15.1. Antacids & Anti Ulcer

RANITIDINE

General information

Drug Code                              Preparation                             Strength

      159                                    Inj. Ranitidine HCI                    50 mg/2 ml

      160                                    Tab. Ranitidine                                     150 mg

Description of the Drug

            It is a histamine H2 receptor antagonist.

Mode of Action:

It competitively blocks the H2 receptor and therapy blocks histamine induced gastric acid secretion and reduces pepsin output. Both basal and acid secretion is stimulated by food and other stimuli are reduced.

Pharmacokinetics :

It is absorbed from the GIT but has only 50% bioavailiability due to first pass metabolism. Rapidly absorbed following IM injection with in 15 minutes and bioavailaability is 90%. Duration of action is 24 hours. Following IM or IV administration, clearance is rapid – 6 –8 hours. Excretion is mainly as unchanged drug in the urine.

Clinical Information

Indications  

·    Acid peptic disease – gastric and duodenal ulcers, both in active management and in maintenance therapy.

·    Zollinger – Ellison syndrome.

·    Gastro esophageal reflux disease, erosive esophagitis.

·    Prophylatic use in prevention of stress induced ulcers and prevention of acid aspiration in obstetric patients (mendelson syndrome) and during surgeries.

Dosage

Oral :

Duodenal and gastric ulcer:

Single daily dose of 300 mg by mouth at bedtime or 150 mg twice daily, initially for at lease 8 weeks. Maintenance therapy after 8 weeks of 150 mg daily at bedtime.

Reflux Oesophagitis and zollinger – Ellison syndrome: 150 mg bd for 8 weeks.

Parenteral :

            50 mg IM or IV every 6 – 8 hours.

Routes of Administration   Oral, IM, IV:

Contraindications  

·    Known hypersensitivity.

·    Porphyria.

Precaution / Practice Points

·    The Dosage is to be reduced in patients with impaired renal functions (see appendix).

·    Use with caution in children less than 12 years and hepatic dysfunction.

·    While on treatment, monitor renal and hepatic parameters and for signs of ulcer healing.

·    Administration instruction:

-     When given I.V. dilute 50 mg in 20 ml and give slowly over at least 2 minutes.

-     Do not mix diazepam, barbiturate, clindamycin, and amphotericin B in same syringe, due to physical incompatibility.

Drug Interactions

Potentially fatal:

·    Increases toxicity of cyclosporin, glipizide, glibenclamide, phenytoin and quinidine.

·    Potentiates the effects of gentamicin and may cause neuromuscular blockade.

Non fatal:

·    Decreases absorption of  ketoconazole, cyanocobalamine and some antibiotics.

Adverse Effects

Common effects:

·    Headache, dizziness.

·    Diarrhoea or constipation.

Rare effects:

·    Reversible hepatitis, elevation of liver enzymes.

·    Sedation, malaise, fatigues.

·    Skin rashes and dermatitis.

·    Thrombocytopenia, neutropenia, agranulocytosis.

Drug of Toxicity

Symptoms like malaise, headache, dizziness, disturbance of gait, tremors, vomiting, rapid respiration, renal failure CNS depression, hypotension, hepatic injury may occur.

Treatment of Toxicity

Gastric lavage or emesis induction with in 4 hours of ingestion of drug, followed by supportive and symptomatic management.

Storage

            Keep in a cool, dark place.

Shelf    Life       2 years.

ANTACID

General information

Drug Code                              Preparation                             Strength

       274                                   Liquid Antacid                                      120 ml bottle

       777                                   Tab. Antacid                                        100 tab.

Description of the Drug

            Liquid Antacid is compound preparation containing

            Aluminum hydroxide gel – 250 mg.

            Magnesium trisilicate  - 250 mg.

            Methyl polysilozane      - 50 mg per 5 ml.

            Tablets antacid contains :

            Aluminum hydroxide gel – 120 mg.

            Magnesium trisilicate  - 250 mg.

            Peppermint oil.

