Diuretic Agents Flashcards
Every nerve coming out of the CNS release ACh on what receptors?
N
What is the effect of all of the sympathetic pathways being “linked”?
Act cohesively (do not have sympathetic response in only part of the body)
Muscarinic M2 receptors:
- Act via what G protein?
- Phosphorylate or dephosphorylate Ca2+ channels?
- Phosphorylate or dephosphorylate K+ channels?
- Are all pre- or post- synaptic?
Gi, dephosphorylates Ca2+, phosphorylate K+, all pre
Beta1, 2, and 3 receptors:
- Act via what G protein?
- Phosphorylate or dephosphorylate Ca2+ channels?
- Have what effect on Ca2+ channels?
Gs, phosphorylate Ca2+ channels
Then opens them, causes slight depolarization and releases insulin
Alpha receptor concentration is greatest where?
Large veins > resistance arteries (skin, elsewhere)
How does the baroreflex work?
Stretch receptors in carotid sinus and aortic arch → fire in response to ↑ stretch/BP to maintain homeostasis
Short-term regulation of BP via the baroreflex happens in how long?
~3-5 heart beats
Long-term regulation of BP happens when what?
MAP is high/ low for an extended time?
What is the drug response to a decrease in BP (immediate effect)?
Reflex tachycardia
What is the drug response to a decrease in BP (long-term effect)?
↑ renin release = ↑ Na+ and H2O retention
Altered blood circulation, altered blood composition, and inadequate lymphatic draining are conditions that promote the development of what?
Edema
What drugs are Carbonic Anhydrase Inhibitors
Acetazolamide, Dorzolamide, Brinzolamide
What drugs are Loop Diuretics?
Furosemide, Ethacrynic Acid
What drugs are Thiazide Diuretics?
Hydrochlorothiazide
Compounds related to Thiazides: Metolazone, Indapamide
What drugs are Potassium Sparing Diuretics?
Aldosterone Antagonist: Spironolactone, Eplerenone
Direct Inhibitors of Sodium Flux: Amiloride, TriamtereneE
What drugs are Osmotic Diuretics?
Mannitol, Isosorbide, GLycerin, Urea
What drugs are ADH Agonists and Antagonists?
Desmopressin, Conivaptan, Tolvaptan
Reabsorption in what part of the kidney cannot be influenced by drugs?
Proximal tubule
Exchange of Na+ with K+ in the DCT of the kidney can be modified by drugs that belong to which classes?
Aldosterone-antagonists and K+ sparing diuretics
Physiologically, what do thiazide diuretics do?
↑ Ca2+ reabsorption
Physiologically, what do loop diuretics do?
↑ Ca2+ and Mg2+ excretion
What do acidic drugs compete for? What can this lead to?
Uric acid excretion
Can lead to gouty attack
What drug class has the following MOA?
- Inhibits CA enzyme
- Blocks H2CO3 production
- ↓ H+ for exchange w Na+, resulting in ↑ Na+ (and H2O) loss
Carbonic anhydrase inhibitors
What are the indications for CA inhibitors? (3)
Glaucoma (↓ aqueous humor and CSF)
Alkalinization of the urine
Alkalosis (met and resp)
Acute mtn sickness = resp alkalosis
What important pharmokinetic property do CA inhibitors have?
Diuretic effectiveness decreases in several days
The following are the main adverse effects for what drug class?
Hyperchloremic metabolic acidosis
Hypokalemia
Hyperuricemia
CA inhibitors
What are the c/i’s and precautions for CA inhibitors? (2)
Hepatic cirrhosis
Sulfonamide hypersensitivity
The following is the MOA for which drug class?
Block the NaKCl2 co-transporter (impair concentrating/ diluting)
Induce kidney PGs (vasodilation)
Loop diuretics
What are the indications for loop duiretics? (4)
HF
Pulmonary edema (↑ systemic venous capacitance)
Hypercalcemia
Work well at low GFR
The following are adverse effects of which drug class? Hypokalemic metabolic alkalosis Hypocalcemia/ hypomagnesemia Hyperuricemia Irreversible ototoxicity
Loop diuretics
Sulfonamide hypersensitivity is a c/i/ precaution for which loop diuretic?
Furosemide
What drug interactions may occur with loop diuretics?
Aminoglycosides and Digoxin
What are the differences between Furosemide and Ethacrynic Acid?
Ethacrynic Acid is not a sulfonamide derivative and has the highest risk of ototoxicity
What is the MOA for thiazide diuretics?
