Pharmacology Of Sympathetic System PDF

Pharmacology of sympathetic system  ADRENERGIC STIMULANTS (Sympathomimetics) Introduction: Adrenergic receptors (adrenoceptors): 1 and 2 1, 2 and 3 Bronchial smooth muscle(2) Heart (1) Blood vessels of skin and mucus membranes (1). SYMPATHOMIMETICS They pro...

Pharmacology of sympathetic system  ADRENERGIC STIMULANTS (Sympathomimetics) Introduction: Adrenergic receptors (adrenoceptors): 1 and 2 1, 2 and 3 Bronchial smooth muscle(2) Heart (1) Blood vessels of skin and mucus membranes (1). SYMPATHOMIMETICS They produce effects similar to stimulation of postganglionic sympathetic adrenergic nerves. They are used as: bronchodilators, CVS stimulants, mydriatics, nasal decongestants,.....  Classification : According to receptor selectivity: Selective. Non-selective.  Non- selective ( Mixed Alpha & Beta Agonists) 1. Adrenaline (Epinephrine) 2. Noradrenaline 3. Amphetamine 4. pseudoephedrine Adrenaline Stimulates all four adrenergic receptor subtypes (α1, α2, β1 and β2). Adrenaline has a rapid onset and brief duration of action (t1/2  2 minute). Oral administration is ineffective. It may be given subcutaneously, intramuscularly, intracardiac, by inhalation or topical to the eye.  Norepinephrine (Noradrenaline) Binds to both types of alpha receptors (α1, α2), and to β1 receptors to a lesser extent, and it shows little or no affinity for β2 receptors Norepinephrine (IV infusion) is used to treat many types of shock, e.g., septic shock. It is considered the vasopressor of first choice; as it has predominantly α-adrenergic properties, and its modest β-adrenergic effects help to maintain cardiac output.  Pseudoephedrine (oral) Directly stimulates α1, α2 and β1 receptors Based on its vasoconstrictor action, it is used to treat nasal and sinus congestion combined with other agents (antihistamines) in cold products.  Amphetamines such as methamphetamine Have a marked central stimulatory action with a mood-elevating effect (euphoria); this effect is the basis for the widespread abuse of this drug group. Produce insomnia, improve attention. They have peripheral adrenergic actions such as cardiac stimulation and increase in the blood pressure  Therapeutic uses 1. Is used in treatment of attention deficit hyperactivity disorder (ADHD), a behavioral syndrome in children consisting of short attention span, hyperkinetic physical behavior, and learning problems. 2. amphetamine salts can be used to treat narcolepsy, a rare sleep disorder that is characterized by abrupt bouts of sleepiness during the day in adults.  Adverse Reactions of non-selective (α and β) agonists: 1. CNS excitation in the form of anxiety, fear, and tremors. 2. High doses of amphetamines can produce psychosis and convulsions, while chronic use is limited by tolerance and psychological and physical dependence. 3. Cardiovascular stimulation tachycardia, arrhythmias and even cardiac arrest. 4. Marked elevation of the blood pressure that can induce cerebral haemorrhage. II.Selective Adrenergic Agonists  Selective Alpha2 Agonists: Alpha-Methyldopa(Oral) is on one of the primary lines antihypertensive drugs that are safely used in pregnancy.  Selective Beta1 Agonists: Dopamine is used in thetreatment of shock as hypovolemic and septic shocks in different doses according to the type of shock. 2) Selective Beta2 Agonists: Salbutamol and Terbutaline (inhalation/IV) are used to treat the bronchospasm associated with respiratory diseases, such as bronchial asthma, bronchitis, and emphysema.  ADRENERGIC ANTAGONISTS SYMPATHOLYTIC 1. Alpha-adrenoceptor blockers: They block the vasoconstrictor action of adrenaline and noradrenaline. 2. Beta-adrenoceptor blockers: They block the cardiac and vasodilating actions of adrenaline. Adrenergic Receptors Blockers: Alpha adrenergic receptors blockers: They block V.C. action of adrenaline and noradrenaline Beta adrenergic receptors blockers: They block cardiac and V.D. actions of adrenaline. Combined α and β-blockers: labetalol & carvedilol. Alpha-receptor Antagonists =.  SELECTIVE 1-BLOCKERS Selective competitive blockers of post synaptic 1- receptor → peripheral V.D. of arterial and venous smooth muscles. They cause much less reflex tachycardia than non- selective blockers SELECTIVE 1-BLOCKERS Alpha1 receptors are expressed in the base of the bladder and the prostate, and their blockade causes relaxation of this smooth muscle and decreases resistance to the urine flow. SELECTIVE 1-BLOCKERS Prazosin is a highly selective, reversible pharmacologic blocker. Doxazosin and terazosin are similar drugs with longer half-lives (allowing once daily dosing).  Therapeutic uses 1. Severe hypertension (in combination ) added to treatment with first- and second-line drugs. 2. Symptomatic treatment of urine obstruction: alternative to surgery in benign prostatic hyperplasia improving urine flow..  SIDE EFFECTS Orthostatic hypotension & syncope This could be minimized by adjusting the first dose to 1/3 or 1/4 normal dose at bed time Beta Adrenoceptors blocking agents Classification 1. Non-selective beta-blockers, e.g.,propranolol, and timolol. 2. Selective beta1-receptor blockers, e.g.,atenolol, esmolol,  Propranolol The prototype of beta blockers. It has equal affinity for β1 & β2 It is highly lipophilic It possess local anesthetic action Pharmacokinetic 70% of the drug is destroyed in liver by 1st pass hepatic metabolism &only 30 % of the oral dose reaches systemic circulation. 90-95 % is bound to plasma proteins. It can cross B.B.B. and it is excreted in urine.  Pharmacological action Heart 1 - ve chronotropic , - ve inotropic - ve dromotropic  COP  Respiratory system: Bronchoconstriction in susceptible patients (β2- blocking effect). Eye: Topical beta-blockers eye drops reduce the intraocular pressure, which is of special benefit in open-angle glaucoma.  Therapeutic Uses 1. Hypertension. 2. Angina pectoris (effort- induced) 3. Myocardial infarction(mild & early cases)  Therapeutic Uses 4. Cardiac arrhythmia delays A-V conduction. reduces ventricular rate. 5. Hyperthyrodism protects heart.  T4  T3 (the active form).  Therapeutic Uses 6. Open-angle Glaucoma: Timolol 7. Prophylaxis of Migraine headache 8. Management of familial tremors & anxiety  Adverse effects: 1. Block of cardiac 1-receptors: -ve inotropic (contraction)  heart failure. -ve chronotropic ( rate) bradycardia (Treated by atropine). -ve dromotropic (conduction)  heart block. Hypotension. Adverse effects: 2. Blockade of 2 (nonselective): Bronchospasm and asthma. Hypoglycemia (symptomless hypoglycemic coma). Vasoconstriction (cold extremities).  Sudden withdrawal - Exacerbates angina, tachycardia, may lead to arrhythmias/Rebound hypertension. - must be withdrawn gradually.