B4.014 Prework 2 Adverse Drug Reactions Flashcards
what are the 2 classes of cholinesterase inhibiting insecticides?
organophosphates
carbamates
how do organophosphates and carbamates differ
organophosphates are irreversible
carbamates are reversible
compare the normal mode of action of ACh + AChE with physostigmine + AChE and DFP + AChE
normal: ACh degraded and regenerated very fast, t0.5 = microseconds
physo: carbamoyl enzyme intermediate, degradation and regeneration progresses more slowly, t0.5 = 15-20 min
DFP: phosphoryl enzyme intermediate, enzyme ages but is never degraded and regenerated, AChE inactive, t0.5 = hours or days
symptoms of cholinesterase inhibiting insecticides poisoning
SLUD: salivation lacrimation urination defecation
mild/moderate/severe insecticide poisoning
mild: anorexia, headache, dizziness, nausea
moderate: excessive sweating, vomiting, ab cramps
severe: pinpoint and nonresponsive pupils, heat block, coma
cholinesterase inhibiting insecticides poisoning treatment options
atroping: small dose, increase as needed
2-pralidoxime: reactivate AChE enzyme prior to “aging” (contraindicated for carbamates)
describe how 2-pralidoxime (2-PAM) works as a treatment for organophosphate poisoning
still an AChE inhibitor, but reversible
binds AChE before organophosphate can
therefore exerts a shorter lasting blockage
what are 2 chemical that affect heme protein
methemoglobin
CO
cyanide
what is methemoglobin and how is it induced
oxidized hemoglobin (F3+ ferric form)
incapable of carrying oxygen
produced via nitrates from Fe2+ (ferrous)
how does CO affect hemoglobin
binds to produce carboxyhemoglobin
binds much tighter than O2 and inhibits O2 carrying
cyanide mechanism
inhibits cytochrome C oxidase, an enzyme in the ETC
blocks oxidative phosphorylation and respiration
symptoms of nitrate induced methemoglobinemia
choclate colored blood
hypotension, hypoxia, cyanosis
convulsions, coma, resp failure
nitrate induced methemoglobinemia treatments
only necessary when 35% or more Hb is in the oxidized form
methylene blue will convert methemoglobin back to hemoglobin \
in severe cases: O2 admin and exchange transfusions
normal carboxyhemoglobin levels
nonsmokers- 1%
smokers- 5-10%
auto exhaust- 4-7%
symptoms of CO poisoning
headache
dizziness and stupor (progressive brain anoxia)
cherry red blood (healthy looking mucous membranes)
treatment for CO poisoning
terminate exposure
administer oxygen
avoid respiratory stimulating drugs (increases absorption of CO)
mechanism of cyanide toxicity
complexes with ferric iron of cytochrome oxidase and produces cellular anoxia by inhibiting oxygen utilization in the mitochondria; extremely rapid action
symptoms of cyanide poisoning
dizziness headache hypotension unconsciousness convulsions resp failure
treatment of cyanide poisoning
- induce methemoglobin formation by admin of nitrates
methemglobin competes with cytochrome oxidase for CN- - rhodanese is a mitochondrial matrix enzyme which catalyzes the conversion of CN- to SCN- sing sulfur as a cofactor
-give sodium thiosulfate to replenish sulfur - hydroxocobalamin tightly binds to CN- and the complex is secreted
5 major metals which induce toxicity
arsenic lead mercury cadmium manganese
arsenic
naturally occurring, most widespread and common environmental metal contaminant
lead
anthropogenic
accumulates in body
differential effects in adults and children
mercury
bio-magnification issue
accumulates in fish
cadmium
multi-organ carcinogen
no chelator
manganese
Parkinson’s like symptoms
no chelator
mechanism of arsenic toxicity
occur in many chemical forms
causes toxicity by binding to sufhydryl groups on enzymes and interfering with cellular metabolism
toxicity index: organic <
acute arsenic poisoning symptoms
hemolysis and hemoglobinurea GI issues ventricular arrhythmias vasodilation hyperpigmentation of skin kidney tubular damage
chronic arsenic poisoning symptoms
nephritis
dermatitis
cancer of multiple tissues: bladder, liver
arsenic toxicity treatment
remove ingested arsenic by lavage or emesis
dimercaprol chelator for acute
succimer chelator for chronic
acute lead poisoning
kidney damage
GI irritation
chronic lead poisoning
lumbism
interference with heme biosynthesis leading to microcytic anemia
constipation and ab pain
neurological damage
children vs adult lead poisoning
children: developmental deficits, low IQ, growth retardation, irritability
adults: hypertension, cholic, anemia
lead toxicity treatments
remove unabsorbed via gastric lavage
calcium gluconate for GI effects
chelation therapy
treatment recommended by CDC for kids w >5 mg/dL
different lead chelation therapy options
Ca Na2EDTA
BAL (dimercaprol)
penicillamine (oral)
succimer (oral)
