Pharmacology-1 (Basic Pharmacology) Part 2 PDF

Pharmacology-1 Basic pharmacology) Part 2 By Prof. Dr. Ihab Talat College of Pharmacy, Damanhur University 2024  Autonomic Nervous System Sympathetic Nervous System 2. Noradrenaline (Norepinephrine): Noradrenalin...

Pharmacology-1 Basic pharmacology) Part 2 By Prof. Dr. Ihab Talat College of Pharmacy, Damanhur University 2024  Autonomic Nervous System Sympathetic Nervous System 2. Noradrenaline (Norepinephrine): Noradrenaline is the chemical transmitter liberated by postganglionic adrenergic nerves. It is mainly a direct stimulant of the α-receptors but has a very weak action on β-receptors. Cardiovascular actions: Noradrenaline causes a rise in peripheral resistance due to intense vasoconstriction of most vascular beds, including the kidney (an α1-receptor effect). Both systolic and diastolic blood pressures increase. In vivo, noradrenaline produces reflex bradycardia. Therapeutic uses: Noradrenaline is used to treat shock because it increases blood pressure; however, dopamine is better, because it does not reduce blood flow to the kidney as does noradrenaline. Adverse effects:  Bradycardia, headache and anxiety are common adverse effects of noradrenaline.  3. Dopamine (β1) Dopamine is an endogenous catecholamine and is the metabolic precursor of noradrenaline found in adrenergic neurons and adrenal medulla. It is also present in the brain especially in the hypothalamus and in the basal ganglia. Pharmacological actions: Cardiovascular system: Dopamine is a direct agonist acting on β1-receptors of the heart, having both inotropic and chronotropic effects. At high doses, it acts on α1-receptors on the vasculature and causes vasoconstriction.  Renal and visceral: Dopamine dilates renal arterioles by activating dopaminergic receptors (D1), thus increasing blood flow to the kidneys and other viscera. These receptors are not affected by α- or β-blocking drugs. Therefore, dopamine is clinically useful in the treatment of shock, by increasing blood pressure without reducing blood flow to the kidney or affecting renal function 3. Dopamine (β1): Therapeutic uses: Dopamine is administered by IV infusion for the treatment of shock resulting from myocardial infarction, trauma or renal failure. It raises the blood pressure by stimulating the heart (β1 action). An enhanced blood flow to the kidney increases the glomerular filtration rate, sodium excretion and urinary output. Adverse effects: An overdose of dopamine produces tachycardia, arrhythmia, anginal pain, hypertension, nausea and vomiting. Dopamine mechanism of action  Drug Receptors Pharmacological Therapeutic effects uses: ✓ Direct CVS: a. Heart 4- stimulant on β1→↑HR+↑Contractility block. Isoproterenol β-receptors (↑Systolic blood b. Acute (Isoprenaline) (β1, β2 and pressure) bronchial β3) β2→↓TPR (↓Diastolic bl. asthma ✓ Very weak Pr.) on α- Bronchi: receptors β2→Bronchodilator 8  Drug Receptors Pharmacological Therapeutic uses: effects Selective α1- α1→ 1- Both used to treat 5- receptor vasoconstriction in hypotension and Phenylephrine agonists. most blood shock and vessels→↑TPR→ 2- Phenylephrine is Methoxamine ↑blood pressure also used in topical preparations as a mydriatic (α1) and nasal decongestant. 9  Drug Receptors Pharmacological Therapeutic uses: effects 6- Selective It acts centrally Used in Clonidine α2-receptor on Presynaptic α2 treatment of agonists. -receptors→(↓NE hypertension. release) → (↓blood pressure) 10 Mechanism of Clonidine  Drug Receptors Pharmacological Therapeutic uses: effects 7- Terbutaline, Bronchi: 1- Terbutaline, Albuterol β2→bronchdilataion Albuterol , Salbutamol Effective when Salbutamol delivered by the used as Selective β2- inhalation route bronchodilator in receptor bronchial asthma. agonists. 