exam iii - antiviral agents for HIV infections and diuretics

do nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) treat HIV?

yes

what are nucleoside/nucleotide reverse transcriptase inhibitors active against?

HIV-1/HIV-2

what are the AE of NRTIs associated with?

mitochondrial toxicity

as an AE of nucleoside/nucleotide reverse transcriptase inhibitors, mitchondrial toxicity can occur. what are some results of mitochondrial toxicity? 2

lactic acidosis and hepatomegaly?

what is the prototype for nucleosides/nucleotides reverse transcriptase inhibitors?

abacavir

what was formally the first NRTI? is it still recommended in the U.S.?

zidovudine

what is the MOA for abacavir?

inhibits HIV replication by suppressing the synthesis of viral DNA through converting to its active form and acting as a substrate for reverse transcriptase

what are the 4 therapeutic benefits of nucleosides/nucleotides reverse transcriptase inhibitors? specifically with the viral load, CD4 t-cell count, onset of symptoms, and symptom severity? (increases or decreases?)

decreases viral load, increases CD4 T-cell count, decreases onset of disease symptoms, and decreases severity

what are the 4 major AE for nucleoside/nucleotide reverse transcriptase inhibitors

fatigue/h/a, lactic acidosis, hepatomegaly, and rarely a hypersensitivity rxn

why should you not drink alcohol when taking abacavir?

because both the NRTI and alcohol compete for the same enzyme that is needed to metabolize alcohol

true or false: non-nucleoside reverese transcriptase inhibitors have a structural relationship with naturally occuring nucleosides

false; they have no structual relationship

when non-nucleoside reverese transcriptase inhibitors bind to the center of reverse transcriptase, what does that cause?

direct inhibition of binding of nucleosides in DNA formation

true or false; non-nucleoside reverse transcriptase inhibitors do not undergo active conversion in the cells

true

non-nucleoside reverse transcriptase inhibitors are only active towards what?

HIV-1

what is the prototype for non-nucleoside reverse transcriptase inhibitors

efavirenz

what is the MOA for efavirenz?

binds directly with HIV reverse transcriptase and suppresses enzyme activity and replication

what are the 3 types of AE that you could get when taking efavirenz? which is more common?

CNS symptoms (most common), rash, and teratogenicity

how common is obtaining CNS symptoms when taking efavirenz? what do these symptoms include?

50%, dizziness, insomnia, and nightmares

what is the onset of a rash when taking efavirenz?

11d

if the rash from taking efavirenz is severe, then it may progress into what?

stevens-johnson syndrome

wof you must take efavirenz during pregnancy, what can you do to prevent teratogenicity?

use 2 forms of bbirth control

what are protease inhibitors active against?

HIV-1 and HIV-2

how can you make protease inhibitors more effective?

when used in combination with NRTIS

fill in the black: all protease inhibitors are substrates of cytochrome ____ enzymes?

p450

can protease inhibitors act as a inhibitor, inducer, or both?

both

if protease inhibitors can act as either an inhibitor or inducer, what may that lead to?

multiple drug interactions

what is the prototype for protease inhibitors?

darunavir

how can you boost hte effects of darunavir?

taking it with ritonavir

what is the MOA of darunavir?

preventing HIV naturation by binding to the active site of HIV protease and preventing cleaving of HIV polyproteins

true or false: immature HIV are infectious

false

in terms of darunavir's pharmacokinetics, does it acts as a substrate, inhibitor, or both for CYP3A4?

both

in terms of darunavir's pharmacokinetics, what does it induce?

CYP2C9

what are the main 4 AE of darunavir?

hyperlipidemia, hyperglycemia, rash, and n/v/d

can darunavir cause many or little potential drug interactions?

many

what metabolizes darunavir, a protease inhibitor?

CYP3A4 and CYP2C9

fix the sentence: (inhibitors/inducers) of CYP3A4 can accelerate metabolism of darunavir, leading ot (therapeutic/subtherapeutic) levels

inducers, subtherapeutic

what medication reduces HIV acquisition in HIV negative person by 44-73%?

tenofovir

what are the indications for use for tenofovir?

those who are at high risk for HIV exposure and acquisition

can tenofovir be used for pre-exposure anaphylaxis, post-exposure anaphylaxis, or both?

both

if exposed to HIV, you msut be treated immediately after. how long should you take tenofovir?

28 days

when exposed to HIV, you must be treated under how many hours for it to be most effective?

<72h

what is the most frequently prescribed loop diuretic's prototype?

furosemide

what is the MOA for furosemide

acts on primarily the ascending limb of loop of henle to block reabsorption of sodium and chloride

in terms of furosemide's pharmacokinetics, how fast is the onset if taken po?

60 mins

in terms of furosemide's pharmacokinetics, how fast is the onset if taken iv?

5 mins

what are the 4 therapeutic uses for furosemide?

rapid diuresis, hypertension, pulmonary edema, and edema

what are the main 5 AE for furosemide? which is rare?

dehydration, hypotension, hypokalemia, hyponatremia/chloremia, and rarely ototoxicity

why should you not take digoxin when taking furosemide?

because it can cause arrhythmias and electrolyte imabalances

what other drug should you not take when taking furosemide?

any ototoxic drug

what drug may bring a beneficial effect on furosemide?

potassium-sparing diuretics

what makes thiazides similar to loop diuretics?

it increases the excretion of sodium, chloride, potassium, and water

as a therapeutic effect of thiazides, what are elevated? 2

levels of glucose and uric acid

when are thiazides INEFFECTIVE?

when urine flow is scant

what is the prototype for thiazides and is most widely used?

hydrochlorothiazide

where is the site of action for hydrochlorothiazide?

early segment distal convoluted tubule

when does hydrochlorothiazide peak?

4-6 h

what are the therapeutic uses/indications of use for hydrochlorothiazide?

essential hypertension and edema

why should you take hydrochlorothiazide with food?

because the most common AE is GI upset

as a result of excretion of sodium, chlroide, potassium, and water, what is a possible AE of hydrochlorothiazide?

electrolyte imabalance

because hydrochlorothiazide excretes water, what is a possible AE?

dehydration

why should you not take digoxin with hydrochlorothiazide?

increases the risk for toxicity related to hypokalemia

what brings a positive interaction to thiazides?

augmentation of hypertensive drugs

true or false: thiazides can be combines with ototoxic agents without increasing the risk of hearing loss

true

true or false: postassium-sparing diuretics are rarely used alone for therapy

true

what are the therapeutic effects of potassium-sparing diuretics? 2

increasei n urine production and substantial decrease in potassium excretion

what is the prototype for potassium-sparing diuretics?

spironolactone

what kind of potassium-sparing diuretic derivative is spironolactone?

steroid

what is the MOA for spironolactone?

blocks aldosterone in the distal nephron, retention of potassium, and increases sodium excretion

what are the 3 therapeutic uses for spironolactone?

hypertension, edema, and heart failure

what are the main 2 AE of spironolactone?

endorine effects and hyperkalemia

should you take potassium supplements when taking spironolactone?

no

what are 3 contraindications fr spironolactone?

pts with hyperkalemia, severe kidney disease, and electrolyte inbalances