Renal Flashcards

Question

Sevelamer

Answer 1

Phosphate binding polymer for elimination in the gut Eliminates phosphate to prevent phosphate binding up all the calcium and creating bone damage in renal failure

Answer 2

"Calcimimetic"; inhibits PTH be making CaSR more sensitive Treatment of secondary hyperparathyroidism due to chronic renal failure Another drug used AFTER levels of calcium and phosphate have been corrected

Answer 3

ACUTE Gout Drug (nothing to do with Uric Acid production or reabsorption) Get inflammation under control first so you don't spread it around (NSAIDs first!!!) NSAIDs: Naproxen, Indomethacin, Sulindac (the big-Gunns) Interferes with mitotic spindle function - Inhibits migration and phagocytic actions of granulocytes - Inhibits neutrophil elaboration of inflammatory glycoprotein - Side effects: Nausea, vomiting, affects rapidly proliferating epithelial cells in GI tract

Answer 4

FIRST LINE = NSAIDs (Naproxen, Indomethacin, Sulindac) AFTER NSAIDs don't work = Colchicine

Answer 5

Keeping uric acid levels low to prevent further gout attacks **Allopurinol**: Xanthine oxidase inhibitor (metabolite alloxanthine) to decrease uric acid synthesis (can be used with impaired renal function). Inhibits metabolism of some purine chemotherapeutics, like azothioprine or 6-MP, so you have to watch dosages. **Febuxostat**: Nonpurine xanthine oxidase inhibitor (liver function abnormalities, diarrhea, nausea but less drug interactions) **Probenecid**: Uricosuric agent, inhibits uric acid renal tubular reabsorption (originally developed to inhibit renal tubular secretion of penicillin and multiple drug interactions) **DO NOT GIVE IF PATIENT IS PRONE TO DEVELOPING URATE STONES AS YOU ARE INCREASING CONCENTRATION OF URATE IN THE TUBULES**\*\*\* **Rasburicase**: Recombinant urate oxidase that oxidizes uric acid into soluble and inactive metabolite allantoin; used to manage plasma uric acid levels in **PEDIATRIC** patients receiving chemotherapy

Answer 6

Used to reduce immune system for kidney transplants **Cyclosporine/tacrolimus**: targeting specific pathway for T-cells. **Inhibits calcineurin phosphatase activity,** which prevents activation of NFAT (via dephosphorylation) acting as transcription factor of IL-2 gene, and thus prevents chemokine production. They are AWESOME because we **preserve neutrophil production**, platelet production, blood cell production, B-cell production, etc. Cyclosporine can have renal toxic effects, tacrolimus can have a hyperglycemic effect (watch for this in diabetics). **Sirolimus**: Doesn't decrease IL-2 production, but leads to less response to IL-2 by T-cells (lessens mTOR pathway). Has hyperlipidemia as an adverse effect **Everolimus**: same as sirolimus, but with a shorter half life (faster steady state) **Azothioprine, methotrexate, cyclophosphamide, and mycophenalate** mofetil are all big guns brought in to non-specifically depress the immune system in acute rejection via decreased DNA synthesis. They also suppress the bone marrow

Answer 7

Used to get someone through an acute reaction to kidney transplant Expensive and IV infusion Antibody blocks binding of APC to T-cell, which blocks T-cell function and decreases functional T-cell number because new populations arise that don't have CD3 to prevent inhibition... but they suck because they don't have CD3... jokes on them Initial stimulation of cytokine release syndrome (feels like the worst case of the flu they have ever had because of all the IL-2). This can be avoided by pretreatment with prednisone

Answer 8

Used to prevent acute reactions to kidney transplants Monoclonal antibodies against IL-2 receptor Blocks IL-2 mediated T-cell activation

Answer 9

B2: Relaxes bladder smooth muscle A1: Contracts bladder at base, urethral sphincter, prostate B1: Increases renin release Side note: M3 agonists stimulate voiding

Answer 10

Bethanacol, neostigmine Stimulates bladder emptying Treatment of urinary retention problems POST-SURGERY ONLY use when NO OBSTRUCTION present... or very painful

