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- 1. AUTONOMIC NERVOUS SYSTEM •Autonomic Nervous System • Somatic & Autonomic Nervous System • Parasympathatic & Sympathatic nervous system • Neurohumoral Transmission • • Receptors -Cholinoceptors -Adrenergic receptors • Drugs affecting parasympathetic NS • Drugs affecting sympathetic NS
- 2. Organization of TheNervous System Central Nervous System “Brain and spinal cord” Peripheral Nervous System Somatic Nervous System (voluntary) Autonomic Nervous System (involuntary) Sympathetic “thoracolumbar” Parasympathetic “craniosacral” Efferent Division Afferent Division
- 3. Efferent division ofthe peripheral nervous system
- 4. In the nervoussystem, chemical transmission occurs between nerve cells and between nerve cells and their effector cells Chemical transmission takes place through the release of small amounts of transmitter substances from the nerve terminals into the synaptic cleft The transmitter crosses the cleft by diffusion and activates or inhibits the postsynaptic cell by binding to a specialized receptor molecule
- 5. Neurohumoral Transmission • Itshould be present in the presynaptic neurone (usually along with enzyme synthesizing it) • It should be released in the medium following nerve stimulation • Its application should produce responses identical to those produced by nerve stimulation • Its effects should be antagonized or potentiated by other substance which similarly alter effects of nerve stimulation
- 6. • Almost allautonomic nerves (Syp+Parasaymp) have relay centre in between called as ganglion Which lies outside the CNS Preganglionic Neuron Postganlionic neuron
- 7. Efferent neurons of theautonomic system Brainstem or spinal cord Cell body Ganglionic transmitter Neuroeffector transmitter Preganglionic neuron Postganglionic neuron 1 2 Effector organ
- 8. The Synapse Afunctional connection between surfaces Signal transmission zone Synapse – synaptic cleft, presynaptic cell, and postsynaptic cell Synaptic cleft – space in between the presynaptic and postsynaptic cell Postsynaptic cell – neurons, muscles, and endocrine glands Neuromuscular junction – synapse between a motor neuron and a muscle
- 9. Comparison of Somaticand Autonomic Systems
- 11. Steps in neurohumoraltransmission • Impulse conduction • Transmitter release • Transmitter action on postjunctional membrane -EPSP -IPSP • Post-junctional activity • Termination of transmitter action
- 12. • Presynaptically releasesneurotrnsmitter is regulated by By homotropic receptor ineraction By heterotropic receptor ineraction
- 13. Sympathetic Responses to Fight-or-Flight Pupilsshould dilate HR and contractility increase Bronchials should dilate GI tract should shut down Bladder should be shut down Blood should be shunted from GI tract and skin to muscles Metabolism should increase supply of glucose
- 14. Parasympathetic Nervous System assimilation offood, conservation of energy
- 15. Preganglionic neurons • Long •Synapse with postganglionic neurons at or near organ • Release acetylcholine (ACh) to activate nicotinic receptors on postganglionic neurons Postganglionic neurons • Short • Synapse on the target organ • Release ACh to activate muscarinic receptors on the target organ Cholinergic fibers: i.e., act by releasing acetylcholine. • Include: – all preganglionic efferent autonomic fibers – the somatic (non-autonomic) motor fibers to skeletal muscle – most parasympathetic postganglionic and a few sympathetic postganglionic fibers Parasympathetic Neurons & Synapses
- 16. Presynaptic autoinhibitory receptors •Presynaptic release of NT • Homotropic receptors interaction • Heterotropic receptors interaction
- 17. Cholinergic System &Drugs Synthesis Store & estruction Ach
