3.  ANTI ALLERGICS & DRUG USED IN ANAPHYLAXIS                                                                                 

CETRIZINE  HYDROCHLORIDE

 

General   Information

Drug Code                     Preparation                                         Strength

         442                         Tab. Cetrizine                                           10 mg.        

Description of the Drug

Cetrizine hydrochloride, a newer second generation drug, is a selective H1 receptor antagonist.

Mode of Action

It is a reversible, competitive inhibitor of H1 receptors.  It’s advantage is that it penetrates the CNS poorly, hence has minimal sedative action when compared to other antihistaminic agents.

Pharmacokinetics

It is well absorbed from the GIT, but absorption rate is decreased by the presence of food.  Onset of action is 10-30 minutes and the action lasts for 12-24 hours.  Metabolized in the liver and excreted in the urine as metabolities and 50% as unchanged drug. 

Clinical  Information

Indications

Short term use:

·  Symptomatic relief in allergic states for relief of sneezing, rhinorrhoea, postnasal discharge.

·  Symptomatic relief in common coughs and colds.

·  Chronic urticaria, atopic dermatitis or contact dermatitis and pruritic skin disorders.

Dosage

Adult – 10 mg daily, single dose orally.

Children  From 6-12 years : 5 mg.

Routes of Administration    IM, IV, SC.

Contraindications

·  Hypersensitivity to the drug.

·  Pregnancy and breast feeding.

Precautions / Practice points

·  Not recommended for children under 6 years.

·  Reduce dose to 5 mg in

-     Renal impairment.

-     Hepatic dysfunction.

-     Elderly patients.

-     Patients on haemodialysis.

Drug Interactions

Avoid concomitant CNS depressants like alcohol, barbiturates and sedative hypnotics.

Adverse Effects

Common effects:

·  Somnolence.

·  Fatigue, malaise, headache.

·  Dry mouth

Rare effects:

·  Paradoxical CNS stimulation in children, dizziness, tinnitus, incoordination, blurred vision, diplopia, euphoria and nervousness.

·  Antimuscarinic side effects.

Drug Toxicity

Acute poisoning is more common in children which is mainly due to central excitatory effects, such as hallucinations, excitement, ataxia, inco-ordination; may progress to convulsions, irritability, respiratory depression and coma.

Treatment of Toxicity

·  Symptomatic and supportive treatment.

·  Physostigmine may used to reverse the anticholinergic effects.

Storage

Store in cool, dry, dark place.

Shelf Life                    3 years.

                                                DEXAMETHASONE

General   Information

Drug Code                        Preparation                                         Strength

         75                           Inj. Dexamethasone                                   2 mg/2ml.        

Description of the Drug

Dexamethasone is synthetic, long acting glucocorticoid.  It is 30 times more potent than hydrocortisone.

Mode of Action

Dexamethasone acts via glucocorticoid receptors in tissue to cause a variety of effects:

Catabolic effects : Increased breakdown of proteins, increased lipolysis, etc.,

Hyperglycaemic effects: Increased glycogenolysis and gluconeogenesis.

Antiinflammatory effects: Depression of levcocyte activity and functions, decreased migration of leucocytes, decreased producion of lymphokines, prostaglandins, leukotrienes and other mediators of inflammation.

Pharmacokinetics

It is readily absorbed from the GIT and is widely distributed throughout the body.  Duration of action is around 36 hours.  Clearance is similar to clearance of endogenous steroids.

Clinical  Information 

Indications

Replacement therapy:

-     Adrenal insufficiency  - primary or secondary.

-     Panhypopituitarism.

-     Congenital adrenal hyperplasia.

Diagnostic uses

·  Dexamethasone suppression test for diagnosis of cushing’s syndrome, disorders of hypothalamo – pituitary – adrenal axis, depression and other psychiatric disorders.

As an anti-inflammatory agent in

1.        Autoimmune disorders.

·  Rheumatoid arthritis, ankylosing spondylitis.

·  Collagen disorders like systemic lupus erythematosus,polyarteritis nodosa, vasculitides, dermatomyositis etc.,

·  Thyroiditis.

·  Rheumatic carditis.

·  Pemphigus, exfoliative dermatitis etc.

·  Ulcerative colitis, inflammatory bowel disease.

·  Idiopathic thrombocytopenic purpura, autoimmune haemolytic anaemia.

·  Nephrotic and  nephritic syndromes.

2.         Allergic states.

·  Bronchial asthama, angioneurotic edema.

·  Drug hypersensitivity, Steven Johnson’s syndrome.

·  Loeffler’s syndrome, serum sickness, atopic or contact dermatitis.

·  Allergic conjunctivitis, irido cyclitis, optic neuritis etc. 

3.         Infections – (Given under antibiotic cover only)

·  TB meningitis, adrenal tuberculosis, TB of the genito urinary tract, renal TB, pleural effusion (given intrapleurally)

·  Leprosy – treatment of reactional states.

