Drug toxicity Flashcards
Type I hypersensitivity rxn
Immediate hypersensitivity; results from production of IgE after exposure to an antigen
Antigen may be a foreign protein or an endogenous protein modified by a hapten to become immunogenic
Type II hypersensitivity rxn
Antibody-dependent cytotoxic hypersensitivity
Occurs when a drug binds to cells and is then recognized by immune system usually IgG
Type III hypersensitivity rxn
Immune-complex mediated hypersensitivity
Antibodies formed against soluble antigens
Antigen-antibody complex deposited in tissues initiating serum sickness (inflammatory response in tissues)
Type IV hypersensitivity rxn
Delayed-type hypersensitivity
Activation of cytotoxic T-cells
Which drugs cause autoimmune reactions?
Methyldopa- hemolytic anemia
Hydralazine, Isoniazin, Procainamide- Lupus like syndrome
Which drugs are reported in Stevens-Johnson syndrome (big rash that can kill you)
Reported with barbituates, sulfonamides, phenytoin, carbamazepine, allopurinal, NSAID’s, Penicillins. Mechanism not understood.
What is an example of the metabolite of a drug that can cause hepatotoxicity (liver damage)?
Acetaminophen (Tylenol) oxidation to N-acetyl-p-benzoquinoneimine (NAPQ-phase I,This is the toxic metabolite.).
Phase II- NAPQ conjugated. No longer toxic. With an overdose, you run out of the conjugate. Now left with this toxic metabolite. Can occur chronically or acutely. Liver damage.
What are some drugs implicated in renal toxicity?
NSAID’s (ibuprofin), ACEI (ace inhibitors), some antibiotics, antineoplastic agents, immunomodulators
Gentamicin- renal tubular injury reversible upon cessation
Amphotericin B- (anti-fungal) High frequency of injury because mechanism for efficacy is shared by the mechanism responsible for toxicity
Contrast-Media- Dose related nephrotoxicity
What are the 3 major mechanisms for cardiovascular toxicity?
1-Drug interacts with cardiac potassium channels to cause QTc prolongation, delayed repolarization, and cardiac arrythmia
2-Directly cytotoxic to myocytes
(Doxorubicin leads to production of reactive oxygen species)
3-Toxic to heart valves
What are the 2 drugs implicated in pulmonary toxicity?
Bleomycin
Amiodarone
Effects of teratogen intake at pregnancy week 3, weeks 3-8, and after organogenesis
Prior to week 3 usually result in death to embryo
Week 3-8 organogenesis occurs so very profound effects on developing organs
After organogenesis drugs may affect growth and maturation of organ but not the developmental plan
What are the 4 categories for ADRs?
1-ADR’s resulting from drug binding to intended receptor but at inappropriate concentration, with suboptimal kinetics, or in incorrect tissue
2-ADR’s resulting from drug binding to a target or receptor not intended (ex. Histamines)
3-ADR’s mediated by the immune system
4-Idiosyncratic responses (mech is unknown)
