Thiazide Diuretics Flashcards
1
Q
Thiazide diuretics are used in the treatment of ___?
A
HTN, edema
2
Q
What are the 4 main thiazide diuretics?
A
HCTZ, chlorothiazide, Metolazone, & Chlorathalidone
3
Q
MOA for thiazide diuretics?
A
- 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
Q
Effects of HCTZ?
A
- ↑ urinary excretion of Na+ & H2O
- ↑ Urinary excretion of K+ & Mg2+ –> potassium losing diuretic
5
Q
Clinical Application of HCTZ?
A
- 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
Q
PKs of HCTZ?
A
- 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
Q
HCTZ Toxicities?
A
- 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
Q
Issues with chlorothiazide?
A
Similar axn as HCTZ but with poor PO absorption
9
Q
Thiazide Drug Interactions?
A
- 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
Q
Chlothalidone
A
- 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
Q
Metolazone
A
- Long-acting thiazide diuretic
- Favorite of cardiologists –> use as an adjunct diuretic in trx of CHF
12
Q
Overlooked facts on HCTZ
A
- 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
Q
Thiazides are ____ with Na+ loss, are __ -losing, and cause larger ____ loss d/t inhibition of distal H+ secretion.
A
Intermediate
K+
Bicarb
