jdlevenson's version from 2015-04-20 02:16

Section 1

Question Answer
What is narrow range for potassium and why important3.5-5 mEq/L. Intracellular to extracellular K defines resting membrane potential.
What is main driver of K+ inside cellNa/K ATPase. 2 K+ in and 3 Na+ out. K ICF =120-150 .
K+ has a role in what biochem reactionProtein and glycogen synthesis.
K+ always governed by 3 processes1. Dietary intake. 2. Internal distribution of K+ and 3. Excretion of K+.
Why can’t you overdose from OJ after workout?It distributes. Hyperkalemia rarely occurs in normal subjects. Excretion takes a little longer.
Insulin effect on cellsIncreases NaK ATPase resulting in more K+ uptake.
Catecholamines lead tomore NaK ATPase (via B2 -> cAMP)
Factors that promote entry of K+ into cellsInsulin availability and B-adrenergic activity.
2 ways to excrete KKidneys and GI tract.
Net urinary K+ excretion in kidney is determined byK+ secretion in distal nephron. Particularly K+ secretion by principal cells via ROMK. K+ absorption by intercalated cells also important but secondary to ROMK. Also #3 -> FLOW RATE.
Bartter syndromeReabsorptive defect in thick ascending loop of Henle. Autosomal recessive. Affects Na+/K+/2Cl– cotransporter. Results in hypokalemia and metabolic alkalosis with hypercalciuria.THINK FUROSEMIDE.
Aldosterone stimulated byActivation of RAAS and increase in plasma k+.
Mineralocorticoid excessMetabolic alkalosis. Hypokalemia. Na+ retention (at first before -> volume expansion and HTN in absence of volume depletion).
Mineralocorticoid deficiency (hypoaldosteronism) will present withHyperkalemia, Na wasting, metabolic acidosis.
Aldosterone intracellular actionsIncreases ENaC and increases Na/ K ATPase and K+/ H+ antitransproter (in alpha interacalated cell).
Liddle’s has what effect on potassiumHypokalemia.
Pseudohypoaldosteronism/ ENaC loss of function on potassiumHyperkalemia.

