Renal Pharm Flashcards
competitive antagonist for alpha1 receptor used for BPH to inhibit prostate smooth muscle contraction, improving urine flow
tamsulosin
(Other alpha blockers: prazosin, terazosin, doxazosin)
All these drugs cause orthostatic hypotension, but tamsulosin (aka Flomax) has less of that..why it is used more frequently.
decrease renin release by beta blockade: 2 are selective for beta1 and 1 is nonselective
propanolol (nonselective), metoprolol, atenolol
Can be used to treat stress incontinence by alpha receptor activation, mediating contraction of the bladder base, urethral sphincter and prostate
ephedrine, pseudoephedrine
Why does GBM damage increase clearance of drugs?
many drugs are protein-bound and leak of albumin can increase clearance
Requirements for dialysis to remove a drug
- not protein-bound
- small volume of distribution (meaning in the vascular space)
- water-soluble
Renal effects of prostaglandins
- increase renal blood flow
- decreased water absorption mediated by ADH (AVP)
- decrease chloride resorption in the LOH
- increase renin release (macula densa sensing)
muscarinic agonist (M1-M3) used for post-surgical difficulty urinating or neurogenic bladder from spinal injury
bethanechol
Cholinergic agonists contract bladder wall and relax the GU sphincter
cholinesterase inhibitor used to contract the detrusor muscle and relax the trigone and GU sphincter (indirect-acting cholinergic agonist)
neostigmine
Cholinergic receptor blockers used to treat overactive bladder
Darifenacin, Solifenacin
Cholinergic receptor blocker that relieves bladder spasm after urologic surgery and reduces involuntary voiding in neurologic disease
oxybutynin
nonselective cholinergic blocker used to overactive bladder
trospium
cholinergic blocker used in incontinent institutionalized elderly patients. Relaxes smooth muscle in ureters and bladder wall to slow voiding
propiverine
Other cholinergic blockers (2)
Tolterodine, Fesoterodine
What speeds clearance of salicylates?
alkalinization of the urine
What types of drug poisoning does dialysis treat?
salicylates, methanol, ethylene glycol, lithium, carbamazapine, valproic acid
what enzyme is activated by calcium and calmodulin, and therefore affected by drugs that reduce calcium availability?
phospholipase A2
glucocorticoids indirectly inhibit PLA2
Why can long-term use of NSAIDs cause HTN, edema and CHF?
PGE2 maintains RBF and salt excretion. NSAIDs inhibit COX and therefore prostaglandin synthesis
weak inhibitor of COX but does not acetylate
salicylic acid
Why is O2 consumption and CO2 production increase with aspirin?
uncoupling of oxidative phosphorylation
Which potassium-sparing diuretic has fewer progesterone-related side effects?
eplerenone
Adverse effect of spironolactone
impotence
Which potent steroid with both mineralocorticoid and glucocorticoid activity is used to treat aldosterone deficiency?
fludrocortisone
(aldosterone deficiency = “salt-wasting”)
This is never used primarily for glucocorticoid effects, because it causes significant salt retention.
Increases the sodium reabsorption at the distal nephron/collecting duct by increasing the # of sodium channels
Aldosterone
(increased sodium reabsorption leads to increased water reabsorption, H+ secretion and generation of bicarb. When H+ is sent to the lumen, bicarb is sent to the blood).
Side effects of MR antagonists
hyperkalemia, metabolic acidosis, gynecomastia, impotence, GI
Potent GR (glucocorticoid receptor) agonists
betamethasone, dexamethasone
Enzyme that converts cortisol (active) to cortisone (inactive)
11beta HSD2
phosphate binding polymer that binds phosphate and eliminates it in the gut
sevelamer
calcimimetic that imitates calcium & inhibits PTH secretion by lowering the concentration sensitivity of the calcium sensor (make it more sensitive to lower concentration of calcium). Use: secondary hyperparathyroidism from chronic renal failure
cinacalcet
calcitriol analog used in chronic renal failure and acting directly on the parathyroid to reduce PTH without hypercalcemia. Used to treat hyperparathyroidism.
paricalcitriol
used in chronic renal failure and hyperparathyroidism to suppress PTH gene expression; has low affinity for serum binding proteins so it has a shorter half-life than calcitriol
22-oxacalcitriol
Decrease plasma uric acid production by inhibiting xanthine oxidase. Maintenance drugs to prevent gout.
