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AUTONOMICS

AUTONOMICS. MA. JANETTH B. SERRANO, M.D. DPBA. SYMPATHETIC DRUGS. Site and Mode of Action: 1. Direct Acting Epinephrine - Dobutamine Phenylephrine - Norepinephrine Isoproterenol - Clonidine 2. Indirect Acting Tyramine, Amphetamine, Cocaine 3. Mixed Acting Agonists

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AUTONOMICS

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  1. AUTONOMICS MA. JANETTH B. SERRANO, M.D. DPBA

  2. SYMPATHETIC DRUGS • Site and Mode of Action: 1. Direct Acting • Epinephrine - Dobutamine • Phenylephrine - Norepinephrine • Isoproterenol - Clonidine 2. Indirect Acting • Tyramine, Amphetamine, Cocaine 3. Mixed Acting Agonists • Dopamine - Ephedrine • Amphetamine - Phenylpropanolamine • Metaraminol

  3. Sympathetic Agonists SYMPATHOMIMETICS

  4. Sympathetic Agonists(Sympathomimetics) EPINEPHRINE DOBUTAMINE NOREPINEPHRINE DOPAMINE IBOPAMINE AMPHETAMINE ISOPROTERENOL METHAMPHETAMINE EPHEDRINE PSEUDOEPHEDRINE

  5. Sympathetic Agonists(Sympathomimetics) PHENYLEPHRINE METHOXAMINE MEPHENTERMINE MITODRINE METARAMINOL

  6. Sympathetic Agonists(Sympathomimetics) METHYLDOPA CLONIDINE GUANABENZ GUANFACINE

  7. Sympathetic Agonists(Sympathomimetics) NAPHAZOLINE TETRAHYDROZOLINE OXYMETAZOLINE XYLOMETAZOLINE

  8. Sympathetic Agonists(Sympathomimetics) METAPROTERENOL TERBUTALINE, ALBUTEROL RITODRINE ISOETHARINE, PILBUTEROL BITOLTEROL, FENOTEROL FORMOTEROL, SALMETEROL PROCATEROL

  9. Sympathetic Agonists(Sympathomimetics) • Special sympathomimetics: COCAINE • Local anesthetic • Inhibits uptake 1  Peripheral sympathomimetic action • CNS  inhibits reuptake of dopamine into neurons in the “pleasure centers” of the brain

  10. Sympathetic Agonists(Sympathomimetics) • Special sympathomimetics: TYRAMINE • Normal by-product of tyrosine metabolism • Fermented foods  cheese, red wine • Metabolized by MAO • Release of stored catecholamines  indirect sympathomimetic action

  11. Sympathetic Antagonists SYMPATHOLYTICS

  12. Sympathetic Antagonists(Sympatholytics) • Adrenergic Neuron Blockers (ANB) • Guanethedine, Reserpine • Adrenergic Receptor Blockers (ARB) • Reversible – Prazosin, Phentolamine, Tolazoline, Labetalol, Ergot alkaloids • Irreversible – Phenoxybenzamine, Dibenamine

  13. Sympathetic Antagonists(Sympatholytics) YOHIMBINE LABETALOL CARVEDILOL BUTOXAMINE

  14. Sympathetic Antagonists(Sympatholytics) PRAZOSIN, TERAZOSIN DOXAZOSIN, TRIMAZOSIN INDORAMIN, URADIPIL KETANSERIN, ALFUZOSIN BUNAZOSIN, TAMSULOSIN

  15. Sympathetic Antagonists(Sympatholytics) PHENOXYBENZAMINE PHENTOLAMINE ERGOT ALKALOIDS NEUROLEPTIC DRUGS

  16. PHENOXYBENZAMINE • irreversible noncompetetive blockade (14-48 hrs) • inhibits NE reuptake • Blocks H1, Ach and serotonin receptors • Blocks catecholamine-induced vasoconstriction • Epinephrine- reversal • Cl. Indication: pheochromocytoma male erectile dysfunction peripheral vascular diseases • Adv. Eff: postural hypotension, tachycardia

  17. PHENTOLAMINE • Competetive antagonist (4 hrs) • Epinephrine- reversal • reduce PVR • Cardiac stimulation  baroreflex & ↑ NE release • Inhibits serotonin responses • Indic: Pheochromocytoma, male erectile dysfunction • Adv. Eff: severe tachycardia, arrhythmia, myocardial ischemia, GI stimulation

  18. Beta-AdrenergicBlocking Agents BETA - BLOCKERS

  19. Sympathetic Antagonists(Sympatholytics) METOPROLOL ATENOLOL ACEBUTOLOL BETAXOLOL CELIPROLOL ESMOLOL

  20. Sympathetic Antagonists(Sympatholytics) PROPRANOLOL NADOLOL, TIMOLOL PINDOLOL, LEVOBUNOLOL CARTEOLOL, BISOPROLOL

  21. Beta- blockers • Pharmacokinetics: • oral: peak in 1-3 hrs • extensive first-pass metabolism • half- lives: 3 to 10 hrs * Esmolol – 8 – 10 min * Nadolol – 24 hrs

  22. Beta- blockers • PHARMACODYNAMICS: • CVS: (-) chronotropic, (-) inotropic effects • Respiratory: bronchoconstriction • Eye: reduce IOP • Metabolic & Endocrine: • inhibits lipolysis • partial inhibition of glycogenolysis • ↑ VLDL and ↓ HDL • ↓ HDL: LDL ratio • ISA; MSA

  23. Properties of Beta-receptor blocking agents:

  24. Properties of Beta-receptor blocking agents:

  25. Beta- blockers • CLINICAL INDICATIONS: • Hypertension • Cardiac arrhythmias • Angina • CHF: Metoprolol, Bisoprolol, Carvedilol • Glaucoma: Timolol, Betaxolol, Carteolol, Levobunolol, Metipranolol • Neurologic: Migraine, somatic mgt. of anxiety, alcohol withdrawal • Misc: reduce portal vein pressure in cirrhosis

  26. Beta- blockers • Clinical toxicities: • Drug allergy – rare • CNS effects – sedation, sleep disturbances, depression, psychotic rxns • Worsening of preexisting asthma & airway obstruction • Depress myocardial contractility & excitability • Hypoglycemic episodes

  27. Beta- blockers • DRUG INTERACTION: • Calcium- channel VERAPAMIL • Severe hypotension • Bradycardia • CHF • arrhythmia

  28. “A heartfelt apology can’t change the past, but it can brighten the future.”

  29. QUIZ • Major neurotransmitter of the Sympathetic Nervous System Write A if Agonist or B if Antagonist: 2. Epinephrine 7. Phentolamine 3. Labetalol 8. Cocaine 4. Clonidine 9. Phenylephrine 5. Prazosin 10. Ephedrine 6. Terbutaline

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