Rest and Digest

Pharmacologic arithmetic: if you administer noradrenaline + phentolamine which receptor would be stimulated

a/ Beta 2 b/ Beta 1 c/alpha 2 d/ alpha 1

CVS Effects of Alpha 1 Antagonists

block vasoconstriction

fall in TPR leads to a fall in mean BP

a reflex tachycardia.

Prazosin
prototype potent and very selective alpha 1 receptor antagonists.
short acting /7 to 10 hours/

decrease in TPR

Terazosin Intermediate duration of action, / 18 hours/ Doxazosin long duration of action, ie 36 hours.

Adverse effects: "first dose phenomenon".

That is marked postural hypotension and fainting 30-90 minutes after the first dose

Therapeutic Uses of Alpha Adrenergic Receptor Blockers

1/Pheochromocytoma

a tumor of the adrenal medulla or sympathetic ganglion cells.

The tumor secretes catecholamines, especially NE and epinephrine. intermittent or sustained hypertension, headaches, palpitations, and increased sweating. useful in the preoperative management of patients with pheochromocytoma

2/Hypertension 3/ treatment of peripheral vasospastic disease ie Raynauds disease to improve perfusion

4/ Treatment of local excess concentration of a vasoconstrictor in order to prevent necrosis.

5/ Urinary Obstruction: BPH common in elderly men: weak stream, urinary

frequency, and nocturia.

surgical treatments drug therapy : Prazosin, doxazosin, terazosin tamsulosin/Alpha1A/

improving urine flow partial reversal of smooth muscle contraction in the enlarged prostate and in the bladder base.

Alpha blockers; Adverse effects

Postural hypotension Tachycardia Sedation Nasal stuffiness Miosis inhibits ejaculation

Ergot Alkaloids
Action Alpha blocking Direct vasoconstriction Oxytocic action Ergotamine + potent Ergometrine Slight

Slight delayed

Potent, rapid, short DOA PPH

CNS action use

++ CTZ migraine

Side effects /Ergot Alkaloids

Nausea and vomiting Tingling and numbness of toes and fingers Gangrine Abortion Angina pectoris

Pharmacological Actions Beta Blockers

1. CVS: 13 a. Heart (1): myocardial contraction HR AV-conduction & automaticity b. BV to Sk. Muscle (2): Vasoconstriction, muscle pain & fatigue ( with non- selective)

c. JG cells (1): renin release, aldosterone , angiotensin : Na & water retention,

 EYE: IOP CNS/Neurological: Sedation ( propranolol, carvedilol)

Respiratory: Broncho-constriction, Metabolic: gluconeogenesis glycogenolysis and lipolysis

Clinical applications
a. Hypertension:

b.

Chronic HF: bisoprolol,

metoprolol, carvedilol

C. Glaucoma: (timolol)

diminish IOP in glaucoma by decreasing the secretion of aqueous

humor by the ciliary body.

d. Hyperthyroidism: blunting the widespread sympathetic stimulation that occurs in hyperthyroidism

Beta-Blockers -Therapeutic Uses

Ischemic heart disease Neurologic diseases:

Arrhythmias

-Migraine prophylaxis: blockade of catecholamine-induced vasodilation in the brain vasculature

-tremor -performance Anxiety / stage fright/ -alcohol withdrawal

Beta-Blockers - Adverse Effects B1 blockade /cardiac/: heart failure; heart block -bradycardia; hypotension -bradyarrhythmias B2 blocked :Bronchocostriction; muscle fatigue -PVD -decreased blood flow to vital organ-Liver

 Metabolic: - Increase hypoglycemic effect of insulin(IDDM) - Increase triglycerides - Decrease HDL CNS; depression, nightmares Sudden withdrawal : angina pectoris ,sudden death - tapering the dose of the B- blocker for several weeks before discontinuation.

Rest and Digest

The diastolic BP is decreased if adrenalin is given a/in a large dose b/after phentolamine c/after atropine d/after proranolol

Rest and Digest

The graphs depict the changes in BP caused by the IV administration of epinephrine before and after an unknown Drug X.
Which of the following drugs is most likely Drug X? A. Atropine. B. Phenylephrine. C. Physostigmine. D. Prazosin. E. Propranolol.

 A 38-yo male has recently started monotherapy for mild hypertension. At his most recent office visit, he complains of tiredness and not being able to complete three sets of tennis. Which one of the following drugs is he most likely to be taking for hypertension? A. Albuterol. B. Atenolol. C. Ephedrine. D. Phentolamine. E. Prazosin.

 A 60-Yo asthmatic man comes in for a checkup and complains that he is having some difficulty in starting to urinate. PE indicates that the man has a BPof 160/100 mm Hg and a slightly enlarged prostate. Which of the following medications would be useful in treating both of these conditions?
A. Doxazosin. B. Labetalol. C. Phentolamine. D. Propranolol. E. Isoproterenol.