Beta blockers Flashcards
What differentiates 3rd gen B blockers?
They have vasodilatory properties: alpha block or NO release.
They can be either non-selective or B1-selective.
Example of lipophilic BB?
propanolol, penbutolol
Example of hydrophilic BB?
atenolol, nadolol
Which BB has an uncharacteristic short duration and fast onset?
esmolol
Which enzyme’s genotype is a major determinant in interindividual differences of metabolism?
CYP2D6
General effects of SHORT-TERM use of BBs on CVS:
Decreased CO (B1 block) Increased PVR (B2 block = A1 vasoconstriction is unopposed)
BBs Anti-HTN properties can be explained by:
1) Sustained use results in decreased TPR in HTN patients
2) B1 block –> decreased renin secretion from JG cells (PINDOLOL does not affect)
3) Vasodilatory properties of some BBs
This effect or property of some BBs involves the inhibition or total abolition of action potential from being propagated across the membrane via SODIUM CHANNEL BLOCK.
What is the physiological basis behind treatment with these drugs?
Which drugs exhibit this pharmacological effect?
Membrane Stabilizing Activity. Decreased sinus rhythm, conduction –> generalized suppression of myocardial function.
PALOCA: Propranolol Alprenolol Labetalol Oxprenolol Carvedilol Acebutolol
Advantages of sodium channel blockade include:
prophylaxis to prevent recurrent MI and sudden death
limits size of infarct
reduce mortality
Disadvantages of sodium channel blockade
latent heart failure to overt heart failure
Cardioselective BB blockers block which receptor?
B1
Cardioselective BBs include the following drugs:
CABNAME: Celiprolol Acebutolol Betaxolol Nebivolol Atenolol Metoproplol Esmolol
Cardioselective BBs are preferred in patients with:
Bronchospasm/asthma/COPD
DM
Raynaud’s
(because B2 is not blocked…B2 blockage results in vasoconstriction and bronchoconstriction)
Beta blockers with partial agonist properties are said to exhibit:
Intrinsic sympathomimetic activity (ISA).
The structural specificity of the drugs allowing competitive binding to the receptor (antagonist activity) and partial interaction at the receptor’s activation site (agonist activity).
BBs with partial agonistic activity include:
APOCAP Alprenolol Pindolol Oxprenolol Carteolol Acebutolol Penbutolol
Respiratory effect from BB
Nonselectives cause bronchoconstriction
Selective B1 and those with ISA at B2 are less likely to cause this.
Metabolic effects from BB
Hypoglycemia
FFA release
BBs effects on eyes
Decrease aqueous humor production
Non-selective beta blocker used in CHF, Thyroid storm. High Vd, enters CND readily, low oral bioavailability due to extensive first-pass metabolism.
Propranolol
Non-selective BB with no ISA or MSA activity. Does not cross BBB. Used in HTN, agina; off-labeled in migraine prophylaxis, parkinsonian tremors, variceal bleeding in portal HTN.
Nadolol
Non-selective BB used in HTN, CHF, acute MI and OPEN-ANGLE GLAUCOMA (fewer side-effects than anti-cholinesterase or muscarics)
Timolol
Non-selective BB with ISA, low MSA. Used in HTN, angina. Blocks exercise-induced increase in HR and CO.
Pindolol
B1 blocker with MSA but no ISA.
Used in HTN, angina, tachycardia, heart failure, hyperthyroidism, migraine prophylaxis.
Metoprolol
B1 blocker with (-) ISA, (-) MSA. Water soluble, longer half life than metoprolol.
Atenolol
Ultra-short duration B1 blocker. Little ISA, (-) MSA. Used in critically ill, controlling supraventricular arrhythmias, thyrotoxicosis arrhythmias, perioperative HTN.
Esmolol
A1 and non-selective B blocker. Partial agonist at B2. Used in pregnancy HTN.
Cocaine-like effect.
Labetalol
A1 and non-selective B blocker.
Vasodilator, antioxidant, antiproliferative.
Carvedilol
Very popular for use in CHF
3rd gen: A1 and non-selective B blocker. Partial B2 and B3 agonist. Reduces afterload. Increase plasma HDL.
Bucindolol
BB Treatment of arrhythmias:
Esmolol
BB Treatment of MI:
1) long-term use of timolol, propanolol, or metoprolol improve survival
2) esmolol, B blockers with MSA, carvedilol
BB Migraine prophylaxis:
Propanolol (high lipid solubility)
Less extent: metoprolol
Also: atenolol, timolol, nadolol
BB Treatment of thyrotoxicosis:
Propanolol and other B blockers
BB Treatment of pheochromocytoma:
A blocker then B blocker
BB (wide angle) Glaucoma
Timolol
4 BBs with vasodilatory properties
Carvedilol
Labetalol
Celiprolol
Nebivolol
Which BB is most likely to cause lethargy, mental depression, hallucinations?
propanolol
Most lipid solubility so it can cross BBB readily.
Adverse metabolic effects of BBs
Increased triglycerides (except ISA)
impaired insulin release
impaired hepatic gluconeogenesis
