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Phcol 402 > 01/25/16 > Flashcards

01/25/16 Flashcards

1
Q

Renal Physiology

A
  • Nephron: basic structural unit of the kidney
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2
Q

Renal Epithelial Cells

A
  • “polarized” cells
  • apical membrane: nephron lumen
  • basolateral membrane: interstitium, capillaries
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3
Q

Kidney Physiology: Segment, Function, H2O, Drugs, Target

A
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4
Q

Kidney: Sites of Action

A
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5
Q

Osmotic Diuretics

A
  • Do not interact with receptors or directly block renal transport
  • Actively dependent on development of osmotic pressure
  • Drugs:
    • Mannitol (Osmitrol)
    • Urea
    • Glycerol
    • Isosorbide
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6
Q

Osmotic Diuretics: MOA

A
  • Osmotic diuretics are freely filtered, not reabsorbed
  • Increase osmotic pressure in PT and TDLOH
  • Decrease passive reabsorption of H2O
  • Osmotic force lumen>osmotic force interstitium
  • Increase H2O and Na+ excretion
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7
Q

Osmotic Diuretics: Pharmacokinetics

A
  • Freely filtered through glomerulus
  • Not reabsorbed or secreted
  • Poorly absorbed in the GI tract→diarrhea
  • Excreted unchanged in 30-60 min
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8
Q

Osmotic Diuretics: Clinical Uses

A
  • Decreases intracranial pressure
  • Decreases intraocular pressure
  • Increases urine volume→prevent hemolysis, rhabdomyolysis during surgical procedures
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9
Q

Osmotic Diuretics: Toxicity

A
  • Pulmonary edema
  • Headache, nausea,vomiting
  • Dehydration
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10
Q

Carbonic Anhydrase Inhibitors

A
  • Acetazolamide (Diamox)
    • protype
    • developed from sulfanomide
    • replaced mercurial diuretics in 1950’s
  • Dorzolamide
  • Brinzolamide
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11
Q

Carbonic Anhydrase Inhibitors: MOA

A
  • Active in proximal tubule
  • Inhibits the enzyme carbonic anhydrase
  • HCO3- + H+→H2CO3→ H2O + CO2
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12
Q

Electrolyte effects of CA administration

A
  • Decreases HCO3- reabsorption and whole body HCO3-
    • Urine alkalinization
    • Metabolic acidiosis
  • Increases Cl- reabsorption
    • hyperchloremia
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13
Q

Carbonic Anhydrase Inhibitors: Clinical Uses

A
  • Glaucoma: topical brinzolamide or dorzolamide
  • Uric acid stones
  • Metabolic alkalosis
  • Acute mountain sickness
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14
Q

Carbonic Anhydrase Inhibitors: Pharmacokinetics

A
  • Oral, IV, topical
  • well absorbed
  • 0.5-2 hours onset of action
  • 3-9 hour of duration
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15
Q

Carbonic Anhydrase Inhibitors: Toxicity

A
  • hyperchloremic metabolic acidosis
  • Ca2+ renal stones
  • Fatigue, drowsiness
  • Parasthesias (pins and needles under skin)
  • sulfa allergy
  • fever, rash, bone marrow suppression
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16
Q

Loop Diuretics

A
  • Furosemide
  • Bumetanide
  • Torsemide
  • Ethacrynic acid
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17
Q

Loop Diuretics: MOA

A
  • Active in Thick Ascending Limb of Henle
  • Inhibits Na+/K+/2Cl transporter (NKCC2)
  • Compete with Cl- binding sites
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18
Q

Electrolyte effects of loop diuretic administration

A
  • Decreases reabsorption of GFR filtrate by ~25%
    • Rapid diuresis
  • Increases Mg2+ excretion
    • hypmagnesemia
  • Increases Ca2+ excretion
    • hypercalciuria
  • Increases K+ excretion
    • hypokalemia
  • Increases H+ excretion
    • metabolic alkalosis
19
Q

Loop Diuretics: Pharmacokinetics

A
  • Oral or IV injection
  • Rapid absorption, onset of action (minutes)
  • duration 2-4 hours
  • Enter nephron lumen via organic acid transporter in PCT
  • Inhibitors of organic acid ion transport decrease potency (i.e. probenecid, NSAIDs)
20
Q

Loop Diuretics: Clinical Uses

A
  • Edema: cardiac, pulmonary, renal
  • Hypertension
  • Acute hypercalcemia
  • Acute and chronic hyperkalemia
  • Anion overdose
21
Q

Loop Diuretics: Toxicity

A
  • hypokalemic metabolic alkalosis
  • ototoxicity
  • hyperuricemia
  • hyponatremia
  • hypmagnesemia
  • allergic reactions
22
Q

Thiazides

A
  • Chlorothiazide (Diuril)
  • Bendroflumethiazide
  • Chlorthalidone
  • Hydrocholorthiazide (Microzide)
  • Hydroflumethazide
  • Methylclothiazide
  • Polythiazide
  • Trichlormethiazide
23
Q

Thiazides: MOA

A
  • Active in distal convoluted tubule
  • inhibit Na+/Cl- co-transporter (NCC)
24
Q