- allopurinol
2. febuxostat (nonpurine and has fewer drug interactions)
Uricosuric agent that inhibits reabsorption of urate by URAT-1; inhibits transporter so elimination of negatively charged drugs is inhibited. It was developed to inhibit secretion of PCN in WWII
probenacid
Do not use if patient tends to form urate stones, because since this is increasing elimination in the urine it increases likelihood of stone formation. Give allopurinol for urate stones instead (blocks urate LOAD)
Used in acute gout attack to inhibit neutrophil motility, limit neutrophil adhesion, histamine granule release from mast cells. (Several other MOAs) Drug has narrow therapeutic index and high rate of side effects, including nausea & vomiting
Colchicine
If patient has hx of gout that wasn’t responsive to NSAIDs, Colchicine can be used first. Generally it is second-line.
recombinant urate oxidase that catalyzes oxidation of uric acid to allantoin and is used in pediatric patients with leukemia, lymphoma, solid tumor malignancies receiving tx which causes tumor lysis & hyperuricemia
rasburicase
What medication increases renal calculi in gout?
aspirin
pegylated rasburicase with half-life of 12 days
pegloticase
HTN induced by eating black licorice is due to inhibition of this enzyme, allowing cortisol to interact with the MR
11beta-hydroxysteroid dehydrogenase
(11B-HSD2)
**remember this for boards!
MR antagonists (aka: aldosterone antagonists) used for aldosterone and cortisol overproduction
spironolactone
eplerenone
What vitamin D analog bypasses renal activation and is useful for hypocalcemia in renal failure?
calcitriol
it is in the fully active form
Vitamin D analogs used for rickets (these require renal activation)
- cholecalciferol
- ergocalciferol
- calcifediol
NSAIDs used to treat acute gout
- indomethacin
- naproxen
- sulindac
Which drug used for acute transplant rejection causes hyperglycemia?
tacrolimus
Which drug used for acute transplant rejection can accumulate in tubules and cause renal toxicity?
cyclosporine
Monoclonal Abs against IL-2 receptor used for prophylaxis against rejection
- Daclizumab
2. Basiliximab
Why would you pretreat with prednisone before giving Muromonab CD3 in acute transplant rejection?
Muromonab blocks T cell function, but an adaptive response is a little cytokine release which becomes lots of cytokine release systemically (cytokine release syndrome) -> makes the patient feel like has the worst flu
Why are carbonic anhydrase inhibitors not great diuretics?
- other places for sodium reabsorption downstream
- TGF is triggered since more sodium delivered to macula densa -> get decreased GFR therefore less filtration
Other uses:
- alkalinize the urine (bicarb not being converted to carbonic acid since Na-H exchanger activity is being inhibited) -> use for stones that form in acid urine
- help eliminate bicarb. More bicarb in the filtrate not being consumed and H+ secretion into the lumen inhibited. If H+ secretion is limited, less bicarb goes to the blood. Remember when H+ goes to the lumen, bicarb goes to the blood.
Why use mannitol for dialysis dysequilibrium syndrome?
Rapid loss of electrolytes in dialysis can cause hypotonic ECF and make fluid tend to move intracellular (bad for the brain). Mannitol holds the fluid in the ECF.
Why do loop diuretics inhibit absorption of calcium and magnesium?
Loop diuretics inhibit the Na/Cl/K symporter in the TAL. This transporter sets up the lumen positive charge in the TAL which is responsible for paracellular reabsorption of calcium and magnesium. (loss of transepithelium charge)
Why are loop diuretics so effective?