·  Gram negative septicaemia.

·  Herpes simplex infection.

·  Aspiration pneumonitis.

4.            Organ transplants – brain surgery  ( to decrease cerebral edema, dexamethasone

   Preferred due to its minimal mineralocorticoid activity).

5.            In neoplastic diseases –

·  Acute lymphoblastic  leukemia – in CNS or meningeal infiltration.

·  In management of paraneoplastic conditions like hypercalcemia,

·  As an antiemetic prior to cytotoxic chemotherapy.

6.              *   As intraarticular or soft tissue injection in

-     Synovitis of osteoarthritis.

-     Rheumatoid arthritis and gouty arthritis.

-     Epicondylitis, tenosynovitis, bursitis.

      *   Intralesional injections in

-     Psoriasis, keloid, lichenplanus.

-     Ganglion.

-     Granuloma annulare.

Dosage

      For allergic conditions : systemic administrationof steroids can be given

-    days 1 : 4-8 mg I.V injection, bolus dose.

-     days 2 and 3 :3 mg in divided doses.

-     days 4 and 5 : 1 to 5 mg in divided doses.

-     Days 6 and 7 : 0.25 mg in divided doses.

Doses to be individulised depending on severity of the condition.

For severe shock : IV – 2-6mg/kg repeated within 2-6 hours: taper slowly over next 5 days.

For cerebral oedema; IV – 10 mg followed by 4 mg 6 hourly and then continued over  5-7 days by gradual reduction of the drug dose.

As an antiemetic (prior to chemotherapy ) : 5-10 mg/m2/dose of chemotherapy, every 6 hours.

Oral doses : 0.5-9 mg/kg/day in divided doses – as the condition requires, when the patient is being transferred from parenteral form to oral form of therapy.

Intra articular, intra lesional, soft tissue injections : 0.8-6 mg as the condition requires.

Routes of Administration    IM, IV, SC.

            Oral, IM,IV Intra articular, Intra lesional, soft tissue injection.

Contraindications

Absolute : Systemic fungal infections or any untreated infections:

Relative   : Acid peptic disease, hypertension, diabetes mellitus, herpes infection, psychosis, epilepsy, congestive cardiac failure.

Precautions / Practice points

·  Lowest possible dose to be used for least amount  of time.

Withdrawal of steroids should be gradual to prevent secondary, drug induced  adrenal insufficiency ( malaise, fatigue, hypokalemia etc.).

·  Patients to be monitored for (who are on long term therapy)

-     blood, urine sugar (diabetogenic state).

-     Acid peptic disease, gastro-intestinal bleeds.

-     Skeletal system – osteoporosis, aseptic necrosis of hip,myopathies and muscle wasting.

-     Cataracts.

-     Psychosis.

·  Steroids may mask signs of infection, hence condition should be properly diagnosed and localized prior to therapy and antibiotic cover should be adequate.

·  Dexamethasone has minimal mineralocorticoid activity, hence does not produce salt and water retention and hypertension (unlike cortisone).

·  Lactation should not be done while on steroids (excreted in milk and may cause suppressionof fetal adrenals).

·  Live vaccines should not be administered to patients on steroids.

·  In hypothyroidism and cirrhosis – dosage should be reduced because of enhanced activity.

·  Increase the dose during surgery, stress and trauma.

Drug Interactions

Potentially fatal:

With potassium depleting diuretics, hypokalemia may occur.

Non fatal :

Drugs which increase metabolism of steroids – phenytoin, barbiturates, rifampicin, ephedrine.

Adverse Effects

·  Depends on dose and duration of therapy.

· Cushingold features – moonface, easy bruising, purple striae, fragile skin, hirsutism, acne, fatigue, malaise, buffalo hump, central obesity, myopathy, osteoporosis etc.

·  Growth retardation in children.

·  Exacerbation of psychosis.

Storage

Store in airtight containers, protected from light.

Shelf Life                    2  years.

HYDROCORTISONE

General   Information

Drug Code                        Preparation                                         Strength

         76                           Inj. Hydrocortisone Sodium                    100 mg.        

Description of the Drug

It is a synthetic Preparation of hydrocortisone which is a naturally occurring steroid (a glucocorticoid, secreted by the adrenal cortex) in the form of water soluble esters.

Mode of Action

Hydrocortisone acts via glucocorticoid receptors in tissue to cause a variety of effects:

·  Catabolic effects:  Increased breakdown of proteins, increased lipolysis.

·  Hyperglycaemic effect: Increased glycogenolysis and glucogenesis.

·  Anti-inflammatory effects: Depression of leucocyte activity and functions, decreased migration of leucocytes, decreased production of lymphokines, prostaglandins, leukotrienes and other mediators of inflammation.

·  Mild salt retaining actitivty.