- 18. Cholinestrase: Two types •True Acetylcholinestrase: • Location: neuronal membrane, RBC, Placenta • Plasma Cholinestrase (pseudocholinestrase, Butyrylcholine-estrase): Succinylcholine, Butyrylcholine, Ingested esters
- 19. • Muscarinic receptors:parasympathetic neuroeffector junction • M1 Sympathetic ganglia, gastric glands, cerebral cortex • M2 Myocardium, presynaptic terminal of peripheral & central neurones • M3 Glandular & visceral smooth muscle • M4 • M5 • Nicotinic receptors • NM : Skeletal muscle end plate • NN: Ganglionic cells(SP &PSP), Adrenal medulla
- 20. Cholinoceptors • Muscarinic • AGONIST:Muscarine • ANTAGONIST: Atropine • M1: • Autonomic ganglia • Gastric glands: histamine release • CNS: learning,memories, motor function • Agonist : Oxotremorine • Antagonist: pirenzepine , telenzepine
- 21. • M2: SANode Rate of impulse generation • AV Node Velocity of conduction • ATRIUM Contractility • VENTRICLE Contractility (SLIGHT) • Visceral smooth muscle :Contraction • Agonist : Methacholine • Antagonist: Methoctramine,
- 22. • M3: VisceralSM: Contraction • IRIS: Constriction • CILIARY MUSCLE: Contraction • EXOCRINE GLANDS: Secretion • Vascular endothelium: EDRF (NO) Vasodilatation Agonist : Bethanechole Antagonist: Hexahydrosiladifenidiol, Darifenacin
- 23. NICOTINIC RECEPTORS • NM •AGONIST PTMA, NICOTINE • ANTAGONIST TUBOCURARINE • NN AUTONOMIC GANGLIA AGONIST DMPP, NICOTINE ANTAGONIST HEXAMETHONIUM
- 24. The main effectsof the autonomic nervous system ORGAN SYMPATHETIC EFFECT ADRENERGIC RECEPTOR TYPE PARASYMPATHETIC EFFECT CHOLINERGIC RECEPTOR TYPE Heart Sinoatrial node Atrial muscle Atrioventricular node Ventricular muscle Rate Force Automaticity Automaticity Force b1 b1 b1 b1 Rate Force Conduction velocity No effect M2 M2 M2 M2 Blood vessels Arterioles Coronary Muscle Viscera Skin Brain Erectile tissue Salivary gland Veins Constriction Dilatation Constriction Constriction Constriction Constriction Constriction Dilatation a b2 a a a a a b2 No effect No effect No effect No effect Dilatation Dilatation No effect No effect ? M3 ? M3 Viscera Bronchi Smooth muscle Glands Gastrointestinal tract Smooth muscle Sphincters Glands Uterus Pregnant No sympathetic innervation, but dilated by circu-lating adrenaline No effect Motility Constriction No effect Contraction b2 a1, a2, b2 a2, b2 a b2 Constriction Secretion Motility Dilatation Secretion Gastric acid secretion Variable M3 M3 M3 M3 M3 M1
- 25. ORGAN SYMPATHETIC EFFECT ADRENERGIC RECEPTOR TYPE PARASYMPA- THETIC EFFECT CHOLINERGIC RECEPTORTYPE Male sex organs Ejaculation a Erection ?M3 Eye Pupil Ciliary muscle Dilatation Relaxation (slight) a b Constriction Contraction M3 M3 Skin Sweat glands Pilomotor Secretion (mainly cholinergic) Piloerection a a No effect No effect Salivary glands Secretion a, b Secretion M3 Lacrimal glands No effect Secretion M3 Kidney Renin secretion b2 No effect Liver Glycogenolysis Gluconeogenesis a, b2 No effect
- 26. • Heart M2 Atria-ve chronotropic -ve ionotropic Decrease in conduction velocity RP (increase) Ventricular: Sweat glands: M3 receptors Innervation sympathetic but cholinergic in nature
- 27. Classification of drugsaffecting the ANS • Parasympathetic nervous system Mimic acetylcholine = cholinergic = muscarinic agonists = parasympathomimetic Block acetylcholine = anticholinergic = muscarinic antagonist = parasympatholytic • Sympathetic nervous system Mimic norepinephrine = adrenergic = adrenergic agonist =Adrenoceptors= sympathomimetic Block norepinephrine = antiadrenergic = adrenergic antagonist = sympatholytic
- 28. CHOLINERGIC AGONISTS CHOLINESTERS • Acetylcholine •Methacholine • Carbachol • Bethanechol • ALKALOIDS • Muscarine • Pilocarpine • Arecoline
