Pharmacology Flashcards
Describe the mechanism of NRTI induced mitochondrial toxicity
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
what is the prodrug of tenofovir disoproxil fumarate
tenofovir diphosphate
Which ntrti is only used for HBV
adefovir dipivoxil
What NTRTI has less renal toxicity and therefore more effective for patients that have renal impairment
Tenofovir alafenamide fumarate
What are adverse effects of TDF
fanconi syndrome and bone loss
Interferon alpha Is Contra indicated for what
Decompensated liver cirrhosis
What strains of viral hepatitis Can be treated with interferon alpha
Hbv and HCV
What are important adverse effects of interferon alpha
Hypotension and rebound tachycardia (cytokine induced vasodilation)
Flu like symptoms, muscle pain, depression, seizures, hypothyroidism
What is the mechanism of action for interferon alpha
It’s an inflammatory cytokine that activates inflammatory cells:
t cells
NK cells
macrophages
what is the proposed mechanism for the neurological effects of interferon alpha
Cytokines activate the hypothalamic pituitary axis which can contribute to mood changes
they also inhibit the synthesis of Norepinephrine and Serotonin
Interferon activates what signaling cascade pathway
JAK-STAT pathway
Mechanism of action for Ribavirin
Inhibit Guanine synthesis
What other viruses are implicated for ribavirin
rsv
hemorrhagic viruses: hanta & Lassa
What are the adverse effects of ribavirin
Bone marrow suppression and hemolytic anemia
Extremely tetatrogenic: pts. should use oral contraceptives up to 6-month after treatment termination
What is the mechanism of action for sofosbuvir
Inhibits HCV NS5B RNA-dependent RNA polymerase
What is the mechanism of action for ledipasvir
inhibits HCV NS5A protein
Which hcv serotype Is the most common
serotype 1
Ledipasvir conversion to its active form is pH dependent. what drugs should be avoided with this medication
Proton pump inhibitors and H2 receptor antagonist
why is amiodarone w/ sofosbuvir CI?
Both of these drugs decrease heart rate which can cause Brady Cardia
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
UDP, acetyly CoA & GSH
Are important cyp inhibitors you need to know about
grapefruit juice
PPIs
amiodarone
cimetidine
azoles
sulfonamides
isoniazid
erythromycin
acute ethanol
What are important CYP inducers you need to know about
St. John’s Wort
rifampin
antiepileptics: phenobarbital, carbamazepine, phenytoin
chronic ethanol
Chloramphenicol is metabolized by UDP. What causes Gray baby syndrome
neonates are missing UDP cofactors
alcohol is metabolized by what CYP?
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
What drug reaction is associated with slow acetylators
lupus-like butterfly rash
What are the clinical presentations for acetaminophen overdose
Central lobular necrosis and acute renal tubular necrosis
What antidotes can be given to reduce the toxic effects of acetaminophen
charcoal
N-acetylcysteine
Must be administered within eight hours of overdose
The mechanism of action for in acetylcysteine
increases glutathione reserves and the body by donating sh groups
Describe the hepatotoxic mechanism of isonazide
Acetylated toxic free radicals
What is the hepatotoxic metabolite of Valpro 8
4-pentenoic acid
Valproic causes what histological liver changes
microvesicular steatosis
What are the mechanisms of action for vel proic acid
CCB, NaCB, decreases glutamate at NMDA; enhances GABA
What antidote can be given to reverse the hepatotoxic effects of velpro 8
carnitine
What is the mechanism of action for carnitine in the context of valproate toxicity
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
valproic acid is not indicative or pediatric patients what can you give them instead
ehosuximide
What is the hepatotoxic mechanism of phenytoin
CYP conversion creates a highly reactive arene oxide metabolite
This metabolite binds covalently to hepatic macromolecules interfering with a lot of different liver functions
What is the mechanism of phenotyne
NaCB
what is Nitrofurantoin used for
E. coli cystitis
Why is nitroferantoin indicated for treatment of E coli Induced cystitis
it inhibits acetyl Coenzyme A
What is the mechanism for hepatic toxicity induced by nitrofurantoin
auto antibodies against nuclear components hepatic smooth muscle and mitochondria\
autoimmune like hepatitis
Similar patterns of drug induced autoimmune like hepatitis can also be observed with what other drugs
minocycline
hydralazine
methyldopa
What are the mechanisms of action for amiodarone
KCB, CCB, NaCB, beta-adrenergic
What is an extra hepatic adverse effect of nitrofurantoin
pulmonary fibrosis
Describe the hepatotoxic mechanism of amiodarone
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
What is an hepatic adverse effect associated with erythromycin estolate
acute colostasis & pruitis
Induces portal inflammation
What is the hepatotoxic mechanism of oral contraceptives
Inhibition of Bill Rubin and bio acid secretion leading to colostasis
FYI anabolic steroids lead to profound colostasis
What is the hepatotoxic mechanism of statins
acute hepatitis histologic characteristics
central lobular necrosis and colostasis and oxidative stress
What is the hepatic toxic mechanism of thioomides like propylthiouracil
Increases oxidative stretch which can activate inflammatory and immunological pathways
What is the mechanism of action for propylthiouracil
inhibits incorporation of iodine into tyrosine residues
Tx hyperthyroidism
Describe the hepatotoxic mechanism of inhaled anesthetic “Halothane”
trifluoroacetyl metabolis covalently binds to hepatocyes stimulating activation of IFs, NK cells, and oxidative mechanism
What other inhaled anesthetics can be used instead of halophane
enflurane & sevoflurane
What is the mechanism of action for methotrexate
inhibitor of dihydrofolate reductase
What is the hepatotoxic mechanism of methotrexate
The strike is a pro oxidant and leads to oxidative stress and mitochondrial injury
depletes of hepatic folate stores
