This action might not be possible to undo. Are you sure you want to continue?
Adverse Drug Effects
• Any undesirable or unintended consequence of drug administration • “Any response to a drug that is noxious and unintended and that occurs at doses used in man for the prophylaxis, diagnosis, or therapy of disease or for modification of physiological function” – WHO • Adverse event: Any untoward event that occurs during treatment not necessarily with causal relation ship to treatment
Adverse Drug Reactions [ADR]
• Drugs used for favorable response • Unfortunately also produce ADR
• • • • • • • • Minor: No tt required Moderate: Requires change in tt, change of drug Severe: Potentially life threatening, permanent damage Lethal: Directly or indirectly contributes to death
Type A[Augmented] • Extension of pharmacological actions • Predictable • Dose dependent • High incidence • Low mortality • Dose reduction • Eg. Blurring of vision & dryness of mouth [atropine] Hypoglycemia[Glipizide] Type B [Bizarre] • Immunological/genetic • • • • • • Not predictable Qualitative[not dose dependent] Low incidence High mortality Discontinue drug Eg. Anaphylaxis due to Penicillin , Hemolysis due to primaquine
ADR Type A[augmented]
• Side effects: • Unwanted ,unavoidable pharmacodynamic effects at therapeutic doses • Eg. Antihistaminics cause sedation • Secondary effects: • Indirect consequence of primary action of a drug • Eg. Tetracyclines cause super infection • Toxic effects: • Due to overdose or prolonged use • Eg. Respiratory failure by morphine • Coma by barbiturates
• • • • • Type B[Bizarre] Allergy/hypersensitivity Idiosyncratic Type C[Continuous use] [dependence, organ toxicity] • Type D[Delayed effect] • Mutagenicity, carcinogenicity, teratogenic effect • Type E[End of use] • [withdrawal, HPA axis suppression]
• Low threshold to the action of drug • Eg. EPS with single dose of Metoclopromide
• A genetically determined reaction • An unusual individual reaction to food or a drug Eg. Barbiturates cause excitement and mental confusion Chloramphenicol causes aplastic anemia
Drug allergy (drug hypersensitivity)
• Immunologically mediated reaction • Types of drug allergy 1. Anaphylactic-Type I 2. Cytolytic-Type II 3. Immune complex mediated[Arthus]: -Type III 4. Delayed hypersensitivity -Type IV
Eg. Betalactam antimicrobial agents
Type 1 [Anaphylactic]
Exposure to drug Eg.Penicillin IgE AB Fixed to mast cells Re-exposure
•Medical emergency •Inj.Adrenaline[1:1000] 0.3 to 0.5 ml i.m. •Inj.Hydrocortisone 100 mgi.v. •Inj.Diphenhydramine 25mg i.v. •Oxygen •i.v. fluids
Release of mediators: Histamine, 5-HT, PGs, LTs, PAF
Anaphylactic shock: Hypotension, Bronchospasm, Urticaria Etc.
Eg. Sulfa, thiazides, quinidine→puprura, hemolysis
Type II [Cytolytic]
Drug+Tissue=AG IgG, IgM- AB Re exposure
Exposure to drug Eg.Quinine
Eg. Hemolysis by Quinine, Quinidine
AG+AB IgG Eg. • Serum sicknes [Fever, urticaria, joint pain, lymphadenopathy]
Deposited on vascular endothelium
• Penicillin, • Sulfa •NSAIDs
Destructive inflammatory response
Type IV[cell mediated, delayed]
Eg.Contact dermatitis by metals, ointments
Type IV [Delayed]
•Inflammatory response •Delayed by 2-3 days •Not AB related •Cell mediated •Eg. Contact dermatitis with LA creams
[Pt. taking a drug develops reaction on body parts exposed to light]
• • • • • • • •
Phototoxicity [hyperpigmentation[desquamation] Sensitization of the skin by drugs UV radiation Cutaneous reaction-Photosensitivity Stopped when drug stopped Photo allergy [eczematous, papular] Persists even after drug withdrawal Examples????
