B4.014 Prework 2 Adverse Drug Reactions

Question 1

what are the 2 classes of cholinesterase inhibiting insecticides?

Answer 1

organophosphates

carbamates

Question 2

how do organophosphates and carbamates differ

Answer 2

organophosphates are irreversible

carbamates are reversible

Question 3

compare the normal mode of action of ACh + AChE with physostigmine + AChE and DFP + AChE

Answer 3

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

Question 4

symptoms of cholinesterase inhibiting insecticides poisoning

Answer 4

SLUD:
salivation
lacrimation
urination
defecation

Question 5

mild/moderate/severe insecticide poisoning

Answer 5

mild: anorexia, headache, dizziness, nausea
moderate: excessive sweating, vomiting, ab cramps
severe: pinpoint and nonresponsive pupils, heat block, coma

Question 6

cholinesterase inhibiting insecticides poisoning treatment options

Answer 6

atroping: small dose, increase as needed

2-pralidoxime: reactivate AChE enzyme prior to “aging” (contraindicated for carbamates)

Question 7

describe how 2-pralidoxime (2-PAM) works as a treatment for organophosphate poisoning

Answer 7

still an AChE inhibitor, but reversible
binds AChE before organophosphate can
therefore exerts a shorter lasting blockage

Question 8

what are 2 chemical that affect heme protein

Answer 8

methemoglobin
CO
cyanide

Question 9

what is methemoglobin and how is it induced

Answer 9

oxidized hemoglobin (F3+ ferric form)
incapable of carrying oxygen
produced via nitrates from Fe2+ (ferrous)

Question 10

how does CO affect hemoglobin

Answer 10

binds to produce carboxyhemoglobin

binds much tighter than O2 and inhibits O2 carrying

Question 11

cyanide mechanism

Answer 11

inhibits cytochrome C oxidase, an enzyme in the ETC

blocks oxidative phosphorylation and respiration

Question 12

symptoms of nitrate induced methemoglobinemia

Answer 12

choclate colored blood
hypotension, hypoxia, cyanosis
convulsions, coma, resp failure

Question 13

nitrate induced methemoglobinemia treatments

Answer 13

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

Question 14

normal carboxyhemoglobin levels

Answer 14

nonsmokers- 1%
smokers- 5-10%
auto exhaust- 4-7%

Question 15

symptoms of CO poisoning

Answer 15

headache
dizziness and stupor (progressive brain anoxia)
cherry red blood (healthy looking mucous membranes)

Question 16

treatment for CO poisoning

Answer 16

terminate exposure
administer oxygen
avoid respiratory stimulating drugs (increases absorption of CO)

Question 17

mechanism of cyanide toxicity

Answer 17

complexes with ferric iron of cytochrome oxidase and produces cellular anoxia by inhibiting oxygen utilization in the mitochondria; extremely rapid action

Question 18

symptoms of cyanide poisoning

Answer 18

dizziness
headache
hypotension
unconsciousness
convulsions
resp failure

Question 19

treatment of cyanide poisoning

Answer 19

1. induce methemoglobin formation by admin of nitrates
   methemglobin competes with cytochrome oxidase for CN-
2. 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
3. hydroxocobalamin tightly binds to CN- and the complex is secreted

Question 20

5 major metals which induce toxicity

Answer 20

arsenic
lead
mercury
cadmium
manganese

Question 21

arsenic

Answer 21

naturally occurring, most widespread and common environmental metal contaminant

Question 22

lead

Answer 22

anthropogenic
accumulates in body
differential effects in adults and children

Question 23

mercury

Answer 23

bio-magnification issue

accumulates in fish

Question 24

cadmium

Answer 24

multi-organ carcinogen

no chelator

Question 25

manganese

Answer 25

Parkinson’s like symptoms

no chelator

Question 26

mechanism of arsenic toxicity

Answer 26

occur in many chemical forms
causes toxicity by binding to sufhydryl groups on enzymes and interfering with cellular metabolism
toxicity index: organic <

Question 27

acute arsenic poisoning symptoms

Answer 27

hemolysis and hemoglobinurea
GI issues
ventricular arrhythmias
vasodilation
hyperpigmentation of skin
kidney tubular damage

Question 28

chronic arsenic poisoning symptoms

Answer 28

nephritis
dermatitis
cancer of multiple tissues: bladder, liver

Question 29

arsenic toxicity treatment

Answer 29

remove ingested arsenic by lavage or emesis
dimercaprol chelator for acute
succimer chelator for chronic

Question 30

acute lead poisoning

Answer 30

kidney damage

GI irritation

Question 31

chronic lead poisoning

Answer 31

lumbism
interference with heme biosynthesis leading to microcytic anemia
constipation and ab pain
neurological damage

Question 32

children vs adult lead poisoning

Answer 32

children: developmental deficits, low IQ, growth retardation, irritability
adults: hypertension, cholic, anemia

Question 33

lead toxicity treatments

Answer 33

remove unabsorbed via gastric lavage
calcium gluconate for GI effects
chelation therapy
treatment recommended by CDC for kids w >5 mg/dL

Question 34

different lead chelation therapy options

Answer 34

Ca Na2EDTA
BAL (dimercaprol)
penicillamine (oral)
succimer (oral)