2013-09-10 Antihypertensives I Flashcards
1
Q
Describe the “targets of opportunity” for the different classes of drugs used to treat HTN DRAW IT OUT
A
2
Q
List the different classes of antihypertensive drugs
A
Diuretics Inhibitors of the RAA System Vasodilators Sympatholytic agents
3
Q
Explain the rationale for treating HTN
A
See HTN Lecture in SBM Cardio
4
Q
What are subclasses of diuretics w/ example of each?
A
– Thiazides (1. Hydrochlorothiazide, chlorthalidone) – Loop Diuretics (furosemide) (Term 5) – K sparing diuretics (spironolactone)(Term 5)
5
Q
What are subclasses of RAAS inhibitors w/ example of each?
A
– ACE inhibitors (2. Lisinopril) – Angiotensin receptor blockers (3. Losartan)
6
Q
What are subclasses of vasodilators w/ example of each?
A
– Direct acting (4. Nitroprusside, 5. Hydralazine) – Calcium entry blockers (6. Verapamil, nifedipine)
7
Q
Hydrochlorothiazide (HydroDiurilTM; also chlorthalidone, total of 5 in class; $4-$50 per month)
[see RANG 13]
–Class
- PD
- PK
–Toxicity
–Interactions
–Special Considerations
–Indications and dose/route
–Monitor
[See Rang]
A
Drug class: pharmacologic class–thiazide diuretic; therapeutic class–diuretic, antihypertensive
- Pharmacodynamics: block reuptake of Cl and Na from tubular fluid after glomerular filtration; also appears to cause decrease in SVR via unclear mechanism; will lower BP by up to 10-15 mm in many patients; useful as monotherapy or in combinations; HCTZ most commonly used, but perhaps some slight edge to chlorthalidone (duration, efficacy)(see Flack et al: Hypertension 2011; 57:665-6)
- Pharmacokinetics: F ~70%, excreted unchanged in urine; short half-life (hours); HCTZ not available in IV formulation; onset 2 h, peak 5 h, duration 10 h
- Toxicity: allergy to sulfa antibiotics (?); cause K and Mg depletion; cause Na and Cl depletion, metabolic alkalosis; volume depletion; worsen hyperuricemia
- Interactions: additive effects with most other antihypertensives
- Special considerations: more side effects in geriatric patients; Pregnancy Class D; much less effective in patients with reduced GFR
- Indications and dose/route: 12.5 mg or 25 mg po every morning; little benefit (and more toxicity) when given in higher doses
- Monitor: BP, weight, edema, K, Mg, BUN, creatinine
8
Q
- Lisinopril (PrinivilTM, ZestrilTM; also captopril, enalapril, ramipril, total of 10, $4 to $56 per month) –Class –PD –PK –Toxicity –Interactions –Special Considerations –Indications and dose/route –Monitor
[See Captopril card in Rang cards 6.01]
A
- Drug class: pharmacologic class–ACE inhibitor; therapeutic antihypertensive, treatment of CHF, preserving renal function, preserving LV function after MI, acute management of MI
- Pharmacodynamics: inhibits conversion of AT I to AT II by ACE; diminishes both vasocontriction and stimulation of aldosterone secretion by AT II
- Pharmacokinetics: well absorbed; onset 1 h, peak 6 h, duration 24 h; once a day is fine; excreted primarily in urine as unchanged drug
- Toxicity: orthostatic hypotension; use with caution in patients with impaired renal function, or renal artery stenosis; be careful in patients on diuretics, or those with aortic stenosis; angioedema, cough; acute renal failure
- Interactions: additive effects with most other antihypertensives; NSAIDs may reduce ability to lower BP; hyperkalemia with KCL, others
- Special considerations: often discontinue diuretics prior to beginning use to reduce hypotension; Category C/D in pregnancy, abnormal cartilage development
- Indications and dose/route: begin 10 mg per day, titrate slowly upward to 40 mg per day max
- Monitor: BP, weight, edema, K, BUN, creatinine!!!!!
9
Q
How do ACEIs and ARBs help preserve renal function?
A
I think it is because AII constricts the EA increasing intraglomerular pressure. –BAD in renal failure b/c they have a low renal perfusion capacity –l/u if you have time to be sure
10
Q
- Losartan (CoZaarTM; total of 7 in class, $55-$74) –Class –PD –PK –Toxicity –Interactions –Special Considerations –Indications and dose/route –Monitor
[See Rang card, too]
A
- Drug class: pharmacologic class–angiotensin-1 receptor blocker (ARB); therapeutic class—antihypertensive, preserve renal function, treatment of CHF
- Pharmacodynamics: block stimulation of AT I receptor by angiotensin II, thereby reducing vasoconstriction and production of aldosterone
- Pharmacokinetics: F ~30%; onset 6 h; extensive first pass effect; active metabolite is 40x more potent, much longer half-life
- Toxicity: dizziness; orthostatic hypotension; worsening of renal failure • Interactions: additive effects with most other antihypertensives
- Special considerations: Pregnancy class C/D; use care in patients on diuretics, those with renal artery stenosis, those with mitral or aortic stenosis
- Indications and dose/route: For HTN, daily doses 25-100 mg q day
- Monitor: BP, weight, edema, lytes, BUN, creatinine!!!