Answer 11

Tolterodine, oxybutynin, darifenacin, solifenacin Relaxes the bladder to counteract bladder spasms because of infection or post-surgery Used to treat leaking urine here/urinary incontinence due to a hyperactive bladder

Answer 12

Ephedrine, pseudoephedrine Treatment of urinary incontinence Promote retention/sphincter contraction Watch for hypertension, but try to keep doses low

Answer 13

Prazosin, terazosin, doxazosin, tamsulosin Treatment of symptoms of urinary obstruction (BPH), **so typically seen/used in older men** Tamsulosin (Flomax) has **greater potency in inhibiting contraction in prostate smooth muscle vs vascular smooth muscle**. This means you more selectively hit prostate muscle rather than the vasculature muscle that prevents orthostatic hypotension upon sudden-standing

Answer 14

**Acetazolamide, Methazolamide, Dichlorphenamide** Act in proximal tubule Prevents carbonic anhydrase (lumen) from combining H+ and HCO- from combining and creating CO2 and H2O that will freely travel into the cell and be reformed via CA (cytosolic) into H+ and HCO3- internally. This prevents H+ formation that will be exchanged for Na+ across the apical membrane (NHE3 exchanger). Na+ isn't reabsorbed and thus water stays in the lumen **THESE ARE WEAK AS SHIT. **You can reabsorb Na+ elsewhere in greater quantities and thus you don't really lose much Na+ or H2O. These also trigger tubuloglomerular feedback via the macula densa (sensing a high load of NaCl). This triggers a constrictor signal to drop GFR and thus are self-limited diuretics Increased bicarb secretion/urinary alkalinization. This is a good way to treat renal stones that form in acidic conditions, get rid of an acidic drug, treat metabolic alkalosis, etc. Can also be used for glaucoma. Toxicity: metabolic acidosis, renal stone formation (from alkaline conditions), hypokalemia, and allergic sulfur reactions

Answer 15

Mannitol, Isorbide, Urea Limit Na+ and H2O reabsorption, expand ECF leading to decrease in renin release and increase in RBF Increase urinary excretion of nearly all electrolytes including Na+, K+, Ca2+, Mg2+, Cl-, Phosphate Treatment of acute renal failure (runner in our cases), dialysis disequilibrium syndrome, and reduction of intracranial and intraocular pressure Trying to increase blood flow and increase pressure to unblock whatever is blocked Don't want to dose more than once if it doesn't work as it will suck all the water out of the brain and will create loads of pressure Side-effects: Increased ECF that will kill patients with CHF or pulmonary edema, as well as electrolyte loss

Answer 16

Furosemide, Bumetanide, Ethacrynic acid, Torsemide Act on Loop of Henle in the TAL Inhibits the **NKCC2** from moving Na+, 2Cl-, and K+ into the cell. Potassium typically back-leaks **to make the lumen positively charged**. This positive lumen charge (+70mV) is higher than the interstitial positive charge (+60mV) which drives positive ions paracellularly into the interstitial space. SO, if you block this transporter you **block Na+, Cl-, K+, Ca2+, and Mg2+ reabsorption**. This also decreases osmolar gradient in medulla, decreasing concentrated urine production Loop diuretics **block the SENSING MECHANISM** that prevent the macula densa from responding to the increased solute loads. In fact, it actually doesn't sense anything so it increases blood flow and GFR even more, which leads to even more loss of fluids and electrolytes. Also in the TAL you're moving solutes without water movement (gap junctions are impermeable to H2O) and therefore you typically set up the concentrated interstitial gradient of the medulla. Without this gradient, you cannot reabsorb water later on like you typically would STRONG MUTHAFUCKAS - Use in pulmonary edema, CHF, acute renal failure, and HTN (use thiazides first) Side Effects: Electrolyte loss, ototoxicity, metabolic alkalosis, sulfer hypersensitivity (except Ethacrynic acid)

