Side effects
off target response
marginal impact on health
may impact patient compliance
EX: dry mouth with antidepresssents
Augmented responses
extension of pharmacologic effect
usually dose-dependent
may seriously impair health
EX: bradycardia with propranolol
Toxic reactions
not predicted from pharmacology of drug
sometimes not dose-dependent
can seriously impact health
EX: carbamazepine-induced liver injury
Determinants of toxic responses
- Individual susceptibility (diet, genetics, environment, underlying disease)
- accessibility of drug to target ( ADME)
- compensatory mechanisms (acidosis, alkalosis)
- reactivity of drug with target
Cellular dysfunction
Disruption of normal cellular function that does not result in cell death
Increased oxidative stress in RBC–> increased methemoglobin
decrease in G6PD in RBC–> increased methemoglobin
Cellular destruction
Dysregulation of cellular processes provoked by a toxicant resulting in the death of the cell
Targets: ATP depletion, Ca accumulation, ROS/RNS generation
Genotoxicity
Damage to genetic material caused by an external agent (e.g., chemicals,
ionizing radiation)
Clinical consequences of genomic damage
Somatic cells=cancers
Germ cells=birth defects, childhood cancers
Developing embryo= miscarriages, stillbirths, birth defects
Teratogenicity
Damage to an organism that causes an abnormality in development
Taratogen
an agent that causes an abnormality in development
smoking, alcohol, radiation, HPV
Criteria for classification as a teratogen
- exposure results in a characteristic set of malformations
- effect occurs with exposure at a specific stage of development
- effect is dose-dependent
Provided a specific gestational stage for a woman, identify whether a teratogen is
likely to result in: 1) embryo death, 2) major congenital anomalies, or 3)
functional defects and minor anomalies
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