Mode of Action

Being basic compound, aluminum hydroxide and magnesium trisilicate react with gastric acid  to form chloride salts of magnesium, aluminum and water. This reaction neutralizes the acid  and raises the pH of the stomach contents. It acts as a demulcent and forms a coating over the ulcer crater and prevents irritation from food contact. Aluminum tends to cause constipation by smooth muscle relaxation, while magnesium may produce diarrhoea by its action as an osmotic purgative. Hence both are combined to equalize each other’s effects. Methyl polysilozane is a silicon polymer, which reduces surface tension and collapse air bubbles. Thus it helps to reduce distension and flatulence.

Pharmacokinetics :

On oral administration, none of the components are absorbed significantly. Some aluminum, which is absorbed, is excreted in the urine (this is impaired in renal failure). It also binds to phosphates in the GIT and prevents its absorption.

Clinical Information

Indications  

·    Symptomatic relief of hyperacidity in

-     Acid peptic disease.

-     Gastritis, gastro oesophageal reflux.

-     Peptic oesophagitis.

-     Hiatus hernia.

·    Prophylactic in gastritis and irritation when given with drugs like NSAIDS, steroids.

Dosage

Adult:

            10 – 20 ml (2 –4 teaspoons) of liquid antacid – 4 times a day and at bedtime.

            Tablets -  1 – 3 tablets – 4 times a day and at bedtime.

Child :

            6 – 12 years – 5 ml tds.

Routes of Administration          Oral

Contraindications

·    Renal failure (In renal failure patients – systemically absorbed aluminum is not excreted leading to encephalopathy and osteomalacia due to aluminum deposition in target tissue).

·    Hypophosphatemia.

Precautions / Practice Points:

·    Prolonged use of aluminum containing antacids may cause hypophosphatemia and osteoporosis.

·    Administration   instructions:

            Liquid – administered 20 minutes to 1 hour after meals and at bedtime.

Tablet  - instruct to chew well before swallowing, 4 times a day, 20 minutes to 1 hour after meals and at bedtime.

Drug Interactions

Non fatal:

Antacids decrease the absorption of tetracyclines, iron salts, ketoconazole, fluroquinolones, H2 blockers, phenothiazines, phenytoin, diazepam, ACE inhibitors, isoniazid, rifampicin, ethambutol, ciprofloxacin, norfloxacin, chloroquine and digoxin.

Adverse Effects

Common effects:

            Nausea, vomiting, abdominal pain may occur.

Rare effects:

In prolonged use – muscle weakness, fatigue, osteomalacia due to hypohphosphatemia can occur.

Drug Toxicity

·    On prolonged use, chronic poisoning due to aluminum may cause:

Encephalopathy, dementia.

Microcytic anaemia.

Osteomalacia

Treatment of Toxicity

Withdrawal of the drug.

Storage

Store in a cool, dark, dry place.

Shelf life                      3 years.

OMEPRAZOLE

General information

Drug Code                              Preparation                             Strength

      488                                    Cap Omeprazole                      20 mg       

Description of the Drug

Omeprazole is a proton pump inhibitor.

Mode of Action

            It prevents secretion of  gastric acid by inhibiting the H+K+ ATP ase mechanism.

Pharmacokinetics :

Oral absorption is dependent on PH – best absorbed when acidity is present. Plasma half-life is only 1 hour, but it is tightly bound to its target enzymes. Hence, effects of the drug lasts for 24 hours. It is metabolized in liver and excreted in the urine.

Clinical Information

Indications  

·    Acid peptic disease – both active disease treatment and for maintenance therapy.

·    Gastroesophageal reflux disease and erosive esophagitis.

·    Hypersecretory states like Z.E. syndrome etc.

Dosage

·    Reflux oesophagitis – 20 mg o.d. or 4 – 8 weeks.

·    Maintenance dose of 20 mg o.d.

·    Peptic ulcers:

·    Gastric ulcer: 40 mg o.d. for 4 – 8 weeks.

·    Duodenal ulcer 20 mg o.d. for 4 – 8 weeks.

·    Zollinger – Elliswon syndrome – 60 to 120 mg once daily.

Route of Administration       Oral

Contraindications  

            Hypersensitivity.

Precaution / Practice Points

·    Therapy with omeprazole produces rebound hypergastrinemia.

