4 Flashcards
APOL1 G1 & G2 variants
-In 30 – 50% of African Americans
-Predisposes to FSGS (na retention) nephropathy
-Increases risk of HTN and HIV+ nephropathy
Cytochrome P450 2D6
-Absent in 7% of Caucasians
-Hyperactive in 30% of East Africans
-met. of beta blockers
-Inhibited by
* fluoxteine
* haloperidol
* paroxetine
* quinidine
Hydralazine
For BP control, QID
-Slow acetylators have BP controlled by just QD
-Higher doses = lupus like syndrome
-Acetylated in liver by NAT2
NAT2 (G, P, CR)
Decreased ___ synthesis made them more sensitive to UV conversion of vitamin D
Melanin
-Important since not as much UV exposure further from equator
Decreased lactase regulation
Allowed for increased use of milk as a food source
Decreased renal tubular Na transporter expression results in ____
More salt excretion
-Polymorphism in NEDD4 protein (regs. na trans. degradation) results in less Na transporters
HCTZ Response
-White ppl less responsive to HCTZ
-HCTZ blocks ADH stimulation of Na transporter expression
-But they already have less Na transporters to begin with
RAAS System Sensitivity
-White ppl also have more sensitive RAAS systems
-RAAS decreases exp. of NEDD2 (more Na trans. exp. and Na retention)
-White ppl therefore more responsive to ACEI/ARBs
Catecholamine Synthesis
-#1: L-tyrosine to adrenaline
-Rate limiting is tyrosine hydroxylase
-Stress increases TH production (elevated adrenaline)
Sleep apnea (stress) affects 10-50% of HTN pts = more adrenaline = more responsive to BETA BLOCKERS (block sympathetic NS for BP)
Beta Blockers
All metabolized by CYP2D6 (like codeine)
ABSENT IN 7% of white ppl
BUT, HTN drugs have a log dose response
-Increasing dose doesn’t increase efficacy much (DOES INCREASE AEs)
If you have G1 and G2 variant, you were protected by _____
African sleeping sickness
African sleeping sickness was caused by this parasite Trypanosoma brucei
G1 and G2 predominantly in West Africa
