ADRENERGIC ALPHA-1 RECEPTOR ANTAGONIST

Adrenoceptor antagonist drugs

Binds to adrenoceptors but DO NOT trigger the usual receptor-mediated intracellular effects

Alpha adrenoreceptor antagonist

Synonym of Alpha blocker

Reversible

Irreversible

Division of Alpha blocker

Reversible

This is can dissociate from receptors and can surmountable

Irreversible

This cannot be dissociate from the receptor and cannot be surmountable

Vasodilation = low Pulmonary vascular resistance causing Postural hypotension lowering the blood pressure

Effect of alpha-1 receptor antagonist in BV

At night

When do you usually take an alpha-1 receptor?

Miosis

Nasal stuffiness

Urination

Other effect of Alpha-1 receptor in

Eyes:

Nasal cavity:

Base of bladder:

IRREVERSIBLE: PHENOXYBENZAMINE

REVERSIBLE: PHENTOLAMINE, TOLAZOLINE

Non-selective alpha blocker

Prazosin

Terazosin

Doxazosin

Tamsulosin

Alfuzosin

Silodosin

Indoramin

Urapidil

Selective a-1

YOHIMBINE, RAUWOLSCINE

Selective a-2

Alpha blocker → Vasodilation → (for long standing) → Orthostatic hypotension causing a decrease BP and dizziness → Compensatory (or the mechanism to maintain the balance) → Increase pulse rate causing a reflex tachycardia

Explain the full mechanism of a alpha-1 receptor antagonist

1. Phentolamine

2. Tolazoline

3. Ergot derivatives— eg, ergotamine, dihydroergotamine

Reversible alpha blockers

Phentolamine

This is used for pheochromocytoma and for male erectile dysfunction (intracavernosally & orally) given with papaverine

fibrotic reactions

ADR in long term administration of phentolamine with papaverine

orthostatic hypotension

Sytemic absorption effect of phentolamine with papaverine

Pheochromocytoma

a rare, usually noncancerous (benign) tumor that develops in an adrenal gland. Usually, this type of tumor affects one of your two adrenal glands, but it can affect both.

episodic or persistent high blood pressure

If you have a pheochromocytoma, the tumor releases hormones that cause either _____.

pheochromocytoma

Untreated, a ____ can result in severe or life-threatening damage to other body systems, especially the cardiovascular system.

Phentolamine

Imidazole derivative

tachycardia, arrhythmias, myocardial ischemia

ADR of phentolamine in IV administration

tachycardia, nasal congestion, headache

ADR of phentolamine in oral administration

Tolazoline

For in the treatment of pulmonary hypertension in newborn infants with respiratory distress syndrome

Phenoxybenzamine

binds covalently to alpha receptors

14-48 hrs or longer

Duration of action of Phenoxybenzamine

Phenoxybenzamine

Use in Pheochromocytoma and relieve vasospasm in Raynaud’s syndrome

Raynaud’s syndrome

This is an excessive reduction in blood flow

Blocks alpha receptor causing dilation

Inhibits the reuptake of released norepi

Block histamine, Ach, and Serotonin receptor

MOA of phenoxybenzene

Postural hypotension

Nasal stuffiness

Nausea

Vomiting

ADR of phenozybenzine

Selective alpha-1 blocker

Management of hypertension and urinary retention in BPH patients

■ Symptomatic relief or urinary retention

3 hrs

Half life of Prazosin

9-12 hours

Half life of Terazosin

22 hours

Half life of Doxazosin

9-15 hours

Half life of Tamsulosin

Doxazosin

Longest half life in selective alpha-1 blocker

Tamsulosin

Potent action of a-1 and less effec ton BP

Tamsulosin

increase IFIS (intraoperative floppy iris syndrome) for patients undergoing cataract surgery

QT prolongation

Risk of Alfuzosin

Iris billowing

Progressive intraoperative miosis

Iris prolapse

Intraoperative floppy iris syndrome triad of symptomps

first dose phenomenon “SYNCOPE”

Orthostatic hypotension

ADR of Alfuzosin

Adjust the dose to 1/3 or ¼ of normal dose

What to do in a syncope phenomenon

Chlorpromazine

Haloperidol

NEUROLEPTIC DRUGS

Trazodone

ANTIDEPRESSANT

Yohimbine

Tx of orthostatic hypotension and treats male erectile dysfunction (PDE-5 inhibition)

Yohimbine

In veterinary medicine: use to reverse anesthesia produced by xylazine (a2 agonist-used calm animals

Yohimbine

Available as “nutritional” supplement

Beta blocker

Suffixes with “-olol” and used for tx of hypertension

Propranolol

Carteolol

Nadolol

Penbutolol

Pindolol

Sotalol

Timolol

NON-SELECTIVE Beta blocker

Propanolol

Prototype in non selective beta blocker

↓ CO, (-) inotropic and chronotropic effects

O2 consumption is decrease – used in ANGINA

Action of Propanolol in Cardiovascular

CO leads to ↓ BP

Hypotension triggers a reflex peripheral vasoconstriction

Action of peripheral vasoconstriction of propanolol

Due to blockade of Beta 2 receptors

Can ppt respiratory crisis in patients with COPD or asthma

Action in Bronchoconstriction of Propanolol

Beta blockade ---- ↓ glycogenolysis and ↓ glucagon secretion

Action of propanolol in Disturbance in glucose metabolism

Isoproterenol

Propanolol also blocks?

