Adverse Effects Flashcards
Susceptibility Alleles Associated with ADR for Ethanol
ALDH2*2 (G1510A; Glu487Lys) is an inactive allele →
‘Asian flush’ sx due to accumulation of acetaldehyde (genetic Disulfiram)
↑ ikelihood of esophageal ca in chronic alcoholics
Susceptibility Alleles Associated with ADR for Phenytoin
Inactive CYP2C9 and CYP2C19
alleles → improper drug metabolism → drug accumulates → ADR (ataxia, slurred speech, decreased coordination and mental confusion)
Hyperactive MDR1 promoter allele → high levels of MDR1 protein at BBB → not enough drug available to inhibit VGSC → non- responder
Low affinity VGSC allele→ ↓ binding of drug to VGSC protein → non-responder
Susceptibility Alleles Associated with ADR for 5-fluorouracil (5FU)
~3% of pt pop heterozygous for inactive ‘A’ allele found in intron (dominant allele)
→ improper splicing → inactive DPD enzyme → 5FU not properly inactivated
Potential fatal myelosuppression
2R/2G,2R/2Cor3R/3C allele of TS gene (also known as TYMS gene) has low transcriptional activity l→ low levels of TS enzyme → patients responsive to 5FU
3R/3GalleleofTS(or TYMS) gene has high transcriptional activity → high levels of TS enzyme→ patients non-responsive to 5FU
Susceptibility Alleles Associated with ADR for Codeine
Inactive allele (poormetabolizer): multiple inactive alleles such as CYP2D6*10 → poor to no conversion of codiene
CYP2D6*2xN allele(ultra-metabolizer): ultra efficient conversion of codeine → too much conversion to morphine → fatal respiratory depression
Susceptibility Alleles Associated with ADR for Warfarin
Multiple alleles including CYP2C92 and CYP2C93 (most prevalent inactive alleles in European American population) → ADR
VKORC1”A”allele has low transcriptional activity and associated with ADR (↑ likelihood of excessive bleeding)
Benzimidazole
GI disturbance
Bone marrow suppression
Ivermectin
Mazzotti-like rxn due to dying microfilariae → use steroids
Pyrantel Pamoate
GI disturbances
HA
Diethylcarbamazine
Mazzotti-like rxn due to dying microfilariae → use steroids
Praziquantal
GI disturbances
HA
Artemisinins
Rare, dose‐related and reversible
ACT with Lumefantrine
Coartem
GI distress, HA, N/V
Cardiac arrhythmias/neuro sx w/ high doses
If vomit in 1st 30 mnin → reapeat dose
Chloroquine Phosphate
Visual disturbances
Puritis on palms and feet in AA
Discoloration of nail beds/mucous mem
Parenteral doses >5g → fatal
Toxicities w/ high dosr → CV and CNS
Hemolysis (↑ w/ G6PD deficiency)
Quinne Sulfate
Cinchonism: tinnitus, deafness, visual disturbance, HA, N/V dizziness, postural hypotension (reversible)
Blackwater fever: black urine, severe hemolysis, hemoglobinemia, hemoglobinuria →
STOP Tx
Hypoglycemia, hypotension
Fatal oral dose = 2-8 g
Hemolysis (↑ w/ G6PD deficiency)
Primaquine
Hemolytic anemia in G6PD deficiency
Isoniazid (INH)
Hepatic toxicity (especially in slow acetylators) → age dependent >35 yo
Potentially fatal hepatitis
Peripheral neuropathy (↑ in slow acetylateors) due to vit B6 AKA pyridoxine deficiency
Pyrazinamide
Hepatic toxicity
Hyperuricemia 100% of pts → exacerbates gout
Arthralgias
Ethambutol
Optic neuritis (rare) but causes red-green color blindness