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Centrally-acting alpha-2 agonists
- Clonidine (Catapres)
- Guanfacine (Tenex)
- Methyldopa (Aldomet) - and false transmitter
- MOA: by activating pre-syn alpha-2 ARs in vasomotor ctr --> decrease NE release and decrease SNS --> decrease HR and cause vasodilation
- barorecpetor reflexes remain functional --> minimal orthostasis
- will have fluid retention due to kidneys compensating for decrease BP --> weight gain & decrease antihypertensive effect
- SE: fluid & sodium retention, xerostomia (decrease stimulation beta-1 in salivary glands), sedation, dizziness, constipation (alpha-2 stimulation relaxes GI smooth muscle --> increase sodium and water reabsorption), diarrhea may occur as a response to chronic constipation & bacterial growth, sexual dysfunction, rebound HTN
- Therapeutic Use: HTN (limited due to more intense SE than other anti-hypertensive meds); best in combo with diuretic
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clonidine
- Brand Name: Catapres
- more severe SE (xerostomia, sedation, rebound HTN)
- strucutally it's an imidazoline
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clonidine uses
- menopausal hot flashes (vasomotor symptoms of increased warmth, flushing and sweating)
- pheochromocytoma diagnosis (overnight clonidine suppression) - NE levels decreased = CNS-HTN, NE levels DON'T decrease = pheochromocytoma
- opiate, alcohol, benzodiazpine withdrawl -> deactivating SNS blocks cravings
- ADHD - only witih extended-release products
- diabetic diarrhea of autonomic neuropathy: relaxes GI sm muscle --> increase sodium and water reabsorption --> decrease diarrhea/constipates
- epidural administration for severe pain in cancer patients
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guanfacine
- Brand Name: Tenex
- once daily dosing, longer half-life
- more selective for alpha-2 than clonidine
- SEs are milder and less frequent
- less rebound HTN: less severe may be due to longer half-life
- ER tabs (Intuniv) approved for ADHD tx (must be 17 YOA)
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methyldopa
- Brand Name: Aldomet
- prodrug for alpha-mehtylnorepinephrine (AMN)
- decrease NE release & interferes with its action
- AMN functions as centrally-acting alpha-2 AR agonist and false transmitter: AMN taken up & stored in pre-syn vesicle; AMN released after depolarization (agonist on pre-syn alpha-2 and weak agonist at post-syn alpha-1)
- preferred HTN tx during pregnancy b/c effective and safe for mother and fetus
- SE: liver dysfunction and positive Coombs test (reveresible condition developing antibdodies against RBCs --> hemolytic anemia)
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Ganglionic blockers
- Reserpine and Metyrosine
- Overall actions: decrease SNS on alpha-1 receptors --> vasodialation and venodilation --> decrease afterload and preload; ;decrease SNS on beta-1 --> decreases HR
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Reserpine
- MOA: tightly binds and eventually destroys catecholamine storage vesicles in AR neurons --> biogenic amines leaky ("leaky granules") into nerve terminal --> end up in cytoplasm of NT --> metabolized by MAO --> slowly depletes stores
- delyaed anti-hypertensive effect which takes days to weeks to significantly deplete stores (SLOW DEPLETION) of NE, 5HT, DA
- Post d/c: new vesicles (non-leaky) must be synthesized and supplied with new catecholamines
- SE: sedation, inability to concentrate/perform complex tasks, mental depression, ab cramps & diarrhea, increased gastric HCL leads to reactivation of aggravation of peptic ulcer, nasal congestion, flushing of the skin, sodium retention and edema,, erectile and ejactulatory dysfunction, decreased concentration of DA
- CI: mental depression
- Indications: HTN and pyschotic states
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metyrosine
- MOA: inhibits tyrosine hydroxylase at central & peripheral sites
- Indication: ONLY used for pheochromocytoma tx
- SE: crystalluria, orthostatic hypotension, sedation, severe diarrhea, anxiety, extrapyrimidal signs (EPS)
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NSAB
- phenoxybenzamine: irreversible antagonist
