Sympatholytic HTN Drugs

centrally acting a2-adrenergic agonists

-clonidine, guanficine, methyldopa

unique feature of methyldopa

-default treatment for pregnant women

centrally acting a2 agonists site of action 

-brainstem 

-sympathetic nerve terminals (peripheral sites)

a2 agonist moa - brainstem 

-decreases sympathetic outflow from CNS to the heart and blood vessels 

a2 agonist moa - sympathetic nerve terminals at peripheral sites

-decreases NE release

-decreases sympathetic tone in peripheral tissues

methyldopa moa

-prodrug (L-dopa analog)

-enters CNS adrenergic neurons

common a2 agonist ADE

-sedation and dry mouth

-rebound HTN

methyldopa unique ADEs

-hemolytic anemia

-hepatotoxicity

clonidine clinical use 

-resistant HTN and hypertensive emergency 

-ADHD, opioid/alcohol withdrawal 

methyldopa clinical uses

-first line HTN treatment in pregnant women

guanficine clinical uses

-primarily for ADHD

clinical pearls of a2 agonists 

-s/e limit use as first line agent 

-used as asjuncts in resistant HTN 

-used with diuretics during chronic therapy 

-gradual taper to prevent rebound HTN 

adrenergic neuron blockers

-reserpine, guanethidine

reserpine moa

-inhibits VMAT

-prevents vesicular storage of NE, dopamine, and serotonin

-depletion of NE

guanethidine moa 

-enters adrenergic neurons via NET

-replaces NE with inactive neurotransmitter in vesicles 

-prevents NE release 

adrenergic neuron blockers ADEs

-severe depression, sedation, orthostatic hypotension, GI upset

adrenergic neuron blockers clinical uses

-rarely used due to poor tolerability and safer alternatives

selective a1 blockers 

-osin’s 

first gen selective a1 blocker

-prazosin

-short acting

second gen selective a1 blockers

-terazosin, doxazosin

-long acting

third gen selective a1 blockers 

-tamsulosin, silodosin 

-selective prostatic a1A blockers (BPH) 

selective a1 blockers moa

-block vascular a1B receptors

-prevent NE-induced vasoconstriction via vasodilation and venodilation

prazosin, doxazosin, terazosin ADEs

-postural hypotension, syncope, reflex tachycardia, dizziness, nasal congestion

clinical pearl of selective a1 blockers 

-administer first dose at bedtime 

-modest improvement of lipid profile 

selective a1 clinical uses 

-mild to mod HTN 

-adjunct therapy for severe/resistant HTN (combined with diuretics) 

-BPH in pts with HTN 

vasodilators as monotherapy

-trigger compensatory mechanisms to increase BP

-baroreceptor reflex activated (reflex tachycardia)

-decreased renal perfusion activates RAAS (rebound HTN)

combination therapy to prevent reflex tachycardia

-vasodilator + B-blocker

combination therapy to prevent Na/H20 retention 

-vasodilator + diuretic 

selective B1 blockers without ISA

-atenolol, esmolol, metoprolol, nebivolol

selective B1 blockers with ISA

-acebutolol

non selective B1+B2 blockers without ISA 

-propranolol, nadolol, timolol 

non selective B1 + B2 blockers with ISA

-pindolol

mixed a1 selective and non selective B blockers

-carvedilol, labetalol

MOA of all B-blockers 

-blockade of B1 receptors (2 mechanisms) 

B-blockers MOA - heart

-decreases HR, contractility and CO 

-immediate effect

B-blockers MOA - kidney

-decreases renin release (suppressed RAAS)

-long term effect 

B-blocker with vasodilator properties

-nebivolol

Nebivolol MOA

-decreases CO and suppresses RAAS

B-blocker for improved peripheral blood flow (PAD or cold extremities)

-nebivolol

MOA - mixed a1 selective and non selective B blockers

-B blockade decreases HR, contractility, CO and suppresses RAAS

-a1 blockade decreases TPR

labetalol unique features 

-rapid balance of a1/B blockade, avoids reflex tachycardia 

-safe in pregnancy (IV)

-not for chronic use (fetal risk) 

carvedilol unique features

-dual a1/B blockade, avoids reflex tachycardia

-antixidant effects

-inhibits cardia remodeling (cardioprotective)

ADEs - all B-blockers

-bradycardia, exercise intolerance, fatigue

-masked warning s/s of hypogylcemia (esp. pt on insulin)

-acute heart failure

ADEs - non selective B blockers 

-worsens peripheral artery disease 

-bronchocronstriction (not for asthma pt)

-delayed recovery from hypoglycemia (in diabetics) 

-dyslipidemia 

-CNS effects 

clinical uses - B blockers

-HTN, heart failure, angina, arrhythmias

clinical uses - B1 selective

-preferred in pts prone to bronchospasm, diabetes or PAD

clinical uses - B1 selective with ISA 

-useful in pts with bradycardia and dyslipidemia 

clinical uses - B blockers with vasodilator properties (nebivolol)

-PAD or cold extremities

clinical uses - B blockers with vasodilator properties (labetalol)

-HTN emergencies during labor/pregnancy

-IV

clinical uses - B blockers with vasodilator properties (carvedilol) 

-heart failure 

all B blockers contraindications 

-sinus bradycardia, acute heart failure, partial AV block 

non selective B blockers contraindications

-asthma, COPD

B blocker withdrawal syndrome

-rebound HTN, arrhythmias or angina