Renal Flashcards
Degarelix
Hormonal treatment for prostate cancer
GnRH antagonist: Directly blocks the binding of GnRH to its receptor directly
Do not get initial androgen flare like you do with the GnRH agonists (leuprolide and goserelin)
This drug lacks the initial androgen flare that is seen with the agonists
Leuprolide
Decapeptide hormonal treatment for prostate cancer
GnRH normally released in pulsatile fashion, but the synthetic agonists are given so that they simulate a sustained release of GnRH, after 2-4 weeks of treatment, you down regulate the testosterone levels
GnRH agonist: MOA is to desensitize/downregulate the GnRH receptors on the pituitary
Modified to lengthen half-life and minimize break down
Used in combination with androgen receptor antagonists to avoid the androgen flare associated with these drugs
Goserelin
Decapeptide hormonal treatment for prostate cancer
GnRH normally released in pulsatile fashion, but the synthetic agonists are given so that they simulate a sustained release of GnRH, after 2-4 weeks of treatment, you down regulate the testosterone levels
GnRH agonist: MOA is to desensitize/downregulate the GnRH receptors on the pituitary
Modified to lengthen half-life and minimize break down
Used in combination with androgen receptor antagonists to avoid the androgen flare associated with these drugs
Flutamide, Nilutamide, Bicalutamide, Cyproterone, Spironolactone
Hormonal treatment of prostate cancer
Androgen receptor antagonists: Bind to steroid receptor intracellularly and prevent its translocation into the nucleus
Used in conjunction with GnRH agonists
Flutamide: has diarrhea nausea and vomiting for toxicity
Bicalutamide: less side effects and most used
Cyproterone: also has slight agonist activity. Have to watch out for this
Abiraterone
Irreversible inhibitor of 17-hydroxylase and C-17,20-lyase (CYP17) activity that blocks testosterone biosynthesis
Used with prednisone. It is better than ketoconazole
Use if patient isn’t responding well to leuprolide and androgen blocking agents or in conjunction with them
Mitoxanthrone
Used for hormone-refractory prostate cancer
Doxorubicin analog with less cardiotoxicity
Sometimes used with prednisone
Docetaxel and cabazitaxel
Used for hormone-refractory prostate cancer
Inhibits microtubule disassembly
Cabazitaxel used with prednisone, most widely used today
Toxicity is neutropenia and neurotoxicity
Sipuleucel-T (PROVENGE)
Autologous cellular immunotherapy for the treatment of asymptomatic or minimally symptomatic, metastatic, hormone refractory prostate cancer
Toxicity is infusion reactions
Bladder cancer chemotherapy
Intravesicular agents (given as a catheter in the bladder in conjunction with transurethral resection)- bacillus calmette-guerin, thiotepa, mitomycin, valrubicin, agents are very toxic if given systemically** **
Bacillus calmette-guerin: it is an attenuated organism, causes a granulomatous reaction that kills the cancer
Thiotepa: activated by CYP450 and is an alkylator and damages DNA, absorbed a little and causes myelosuppression
Mitomycin: Alkylator that is not absorbed at all
Valrubicin: Synthetic analog of doxirubicin for BCG resistant bladder cancer
MVAC for advanced cases (methotrexate, vinblastine, doxorubicin, cisplatin-more renal damage than carboplatin)
MVAC
Systemic agents for advanced cases of bladder cancer
Methotrexate, vinblastine, doxorubicin, cisplatin
Renal damage from cisplatin is reduced by hydration/saline diuresis, can use carboplatin in combo with paclitaxel in patients with renal dysfunction
Can also use gemcitabine with cisplatin or carboplatin
IL-2
Differs from native IL-2 in that it is not glycosylated, so it is more stable
Stimulates proliferation and activities of tumor-attacking lymphokine-activated killer cells and CTLs
Toxicities: inflammation/capillary leak, hypertension, arrythmias, peripheral edema, nausea, diarrhea, vomitting, and fever
Used to treat patients with cancers that are refractory to conventional treatment, such as renal cell carcinoma and melanoma
Sunitinib
Renal cell carcinoma treatment
