Pharmacology

Question 1

Describe the mechanism of NRTI induced mitochondrial toxicity

Answer 1

Inhibits mitochondrial dna polymerase gamma
This causes subsequent inhibition of the use of free fatty acids for the electron transport chain
Consequently triglycerides accumulate leading to hepatic steatosis and lactic acid

Question 2

what is the prodrug of tenofovir disoproxil fumarate

Answer 2

tenofovir diphosphate

Question 3

Which ntrti is only used for HBV

Answer 3

adefovir dipivoxil

Question 4

What NTRTI has less renal toxicity and therefore more effective for patients that have renal impairment

Answer 4

Tenofovir alafenamide fumarate

Question 5

What are adverse effects of TDF

Answer 5

fanconi syndrome and bone loss

Question 6

Interferon alpha Is Contra indicated for what

Answer 6

Decompensated liver cirrhosis

Question 7

What strains of viral hepatitis Can be treated with interferon alpha

Answer 7

Hbv and HCV

Question 8

What are important adverse effects of interferon alpha

Answer 8

Hypotension and rebound tachycardia (cytokine induced vasodilation)
Flu like symptoms, muscle pain, depression, seizures, hypothyroidism

Question 9

What is the mechanism of action for interferon alpha

Answer 9

It’s an inflammatory cytokine that activates inflammatory cells:
t cells
NK cells
macrophages

Question 10

what is the proposed mechanism for the neurological effects of interferon alpha

Answer 10

Cytokines activate the hypothalamic pituitary axis which can contribute to mood changes
they also inhibit the synthesis of Norepinephrine and Serotonin

Question 11

Interferon activates what signaling cascade pathway

Answer 11

JAK-STAT pathway

Question 12

Mechanism of action for Ribavirin

Answer 12

Inhibit Guanine synthesis

Question 13

What other viruses are implicated for ribavirin

Answer 13

rsv
hemorrhagic viruses: hanta & Lassa

Question 14

What are the adverse effects of ribavirin

Answer 14

Bone marrow suppression and hemolytic anemia
Extremely tetatrogenic: pts. should use oral contraceptives up to 6-month after treatment termination

Question 15

What is the mechanism of action for sofosbuvir

Answer 15

Inhibits HCV NS5B RNA-dependent RNA polymerase

Question 16

What is the mechanism of action for ledipasvir

Answer 16

inhibits HCV NS5A protein

Question 17

Which hcv serotype Is the most common

Answer 17

serotype 1

Question 18

Ledipasvir conversion to its active form is pH dependent. what drugs should be avoided with this medication

Answer 18

Proton pump inhibitors and H2 receptor antagonist

Question 19

why is amiodarone w/ sofosbuvir CI?

Answer 19

Both of these drugs decrease heart rate which can cause Brady Cardia

Question 20

If a drug is not polarized enough to be excreted after phase one it goes on to phase two. what cofactors are often required for phase two drug metabolism

Answer 20

UDP, acetyly CoA & GSH

Question 21

Are important cyp inhibitors you need to know about

Answer 21

grapefruit juice
PPIs
amiodarone
cimetidine
azoles
sulfonamides
isoniazid
erythromycin
acute ethanol

Question 22

What are important CYP inducers you need to know about

Answer 22

St. John’s Wort

rifampin

antiepileptics: phenobarbital, carbamazepine, phenytoin

chronic ethanol

Question 23

Chloramphenicol is metabolized by UDP. What causes Gray baby syndrome

Answer 23

neonates are missing UDP cofactors

Question 24

alcohol is metabolized by what CYP?