Carcinogenicity & mutagenicity
• Ability of the drug to cause cancer and genetic defects respectively • Eg. Tobacco, anticancer drugs
• • • • • iatros = physician (physician induced diseases): Parkinsonism – Phenothiazines Peptic ulcer – Aspirin,corticosteroids Hepatitis - Isoniazid
Drugs frequently cause allergic reactions
• • • • • • • Penicillins Cephalosporin Sulfonamides Tetracyclines Quinolones Antitubercular drugs Salicylates • Carbamazapine • ACE inhibitors • Local anesthetics
• terataos = monster • Capacity of the drug to cause fetal abnormalities when administered to pregnant mother • I. Pre-implantation: conception to 17 days-Abortion • ii.Organogenesis: 18-55 days-Deformities • iii.Growth and development: 56 days onwards
• Thalidomide – Phocomelia • Corticosteroids – Cleft lip • TC- Discolouration of teeth, retarded bone growth
Category A [ANIMALS [-] Humans[-]-------------No risk Studies have failed to demonstrate a risk to the fetus Category B [ANIMALS [-] Humans[Not known] [ANIMALS [+] Human[none] ---No evidence of risk Animal reproduction studies have failed to demonstrate a risk to the fetus and there are no studies in pregnant women.
Category C [ANIMALS [++] Humans[Not known] [Consider risk benefit before use] Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.
Category D [Humans risk ++] [Benefit may outweigh risk] There is positive evidence of human fetal risk - but potential benefits may warrant use of the drug in pregnant women despite potential risks. Category X [Abnormalities demonstrated] [Not to be used in pregnant women] Studies in animals or humans have demonstrated fetal abnormalities and/or there is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience and the risks involved in use of the drug in pregnant women clearly outweigh potential benefits.
• Hepatotoxicity: INH, Rifampicin • Nephrotoxicity: Aminoglycosides • Ototoxicity: Aminoglycosides, Frusemide
• Ocular toxicity: Ethambutol, Chloroquine
• • • • • A state of Psychological or physical dependence Due to interaction - living organism+Drug Characterized by behavioral and other responses Always includes a compulsion to take the drug continuously or periodically
• Psychological: Intense desire to take drug and immense satisfaction later • Physical: Physiological equilibrium is maintained by drug
• Poisons in small doses are the best medicines; and useful medicines in too large doses are poisonous” William Withering 1789
• Large enough dose of a drug • Substance which endangers life • Accidental or suicidal
Poisoning Principles of treatment
• • • • • • • • • 1.Resuscitation and maintenance of vital functions Airway, BP, Body temp., Blood sugar 2. Termination of exposure Fresh air, remove wet clothes, wash, 3. Prevention of absorption Gastric lavage, Activated charcoal, 4. Hastening elimination Diuresis, Altering urine pH, Hemodialysis 5. Antidotes if available
Prevention of adverse effects
• Right dose, route, frequency • Previous history drug allergy and allergic diseases • Rule out drug interactions • Correct technique of administration • TDM if appropriate
Clinical significance of ADR
• Common• 3-5% of admissions • Increases duration of stay • Initially reversible • Awareness-ADR or new symptoms • Surgeries are avoided [gynecomastia and spironolactone] • Reduce the no.of drugs
• Actively look for adverse drug effects • “Activities relating to detection, assessment, understanding and prevention of adverse effects or any other drug related problem” • Causality assessment 1. Temporal relationship 2. Previous knowledge 3. Dechallenge 4. Rechallenge
Information collected by Regional centers to Zonal centers to National centers to Uppsala monitoring center (Sweden)
Definite, probable, possible or doubtful
This action might not be possible to undo. Are you sure you want to continue?
We've moved you to where you read on your other device.
Get the full title to continue listening from where you left off, or restart the preview.