- 29. ACTIONS (of AChas prototype) • Heart • Smooth muscle • Blood vessels • Glands: Secretion from all parasympathetically innervated • Eye
- 30. Nicotinic: Autonomic gangliaBothsympathetic and parasympathetic ganglia are stimulated • This effects manifested at higher doses Skeletal muscles • Iontophoretic application of ACh to muscle endplate causes contraction of the fibres • High dose can cause twitching and fasciculations,buti.v. injection • CNS
- 31. Uses • Pilocarpine • Acetylcholine •Bethanechol • Carbachol • Methacholine
- 32. ANTICHOLINESTERASES • Reversible • Carbnmates •Physostigmine(Eserine) • Neostigmine • Pyridostigmine • Edrophonium • Rivastigmine, Donepezil • Galantamine lrreversible lrreversible • Organophosphates • Dyflos (DFP) • Echothiophate • Parathion • Acridine • Tacrine Carbamates • Carbaryl • Propoxur
- 33. • Uses • Inglaucoma • Myasthenia gravis • Postoperative paralytic ileus/urinary retention • Postoperative decurarization • Belladona poisoning • Alzheimer's disease
- 34. •ANTICHOLINERGIC DRUGS •(Muscarinic ReceptorAntagonist, Parasympatholytics, •Atropine-like Drugs) Atropine, the prototype drug of this class
- 35. Natural alkaloids: Atropine,Hyoscine (Scopolamine), Semisynthetic derivatives • Homatropine, Hyoscine butyl bromide, Ipratropium bromide, • Tiotropium bromide Synthetic compounds • (A) Mydriatics: Cyclopentolate, tropicamide • (B) Antisecretory-antispasmodics: • Quaternary compounds: Oxyphenonium, clidinium, glycopyrrolate • Tertiary amines: dicyclomine, pirenzipine • (C) Vesicoselective: oxybutynine, flavoxate, tolterodine • (D) Antiparkinsonian (central Anticholinergics): Biperiden, Trihexyphenidyl(benzhexol) •ANTICHOLINERGIC DRUGS
- 36. •CNS An overallstimulant action but not appreciable at low doses which •produce peripheral effects because of restricted entry •Hyoscine produces central depressant effects even at low doses •Atropine stimulates many medullar centers – • vagal, respiratory, and vasоmotor • Basalganglia, it suppresses tremor and rigidity in parkinsonism •High doses cause cortical excitation, rest- • lessness, disorientation, hallucinations, and delirium • followed by respiratory depression and coma.
- 37. CVS • Atropine causestachycardia, due to blockade of •M2-receptors on SA node •Tachycardia is more marked in young adults than in children and the elderly. •Atropine shortens the refractory period of AV conduction, •Atropine does not influence BP
- 38. Eye • Topical instillationof atropine (0.1%) causes mydriasis, abolition of light reflex, and cycloplegia, lasting 7–10 days. • Results in photophobia and blurring of near vision. • Intraocular tension? • Specially in narrow angle glaucoma
- 39. •Smooth muscles. •All visceralsmooth muscles with parasympathetic innervation are relaxed (M3- blokade). •Tone and amplitude of GIT are reduced. •Spasm may be reduced, constipation may occur. •Peristalsis is only incompletely •Atropine causes bronchodilation and reduced airway. Inflammatory •mediators (histamine, PGs, and kinins) increase vagal •activity in addition to their direct action on bronchial •muscle and glands. Atropine attenuates their action •by antagonizing the reflex vagal component.It has a •relaxant action on urinary bladder •Urinary retention can occur in older men with prostatic hyperplasia.
- 40. Glands •Atropine decreases sweat,salivary, tracheo-bronchial, and lacrimal secretion (M3-blockade) •Eyesdry, talking, and swallowingdifficult. •Atropine decreases less the secretion of acid and pepsin and more of the mucus in the stomach. Body temperature •Rise in body temperature occurs at higher doses, and is due to both inhibition of sweating as well as stimulation of the temperature regulating centre in the hypothalamus. •Children are highly susceptible.