2- Ritodrine and Hexoprenalin Ritodrine and Pregnant Uterus: used reduce Hexoprenalin β2→Relaxation uterine contractions in premature labor 12  Drug Receptors Pharmacological Therapeutic uses: effects Formoterol Long acting β2- Long-Acting formoterol and receptor Beta2-Agonists mometasone for Long-Term Salmeterol agonists. Control of Asthma when Salmeterol and combined with fluticasone CS 13  Indirect-acting adrenergic agonists: (amphetamine 2. and tyramine) These agents cause noradrenaline release from sympathetic neurons. They potentiate the effects of noradrenaline produced endogenously, but these agents do not directly affect adrenergic receptors. 1. Amphetamine: Amphetamine is a synthetic non-catecholamine related in its structure to adrenaline. It stimulates both α- and β receptors through an indirect mechanism. The drug is easily absorbed from mucous membranes, gastrointestinal tract and parenteral sites. A large percentage is excreted unchanged in urine. (XX adrenaline) Pharmacological actions: a. Cardiovascular system:  Amphetamine can increase blood pressure significantly by α agonist action on the vasculature as well as β-stimulatory effects on the heart b. Central nervous system:  The central stimulant actions of amphetamine appear to result from its ability to cause the release of dopamine and block its reuptake in limbic regions of the brain. Amphetamine stimulates the entire cerebrospinal axis, cortex, brain stem and medulla. This leads to increased alertness, decreased fatigue, depressed appetite and insomnia. In high doses, convulsions can occur. c. Smooth muscle:  The contractile effect on the urinary bladder sphincter is particularly marked, and has been used in treating enuresis and incontinence. Therapeutic uses: a. Psychic depression. b. Obesity. c. Mental and physical fatigue. d. Parkinsonism: to elevate the mood of the patient. e. Nocturnal enuresis. Adverse effects: a. Central effects: These include insomnia, irritability, weakness, dizziness and tremor. b. Cardiovascular effects Amphetamine causes cardiac arrhythmias, hypertension and anginal pain. c. Gastrointestinal effects: Amphetamine acts on the gastrointestinal system, causing nausea, vomiting, diarrhea and abdominal cramps. d. Prolonged use produces habituation and addiction.  2. Tyramine: Tyramine is not a clinically useful drug, but it is found in fermented foods such as ripe cheese.  It is an indirectly acting sympathomimetic amine which acts by releasing noradrenaline from tissue stores. Normally, it is oxidized by MAO, but if the patient is taking MAO inhibitors (MAOIs) (e.g. the antidepressant drugs phenelzine and tranylcypromine), it can precipitate serious hypertensive crisis.  3. Mixed-action adrenergic agonists (Ephedrine and Metaraminol)  These drugs induce the release of noradrenaline from presynaptic terminals and activate adrenergic receptors on the postsynaptic membrane. 1. Ephedrine: Ephedrine is a non-catecholamine obtained from Ephedra plants, but may also be prepared synthetically. It stimulates both α- and β-receptors. This effect is partly by a direct action on the receptors and partly indirectly by releasing noradrenaline from its tissue stores. Ephedrine is absorbed when taken orally. It is resistant to COMT and MAO, so that its action is prolonged. The greater proportion of the drug is excreted unchanged in the urine. Pharmacological actions: Cardiovascular system: Ephedrine produces an increase in heart rate, contraction and excitability of the heart. It increases arterial pressure by causing peripheral vasoconstriction. Smooth muscles: Its effects on the bronchi (Bronchodilator) and other smooth muscle are qualitatively similar to those of adrenaline. Skeletal muscles: Ephedrine facilitates neuromuscular transmission more than adrenaline (increase contraction). Central nervous system: Ephedrine stimulates the vasomotor center, respiratory center, cerebral cortex. Therapeutic uses: a. Prophylaxis of bronchial asthma. b. Mydriatic eye drops. c. Myasthenia gravis as adjuvant with neostigmine (Sk. Ms). d. Nasal decongestant. e. Nocturnal enuresis. f. Heart block. g. To elevate blood pressure in postural hypotension. h. As analeptic in toxicity with CNS depressant drugs. Adverse effects: a) Insomnia, anxiety, tremors and convulsions. b) Hypertension, tachycardia and palpitations. c) Tolerance and tachyphylaxis (↓response) on repeated administration.  Thank YOU