Answer 24

CYP2E1 Previously I’m lost the only way to think I have a job is to get you to go back here let’s move back no no i’m supposed to do

Question 25

What drug reaction is associated with slow acetylators

Answer 25

lupus-like butterfly rash

Question 26

What are the clinical presentations for acetaminophen overdose

Answer 26

Central lobular necrosis and acute renal tubular necrosis

Question 27

What antidotes can be given to reduce the toxic effects of acetaminophen

Answer 27

charcoal N-acetylcysteine Must be administered within eight hours of overdose

Question 28

The mechanism of action for in acetylcysteine

Answer 28

increases glutathione reserves and the body by donating sh groups

Question 29

Describe the hepatotoxic mechanism of isonazide

Answer 29

Acetylated toxic free radicals

Question 30

What is the hepatotoxic metabolite of Valpro 8

Answer 30

4-pentenoic acid

Question 31

Valproic causes what histological liver changes

Answer 31

microvesicular steatosis

Question 32

What are the mechanisms of action for vel proic acid

Answer 32

CCB, NaCB, decreases glutamate at NMDA; enhances GABA

Question 33

What antidote can be given to reverse the hepatotoxic effects of velpro 8

Answer 33

carnitine

Question 34

What is the mechanism of action for carnitine in the context of valproate toxicity

Answer 34

so Valproic acid inhibits fatty acid oxidation leading to the depletion of acetyl coa needed to make ATP carnitine allows for transport of long-chain fatty acids into muscle mitochondria To counteract this effect

Question 35

valproic acid is not indicative or pediatric patients what can you give them instead

Answer 35

ehosuximide

Question 36

What is the hepatotoxic mechanism of phenytoin

Answer 36

CYP conversion creates a highly reactive arene oxide metabolite This metabolite binds covalently to hepatic macromolecules interfering with a lot of different liver functions

Question 37

What is the mechanism of phenotyne

Answer 37

NaCB

Question 38

what is Nitrofurantoin used for

Answer 38

E. coli cystitis

Question 39

Why is nitroferantoin indicated for treatment of E coli Induced cystitis

Answer 39

it inhibits acetyl Coenzyme A

Question 40

What is the mechanism for hepatic toxicity induced by nitrofurantoin

Answer 40

auto antibodies against nuclear components hepatic smooth muscle and mitochondria\ autoimmune like hepatitis

Question 41

Similar patterns of drug induced autoimmune like hepatitis can also be observed with what other drugs

Answer 41

minocycline hydralazine methyldopa

Question 42

What are the mechanisms of action for amiodarone

Answer 42

KCB, CCB, NaCB, beta-adrenergic

Question 43

What is an extra hepatic adverse effect of nitrofurantoin

Answer 43

pulmonary fibrosis

Question 44

Describe the hepatotoxic mechanism of amiodarone

Answer 44

amiodarone is converted to a hepatotoxic metabolite: desethylamiodarone This metabolite accumulates and hepatose ms and mitochondria and also bioduct epithelium Accumulation leads to formation of Mallory bodies, steatosis, Intra lobular inflammation, phospholipidosis, and fibrosis

Question 45

What is an hepatic adverse effect associated with erythromycin estolate

Answer 45

acute colostasis & pruitis Induces portal inflammation

Question 46

What is the hepatotoxic mechanism of oral contraceptives

Answer 46

Inhibition of Bill Rubin and bio acid secretion leading to colostasis FYI anabolic steroids lead to profound colostasis

Question 47

What is the hepatotoxic mechanism of statins

Answer 47

acute hepatitis histologic characteristics central lobular necrosis and colostasis and oxidative stress

Question 48

What is the hepatic toxic mechanism of thioomides like propylthiouracil

Answer 48

Increases oxidative stretch which can activate inflammatory and immunological pathways

Question 49

What is the mechanism of action for propylthiouracil

Answer 49

inhibits incorporation of iodine into tyrosine residues Tx hyperthyroidism

Question 50

Describe the hepatotoxic mechanism of inhaled anesthetic "Halothane"

Answer 50

trifluoroacetyl metabolis covalently binds to hepatocyes stimulating activation of IFs, NK cells, and oxidative mechanism

Question 51

What other inhaled anesthetics can be used instead of halophane

Answer 51

enflurane & sevoflurane

Question 52

What is the mechanism of action for methotrexate

Answer 52

inhibitor of dihydrofolate reductase

Question 53

What is the hepatotoxic mechanism of methotrexate

Answer 53

The strike is a pro oxidant and leads to oxidative stress and mitochondrial injury depletes of hepatic folate stores