- 41. •Local anaesthetic action.Atropine has a mild anaesthetic action on the cornea. •The sensitivity of different organs and tissues •to atropine varies and can be graded as •saliva, sweat, bronchial secretion > eye > •bronchial muscles > heart > intestinal and •bladder smooth muscles > gastric glands •and gastric smooth muscles
- 42. •Pharmacokinetics •Atropine and hyoscineare rapidly absorbed from •GIT. Applied to the eyes they penetrate the cornea. •Passage across BBB is somewhat restricted. 50% •of atropine is metabolized in the liver and excreted •unchanged in urine. It has t1/2 3–4 h. Hyoscine is •more completely metabolized and has better BBB •penetration. Some rabbits have a specific atropine •esterase which degrades atropine very rapidly.
- 43. Unwanted effects •Dry mouth,difficulty in swallowing and talking; •Dry and hot skin (especially over the face and neck); •fever difficulty in micturition; •Photophobia , blurring of near vision; •Palpitation •Contraindication:
- 44. Atropine (atropine sulphate0.6mg) i.v./i.m. ointment/eye drop) Homatropine (Homide 1%, 2%) Hyoscine butylbromide (tab buscopan 10mg/inj 20 mg), Ipratropium bromide (IPRAVENT 40 microgram) Tiotropium bromide (TIOVA 18 Microgram) •ANTICHOLINERGIC DRUGS •Atropine •Homatropine •Cyclopentolate •Tropicamide •Tropac-p
- 45. Clidinium (NORMAXIN 2.5mg, dicyclomine 10 mg, chlordiazepoxide) Glycopyrrolate (Pyroalte 0.2 mg/ml, 10 ml vial) Tertiary amines: Dicyclomine (colimex drops 10 mg/ml with dimethicone) Pirenzipine Drotavarine (tab drotakind-M) VESICOSELECTIVE oxybutynine, flavoxate, tolterodine
- 46. USES • Preanaesthetic medication •Peptic ulcer • Pulmonary embolism??? • COPD & Bronchial asthma • As mydriatic agent for diagnosis refraction errors, • Iridocycltis • Adhesions between iris and lense • Bradycardia • Parkinsonism • Motion sickness • Lie detector test • Relieve urinary frequency • Dysmenorrhoea
- 47. CATECHOLAMINE STORAGE OFCA NA+ATP(4:1 ) IS ABSORBED ON A CHROMOGRANIN IN ADRENAL MEDULLA: NA DIFFUSES OUT OFCYTOPLASMMETHYLATED TO ADR CYTOPLSM POOL OF CA IS KEPT LOWBY MAO
- 48. RELEASE OFCAS ALONG WITH NA OR ADR+ATP+DOPAMINE HYDROXYLASE+CHROMAGRANIN UPTAKE OF CAS AXONAL UPTAKE : ACTIVE AMINE PUMP NETTRANSPORT NA BY A Na+ coupled mechanismcocain,desipramine can block this pump VESICULAR UPTAKE: VMAT (VESICULAR MONOAMINE TRANSPORTER) RESERPINE can block this pump METABOLISM CAS: MAO IN CYTOPLASM COMT (CATECHOLE-O-METHYL TRANSFERSE) LIVER & OTHER VMA (VANILLYLMANDELIC ACID), 3-METHOXY-4-HYDROXY PHENYLETHYLENE GLYCOL, NORMETANEPHRINE, 3,4 DIHYDROXY MANDELLIC ACIDCONJUGATIONEXCRETION IN URINE
- 49. Classification of drugsaffecting the ANS Parasympathetic nervous system Mimic acetylcholine = cholinergic = muscarinic agonists = parasympathomimetic Block acetylcholine = anticholinergic = muscarinic antagonist = parasympatholytic Sympathetic nervous system Mimic norepinephrine = adrenergic = adrenergic agonist =Adrenoceptors= sympathomimetic Block norepinephrine = antiadrenergic = adrenergic antagonist = sympatholytic
- 50. ADRENALINE • HEART: increasesHR by increasing slope of slow diastolic depolarization of cells in the SA node • Activates latent pacemaker in AV node • Cardiac contraction incraesed
- 51. • BLOOD VESSELS:vasoconstriction & vasodilation can occur depending on drug, dose, vascular beds • Cutaneous,mucus membrane,renal beds • Dose • Skeletal muscle •
- 52.
