Pharm 2 - Urogenital 2

drraythe's version from 2015-09-30 22:20

Collecting Ducts

Question Answer
What are the 2 different types of cells in the collecting ducts & what are their functions?(1) Principal cells: Reabsorption of Na+ & secretion of K+
(2) Intercalated cells: Secretion of H+
What is the function of the tight junction btwn the cells of the collecting ducts?Transport of H20 & ions can be individually regulated by hormones
What controls Na/Cl absorption in the in the collecting ducts?Aldosterone
What controls H20 reabsorption in the collecting ducts?Anti-diuretic hormone (ADH/Vasopressin)
What does Aldosterone do? What blocks it?Na/Cl reabsorption & K excretion. Effect is blocked by K+ sparing diuretics
Explain the quick effect/delayed effect of AldosteroneQuick effect: Stimulation of the Na+/H+ exchanger (binding to membrane Aldosterone receptors)
Delayed effect: Binding to cellular receptors → mediator proteins that activate Na channels
What does ADH do? (What blocks it?)↑ H20 reabsorption (stimulates V2 receptor which results in ↑ numbers of aquaporins or H20 channels in the apical membrane) Blocked by Lithium carbonate, Demeclocycline, Colchicine (in Class he said we just need to know that it can be blocked. I don't trust him)
Explain K+ balance in the collecting ducts & how it relates to the tubular membranes & Na+ (in his words)The higher permeability of the luminal membrane for Na+ depolarizes the luminal membrane but not the basolateral membrane. This creates a lumen-negative trans-epithelial potential difference. This in turn creates an important driving force for the secretion of potassium via K-channels. Delivery of more Na to this part of the kidney augments depolarization of the luminal membrane, enhances the lumen negative potential difference & facilitates K excretion
Explain K+ balance when non-K-sparing drugs are usedK loss will ↑ when ↑ Na reaches the collecting ducts (this happens w/ Thiazide & Loop Diuretics) (my notes say: Membrane on side of urine is depolarized, but the cells lining the UT & blood are not. So btwn the urine & interstitium, there is a bigger trans-epithelial potential difference. The more Na that reaches that part of the kidney (collecting duct), will further facilitate K secretion. W/ more Na in urine, there is a bigger diff btwn luminal side & basolateral side, which forces K back into urine)
Explain how K+ balance & K-sparing diuretics workK loss will be ↓ when Na reabsorption is ↓ in the collecting ducts (this is what K-sparing diuretics do)
How does Spironolactone work? Where is it absorbed/How well is it absorbed? SFx?Works by competing w/ Aldosterone. Well absorbed from GIT. SFxs are GI upset, hyperkalemia, gynaecomastia, menstrual disorders, testicular atrophy, peptic ulcers
Which K-sparing diuretic has an active metabolite? What is the Name of the a.m.?Spironolactone does, it is called Canrenone (SPIRO CAN do it!)
**Which K-sparing diuretic's onset takes several days?Spironolactone (going in a spiral takes longer than a straight line) (think about this when deciding which diuretic would be better in emergancy cases, you wouldn't want to give this one!)
How does Amiloride work? Where/How is it absorbed? How is it excreted? SFx?Directly ↓s activity of the pump (Na/K) . Poorly absorbed from GIT. It is excreted mostly unchanged. SFx is hyperkalemia (Ami wont let much change her & she doesnt care that you can't stomach her. She'll punch you right in the banana)
How does Triamterene work? Where/How well is it absorbed? How is it excreted? SFx?Directly ↓s activity of the pump (Na/K) . Well absorbed from GIT. Excreted partly unchanged. SFx is hyperkalemia (its acts quickly & directly so its better for emergancies than Sprinolactone is) (Tri-s to be like Ami, but that's why it partly changes itself in order to convince itself to punch you in the pump. However, when not around any, is easy to stomach)
What are K-sparing diuretics used to Tx?hypokalemia 2⁰ to other diuretic use (CHF), Tx edema & ascites (think hepatic dz & portal hypertension) (special K for your liver, eat it up & your belly will swell & your heart will explode)
When are K-sparing diuretics less effective?Poor diuretic effect is ↑ when Na load or Aldosterone concentrations are high
What are the Aldosterone-mediated effects on the tubule? (6)[Remember, Aldosterone is interested in absorbing Na+, Cl- & excreting K]
(1) De novo (new) synthesis of Na channels
(2) Redistribute Na channels to luminal membrane
(3) Activate Na channels
(4) De novo (new) synthesis of Na/K ATPase
(5) Redistribution of Na/K ATPase to the basolateral membrane
(6) Activation of Na/K ATPase (pump)
Which drug ↑ long-term survival in canine CHF & why? (NOTE: I have no idea where I got this. So. Feel free to ignore at your own risk)Spironolactone, bc it competes w/ Aldosterone (Aldosterone ↑s Na → ↑ H20 → ↑ BP. So inhibiting these ↓s edema & cardiac workload) (spiro the dragon helps all fellow animals long term)