11
Q
- Nitroprusside (NiprideTM, NitropressTM; not given chronically) –Class –PD –PK –Toxicity –Interactions –Special Considerations –Indications and dose/route –Monitor
A
- Drug class: pharmacologic class– vasodilator; therapeutic class–antihypertensive, management of severe CHF, management of pulmonary hypertension, produce controlled hypotension to reduce bleeding during surgery
- Pharmacodynamics: acts “directly” on vascular smooth muscle to cause dilatation of both veins and arterioles; metabolized to release CN- and NO, which activates guanylate cyclase, leads to production of cGMP from GTP, which then leads to vasodilation; cGMP then hydrolyzed to GMP by PDE
- Pharmacokinetics: only route is iv; rapid onset (minutes) and cessation (minutes), thereby allowing minute-by-minute titration; CN- metabolite is converted to SCN in liver, then excreted in urine; must be given by continuous infusion
- Toxicity: excessive hypotension; accumulation of CN- and thiocyanate; headache; decreased blood flow to brain
- Interactions: additive effects with most other antihypertensives
- Special considerations: monitor patient VERYclosely—must be in ICU with arterial line; avoid high infusion rates or prolonged infusions, to prevent accumulation of CN-; use with caution in patients with increased intracranial pressure
- Indications and dose/route: for treatment of hypertensive crisis, given as IV infusion at 0.3-10 mcg/kg per minute
- Monitoring: BP, HR, metabolic acidosis; most often requires arterial line
12
Q
- Hydralazine (ApresolineTM; rarely given chronically; $4 per month or more for branded ) –Class –PD –PK –Toxicity –Interactions –Special Considerations –Indications and dose/route –Monitor
[see Rang card, too]
A
- Drug class: pharmacologic class–peripheral vasodilator; therapeutic class– antihypertensive, treatment of CHF, vasodilator
- Pharmacodynamics: “direct” acting vasodilator; seems to act by inducing endothelium to produce NO, which then passes to SM cells and induces production of cGMP, minimal venodilating effect
- Pharmacokinetics: given po, im, iv; metabolized extensively in GI mucosa and in liver, eventually excreted as metabolites in urine; F ~40%; onset 30 after po dose, 10 min after iv dose; persist for 2-6 hours
- Toxicity: more dangerous in patients with renal disease, prior stroke, angina; watch for hypotension, edema, occasionally drug-induced lupus
- Interactions: additive effects with most other antihypertensives
- Special considerations: never use as chronic oral monotherapy for treatment of hypertension, since edema and reflex tachycardia will result; concern giving to patients with CAD
- Indications and dose/route: dose 10-50 mg po four times daily • Monitor: BP, weight, edema, BUN, creatinine, symptoms of lupus or angina
13
Q
- Verapamil (IsoptinTM, CalanTM, similar to nifedipine, amlodipine, diltiazem, nicardipine, total 8 in class, $4 to $86 per month ) –Class –PD –PK –Toxicity –Interactions –Special Considerations –Indications and dose/route –Monitor
[See Rang card, too]
A
- Drug class: pharmacologic class–calcium entry blocker; therapeutic class– antihypertensive, antianginal, antiarrhythmic
- Pharmacodynamics: reduces BP by inhibiting influx of calcium through “slow channels”, thereby dilating peripheral arterioles; produces negative inotropic effect as well; for angina, reduces afterload, thus decreasing oxygen consumption; also, inhibits spasm of coronary arteries in vasospastic angina; blocks reentry paths through AV nodes in paroxysmal SVT
- Pharmacokinetics: absorbed rapidly, but F ~30%; also available in SR tablets; cleared by kidney and liver (produces active metabolites); onset 2 h po, 1-5 min iv; half-life 6-12 h; may be given po or iv
- Toxicity: hypotension, AV block, worsening of CHF, bradycardia
- Interactions: additive effects with most other antihypertensives; additive toxic effects on heart when given with beta-blockers
- Special considerations: use reduced doses in patients with both renal and hepatic disease; short-acting nifedipine (and similar CEBs) can increase risk of MI (unclear why); Pregnancy C
- Indications and dose/route: 80 mg thrice daily, or 240 mg SR once daily
- Monitor: weight, edema, BP
14
Q
In black patients, which drugs work better?
A
CEBs and diuretics seem to work better than b-blockers, ACEIs and ARBs
15
Q
Starting tx options (see special one for black patients)
A
– A thiazide diuretic remains a reasonable choice for initial Rx – Chlorthalidone may be more effective than HCTZ in lowering BP, and is as effective as a CEB or ACEI in preventing CV events in patients with HTN and coronary risk factors – ACEI, ARB, or CEB may also be a good initial drug
