1. 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
  2. clonidine
    • Brand Name: Catapres
    • more severe SE (xerostomia, sedation, rebound HTN)
    • strucutally it's an imidazoline
  3. 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
  4. 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)
  5. 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)
  6. 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
  7. 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
  8. 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)
  9. 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
  10. 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)
  11. 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)
  12. Propanolol
    • prototype BB
    • most versatile
    • non-selective
    • Indications: migraine prophylaxis, post-MI, pheochromoctyoma
  13. esmolol
    • beta-1 antagonist
    • IV administration only
    • half-life = 8 min
    • used in acute situation when you need rapid and short term effects
  14. 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
  15. carvedilol
    • blocks beta-1 &2, alpha-1 AR
    • antioxidant and anti-proliferative effects (HF)
    • beneficial in LVH, HF, and post-MI
  16. Cardioselective BBs
    • (MEN-ABBA)
    • metoprolol (Lopressor, Toprol XL)
    • esmolol (Breviblock)
    • nebivolol
    • acetbutolol
    • betaxolol
    • bisoprolol
    • atenolol (Tenormin)
  17. Non-selective BBs
    • cartelol
    • carvedilol (Coreg)
    • labetalol (Trandate)
    • nadolol
    • penbutolol
    • pindolol
    • propanolol (Inderal)
    • sotalol
    • timolol
  18. 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
  19. BB agents with intrinsic sympathomimetic activity (ISA)
    • partial agonists to stimulate beta ARs
    • Agents: acebutolol, cartelol, penbutolol, pindolol
  20. 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
  21. BB Tx for hypertension
    all BB's except esmolol and sotalol
  22. Angina pectoris BB tx
    atenolol, metoprolol, nadolol, propanolol
  23. BB tx for migraine prophylaxis
    propanolol and timolol
  24. post-MI BB tx
    atenolol, carvdeilol, metoprolol, propanolol, timolol
  25. HF w/ BB
    • start low and titrate up slowly
    • bisoprolol, carvedilol, metoporolol succinate
  26. open angle glaucoma
    betaxolol, carteolol, timolol, levobunolol, metipranolol
  27. General Contraindications for BB
    • specific stages of HF
    • cardiogenic shock
    • persistently severe bradycardia
    • heart block
  28. Warning and Precautions of BBs
    • abrupt withdrawl
    • diabetes and hypoglycemia
    • CNS effects
    • pulmonary effects
Card Set
Cardio Exam #2