- 53. • RESPIRATION • ADR •NA • ISPRENALINE
- 54. EYE • a1 vasoconstrictionof ciliary musclereduced aqueous fprmation • a2 reduced secretary activity of ciliary epithelium • b2 enhanced secretary activity of cilliary epithelium
- 55. GIT • Relaxation: a& b • Bladder: Detruser relaxes b & • Trigone constricted a1 • Uterus: • Human: contractionnonpreg • relaxation:pregnant • Skeletal muscle: neuromuscular transmission facilitated • CNS: • METABOLIC:
- 56. • Adrenaline • Forsystemic action, 0.2-0.5 mg s.c., i.m., action lasts 1/2 to 2 hrs. • ADRENALINE 1mg/ml inj. • As local vasoconstrictor, 1 in 200,000 to 1 in 100,000 added to lidocaine; in xylocaine with Adrenaline: lidocaine 21.3 mg + adrenaline O.005mg/ ml . • Noradrenaline (levarterenol) • 2-4 ug/min I.V.. infusion; local tissue necrosis occurs if the solution extravasates; • do not mix with NaHCO3 same bottle (rapid oxidation occurs); • Action starts declining within 5 min of discontinuing infusion. adrenor 2 mg (base)/2 ml amp. • Isoprenaline (Isoproterenol) 20 mg sublingual, 1-2 mg i.m., 5-10 ug/min i.v. infusion; action lasts 1-3 hrs. • It is occasionally used to maintain idioventricular rate till pacemaker is implanted. For bronchial asthma
- 57. • Adverse effectsand contraindications: • Marked rise in BPcerebral haemorrhage, ventricular tachycardia/fibrillation, angina, MI doses • Adr is contraindicated in hypertensive, hyper-thyroid • AP patients. Adr not be given during anaesthesia halothane (risk of arrhythmias) • In patients receiving beta blockers (markecd rise in BP can occur due to unopposed action).
- 58. • THERAPEUTIC CLASSIFICATIONOF ADRENERGIC DRUGS • Pressor agents • Noradrenaline • Phenylephrine • Ephedrine, Methoxamine • Dopamjne, Mephentermine • Cardiac stimulants • Adrenaline, Dobutamine, Isoprenaline • Bronchodilarors • Salbutamol (Albuterol), Isoprenaline Terbutaline Salmeterol, Formoterol, Bambuterol • Nasal decongestants • Phenylephrine Naphazoline Xylometazoline Pseudoephedrine Oxymetazoline Phenyl propanolamine • CNS stimulants Amphetamine Dexamphetamine • Anorectics • Fenfluramine, Sibutramine Dexfenfluramine • Uterine relaxant and vasodilators Ritodrine, Salbutamol , Isoxsuprine,Terbutaline • . •
- 59. • Dopamine: (Dland D2) as well as adrenergic a & b1 agonist. • D1 b1 a1 action • Low dose of DA : Dl in renal & mesenteric BV are the most sensitive • Moderately doses : positive inotropic (direct b1 & Dl action + that due to NA release) & little chronotropic effect on heart. • Large doses infused: a1 action • At doses normally employed, it raises cardiac output and systolic BP with little effect on diastolic BP. • Does not penetrate BBBCNS effects. • DA : cardiogenic or septic shock and severe CHF to increase BP & urine outflow • i.v. infusion (0.2-1 mg/min): DOPAMINE, 200 mg in 5 ml amp
- 60. • Dobutamine: nota Dl or D2 receptor agonist. • b1 (prominent action) + a • At 2-8ug/kg/ min i.v. infusion: increased force of cardiac contraction and output, without significant change in heart rate, peripheral resistance • Dobutamine is b1 selctive agonist • Ephedrine: • Mainly acts indirectly but has some direct action on alpha and beta receptors also. • Repeated injections Tachyphylaxis • Resistant to MAO orally.
