2B : DIURETICS - THIAZIDES

Question 1

Thiazide
Diuretics examples

Answer 1

Hydrochlorothiazide
Chlorthalidone
Indapamide
Metolazone
Bendroflumethiazide
Polythiazide

Question 2

MOA:
Mechanism of Action of Thiazides

Answer 2

1. Inhibit reabsorption of NaCl from lumen to blood n the DCT DCT (s/e:
   Hyponatremia)
2. Inhibit secretion of Calcium
   from blood to lumen (s/e: hypercalcemia
3. Promote Mg secretion but inhibit Calcium secretion (s/e:Hypomagnesemia)
4. Increase reabsorption of UREA in proximal tubule –>increase plasma
   URIC ACID –> lead to Gouty Arthritis (s/e: Hyperuricemia)
5. Can cause HYPERPOLARIZATION of ATP dependent K channels
   (pancreatic beta cells) and no insulin release (s/e: hyperglycemia)

Question 3

MOA:

Answer 3

Inhibitors of Na+Cl Symport in the DCT (reabsorbs 7% of filtered Na+) but increased
Ca2+ REABSORPTION (opposite to Loop diuretic effect)

Question 4

thiazide in full doses

Answer 4

moderate but sustained Na+ and Cl
excretion

Question 5

Predominant effect:

Answer 5

1. increased NaCl excretion,
   K+, HCO3, Mg, Cl and PO4 excretion and
2. but can blunt uric acid secretion and increase serum uric acid level

Question 6

THIAZIDE DIURETICS s/e

Answer 6

HYPER
GLUC

• HyperGlycemia
• HyperLipidemia
• HyperUricemia
• HyperCalcemia

Question 7

THIAZIDE: ADVERSE EFFECTS

Answer 7

Most serious adverse effects are related to abnormalities of fluid and
electrolyte balance:

• Hypercalcemia
• Hyperuricemia
• Hyperlipidemia – 5-15 % increase in serum cholesterol, LDL and TAG
• Hyperglycemia - Decreased glucose tolerance (r/t potassium
  depletion)

Question 8

THIAZIDE: ADVERSE EFFECTS

Answer 8

• Hypokalemia
• Metabolic alkalosis (low HC03)
• Hypochloremia
• Hypomagnesemia
• Hypotension
• Hyponatremia
  ––(hypovolemia induced elevation of ADH so limit
  intake of water, reduce TD use)
• Erectile dysfunction/ impotence –>
  greatest incidence among
  anti HTN agents , r/t to volume depletion but tolerable

Question 9

THIAZIDE: Therapeutic use

Answer 9

A. EDEMA associated with disease of:
1. Heart (Congestive Heart Failure)
2. Liver (Hepatic Cirrhosis)
3. Kidney (Nephrotic syndrome, CRF,AGN)

B. Nonedematous conditions
1. Hypertension
2. Ca2+ nephrolithiasis (to reduce Ca2+ excretion)
3. Osteoporosis
4. Nephrogenic Diabetes Insipidus (TD reduces urine
volume by 50%)

Question 10

Thiazides are ineffective when GFR less than 30-40 mL/min
except

Answer 10

metolazone and indapamide

Question 11

Non
edematous conditions for thiazide use

Answer 11

1. Hypertension
2. Ca2+ nephrolithiasis
3. Osteoporosis
4. Nephrogenic Diabetes Insipidus

Question 12

edematous condition for thiazide use

Answer 12

1. Heart (Congestive Heart Failure)
2. Liver (Hepatic Cirrhosis)
3. Kidney (Nephrotic syndrome, CRF,AGN)

Question 13

thiazide diuretics Enhance effects of anaesthetics , diazoxide, digitalis glycosides, lithium,
Loop Diuretics, vit D

TRUE OR FALSE

Answer 13

TRUE

Question 14

Efficacy reduced by

Answer 14

NSAIDs
(inhibit synthesis of PG
important in maintaining GF)

Question 15

increase risk of
hypokalemia

Answer 15

Amphotericin B and corticosteroids

Question 16

Hypokalemia increases risk of

Answer 16

TDP
Torsades De Pointes

Question 17

TD + quinidine

Answer 17

LETHAL

why?

Quinidine prolongs QT interval to lead to polymorphic ventricular tachycardia

Question 18

Diminish effects of

Answer 18

anticoagulants, uricosurics, sulfonylureas, insulin

Question 19

MOA:

Answer 19

Inhibit Na+/Cl
transporter in DCT

Question 20

Uses:

Answer 20

• Hypertension,
• Heart failure,
• Renal calcium stones,
• Nephrogenic DI

Question 21

SE:

Answer 21

HYPER
GLUC

• HyperGlycemia
• HyperLipidemia
• HyperUricemia
• HyperCalcemia

Question 22

Synergistic effect with loop diuretic

TRUE OR FALSE

Answer 22

TRUE

Question 23

Efficacy decreased by

Answer 23

NSAIDs