critical factors in toxicokinetics
time to peak drug concentration
rate of drug clearance from systemic circulation
5 types of drug toxicity
on target
off target
biological activation
hypersensitivity reactions
idiosyncratic reactions
on target toxicity
result of the interaction of a drug and its primary pharmacologic target
off target toxicity
result of the interaction of a drug with targets other than the intended pharmacological targets
biological activation
drug is biologically activated to a toxic metabolite that is capable of causing organ or tissue specific toxicity
hypersensitivity reactions
type 1 - anaphylactic rxns
type 2 - cytolytic rxns
type 3 - arthrus rxn
type 4 - delayed hypersensitivity rxn
type 1 anaphylactic reaction
immediate hypersensitivity reaction d/t short amount of time from exposure to response
mediated by IgE antibodies
main targets: GI, skin, respiratory system, vasculature
-causes vasodilation, edema, inflammatory response
type 2 cytolytic reaction
mediated by IgG and IgM
targets circulatory system
-often causes anemia or changes in blood cell counts
reaction subsides w/i several months after offending agent is removed
type 3 arthus rxn
mediated by IgG antibodies
forms complex that deposits into the vascular endothelium causing inflammatory response known as serum sickness
Sx: skin eruptions, arthralgias, arthritis, lymphadenopathy, fever
rxn lasts 6-12 days and resolved once offending agent eliminated
type 4 delayed hypersensitivity reaction
mediated by T lymphocytes and macrophages
causes local inflammation and edema of the skin
ex. poison ivy rash
idiosyncratic rxns
abnormal reaction to drug that is unique to individual
involves pt w pharmacogenetic predisposition
3 types: drug induced liver injury, SJS, toxic epidermal necrosis
carbon monoxide MOA
bind tightly w oxygen binding site of hemoglobin
oxygen cannot bind when CO bind, hemoglobin cannot transport oxygen to the tissues
carbon monoxide symptoms (increasing carboxyhemoglobin %)
psychomotor impairment
headache
confusion, loss of visual acuity
tachycardia, tachypnea, syncope, coma
deep coma, convulsions, shock, respiratory failure
lead clinical effects
peripheral neuropathy
nephropathy
cardiovascular: HTN, anemia, mortality
CNS: deficits and encephalopathy
mercury clinical effects
CNS: tremor, behavior changes
renal: acute tubular necrosis and renal failure
peripheral neuropathy
birth defects
pesticides
easily absorbed through skin, GI, respiratory
organophosphate ester-induced delayed polyneuropathy (OPIDP)
intermediate syndrome
arsenic clinical effects
cardiovascular: shock, arrhythmias
CNS: encephalopathy and peripheral neuropathy
pancytopenia
cancer
acetaminophen presentation and treatment
24-36 hours later evidence of liver injury which can lead to metabolic acidosis, hypoglycemia, encephalopathy, and death
treatment: N-acetylcysteine
aspirin presentation and treatment
hyperventilation, respiratory alkalosis, and metabolic acidosis w an anion gap
increased body temp
treatment: sodium bicarbonate
beta blockers presentation and treatment
bradycardia and hypotension
seizures and cardiac conduction block seen w some agents
treatment: glucagon
cyanide presentation and treatment
SOB, agitation, tachycardia followed by seizures coma hypotension
severe metabolic acidosis
treatment: hydroxocobalamin (Cyanokit)
digoxin presentation and treatment
vomiting, vision change, hyperkalemia
cardiac rhythm changes: bradycardia, AV block, PVCs, and ventricular arrhythmias
treatment: DigiFab (digoxin antibodies)
sympathomimetic presentation
agitation
increased HR, BP, RR and temp
dilated pupils and sweating
tremor and seizures may be observed
sympathomimetic toxidrome cause and treatment
stimulants such as cocaine, meth
treatment: seizures with benzodiazepines
manage hyperthermia with cooling or paralytic
