Flashcards in Thiazide Diuretics Deck (13):
Thiazide diuretics are used in the treatment of ___?
What are the 4 main thiazide diuretics?
HCTZ, chlorothiazide, Metolazone, & Chlorathalidone
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.
Effects of HCTZ?
- ↑ urinary excretion of Na+ & H2O
- ↑ Urinary excretion of K+ & Mg2+ --> potassium losing diuretic
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
- Off label: calcium nephrolithiasis (helps with reabsorption of calcium --> ↓ urinary excretion of calcium); nephrogenic diabetes insipidus
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
- Orthostatic hypotension
- Hypokalemia, hypomagnesemia, hyponatremia, hypochloremic metabolic alkalosis
- Hypercalcemia, hyperglycemia, hyperuricemia (↑ risk of gout), & ↑ lipid levels
- Do not start during pregnancy
- Sulfonamide drug --> HS rxn
Issues with chlorothiazide?
Similar axn as HCTZ but with poor PO absorption
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
- 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
- Long-acting thiazide diuretic
- Favorite of cardiologists --> use as an adjunct diuretic in trx of CHF
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