Electrolyte effects of thiazide administration

A
  • Decreases Na+ reabsorption
    • hyponatremia
  • Decreases Cl- reabsorption
    • hypochloremia
  • Increases Ca2+ reabsorption
    • hypocalciuria
  • Increases K+ excretion
    • hypokalemia
25
Thiazides: Pharmacokinetics/Dosing
* oral, IV * Slowly absorbed, moderate duration (~5-12 hours) * Secreted by organic acid transporter in PT * many combination therapies
26
Thiazides: Clinical Uses
* Hypertension * Congestive heart failure * Hypercalcuria * Nephrogenic diabetes insipidus * Osteoporosis * Li+ toxicity
27
Thiazides: Toxicity
* _Hypokalemic metabolic alkalosis_ * hyponatremia * hyperglycemia * hyperlipidemia * hyperuricemia * allergic reactions
28
K+ sparing diuretics
1. Na+ channel (ENaC) blockers * Triamterene (Dyrenium) * **Amiloride** 2. Aldosterone receptor antagonists * Eplerenone (Inspra) * **Spironolactone** (Aldactone)
29
Effects of Aldosterone and Blocking ENaC
30
Na+ channel blocker and Aldosterone antagonist: MOA
* Na+ channel blockers: * **Amiloride** * Inhibit Na+ (ENaC) in CCD * Aldosterone antagonists: * **Spironolactone** * Inhibit aldosterone receptor in CD * Decrease Na+ pump expression/activity
31
Electrolyte effects of potassium sparing diuretics adminstration
* Decreases exchange of Na+ for K+ in CCD * Increases Na+ excretion * hyponatremia * Decreases K+ excretion * prevent hypokalemia
32
Na+ channel blocker and Aldosterone antagonist: Clinical Uses
* Counter K+ wasting effects of thiazides/diuretics * Inhibit effects of excessive aldosterone production * Conn's syndrome * Secondary hyperaldosteronism * Hypertension, congestive heart failure, cirrhosis * Potency: loops\>thiazides\>aldosterone
33
Na+ channel blocker and Aldosterone antagonist: Toxicity
* Antiandrogen effects with spironolactone * Gynecomastia, hypogonadism * Eplereone lacks anti-androgen effects * Aldosterone antagonsists have slow onset of action (weeks) * hyperkalemia with Na+ channel blockers and aldosterone receptor antagonists
34
V2 vasopressor receptor antagonists
* **Tolvaptan (Samsca)** * Lixivaptan (VPA-985) * Mozavaptan * Satavaptan
35
V2 vasopressor receptor antagonists: MOA
* Inihibit V2 vasopressin receptor in DCT and CCD * Decrease aquaporin-2 insertion into apical membrane * Increase H2O excretion
36
V2 vasopressor receptor antagonists: clinical uses
* Hyponatremia * CHF * Cirrhosis * SIADH
37
V2 vasopressor receptor antagonists: Toxicity
* nephrogenic diabetes insipidus * liver damage with prolonged use (\>30 days)
38
Mannitol: Drug Card
* Brand Name: * Osmitrol * MOA: * Increases nephron osmolarity in proximal tubule and thin descending limb of Henle * Clinical Uses: * Decrease intraocular/intracranial pressure * Drug overdose * Toxicities: * Pulmonary edema * Dehydration * Extra Info: * Freely filtered through glomerulus * Excreted unchanged in 30-60 min
39
Acetazolamide: Drug Card
* Brand Name: * Diamox * MOA: * Carbonic anhydrase inhibitor * Clinical Uses: * glaucoma * metabolic alkalosis * acute mountain sickness * Toxicities: * hyperchloremic metabolic acidosis * paresthesias * sulfa allergy * Extra Info: * Active in proximal tubule * HCO3- + H+→H2CO3→H2O + CO2
40
Furosemide: Drug card
* Brand name: * Lasix * MOA: * inhibit NKCC2 in thick ascending limb of Henle * Clinical Uses: * Edema in CHF, cirrhosis, nephrotic syndrome * hypertension * hypercalcemia * Toxicities: * hypokalemia * ototoxicity * dehydration * Extra info: * "high ceiling diuretic" * rapid onset of action (minutes)
41
Hydrochlorothiazide: Drug card
* Drug name: * Microzide * MOA: * inhibit NCC in distal convoluted tubule * Clinical Uses: * hypertension * CHF * idiopathic hypercalcuria * Toxcities: * hypokalemic metabolic alkalosis * hyponatremia * hyper-lipidemia, uricemia, calcemia * Extra Info: * "low ceiling diuretic" * component of many combination therapies
42
Amiloride: Drug Card
* Brand Name: * Midamor * MOA: * Inhibit ENaC in cortical collecting duct * Clinical uses: * CHF * Hypertension * Hypokalemia * Toxicity: * hyperkalemia * Extra Info: * "K+ sparing diuretic" * used in combination with loop and thiazide diuretics
43
Spironolactone: Drug Card
* Brand Name: * Aldactone * MOA: * Competitive antagonist of aldosterone receptor * Clinical uses: * hyperaldosteronism * CHF * HTN * Toxicities: * Hyperkalemia * endocrine effects (gynecomastia) * Extra Info: * Used in combination with loop diuretics to prevent hyperkalemia * eplerenone lacks anti-androgen effects
44
Tolvaptan: Drug Card
* Brand Name: * Samsca * MOA: * V2 vasopressin receptor antagonist * Clincal Uses: * symptoms of inappropriate anti-diuretic hormone (SIADH) * hyponatremia * Toxicities: * nephrogenic diabetes insipidus * hepatotoxicity * Extra Info: * In clinical trials for CHF, polycystic kidney disease

Phcol 402 (11 decks)

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