B-1 (cardio-selectivity), partial agonist, membrane stabilizing, mostly low lipid soluble

Metaprolol - not partial agonist, medium lipid solubility

B-blockers act as competitive agonists @ B-1 rec.

- reversibly occupy sites where B-agonists (NE) would normally bind

-usually NONSELECTIVE B-blockers

-CARDIOSELECTIVE: B-1 rec. antagonized

-@ High doses, B-1 antag can inhibit B-2 also

-Some are partial agonists: partially activate B-rec and competitively antag. full B-rec agonists

-Net effect: preserve @ least small amount of B-rec function

-also called ISA: Intrinsic Sympathomimetic/Sympathetic Activity 

-Some can stabilize cell membranes ("local anesthetic"), usually only seen @ high concen., so it's more important as a side effect

- Lipid Solubility varies (L, M, H) - the more lipid soluble, the more likely it will enter the brain (CNS) and be cleared by the liver. if not then excreted thru kidneys. EXCEPT ESMOLOL.

- Dec HR, contractility, automaticity, conduction velocity

- Dec myocardial O₂ deficit that causes angina. Antianginal use.

-Dec Cardiac Output, which lowers arterial pressure in hypertensive patients also dec in renin secretion in kidney JG cells

-Prevent post M.I.-arrythmias by slowing conduc v. Prevent supraventricular tachycardias and arrythmias from getting thru ventricles

- Protect the heart from catechol-induced tachycardias/arrythmias during 

1. surgical removal of pheochromocytoma

2. thyroid storm in hypothyroidism

- Not always clear

- In ciliary epithelium (eye), used to topically treat glaucoma, reduced intraocular P (Timolol)

- Timolol has no membrane stabilizing (local anesthetic) action (desired bc you don't want a numb eye)

B-Blockers with ISA can be used same as those without ISA.

-Partial activity ensures that at least some level of B-rec function is working. Net inhibiting effect of those w/ISA not as intense as w/o ISA

- Unlike non-selec B blockers w/o ISA, those w/ISA (pindolol) do not interfere with B2 vaso-relaxation in skel musc. In fact they enhance relaxation to dec total periph arter resist. Therefore good for treating hypertension

- Lipid sol means more likely to enter brain (CNS), leads to ANTIHYPERTENSIVE mechanisms

-B blockers w/more lipid sol are more likely to be inactivated by LIVER so patient must have good liver function and those with less lipid sol need good renal function bc less lipid sol = more likely to be inactivated by renal excretion

- Esmolol is Exception. Rapid inactivation by plasma and blood cell Esterases. (short duration) for acute conditions

-Nadolol (long duration) for chronic conditions

-Both used for supraventricular arrythmia, perioperative hypertension, myocardial ischemia

1. Migraine

2. Stage fright

3. Mechanisms not well understood.

- Excessive depression of myocardial B1 receptor functions

--> bradycardia, dec cardiac output, may aggravate Raynaud's and intermittent claudication, cause exercise intolerance

- Masks tachycardia: removes warning sign of severe hypoglycemic rxn to insulin (tachycard)

- Rebound hypertension/angina- with sudden withdrawal of drug use

1. Bronchoconstriction in asthmatics (inhibits brochorelaxation)

2. More intermittent claudication and exercise intolerance (inhibit vasorelaxation of skeletal musc)

3. Delayed recovery from insulin induced hypoglycemic episodes (bc dec glucose output from liver)

- Combination non-selective B-blocker AND selective a-1 blocker, treat moderate to severe hypertension.

- arterial P falls from dec peripheral arterial resistance by a-blockers; b-blockers dec cardiac output and renin secretion

- Side effects: a: orthostatic HYPOtension, B: bronchoconstriction

- Much less aggravation to Raynaud's so good for them