazine. 

Pharmacokinetics :

Absorbed well from the GIT. It under goes first pass metabolism. Metabolized in the liver excreted in the urine. Duration of action is 12 – 14 hours. 

Clinical Information  

Indications

·    Neuroleptic agent used in psychotic conditions.

·    Acute and chronic schizophrenia.

·    Manic phase of manic depressive disorder associated with psychotic tendency.

·    Severely disturbed agitated or violent behavior in children and elderly.

·    Adjunctive therapy of generalized anxiety disorder. 

Dosage

·    Psychotic conditions: 5 mg b.d increased after 3 –7 days to 15 mg depending on clinical response.

·    Anxiety disorder: 2 – 4 mg/day. 

Route of Administrations Oral 

Contraindications

·    In patients with preexisting CNS depression or coma.

·    Preexisting hepatic damage.

·    Bone marrow suppression and blood dyscrasias.

·    Pheochromocytoma.

·    Hypersensitivity. 

Precaution / Practice points:

·    Risk of side effects – dystonia and extra pyramidal effects are more common with trifluoperazine. Therefore careful selection of patient is necessary.

·    With caution in prostatic hypertrophy, closed angle  glaucoma., myasthenia gravis, Parkinson’s, cardio vascular dieases, seizure disorder.

·    Instruct patients not to drive or operate machinery.

·    Give in the lowest dose possible.

·    While on therapy monitor for extrapyramidal effects and cardio vascular status.

·    Administration Instructions :

-     Avoid contact with bare skin and avoid crushing the tablet take with food. 

Drug Interactions

Potentially fatal:

·    CNS depression may be enhanced by concomitant administration of other drugs with CNS – depressant properties like alcohol, sedative – hypnotics, opioid analgesics etc.,

·    With lithium  may cause encephalopathy like syndrome.

·    Increases serum levels and toxicity of propranolol.

Non fatal:

·    With other anti muscarinic, tricyclics, and MAO inhibitors agents – increased anticholiergic side effects.

·    Metaclopramide increases the risk of extra pyramidal side effects.

·    Dose adjustment of anti epileptics may be necessary as it lowers seizure threshold and may precipitate fits.

 Adverse effects:

Common effects:

·    Extrapyramidal effects – acute dystonia  oculogyric crisis, akathesia, and tardive dyskinesia perioral.

·    Parkinsonism like syndrome.

·    CVS – hypotension, ECG changes (QT interval widening)and CVS arrhythmias

Rare effects:

·    Neuroleptic malignant syndrome – hyperpyrexia, muscle rigidity, autonomic instability. Treat with measures like with drawl of the drug, monitoring of CVS status and vital signs and symptomatic therapy.

·    Endocrine disturbances – amenorrhoea, galactorrhea due to hyperprolactinemia resulting from dopamine receptor blockade.

·    Hypersensitivity reactions, skin rashes, photosensitivity.

·    Rential and corneal pigmentation, visual changes.

·    Cholestatic jaundice, anemia, leucopenia , thromobocytopenia. 

Drug Toxicity

CNS depression, stupor, coma, extra pyramidal reactions, hyperpyrexia, cardiac arrhythmias, hypotension and cardio vascular collapse. 

Treatment of Toxicity

·    Gastric lavage.  EMESIS IS CONTRAINDICATED.

·    CNS stiumulants like caffeine and amphetamine; I.V. fluids trendlenburg’s position and judicious use of vasopressor’s to combat hypotension.

·    Diphenhydramine for extra pyramidal reactions.

·    ECG, vital sign monitoring. 

Storage

            Store in airtight containers. 

Shelf life         3 years. 

NITRAZEPAM

General Information 

Drug code                   Preparation                                         Strength

     463                         Tab.Nitrazepam                                    5 mg.

 Description of the Drug

            It is a long acting benzodiazepine which  is used as a hypnotic.

 Mode of Action

Action mediated by enhancement of the activity of GABA (gamma aminobutyric acid), a major inhibitory neurotransmitter in the brain, due to effects on the GABA receptor producing  CNS depression and sedation.

  Pharmacokinetics

It is readily absorbed from the GIT. Onset of action is ½ hour after ingestion. Duration of action 12 to 18 hours. Extensively bound to plasma proteins and has elimination half-life of about 36 hours. It crosses blood brain barrier and placental barrier and traces are found in breast milk. It is metabolized in liver and excreted in urine.

 Clinical Information

 Indications

            For occasional relief of insomnia.

 Dosage

                        As  hypnotic – 5 mg.

 Route of Administration       Oral

Contraindications

·    In patients with preexisting CNS depression or coma.

·    Acute pulmonary insufficiency and respiratory depression.

·    Severe hepatic impairment, myasthenia gravis.

·    Pregnancy, neonates, children, lactation.

·    Prophyria, acute narrow angle glaucoma.

·    Sleep apnoea syndrome.

 Precaution / Practice points

·    Should not be given for long period of time, cumulative toxicity may develop.

·    Warn patient not to drive or operate machinery.

·    Tendency for abuse is present. So avoid in patients with history of drug and alcohol abuse.