Section 2

Question Answer
Source of vasopressin/ ADH in body and what is it made ofParaventricular and supraoptic nuclei of HT which projects to PP. Made of Arginine.
V1 receptor locationCardiac and smooth muscle of vasculature.
V1 receptor second messenger systemGq. PIP2. IP3 DAG Ca -> PKC.
V1 receptor actionVasoconstriction. Recall Gq = PIP2 = IP3 DAG Ca -> PKC. Increases Ca -> increases contract => Increases SVR => Increases arterial pressure.
V2 receptor locationKidney collecting duct luminal epithelium.
V2 receptor second messenger systemGs = cAMP = PKA. cAMP leads to stored aquaporins fusing and endocytosing with luminal side of tubule.
V2 receptor actionAbsorption of free water. Increases blood volume -> Increases arterial pressure.
ADH triggered by1. Osmoreceptors (faster response to keep sodium osmolarity the same) 2. Baroreceptors (slower, stronger, longer lasting).
And case where ADH has two opposites triggersCirrhosis with low serum sodium. Low serum sodium wants to stop ADH/ wants to excrete water. Low EAV wants to correct hypotension with ADH. BARORECEPTOR RESPONSE IS HIGHER AND MORE BRISK.
Desmospressin difference from Vasopressin?Desmo -> More selective for V2. 3000 fold more selective in fact. Deamination of N terminal does the trick.
When to use desmopressin?Strictly V2 stuff. -> 1. DI (so long as its Central, not nephrogenic). 2. Hemophilia A/ VWF def. Will help PLT be more functional. 3. Primary nocturnal enuresis. Kids bed wetting.
Vaso vs desmo pharmacokineticsVaso is only IV and Desmo is any way. But desmo has super low bioavailability so need big dose. Both renal elimination with vasopressin also being eliminated by hepatic.
SIADH basic treatmentFluid restriction.
Vasopressin a/eVasoconstriction including coronaries and increased intestinal activity (n, cramps, gas)
CONTRAINDICATIONS for VASOPRESSIN AND DESMOPRESSINHyponatremia. (Also renal impairment). But mainly hyponatremia.
Euvolemic hyponatremia isSIADH. Urine sodium may be high but definitely not low. Urinary osmolarity will be high.
CYP inducers mnemonic, Cut Carbs Before Getting RiPed SonCarbamazepine, Chronic Ethanol, Barbiturates, G Rifampin, Phenytoin, S
CYP inhibitors, super popular 6Cimetidine, Omeprazole (GERD!), INH/ Isoniazid, Erythromycin, Ketoconazole, Grapefruit juice.
Most important CYP inhibitor of allKetoconazole. Just cause.
Vaptan meansVasopressin/ ADH receptor antagonist.
Conivaptan mechanismV1a and V2 receptor antagonist. Less water reabsorbed.
Conivaptan usesSIADH (euvolemic hyponatremia), only really used in ICU though because expensive.
Conivaptan should never be used for patients thatAre hypovolemic/ hyponatremic. That is, patients that really need ADH.
Conivaptan contraindicationsHypovolemic hyponatremia and use of other CYP 3A4 inhibitors.
Tolvaptan, what is itJust another ADH antagonist. It is selective V2.
Demeclocycline, mechanismPrevents tRNA from 30 subunit and prevents making of proteins. Prevents ADH from working then.
Demeclocyline useAfter fluid restriction and vaptans, then demeclo. So, refractory SIADH.
Demeclocyline major a/eMay cause nephrogenic DI.
Hyperkalemia two goals and why importantMove K+ intracellularly. Eliminate K+ via kidneys or GI. Important because extracellular K can cause arrhythmias.
Kayexalate mechanismAntihyperkalemic drug. In intestines, there is an exchange of Na+ for K+ on the resin. So Na+ into body and K+ out. Kayexalate also has sorbitol so -> diarrhea. (But only when not liquid).
Kayexalate as a resin has unique pharmacokineticsIt is not absorbed so only has local action.
Kayexalate is contraindicated inImmediate post-op setting or in patients with impaired intestinal function. Or just anyone with intestinal issues.
Kayexalate has 1 major A/EColonic necrosis with crystalline deposits. However, it may have been the sorbitol in the kayexalate.