- block macula densa sensing (and therefore TGF that would normally decrease GFR)
- inhibit the pump (Na/Cl/K) that acts in the section of the tubule that sets up the interstitial gradient for water reabsorption. If the interstitial isn’t high concentration, urine cannot be concentrated (ie water reabsorbed). Remember that this pump is located in the TAL which is impermeable to water. Only solute moves in this section of the nephron.
Which loop diuretic can be given in sulfur allergy?
ethacrynic acid
Sodium channel blockers
- amiloride
- triamterene
These block sodium channels (ENaCs) in the late DCT and collecting ducts, so the potassium that is normally excreted when sodium is absorbed is retained.
Potassium-sparing diuretics that act by antagonizing the MR receptor, blocking aldosterone-mediated synthesis of sodium channels and Na/K ATPases.
- spironolactone
2. eplerenone
Why are potassium-sparing diuretics typically additional therapy for loop and thiazide diuretics?
Since potassium-sparing diuretics act in a region of the nephron that has little sodium reabsorption under normal conditions (and is load-dependent), they don’t work well alone. If you give with a drug that increases the sodium load, then they are more effective and can prevent the potassium loss that would normally occur.
Adverse: HYPERkalemia (if give too much), metabolic acidosis (where potassium goes, H+ goes), gynecomastia, impotence
Tetracycline that is resistant to efflux pumps so overcomes tetracycline resistance
Tigecycline
Tetracycline not eliminated by the kidney but in the feces
Doxycycline
MOA: binds to 30s and inhibits protein synthesis
Other tetracyclines: minocycline and demeclocycline
PCN analog used in combination with cilastatin and is very effective for Pseudomonas and chromosome-inducible beta lactamases that are a problem in the hospital setting
Aztreonam
No PCN hypersensitivity reaction
Very resistant to chromosomal beta lactamases (better than aztreonam). Only used in extremely ill hospital patient and with cilastatin
Imipenem
Inhibits dehydropeptidase in proximal brush border. Given with imipenem and aztreonam
Cilastatin
IV or IM medication given to overcome efflux pump resistance to tetracyclines
Tigecycline
Compete with PABA so inhibits folate synthesis by dihydropteroate synthase
Sulfonamides
This only in microbe. Mammals do not synthesize folate
Preferentially inhibits DHFR in bacteria
Trimethoprim
Competitive inhibition of binding of ATP to VEGF receptor
Sunitinib (bone marrow suppression)
Sorefenib (bleeding, HTN, thromboembolus)
Use: mets renal cell carcinoma
Non steroidal androgen receptor antagonists - bind androgen receptor and prevent its translocation to the nucleus
These are given during the first two weeks of GnRH agonist therapy to prevent androgen flare
- Bicalutamide (used most, few side effects)
- Nilutamide
- Flutamide (diarrhea, nausea, liver abnormality)
Second line for S mansoni treatment, after praziquantel
MOA: alkylator of worm DNA
Oxamniquine
Quinolones that inhibit DNA gyrate in gram negative bacteria
Nalidixic acid
Cinoxacin
Used for prophylaxis against chronic UTI. Metabolized to formaldehyde at low urine pH
Methenamine
Drug that is activated by bacteria in the urine, forming highly reactive intermediates that damage DNA. Effective against gram positive enterococci and E. coli (neg)
Nitrofurantoin
Inhibits worm acetylcholinesterase and used for S haematobium
Metrifonate
First choice for all strains of Schistosoma, causing worm paralysis
Praziquantel
Adverse: GI
DNA alkylator given directly to the bladder. Some absorption so get myelosuppression
Thiotepa
Intravesicular agent for bladder cancer. No absorption so no myelosuppression
Mitomycin
Intravesicular agent used for BCG resistant bladder cancer
Valrubicin
Steroidal androgen antagonist (partial agonist)
Cyproterone
GnRH antagonist
Degarelix
Inhibits 5 alpha reductase, enzyme that converts testosterone to DHT
Used for BPH not prostate cancer
Finasteride
GnRH agonists
Leprolide
Goserelin
Irreversible inhibitor of CYP17, blocking testosterone synthesis
Abiraterone