- 61. • Amphetamines • Centraleffects: alertness, jncreased concentration & attention span, euphoria, talkativeness, increased work capacity. Fatigue is allayed. Athletic performance is improved temporarily followed by deterioration • 'dope test' for athletes. • Reticular activating system is stimulated resulting in wakefulness and postponement of sleep deprivation • But short-lived & may be accompanied by anxiety, restlessness, tremor, dysphoria and agitation • Use in examinations can only be condemned • Potentiate antiepileptics, analgesics and anti motion-sickness drugs. Peripheral effects on heart and BP are not significant at the usual doses • Amphetamines are drugs of abuse & capable of producing marked psychological but little or no physical dependence
- 62. • Phenysephrine:selective a1agonist, has negligible beta action • raises BP by causing vasoconstriction little cardiac actionreflex bradycardia. Topical nasal decongestant Producing mydriasis when cycloplegia is not required. Phenylephrine tends to reduce IOT by constricting ciliary body blood vessels Orally administered nasal decongestant preparations. Central effects are not seen with usual clinical doses DECOLD PLUS 5 mg with paracetamol 400 mg + chlorpheniramine 2 mg + caffeine 15 mg DROSYN EYE DROPS 10%
- 63. • Methoxamine :a1 agonist • Mephentermine a & b+NA release • Not substrate for MAO &COMT
- 64. • SELECTIVE BETA-2STIMULANTS • Salbutamol, Terbutaline, Salmeterol, Formoterol & Ritodrine • As uterine relaxant to delay premature labour (Ritodrine, Isoxsuprine) • In hyperkalemic familial periodic paralysis— BETA-2 agonists benefit by enhancing K+ uptake into muscles lowering plasma K+ levels • The most important side effect is muscle tremor; tachycardia
- 65. • Nasal decongestants •Phenylephrine Naphazoline Xylometazoline Pseudoephedrine Oxymetazoline PhenylPropanolamine • Anorectics • Non adrenergic appetite centre • Phenylpropanolamine • Serotonergic satiety centre • Fenfluramine, Dexfenfluramine • Non adrenergic/Serotonergic : Sibutramine
- 66. Therapeutic uses • Hypotension •Along with local anaesthetic agent • As an styptics • Nasal decongestant • Cardiac arrest • AV block: Isoprenaline • CHF • Bronchial asthma • Mydriatic • Hyperkinetic children • Narcolepsy • Obesity • Uterine relaxant • Insulin hypoglycemia • Nocturnal enuresis in children
- 67. a-ADRENERGIC BLOCKING DRUGS •adrenergic neurone blocking agents • a- adrenergic blocking Drugs
- 68. • CLASSIFICATION • Nonequilibriumtype (non-competitive) • Phenoxybenzamine • Equilibrium type (competitive) • A. Nonselective Ergot alkaloids: Ergotamine, Ergotoxine Hydrogenated ergot alkalolds: Dihydroergotamine, Dihydroergotoxine Imidazolines: Tolazoline, Phentolamine • B. a1 selective: Prazosin, Terazosin, Doxazosin, Tamsulosin • C. a2 selective: Yohimbine
- 69. • GENERAL EFFECTSOF a BLOCKERS • Blockade of a1TPR & VENOUS RETURN DECREASED & CO………..BP??? POSTURAL HYPOTENSION • Reflex tachycardia • Nasal stuffiness & miosis • Intestinal motility is increased • Hypotension reduce renal blood flow & g.f.r more complete reabsorption of Na & water increase in blood volume • Tone of s.m. in bladder trigone, sphincter & prostate is reduced(a1 blockade) improvement in BPH patients • • Contractions of vas deferensEjaculation(a response)
- 70. • Phenoxybenzamine • • Venodilatationis more prominent than arteriolar dilatation • In recumbent subjects cardiac output and blood flow to many organs are increased due to reduction in peripheral resistance & increased venous return • It tends to shift fluid from extravascular to vascular compartment. • Phenoxybenzamine is lipid soluble, penetrates brain and can produce CNS stimulation, nausea and vomiting on rapid i.v. injection • Oral doses produce, depression, tiredness and lethargy. postural hypotensiory , palpitation, nasal blockage, miosis, inhibition of ejaculation