·    Use with caution in liver disorders, pregnancy and breast-feeding.

·    Administration instructions:

-     Take 1 hour before meals, first thing in the morning.

Drug Interactions

Potentially fatal:

·    Inhibits metabolism of drugs metabolized by hepatic cytochrome p450 enzyme system hence increases plasma concentration of diazepam, phenctin warfatin, disulfiram, and benzodiazepines. Plasma concentration of digoxin may be increased.

Non fatal:

·    May alter absorption of certain drugs like iron, salts, and ampicillin, ketoconazole which  depends on gastric PH.

Adverse Effects

Common effects:

·    Headache, diarrhoea, abdominal pain, flatulence, nausea, vomiting, rashes, constipation.

Rare effects:

·    Hypersensitivity reaction – skin eruption, erythema multiforme, photosensitivity reactions, angioedema and bronchospasm.

·    Precipitaion of encephlopathy in hepatic disorders, reversible mental confusion, hallucinations.

·    Nephrotoxicity : interstitial nephritis.

·    Gynaecomastia, impotence.

Drug Toxicity

Confusion, drowsiness, blurred vision, tachycardia, hypothermia, sedation, convulsion, nausea,
sweating, flushing headache may occur.

Treatment of Toxicity

            Symptomatic and supportive treatment.

Storage

            Store in airtight containers. Protect from light.

Shelf life          2 years.

15.2.              Anti Emetics

METACLOPRAMIDE

General information

Drug Code                              Preparation                             Strength

      158                                                Inj. Metaclopramide                 10 mg / 2 ml.

Description of the Drug

            A widely used antiemetic and prokinetic agent.

Mode of Actions

It acts by sensitizing the gastro – intestinal smooth muscle to acetylcholine. It also has an inherent cholinomimetic property. It increases peristalitic activity, tone of lower esophageal sphincter and gastric motility. It decreases the emptying time and relaxes the pyloric sphincter. The antiemetic action of metaclopramide is due to dopamine receptor antagonist properties. It blocks the stimulation of CTZ in the medulla by dopamine.

Pharmacokinetics :

After IV administration, onset of action is 1 – 3 minutes and after IM administration 10 –15 minutes. Plasma half-life is 5 –6 hours. Excreted in the urine unchanged and as metabolites.

Clinical Information

Indications  

·    Antiemetic action:

Prevention of nausea and vomiting during the postoperative period, cancer chemotherapy, drug induced emesis, due to migraine or radiation therapy.

·    Gastro kinetic agent:

            Statsis due to diabetic gastro paresis, post surgical, post vagotomy.

·    For radiological examination – emergency barium meal series.

·    For management of gastro esophageal reflux disease.

·    For facilitation of small bowel intubation  (it relaxes the pyloric sphincter).

·    For prevention of aspiration in emergency G.A. procedures.

Dosage

·    10 mg IM or IV.

·    If used as an adjunct with cancer chemotherapy where greater antiemetic action is required, a larger dose of 2 mg/kg can be used.

Routes of Administration    IM,   IV

Contraindications

·    Whenever stimulation of gastro-intestinal motility is dangerous: haemorrhage, perforation, and
obstruction of GIT.

·    In pheochromocytoma: it may precipitate hypertensive crisis due to catecholamine release.

·    In epilepsy and extra pyramidal diseases of  CNS.

·    Hypersensitivity.

Precaution / Practice points

·    Use with caution in hypertensive patients especially when given IV – hypertensive crisis may occur due to endogenous catecholamine release.

·    Patients to be instructed not be drive or operative machinery as it causes sedation and drowsiness.

·    Avoid in pregnancy and lactation

·    Reduce dose in renal impairment (see appendix).

·    Use with caution in hepatic disorders, elderly and children.

·    May exacerbate porphyria.      

·    Instruct patient to abtain from alcohol.

·    Monitor for dystonic reactions and renal function tests when on treatment.

·    Administration instructions:

-     Give I.V. injection slowly: 10 mg over 1 –2 minutes: can be given undiluted.

-     Do not mix with cephalosporines, chloramphenicol, sodium bicarbonate  (because of chemical incompatibility) in the same syringe.