- phentolamine
- MOA: dilate blood vessels, venodialation prominent, stimulates peripheral beta-1 adrenoceptors
- SE: orthostatic hypotension via venodialation, reflex tachy, fluid retention, nasal congestion, ejaculatory disorders
- Used: chronic tx of hypertension; tx short term symptoms of pheochromoctyoma
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alpha-1 selective antagonists
- prazosin
- terazosin
- doxazosin
- alfuzosin
- tamulosin
- BPH tx: alfuzosin & tamulosin
- HTN tx: prazosin, terazosin, doxazosin
- QD dosing: terazosin, doxazosin
- MOA: competitive blockade of alpha-1 AR aterioles & veins; decreases TG & LDL, increase HDL
- SE: orthostasis, fluid retention, drowsiness, HA, impotence, decreased resistance to urinary outflow minimal reflex tachy
- Uses: HTN, BPH, HF (not first line)
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BBs
- MOA: block the effects of NE at beta ARs --> decrease CO, HR, ionotropy, inhibits renin secretion, intereferes with SNS outflow
- DI: calcium channel blockers, NSAIDS (Sulindac is ok)
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Propanolol
- prototype BB
- most versatile
- non-selective
- Indications: migraine prophylaxis, post-MI, pheochromoctyoma
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esmolol
- beta-1 antagonist
- IV administration only
- half-life = 8 min
- used in acute situation when you need rapid and short term effects
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sotalol
- beta-1 & 2 antagonist
- anti-arrythmic action in addition to BB activity
- slows conduction at the nodes and conducting branches; helps control surpraventricular tachy
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carvedilol
- blocks beta-1 &2, alpha-1 AR
- antioxidant and anti-proliferative effects (HF)
- beneficial in LVH, HF, and post-MI
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Cardioselective BBs
- (MEN-ABBA)
- metoprolol (Lopressor, Toprol XL)
- esmolol (Breviblock)
- nebivolol
- acetbutolol
- betaxolol
- bisoprolol
- atenolol (Tenormin)
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Non-selective BBs
- cartelol
- carvedilol (Coreg)
- labetalol (Trandate)
- nadolol
- penbutolol
- pindolol
- propanolol (Inderal)
- sotalol
- timolol
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BB agents with vasodialating activity
- Vasodialation secondary to alpha-1 blocking (alpha and beta) --> labetalol, carvedilol
- vasodialation secondary to activation of vascular NO synthase (NOS) --> nebivolol
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BB agents with intrinsic sympathomimetic activity (ISA)
- partial agonists to stimulate beta ARs
- Agents: acebutolol, cartelol, penbutolol, pindolol
-
BBs SE
- impaired exercise tolerance: decrease CO, muscle perfusion --> muscle and physical fatigue
- CV effects: bradycardia, hypotension, syncope, cold peripheries, physical fatigue
- CNS: sedation, mental depression, sleep disturbances
- GI: N/V/D, constipation, ab cramps
- Respiratory: bronchoconstriction
- GU: impotence/decreased libido
- metabolic: increase VLDL and TG, decrease HDL
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BB Tx for hypertension
all BB's except esmolol and sotalol
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Angina pectoris BB tx
atenolol, metoprolol, nadolol, propanolol
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BB tx for migraine prophylaxis
propanolol and timolol
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post-MI BB tx
atenolol, carvdeilol, metoprolol, propanolol, timolol
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HF w/ BB
- start low and titrate up slowly
- bisoprolol, carvedilol, metoporolol succinate
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open angle glaucoma
betaxolol, carteolol, timolol, levobunolol, metipranolol
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General Contraindications for BB
- specific stages of HF
- cardiogenic shock
- persistently severe bradycardia
- heart block
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Warning and Precautions of BBs
- abrupt withdrawl
- diabetes and hypoglycemia
- CNS effects
- pulmonary effects
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