PART 1 : BETA SYMPATHOPLEGICS

Centrally acting alpha-2 agonist

Beta blockers

Alpha blockers

Adrenergic neuron blocking agents

Storage inhibitors

Release inhibitors

Ganglionic blockers

-These are drugs that affect the sympathetic / adrenergic nervous system:

Beta

Alpha

Adrenergic receptor anatagonsi types

Nonselective

Alpha-1

Alpha-2

Alpha receptor antagonist types

Phenoxybenzamine

Phentolamine

Alpha antagonist non selective drugs

(ZOSIN)

Prazosin

Terazosin

Doxazosin

Alfuzosin

Indoramin

Urapidil

Bunazosin

Alpha-1 selective receptor antagonist

Yohimbine

Alpha-2 Selective antagonist

Non selective (1st generation)

Beta-1 selective (2nd generation)

Non selective (3rd generation)

Beta-1 selective (3rd generation)

Beta receptor antagonist types

Nadolol

Penbutolol

Pindolol

Propranolol

Timolol

Beta Nonselective (1st generation) antagonist

Acebutolol

Atenolol

Bisoprolol

Esmolol

Metoprolol

Beta-1 selective (Second Generation) antagonist

Carteolol

Carvedilol (also blocks A1 receptors)

Bucindolol

Labetalol (also blocks A1 receptors)

Beta Nonselective (Third Generation) antagonist

Betaxolol

Celiprolol

Nebivolo

B1 selective (Third Generation) antagonsit

Type 2

G protein linked

Metabotropic

Beta-1 is classified under ____ receptors

• ____ receptors: ____ receptors

Gs protein

Beta-1 is a coupled to?

adenylyl cyclase

CAMP

2nd messenge

Cyclic adenosine monophosphate

protein kinase A

calcium channels

In beta 1

Gs proteins stimulate the ____and increase____ levels (____r= ____) → activate ___ → opening of____

Entry of calcium into the cells (cytoplasmic reticulum) cause contractions (Heart contractions→ inc cardiac output → B1 activation → inc blood pressure)

Explain what happend when the calcium now enters the cytoplasmic reticulum for beta 1 blockers

block Beta receptors thereby blocking heart contractions

Beta blocker Mechanism of Action

1. inhibition of prejunctional beta receptors on the terminal neurons.

2. KIDNEY: Inhibition of renin-angiotensin system

3. Decreased Central Sympathetic outflow

Anti Hypertensive Effect of beta -1 blocker

• (-) Inotropic (results to dec. Cardiac Cycle dec. SV dec. CO dec. BP)

• (-) Chronotropic (dec. HR dec. CO dec. BP)

• (-) Dromotropic (Due to dec conduction velocity)

• Can inhibit RENIN release in the kidney that can result in vasodilation.

Effects of beta-1 blockers

• Decrease heart rate

• Decrease contractility

• Decreased conduction

Effects (Third Generation Beta Blockers) in the heart

Vasodilation

• a1-adrenergic receptor blockage

• Increased NO bioavailability

Effects (Third Generation Beta Blockers) in the Blood Vessels

Decreased renin release from renal juxtaglomerular cells

Decreased RAAS

Effects (Third Generation Beta Blockers) in the Kidneys

Decreased blood pressure

Decreased myocardial oxygen demand

Decreased water and salt retention

Decreased oxidative and inflammatory stress

Attenuated cardiovascular remodeling

Effects (Third Generation Beta Blockers) in the Cardiovascular beneficial effects

Hypotension and bradycardia (decrease BP and HR)

Pharmacological effect of beta-1 blockers in cardiovascular

Respiratory depression and apnea

Non Selective b blockers can also block b2 receptors in the lungs → difficulty in breathing

Pharmacological effect of beta-1 blockers in Pulmonary

Delirium, coma, and seizures

Pharmacological effect of beta-1 blockers in CNS

Hypoglycemia

Pharmacological effect of beta-1 blockers in Metabolic

Because these drugs block glycogenolysis and gluconeogenesis in the liver decreasing blood sugar

B receptors in the liver activate to produce glucose through the process of gluconeogenesis. glycogenolysis = break glycogen to form glucose → low sugar levels

Why do Beta blockers cause hypoglycemia?

Beta blockers prevent reflex tachycardia that often results from treatment with direct vasodilators

Pharmacological effect of beta-1 blockers in severe hypertension

Selective

Non-selective

ISA (Intrinsic sympathomimetic activity)

MSE (Membrane stabilizing effect) - local anesthetcci property

Classification of Beta blockers

Propanolol (Inderal)

Prototype β blocking drug (possesses all characteristics of the group)

Propanolol (Inderal)

Antagonizes catecholamine action at both β 1 and β2 receptors thus reducing heart rate and contractility

Propanolol (Inderal)

This drug decreases renin release and undergoes extensive first pass metabolism resulting in low and dose dependent bioavailability

Nonselective

What classification is Propanolol (Inderal) ?