Osmotic Diuretics (not used often now)

Question Answer
How do Osmotic Diuretics work?They are filtered through the glom but not reabsorbed in the tubules & act on those parts of the nephron that are freely permeable to H20 (PCT - descending limb of the loop of Henle, collecting duct). Prevents reabsorption of H2O by ↓ osmotic gradient.
What is the 1⁰ effect of Osmotic Diuretics & what is the 2⁰ effect?1⁰ → osmotic pull keeps H20 in the lumen of tubules
2⁰ → ↓ Na reabsorption (Na is leaked back from leaky membrane to stay w/ H2O bc of diff osmotic gradient)
2 clinical indications of Osmotic Diuretics?(1) Acutely raised intracranial or intraocular pressure
(2) Prevention of acute renal failure (reduced GFR - urine flow ceases)
What are the SFx of Osmotic Diuretics in the body?Transient expansion of extracellular fluid (I have written: Pull fluid from all your tissues, so transient dehydration of all of them)

Check yo'self before you wreck yo'self

Question Answer
Where do Carboanhydrase Inhibitors work?PCT
Acetazolamide belongs to which class of diuretics?Carboanhydrase Inhibitors
Acetazolamide works where? What is it used to Tx?PCT, Tx glaucoma (bc it only has a mild diuretic effect)
Acetazolamide works how & has what effects? (basics)↑ excretion of Bicarb, Na+ & K+. Leads to mildly alkaline urine & a metabolic acidosis
Which diuretics are the most powerful?Loop Diuretics
Torasemide belongs to which class of diuretics?Loop
Bumetanide belongs to which class of diuretics?Loop
Furosemide belongs to which class of diuretics?Loop
Loop Diuretics do what & what are the SFx from this?Inhibit the Na+/K+/Cl- carrier → lose Na+, K+ & H+ → HYPOKALEMIA, loss of ions means metabolic alkalosis & bc they are such powerful diuretics, hypovolemia & hypotension
Which 2 Loop Diuretics are metabolized by using CYP450 pathways?Torasemide & Bumetanide
Which Loop Diuretic drug is metabolized via Glucuronidation?Furosemide
Thiazide Diuretics affect which part of the nephron?DCT
K-sparing diuretics are the ones that act where?Collecting duct
Aldosterone works where, does what & is blocked by what?Collecting duct, does Na/Cl reabsorption & K excretion. Blocked by K+ sparing diuretics
What does ADH do? Where does it exert its effect? What blocks it?↑ H2O reabsorption in the collecting duct. Blocked by Lithium Carbonate, Demeclocycline, Colchicine (in Class he said we just need to know that it can be blocked. I don't trust him)
Chlorothiazide belongs to which class of diuretics?Thiazides
Hydrochlorothiazide belongs to which class of diuretics?Thiazides
Spironolactone belongs to which class of diuretics?K-sparing (meaning it could possibley cause hyperkalemia)
Amiloride belongs to which class of diuretics?K-sparing (Ami likes to take special K)
Triamterene belongs to which class of diuretics?K-sparing
How do non-K-sparing diuretics effect K balance?K loss will ↑ when ↑ Na reaches the collecting ducts
How do K-sparing diuretics effect K balance?**K loss will be ↓ when Na reabsorption is ↓ in the collecting ducts (if Na doesn't go in, K doesn't go out)
Which drug works by competing w/ Aldosterone?Spironolactone
Which K-sparing diuretic has an active metabolite? Name it?Spironolactone, Canrenone
What is Canrenone?Active metabolite of Spironolactone (K-sparing diuretic)
Which diuretic not only causes possible hyperkalemia, but also other SFx? Name all the SFxSpironolactone → GIT upset, gynaecomastia, menstrual disorders, testicular atrophy, peptic ulcers
Which drug ↑ long-term survival in canine CHF & why?Spironolactone, bc it competes w/ Aldosterone (Aldosterone ↑ Na → ↑ H20 → ↑ BP. so inhibiting these ↓ edema & cardiac workload)
Which group can act as venodilators, bc they cause the endothelium to release Nitric Oxide & prostaglandin 1, which causes vasodilation?Loop Diuretics (a single loop can only get around the veins, not the veins & arteries)
This group helps w/ Diabetes Insipidus & bone loss?Thiazides (cause they are the Ca-sparing diuretics duh!)
This group acts as vasodilatorsThiazides
Which group ↑ secretion of Ca & which ↓ secretion of Ca?Loop Diuretics ↑ secretion of Ca (so less Ca in body). Thiazides ↓ secretion of Ca (cause they are the Ca-sparing diuretics)
Can cause hyperglycemiaThiazides (Ca sparing diuretics) more Ca = more sugar (i have no idea why though)
Extra-renal SFx of this group are - Hyperglycemia, Vasodilation, ↑ plasma cholesterol, Male impotence, Hypersensitivity rxnsThiazides (that sugar btwn your thighs is sweet enough to make him go soft)
Poorly absorbed from GITAmiloride
MOA of K-sparking diuretics varies. Name the 3 drugs & their MOA(1) Spironolactone competes w/ Aldosterone
(2) Amiloride ↓ activity of Na/K pump
(3) Triamterene ↓ activity of Na/K pump (directly & quickly)
Which drug causes GI upsets, hyperkalemia, gynaecomastia, menstrual disorders, testicular atrophy & peptic ulcers?Spironolactone

