Toxic effects of drugs on different organs & systems

1. Sarita Sharma
Assistant professor
of pharmacology
Mumbai

2.  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.

3.  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

4.  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

5.  (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)

6.  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.

7.  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

8.  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)

9.  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.

10.  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

11.  Drugs like benzodiazepins, anti-depressants,
anti- psychotic etc.
 Cemitidine causes Gynecomastia in males.

12.  Amphetamine can cause disoriantation, confusion
& inability to concentrate
 Glucocorticoids may cause euphoria, restlessness
& psychosis.
 Benzodiazepines causes amnesia.

13.  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.  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 treatment
Eg: Glucocorticoids may cause hypertension, cardiac
diseases
Repeated doses of NSAIDs causes duodenal ulcer &
liver damage.

15.  Eg: anticancer drugs- cyclophosphamide,
Chlorambucil ,nitrogen mustard etc.
 AIDS therapy- anti-retroviral drugs

16.  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.

17.  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.