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ANS. Sympathetic Nervous System. Parasympathetic Nervous System. Nuclei in CNS. PREGANGLION. GROWTH. POSTGANGLION. Flight Fright Fight. END ORGAN. Ach Nicotinic. O. O. ACh. gut. Parasympathetic. Noradrenaline. Sympathetic. Somatic. Nicotinic. ACh.

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  1. ANS Sympathetic Nervous System Parasympathetic Nervous System Nuclei in CNS PREGANGLION GROWTH POSTGANGLION Flight Fright Fight END ORGAN

  2. Ach Nicotinic O O ACh gut Parasympathetic Noradrenaline Sympathetic Somatic Nicotinic ACh

  3. Stimulation of muscarinic • Circular muscle eye (miosis) • ciliary muscle (accommodation) • bronchial smooth muscle • GIT wall bladder wall • venous sphincters (penis) contract

  4. Stimulation muscarinic • Secretions GIT Bronchi • Heart rate • AV Conduction increase decrease

  5. Parasympathetic organ accommodation Eye Miosis Contract ciliary muscle Aqueous humour outflow Open canal of Schlemm Glaucoma

  6. Parasympathetic organ GIT contract muscle relax sphincters increase secretions digestion

  7. Parasympathetic organ Bladder Urine voiding contract muscle relax sphincter CVS Inhibit AV / SA node metabolism

  8. Parasympathetic organ Respiratory system Bronchoconstriction Mucous secretion metabolism

  9. Parasympathomimeticdrugs Indirect acting acetylcholine esterase inhibitors direct acting muscarinic agonists bethanecol pilocarpine reversible irreversible neostigmine pyridostigmine edrophonium long acting pesticides malathion

  10. Therapeutic uses pilocarpine Eye Glaucoma Post surgical ileus neostigmine GIT Bladder bethanecol neostigmine Urine retention End supra- Ventricular tachycardia CVS edrophonium

  11. Therapeutic uses neostigmine Poisoning Atropine-like diagnosis edrophonium Myasthenia gravis treatment pyridostigmine donepezil rivastigmine Increase CNS ACh levels Alzheimer

  12. Therapeutic uses muscarinic blockers Ophthalmic exam Cycloplegic, atropine homatropine Eye Irritable bowel Syndrome diarrhoea mebeverine diclomine GIT Bladder oxybutinin amitriptyline enuresis bradycardia dry secretions Surgical atropine glycopyrrolate

  13. Therapeutic uses muscarinic blockers Tremor Parkinson's CNS orphenadrine biperidine Respiratory ipratropium bromide Asthma COPD N & V scopolamine antihistamines Stabilize vestibular Motion sickness Pesticide poison atropine Block parasymp over stimulate

  14. Parasympathetic effects CVS Terminate SV Tachycardia Terminate bradycardia Surgery • acetylcholine on AV node edrophonium atropine glycopyrrolate digoxin

  15. Vascular Smooth Muscle Presynaptic inhibition GIT Pancreas platelets Location of receptors Sympathetic Nervous System Alpha 2 Alpha 1 eye

  16. Location of receptors Sympathetic Nervous System Beta Respiratory Uterus SA node myocardium JG Cells Adipose Vascular Smooth Muscle Liver

  17. Sympathetic Nervous System 1 VSM arterioles Radial muscle eye Increase resistance Inhibit presynaptic 2 noradrenaline release Insulin

  18. Sympathetic Nervous System contractility HR 1 increase Renin release Liver glucose

  19. Sympathetic Nervous System bronchi 2 relax dilate Pregnant uterus Blood vessels

  20. Sympathetic agonists alpha-1 phenylephrine / oxymetazoline alpha-2 alpha-methyldopa / clonidine beta-1 dopamine / dobutamine beta-2 dopamine / dobutamine

  21. Multi receptor agonists adrenaline alpha 1+2 / beta 1+2 pseudoephedrine Weak release adrenaline / noradrenaline amphetamine strong release adrenaline / noradrenaline reuptake inhibitor (nor)adrenaline / dopamine cocaine

  22. Sympathomimetic agents Depends on • Location of adrenergic receptor • Specificity for alpha / beta receptors • Reflexes

  23. Sympathetic agonists on organ systems Heart adrenaline noradrenaline beta-1 receptors Stroke volume (+ve inotropic) Heart rate (+ve chronotropic) conduction (+ve dromotropic) amphetamine cocaine dopamine

  24. Sympathetic agonists on organ systems Eye (nor)adrenaline alpha 1 receptors mydriasis (contract radial muscle) Decrease blood flow to ciliary body (constrict)) phenylephrine dipivefrine apraclonidine