Acute/Chronic Kidney Injury

Question Answer
The "specific therapy" of acute kidney injury is what? Examples?Remove the cause!
If toxins → give antidotes
If infectious cause → give antimicrobials
Supportive therapy in acute kidney dz → fluid therapy. Explain why we do thisCorrection of hydration status, acid-base balance & electrolyte status
*Supportive therapy → management of oliguria or anuria. How do we do this? (Order (not sure if actually order or just how he worded it) in which we do things - name specific drugs)Start w/ Furosemide (Loop Diuretic) if that doesn't work → try Osmotic Diuretics → then Fenoldopam (a Dopamine agonist which works better than Dopamine bc it doesnt get degraded so quickly- works on D1 receptors which cause vasodilation for ↑ GFR) → then Diltiazem (a Ca++ antagonist which forces vasodilation to ↑ GFRs) etc, until something works
Supportive therapy → management of polyuria. How do you do this? (Not specific)By monitoring fluid & electrolyte therapies
Supportive therapy → Tx of uremic complications (What are the 2 complications, basic idea on how you tx it?)(1) Vomiting → anti-emetics & inhibitors of gastric acid secretion
(2) Hypertension → adjust fluid administration rates - diuretics - anti-hypertensives
Chronic kidney dz is most common in who?Most common in ageing cats, but also seen in dogs or other animals
Chronic kidney dz is a renal dz that leads to _________ & then _________Renal insufficiency & then renal failure
Chronic kidney dz → pathological changes occur to what structure? Regardless of what?Regardless of the site of initiating renal injury, pathological changes will occur to the glomerulus (it all goes back to glom, baby)
Chronic kidney dz → how is severity of dz usually reflected?Reflected in the magnitude of proteinuria (urine protein-to-creatinine ratio) (if proteinuria is persistent higher than 0.5, def a prob, you want to reduce the ratio by 50% before you can call the treatment sucessful, it needs to be below 0.5)
What is the RAAS? If you have kidney dz, what do you wanna do w/ the RAAS?Renin-Angiotensin-Aldosterone System (hormone system that regulates BP & H2O (fluid) balance. Angiotensin causes vasoconstriction & Aldosterone causes H2O & Na retention) If you have kidney dz, then, you wanna INHIBIT it, bc it will then REDUCE the BP & there will be LESS retention of H2O & salt, which puts less burden on the kidneys (& heart)
What are the 4 ways to inhibit the RAAS system?(1) Angiotensin-Converting-Enzyme (ACE) inhibitors
(2) Angiotensin receptor blockers (Losartan -Telmisartan)
(3) Aldosterone receptor blockers (Spironolactone (K-sparing diuretic))
(4) Renin inhibitors (used in humans & not extensively yet in dogs: Aliskirine)
Angiotensin receptor blockers → what are the receptors these drugs act on? Describe the properties of the receptors(1) AT1. The classic effects of Angiotensin II. Vasoconstriction → Aldosterone & Vasopressin release - Na & H2O retention (sympathetic facilitation). Cell prolif → Left ventricular hypertrophy, nephrosclerosis, endothelial dysfunction
(2) AT2 usually does opposite of the classical AT1, in order to limit the detrimental effects of AT1 activation. Actions are: Vasodilation - Na excretion – Anti-proliferative effects
What is/are the drug(s) used to block Angiotensin (AT) receptors?TELMISARTAN, Losartan (ppl need to stop being so TENSE about their TANs)
Look at slide 38 chartTelmisartan can stop the following
(1) Vasoconstriction + Na & H2O retention + symapthetic stim + pos inotropy → hypertension & arrhythmia
(2) Cellular prolif/growth + ECM protein regulation → vascular & cardiac hypertrophy, modeling, nepherosclerosis
(3) Endothelial dysfunction, modification of LDL → atherosclerosis
Which receptors does Telmisartan bind to? What are the strong effects it exerts?Binds strongly to AT1 (the classic effect receptor) to reverse effects by inhibiting. This causes strong antihypertensive effects
What are the properties of Telmisartan? (Hydro or lipophilic? is there protein binding? How is it absorbed & how is it metabolized?)Lipophilic, binds reversibly to plasma proteins, oral bioavail is 33% in cat & is GLUCORONIDATED (oddly enough, cats still do well w/ it) (my FAT CAT loves to EAT PROTEIN & GLUCOSE & will TEL MI when he wants to)