Sympathomimetics 2024 PDF

Credit-Hours Tanta Medical Program “CHTMP  sympathomimetics By : Dr. Ola Mousa Salem Interactive  Objectives(ILOs) Upon completion of this lesson, the student will be able to: Recognize catecholamine synthesis, storage and release Identify differ...

Credit-Hours Tanta Medical Program “CHTMP  sympathomimetics By : Dr. Ola Mousa Salem Interactive  Objectives(ILOs) Upon completion of this lesson, the student will be able to: Recognize catecholamine synthesis, storage and release Identify different types of adrenergic receptors and their function Recognize sympathomimetics (their action, uses, side effects and contraindication).  central Symp sensory Nervous system Preph. motor  Neuronal uptake: major part Granular uptake (vesicular uptake) Metabolism by specific enzymes (MAO-COMT) Stimulate presynaptic alpha adrenoreceptors  Alpha adrenoreceptors (α 1) (post) Contraction of erector pilae muscle DPM mydriasis Generalized VC Viscid salivation Spasm o GIT & UB sphincter Contract pregnant but relax non preg. Uterus Ejaculation Facilitate Nm transimission Agonist: phenylephrine antagonist: prazocin  Alpha adrenoreceptors (α 2) (pre-post-CNS) ↓Sympathetic outflow from CNS. Presynaptic (Autoreceptors): ↓ Release of noradrenaline. ↓A.Ch release in enteric ganglia → relaxation of intestinl wall ↓Release of renin. ↓Release of insulin. ↓ lipolysis in fat cells. ↑Platelet aggregation. Agonist:clonidine antagonist: yohimbine  Beta adrenoreceptors (beta-1) C.N.S Stimulation. Cardiac Stimulation. ↑Release of Renin. Lipolysis & free fatty acid. Agonist:dobutamine antagonist:atenolol  Beta adrenoreceptors (beta-2) Generalized VD. Bronchodilatation. Stimulate release of insulin. Glycogenolysis in Liver & Skeletal muscles. Relax G. I T & bladder. Relax the Uterus. Skeletal muscle tremors. Agonist:salbutamol antagonist:butoxamine Beta 3 (fat cells-lipolysis)  Sympathomimetics Drugs stimulate adrenoceptors and produce actions similar to sympathetic nerve stimulation.  Adrenaline(epinephrine) ❖Sympathomimetic catecholamine present in adrenal medulla and CNS tract. ❖Prepared in dark brown ampoule (Explain why?). ❖stored in acid medium as it is unstable in alkaline medium.  Kinetics ▪ Absorption: Not absorbed orally. Not taken I.V. or I.M.(s.c-inhalation-eye drops-intra cardiac) ▪ Distribution: all catecholamine not pass BBB ▪ Fate: Nerve and tissue reuptake , metabolism by MAO and COMT ,unchanged in urine 2%  Adrenaline(epinephrine) Dynamics Mechanism of action: Stimulates all adrenergic receptors (alpha 1&2-beta 1&2&3) Pharmacological effects: Local effects: Skin: Subcutaneous (α1 receptor) → vasoconstriction. Mucous membrane as nose → vasoconstriction via α1 receptor → decongestion and homeostasis. Eye: V.C. of conjunctival blood vessels, NO mydriasis with adrenaline (Explain why?) −Effect of adrenaline on aqueous humor dynamics: −α1: Vasoconstriction of ciliary vessels → reduced aqueous formation. −Β2: Facilitation of trabecular outflow. −So, ↓ IOP Bronchi: Decongestion of bronchial mucosa (1). Bronchodilatation (B2).  Systemic effects ❖C.N.S.: Very mild stimulation leads to anxiety. ❖Eye: Systemically (α1) → stimulation of dilator papillae muscle → active mydriasis.  ❖Cardiovascular system: Heart: Increase all cardiac properties Blood Vessels: V.C. of skin, mucous membrane, and renal blood vessels (α1). V.D. of skeletal muscle and coronary blood vessels (β2). Blood Pressure:COPXPR PR Adrenaline reversal:  Adrenaline(epinephrine) Respiratory system: Decongestion of bronchial mucosa (1). Bronchodilatation (B2). Gastrointestinal tract: Constriction of sphincters (α1) and relaxation of intestinal wall (β2). Urinary bladder: Bladder sphincter is constricted (α1) and bladder wall is relaxed (β2) → urine retention. Uterus: In early pregnancy: it contract uterus due to dominance of α receptor. In late pregnancy: it relaxes uterus.  Adrenaline(epinephrine) Skeletal Muscles………….. Anti-Allergic: Adrenaline is a physiological antagonist of histamine, so it is the drug of choice in anaphylactic shock due to its bronchodilator and vasoconstrictor effects. Metabolism: Carbohydrates: glycogenolysis → hyperglycaemia (β2). Lipid: lipolysis → ↑ in plasma free fatty acid (β2 + β3) due to direct action on liver, muscle and adipose tissue cells. Transient hyperkalaemia ????  Adrenaline(epinephrine) Uses Local uses: Open angle glaucoma Haemostatic nasal pack in epistaxis → haemostasis. With local anesthetics → S.C → α → V.C. → ↓absorption of local anesthesia →↑Duration & ↓systemic toxicity and bleeding.  Adrenaline(epinephrine). Uses Systemic uses: Anaphylactic shock & Urticaria Acute bronchial asthma Acute insulin hypoglycemia. Cardiac resuscitation in Cardiac arrest. Contracting ring of uterus during labor.  