1. Sympathomimetics (continue)
Lecture 11c
Sympathomimetics (continue)

2. 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

4. 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.

5. 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.

6. 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.

7. 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)

8. 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

9. 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”

10. 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)

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

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

13. 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)

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

15. 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

16. 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)

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