Drug Interactions

Potentially fatal:

·    CNS depressants like alcohol, sedative hypnotics; narcotics may increase the sedative effects.

·    Increased risk of toxicity due to lithium may occur if given concomitantly.

·    When given to patients on MAO inhibitors, hypertensive crisis may occur due to release of endogenous catecholamines.

Non fatal:

·    Anti-muscarinic agents and opioid analgesics antagonise the actions of metaclopramide.

·    It decreases the absorption of digoxin, aspirin, paracatamol, l- dopa, and tetracycline.

·    With anti psychotics, there is increased risk of extra pyramidal effects.

Adverse Effects

Common effects:

·    Drowsiness, fatigue and lassitude; mental depression with suicidal tendency, confusion and disorientation may occur.

·    Diarrhoea.

·    Extrapyramidal symptoms – acute dystonic reactions, involuntary limb movements oculogyric crisis, grimacing, tongue protrusion, trismus, caryngospasm and death may occur, (treatment – 50 mg of diphenhydramine or 1 –2 mg IM of benztropine).

Rare effects:

·    Tardive dyskinesia, and parkinsonism may occur when used for longer periods of time.

·    Endocrine:

·    Hyperlactinemia (due to dopamine receptors antagonism) causes galactorrhoea, amenorrhea, and gynaecomastia.

·    CVS – hypertension, tachyarrhythmias (on administration).

·    Hepatotoxicity on prolonged use.

·    Allergic reactions like rashes,urticaria.

Drug Toxicity

Drowsiness, ataxia, disorientation, seizures and extrapyramidal reaction, methaemoglobinemia in
infants.

Treatment of Toxicity

Symptomatic treatment:

            Anticholinergics, diphenhydramine for extrapyramida reactions.

Storage:

            Store in a cool, dry place.

Shelf life          3 years.

DOMPERIDONE

General information

Drug Code                              Preparation                             Strength

      387                                    Tab. Domperidone      10 mg.

Description of the Drug

Domperidone is a benzimidazole derivative which possesses prokinetic and antiemetic properties.

Mode of Action

It is a dopamine receptor antagonist . It penetrates the blood brain barrier poorly. Hence, action is mainly in the periphery and less efficient than that of metaclopromide, but the risk of extrapyramidal side effects is much lower when compared to metaclopramide. However it acts on the posterior pituitary to produce hyperprolactinemia by D2 antagonism.

Pharmacokinetics :

It is absorbed from the GIT, but undergoes first pass metabolism in liver. Bioavailability is only 5 % following oral administration. Its metabolites are excreted in faeces mainly and also in the urine. Plasma half-life is 7 – 8 hours. Onset of action is within 1 hour of administration.

Clinical Information

Indications  

            As an anti-emetic for relief on nausea and  vomiting of any cause.

-     Radiation, uremia.

-     Drug induced (L-dopa, bromocriptine, chloroquine etc.,).

-     Postoperative situations.

-     Reflux oesophagitis.

Dosage

Adult   20 – 40 mg t.d.s

Children  - 0.3 mg / kg t.d.s.

Route of Administration     Oral.

Contraindications.

·    Gastro intestinal obstruction or perforation.

·    Pheochromocytoma.

·    CNS disorders like epilepsy.    

Precaution / Practice Points

·    Not recommended for chronic use or long-term administration.

·    Administer cautiously in psychotic patients.

·    Use with caution in renal impairment pregnancy and lactation.

·    Administration instruction:

-     For prevention of drug-induced emesis, administer doperidone half to one hour before giving the particular emetogenic drug.

Drug Interactions

Non fatal:

            Opioid analgesics and  antimuscarinics antagonise its effects.

Adverse Effects

Are rare.

·    Headache, skin rashes, loose stools.

·    Hyperprolactinemia – galactorrhoea, amenorrhoea , gynaecomastia etc.,

·    Extra- pyramidal side effects like dystonic reactions may occur very rarely.

·    Allergic reactions.