Answer 17

Chlorothiazide, Hydrocholothiazide, Chlorthalidone, Indapamide, Metolazone, Quinethazone, etc. Past the macula densa, so we don't worry about if it will provide the macula densa with a greater solute load to affect GFR through TGM feedback. Inhibits NCC in the DCT and thus also blocks H2O reabsorption Can cause hypokalemia like all the others (save for potassium sparing diuretics) because you increase sodium presentation to the principal cells which excrete potassium after uptaking sodium DECREASE **Ca²⁺ excretion (increase Ca²⁺ absorption)**, so prevents calcium stones in those who are prone to them Treats HTN, edema, calcium nephrolithiasis, hypocalcemia Side effects: hyponatremia, hypokalemia, metabolic acidosis, hypercalcemia, allergic sulfur reaction

Answer 18

Amiloride and Triamterene (Na+ channel inhibitors) Spironolactone, Eplerenone (Aldosterone receptor inhibitors) Increase urinary excretion of Na+, decrease urinary excretion of K+ and H+ (because you aren't bringing in Na+ to push out K+ and H+). Not extremely strong diuretics but are used in combination with thiazides/loops to prevent the hypokalemia. Treat HTN and edema (spironolactone and eplerenone can treat hyperaldosterone) Side effects: Hyperkalemia, metabolic acidosis, gynecomastia, impotence (spironolactone)

Answer 19

Brain natriuretic peptide Binds to specific receptors all along the nephron (mainly MCD) via c-GMP signaling, which inhibits Na+ reabsorption in the IMCD and thus increase Na+ excretion Also inhibits renin-AngII-aldosterone pathway Peptide so given IV New drug used to acutely decompensated CHF

Answer 20

**Carbapenem that is resistant to chromosomal beta-lactamases** Always administered with **cilastatin** (inhibitor of dehydropeptidase in proximal tubule brush border that breaks down imipenem) Toxicity: Hypersensitivity, causes nausea, vomitting, and seizures in high doses. Only give when you have an extremly ill patient that needs IV antibiotics

Answer 21

Resistant to **plasmid extended** spectrum beta-lactamases (not as resistant as imipenem) Effective against enterobacteriaceae and pseudomonas aeruginosa (like imipenem) in pyelonephritis **Has no pencillin hypersensitivity reaction!** Toxicity: well-tolerated, lacks hypersensitivity

Answer 22

Gentamicin, neomycin, streptomycin, tobramycin, amikacin (most resistant to resistance development), netilmicin Great for Gram Negatives! Used to treat urinary catheter associated UTI usually caused by Enterobacteriaceae (gram negative bacilli) Treat with aminoglycoside plus fluoroquinolone, third-generation cephalosporin, or piperacillin/tazobactam **MOA-** binds to 30S ribosomal subunit--\> blocks the initiation of protein synthesis, blocks translation and elicits premature terminatin of translation with detachment of ribosomal complex, and causes incorporation of incorrect amino acids resulting in protduction of abnormal/nonfuctional proteins **Renal toxicity-** (all reversible to a point) accumulation and retention of aminoglycoside in proximal tubular cells, impaired renal concentration ability, proteinuria, and appearance of hyaline and granular casts, GFR is reduced after several days, reduced sensitivity of collecting-duct epithelium to endogenous antidiuretic hormone, **severe acute tubular necrosis** is rare but may occur, most commonly there is a mild rise in plasma creatinine, ***reduced exretion of drug (itself/renal damage)** predisposes to ototoxicity which is irreversible* **Other toxicities-** ototoxicity (**irreversible** damage to vestibular and cochlear sensory cells, irreversible), produces neuromuscular blockade by inhibiting ACh release via competition with Ca2+ (important for anesthesia administration, as you can lower dosages)

Answer 23

UTI's in women with risk factors for sexually transmitted diseases, give doxycycline twice daily for 7 days or azithromycin 1 gram single dose **Tetracycline-** can produce renal tubnular acidosis, azotemia, and Fanconi's syndrome (expired drugs), excreted as nephrotoxic metabolites by kidney except for doxycycline (feces) **Tigecycline**- it is a glycycycline, not absorbed orally so it is given IM, **can overcome tetracycline resistance** (can avoid efflux pump and ribosomal protection proteins) **Macrolides**- azithromycin, clarithromycin, erythromycin