Section 3

Question Answer
Furosemide mechanismIncreased Na+ loss at TAL and subsequent water loss via inhibition of Na-K-2Cl symporter. And also by decreaseing NaCl deposition in renal medulla, it decreases the medullary osmotic gradient. (LESS ABILITY OF ADH TO PULL OUT WATER IF IT WANTS)
RAMK isBack leak of K+ for Na/K/ 2Cl to keep working. Rate limiting step.
Furosemide, acetazolamide, thiazide all shareSulfa base → all have sulfa allergy as a toxicity.
How do Mg and Ca normally get in at TAL?Via RAMK (responding to NAK2CL) which then promotes Mg and Ca reabsorption paracellularly.
Furosemide leads to HypoMagnesmia but not Hypocalcemia, why?Loss of RAMK/ K+ back leak means lumen is not as positively charged/ less paracellualr transport of Mg and Ca. But Ca wil be reabsorbed in the distal tubule**.
Why will Furosemide immediately provide relief?Acutely increases systemic venous capacitance via prostaglandins. Decreases cardiac preload and pulmonary edema even before diuresis that furosemide promotes.
Furosemide may lead to what kind of acid base disturbance and howMetabolic Alkalosis. Loss of Na+ at TAL will lead to more ENac activity causing more H+ (at alpha intercalated cell) and K+ to leave (at principal cell). So you can see hypokalemia but also loss of H+ = Metabolic Alkalosis.
Furosemide will vasodilate the afferent arteriole by...Stimulating PGE release.
Furosemide may cause arrhythmias howHypokalemia from overactive ENac in response to more Na delivering. (More ENac and RAAS too maybe)
Furosemide OH DANGO – Ototoxicity (tinnitus, loss of hearing, vertigo; usually reversible; thought to be due to ionic alteration in endolymph; from too much*); H – Hypokalemia, D – Dehydration, A – Allergy, N – Nephritis (interstitial), G – Gout/ Hyperuricemia. Also Hypomagnesemia. And Metabolic Alkalosis.
Why does Furosemide cause gout/ hyperuricemia?Loop diuretics and uric acid are transporter into lumen by OAT/ Organic Acid Transporters. Competitive transport will decrease transport of uric acid out into urine.
If something lasts for 6 hours/ steady state, then half life isRecall steady state is half life x 3-4.
GLUT-2 is whereB islet cells, liver, kidney, small intestine.
Furosemide/ loop diuretics/ bumetanide/ torsemide indicationsAcute pulmonary edema, edema from CHF, cirrhousis, renal failure and proteinuria. ALSO HTN (but Thiazides used more often) and Hypercalcemia**.
Why Thiazides less powerful than Loop DiureticsDo not interfere with medullary gradient and also only 5-7% of filtered sodium is reabsorbed at DCT.
Thiazide Hyper GLUC ToxHypokalemic metabolic alkalosis and G – hyperglycemia, L – hyperlipidemia, U – hyperuricemia, C – hypercalcemia.
Thiazide adverse effects beyond HyperGLUCVolume depletion, hypotension, hyponatremia (Na+ loss with no reduction in ability to reabsorb water in the CD), hypochloremia. Hypomagnesemia, hypercalcemia, hyperuricemia, hypokalemia, metabolic alkalosis.
Furosemide and Thiazides may lead to new DM butNot a contraindication. Just monitor while treating.
Characteristic severe sulfur effect from what drugBACTRIM.
Thiazides clinical use, primary (2) and secondary (2)HTN and EDEMA (CHF, cirrhosis, renal failure and proteinuria; remember though, loop diuretics are much stronger). Secondary – Calcium nephrolithiasis/ osteoporosis and Nephrogenic DI.
Amiloride is and works byPotassium sparing diuriet that works by inhibiting ENaC in late distal convoluted tubule and CD. Decreases K+ excretion and H+ excretion as well as Ca and Mg excretion. Contrast to Loop and Thiazides that increase K+ and H+ excretion via increasing delivery of Na+ and increasing RAAS.
Amiloride major a/eHyperkalemia.
Amiloride 3 uses1. Combination with other potassium lowering diuretics, 2. Liddle’s syndrome, 3. Li induced Nephrogenic DI by blocking Li entry into collecting duct.
Liddle’s SyndromeAD mutation in ENac subunit. Treated with Amiloride.
Spironolactone/ Eplerenone mechanism, exactCompetitive antagonists of aldosterone at cytoplasmic mineralocorticoid receptor**; accesses cell from basolateral surface.
Aldosterone how does it work1. Increases activation and synthesis of luminal ENaC and 2. Increase activity of basolateral Na/ K-ATPase.
Lots of aldosterone can lead toFibrosis of vasculature and heat. Endothel dysfunction and LVH.
Spironolactone has antagonist activity at androgen and progestereone receptors as well as aldosterone receptor which lead to a/eGynecomastia, impoetence, decreased libido, menstrual irregularities. Eplerenone is more selective but insurance doesn’t pay for it.
Spironolactone contraindicationMetabolic acidosis.
Spirinolactone antagonistsHTN, Edema from CHF, Cirrhosis, Proteinuria; Primary hyperaldosterinism and may be used to decrease mortality in Clsas III and IV CHF and ventricular arrhythmias. FAVORED DIURETIC IN PTS WITH ASCITES.
Acetazolamide mechanismInhibits CA in proximal tubule. Decreases HC03 absorption -> Decreased Na reabsorption. BICARBONATE WASTING GRABS NA. (Limited effect though bc Na can be absorbed later).
Mannitol is not used inHF or volume overloaded patients (where it may pull water out of cells). Or in patients with anuria. So a/e is its extracellular fluid expansion that makes it not used in fluid overloaded people.
Mannitol use1. Increased intraocular pressure/ acute angle-closure glaucoma (it will force water out of cells reducing pressure). 2. And increased intracranial pressure. Forces water out of brain cells reducing intracranial pressure (this may happen in acute fulminant hepatic failure for example). 3. Increase urine volume and flow.
Mannitol may also be used (according to first aid)Drug overdose.
Mannitol toxicityPulmonary edema and dehydration.