• mech.- block alpha one
• prototype- phenoxybenzamine
• duration of action 24 hrs (must syn. new receptor to recover alpha one effect)

• mech.- block alpha one and two receptors
  • alpha one block decrease bp
  • alpha two prevent feedback inh. by released NE, so more NE released onto beta one receptors, so greater tachycardia than with selective blockers
• prototype- phentolamine

• TPR fall
• baroR reflex leads to increase symp. outflow
• more NE released
• tachycardia

• prazosin for HTN
• pheonoxybenzamine and phenatolamine used (in combo with propanolol) for pheochromocytoma management
• phenoxybenzamine, prazosin, and terazosin have been used for BPH
  • relax smooth muscle in bladder, prostate capsule, and prostatic uretrha
  • improve urinary flow

• postural hypotension (alpha one blockade)
• reflex tachyardia (worse with nonselective alpha blockers)
• nasal stuffiness (alpha stimulation relieves nasal stuffiness)
• inhibit ejaculation

• when epi is released, in lower levels, it stimulates beta two receptors leading to a decrease in bp
• at higher levels, blood pressure increase due to stimulation of alpha one receptors
• however, if you give epi in the presence of an alpha blocker, you see a purely DEPRESSOR effect
  • THIS IS EPI REVERSAL

• we dont make selective beta two blockers, but the selectivity is not so great that we will not block beta two while attempting to block beta one
• even the most selective (100 fold)

• some beta blockers have partial agonist activity
• thes drugs partially activate beta receptor, but block full agonist NE
• ex: pindolol and acebutalol

• decrease HR (beta 1)
• decrease CO (more pronounced on exercise)
• decrease conduction velocity, myocardial oxygen demand, spontaneous rate of depol.

• reduction of bp via:
  • reduce plasma renin
  • reduce CO
  • reduce symp. tone via effects in CNS

Even though it could increase TPR slightly based on partial agonist property, its NET effect is reduction of bp

• no effect on plasma glucose in normal person
• does slow recovery from hypoglycemia in DM
  • less problem with beta 1 selectives
• increases triglycerides (VLDL)
• decrease HDL

• cardiac effects similar to nonselective
• decrease danger of resp. side effects

BUT IN HIGH DOSES, LOSES SELECTIVITY

Labetalol

Carvedilol

• beta:alpha one blocking ratio is 4:1
• used for:
  • accute managment of hypertensive crisis secondary to excessive catecholamines
  • used for chronic HTN

• used for:
  • HTN
  • CHF (reduce mortaity)
  • some antioxidant properties
• mech: beta to alpha one blocking ratio is 10:1

• HTN (usually with diuretics, vasodil.)
• cardiac arrhythmias
• angina
• prophylaxis of migraine
• early in MI (reduce symp. tone)
• prophylactic to decrease mortality after MI
• pheochromocytoma (w/alpha blocker)
• glaucoma
• HF (carvedilol)
• performance anxiety

• decreased CO, heart block, bradycardia (beta 1)
• bronchoconstriction (beta 2)
• CNS
  • depression
  • lethargy

• used as antihypertensive
• side effects
  • postural hypotension
  • impaired sexual function
  • diarrhea

All related to peripheral antiadrenergic infection

• used for HTN
• side effects
  • CNS- depression
  • peripheral- orthostatic hypotension

• in brain- block symp. outflow at pre and post synaptic sites
• act at presyn. alpha 2 in post ganglionic adrenergic neurons

• clonodine (work direct aly alpha 2 R)
• alpha methyl dopa (must be metabolized to alpha methyl NE)

• essential HTN
  • alpha methyldopa safe in pregnancy
• reduce side effects of opiod withdrawl (clonodine)
• open angle glaucoma (apraclonidine also decrease prod. of aqueous humor)
• ADHD (clonodine)

• dry mouth
• sedation
• HTN crisis upon withdrawl of clonodine
• alpha methyl dopa produce high incidence of autoimmune response (positive Coombs test)