Adrenaline(epinephrine) Adverse effects CNS: anxiety, headache α effects: Gangrene if injected around finger or toe, hypertension, and cerebral hemorrhage (prevention and treatment by α blockers as Prazocin). β1effects : Tachycardia, palpitation, angina, and arrhythmia (prevention and treatment by β1 blockers as Atenolol). β2: Skeletal muscle tremors.  Adrenaline(epinephrine) Contraindications and drug interaction Around finger and toes → Gangrene. Hypertension. Hemorrhagic shock (Hemorrhage → hypovolemia → hypotension → reflex V.C. → renal V.C → renal failure →death).  Thyrotoxicosis, pulmonary embolism, with digitalis, and with general anesthesia → cardiac arrhythmia. Non selective beta blocker → unopposed α → severe hypertension and hyperkalemia. Gnglion blockers, adrenergic neuron blockers, and M.A.O. inhibitors → supersensitivity  Noradrenaline (Norepinephrine) Kinetics Natural sympathomimetic catecholamine Not orally, not pass BBB, fate like adrenaline, used by IV infusion Dynamics Mechanism of action: Noradrenaline is a very effective α- adrenergic receptor agonist but exhibits limited β2-adrenergic receptor activity.  Pharmacological effects: ❖ C.V.S.: Blood vessels: generalized VC (Except Coronary) Blood pressure: COPx PR PR Bradycardia: ??? ↑Stroke volume(β1) but decrease COP (due to bradycardia). ↑Excitability and automaticity (β1) leading to arrhythmia.  Uses of noradrenaline: 1. Acute hypotension during spinal anesthesia or post-operative shock. N.B. Precaution during administration: Needle strictly in vein if extravasation → Gangrene. Monitor blood pressure and E.C.G. during infusion. Stop infusion gradually. If sudden stop → Severe hypotension. 2. Added to local anesthetics.  Adverse effects of noradrenaline: Necrosis and gangrene if extravasation occurs. Hypertension → cerebral Hemorrhage. Reflex bradycardia. Headache and anxiety.  Isoprenaline (Isoproterenol) Synthetic direct acting sympathomimetic, Catecholamine, Non selective B agonist was used in acute heart block and acute bronchial asthma. Its main adverse effects are tachycardia, angina, and arrhythmia.  Dopamine Kinetics Natural sympathomimetic, Catecholamines. Dynamics Mechanism of action: It stimulates dopaminergic receptors, α, and β receptors. Dopaminergic receptor: D1: stimulation leads to most of peripheral effects. D2:stimulation leads to most of central effects. D3: (presynaptic auto receptor) stimulation lead to decrease release of dopamine. Peripheral Effects ▪Small dose:D1:VD→↑RBF ▪Moderate dose:D1+β1→ +ve inotropic ▪Large dose:α1: VC→↑PR  Central effects Dopamine doesn`t pass BBB , l- dopa precursor pass and converted to Dopamine Limbic system: Euphoria and psychosis. Basal Ganglia: Anti-parkinsonism. Hypothalamus: Pyrexia & ↓ appetite &↓ prolactin Secretion. C.T.Z.: Nausea & vomiting.  Uses ❖shock (positive inotropic, improve microcirculation and increase renal blood flow) (restore blood volume) ❖Resistant heart failure Side effects ❖Tachycardia and arrhythmia. ❖Nausea and vomiting. Dobutamine ❑Selective beta 1 agonist ❑Positive inotropic, dromotropic ❑Minimal tachycardia and minimal change in peripheral resistance ❑Cardiogenic shock, resistant HF & resistant HB fenoldopam Direct selective D1 agonist → vasodilatation →↓total peripheral resistance and blood pressure.  1-Vasopressors Stimulation of α1-receptors →V.C. → ↑ TPR→↑BP so treat hypotension and include: Noradrenaline…… Ephedrine…… Phenylephrine Midodrine  Uses: Local uses: Nasal decongestant. Open angle glaucoma. Systemic uses: Hypotension. End attack of paroxysmal atrial tachycardia. Adverse effects: Hypertension and reflex bradycardia.  2-Nasal decongestants These are α1 agonists on topical application → local V.C. of nasal mucosal membrane. They have a longer duration of action (12 hours) than ephedrine. Uses: ▪Allergic rhinitis. ▪Common cold.  2-Nasal decongestants Side effects: Orally → hypertension so used cautiously in hypertensives and in MAO inhibitors patients Chronic use → atrophic rhinitis due to persistent vasoconstriction. Repeated local administration → severe rebound congestion. Preparations: Oral decongestant: Pseudoephedrine, and phenylephrine. Topical nasal decongestant: Xylometazoline, Naphazoline, Tetrahydrozoline, and Oxymetazoline.  Ephedrine Mechanism of action: Mainly acts indirectly with some direct action on α and β receptors. Effects similar to adrenaline but weaker (100 times less potent than adrenaline), slower, longer, and tachyphylaxis. Pharmacological effects: Similar to adrenaline but weaker and longer. assignment A patient received penicillin antibiotic intravenous then he brought to emergency room and diagnosed as anaphylactic shock which of the following drugs can be used? Norepinephrine Epinephrine Phenylephrine dobutamine Prazocin before noradrenaline administration can resulted in Sustained hypertension Hypotension Abolish hypertension No effect Reflex bradycardia induced by noradrenaline can be blocked by: Dopamine Isoprenaline Atropine ephedrine