Prophylaxis for angina pectoris, supraventricular and ventricular dysrhythmias

Antihypertensive

Negative chronotropic agent in anxiety for stage frigth

For myocardia infarction

Migraine headache

Hyperthyrodism

For chronic glaucoma

Uses of propanolol

Anti-hypertensive

Low CO and a negative inotropic agent in hypertrophic obstructive cardiomyopathy

Beta blockers have a protective effect on the myocardium

↓ infarct size and hastens recovery

MOA: to ↓ the O2 demand in already ischemic heart muscle by blocking the actions of circulating catecholamines

Action of propanolol to myocardial infaction MOA

↓ incidence and severity of attacks

Blocks the catecholamine – induced vasodilation in the brain vasculature

MOA of propanolol for migraine headache

Hyperthyrodism

Inhibits the conversion of T4 to T3 that is used by propanolol too

Pilocaine

In chronic glaucoma, in actue attach administer?

↓ IOP by ↓ the secretion of aqueous humor by the ciliary body

Only used to treat this disease chronically

MOA of the chronic glaucoma

Bronchoconstriction

Arrhythmias

• Mgt: Tapered the dose gradually for 1 week

Sexual impairment

Disturbances in metabolism

Monitor patients taking insulin (HYPOGLYCEMIA)

Beta blockers elevate levels of triglycerides and LDL

ADR of Propanolol

Nadolol (Corgard)

This beta blocker is with long duration of action t1/2 of 24 hours

Esmolol

Ultra short acting beta blocker t1/2 of 10mins.

Bisoprolol

Acebutolol

Esmolol

Metoprolol

Atenolol

Celiprolol

Nebivolol

B1-selective blocker

Nebilol

Most highly selective beta1 blocker

Pindolol (Visken©)

Acebutolol (Sectral©)

Labetalol (Trandate©)

What beta blocker is with ISA (Intrinsic sympathomimetic activity) partial agonists effect

less associated with rebound hypertension or tachycardia upon withdrawal.

Pindolol (Visken©)

Acebutolol (Sectral©)

Labetalol (Trandate©)

What is their advantages?

Pindolol

Propranolol

Acebutolol

Metoprolol

Labetalol

What beta blocker is with MSA (MEMBRANE STABILIZING ACTIVITY) or relaxed effect?

cannot be given as ocular topical agents.

Disadvatages of a beta blocker that can cause anesthetic effect

Labetalol (Trandate)
Carvedilol (Coreg)

Mixed alpha and beta blockers

Labetalol (Trandate)

alternative to hydralazine in treatment of pregnancy-induced hypertension (PIH).

Timolol

Levobunolol

Non selective beta blocker used for glaucoma

Betaxolol

Selective beta-1 blocker used for glaucoma

Carteolol

Partial agonist beta blocker used for glaucoma

Metipranolol

Other beta blocker used for glaucoma

Guanethidine

Guanadrel

Bethanidine

Debrisoquin

Adrenergic neuron-blocker agents

Guanethidine

lower blood pressure by preventing normal physiologic release of norepinephrine from postganglionic sympathetic neurons. and it is with local anesthetic activity

Guanethidine

For the use of severe hypertension

↓ CO due to bradycardia and relaxation of capacitance vessels.

With long-term therapy: ↓ PVR

Cause of guanethidine in the course of theraphy

Sodium and water retention

Compensatory effect of guanethidine

no CNS effect

Guanethidine is polar causing?

5 days

Half life of Guanethidine

Guanethidine

onset of sympathoplegia is gradual (maximal effect in 1–2 weeks)

Guanethidine

DO NOT increase the dose at intervals shorter than 2 weeks

postural hypotension, diarrhea (PS), and impaired ejaculation (S)

Toxicities of guanethidine

Reserpine

Plant alkaloid

Reserpine

Drug affecting storage of catecholamines

Reserpine

Used for treating mild to moderate hypertension

blocks the uptake and the storage of biogenic amines

MOA of reserpine

↓CO ↓PVR causing hypotension

The cardiac output and pulmonary vascular resistance in the reserpine