Drug Toxicity

Question 1

What are on-target effects?

Answer 1

Adverse effect may be an exaggeration of the desired pharmacological action, such as observed in drug overdose

Question 2

What is an example of on-target effects?

Answer 2

CNS depression is predictable in dose-dependent fashion

- progression of clinically effects go from anxiolysis to sedation to somnolence to coma

Question 3

What is an example of how duration of a drug can have on-target effects?

Answer 3

Tardive dyskinesia, an extrapyramidal motor disorder associated with use of antipsychotic medications, may be dependent upon duration of exposure

Question 4

What are off-target effects?

Answer 4

Drug designed to bind to target A for therapeutic efficacy, but also binds to target B leading to toxicity

Question 5

What is an example of off-target effects?

Answer 5

Antihistamine terfenadine – H1 antagonist – therapeutic site - also binds to hERG which causes cardiac arrhythmia.

Thalidomide with its 2 different enantiomers.

Beta-blockers for the heart can block the beta receptors that lead to the dilation of airways, leading to toxicity for asthmatic patients in particular.

Question 6

What is idiosyncratic toxicity?

Answer 6

Toxicity that is unpredictable and mechanism is unknown

Question 7

Interaction of absorption

Answer 7

A drug may cause increase or decrease in absorption of a second drug from the intestinal lumen

Question 8

Interaction with protein binding

Answer 8

Drugs can be highly protein bound in the plasma binding sites can become saturated in physiological states that lead to hypoalbuminemia

Question 9

Interaction of metabolism

Answer 9

Drug can influence the metabolism of another drug

Ex: Ethanol and acetaminophen

Question 10

How does alcohol affect acetaminophen metabolism?

Answer 10

A small amount of acetaminophen is metabolized by CYP2E1 to N-acteyl-p-benzoquinoneimine (NAPQI) which is toxic.

Some ethanol is metabolized by CYP2E1 as well which can induce CYP2E1 expression that can cause NAPQI to reach toxic levels if acetaminophen is taken with alcohol.

Question 11

Interaction of receptor binding

Answer 11

Antagonists can be used to block the effects of receptor drugs

Question 12

Interaction of therapeutic action

Answer 12

Drugs with overlapping effects can lead to toxicity

Ex: Aspirin and heparin

Question 13

Additive

Answer 13

Combined effect of two drugs equals sum of effect of each drug given alone

Question 14

Synergistic

Answer 14

Combined effect exceeds the sum of effects of each drug given alone

Question 15

Potentiation

Answer 15

Creation of a toxic effect from one drug due to presence of another drug

Question 16

Antagonism

Answer 16

Interference of one drug with the action of another

Question 17

Function or physiological antagonism

Answer 17

Two drugs have opposite effect on the same physiological function

Question 18

Chemical antagonism

Answer 18

Chemical reaction between two drugs to neutralize their effects – chelation therapy

Question 19

Dispositional antagonism

Answer 19

Alter absorption/distribution/excretion (i.e. disposition) so that less drug gets to site of action

Ex: Protein binding of the drug

Question 20

Receptor antagonism

Answer 20

Block drug binding to receptor with another drug

Question 21

What is Type I Hypersensitivity?

Answer 21

Allergic reactions mediated by IgE

Question 22

What is Type II Hypersensitivity?

Answer 22

Ab directed against tissue Ag mediated by IgG

Question 23

What is Type III Hypersensitivity?

Answer 23

Immune complex mediated disease caused by Ag-IgG complexes

Question 24

What is Type IV Hypersensitivity?

Answer 24

Delayed hypersensitivity mediated by T cells

Question 25

Red Man Syndrome

Answer 25

Drugs acting directly on mast cells, causing cell to degranulate and is like Type I but NOT mediated by IgE.

Question 26

Stevens-Johnson Syndrome

Answer 26

Most severe type of skin rash; can be life-threatening

Question 27

Indirect Immunotoxicity

Answer 27

Non-selective cancer drugs target or kill proliferating neoplastic cells also damage the cells in the bone marrow, lymphoid tissues, intestines and hair follicles at therapeutic doses

Question 28

Direct Immunotoxicity

Answer 28

Immune system can be targeted directly to dampen immune system such as with the use of corticosteroids

Question 29

What is an example of drugs causing liver drug toxicity?

Answer 29

Acetaminophen overdose will lead to NAPQI accumulation

Question 30

What is an example of drugs causing renal toxicity?

Answer 30

NSAID

Question 31

What is an example of drugs causing neurotoxicity?

Answer 31

Anti-cancer drugs

Question 32

What is an example of drugs causing skeletal muscle toxicity?

Answer 32

Statins