Inhibitor of receptor tyrosine kinases (VEGF-R2, PDGF-R, c-KIT, and other tyrosine kinases)
Reduces proliferation and angiogenesis
Resistance is through receptor tyrosine kinase mutation
Toxicity: bleeding, hypertension, proteinuria, thromboembolism, intestinal perforation, and myelosuppression
Sorafenib
Renal cell carcinoma treatment
Oral inhibitor of VEGF-R1,2,3 tyrosine kinases within tumor cells to reduce proliferation and angiogenesis
Toxicity: bleeding, hypertension, proteinuria, thromboembolism, intestinal perforation, and myelosuppression
Bevacizumab
Renal cell carcinoma treatment
Humanized mAb against VEGF
Inhibits interaction with VEGF receptors which inhibits angiogenesis in tumors
Often given with interferon-alpha
Toxicity: CNS hemorrhage, severe hypertension, congestive heart failure, gastric perforation, and proteinuria
Pazopanib
Renal cell carcinoma treatment
Inhibits tyrosine kinase activity of VEGF-R2
Toxicity: bleeding, hypertension, proteinuria, thromboembolism, intestinal perforation, and myelosuppression
Temsirolimus, Everolimus, Sirolimus
Rapamycins
mTOR forms the mTORC1 complex with the FK506-binding protein family, FKBP12. mTORC1 phosphorylates S6 kinase and relieves inhibitory effect of 4EBP on initiation factor elf-4E thereby increasing protein synthesis and metabolism
Antitumor actions result from binding FKBP12 and inhibition of mTORC1
Temsirolimus is metabolized to sirolimus
Inhibit cell-cycle progression and angiogenesis, promote apoptosis
Resistance: mTORC2 can take over for mTORC1 complex
Toxicity is mild: rash, small chance of leukopenia, inhibit CYP450s
Treatment of UTI’s
Main outpatient pathogens are E. coli, then Klebsiella and Proteus, then Staph. saprophyticus
Pseudomonas is rare in outpatient but common in hospital setting
Treat cystitis with TMP-SMX, ciprofloxacin/levofloxacin (resistance is increasing to fluoroquinolones), cefpodoxime proxetil
Treat pyelonephritis with fluoroquinolones (high doses to overcome resistance), treat susceptible strains with TMP-SMX
Treat suspected bacteremia with IV antibiotics (third generation cephaolsporins, ciprofloxacin, gentamycin, aztreonam)
Extremely sick treat with IV cefepime, ciprofloxacin, carbepenem
Mineralocorticoids
Aldosterone is the naturally occurring mineralocorticoid (because it is protected from 11B-HSD2 deactivation)
Increase Na+ reabsorption in distal nephron/collecting duct (mainly through prinicipal cells)
Leads to increase H20 reabsorption, K+ secretion (worry about hypokalemia if we over-do it), H+ secretion, and bicarb generation (can create alkalosis if we secrete too much H+ and generate too much bicarb)
Side effects: HTN, edema via sodium and water retention
Glucocorticoids are more abundant than Mineralocorticoids and bind GR and MR however: 11B-HSD2 oxidizes -OH (Carbon11) to =O (C11) that cannot bind to the mineralocorticoid receptor*** - We can flood this system and the glucocorticoids can eventually bind to the MR and lead to aldosterone-like effects
Component in licorice that inhibits 11B-HSD2 and allows these glucocorticoids to remain capable of binding MR
Fludrocortisone
Binds very well to mineralocorticoid receptor***
Binds POTENTLY to GR and MR
Both a glucocorticoid and a mineralcorticoid
NEVER use as an anti-inflammatory as it will cause severe edema, water-retention, HTN
Use when Pts cannot make aldosterone themselves
Triamcinolone
A glucocorticoid that has ABSOLUTELY NO activity at the mineralocorticoid receptor (thus no aldosterone-like activity)
Useful treatment if you need to switch a patient to an anti-inflammatory without water retention/due to their HTN with the other glucocorticoids (such as prednisone, which has a slight affinity for the MR)
Mineralocorticoid Receptor Antagonists
Aldosterone antagonists***
Spironolactone (gynocomastia, impotence for this one too) - Eplerenone
Can cause hyperkalemia and metabolic acidosis as they are no longer allowing K+ secretion, H+ secretion, or HCO3- creation
Can treat aldosterone or cortisol excess
Calcitriol
People who are in renal failure do not make active vitamin D (Calcitriol, AKA 1,25-dihydroxy-cholecalciferol)