Drug Toxicity

Toxicity results when dose exceeds 500 microgram/kg body weight daily for prolonged periods of time. The symptoms are acute dystonic reaction, restlessness, drowsiness, headache, GI disturbances etc.,

Treatment of Toxicity

            Gastric lavage and symptomatic treatment.

            Diphenhydramine can be used to treat extra pyramidal reactions.

Storage

            Store in airtight container, protect from light.

Shelf life          3 years.

15.3.             Anti spasmodic drugs

DICYCLOMINE HCL

General information

Drug Code                              Preparation                             Strength

      164                                    Tab.Dicyclomine Hcl   10 mg.

      458                                    Tab.Dicyclomine Hcl   10 mg/ml

      459                                    Oral. .Dicyclomine Hcl              10 mg/ 5 ml..

Description of the Drug

             It is a antispasmodic and antimuscarinic agent.

Mode of Actions

It has a dual effect on visceral smooth  muscles; it relaxes the smooth muscle by its anticholinergic effect as well as by its direct action.

Pharmacokinetics :

It is readily absorbed from gastro-intestinal tract; it crosses the blood brain barrier and placenta and traces appear in milk. It is excreted in the urine.

Clinical Information

Indications  

As an antispasmodic agent:

·    Used in gastro intestinal disorder associated with smooth muscle spasm as in irritable bowel
syndrome.

·    Dysmenorrhoea.

Dosage

Adult              - 10 – 20 mg. 4 times daily. (Maximum 160 mg/day).

Children          - 6 months to 2 years – 5 –10 mg, 3 –4 times/daily.

                           2 years – 12 years – 10 mg 3 times/daily.

Routes of Administration   Oral,  I.M.

Contraindications

·    Obstructive breathing, obstructive lesions of GIT, paralytic ileus.

·    In sever ulcerative colitis it may   suppress intentional motility to the point of causing toxic mega colon.

·    Infants less than 6 months and nursing mothers.

·    Myasthenia gravis.

·    Closed angle glaucoma.

Precaution / Practice Points

·    Use with caution in patients with

-     Prostatic enlargement as it may cause urinary retention.       

-     Obstructive diseases of GIT, hiatus hernia, reflux esophagi is (produces sphincter relaxation and aggravates the disease).

-     Cardio vascular disorders like tachyarrhythmias, congestive cardiac failure, cornorary heart disease and hypertension (due to its antimuscarinic effects).

-     Hepatic and renal disease.

·    May cause drowsiness or blurred vision. So, instruct patients not to derive or operate machinery and abstain from alcohol as excessive CNS depression may occur.

·    Use with caution in elderly, children and patients with Down’s syndrome (increased risk of side effects).

·    Administration Instructions:

-     Never give I.V. only I.M.

-     Take 30 – 60 minutes before meals.

Drug Interactions

Potentially fatal:

·    Increases toxicity of anticholinergics, narcotic analgesics and type I antiarrhythmic agents.

Non-fatal

·    Drugs possessing anticholinergic activity (phenothiazines, MAO inhibitors, tricylic antidepressants, etc) and sympathomimetics potentiates side effects of dicyclomine.

·    Dicyclomine may retard absorption of drugs like digoxin by decreasing intestinal motility.

Adverse Effects

Common effects :

·    Due to its anticholinergic properties dry mouth, blurred vision, anorexia, nausea, tachycardia, palpitations, difficulty in defecation and micturition.

·    Local irritation and pain onparenteral administration.

Rare effects:

·    Dizziness, light-headedness, drowsiness, numbness, mental confusion, disorientation, hallucinations.

·    Dyspnoea and respiratory collapse have been reported in infants.

Drug Toxicity

·    Toxic dose: 1500 mg (adult).

·    Headache, nausea, vomiting, blurred vision, mydriasis, hot dry skin, tachycardia, rapid respiration, hyperpyrexia, and confusion. A curare like neuromuscular blockade may also occur.

Treatment of Toxicity

·    GI decontamination : emesis, lavage activated charcoal adminstration.

·    Symptomatic treatment: sedatives to decrease CNS excitation, appropriate cholinergic agents can be used judicious use of physostigmine to combat its anticholinergic effects.

Storage

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

Shelf life          3    years.