Therapeutics of Hypertension Part 4 Flashcards
Direct arterial vasodilators
*Agents: hydralazine, minoxidil (usually need a loop diuretic with it)
*Last-line therapy for HTN
*Reserved for patients w/ special indications or very difficult to control BP (i.e. severe CKD or hemodialysis)
*Minoxidil is more potent than hydralazine
*Concomitant therapy w/ diuretic and beta blocker needed (to decrease likelihood of SEs)
Direct arterial vasodilators frequency
hydralazine: 2-4
minoxidil: 1-3
Adverse effects:
* Palpitations, tachycardia, chest pain, GI side effects, headache, hematologic dyscrasias, hepatotoxicity, lupus-like syndrome/rash (hydralazine), fluid retention, hair growth (minoxidil)
Minoxidil Boxed Warning Summary
*May cause pericarditis and pericardial effusion that may progress to tamponade
*May increase oxygen demand (increase HR, muscle needs more oxygen) and exacerbate angina pectoris
*Maximum therapeutic doses of a diuretic and two other antihypertensives should be used before this drug is ever added. Should be given with a diuretic to minimize fluid gain and a betablocker.
Direct Arterial Vasodilators Caution with
Caution with:
*CVA (h/o stroke)
* Renal impairment
* CAD (due to the SEs that can occur)
* Liver disease
* SLE (lupus)
Alpha-1 Blockers
*Agents: doxazosin, prazosin (can also be used to treat nightmares from PTSD), terazosin
*NEVER considered first line for HTN
* Second-line for patients with concomitant BPH
*Associated with orthostatic hypotension (esp. in elderly)
Central Alpha-2 Agonists
*Agents: clonidine, methyldopa, guanfacine Last line due to adverse effects
* CNS depression, dizziness, fatigue, anticholinergic effects, bradycardia, reflex tachycardia, fluid retention
*Avoid abrupt cessation due to rebound hypertension
*Methyldopa is preferred in pregnancy
Central Alpha-2 Agonists Cont.
Clonidine
* PO: usual range 0.1-0.2 mg BID-TID (max 2.4 mg/day)
Transdermal weekly patch (better for adherence): usual range 0.1mg-0.3mg/24 hours
* Available in 0.1, 0.2, and 0.3mg/24 hour patch
* Lower risk of rebound hypertension and improved adherence with patch!
Methyldopa
* Usual range 250-500 mg BID
Guanfacine
* Usual range 0.5-2 mg daily
Clonidine Clinical Pearls
Titrating off
* Slow wean - half dose every 2-3 days
* Concomitant beta blocker prescribed
* Wean BB several days prior to clonidine wean
Oral to transdermal patch: Overlap oral regimen for 3-4 days * Day 1: Place patch, administer 100% of oral dose of clonidine
* Day 2: Administer 50% of oral dose
* Day 3: Administer 25% of oral dose
* Day 4: Patch only
Patch to oral:
* Consider starting oral clonidine no sooner than 8 hours after patch removal
Monitoring Summary for Common Agents
ACEi/ARBs: BUN/SCr, potassium
CCBs: heart rate (non-dihydropyridine)
aldosterone antagonists: BUN/SCr, potassium
other diuretics: BUN/SCr, electrolytes (K, Mg, Na), uric acid (thiazides)
BBs: heart rate
What if My Patient isn’t at Goal?
*Consider nighttime dosing of one antihypertensive (never switch diuretics to nighttime)
Assess adherence
* Once daily vs multiple daily dosing
* Combination products
*Educate on diet, exercise, and smoking cessation *Rule out white coat hypertension
*Discontinue interfering substances
*Patient may have resistant hypertension
Resistant HTN
*Definition: failure to attain goal BP while adherent to a regimen that includes at least 3 agents at maximum dose (including a diuretic) or when 4 or more agents are needed
*Estimated 17% of HTN pts with new BP cut offs
*Risk factors: older age (blood vessels get more stiff as we age), obesity, CKD, diabetes, African American
*Disease of exclusion: must rule out secondary causes of HTN, nonadherence, whitecoat HTN, etc.
American Heart Association Step-wise Guidance for the Management of Resistant HTN (Sept 2018)
step 1:
* Maximize lifestyle interventions
* Optimize 3-drug regimen (ACEi or ARB, CCB, and diuretic)
step 2:
* Substitute optimized thiazide-like diuretic (chlorthalidone, indapamide)
step 3:
* Add mineralocorticoid receptor antagonist (spironolactone, eplerenone, really only used if pt has severe gynecomastia from spironolactone)
PATHWAY-2 Trial
335 patients aged 18-79 years with SBP >140 mmHg (>135 w/diabetes) and home SBP readings >130 mmHg
* Had to be on maximized ACEi or ARB, CCB, and thiazide for at least 3 months
Double-blind, placebo-controlled, crossover trial
* 4 phases: placebo, spironolactone, doxazosin, bisoprolol
Results: spironolactone > placebo/doxazosin/bisoprolol as add-on therapy in resistant hypertension
American Heart Association Step-wise Guidance for the Management of Resistant HTN (continued)
step 4:
* Add BB if heart rate >70 bpm
* Consider central alpha-2 agonist (clonidine patch or guanfacine at bedtime) if BB contraindicated and/or heart rate <70 bpm *diltiazem
step 5: (had to have already been on a diuretic and beta-blocker before going to steps 5-6)
* add hydralazine
step 6:
* Substitute minoxidil for hydralazine
(these are based on expert opinions)
De-escalating Therapy
*Presence of co-morbidities that would impact drug choice?
* DM? CKD? CAD? AFIB? HF? BPH?
*Identify first vs second-line agents
*Which has the most potential for adverse effects?
*Can we stop abruptly?