Pharmacokinetics

Hydrocortisone sodium semisuccinate is a water soluble ester and hence is easily absorbed from place of administration.  It has a rapid onset of action but of short duration (hence most suitable for acute conditions) Plasma half life is only 60-90 minutes but since its action is due to receptor binding the actual effects lasts for 6-12 hours.  Clearance is by the liver and similar to endogenous steroid clearance.

Clinical  Information

Indications

Replacement therapy:

-  Acute adrenal insufficiency, primary or secondary adrenocortical insufficiency.

-  Congenital adrenal hyperplasia.

-  Panhypopituitarism.

In treatment of following disorders for its anti-inflammatory effects:

·  Rheumatic disorders – acute exacerbation of rheumatoid arthritis, ankylosing spondylitis, acute gouty arthritis, tenosynovitis, epicondylitis.

·  Collagen disease – SLE, polyarteritis etc, giant cell arteritis, polymyalgia.

·  Allergic states – bronchial asthma, atopic or contact dermitis serum sickness, angioneurotic edema, drug hypersensitivity reactions, Loefflers syndrome, Steven Johnson’s syndrome, allergic conjunctivitis, iridocyclitis, uveitis,chorioretinitis, optic neuritis.

·  Auto immune disorders (acute episodes)

-  Thyroiditis.

-  Herpes zoster ophthalmicus, keratitis.

-  Aspiration pneumonitis.

-  Gram negative septicaemia.

·  Organ transplants.

·  Neoplasms – leukemias or lymphomas, acute lymphatic leukemia to reduce symptoms of meningeal infiltration, to combat hypercalcemia ( which occurs as a para neoplastic syndrome).

Dosage

·  Acute adrenal insufficiency:

·  Intially, 1-2 mg/kg in children ; 100 mg in adults as IV bolus injection. Maintenance dose is 25-150 mg/day in 4 divided doses for children; for adults : 300 mg/day in 4 divided doses, gradually taper the parenteral regime and change over to oral steroids, once patient is stable.

·  Anti-inflammatory and immuno suppressive Indications:

Children : 15-240 mg/day in 4 divided doses.

Adults: 15-240 mg/day in 2 divided doses.

Doses to be individualized to each patient.

In shock : 50 mg  IV bolus initially; followed by 500 mg to 2 gm every 6

hours.

Status asthmaticus : 1-2 mg/kg/dose, every 6 hours initially; maintenance

dose is 0.5-1 mg/kg, 6 hourly.

For intralesional, intraarticular, soft tissue infiltration: 25-50 mg as required.

Routes of Administration    IM, IV, SC.

            IM,  IV,  Intra articular, Intra Lesional, Soft tissue injection.

Contraindications

Absolute :

·  Systemic fungal infections .

Relative   :

·  Diabetes mellitus.

·  Hypertension with congestive cardiac failure.

·  Acid peptic disease.

·  Osteoporosis.

·  Herpes simples infections.

·  Psychosis.

·  Glaucoma.

Precautions / Practice points

·  Give the lowest possible dose for the least amount of time.

Withdrawal of therapy should be gradual.  Patients receiving this drug must be monitored for hyperglycemia, sodium retention with edema, hypokalemia, hypertension and stress ulcers.

·  Steroids may mask signs of infection and prevent localization.  Hence, the condition should be clearly delineated, before steroid adminstration.

·  Appears in breast milk and may result in fetal adrenal suppression.  Hence, avoid nursing while on steroid therapy.

·  Live vaccines not to be administered to patients on steroids.

·  Enhanced effects of steroids are seen in hypothyroidism and cirrhosis.

·  Should be given always with antacids to prevent gastric irritation.

·  Increase the dose during stress, surgery and trauma.

·  Administration instructions:

-  While giving intravenously dilute it to a concentration of 50 mg/ml and administer slowly.

Drug Interactions

Potentially fatal:

With potassium depleting diuretics, hypokalemia may occur.

Non fatal :

Drugs which incease metabolism of steroids – phenytoin, barbiturates, rifampicin, ephedrine.

Adverse Effects

·  Since it has salt retaining properties – sodium and water retention,  hypertension and precipitation of congestive cardiac failure may occur.

·  Stress ulcers and GIT bleeding.

·  Impaired wound healing.

·  Headache, vertigo, psychic disturbances, mood swings.

·  Endocrine – hyperglycemia, worsening of diabetes mellitus.

·  Weight gain, nausea, malaise or increased appetite. 

Drug Toxicity

When excess drug is administered for too long:

·  Cushingoid features – moonface, easy bruising, purple striae, fragile skin, hirsutism, acne, fatigue, malaise buffalo hump, central obesity, myopathy, osteoporosis etc.

·  Sudden withdrawal leads to withdrawal symptoms such as muscle weakness and wasting. 

Treatment of Toxicity

·  Gradual withdrawal of the drug.

·  Symptomatic treatment. 

