Autonomic Nervous System PDF

1- sympathetic 2- parasympathetic  sympathetic parasympathetic ganglia Ach Ach postganglionic NE Ach Cholinergic Adrenergic  α1 (Gq) α2 (Gi) β1(Gs) β2(Gs) β3(Gs) VC Inhibits...

1- sympathetic 2- parasympathetic  sympathetic parasympathetic ganglia Ach Ach postganglionic NE Ach Cholinergic Adrenergic  α1 (Gq) α2 (Gi) β1(Gs) β2(Gs) β3(Gs) VC Inhibits Increase all V.D. of Increase Mydriasis release of cardiac coronary& Lipolysis Increases NE properties skeletal BV tone of BD urinary Increase bladder renin release Relaxes sphincter bronchi Relaxes wall of uterus. ↓ K and muscle tremor  Sympathomimetics  Sympatholytics  Parasympathomimetics  Parasympatholytics  Sympathomimetic: Drugs that mimic the actions of epinephrine or norepinephrine. A) According to the mechanism of action:  Catecholamines Non catecholamines Rapidly metabolized by COMT and Not metabolized by COMT and MAO MAO Short duration of action Longer duration of action Not absorbed orally. Absorbed orally. These drugs cannot cross BBB. These drugs can pass BBB, so have CNS effects  Epinephrine (Adrenaline) : Direct, acts on α1, α2, β1, β2, β3 adrenoceptors. A- Local:  Because of its intensive V.C of skin and mucous membrane blood vessels: 1- Decongestion and hemostasis. 2- Delay absorption of local anesthetics and prolong their duration. 1- Cardiovascular system (CVS): Heart: β1 epinephrine increases all cardiac properties.  Increases force of cardiac contraction.  Increases heart rate.  Increases conduction velocity of the heart.  Increases automaticity [can cause arrhythmia]. Blood vessels:  V.C of skin and mucous membrane blood vessels (alpha 1)  V.D of skeletal muscle, and coronary blood vessels (beta 2)  Blood pressure:  Systolic blood pressure as a result of cardiac output.  The diastolic blood pressure either shows slight increase or decrease depending on which type of receptor is stimulated.  If α1-receptor stimulation predominates ® V.C.® with increase diastolic BP.  If β2 stimulation predominates, it will lead to V.D with decrease diastolic BP. 2- Respiration: bronchodilatation [β2]. 3- GIT: Inhibits tone and motility (β2) contract sphincter (α1). 4- Urinary bladder: relaxes wall (β2) contracts sphincter (α1). 5-Uterus: relaxation of the pregnant uterus. 6-Antiallergic action: it is a physiologic antidote to histamine. 1- Anaphylactic shock and angioneurotic edema (I.M). why 2- With local anesthetic to delay absorption, prolongs duration, decreases toxicity of local anesthetic. 3- In epistaxis (locally). 4- Bronchial asthma. 5- In cardiac arrest (intracardiac).  Tachycardia, arrhythmia, anginal pain, hypertension, cerebral hemorrhage. 1- Coronary heart disease. 2- Hypertension. 3- Arrhythmias. 4- Peripheral vascular disease.   Norepinephrine (Noradrenaline)  Directly acting on 1, 2 and 1 adrenoceptors. (No β2)  Pharmacological actions: CVS: 1. Heart: increases contractility (β1) but heart rate is slowed by reflex vagal stimulation as a result of increased blood pressure, 2. Blood vessels: V.C of skin and mucous membrane blood vessels peripheral resistance elevation of both systolic and diastolic blood pressure.  Hypotensive states e.g after sympathectomy or in spinal anesthesia.  Adverse effects: 1. Bradycardia and hypertension. 2. Extravasation severe V.C gangrene and sloughing of skin. If this occurs, rapid injection of phentolamine locally is advised.  Preparations & dosage: I.V. drip, 4ml in 1liter saline 0.5ml/min. Recording blood pressure is necessary.  Synthetic Sympathomimetic Direct Acting Sympathomimetic 1- α1 selective agonists Midodrine: treatment of hypotension. Xylometazoline and oxymetazoline: topical decongestants because of their ability to promote vasoconstriction of the nasal mucosa.  2- Beta-agonists Non- selective beta agonists Isoprenaline : Catecholamine. Pharmacological actions: C.V.S: Heart: stimulates β1 increase all cardiac properties. B.V: V.D skeletal muscle and coronary B.V Bl.p: diastolic B1.p is decreased.  Bronchi: bronchodilatation (β2).  Uterus: relaxation (β2). Therapeutic uses:  Bronchial asthma  Heart block. Adverse effects: tachycardia, arrhythmia, angina, tremors.  Beta 1 selective Dobutamine: catecholamine.  Selective β1 agonist increasing contractility with minimal increase in heart rate (H.R).  It is given by I.V infusion.  It is used in acute heart failure.  Adverse effects: Tachycardia, palpitation, angina, arrhythmia.  Selective β2 agonists Pharmacological actions 1- Bronchodilators 2- Uterine relaxant 3- Hyperglycemia : due to enhanced liver glycogenolysis 4- Vasodilators of skeletal muscle Bl.Vs.  Salbutamol, terbutaline: short-acting.  Formeterol and salmeterol: long-acting  Ritodrine: uterine relaxant. Therapeutic uses:  Treatment of bronchial asthma.  Ritodrine: used as uterine relaxant to prevent preterm labour. Adverse effects: skeletal muscle tremors. In large doses, stimulate β1 receptors tachycardia, palpitation.  Mixed-Acting Sympathomimetics Ephedrine An alkaloid obtained from ephedra plant or synthetic. Pharmacokinetics:  It is absorbed orally and parenterally.  Distributed all over the body and passes BBB.  Excreted in urine.  Acidification of urine by ammonium chloride increases its excretion. Pharmacological actions: 1- It is mixed sympathomimetics. It acts mainly indirectly; its actions are slower in onset and have longer duration. 2- It shows the phenomenon of tachyphylaxis. CNS:  Insomnia, anxiety, tremors and convulsions.  Stimulates R.C. , CTZ.  Heart: Stimulates all cardiac properties.  B.V: V.C of skin and mucous membrane B.V increases systolic & diastolic Bl.p.  Bronchi: bronchodilatation (β2) (mild), and V.C of mucous membrane B.V.  GIT and urinary bladder: contraction of sphincters (α1) and relaxation of walls (β2). Therapeutic uses:  Analeptic in toxicity with CNS depressants.  Mydriatic eye drops 1-3%.  Nasal decongestant  Adverse effects:  CNS: stimulation: insomnia, tremors, anxiety, convulsions and vomiting (CTZ).  CVS: tachycardia, palpitation, angina, arrhythmia, hypertension.  Urine retention (in old age where senile enlargement of prostate predominates).  Tolerance and tachyphylaxis.  Indirect-Acting Sympathomimetic Amphetamine Pharmacokinetics: absorbed and excreted as ephedrine. Pharmacological actions:  It stimulates cerebral cortex, reticular activating system, midbrain and spinal cord. These effects are manifested as euphoria, increased mental activity, alertness and wakefulness.  it has analeptic and antifatigue action.  It decreases appetite.  Tachyphylaxis.  Addiction (dependence): on prolonged use. Therapeutic uses: not used due adverse effects and addiction Adverse effects: Palpitations, hypertension, arrhythmia, mydriasis, anxiety, anorexia, insomnia, hallucination, convulsions, dependence, psychosis and coma. Thank you