- 71. • Phentolamine • Rapidlyacting a blocker with short duration of action (in minutes). • a1 & a2 equally blockade • NA release increased and venodilatation predominates over arteriolar dilatation • Diagnosis & intraoperative management of Pheochromocytoma • and for control of hypertension due to clonidine withdrawal, cheese • Reaction • It is the most suitable a blocker for local infiltration to counteract vasoconstriction due to extravasated NA/DA
- 72. Prazosin • Highl selectivea1: a2 100o:1 • Only mild tachycardia; NA released is not increased due to absence of a2 blockade • Prazosin dilates arterioles more than veinPostural hypotension is less marked • ‘first dose effect can be minimized by: • Starting with a low doses • Taking it at bedtime. • Prazosin is effective orally (bioavailab - • -60%), highly bound to plasma proteins • Antihypertensive • BPH
- 73. • Tamsulosin • Thisuroselectivec a1A /a1D • a1B BLOOD VESSEL • Tamsulosin : URIMAX,
- 74. • Pheochromocytoma &Phentolamine test • Hypertension • Clonidine withdrawal & Cheese reaction • Benign hypertrophy of prastate (EHP) • Secondary shock Shock due to blood or fluid loss is accompamed by reflex vasoconstriction • Peripheral vascular disease • Papaverine & Phentolamine induced penile erection therapy for impotence (inj corpus cavernosum ) • Cangestive heart fatlure (CHF)??? USES OF a BLOCKERS
- 75. CLASSIFICATION b ADRENERGTCBLOCKTNGD RUGS • Nonselective (b1 & b2) • Without intrinsic sympathomimetic activity • Propranolol, Sotalol, Timolol. • With intrinsic sympathomimetic activity • Pindolol • With additional a blocking property • Labetalol, Carvedilol • Cardioselective (b1 ) • Metoprolol, Atenolol, Acebutolol, Bisoprolol • Esmolol, Betaxolol, Celiprolol, Nebivolol
- 76. PHARMACOLOGICAL ACTIONS • HeartPropranolol decreases HR, FC (at relatively higher doses) & C.O. • Effects on a normal resting subject are mild, but become prominent under sympathetic over-activity (exercise, emotion). • Cardiac work & oxygen consumption are reduced • Coronary flow is reduced but this is largely restricted to the subepicardial region. • Overall effect in angina patients is improvement exercise tolerance is increased • The A-V conduction is delayed.
- 77. • Blood vesselsPropranolol blocks vasodilatation • On prolonged administration BP gradually falls in hypertensive subjects but not in normotensive • Total peripheral resistance (t.p r.) is increased • With continued treatment, resistance vessels graduallv adapt to chronically reduced c.o. so that t.p.r. decreases-both systolic and diastolic BP fall • • Reduced NA release from sympathetic terminals due to blockade of presynaptic beta -receptor mediated facilitation of the release process • Decreased renin release from kidney • Central action reducing sympathetic outflow.
- 78. • Respiratory tract:B2 • CNS: anxiety & migrain • Metabolic: Hypglycemia, HDL/LDL: (B2) • Skeletal muscle: B2 • Eye: • Tremors: B2 • PHARMACOKINETICS
- 79. • Uses • Hypertension •AP • Cardiac arrhythmias • MI • By preventing reinfarction • By preventing sudden ventricular fibrillation at the second attack of MI • Myocardial salvage during evolution of MI • CHF • THYROTOXICISIS • MIGRAINE • ESSENTIAL TREMORS BETA-2 action • GLAUCOMA • Anxiety • Pheochromocytoma • ADRs & contraindications