Storage

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

Shelf Life                    2  years.

                                                BETAMETHASONE

General   Information

Drug Code                        Preparation                                          Strength

         78                           Inj. Betamethasone                                   0.5 mg

        376                          Betamethasone Valerate Ointment           0.12%

Description of the Drug

Betamethasone is a synthetic long acting glucocorticoid, 25 times more potent than hydrocortisone.

Mode of Action

Betamethasone acts via glucocorticoid receptors in tissue to cause a variety of effects:

·    Hyperglycaemie effect:  Increased glycogenolysis and gluconeogenesis.

·    Anti-inflammatory effect:  Depression of leucocyte actitivy and functions, decreased migration of leucocytes, decreased production of lymphokines, prostaglandins, leukotrienes and other mediators of inflammation.

·    Topicaly applied for its anti-inflammatory, antipruritic and vasoconstrictive properties.

Pharmacokinetics

It is readily absorbed on oral administration and when applied topically exerts a local action on the surrounding tissue.  Onset of action is 30 minutes to 1 hour after ingestion. Duration of action is 24-36 hours.  Clearance is similar to endogenous steroid clearance, by metabolism in the liver.

Clinical  Information

Indications

Replacement therapy:

-     Adrenal insufficiency – primary or secondary.

-     Panhypopituitarism.

-     Congenital adrenal hyperplasia.

As an anti-inflammatory agent in

1.         Autommune disorders.

·  Rheumatoid arthritis, ankylosing spondylitis.

·  Collagen disorders like systemic lupus erythematosus, polyarteritis nodosa, vasculitides, dermatomyositis etc.,

·  Thyroiditis.

·  Rheumatic carditis.

·  Pemphigus, exfoliative determatitis etc.,

·  Ulcerative colitis, inflammatory bowel disease.

·  Idiopathic thrombocytopenic purpura, autoimmune haemolytic anaemia.

·  Nephrotic and nephritic syndrome.

2.         Allergic states:

  •  Bronchial asthma, angioneurotic edema.

  •  Drug hypersensitivity, Steven Johnson’s syndrome.

  • Loeffler’s syndrome, serum sickness, atopic or contact dermatitis.

  • Allergic conjunctivitis, irido cyclitis, optic neuritis etc.

3.         Infections – (given under antibiotic cover only).

·  TB meningitie, adrenal tuberculosis, TB of the genito urinary tract, renal TB, pleural effusion ( given intrapleurally).

·  Leprosy – treatement of reactional states.

·  Gram negative septicaemia.

·  Herpes simplex infection.

·  Aspiration pneumonitis.

4.         Organ transplants and in brain surgery (to decrease cerebral edema), betamethasone can be used due to minimal mineralo corticoid activity.

5.         Neoplasias – in CNS infiltration in acute lymphoblastic leukemia, treatment of
hypercalcemia ( a paraneoplastic syndrome).

6.         Topical application for antipruritic and anti-inflammatory effects on steroid reponsive dermatoses like atopic or can tact dermatitis, allergic skin reactions, psoriasis etc.,

Dosage

·  Topical : as necessary, twice a day.

·  Orally: Adults – 0.5 – 9 mg/day/divided doses, depending on indication, severity of disease and patient response – dose to be individualized, to each patient.

·  Children – 0.25 mg/kg/day in divided doses.

Routes of Administration    IM, IV, SC.           

Contraindications

Absolute :  Systemic fungal infections .

Relative   : Acid peptic disease, hypertension, diabetes mellitus, Herpes infection,

      psychosis, epilepsy, congestive cardiac failure.

Topical : Not to be used in treatment of perioral dermatitis, rosacea.

Precautions / Practice points

·  Give the lowest possible dose for the least amount of time.

Withdrawal of  steroids should be gradual to prevent secondary, drug induced adrenal insufficiency (malaise, fatigue, hypokalemia etc.,)

Patients to be monitoring for (who are on long term theraphy)

-  blood, urine sugar (diabetogenic sate)

-  acid peptic disease, gastro-intestinal bleeds.

-  Skeletal system – osteoporosis, aseptic necrosis of hip,myopathies and muscle wasting.

-  Cataracts.

-  Psychosis.

 

Steroids may mask signs of infection, hence condition should be properly diagnosed and localized prior to therapy and antibiotic cover should be adequate.

·  Betamethasone has minimal mineralocorticoid activity, hence does not produce salt and water retention and hypertension (unlike cortisone).

·  Lactations should not be done while on steroid (excreted in milk and may cause suppression of fetal adrenals).

·  Live vaccines should not be administered to patients on steroids.

·  In hypothyroidism and cirrhosis – dosage should be reduced  because of enhanced activity.

·  Increase the dose during surgery, stress and trauma.

·  Topical application not to be applied on severely inflamed or broken skin.

·  Use with caution in children under 12, when applied topicalhypothalamus – pituitary – adrenal axis.

