Sympathomimetics (continue) Lecture 11c Sympathomimetics (continue)

Isoproterenol predominantly stimulates both β1- and β2 adrenergic receptors. Its nonselectivity is one of its drawbacks and the reason why it is rarely used. Cardiovascular effects Cardiovascular: produces intense stimulation of the heart to increase its rate and force of contraction, causing increased cardiac output. therefore, is useful in the treatment of atrioventricular block or cardiac arrest. Isoproterenol also dilates the arterioles of skeletal muscle (β2 effect), resulting in decreased peripheral resistance. Because of its cardiac stimulatory action, it may increase systolic blood pressure slightly, but it greatly reduces mean arterial and diastolic blood pressure. 2. bronchodilation

Therapeutic uses: Isoproterenol is now rarely used as a broncho-dilator in asthma. It can be employed to stimulate the heart in emergency situations. Pharmacokinetics: Isoproterenol can be absorbed systemically by the sublingual mucosa but is more reliably absorbed when given parenterally or as an inhaled aerosol. Adverse effects: The adverse effects of isoproterenol are similar to those of epinephrine.

Dopamine Dopamine can activate α1and β1-adrenergic receptors. For example, at higher doses, it can cause vasoconstriction by activating α1 receptors, whereas at lower doses, it stimulates β1cardiac receptors. In addition, D1 and D2 dopaminergic receptors occur in the peripheral mesenteric and renal vascular beds, where binding of dopamine produces vasodilation.

Therapeutic uses: Dopamine is the drug of choice for shock and is given by continuous infusion. It raises the blood pressure by stimulating the β1 receptors on the heart to increase cardiac output, and α1 receptors on blood vessels to increase total peripheral resistance. In addition, it enhances perfusion to the kidney and splanchnic areas, as described above. In this regard, dopamine is far superior to norepinephrine, which diminishes the blood supply to the kidney and may cause renal shutdown.

Dobutamine synthetic, direct-acting catecholamine that is a β1-receptors. It increases cardiac rate and output with few vascular effects. Therapeutic uses: Dobutamine is used to increase cardiac output in congestive heart failure, in septic and cardiogenic shock. Given only parenterally (not orally)

Phenylephrine Clinical uses: As a mydriatic agent to examine the fundus of the eye It acts on α1 – receptors in the radial dilator pupillary muscle As a decongestant Used as nasal drops to cause VC in the nasal blood vessels & relief congestion As a vasopressor agent in case of hypotension α1 stimulation causes VC leading to increase BP

Clinical use of Amphetamine-like drugs To suppress appetite In very obese persons Amphetamine can act centrally on the hunger center in the hypothalamus to suppress appetite In narcolepsy Narcolepsy is irresistible attacks of sleep during the day in spite of enough sleep at night Amphetamine stimulates the CNS & makes the patient awake In ADHD “Attention Deficit Hyperactivity Disease”

Ephedrine Clinical uses: Pressor agent (used to increase BP) Decongestant It is no longer used to treated bronchial asthma. (because it’s less potent + slow onset of action)

Pseudoephedrine: Has similar pharmacological activities to ephedrine It is not controlled : OTC (over the counter) It is commonly used as a decongestant

Phenylpropranolamine: Again it is similar to pseudoephedrine, and was used as decongestant, but it was stopped because it may cause cerebral hemorrhage

Salbutamol: It is β2 – selective agonist Can be used orally, IV and by inhalation Formulations: (Tablets; Syrup; Injection; solution and Inhalation) Clinical Uses bronchial asthma by β2 stimulation, which leads to relaxation of bronchial smooth muscle and bronchodilation. Treatment of refractory hyperkalemia (I.V)

Salmetrol and Formoterol: These selective beta agonists, have longer duration of action as compared to Salbutamole. Uses: As inhalors for bronchial Asthma

Clonidine: It is a selective α2 – agonist Mechanism of action : (Acts centrally as a central sympatholytic drug.) Clonidine is Lipid – soluble, so, it freely passes BBB & reaches CNS to stimulate α2 – receptors in medulla and pons causing decreased sympathetic tone and finally decrease BP It act by it self not like Methyldopa Clinical use include: Treatment of mild to moderate hypertension Treatment of morphine withdrawal symptoms As analgesic during labour The dose = 1.25 ug/day It can be given I.M

Adverse affects of Clonidine Depression Dizziness, insomnia, & nightmares Impotence Alopecia تساقط الشعر Urticaria Weight gain Fluid retention Sudden withdrawal leads to rebound hypertension Metyldopa and the comparison between it and clonidine are in the lecture (adrenergic antagonists)

3. Apraclonidine Like clonidine it is selective α2 adrenoceptor agonist, however, main uses as adjuvant therapy for glaucoma via decrease of aqueous humour formation.