Pharmacology- Regal/Trachte Flashcards
What viral envelope protein binds to CD4 on host T-cells?
gp120
What are the co-receptors found on T-cells that the HIV virus also needs to bind?
CXCR4 (later) or CCR5 (early)
What host transcription factor binds to LTR and acts as a promoter for the HIV viral genome?
NFkB!!!!! is a transcription factor that binds to long terminal repeats and acts as a promoter for viral genes
CD4+ count less than what is considered AIDS?
less than 200
What is the main cause of reduced T-cells in HIV?
Provirus (envelope proteins inserted in host membrane) can bind to non-infected cells to induce autophagy
What is the difference between a nuceloside reverse transcriptase inhibitor and a nucleoTide reverse transcriptase inhibitor?
The nucleoside inhibitors require phosphorylation by cellular enzymes to the triphosphate form to be active
Happens in cytosol where RT is
Zidovudine
nuscleoSide reverse transcriptase inhibitor
competitively inhibits RT and terminates DNA production
Lamivudine
nuscleoSide reverse transcriptase inhibitor
competitively inhibits RT and terminates DNA production
Emtricitabine
nuscleoSide reverse transcriptase inhibitor
competitively inhibits RT and terminates DNA production
Abacavir
nuscleoSide reverse transcriptase inhibitor
competitively inhibits RT and terminates DNA production
Tenofovir
nucleoTide reverse transcriptase inhibitor
*already phosphorylated!!
competitively inhibits RT and terminates DNA production
What are the major toxicities of NRTIs?
Mitochondrial toxicity= lactic acidosis
Hepatic steatosis = fatty liver
Fat redistribution
Hyperlipidemia
Efavirnez
Non-nucleoside RT inhibitor
Binds DIRECTLY to RT (at a site distinct from the NRTI)
- Does NOT require phosphorylation to be effective
- No cross resistance with NRTIs
Etravirine
Binds DIRECTLY to RT (at a site distinct from the NRTI)
- Does NOT require phosphorylation to be effective
- No cross resistance with NRTIs
Atazanavir
Protease inhibitor
-Inhibits the protease responsible for post-translational cleavage of the Gag-Pol polyprotein (cannot fold properly).
Ritonavir
Protease inhibitor
-Inhibits the protease responsible for post-translational cleavage of the Gag-Pol polyprotein (cannot fold properly).
Darunavir
Protease inhibitor
-Inhibits the protease responsible for post-translational cleavage of the Gag-Pol polyprotein (cannot fold properly).
Enfuviritde (T-20)
Fusion inhibitor
Binds to gp41 (transmembrane envelope glycoprotein) and prevents conformational change so fusion with host does not occur
Raltegravir
Integrase inhibitor
Binds to integrase, and inhibits strand transfer (the final step for provirus integration)
Maraviroc
CCR5 antagonist
Binds specifically and selectively to host CCR5 (one of the co-receptors used by HIV to gain entry into the host cell)
**note will not work against HIV that utilizes CXCR-4
Resistance if HIV switches chemokine receptors
Why would you add a low does of ritonavir to an HIV regimen?
- Ritonavir is a protease inhibitor that is poorly tolerated
- It is used at lower doses to increase the serum concentrations of other protease inhibitors and decrease the dosage frequency of other protease inhibitors
- POTENT INHIBITOR or CYP3A4 which is the cytochrome that metabolizes a number of other protease inhibitors and decreases their effectiveness
Rifampin
Specifically binds to and inhibits mycobacterial DNA-dependent RNA polymerase
Blocks RNA synthesis/ transcription
Most active mycobacterial agent available- bactericidial activity against dividing and non-dividing M. tuberculosis with sterilizing activity
Isoniazid
Blocks myobacterial reductase and inhibits mycolic acid synthesis (essential requirement for cell wall)
Prodrug that is activated my mycobacterial enzyme
Bactericidial
For latent and TB disease
Effects dividing cells
Pyrazinamide
Exact MOA unclear
Prodrug with metabolite active only in acidic environments
More active against slowly replicating organisms
Hepatoxicity
Ethambutol
Inhibition of arabinosyltransferases involved in cell wall synthesis
BACTERIOSTATIC!!!!
Provides synergy with other drugs
Least potent against M. tuberculosis among first line drugs
Ocular toxicity
Streptomyocin/ Aminoglycosides
Inhibits protein synthesis by binding at site on 30S mycobacterial ribosome
Low level bactericidial activity
Administered only IV or IM
Used infrequently because of toxicity, inconvience, etc.
Ototoxicity, neuropathy, renal toxicity
Pyridoxine
Vitamin B6! Supplemental
Should be given to all HIV pts being treated with isoniazid to reduced CNS & PNS adverse effects
What are the four first-line drugs used for tuberculosis?
Rifampin
Isoniazide
Pyrazinamide
Ethambutol
Which of the 4 first line drugs for tuberculosis is bacterioSTATIC?
Ethambutol
Lispro Insulin
Rapid Acting insulin
Onset is 15 mins
Duration 3-5 hours
Aspart Insulin
Rapid Acting insulins
Onset is 15 mins
Duration 3-5 hours
What is the short acting insulin called?
Regular insulin
Onset 30 mins
Duration 4-8 hours
NPH Insulin
Intermediate Acting
Onset 2-4 hours
Duration 10-20 hours
Glargine Insulin
Long Acting
Onset 1-2
Duration 18-24 hours
When is the peak of long acting insulin?
TRICKED YA!
Theres isn’t one!!!! Hehehehe
Mannitol
Osmotic diuretic
Increases tubular fluid osmolarity
Increases urine flow
Acetazolamide
Carbonic Anhydrase inhibitor
Acts in the PCT
Not used clinically
Furosemide
Loop diuretic
Inhibits NKCC pump in thick ascending limb
Stimulates PGE release (vasodilatory affect on afferent arteriole)
Bumetanide
Loop diuretic
Inhibits NKCC pump in thick ascending limb
Stimulates PGE release (vasodilatory affect on afferent arteriole)
Clorthalidone
Inhibits NaCl reabsorption in the early CT
Hydrochlorothiazide
Inhibits NaCl reabsorption in the early CT
Spironolactone
Competitive aldosterone receptor antagonist
Epleronone
Competitive aldosterone receptor antagonist
Amiloride
Directly block ENaC Channel in principle cells of collecting duct
Triamterene
Directly block ENaC Channel in principle cells of collecting duct
How do the thiazide diuretics cause hyperglycemia?
Thiazide binds SUR on K+ channel and opens it
Leads to hyperpolarization of cell (Ca+ does NOT enter, NO increase in cAMP)
Prevents insulin secretion
NOTE* same MOA of how thiazides cause vasodilation to decreases systemic resistance and lower BP
How does glucose binding to GLUT 2 normal cause insulin release?
Glucose binds GLUT 2 Broken down into ATP ATP blocks K+ channel Leads to depolarization Depolarization activates Ca+ channel Ca+ enters cell- increases cAMP Increased camp causes insulin stored in vesicles to be released!
Demecocyclin
Antibiotic that has ADH antagonist properties
Probenicid
Inhibits renal organic acid transporter to facilitate excretion of (excretes more uric acid, treatment for gout)
Sulfinpyrazone
Inhibits renal organic acid transporter to facilitate excretion of (excretes more uric acid, treatment for gout)
Colchicine
Microtubule inhibitor to treat gout
Allopurinol
Xanthine oxidase inhibitor to treat gout