·    Use with caution in myopathies and muscular disorders.

·    Reduce dose in elderly and debilitated.

·    Reduce dose in hepatic and renal dysfunction.

·    Use with caution in psychiatric patients. Should not be used in treatment patient of phobic and
obsessional states.

·    Instruct patient to abstain from alcohol.

·    Administration instructions:

-  Give at bedtime for treatment of insomnia. 

Drug Interactions:

Potentially fatal:

            Enhanced effects of other CNS depressant, alcohol, barbiturates, opioids etc.,

            Nitrazepam enhances the activity of digoxin and may cause toxicity.

Non fatal:

·    Drugs which increases effects of nitrazepam by inhibiting its hepatic metabolism – INH,
rifampicin, oral contraceptives, ketaconazole, propranolol  and valproate.

·    Aminophyline reduces sedative effect of nitrazepam.

·    Enhanced effects of antihypertensive, sedative effects of antidepressants, muscle relaxants.

 Adverse Effects

Common effects:

·    Drowsiness, sedation and light-headedness in the next day.

Rare effects :

·    Ataxia, nightmares, fatigue, confusion (especially in elderly).

·    Dependence and abuse.

·    Blurred vision, dry mouth.

·    Paradoxical CNS excitation in children and elderly and its effects.

Drug Toxicity

Somnolence, stupor coma, respiratory depression, decreased reflexes and hypotension.

 Treatment  of Toxicity

·    I.V.  Line continuous monitoring of  B.P and pulse rate. If hypotension occurs correct with metaraminol, I.V. fluids and trendlenburg position.

·    Flumazenil – benzodiazepine antagonist can be used if the poison is confirmed to be diazepam.

 Storage

Protect from light. 

Shelf life         3 years. 

ALPRAZOLAM

 General Information 

Drug code                   Preparation                                         Strength

     464                                     Tab.Alprazolam                                    0.5 mg.

 Description of the Drug

Alparazolam is a long acting benzodiazepine with anxiolytic and antidepressant properties.

 Mode of Action

Acts by enhancement of action of the GABA receptor (an inhibitory receptor) in the CNS especially the midbrain ascending reticular formation (sedative effect) and limbic system (action on thought and mental function).

 Pharmacokinetics

The drug is rapidly absorbed from the GIT with peak plasma level 1 –2 hours after
administration. Duration of action is 12 – 14 hours.  It is metabolized in the liver to hydroxyderivatives, which is excreted in urine in very low quantities. 

Clinical Information 

Indications

·    Generalized anxiety disorders and panic attacks.

·    Short-term management of insomnia.

·    Adjunct in management of depression. 

Dosage 

·    To be individualized to each patients.

·    For treatment of panic attacks – 0.25 – 1 mg/day.

·    For treatment of generalized anxiety disorder – 0.25 – 0.5 mg. T.d.s. 

Route of Administrations  Oral

 Contraindications

·    Preexisting CNS or respiratory depression.

·    Severe hepatic failure.

·    Pregnancy due to possible teratogencity), lactation and neonates.

·    Acute angle glaucoma. 

Precaution / Practice points

·    Abuse of alprazolam is possible and difficulty of detection of its metabolites in the urine makes diagnosis even more difficult. Hence not to be administered for long periods of time as in the treatment of chronic psychosis. Phobias etc.,

·    Caution in impaired liver function.

·    In elderly and debilitated patients – dose to be reduced to 250 mcg. 2 –3 times/day.

·    Patient may experience withdrawal symptoms (fits) if drug is stopped suddenly.

·    May impairability  to drive or operate machinery. Patients to abstain from alcohol.

·    Not recommended in children, Patients with history of drug, alcohol abuse.

·    Monitor CVS and RS parameters while on therapy (depression of vital centers may occur). 

Drug Interactions

Potentially fatal:

·    Given with barbiturates, alcohol, opioids, hypnotics and other sedatives may have an excessive
depressant effect and cause depression of the vital centers.

·    Azole type of antifungals, oral contraceptives increases toxicity of alprazolam by decreasing its
metabolism.

Non fatal :

·    With MAO inhibitors may have a hepatotoxic effect.

·    Enhance effects of antihypertensives, muscle relaxants, sedative effects of anti depressants.

·    May increase plasma phenytoin concentration. 

Adverse Effects:

Common effects:

·    Excessive sedation, drowsiness, fatigue, light-headedness.

·    Tachycardia, chest pain and hypotension.

·    Gastro – intestinal disturbances – nausea, vomiting etc.,

Rare effects :

·    Ataxia in-coordination irritability, paradoxical CNS stimulation especially in elderly (headache, vertigo, tinnintus etc.)

·    Rebound CNS stimulation and its effects on stopping the drug.

·    Precipitation of porphyria in susceptiable individuals.

·    Hypersensistivity – skin rashes, dermatitis etc.,

·    Decreased libido, weight gain, tremors , muscle cramps. 

Drug Toxicity

Gastric lavage , CVS, respiratory system monitoring. If hypotension occurs use vasopressors. Flumazenil is the specific antidote for benezodiazepines. 

Storage

            Store in airtight containers.           

Shelf life       3 years.