  25. Sympathetic agonists Respiratory adrenaline ↓ Blood flow to nasal mucosa alpha 1 receptors (constrict) decongestion bronchi beta 2 receptors (dilate) Relieve asthma salbutamol salmeterol phenylephrine oxymetazoline pseudoephedrine

  26. Sympathetic agonists on organ systems Metabolic (nor) adrenaline B cells pancreas alpha 2 (Inhibit insulin) Adipose tissue beta 3 receptors Increase lipolysis JG (renal) beta receptors Increase renin Liver beta 2 receptors Increase glycogenolysis

  27. Sympathetic Nervous System Arterioles - VSM 1 2 Constrict Dilate Blood Pressure

  28. Sympathetic effects on blood vessels constrict Innervated SNS 1 skin splanchnic skeletal muscle VSM dilate luminal (not innervated) 2

  29. Sympathomimetic agents specificity  /  receptor 1 2 1 2 adrenaline noradrenaline dopamine dobutamine phenylephrine pseudoephedrine amphetamine cocaine

  30. Sympathetic effects on 1 Heart chronotropic inotropic 1 2 reflexes Arterioles - VSM

  31. Therapeutic uses dipivefrine apraclonidine Eye Glaucoma Nasal congestion Constrict blood vessel phenylephrine pseudoephedrine Decrease fatigue Appetite suppressant pseudoephedrine amphetamine CNS

  32. Therapeutic uses phenylephrine oxymetazoline red eye allergy Eye salbutamol salmeterol Asthma COPD LRT labour salbutamol hexoprenaline premature relax uterus

  33. Therapeutic uses CVS hypertension alpha-methyldopa anaphylaxis adrenaline Shock Renal failure dopamine adrenaline Acute heart failure Ventricular fibrillation

  34. Adrenoreceptor blocking agents alpha1 + alpha2 - blockers irreversible(phenoxybenzamine) reversible(phentolamine) alpha1selective prazosin doxazosin

  35. Beta – adrenoreceptor blocking agents Block agonist on beta-receptor V AC Gs ATPcAMP Kinase Contraction Ca2+ Ca2+ SR

  36. Beta - adrenergic blockers beta1 + beta2 (non – selective) propranolol / timolol beta1(cardiac – selective) atenolol / bisoprolol beta1beta2 + alpha 1 carvedilol

  37. Adrenergic antagonists on organs CVS Decrease heart rate dilate VSM (alpha) block (nor)adrenaline bronchi increase airway resistance Eye mydriasis (alpha) decrease aqueous JG (renal) decrease renin Liver Block sympathetic hypoglycaemia

  38. Therapeutic uses - blockers bisoprolol carvedilol Heart failure hypertension atenolol bisoprolol CVS Angina pectoris Arrhythmia Post MI

  39. Therapeutic uses - blockers Anxiety Decrease CVS atenolol propranolol Migraine prophylaxis prazosin doxazosin BPH Reduce mass Improve voiding Glaucoma Topical reduce aqueous humour timolol metipranolol Eye

  40. Beta blockers - MOA lower blood pressure heart decrease heart rate decrease SV / SBP renal decrease renin CNS decrease SNS out put VSM Presynaptic decrease NA

  41. Beta - blockers CO =  SV x HR Nonselective • propranolol • timolol • Short half life • Blocks (cardiac) 1and 2receptor

  42. Beta - blockers CO =  SV x HR Cardioselective • atenolol • bisoprolol • Blocks mainly cardiac 1 - receptor

  43. Cardioselective beta - blockers Advantage • in diabetes • asthma • PVD Side effects and CI

  44. Other beta - blockers CO =  SV x HR Acebutolol • Intrinsic sympathomimetic (ISA) • partial agonists • TPR? • prevent bradycardia

  45. Mixed  /  blocker carvedilol • 3:1  /  blocker • TPR • Heart failure • Improves morbidity and mortality

  46. Adverse effects beta blockers block (nor)adrenaline Cardiovascular Asthma COPD Bradycardia AV block Heart failure PVD Limit exercise respiratory diabetes Block sympathetic hypoglycaemia CNS Vivid dreams depression

  47. 1 - adrenergic blockers prazosin / doxazosin • Post-synaptic 1 receptorsantagonist • Block NA induced vasoconstriction • CO / HR unaltered • Benefit HDL:LDL • Now in BPH

  48. 1 - adrenergic blockers • First dose low BP • Postural hypotension • Impotence • Urinary incontinence • CNS depression • Tolerance? • Safety in hypertension?

  49. Centrally acting - receptor agonists alpha-methyldopa – 2agonist (locus coreleus) medulla  - presynaptic receptor NA Reduce central sympathetic output Post - synaptic Preferred in hypertension pregnancy

  50. alpha-methyldopa • Convert to alpha- methylnoradrenaline • Reduce TPR • / reflexes intact • +ve Coombs Test • Sedation • Hepatitis • Fluid retention

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