·  Administration Instructions:

- Do not apply in areas of infection.

- Do not apply on face or inguinal areas or near eyes.

Drug Interactions

Potentially fatal:

·  With potassium depleting diuretics, hypokalemia may occur.

Non fatal :

Drugs which incease metabolism of steroids – phenytoin, barbiturates, rifampicin, ephedrine.

Adverse Effects

·  Cushingoid features – moonface, easy brusing, purple striae, fragile skin, hirsutism, acne, fatigue, malaise, buffalohump, central obesity, myopathy, osteoporosis etc.,

·  Growth retardation in children.

·  Exacerbation of psychosis.

·  On topical application – stinging or burning, pruritis, dryness of the skin may occur.

Storage

Store in airtight containers, protected from light.

Shelf Life                    Topical : 36 months.

                                    Oral       : 3 years.

                                                            PREDNISOLONE

General   Information

Drug Code                        Preparation                                        Strength

         79                           Tab. Prednisolone                                    5 mg       

Description of the Drug

Prednisolone is a synthetic long acting glucocorticoid.  It is four times more potent than hydrocortisone.

Mode of Action

Prednisolone acts via glucocorticoid receptors in tissue to cause a variety of effects:

·    Catabolic effects: Increased breakdown of proteins, increased lipolysis.

·    Hyperglycaemi effects:  Increased  glycogenolysis and gluconeogenesis.

·    Anti-inflammatory effects:  Depression of  leucocytes activity and functions, decreased migration of leucocytes, decreased  production of lymphokiness, prostaglandins, leukotrienes and other mediators of inflammation.

·    Mild salt retaining activity.

Pharmacokinetics

Prednisolone is readily absorbed orally and widely distributed. Plasma half life is 3-5 hours but duration of effect is 12-24 hours (intermediate acting). Clearance is similar to endogenous steroids.

Clinical  Information

Indications

Replacement therapy:

-     Adrenal insufficiency – primary or secondary.

-     Panhypopituitarism.

-     Congenital adrenal hyperplasia.

Therapeutic uses:

As an anti-inflammatory agent in

1.   Auto immune disorders.

a.   Rheumatoid arthritis, ankylosing spondylitis.

b.   Collagen disorders like systemic lupus erythematosus, polyarteritis nodosa, vasculitides, dermatomycositis etc.,

c.   Thyroiditis.

d.   Rheumatic carditis.

e.   Pemphigus, exfoliative determatitis etc.,

f.    Ulcerative colitis, inflammatory bowel disease.

g.   Idiopathic thrombocytopenic purpura, autoimmune haeolytic anaemia.

h.   Nephrotic and nephritic syndrome.

2.   Allergic states:

·  Bronchial asthma, angioneurotic edema.

·  Drug hypersensitivity, Steven Johnson’s syndrome.

·  Loeffler’s syndrome, serum sickness, atopic or contact dermatitis.

·  Allergic conjunctivitis, irido cyclitis, optic neuritis etc.

3.   Infections – (given under antibiotic cover only).

·  TB meningitis, adrenal tuberculosis, TB of the genite uriary tract, renal TB, pleural effusion ( given intrapleurally).

·  Leprosy – treatement of reactional states.

·  Gram negative septicaemia.

·  Herpes simplex infection.

·  Aspiration pneumonitis.

4.   Organ transplants  : To suppress immune response.

5.   Neoplasias –  Leukemia, acute lymphoblastic leukemia for treatemtn of CNS

Or meningeal infiltration; hypercalcemia (a paraneoplastic syndrome).

Dosage

·  Usual dose is 5 to 60 mg/day in two divided doses or as a single daily dose after breakfast.  To be individualized to each patient depending on type and severity of disease.

·  Anti inflammatory and immunosuppressive Indications: 0.1-2 mg/kg/day in 2,3 divided doses.

·  In asthma : 1-2 mg/kg/day.  Withdrawal should be done by gradual tapering of the dose.

Routes of Administration    IM, IV, SC.           

Contraindications

Absolute :  Systemic fungal infections .

Relative   : Acid peptic disease, hypertension, diabetes mellitus, Herpes infection,

      psychosis, epilepsy, congestive cardiac failure.

Precautions / Practice points

·  The lowest possible dose to be used for least amount of time.  Withdrawal of steroids should be gradual to prevent secondary, drug induced adrenal insufficiency (malaise, fatigue, hypokalemia etc).

·  Patients to be monitoried for (who are on long term therapy).

-     blood, urine sugar (diabetogenic state)

-     acid peptic disease, gastro intestinal bleeds.

-     Skeletal system – osteoporosis, aseptic necrosis of hip, myopathies and muscle wasting.

-     Cataracts.

-     Psychosis.

·  Steroids may mask signs of infection, hence condition should be properly diagnosed and localized prior to therapy and antibiotic cover should be adequate.