Answer 24

Sulfonamides inhibit dihydropteroate synthase (folate synthesis in bacteria, not mammals) Trimethoprim inhibits bacterial dihydrofolate reductase Mammals cannot convert aminobenzoic acid to dihydrofolic acid which makes this drug bacteria specific, very affective drug Adverse affects due to the sulfonamide group in hypersensitive patients, causes fever and rash, hives, nausea, vomitting Can be given prophylactically in patients prone to UTIs **Primary treatment for UTIs**

Answer 25

DNA gyrase inhibitors in gram-negative bacteria Topoisomerase IV inhibitors in gram-positive bacteria **Quinolones**- Nalidixic acid and cinoxacin have limited usefulness bc of narrow antibacterial spectrum (gram-negative only). They also required high doses, as they induce mutations in DNA gyrase. **Fluoroquinolones**- ciprofloxacin, ofloxacin, levofloxacin, norfloxacin. Widely used, but now have begun to show increased resistance.

Answer 26

Not used as much anymore Prophylaxis of chronic UTI Metabolized to formaldehyde spontaneously at low urine pH but not in plasma at pH 7.4, formaldehyde is what kills the bacteria

Answer 27

Widely used for **lower UTI uncomplicated cystitis** Effective against gram-positive enterococci and gram negative E.coli, but proteus, pseudomonas, enterobacter, and klebsiella are resistant Not activated by low pH (but low pH does make it more effective), activated by bacteria only, bc of this it can be given prophyllactically, if patient does not have infection the drug will be excreted unchanged/unactivated in the urine Can be given orally and prophyllactically to patients prone to UTIs with sulfonaide allergy, as it will be eliminated unchanged in these scenarios 40% of drug is excreted into urine unchanged where **bacteria reduce nitrofurantoin to form highly reactive intermediates that damage DNA**

Answer 28

First-choice against all strains of Schistosoma Causes muscular contraction and paralysis and at higher drug levels can cause tegumental damage by influx of Ca+ Toxicity is abdominal distress mostly from the drug but also from the killing of the parasites. This can be dose limiting

Answer 29

Second line antischistosomal Only effective against **Schistosoma haematobium** Must be activated to dichlorovos which inhibits AChE in the worm

Answer 30

Second line antischistosomal Not effective against *S. haematobium* or *S. japonicum*, only used for **S.mansoni** An enzyme converts oxamniquine into an ester, the ester spontaneously dissociates and the resulting electrophilic reactant alkylates schistosome DNA

Answer 31

5-alpha-hydroxylase inhibitor used to treat benign prostate hyperplasia This blocks synthesis of dihydrotestosterone, and is therefore not as effective at treating prostate cancer as it does not affect synthesis of testosterone

Answer 32

Same bacteria that cause UTIs cause Prostatitis Usually gram-negative enteric organisms Causes a tender prostate (which you can jam your finger on to elciit screaming) Treat acute with TMP-SMX, chronic with long bouts of TMP-SMX or ciprofloxacin Difficult to get drugs into the prostate. TMP-SMX and ciprofloxacin are both lipid soluble so can actually reach the prostate

Answer 33

PGE2 and PGI2 are main players (made by COX-2, so COX-2 selective inhibitors have same side effects), they: 1) Increase renal blood flow by dilating the afferent arteriole 2) Decrease/antagonize ADH induced blood flow 3) Increase chloride reabsorption in loop of Henle 4) Increase renin release **NSAIDs block these effects, important to keep in mind for patients with compromised renal function**

Answer 34

At high range of therapeutic index, can initially lead to respiratory alkalosis by direct stimulation of respiratory centers in the CNS (more so in adults than children) At toxic levels, can then lead to metabolic acidosis by uncoupling oxidative phosphorylation and by direct presence of an acid in the plasma At highest toxic levels, you can get a combined respiratory and metabolic acidosis as respiratory centers are depressed

Renal Flashcards

(58 cards)