Drug Toxicity

Question 1

Four categories of adverse drug reaction

Answer 1

1) ADRs resulting from drug binding to intended receptor but at inappropriate concentration, with suboptimal kinetics, or in incorrect tissue
2) ADRs resulting from drug binding to a target or receptor not intended
3) ADRs mediated by the immune system
4) Idiosyncratic responses (mechanism is unknown)

Question 2

Hypersensitivity reaction- Type I

Answer 2

Immediate hypersensitivity resulting 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)
These are antibody related

Question 3

Hypersensitivity reaction- Type II

Answer 3

Antibody-dependent cytotoxic hypersensitivity.

Occurs when a drug binds to cells and is then recognized by immune system usually IgG.

Question 4

Hypersensitivity reaction- Type III

Answer 4

Immune-complex mediated hypersensitivity.
Antibodies are formed against soluble antigens
Antigen-antibody complex deposited in tissues initiation SERUM SICKNESS (inflammatory response in tissues)

Question 5

Hypersensitivity reaction- Type IV

Answer 5

Delayed-type hypersensitivity.

Activation of cytotoxic T-cells

Question 6

Biggest difference between hypersensitivity reactions

Answer 6

How quickly each reacts. All are related to antibody antigen complexes being formed.

Question 7

Drugs that initiate autoimmune reactions

Answer 7

Methyldopa (used to tx HTN and is a BP drug that has an alpha receptor). Hemolytic anemia- destruction of the RBC, monitor H&H, CBC.
Hydralazine, Isoniazid, Procainamide- lupus like symptoms. Notify and follow up.

Question 8

Skin rashes

Answer 8

Usually erythema mutiforme
Associated w/ barbituates, sulfonamides, phenytoin, cabamazepine, allipurinal, NSAIDs, and penicillins
Not a completely understood mechanism

Question 9

Steven-Johnson Syndrome

Answer 9

Big rash that can kill you. Causes burning sensation of the skin that necrosis and can fall off.

Question 10

Immune toxicity

Answer 10

Cytotoxic agents used in chemotherapy. These routinely damage proliferating normal cells (dividing cells). Cytotoxic to WBC increasing risk of infection.
Affect blood cells and can cause anemia

Question 11

Hepatotoxicity

Answer 11

Most frequent reason for drug withdrawals.
MOst cases of fulminant hepatitis are idiosyncratic.
Metabolites can cause liver damage

Question 12

Metabolite that causes liver damage- Acetaminophen oxidation to N-acetyl-p-benzoquinoneimine

Answer 12

After oxidation it is conjugated which remves the toxic effect. First step generates toxic metabolite and the second step is conjugation meaning you are adding something to make it not toxic.
In overdose, conjugation is gone and toxicity continues

Question 13

Biggest reason drugs are pulled from or don’t make the market

Answer 13

Hepatotoxicity

Question 14

Renal toxicity manifest

Answer 14

alterations in renal hemodynamics, tubular damage and obstruction, glomerular nephropathy, and interstitial nephritis.

Question 15

Progressive renal failure

Answer 15

NSAIDs, ACEI (ace inhibitors), some antibiotics, antineoplastic agents, immunomodulators.

Question 16

Gentamicin

Answer 16

renal tubular injury reversible upon cessation

Question 17

Amphotericin B

Answer 17

High frequency of injury due to mechanism for efficacy being shared by the mechanism responsible for toxicity.

Question 18

Contrast media

Answer 18

Dose related nephrotoxicity

Question 19

Acute or progressive renal failure seen more with medications

Answer 19

Progressive

Question 20

Three major mechanisms of CV toxicity

Answer 20

1) Drug interacts with cardiac potassium channels to cause OTc prolongation, delayed repolarization, and cardiac arrythmia
2) Directly cytotoxic to myocytes (doxorubicin leads to production of reactive oxygen species)
3) Toxic heart valves

Question 21

Pulmonary toxicity

Answer 21

Ranges from acute reversible exacerbations to chronic remodeling.
Pulmonary fibrosis caused by bleomycin and amiodarone

Question 22

Teratogens

Answer 22

Substance that can induce defects in the developing fetus.

Question 23

Teratogens- timing of pregnancy and drug administration

Answer 23

Prior to week 3 usually results in death to the embryo.
Week 3-8 organogenesis occurs so very profound effects on developing organs.
After organogenesis drugs may affect growth and maturation of the organ but not the developmental plan.

Question 24

Treatment of drug toxicity

Answer 24

Reduce or eliminate exposure to drug.
Provide supportive measures.
Provide an antidote.