·  Lactations should not be done while on steroid (excreted in milk and may cause suppression of fetal adrenals glands).

·  Live vaccines should not be administered to patients on steroids.

·  In hypothyroidism and cirrhosis – dosage should be reduced  because of enhanced activity of steroids.

·  Increase the dose during surgery, stress and trauma.

Drug Interactions

Potentially fatal:

·  With potassium depleting diuretics, hypokalemia may occur.

Non fatal :

Drugs which increase metabolism of steroids – phenytoin, barbiturates, rifampicin, ephedrine.

Adverse Effects

·  Depends on the dose and duration of treatment.

·  Since it has salt retaining properties – sodium and water retention, hypokalemia and hypertension, precipitation of congestive cardiac failure may occur.

·  Cushingoid features – moonface, easy brusing, purple striae, fragile skin, hirsutism, acne, fatigue, malaise, buffalohump, central obesity, myopathy, osteoporosis etc.,

·  Growth retardation in children.

·  Exacerbation of psychosis.

Storage

Store in airtight containers, protected from light.

Shelf Life                    2 years.

ADRENALINE

General   Information

Drug Code                     Preparation                                            Strength

         176                         Inj. Adrenaline                                        1 mg/ml       

Description of the Drug

            Adrenaline is a naturally occurring catecholamine.

Mode of Action

It is a direct sympathomimetic agent acting on both alpha and beta receptors. Beta 2 receptors are more sensitive than beta 1 receptors are more than sensitive than beta 1 receptors.   Its vasoconstrictor effect directly antagonizes the vasodilation and increased capillary permeability produced by histamine.  It thereby restores blood pressure and circulating blood volume. It is a powerful relakant of bronchial smooth muscle by its action on beta 2 receptors, thereby alleviating wheezing, bronchospasm and dyspnoea produced by the allergic reaction.

Pharmacokinetics

It is totally inactive when given by mouth.  It acts rapidly following I.M. and S.C administration in 5-10 minutes.  It is inactivated by processes which include uptake into adrenergic neurons, diffusion and enzymatic degradation by catechomethyl transferase in the liver and body tissue and excreted as 4 hydroxy 3 methody mandelic acid and as conjugates of glucuronide or sulphates.  It crosses the placenta to enter the foetal circulation.

Clinical  Information 

Indications

·  Emergency management of anaphylaxis and anaphylactic shock.

·  In actue attack of bronchial asthma to alleviate asthamatic attacks.

·  It is added to local anaesthetics such as lignocaine hydrochloride to retard diffusion, limit absorption and to prolong the duration of effect of the anaesthetic.

·  To check capillary bleeding, epistaxis, bleeding from the superficial wounds and abrasions.

·  In cardiac resuscitation.

Dosage

Adult

·  Anaphylactic shock : 0.5-1 mg (as a 1:1000 solution) which may be repeated at about 10 minutes intervals, subcutaneously or intramuscularly.

·  For bronchospasm : 0.1 to 0.5 ml of 1:1000 solution, every 4-6 hours.

Children:  10 micro gram/kg, subcutaneously.

                  6-12 years : 0.2 mg.

                  Less than 6 years : 0.1 mg.

·  Along with local anaesthetic: concentration of 1 in 2,00,000 (5 microgram/ml).

·  To control capillary bleeding: Strength of 1: 1000 solution as packs or dressings.

Routes of Administration    IM, IV, SC, TOPICAL           

Contraindications

·  Adrenaline should not be given to patients receiving MAO inhibitors or within two weeks of stopping therapy.

·  In pregnancy, as it may cause foetal anoxia.

·  Patients with ischemic heart disease, cardiac arrhythmias.

·  Acute attack of narrow angle glaucoma.

Precautions / Practice points

·  In patients with hyperthyroidism, arteriosclerosis, hypertension and CVS disorders, great caution has to be taken while administering adrenaline, due to its sympathomimetic action it increases B.P. as well as cardiac work load.

·  Diabetic patients require more insulin and oral hypoglycemics due to its hyperglycemic effect.

·  Should not be used to combat shock due to blood loss (hypovolemic or haemorrhagic shock).

·  Administration Instructions:

- Avoid buttocks for I.M. injection.

- Should not be injected I.V. as it can produce fatal arrythmias.  But, when immediate effects are needed in emergencies and in cardiac arrest after adequate dilution, it can be given slow I.V., but with atmost caution and with continuous ECG monitoring.

- Never to be injected intra-arterially or near a vessel marked vasoconstriction and gangrene may occur.

- Dilute for I.V. administration with normal saline.

- Incompatible with aminophylline, sodium biacarbonate or other alkaline solutions.

Drug Interactions

Potentially fatal:

·  In patients on tricyclic anti depressants such as imipramine and MAO inhibitors, adrenaline can precipitate pressor crisis.