Useful in mild to moderate hypertension

Angina pectoris (decrease heart contraction = decrease oxygen demand)

Arrhythmia (SVT)

Migraine (paradoxical effect)

Familial tremor, ‘stage fright’ (10mg)

• because it manages palpitations and tachycardia

Thyroid storm, thyrotoxicosis, hyperthyroidism

Inhibit conversion of T4 to T3

• T3 is more potent than T4. high levels there of causes palpitation & tachycardia

Uses of propanolol (inderal)

withdrawal syndrome

rebound hypertension

PROPRANOLOL can cause _____

• abrupt withdrawal causes ______

It may cause nervousness, tachycardia, increased intensity of angina, or increase in blood pressure

Propanolol can in cause what symptoms due to withdrawal syndrome that results from abrupt discontinuation of this drug

ISA Intrinsic sympathomimetic activity

All beta blockers cause this withdrawal side effect except those that are classified as____

Tapering the dose for 10-14 days is needed prior to discontinuation.

What is the tapered dose needed for propanolol?

Metoprolol (Lopressor/Neobloc)

Relatively cardio selective

Metoprolol (Lopressor/Neobloc)

It blocks more the β 1 receptors than β 2 receptors

Metoprolol (Lopressor/Neobloc)

Advantageous in treating hypertension in patients with asthma, diabetes and peripheral vascular disease

Metoprolol (Lopressor/Neobloc)

Also used in the management of Stable Heart Failure. (when caused by sympathetic activation)

Unstable Heart Failure

Beta blockers are contraindicated in_____

bisoprolol and carvedilol

_____ are usually used for heart failure.

Nadolol, Timolol, Carteolol, Pindolol, Penbutolol

These agents are similar to propranolol in such a way that they block both β 1 receptors and β 2 receptors.

NADALOL

Beta-1 blocker ____ has an extended duration of action

Carteolol, Celiprolol, Labetalol, Acebutolol, Pindolol, Penbutolol

Beta blocker with ISA/intrinsic sympathomimetic activity or partial agonist effect. (can act as agonist or antagonist)

Carteolol, Celiprolol, Labetalol, Acebutolol, Pindolol, Penbutolol

does not cause rebound htn even upon abrupt withdrawal

Carteolol, Celiprolol, Labetalol, Acebutolol, Pindolol, Penbutolol

good for patients with bradyarrhythmia and peripheral vascular disease

Atenolol (Tenormin)

This beta blocker that oral route is available

Atenolol (Tenormin)

Produces fewer central nervous system related effects

Atenolol (Tenormin)

The drug is excreted largely unchanged in the urine ; thus,it can accumulate in patient with renal failure , and dosage should be reduced when creatinine clearance is <35 ml/min.

<35 ml/min

Atenolol should be reduced when the creatine clearance is?

not extensively metabolized

6 hours;

once daily

Atenolol is _____ and is excreted primarily in the urine with a half life of ____ it is usually dosed ____.

Betaxolol (Kerlone) and Bisoprolol (Zebeta)

Are primarily metabolized in the liver but have long half lives.

Once daily

Betaxolol (Kerlone) and Bisoprolol (Zebeta) is administered only?

RBC esterases

short

9 mins

Esmolol is rapidly metabolized by____; hence, It has a ___ half life (___)

0.5 1 mg/kg, followed by a constant infusion

Esmolol loading dose

Esmolol

Administered by constant IV infusion

Esmolol

Used for management of intraoperative and postoperative hypertension, and when hypertension is associated with tachycardia.

Atenolol

Which is preferred for out patients

Because non selective beta blockers block beta 2 receptors in the lungs that causes bronchoconstriction and could ecacerbate asthma or trigger attacks of asthma

Why non selective beta blockers are contraindicated in asthma?

Bronchospasm

Decreased exercise tolerance

Bradycardia

Heart Block

Dyslipidemia

Decreased sexual activity

ADR of esmolol

Anaphylaxis

Bradycardia/ Heart block

Active bronchial asthma

Unstable Heart Failure

Diabetes mellitus

Concomitant administration of Non-DHP CCBs (which cause bradycardia)

Contraindication of esmolol

Labetalol (Normodyne) and Carvedilol (Coreg)

ALPHA + BETA BLOCKER

Labetalol (Normodyne) and Carvedilol (Coreg)

Administered as racemic mixture

Labetalol (Normodyne) and Carvedilol (Coreg)

Useful in treating hypertension of pheochromocytoma and hypertensive emergencies RELATED TO CLONIDINE WITHDRAWAL