# 8 drug toxicity

Question 1

poison

Answer 1

any substance that has the capacity to harm a living organism

every drug has the potential to harm

Question 2

causes of drug toxicity

Answer 2

1. mechanism of drug action (pharmacological toxicity)
2. size of drug does
3. characteristics and health status of the patient

Question 3

on-target effects

Answer 3

adverse effects that are an exaggeration of the desired pharmacological action. Could be due to an overdose or an extended duration

Question 4

off-target effects

Answer 4

drug designed to bind target A but also binds target B leading to toxicity.

enantiomers- one may cause the desired effect while the other causes toxic effects

unintended activation of a different receptor subtype
(Beta-blockers B1 selectivity vs. B1 and B2 binding)

Question 5

idiosyncratic toxicity

Answer 5

toxicity that is unpredictable and mechanism is unknown

not observed in preclinical and clinical testing

Question 6

types of drug-drug interations

Answer 6

1. interaction of absorption (intestinal lumen)
2. interaction with protein binding (plasma)
3. interaction of metabolism
4. interaction of receptor binding (antagonist/agonist)
5. interaction of therapeutic action (aspirin and heparin)

Question 7

ethanol metabolism

Answer 7

mainly via alcohol dehydrogenase but some via CYP2E1

alcohol increases the expression of CYP2E1

Question 8

Actetamiophen metabolism (tylenol)

Answer 8

primarily by phase II reactions: glucuronidation and sulfation rxns. A small amount is metabolized by CYP2E1 to NAPQI

Question 9

NAPQI

Answer 9

the toxic metabolite of actetaminophen when metabolized by CYP2E1 (normally a very small portion)

it is normally conjugated with glutathione to make a non-toxic metabolite that is excreted

glutathione can easily be depleted leading to accumulation of NAPQI and liver damage

when taken after alcohol consumption increasing CYP2E1 expression increased levels of NAPQI will be produced

Question 10

addative

Answer 10

combined effect of 2 drugs equals the sum of the effect of each drug given alone

Question 11

synergistic

Answer 11

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

Question 12

potentiation

Answer 12

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

Question 13

antagonism

Answer 13

interference of one drug with the action of another

Question 14

function or physiological antagonism

Answer 14

two drugs have opposite effect on the same physiological function

Question 15

chemical antagonism

Answer 15

chemical reaction between tow drugs to neutralize their effects - Chelation therapy

Question 16

dispositional antagonism

Answer 16

alter absorption/distribution/excretion so that less drug gets to the site of action

Question 17

receptor antagonis

Answer 17

block drug binding to the receptor with another drug

Question 18

Immunotoxicity

Answer 18

toxicity do to stimulation the immune system

Possible outcome: compromise immune system and have secondary effects leading to increased risk of infection

Question 19

Red man syndrome

Answer 19

drugs acting directly on mast cells leading to degranulation

• linked to i.v. infusion of drugs (e.g. antibiotic vancomycin)

not caused by IgE

cutaneous wheals and urticarial to neck, arms, upper trunk

• can proceed to angioedema and hypotension in rare cases
• antihistamines prophylactically

Question 20

erythema mutliforme

Answer 20

skin rash due to drug side effect

Question 21

Steven-Johnsons syndrome

Answer 21

• most severe type of skin rash; can be life-threatening

morphologic appearance of mucous membrane and skin inflammation

blisters and separation of the epidermis from the dermis

observed with many commonly prescribed and over-the-counter drugs

Question 22

side effects of Non-selective cancer drugs

Answer 22

target or kill proliferating neoplastic cells
also damage the cells in the bone marrow, lymphoid tissues, intestines and hair follicles at therapeutic doses
- safety margin low for cancer drugs; always risk to damage normal tissues
- increased risk of infection if white blood cells are compromised