·  Increased risk of arrhythmias may occur if it is given to patients receiving cardiac glycosides or thyroxine and on anaesthetized patients.

Non fatal :

·  When non cardioselective beta blockers such as propranolol is administered along with adrenaline, the bronchodilator actions of adrenaline are inhibited.

Adverse Effects

Dose related

·  Feeling of fear, anxiety, restlessness, apprehension.

·  Tachycardia, arrhythmias, anginal pain, palpitation, dizziness, fainting, flushing and rise in blood pressure can occur.

Drug Toxicity

Toxic doses can cause marked pallor, pulselessness, fatal arrhythmias, acute hypertension causing cerebral haemorrhage (especially in the elderly), pulmonary edema due to peripheral vasoconstriction causing cardiac overload and left ventricular failure can be fatal. 

Treatment of Toxicity

·  Prompt injection of rapidly acting alpha adrenoreceptor blocking agent  such as phentolamine followed by a beta blocker such as propranolol and a rapidly acting vasodilato such as nitroprusside or glyceryl trinitrate can be given.

·  Supportive measures such as artificial ventilation for pulmonary edema; if agitation is severe, haloperidol can be given.

Storage

Store in airtight containers, protected from light.

Shelf Life                     1  years.

CHLORPHENIRAMINE MALEATE

General   Information

Drug Code                     Preparation                                                         Strength

         193                         Tab. Chlorpheniramine Maleate                            4 mg

         196                         Inj. Pheniramine maleate                         2 ml amp(22.75 mg/ml)

         197                         Sy. Pheniramine  Maleate                                   15 mg/ml

Description of the Drug

Pheniramine and its chlorinated derivative chlorpheniramine belong to the alkylamine group of antihistaminic agents.

Mode of Action

It is a antagonist at the H1 receptor, preventing actions of histamine, like release of chemical mediators and the resultant inflammatory response.  It causes moderate degree of sedation and also has an anti muscarinic activity.

Pharmacokinetics

It is absorbed well from GIT. Onset of action is 30 min-1 hour after administration.  Duration of action is 4-6 hours.  After injection of pheniramine maleate, duration of action is 12-14 hours.  It crosses the blood brain barrier.  Both unchanged drug and its metabolites are excreted in urine.

Clinical  Information

Indications

·  Relief of hypersensitivity reactions including utricaria, angioedema, rhinitis, conjunctivitis, sinusitis.

·  Sympotomatic treatment of cough and common cold.

·  Prior to blood transfusion, to minimize any hypersensitive reactions.

·  In pruritic skin disorders.

·  In reducting inflammatory reactions following antiparasitic effect of albendazole in neurocysticercosis and in treatment of filariasis by DEC.

·  As an adjunct in the treatment of anaphylactic shock.

Dosage

Oral:

Adult

·  4mg every 4-6 hours upto a maximum of 12 mg/day.

Children:

·  0.5 mg-1 mg/kg/day given every 6 hours.

Routes of Administration Oral   IM,  or Slow I.V. Injection.           

Precautions / Practice points

·  Patients taking the drug should not drive or operate machines since it causes drownsiness; instruct patients to abstain from alcohol.

·  Use with caution in patients with closed angle glaucoma, urinary reention, prostatic hypertrophy or pyloroduodenal obstruction (due to its anticholingergic effects).

·  Use with caution in patients with epilepsy, severe CVS disorders, asthma and liver disorders.

·  Administration Instructions:

-When injecting IV, rate of injection to be very slow.  Do not mix barbiturates and norepinepherne in the same syringe.

Contraindications

·  Chronic renal failure.

·  Should not be given to premature infants and neonates.

·  Pregnancy.

Drug Interactions

Non fatal :

·  Anti histamines may increase the CNS depressant effects of alcohol, barbiturates, hypnotics, opioid analgesics, anxiolytic sedatives and neuroleptics.

·  MAO inhibitors, atropine and tricyclic antidepressants increase the antimuscarinic effect of anti histamines.

Adverse Effects

Common effects:

·  Antimuscuraic effects – difficulty in micturation, blurring of vision.

·  CNS depressant action – sedation, dizziness, lassitude, inco-ordination.

·  GIT disturbances – nausea, vomiting, diarrhoea, epigastric pain.

Rare effects:

·  Paradoxical CNS stimulation in children – insomnia, nervousness, irritability, tremors, hallucinations, convulsions.

·  Extra-pyramidal symptoms may result, if administered with phenothiaziness.

Drug Toxicity

Antimuscuranic effects predominate, with a clinical picture similar to atropine poisoning like tremors, flushed hot skin, dilated pupils, hyperpyrexia, drowiness, coma, convulsions leading to respiratory failure and cardiovascular collapse.

Treatment of Toxicity

·  In case of acute ingestion – gastric lavage, activated charcoal and saline laxatives.

·  Convulsions controlled by diazepam.

