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

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

Stimulation of muscarinic àCircular muscle eye (miosis) àciliary muscle ( àciliary muscle (accommodation) àbronchial smooth muscle àGIT wall bladder wall àvenous sphincters (penis) contract

Stimulation muscarinic àSecretions GIT GIT Bronchi Bronchi àHeart rate àAV Conduction increase decrease

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

Parasympathetic organ GIT contract muscle relax sphincters increase secretions digestion

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

Parasympathetic organ  metabolism Respiratory system Bronchoconstriction Mucous secretion

Parasympathomimetic drugs muscarinic agonists muscarinic agonists bethanecolpilocarpine Indirect acting acetylcholine esterase inhibitors acetylcholine esterase inhibitors neostigminepyridostigmineedrophonium malathion long acting pesticides malathion reversible reversible irreversible irreversible direct acting

Therapeutic uses Eye Eye GIT Bladder CVS Glaucoma pilocarpine bethanecolneostigmine Post surgical ileus Urine retention End supra- Ventriculartachycardia neostigmine edrophonium

Therapeutic uses Poisoning Alzheimer Atropine-like neostigmine donepezilrivastigmine diagnosis Increase CNS ACh levels pyridostigmine Myasthenia gravis treatment edrophonium

Therapeutic uses muscarinic blockers Eye Eye GIT Bladder Surgical Ophthalmic exam Cycloplegic, atropinehomatropine oxybutininamitriptyline Irritable bowel Syndrome diarrhoea enuresis bradycardia dry secretions mebeverinediclomine atropineglycopyrrolate

Therapeutic uses muscarinic blockers CNS CNS Respiratory N & V Pesticide poison TremorParkinson's orphenadrinebiperidine scopolamineantihistamines Asthma COPD Stabilize vestibular Motion sickness Block parasymp over stimulate ipratropium bromide atropine

Parasympathetic effects Terminate bradycardiaSurgery CVS   acetylcholine on AV node edrophonium atropineglycopyrrolate Terminate SV Tachycardia digoxin

Location of receptors Sympathetic Nervous System VascularSmoothMuscle Presynaptic inhibition GIT Pancreas platelets Alpha 1 Alpha 2 eye

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

2222 noradrenalinereleaseInsulin Sympathetic Nervous System 1111 VSM arterioles Radial muscle eye Increaseresistance Inhibitpresynaptic

Renin release increase HR contractility Liverglucose Sympathetic Nervous System 1111

Pregnant uterus bronchi Blood vessels vessels Sympathetic Nervous System 2222 relaxdilate

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

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

Sympathomimetic agents Depends on   Location of adrenergic receptor   Specificity for alpha / beta receptors   Reflexes

Sympathetic agonists on organ systems conduction (+ve dromotropic) Heart amphetaminecocainedopamine Stroke volume (+ve inotropic) Heart rate (+ve chronotropic) beta-1 receptors adrenalinenoradrenaline

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

Sympathetic agonists bronchi beta 2 receptors (dilate) Relieve asthma Respiratory ↓ Blood flow to nasal mucosa alpha 1 receptors (constrict) decongestion adrenaline phenylephrineoxymetazolinepseudoephedrinesalbutamolsalmeterol

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

Sympathetic Nervous System Blood BloodPressure Constrict Dilate 2222 1111 Arterioles - VSM

Sympathetic effects on blood vessels skeletal muscle VSM skinsplanchnic 1111 2222 dilateluminal (not innervated) constrict Innervated SNS

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

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

Therapeutic uses Eye Eye Nasal Nasal congestion CNS Glaucoma dipivefrineapraclonidine Constrict blood vessel Decrease fatigue Appetite suppressant phenylephrinepseudoephedrine pseudoephedrineamphetamine

Therapeutic uses Eye Eye LRT labour red eye allergy phenylephrineoxymetazoline salbutamolhexoprenaline Asthma COPD premature relax uterus salbutamolsalmeterol

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

Adrenoreceptor blocking agents alpha 1 + alpha 2 - blockers selective alpha 1 selective irreversible (phenoxybenzamine) reversible (phentolamine) prazosin doxazosin doxazosin

Beta – adrenoreceptor blocking agents Block agonist on beta-receptor AC Gs Ca 2+ ATP cAMP Kinase Contraction Ca 2+ SR V

Beta - adrenergic blockers beta 1 + beta 2 (non – selective) beta 1 (cardiac – selective) beta 1 beta 2 + alpha 1 carvedilol propranolol / timolol atenolol / bisoprolol

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

Therapeutic uses - blockers CVS Heartfailure hypertension Anginapectoris atenololbisoprolol Arrhythmia Post MI bisoprololcarvedilol

Anxiety Anxiety Migraine Eye DecreaseCVS atenololpropranolol prophylaxis Glaucoma Topical reduce aqueous humour timololmetipranolol BPH BPH Reduce mass Improve voiding prazosindoxazosin Therapeutic uses - blockers

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

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

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

Cardioselective beta - blockers Advantage  in diabetes  asthma  PVD Side effects and CI

Other beta - blockersAcebutolol  Intrinsic sympathomimetic (ISA)  partial agonists  TPR?  prevent bradycardia CO =  SV x HR

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

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

 1 - adrenergic blockers prazosin / doxazosin   Post-synaptic  1 receptors antagonist   Block NA induced vasoconstriction   CO / HR unaltered   Benefit HDL : LDL   Now in BPH

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

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

alpha-methyldopa èConvert to alpha- methylnoradrenaline èReduce TPR è / reflexes intact è+ve Coombs Test èSedation èHepatitis èFluid retention

ReserpinePeripheral  Depletes NA vesicles (centrally)  blocks DA entry  Decreases sympathetic activity  Increases venous tone  Increases venous tone

Reserpine side effects   Postural hypotension   Reb ound PSNS (diarrhoea, bradycardia, peptic ulcer depression, drowsiness   Na + + H 2 O retention   Effect + 3 weeks t½ = + 75 days

 Heart  Resistance  Central  Renin Sympathetic blockers in hypertension

Classes of anti-hypertensivesResistance  Diuretics - Na+/volume  Calcium channel blockers  Direct vasodilators  Angiotensin inhibitors  Resistance  Na/water