Stramula 2

Question 1

What are the Na/Cl Symport Inhibitors

Answer 1

• Prototype=Hydrochlorothiazide
• Thiazide Diuretics
  
  • Hydrochlorothiazide
  • Chlorothiazide
  • Metolazone
• Non-Thiazide Diuretics
  
  • Chlorathilidone
  • Indapamide
• Thiazides=second generation diuretics
  
  • Identify compounds that increase excretion of Na and Cl
    
    • instead of Na and Bicarobnate w/CA inhibitors
  • commonly prescribed diuretic

Question 2

Na/Cl Symport Inhibitors: MOA

Answer 2

Question 3

Na/Cl symport inhibitors: Therapeutic uses

Answer 3

• Hypertension
  
  • first line treatment
  • mono therapy or adjunct therapy
• Mild Edema
  
  • loop diuretics usuallly used to treat edema
• Reduce Ca2+ stone formation
  
  • compared w/loop diuretics

Question 4

Na/Cl symport inhibitors: Side Effects

Answer 4

• Electrolytes- Loss of Na, K, Mg, H+
• Ca2+ retention (HYPERCALCEMIA)
• Hypokalemia
• Hyperglycemia
  
  • reduced insulin secretion and glucose utilization
• Hyperuricemia
  
  • formation of urate crystal-GOUT
• Lipid profile: Increase LDL
• Metabolic Alkalosis
• Impotence
• Allergic Rxns
  
  • due to sulfoamide derivative

Question 5

Why are we shifting emphasis from Hydrochlorothiazide to Chlorothalidone

Answer 5

• Chlorthalidone inhibits some carbonic anhydrase isotypes (e.g. CA III, VII, IX, XII, XIII) more potently than hydrochlorothiazide,
• leads to enhanced generation of Nitric Oxide (NO)

Question 6

Adverse effects of chlorthalidone

Answer 6

• Chlorthalidone increases sympathetic activity and insulin resistance in hypertensive individuals
  
  • These deleterious effects are mitigated by adding spironolactone to chlorthalidone
• Generation of NO-
  
  • additional vasodilation effect
    
    • good for endothelial dysfunction, hypertension and heart failure patients

Question 7

Thiazides vs Loop Diuretics: DDIs

Answer 7

• Thiazides:
  
  • When you add loop diuretic with aminoglycoside antibiotics
    
    • ototoxicity will be increased.
  • Digoxin can cause Arrhythmia that is increased SOME by loop diuretics but LOT MORE by thiazides.
  • Quinidine
    
    • Anti-arrhythmic drug
    • ventricular tachycardia is increased by Thiazides.
  • Serum Lithium levels
    
    • increased by use of Thiazide diuretics.
• Loop diuretics dependent more on PG synthesis than Thiazide diuretics.

Question 9

what is another name for Mineralocorticoid Receptor (Aldosterone) Antagonists

Answer 9

K+-Sparing Diuretics

Question 10

What are the K+ sparing diuretics

Answer 10

Spironolactone

Question 11

What occurs with potassium wasting diuretics

Answer 11

• All K+-wasting diuretics increase RAAS activity; proportionate to their diuretic efficacy
• Aldosterone is released from Adrenal Cortex in response to ACTH – Ang II- AT1R.

Question 12

Mineralocorticoid Receptor (Aldosterone): MOA

Answer 12

Question 13

what is the MOA of M.O.A of Aldosterone Receptor Antagonists

Answer 13

Question 14

Spironolactone effects

Answer 14

• Clinical efficacy proportional to aldosterone Level
• People with high aldosterone
  
  • SL will result in greater K+ retention, greater Na+ loss
  • more beneficial
• Low or minimal aldosterone level
  
  • SL will have less beneficial effects
• Canrenone: active metabolite; T1/2, 16 h
• Access via basolateral membrane
• Exhibits anti-androgen effect (off-label use in women with hirsutism)

Question 15

Spironolactone: contraindications

Answer 15

• peptic ulcer
• pregnancy

Question 16

what is the MOA of Epithelial Na+ Channel Blockers

Answer 16

• Pharmacological antagonism
  
  • binds with channels and blocks them.
• Effect - exactly opposite of loop diuretics.

Question 17

K+ sparing diuretics: Therapeutic uses

Answer 17

• Hardly used by themselves, used as adjunct therapy to counterbalance loss of K+
• Added to loop or HTZ/non
  
  • HTZ diuretics
  • improves BP and metabolic (glucose) outcomes
• Li toxicity:
  
  • reduce Li reabsorption

Question 18

K+ sparing diuretics: Adverse Effects

Answer 18

• Toxicity: Hyperkalemia
• Contraindicated: K+ suppl + ACE inhibitors, ARBs, b-Blockers
• Triamterene: Weak folic acid antagonist, kidney stones
• Amiloride: nausea, vomiting, diarrhea

Question 19

what are Changes in Urinary Electrolyte Patterns and Body pH in Response to Diuretic Drugs

Answer 19

• All diuretics
  
  • regardless of their mechanism of action
    
    • loss of sodium in urine.
• All diuretics
  
  • except K sparing diuretics -
  • loss of potassium in urine.
• Loop and thiazide diuretics
  
  • cause metabolic alkalosis