# 8 drug toxicity Flashcards
poison
any substance that has the capacity to harm a living organism
every drug has the potential to harm
causes of drug toxicity
- mechanism of drug action (pharmacological toxicity)
- size of drug does
- characteristics and health status of the patient
on-target effects
adverse effects that are an exaggeration of the desired pharmacological action. Could be due to an overdose or an extended duration
off-target effects
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)
idiosyncratic toxicity
toxicity that is unpredictable and mechanism is unknown
not observed in preclinical and clinical testing
types of drug-drug interations
- interaction of absorption (intestinal lumen)
- interaction with protein binding (plasma)
- interaction of metabolism
- interaction of receptor binding (antagonist/agonist)
- interaction of therapeutic action (aspirin and heparin)
ethanol metabolism
mainly via alcohol dehydrogenase but some via CYP2E1
alcohol increases the expression of CYP2E1
Actetamiophen metabolism (tylenol)
primarily by phase II reactions: glucuronidation and sulfation rxns. A small amount is metabolized by CYP2E1 to NAPQI
NAPQI
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
addative
combined effect of 2 drugs equals the sum of the effect of each drug given alone
synergistic
combinded effect exceeds the sum of the effects of each drug given alone
potentiation
creation of a toxic effect from one drug due to presence of another drug
antagonism
interference of one drug with the action of another
function or physiological antagonism
two drugs have opposite effect on the same physiological function
chemical antagonism
chemical reaction between tow drugs to neutralize their effects - Chelation therapy
dispositional antagonism
alter absorption/distribution/excretion so that less drug gets to the site of action
receptor antagonis
block drug binding to the receptor with another drug
Immunotoxicity
toxicity do to stimulation the immune system
Possible outcome: compromise immune system and have secondary effects leading to increased risk of infection
Red man syndrome
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
erythema mutliforme
skin rash due to drug side effect
Steven-Johnsons syndrome
- 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
side effects of 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
- safety margin low for cancer drugs; always risk to damage normal tissues
- increased risk of infection if white blood cells are compromised