Inhibition of sodium resorption at the early DCT
What are the main clinical indications for thiazide diuretics?
HTN, HF
Thiazide diuretics increase ATP-dependent K+ channel opening. This results in relaxation of smooth muscle cells and vasodilation (beneficial effect). What is an adverse effect of this?
Reduced insulin secretion
Besides increasing ATP-dependent K+ channel opening, what other therapeutic effects do thiazide diuretics have?
↓ Ca2+ excretion
↓ systemic BP and enhance anti-HTN action of other drugs
With respect to pharmokinetics, how is Indapamide different?
Excreted by the biliary system (vs organic acid secreting system) therefore useful in pts w renal insufficiency
Besides dizziness, weakness, fatigue and leg cramps, which are common adverse effects of thiazide diuretics… what are the 2 more concerning ones?
Hypokalemic metabolic alkalosis
Hyperuricemia
The following are the main adverse effects of which drug class?
Magnesium loss
Hyperglycemia
Elevated serum lipid levels
Thiazide diuretics
Which drug belonging to the thiazide diuretic class does not elevate serum lipid levels?
Indapamide
The following are the c/i’s and precautions of which drug class?
Hypokalemia can precipitate digitalis toxicity
Hyperglycemia and carbohydrate intolerance may occur
C/i in diabetics
Hyperuricemia = acute gouty attacks
Thiazide diuretics
What toxicity is aggravated by thiazides?
Lithium toxicity
Thiazide diuretics can cause what adverse effect in elderly patients?
Necrotizing vasculitis of skin and kidney
Which drug in the thiazide class is able to produce diuresis in patients with a reduced GFR?
Metolazone
What 3 major differences does Indapamide have from all other thiazide drugs?
Pronounced vasodilation
Does not increase plasma lipids
Metabolized in the liver and kidney
Are K+ sparing diuretics strong or weak compared to thiazides and loop?
Weak
What is the primary MOA for aldosterone antagonists that leads to the following?
Less Na+ channels
Blocked Na+ conductance
↓ Na+K+ATPase activity
Competitive inhibitor of aldosterone
What is the most effective drug for treating hyperaldosteronism?
Spironolactone
What is an occasional adverse effect seen with Spironolactone?
Hyperkalemia
What is the primary c/i for Spironolactone?
Hyperkalemia (burn pts)
Which diuretic is a selective aldosterone receptor antagonist (SARA)?
Eplerenone
Pt taking Eplerenone will experience decreased incidence of what?
Endocrine related SE’s
What is a precaution for Eplerenone?
Drug interactions (CYP3A4)
What is the primary MOA for potassium sparing diuretics that leads to the following?
Directly inhibits aldosterone-sensitive Na+ channel
Leads to a ↓ K+ excretion
Inhibits Na+K+ ion exchange mech independently of aldosterone
What is the main use of potassium sparing diuretics?
Combination with K+ losing diuretics
Why do pts taking potassium sparing diuretics do not experience urate retention/ hyperuricemia?
They are not acids
What is the only serious toxicity and only c/i for potassium sparing diuretics?
Hyperkalemia
How are osmotic diuretics given?
IV only (not absorbed orally)
The following are the indications for which drug class?
Prophylaxis of acute renal failure
↓ intraocular/ intracranial pressure
Protect kidney against nephrotoxic substance
Osmotic diuretics
Excessive administration of osmotic diuretics can lead to what adverse effect? Therefore c/i in what populations?
EC volume expansion/ pulmonary edema
C/i in HF
What drug treats sxs of central DI?
Desmopressin (ADH agonist)
What is the indication for Conivaptan (ADH antagonist)?
Tx of eu/hypervolemic hyponatremia in hospitalized pts
How is Conivaptan given?
IV only
What is the main adverse effect associated with Conivaptan?
Hypokalemia
What is the main precaution associated with Conivaptan?
Hyponatremia associated w hypovolemia
The following is the MOA for which ADH antagonist?
Non-peptide V1a and V2 receptor antagonist
Conivaptan
The following is the MOA for which ADH antagonist?
Non-peptide V2 vasopressin receptor antagonist
Tolvaptan
How is Tolvaptan given?
Orally
Which ADH antagonist is initiated and re-initiated in a hospital and then continued on an outpt basis?
Tolvaptan
What is the order of the expected max diuretic effect?
Loops + thiazides»_space; loop»_space; thiazides»_space; CA inhibitors > K+ sparing
Which type of diuretics produce a dose-depdendent diuresis throughout their therapeutic dosage range?
Loop
Thizides have relatively flat dose-response curve and limited max response
