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Flashcards in Thiazide Diuretics Deck (13):
1

Thiazide diuretics are used in the treatment of ___?

HTN, edema

2

What are the 4 main thiazide diuretics?

HCTZ, chlorothiazide, Metolazone, & Chlorathalidone

3

MOA for thiazide diuretics?

- Thiazides block the Na-Cl cotransporter on the tubular lumen side within the DCT, inhibiting sodium

- Impairs distal nephron H+ secretion (direct effect on alpha-intercalated cells?) --> bicarb lossreabsorption.

4

Effects of HCTZ?

- ↑ urinary excretion of Na+ & H2O

- ↑ Urinary excretion of K+ & Mg2+ --> potassium losing diuretic

5

Clinical Application of HCTZ?

- Management of mild-to-moderate HTN alone or in combo w/ another anti-hypertensive agent

- Not effective in pts w/ ↓ GFR

- Edema

- Off label: calcium nephrolithiasis (helps with reabsorption of calcium --> ↓ urinary excretion of calcium); nephrogenic diabetes insipidus

6

PKs of HCTZ?

- well-absorbed PO (65-75% bioavailability)

- Peak at 2 hrs, lasts 6-12 hrs (take in AM)

- Excreted in urine unchanged, with elimination half-time of 6-15 hrs

7

HCTZ Toxicities?

- Orthostatic hypotension

- Hypovolemia

- Hypokalemia, hypomagnesemia, hyponatremia, hypochloremic metabolic alkalosis

- Hypercalcemia, hyperglycemia, hyperuricemia (↑ risk of gout), & ↑ lipid levels

- Do not start during pregnancy

- Sulfonamide drug --> HS rxn

8

Issues with chlorothiazide?

Similar axn as HCTZ but with poor PO absorption

9

Thiazide Drug Interactions?

- Often combined w/ anti-htn meds from other drug classes to potentiate the blood pressure lowering effects

- K_ loss can be offset by combo w/ K+ spraring diuretics

- ↑ risk of digoxin & lithium toxicity

10

Chlothalidone

- 1-2x more potent

- Different chemical structure

- Much longer half-life

- Much larger volume of distribution that HCTZ, but is prescribed much less commonly in US

11

Metolazone

- Long-acting thiazide diuretic

- Favorite of cardiologists --> use as an adjunct diuretic in trx of CHF

12

Overlooked facts on HCTZ

- HCTZ potentiates effex of a second anti-HTN drug, but low doses alone (6.25-25 mg) have never been shown to impact morbidity of mortality

- Chlothalidone in doses 12.5-25 mg/day has been shown repeatedly to ↓ CV morbidity and mortality in randomized, controlled trials --> this is why htn specialists tend to prescribe it over HCTZ

13

Thiazides are ____ with Na+ loss, are __ -losing, and cause larger ____ loss d/t inhibition of distal H+ secretion.

Intermediate
K+
Bicarb