Pharmacology Exam 4 - Part 3

Front 1

clinical relevance of genetic polymorphisms is greatest for drugs with a ________

Back 1

narrow therapeutic range

Front 2

pharmacogenetics for malignant hyperthermia-2

Back 2

increased release of Ca2+ from SR leads to increased mm contraction and heat production

Lys --> Arg in ryanodine receptor may lead to the increased Ca2+ release

Front 3

G6PD deficiency

Back 3

RBC G6PD deficiency occurs in 1 in 10 Africans

X-linked recessive

confers resistance to Plasmodium flaciparum malaria

Front 4

drug in duced hemolytic anemia and G6PD deficiency

Back 4

oxidant drugs like primaquine produce H2O2 which oxidizes glutathione

with G6PD deificiency, hemolysis of RBCs reults

other drugs: quinin, quinidine, sulfonamides, dapsone, methylene blue

Front 5

isoniazid and N-acetyltransferase-2 SNPs

Back 5

NAT-2 variability may lead to rapid metabolism of isoniazid and lack of response to the drug for TB tx

Front 6

Aldehyde Dehydrogenase (ALDH) genetics

Back 6

10 human ALDH genes and 13 alleles --> autosomal dominant trait that lacks catlytic activity

ALDH-2 deficiency leads to accumulation of acetaldehyde, causing facial flushing, palpitations, tachycardia

absent in 45% of Chinese
not absent in Caucasians or Africans

Front 7

Ctyochrom P450 polymorphisms

Back 7

2D6
2C19

Front 8

CYP2C19, aka:

Back 8

poor metabolizer (PM) genotype

Front 9

Clinical relevance of CYP2C19

Back 9

cure rate for H. pylori infection is greater in patients who are genetic poor metabolizers of omeprazole

In Japanese subjects given omeproazole, 20 mg/day for 4 weeks, the plasma AUCs in PMs were 5-10 fold higher than in extenisve metabolizers

Front 10

CYP2D6 inhibited by

Back 10

fluoxetine, paroxetine
haloperidol
quinidine
ritonavir

(a potent inhibitor can mimic a genetic polymorphism)

Front 11

thiopurine methyltransferase (TPMT)

Back 11

catlyzes S-methylation of azthioprine & 6-mercaptopurine

v. low or no activity occurs in <0.5% of studied populations

can have fatal consequences for children treated with 6-mercaptopurine for ALL and cause inability to tolerate azathioprine

Front 12

TPMT polymorphisms are what kind of genetic trait?

Back 12

autosomal codominant

Front 13

TPMT deficiency leads to...

Back 13

accumulation of XC thioguanine, leading to BM toxicity

Front 14

3 types of evidence needed to implicate a polymorphism in clinical care

Back 14

screens of tissues from multiple humans linking the polymorphism to a trait

complementary preclinical functional studies indicating polymorphism plausibly linked to a trait

multiple supportive clinical phenotype/genotype studies

Front 15

4 types of pharmacokinetic interactions

Back 15

absorption
distribution and plasma protein binding
metabolism
excretion

Front 16

pharmacodynamic interactions

Back 16

antagonism
additive
synergistic

Front 17

patient factors in drug interactions

Back 17

disease state
renal function
hepatic function
serum protein concentrations
food
environment - e.g.: pesticides
habits - e.g.: EtOH, tobacco
genetics
age
sex

Front 18

factors leading to high risk for adverse drug reactions

Back 18

drug with low TI
large number of drugs
critically ill
HIV +
passive individual
drug abuser

Front 19

drug types with low TIs

Back 19

oral anticoagulants
anticancer agents
immunosuppressive drugs
antidysrrhythmic drugs
lithium carbonate
oral hypoglycemics
anticonvulsants
theophylline
digoxin
aminoglycosides

Front 20

physicochemical interactions influencing drug absorption

Back 20

changes in gastric pH
chelation
binding to resins
adsorption (e.g.: activated charcoal)

Front 21

other factors influencing drug absorption

Back 21

changes in GI motility
reduction in bacterial flora
alteraltion of blood flow (s.c.)

Front 22

factors influencing drug distribution

Back 22

binding to plasma proteins
competition for active transport
inhibition or induction of P-glycoprotein efflux pump

Front 23

role of P-glycoprotein

Back 23

efflux pump in many epithelial cells
excretory function
found in gut wall
can be induced by drugs (rifampin)
inhibited by drugs (quinidine, verapamil, itraconazole, erthromycin)

Front 24

Inhibition of P-glycoprotein does what to digoxin levels?

Back 24

increases

Front 25

digoxin is secreted in the _____ by P-glycoprotein

Back 25

distal nepohron

Front 26

3 drugs that increase the rate of drug metabolism via enzyme induction

Back 26

phenobarbital
cigarette smoking
rifampin

Front 27

P450 enzyme inhibition

Back 27

cimetidine

Front 28

drug that decreases heaptic blood flow

Back 28

propranolol

Front 29

inducers of CYP450 metabolism

Back 29

phenobarbital
carbamazepine
cigarette smoking
chronic EtOH use
phenytoin
rifampin
tobacco

Front 30

inhibitors of CYP450 metabolism

Back 30

cimetidine
cipro
clarithromycin
erythromyin

Front 31

competition for secretion in proximal tubule

Back 31

probenecid and ampicillin
ibuprofen and hydrochlorothiazide

Front 32

altered tubular reabsorption by changes in urinary pH

Back 32

ASA and sodium bicarb
amphetamine and NH4Cl

Front 33

food that binds to drug and prevents absorption

Back 33

milk and tetracycline

Front 34

food that increase rate of absorption

Back 34

fatty meal and griseofulvin

Front 35

food that inhibits P450 microsomal drug metabolism

Back 35

grapefruit juice and lovastatin

Front 36

drug-grapefruit juice interactions

Back 36

grapefruit juice inhibits intestinal P450 3A4 - responsible for first-pass metabolim of many medications

my inhibit P-glycoprotein in intestinal brush border

Front 37

examples of drug-grapefruit juice interactions

Back 37

felodipine
cyclosporine, tacrolimus
atorvastatin, lovastatin, simvastatin
buspirone, carbamazepine, diazepam, midazolam, triazolam
methadone
sildenafil