TOXIC EFFECTS OF DRUGS ON DIFFERENT

ORGAN & SYSTEMS

Sarita Sharma Assistant professor of pharmacology Mumbai

Drugs can cause ADR or toxic effects to almost all the tissues & organs.

(1) Gastro- intestinal: several drugs causes anorexia, nausea, vomiting (metronidazole, chloroquin)

diarrhoea/constipation (iron salts, morphine) Eg: aspirin & other NSAIDs can cause gastric ulceration & even bleeding.

It ranges from anaemia to blood dyscrasias like leucopenia, agranulocytosis, aplastic anaemia & thrombocytopenia.

The reduction in clotting factors can leads to haemorrhages.

Eg: anti-cancer drugs (chlorambucil, cisplatin, cyclophosphamide) causes bone marrow supression

(2)HAEMOPOIETIC:

Drugs can damage the liver by 2 mechanisms: (a) by direct action: by drugs or their metabolites. Latent period between exposure & liver injury is

usually short. Predictable hepatotoxicity Dose related toxicity can be shown in animal models

Eg: isoniazide, paracetamol, tetracycline etc

(3) HEPATOCELLULAR:

(b) by an immunological rxn: Unpredictable, no animal models are available

Eg: Hepatitis by isoniazide, pyrazinamide, indomethacine etc

Cholestasis interfering with biliary secretion and hyperbilirubinemia (steroids)

Long –lasting Cholestasis/ vanishing bile duct syndrome- complete destruction of intrahepatic biliary ducts (Amitryptalline, azathioprine, tetracycline, co-trimoxazole)

Drugs can cause direct cardiotoxicity results in arrhymias or even cardiac arrest.

Eg: digoxin, quinine, aminophylline, cyclophosphamide etc.

(5) RENAL: drugs can cause albuminuria, hematuria and even tubular necrosis.Nephrotoxocity is either direct or immunologically induced.Eg:  Nephritis-penicillins, cephalosporins, sulfonamides, thiazide diuretics, furosemide, NSAIDs and rifampicin

direct toxicity like acute tubular necrosis- eg, aminoglycosides, amphotericin and ciclosporin.

(4) CARDIAC:

Hypogeusia- a decrease in taste acuity. Ageusia-total loss of ability to recognize any

taste. Dysgeusia: distortion of taste sensation.

Hyposmia, anosmia, dysosmia represant the corresponding abnormalities in sense of smell.

Eg: d-penicillamine, bromocriptine, methimazole, pyrazinamide etc

(6)ABNORMALITIES OF TASTE & SMELL:

Many drugs can cause a variety of ocular injuries. Eg:  cyclosporine &

tacrolimus; minocycline; hydroxychloroquine

(8) Ototoxicity: Some topical preparation and drugs can cause

hearing impairments. Eg: salicylates, anti-malarials (quinine,

chloroquin), anti-cancer(cisplatin),ear drops (chloramphenicol)

(7)OCULAR TOXICITY:

Allergy and photosensitivity.

Eg: anticancer drugs causes hair loss. Metals like arsenic, lead, Hg etc secreted in

sweat and produce skin rashes, pruritis, urticaria, itching etc.

(9) DERMAL:

Diuretics like thiazides and frusemide may produce hyponatremia or hypokalemia.

Chemotherapy drugs (cisplatin) Diuretics (furosemide) Antibiotics (amphotericin B) Corticosteroids (hydrocortisone) NSAIDs may cause Na+ retention and edema.

(11) ENDOCRINE disturbances:

Chlorpromazine may produce menstrual irregularities, galactorrhoea & amenorrhoea.

Combination oral contraceptives may arrest lactation in nursing mothers.

Amiodarone can cause thyroid disease

(10)ELECTROLYTE DISTURBANCES:

Drugs like benzodiazepins, anti-depressants, anti- psychotic etc.

Cemitidine causes Gynecomastia in males.

(12) INFERTILITY & SEXUAL IMPOTENCE:

Amphetamine can cause disoriantation, confusion & inability to concentrate

Glucocorticoids may cause euphoria, restlessness & psychosis.

Benzodiazepines causes amnesia.

(13)CNS & BEHAVIORAL:

Ability to produce cancer. Eg: estrogen therapy mammary carcinoma and

endometrial cancer. Radiations also causes skin cancer.

(15) Teratogenicity: Capacity of a drug to cause foetal abnormalities when

administered to the pregnant mother.

E.g: Thalidomide Phocomelia, multiple defects Anticancer drugs hydrocephalus, multiple defects ACE inhibitors Hypoplasia of organs (lungs, kidney)

(14)CARCINOGENECITY:

Eg: glucocorticoids can unmask latent diabetes Isoniazide can unmask latent epilepsy unmasking of tuberculosis by antiretroviral therapy

(AIDS)

(17) Production of disease(latrogenic disease):Sometime,Drugs produce pathological conditions OR complications arising from a procedure or treatmentEg: Glucocorticoids may cause hypertension, cardiac diseasesRepeated doses of NSAIDs causes duodenal ulcer & liver damage.

(16) UNMASKING OF DISEASE:

Eg: anticancer drugs- cyclophosphamide, Chlorambucil ,nitrogen mustard etc.

AIDS therapy- anti-retroviral drugs

(18) IMMUNOSUPPRESSION:

Occurs when 2 or more drugs are administered concurrently.

Eg: antacid and tetracycline together– no absorption of tetracycline.

Enzyme inhibitors causes accumulation of another drug leads to toxicity.

(19) DRUG INTERACTIONS:

Abrupt cessation of certain drugs after a prolonged use causes problams:

Eg: pituitary suppression by glucocorticoids Withdrawal symptoms after alcohol,

benzodiazepins, morphine etc. discontinuation.

With this type of drugs cessation should be gradual or by decreasing to small doses will be helpful.

(20) ADR DUE TO DRUG WITHDRAWAL: