SYMPATHETIC NERVOUS SYSTEM

OVERVIEW OF ANS
SYMPATHETIC SYSTEM PREGANGLIONIC AND POST GANGLIONIC FIBERS
DISTRIBUTION OF SYMPATHETIC FIBERS
SYNTHESIS OF CATECHOLAMINES AND THERE INHIBITION AT VARIOUS LEVELS
RECEPTORS OF SYMPATHETIC SYSTEM
SYMPATHOMIMETIC DRUGS *DIRECTLY AND INDIRECTLY ACTING DRUGS*
SYMPATHOLYTIC DRUGS
USES OF THESE DRUGS
SUMMARY
ADDITIONAL INFO :ALPHA 2 RECEPTORS ARE MAJORLY PRESENT IN CNS AND DRUG USED IS CLONIDINE

1. Autonomic Nervous System [Sympathetic Nervous System] DR. SACHIN OJHA DEPARTMENT OF ANAESTHESIOLOGY T.S.M.M.C.H MENTOR- DR NEHA SHARMA

2. DOPAMINE  IN KIDNEYS ADRENALINE  IN ADRENAL MEDULLA ACETYL CHOLINE  IN SWEAT GLANDS AND PILO ERECTOR MS. OVERVIEW

3. PARASYMPATHETIC SYMPATHETIC HEART BRONCHUS BRONCHOCONSTRICTION BRONCHODILATATION GIT DIARRHEA ( INC SECRETION AND MOTILITY) CONSTIPATION (DEC SECRETION AND MOTILITY) BLADDER INCREASE OUTFLOW (CONTRACTING DETRUSOR AND RELAXING TRIGOME) DECREASE OUTFLOW (RELAXING DETRUSOR AND CONTRACTING TRIGOME) GLANDS INCREASE SECRETIONS DECREASE SECRETIONS PUPIL MIOSIS MYDRIASIS

4. Definition Sympathetic nerves originates in the spinal cord along with spinal nerves between cord segments T1 and L3 [Thoraco-Lumbar region]. Each sympathetic pathway from the cord to the stimulated tissue is composed of two neurons , a Preganglionic neuron and a postganglionic neuron . The sympathetic nervous system’s primary process is to stimulate Fight fright and flight response.

5. Preganglionic Preganglionic sympathetic nerve fibres- these are short , myelinated and type B fibres. Originates in thoracolumbar division of the spinal cord specifically at T1 to L2~L3 , and travels to a ganglion . Then they synapse with a postganglionic neurons . These fibres are cholinergic and use acetylcholine as their neurotransmitter.

6. Postganglionic Postganglionic sympathetic fibres – Arises from sympathetic ganglia These are long , non myelinated and type C fibres These fibres are adrenergic and use norepinephrine as a neurotransmitter.

7. Distribution of Sympathetic neurons Segmental level T1,T2 T3 ,T4 T5 to T9 T10 to L2 T6 to T12 L1,L2 T1 to T12 Area of distribution Head & Neck Thoracic viscera Upper limb Lower limb Upper abdominal viscera Lower abdominal viscera Thoracic & abdominal vessels

8. Metyrosine is a competetive inhibitor of tyrosine hence lesser tyrosine less norad production RESERPINE MOA IS through inhibition of the ATP/mg 2+  pump responsible for the sequestering of neurotransmitters into storage vesicles located in the presynaptic neuron . Guanethidine is a sympatholytic drug that acts by  displacing norepinephrine from postganglionic sympathetic nerve endings . The drug depletes tissue stores of norepinephrine , decreases reuptake of norepinephrine by the nerve terminals, and lowers sympathetic tone. COCAINE inhibits NET resulting in increased NA hence increased sympathetic activity.

9. RECEPTORS Also present on urinary bladder  mirabegron (in over active bladder)

10. Effects of sympathetic stimulation (DIALATOR PUPILLAE MS)

11. SYMPATHOMIMETICS {DIRECTLY ACTING} Catecholamines - Name is based on their chemical structure (hydroxyl groups at the 3 and 4 position of a benzene ring): High potency - activate both alpha and beta receptors Rapid inactivation - Destroyed by COMT (Catechol O-methyltransferase) and by MAO (Monoamine oxidase) which are present in the gut wall. hence Catecholamines are not effective when given orally Poor CNS penetration - They are polar but they still may cause some CNS effects

12. Non-catecholamines - Not destroyed by COMT and MAO deactivation is limited, so they have longer half lives Better CNS penetration due to increased lipid solubility

13. CATECHOLAMINES ENDOGENOUS ADRENALINE NOR ADRENALINE DOPAMINE EXOGENOUS DOBUTAMINE ISOPRENALINE FENOLDOPAM

14. DOPAMINE SHOCK Dopamine  alpha-1 vasoconstriction↑BP ~Also in shock BP↓↓filtration and pressure leading to renal failure. ~So in shock with oligouria DOC is DOPAMINE as it also stimulates D1 receptor which causing VD resulting in ↑filtration. 0.2-1mg/min regulated by monitoring bp and urine output. CHF Stimulates beta-1 receptors  ↑ heart reate

15. DOBUTAMINE Stimulates beta-1 receptors CHF 5-20mcg/kg/min DOBUTAMINE STRESS TESTING IN ANGINA 10mcg/kg 3 mins 203040 FENOLDOPAM Stimulates D-1 receptors Used in hypertensive emergencies and severe hypertention 0.1-1.6 mcg/kg/min

16. CNS ↑DBP ↓DBP ↑ SYMPATHETIC ↑HEART RATE ↑PARASYMPATHETIC ↓HEART RATE BARO -RECEPTORS

17. Adrenaline , Nor adrenaline , Isoprenaline

18. NOR ADRENALINE Stimulates alpha-1 , alpha-2 ,beta-1 receptors Alpha1 shock , hypertension Beta 1  ↑HR CHF 2-4mcg/min ISOPRENALINE Stimulates BETA-1 and BETA-2 receptors Beta 1  ↑H.R. CHF Beta 2  Bronchodilatation ASTHMA 20mg sublingual,1-2mg IM, 5-10mcg/min IV

19. ADRENALINE Cardiac arrest  C-A-B  adr 1:10000 (0.2-0.5mg) IV > intraosseus > endotracheal ANAPHYLACTIC SHOCK ALPHA-1 TO INCREASE BP BETA 2 FOR BRONCHODILATATION Route im /sc 0.5ml 1:1000 solution(1gm adr in 1000ml of solution) repeat every 10 mins If im fails iv adr 1:10000 solution to be given ADRENALINE WITH LOCAL ANAESTHESIA ADR  VC Systemic flow of LA obstructed  toxicity and shock chances ↓

20. Non catecholamines Alpha1 agonists Phenylephrine mydriasis  fundoscopy Methoxamine,mephentermine ↑BP (in hypotention ) Xylometazoline,oxymetazoline,naphazoline cause vasoconstrictiondegongestant . Overuse causes atrophic rhinitis/ rhinitis medicamentosa . Alpha 2 agonists Clonidine low dose present presynaptic ↓BP Also used to overcome withdrawl symptoms of drugs like morphine Beta 2 agonists Salbutamol,terbutalline inhalational routebronchodilatation  bronchial asthma Ritodrine,isoxsuprine  relaxes uterustocolytic (preterm labour )

21. SYMPATHOLYTICS: Drugs that reduce or inhibit some or all of the actions of the sympathetic nervous system.

22. α blocker α1+α2 blocker Selective and non selective α blockers are used for mild to moderate hypertention

23. Selective α blocker α1 blocker  vasodilation of BV ( ind HTN) increase urine outflow ( ind BPH) So pt with HTN+BPH can be administered with drugs such as PRAZOSIN (0.5-1mg upto 4mg BD or TDS) TERAZOSIN DOXAZOSIN(1mg OD) ALFUZOSIN(2.5mg bd - qid or 10mg OD in er ) These drugs may cause postural hypotension hence given at bed time.

24. On further research it was found out that α1 receptors are of two type α1a (majorly on prostatic urethra) and α1b (on blood vessels) So for pt with BPH without HTN only α1a blocker is given TAMSULOSIN (0.2-0.4mg) SILODOSIN(4-8mg)

25. ß blockers

26. Properties and drugs Cardioselective ß1 blocker Intrinsic sympathomimetic activity/partial agonist Membrane stabilising property/Na+ channel #/local anaesthetic Non lipid soluble/water soluble

27. 1. ß1# or cardioselective or 2 nd gen Safe in asthma ,PVD , DM

28. 2. Intrinsic sympathomimetic activity/partial agonist Celiprolol Pindolol Alprenolol Acebutolol 3. Membrane stabilising property/ Na channel blocker Indicated in arrythmias Not indicated in glaucoma as these drugs masks the corneal reflex Propanolol Metoprolol Labetalol Acebutolol Pindolol

29. 4. Water soluble Contraindicated in renal failure. ATENOLOL NADOLOL (LONGEST ACTING) SOTALOL

30. 3 rd generation Posses properties of  ß blocker and vasodialation (α #) Labetalol Dose : 50mg BD, increase to 100-200mg TDS oral. In hypertensives emergencies 20-40mg iv every 10 mins till desired effect is seen Carvedilol CHF: start with 3.125 mg bd for 2 weeks if well tolerated gradually increase max upto 25mg BD Hypertension/angina: 6.25mg BD initially, titrate to max 25mg BD.

31. Uses of ß blocker