AUTONOMIC NS DRUGS (2) Dr: Samah Gaafar Al-shaygi

ADRENERGIC AGONIST DIRECT ACTING ADRENERGIC AGONIST: 1. Epinepherine: Synthesized in the adrenal medulla. At low doses has β vasodilatation effect. At high doses has α vasoconstriction effect. Action: 1. CVS: β1 +ve inotropic & chronotropic effect, COP & O2 demand. 2. Renal: β1 Renin release, blood flow is decreased.

3. Blood vessels: α1 constrict arterioles to skin, mucous membranes & viscera. β 2 dilate vessels to liver & muscles. 4. Respiratory: β2 bronchodilataion. 5. Hyperglycemia: β2 increases glycogenolysis & glucagon secretion. α2 decrease release of insulin. 6. Lipolysis.

P.kinetics: Rapid onset & short duration of action. Metabolized by MAO & COMT into metanephrine & venillymandilic acid. i.m, i.v, s.c, inhalation & endotracheal.

Therapeutic uses: Emergency bronchospasm.choice Anaphylactic shock.choice Cardiac arrest. Anesthesia. Control bleeding from mucous membranes. A.E: CNS disturbances. Hemorrage. Cardiac arrythmia. Pulmonary oedema.

NOREPINEPHERINE: Is the neurotransmiter. Therapeuticaaly has α activity. action: 1. CVS: 1. Vasoconistriction. 2. Baroreceptor reflex. 2. If atropin is given first it inhibits the vagus so N.e causes tachycardia. P.kinetics: i.v, poor s.c absorption, short duration of action.

Therapeutic uses: Only in shock. A.E: as epi.+ extravasation. ISOPROTERENOL: β receptors. Action: 1. CVS: Heart: +ve ino & chronotrpic effect. Peripheral vasodilation β2, slight increase in SBP due to action on heart.

2. pulmonary stopped, metabolic action. Used in cardiac arrest. A.E: as epi. DOPAMINE: High doses α1 Low doses β1 D1, D2 in mesenteric & renal vascular bed vasodilation.

Action: 1. CVS: +ve inotropic & chronotropic effect, vasoconistriction. 2. Renal & splanhinic vasodilatation. Therapeutic uses: In cardiogenic & septic shock, hypotension, severe CCF with oliguria. Metabolized by MAO & COMT to homovanillic acid. A.E as sympathetic stimulation.

Dobutamine: Selective β1 agonist used to COP in CCF & inotropic support after cardiac surgery. Phenylepherine: α1 agonist, rasis the BP, reflex bradycardia. Used topically as nasal decongestant & for ocular mydriasis. Used in SVT. A.E hypertensive headache & arrythmias.

Albuterol & terbutaline: Short acting β2 agonist, used as bronchodilators. A.E tremor, interaction with MAOIs. Salmeterol & formoterol: Long acting β2 agonist. Used with steroid mainly for nocturnal asthma.

INDIRECT ACTING ADRENERGIC AGONISTS Enhances the release of epi. Presynaptically or inhibit the uptake. AMPHETAMINE: Acts on α1 so BP. On β stimulates the heart. Note ADHS, appetite control, narcolepsy. TYRAMINE: Normal byproduct of tyrosine. Oxidized by MAOI in the gut. COCAINE: Inhibits the reuptake. α1 β effects.

MIXED ACTION ADRENERGIC AGONIST EPHEDRINE & PSEUDOEPHEDRINE: Long duration of action (poor COMT & MAO substrates). Ephedrine increases BP by systoilc & diastolic BP & cardiac stimulation. CNS stimualtion. atheletic performance. Pseudoehedrine:nasal,sinus decongestion.

ADRENER α GIC ANTAGONIST α ADRENERGIC BLOCKING AGENT Mainly affecting the BP. Reflex tachycardia. Phenoxybenzamine: Acts on α1 & α2 receptors. peripheral resistance, reflex tachycardia, COP & restore the decrease in BP. Obsolete in hypertension management. It’s an epinephrine reversal. Used in pheochromocytoma, Raynaud disease.

A.E: nasal stiffness, hypotension. Contraindicated in patients with coronary perfusion. PHENTOLAMINE: Action as phenoxybenzamine. Used for short treatment of pheochromocytoma. Norepinephrine administration. Hypertensive crisis with clonidine & tyramine- MAOI.

Selective α1 inhibitors prazosin, doxazosin, tamsulosin. Used for: HTN, CCF, BPH. A.E: nasal congestion, headache, orthostatic hypotension.

Β-adrenergic blocking agent All are competitive antagonist. Act on both β1 & β2 or are selective β1. Non-selective antagonists: Propranolol: CVS: COP, work, O2 consumption. Blocks β2 peripheral vasodilatation (no postural hypotension). Bronchoconstriction. Hypoglycemia.

P.K: First-pass effect, Cross BBB. Uses: 1. HTN. 2. Hyperthyroidism. 3. Angina pectoris. 4. M.I. A.E: bronchoconstriction, arrythmias, drug interactions. Timolol in chronic open-angle glucoma.

Selective antagonist β1 Atenolol, metoprolol, bisoprolol. HTN, diabetes, asthma. Antagonist with partial agonist activity: E.g pindolol & acebutolol. Hypertensive with moderate bradycardia, DM. Antagonist of both α & β arenoreceptors: Labetalol, carvedilol. Produce peripheral vasodilatation. HTN, PIH, HF.

Drugs affecting neurotransmitter release or uptake resrpine: move dopamine, serotonin & NE into the vesicles. Guanethidine: displaces NE from the vesicles. Cocaine: inhibits reuptake.

Thank you