L7-8: Diuretics

Question 1

Diuretics

Answer 1

Agents that help the body get rid of sodium (natriuresis) and water (diuresis)

Question 2

T/F: Water always goes with sodium

Answer 2

True

Question 3

Diuretics (decrease/increase) blood pressure

Answer 3

Decrease

Decrease in plasma volume = decrease in blood pressure - less burden on CV disease

Question 4

Indications for Diuretics

Answer 4

Edematous states

HTN

Heart failure

ACUTE renal failure

Question 5

Which types of transport are likely drug targets

Answer 5

Mediated and active transport are drug targets - Have carriers

Question 6

Classification of Diuretics Based on MOA

Answer 6

1. Inhibitors of carbonic anhydrase
2. Osmotic Diuretics
3. Inhibitors of Na+-K+-2Cl- Symport
4. Inhibitors of Na+Cl- Symport

5a. Inhibitors of Renal Epithelial Na+ channels

5b. Mineralocorticoid Receptor Antagonists

Question 7

Glomerulus and diuretics

Answer 7

Diuretics do not get filtered in glomerulus
-Most are highly protein bound
Secreted at proximal tubule
Diuretics target and block the action of epithelial proteins involved in solute transport

Question 8

Renal Drug Handling - Glomerular Filtration depends on

Answer 8

GFR
Size of drug
Extent of plasma protein binding: Only unbound is filtered
-Renal excretion of unchanged drug is a major route of elimination for 25-30% of drugs

Diuretics MUST get to active site to express activity
Reabsorption at the distal tubule

Question 9

Active secretion in the proximal tubule: OAT

Answer 9

Furosemide
Thiazides
Penicillin
Cephalosporin
Probenecid
NSAIDs
Non-selective - competitive
All anions - negative charge

Question 10

Active secretion in the proximal tubule - OCT

Answer 10

Amiolride
Cimetidine
Digoxin
Metformin
Morphine
Procainami
Quinidine
Ranitidine
Triameterene
Tremethoprim
Vancomycin

All cations - positive cahrge

Question 11

Active secretion depends on

Answer 11

Amount of protein plasma binding

The rate of delivery of the drug to the secretory site

The degree of saturation of transporters

The presence of drugs that can compete for these transporters

Question 12

OAT in the proximal tubule: penicillin

Answer 12

Penicillin
-Inhibit transpeptidase
Block crosslinking of peptidoglycans
Decrease cell wall synthesis

Mostly cleared by kidneys unchanged
Was extracted and reused during WW2
Competition by probenecid at OAT to slow penicillin excretion and prolong activity

Use both at the same time = slows penicillin = longer duration of action

Question 13

Inhibitors of Carbonic Anhydrase

Answer 13

In the proximal tubule

CA-I inhibit both cytoplasmic CA and membrane-bound CA

CA-I essentially block reabsorption of NaHCO3

Reduction in hydrogen causes acidic blood

Question 14

Structure-Activity Relationships: Carbonic Anhydrase Inhibitors

Answer 14

Sulfanilamide
(show to produce mild diuresis)

Requires both nitrogen and sulfa - nitrogen CANNOT be substituted

Question 15

Carbonic Anhydrase Inhibitors: Types, uses, toxicities

Answer 15

Types:
Acetazolamide
Dichlorphenamide
Methazolamide

Uses
-Low efficacy diuretic
-Acute mountain sickness
-Metabolic Alkalosis
-Glaucoma
-Urinary Alkanlinization

Toxicities
-Hyperchloremic metabolic acidosis
-Renal stones
-Renal potassium wasting
-Drowsiness/paresthesia