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Flashcards in Drug toxicity Deck (12):
1

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

2

Type II hypersensitivity rxn

Antibody-dependent cytotoxic hypersensitivity
Occurs when a drug binds to cells and is then recognized by immune system usually IgG

3

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)

4

Type IV hypersensitivity rxn

Delayed-type hypersensitivity
Activation of cytotoxic T-cells

5

Which drugs cause autoimmune reactions?

Methyldopa- hemolytic anemia
Hydralazine, Isoniazin, Procainamide- Lupus like syndrome

6

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.

7

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.

8

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

9

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

10

What are the 2 drugs implicated in pulmonary toxicity?

Bleomycin
Amiodarone

11

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

12

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)