Hyperphosphatemic and Hypocalcemic- PTH is released because of hypocalcemia which leads to bone resorption, calcium reabsorption in kidney, and phosphate excretion in kidney
However, if the kidney is damaged we don’t see this but we end up seeing secondary hyperparathyroidism - Will see renal osteodystrophy with this excessive resorption***
Calcitriol is already active and will help Ca2+ absorption in the gut, increase Ca2+ in the blood, and STOP PTH production/bone resorption
Don’t give ergocalciferol or other calcitriol analogs lacking the 1-hydroxylation
DHT - Dihydrotachysterol
Synthetic Vitamin D
No 1-OH needed for activation so no renal activation needed to be active Vitamin D
Could also give 1-apha-hydroxycalciferol, but this one needs liver function to be activated
Paricalcitol and 22-oxacalcitriol
Calcitriol analog
Reduces PTH without hypercalcemia and used in chronic renal failure
22-oxacalcitriol is basically the same thing
These drugs are used AFTER you get the calcium, phosphate, etc. back in check but PTH is still elevated for whatever fucking reason
Sevelamer
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
Cinacalcet
“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
Colchicine
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
Acute Gout Drugs
FIRST LINE = NSAIDs (Naproxen, Indomethacin, Sulindac)
AFTER NSAIDs don’t work = Colchicine
Chronic Gout Drugs
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
Immunosuppressive agents
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
Muromonab CD3
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
Daclizumab, Basiliximab
Used to prevent acute reactions to kidney transplants
Monoclonal antibodies against IL-2 receptor
Blocks IL-2 mediated T-cell activation
Adrenergics in the kidney
B2: Relaxes bladder smooth muscle
A1: Contracts bladder at base, urethral sphincter, prostate
B1: Increases renin release
Side note: M3 agonists stimulate voiding
Cholinergic activating agents
Bethanacol, neostigmine
Stimulates bladder emptying
Treatment of urinary retention problems POST-SURGERY
ONLY use when NO OBSTRUCTION present… or very painful
Anti-cholinergics
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
Alpha-1-agonists
Ephedrine, pseudoephedrine
Treatment of urinary incontinence
Promote retention/sphincter contraction
Watch for hypertension, but try to keep doses low
Alpha-1-Antagonists
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
Carbonic Anhydrase Inhibitors (Diuretics)
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
Osmotic Agents (Diuretics)
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
Loop diuretics (Diuretics)
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)
Thiazide diuretics (Diuretics)
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
Potassium Sparing Diuretics
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)
Nesiritide
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
Imipenem
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
Aztreonam
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
Aminoglycosides
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)
Tetracyclines and macrolides
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
Trimethoprim-sulfamethoxazole
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
Quinolones and Fluoroquinolones
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.
Methenamine
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
Nitrofurantion
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
Praziquantel
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
Metrifonate
Second line antischistosomal
Only effective against Schistosoma haematobium
Must be activated to dichlorovos which inhibits AChE in the worm
Oxamniquine
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
Finasteride
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
Treatment of Prostatitis
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
Prostaglandin Effects on the Kidney
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
Aspirin Side Effects
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
