Beta Blockers (Sweatman) Flashcards
Describe the location and physiological role of beta-adrenergic receptors in CV, vascular, and renal tissues.
B-1/2 receptors on the sinoatrial node accelerate the HR when activated.
B-1/2 receptors on the ectopic pacemakers of the heart accelerate HR when activated.
B-1/2 receptors increase contractility of the heart when activated.
B-2 receptors relax skeletal muscle vessels when activated by blocking entry of Ca2+ into the cell, inhibiting contraction –> increased perfusion of muscle (important to fight-flight)
Contrast the effect of a- and B- receptor blockade on EPI and NE-induced change in BP and HR.
-
Explain the adverse CV and non-CV effects of B-blocker treatment and the consequences to a pt treatment plan
Receptor specificity lost in overdose
Membrane stabilizing drugs depress myocardial contractility –> ventricular tachyarrhythmias
Lipid-solubility
Intrinsic sympathomimetic agents (ISAs) (partial agonists) may cause tachycardia and HTN
Sotalol –> K+ blockade –> tarsade de pointes and V-fib
3rd gen drugs with extended actions–> direct vasodilation –> hypotension in overdose
Underlying CV or pulm disease –> incr. risk of lethal outcome
Stimulation of B-1 receptors on juxtaglomerular cells has what effect?
What would B-blockers do to this effect?
Leads to the release of renin, which converts angiotensinogen to angiotensin I and angiotensin II, a potent vasoconstrictor agent.
B-blockers will block the release of renin, and thus the production of angiotensin II having a net effect of lowering BP.
What is intrinsic sympathomimetic activity?
this means that the drugs are actually weak partial agonists that will provide some cardio stimulation but prevent excessive stimulation via the endogenous neurotransmitters EPI and NE.
Utility is in pts who cannot tolerate the profound bradycardia or diminished cardiac contraction force (negative inotropy) that beta blockers can produce.
How do we remember the Beta-blockers that are B-1 selective?
Look at the spelling of the names AND exclude anything that does NOT end in “-olol”. Drugs A–>M are B-1 selective; those from N–>T are non-selective, except nebivolol. Those with an unusual spelling “-ilol” or “-alol” have extended actions in preventing alpha-mediated reflex vasoconstriction (3rd Gens).
What do B-blockers with membrane stabilizing activity do?
Used as antiarrhythmic agents by binding to and block fast Na+ channels that are essential to the initial depolarizing event in the cardiac cycle.
Name the membrane stabilizing (class II) B-blockers.
Propanolol, acebutolol, & carvedilol
How do the 3rd generation B-blockers, those with “extended actions”, prevent reflexive vasoconstriction reducing their clinical effectiveness?
Blockade of L-type voltage gated Ca2+ channels –> neg. inotropy (decreased contractile force, decreased BP)
Antioxidation preventing LDL oxidation, Lipid oxidation, Endothelial dysfunction, & Apoptosis.
What does Nebivolol do?
Nitric Oxide production
Antioxidant activity
BIG PICTURE: Decreased BP, Decreased endothelial damage
What do Carvedilol and Labetalol do?
Carvedilol: Alpha-1 antagonism
Ca2+ entry blockade
Antioxidant activity
Labetalol: Alpha-1 antagonism
BIG PICTURE: decreased contractile force, decreased endothelial damage, lower BPWhat does Betaxolol do?
Ca2+ entry blockade –> decreased contractile force, lower BP
How do B-antagonists help with atrial fibrillation and flutter associated arrhythmias?
By increasing the AV nodal refractory period, B-antagonists slow ventricular response rates in artial flutter and a-fib.
B-blockers are MOST effective in pt with high levels of this enzyme linked to hypertension:
Renin.
Because it’s effect is in part due to the depression of the renin-angiotensin-aldosterone system.
Why can’t you simply give B-agonists in the event of B-blocker overdose?
Receptors are blocked
