Drug Toxicity Flashcards Preview

Pharmacotherapeutics I > Drug Toxicity > Flashcards

Flashcards in Drug Toxicity Deck (24):
1

Four categories of adverse drug reaction

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)

2

Hypersensitivity reaction- Type I

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

3

Hypersensitivity reaction- Type II

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

4

Hypersensitivity reaction- Type III

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

5

Hypersensitivity reaction- Type IV

Delayed-type hypersensitivity.
Activation of cytotoxic T-cells

6

Biggest difference between hypersensitivity reactions

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

7

Drugs that initiate autoimmune reactions

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.

8

Skin rashes

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

9

Steven-Johnson Syndrome

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

10

Immune toxicity

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

11

Hepatotoxicity

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

12

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

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

13

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

Hepatotoxicity

14

Renal toxicity manifest

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

15

Progressive renal failure

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

16

Gentamicin

renal tubular injury reversible upon cessation

17

Amphotericin B

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

18

Contrast media

Dose related nephrotoxicity

19

Acute or progressive renal failure seen more with medications

Progressive

20

Three major mechanisms of CV toxicity

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

21

Pulmonary toxicity

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

22

Teratogens

Substance that can induce defects in the developing fetus.

23

Teratogens- timing of pregnancy and drug administration

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.

24

Treatment of drug toxicity

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