·  Hyperpyrexia controlled by I.V. fluids, external cooling measures and artificial respiration and ventilatory support.

·  Physostigmine is given to combat anti muscarinic effects.

Storage

Store in airtight containers, protected from light.

Shelf Life                     2  years.

PROMETHAZINE

General   Information

Drug Code                      Preparation                                                         Strength

         345                         Inj. Promethazine HC1                                         25 mg/ml        

Description of the Drug

            Promethazine is a H1 receptor antagonist.  It is a phenothiazine derivative.

Mode of Action

Promethazine diminishes or abolishes the actions of histamine by competitive, reversible blockade of H1 receptorsites on tissues.  It  also has antimuscarinic, antiemetic, central sedative, some serotonin – antagonist properties.

Pharmacokinetics

It is, well absorbed after I.M. administration.  Onset of  action is in 20 minutes.  After IV administration, effects starts in a few minutes. Duration of action is 4 to 6 hours.  Crosses the blood brain barrier and the placental barrier.  Metabolised in liver and is excreted via urine and bile.

Clinical  Information

Indications

Antihistaminic effects:

·  Acute treatement of hypersensitivity reactions to any allergen, to treat symptoms of allergy and anaphylaxis like bronchospasm, dyspnoea,laryngeal edema etc.,

·  In allergic conditions such as rhinitis, sinusitis etc.,

Labyrinthine sedative action:

·  Treatement of motion sickness, labyrinthine disorders and Meniere’s disease.

Anti emetic action:

·  Precents and controls postoperative nausea and vomiting.

Central sedative action:

·  In conjuction with chlorpromazine in Menon’s regime for treatment of eclampsia.

·  In surgery.

-     preoperatively to relieve anxiety and for sedation.

-     Post operatively for sedation and adjunct to analgesic in pain relief.

Dosage

Adult  - Deep I.M. 25 to 50 mg (can be repeated after 2 hours for allergic states)

Children  -0.5 mg-1 mg/kg.

Routes of Administration   

            Parenteral : Deep I.M., Slow I.V. injection, I.V. infusion.

Contraindications

·  Comatose states or patients with preexisting CNS depression after consumption of alcohol, barbiturates, sedative hypnotics, opioids etc. or due to any cause.

·  Acute episode of narrow angle glaucoma.

Precautions / Practice points

·  Should be used with caution in conditions such as closed angle glaucoma, urinary retention, prostatic hypertrophy and pyloroduodenal obstruction because of their antimuscarinic action.

·  Patients  should not drive or operate machinery; instruct patients to abstain from alcohol.

·  With extreme caution in children and adults over 60 years (risk of extrapyramidal side effects).

·  Look out for respiratory depression in foetus when used at term for contros of eclampsia.

·  Administration Instructions:

-  I.V. Injection must be slow and concentration of injection not more than 25 mg/ml and rate not more than 25 mg/mi . Rapid IV infusion produces acute fall in BP.

-  Do not give S.C or intra-arterially as intense irritation  and tissue necrosis occurs.

-  If accidentally injected arterially  - sympathetic blood and heparinization.

Drug Interactions

Non fatal :

·  Excessive CNS depression can occur if given with other CNS depressants like alcohol, barbiturates, hypnotics, opioid analgesics, anxiolytics, sedatives and neuroleptics.  Which used concomitantly with promethazine, the dose of barbiturates rates should be reduced to one half and the dose of narcotics, to one quarter.

·  MAO inhibitors and phenothiazines increase risk of extrapramidal side effects.

Adverse Effects

Common effects:

·  Lassitude, dizziness, inco-ordination.

·  Antimuscuraic effects – dry mouth, blurred vision, constipation, urinary retention etc.,

Rare effects:

·  Extrapyramidal symptoms – dystonia, oculogyric crisis etc.

·  Thrombocytopenia.

·  Paradoxical CNS stimulation especially in children with insomnia, nervousness, abnormal movements, delirium, hallucinations, convulsions.

·  Local effects – thrombophlebitis, tissue irritation extravasation occurs.

·  CVS – unstable blood pressure, tachycardia or bradycardia.

·  Hepatic injury – hepatitis may occur.

Drug Toxicity

Clinically drowsiness, stupor and other CNS depressant effects occur. Antimuscarinic effects like dry mouth, dilated and fixed pupils, flushing, dry hot skin, profound
hypotension, hyperpyrexia and tachycardia occurs. Exrapyramidal reactions also may be present.  May progress to respiration depression, coma and death. 

Treatment of Toxicity

Continuous monitoring of vital signs, ECG, maintenance of airway, supportive ventilation.  Vasopressors (phenylepinephrine) to increase B.P. (Epinephrine should not be used) trendelenberg position and IV fluids can be used to combact hypotension.  Treatement of
extrapyramidal effects with diphenhydramine HCI should be done.

Storage

Store in airtight containers, protected from light.

Shelf Life                     3  years.