Practical pharmacology CNS

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Transcript of Practical pharmacology CNS

PRACTICAL PHARMACOLOGY

PRACTICAL PHARMACOLOGY2ND YEAR MEDICAL STUDENTSMODULE IXBYDR. HAZEM ABO SHOUSHA

Dr hazem Abo ShoushaDr hazem Abo Shousha

Main rulesABP: pressure of blood on arterial wall

ABP= COP X PVR

COP= HR X SVMain rules

HEART RATEMain rulesM2

Main rules1 AgonistM2 blocker1 blockerM2 agonistHEART RATE

Main rulesBLOOD VESSELS12

M3

Main rulesBLOOD PRESSURE (Bl.V)VC1 agonist2 blockerVD1 blocker2 agonistM3 agonist

Main rulesBARORECEPTORS

VDVC

NORADRENALINE 11

HAZEM (H) - NORADRENALINE diff. doses

Observation: increased ABP with minimal effect on HR, which increases only with high doses

Explanation of effect of NE on ABP & HR: NE acts mainly on 1 receptors vasoconstriction PVR

With higher doses of NE, it activates also cardiac 1 receptors some increase in the heart rate

PRAZOSIN 1 blocker

What is the effect of Prazosin on ABP and HR? it blocks 1 adrenoceptors vasodilationPVRABPABP slight reflex tachycardia

Noradrenaline cause very minimal in HR 1 stimulation minimal in BP

1 1 2ADRENALINE

Observation: ABP & HR late The ABP before returning to base line level Explanation of the effect of epinephrine on HR & ABPEpinephrine stimulates 1 , 1, 2 adrenoceptors Beta receptors are more sensitive to the effect of epinephrine On heart: b1 activation +ve inotropic & chronotropic effects COP leading to increased ABPOn BV : - 1 activation vasoconstriction PVR. - 2 activation vasodilatation PVR

The net effect of these two opposing effects (1 & 2 ) on bl.v is an in PVR (1 wins at 1st )

At High concentration:EPI stimulates 1 At Low concentration:EPI stimulates 2

AdrenalineNoradrenalineparametersMore increase Mild or no increaseHeart rate Less increase than noradrenalineMore increase Blood pressureBP decreases before reaching base line Reach base line directly BP before Base line

1 blockerCardioselective beta blockerATENOLOL

Observation: blocking 1 receptors by atenolol blocks the effect of epinephrine on HR & decreases the effect on ABP

block alpha1 & beta1 receptors & then inject epinephrine

EPINEPHRINE REVERSAL: The presser effect of epinephrine is reversed due to 1 & 1 blockade, leaving the 2 vasodilating effect acting ABP

1 + 2 blockerNon-selective beta blockerPROPRANOLOL

How to confirm the cause of epinephrine reversal?

No epinephrine reversal since propranolol blocks not only cardiac 1 receptors but also vascular 2 receptors

What is the effect of propranolol on ABP and HR?

Propranolol mechanism as antihypertensive:1-Block 1 in heart so low COP BP2- central sympathetic discharge BP3- Block 1 in kidney Renin BP4- resetting of Baroreceptors BP5- Block 2 presynaptic NE release BP

1 + 2 agonistNon-selective beta agonistISOPRENALINE

Observation: Isoprenaline increases HR Isoprenaline initially decreases ABP. As HR reaches its maximum increase, ABP shows minimal increase before returning to normal Explanation for the effect of isoprenaline on HR & ABP Isoprenaline activates mainly beta adrenoceptor It activates cardiac 1 receptors leading to increase in HR & force of contraction (which increases COP)Activation of 2 receptorsVasodilation decrease in PVR The net effect of the two factors (COP & PVR) is a decrease in blood pressure initially.However, when force of contraction is markedly elevated, the increase of COP overcomes the effect of decrease in PVR and thus ABP starts to increase.

Design an experiment to prove the explanation for the effect of Isoprenaline on HR & ABP

Observation: atenolol abolishes the effect of isoprenaline on HR The initial ABP-lowering effect of isoprenaline is maintained, while its pressor effect is abolished

PROPRANOLOL FOLLOWED BY ISOPRENALINE

Observation: Propranolol blocks 1 & 2 receptors thus abolishes the effect of isoprenaline on ABP

Dr hazem Abo ShoushaDr hazem Abo Shousha

1 agonistselective Alpha agonistPHENYLEPHRINE

Observation: Small dose phenylephrine leads to slight increase in ABP with no effect on HRHigh dose phenylephrine increases markedly ABP with decrease in the HR ( reflex bradycardia)

Explanation of the effect of phenylephrine on ABP & HRActivation of 1 receptors vasoconstrictionPVR

High dose of phenylephrine marked elevation of ABP reflex in sympathetic activity. Parasympathetic activity will take the upper hand HR

prove the explanation of the effect of phenylephrine on HR and ABPObservation: prazosin abolishes the effect of phenylephrine on ABP & reflex bradycardia disappears

prove that reflex bradycardia is due to relative increase in parasympathetic activity

Observation: decreased HR is abolished by atropine despite of elevation of ABP

Nicotinic Nn , NmACETYLCHOLINE ( Ach ) Muscarinic M1 , M2 ,M3

Observation: small doses of acetylcholine lower only ABPHigher doses produce both in the HR & more significant lowering of ABP

Explanation for the effect of acetylcholine on HR and ABPon heart: M2 activation - ve chronotropic effect COPon BV: endothelial cells M3 activation release of NO from vascular endothelial cells vasodilatation PVRDecrease in heart rate & decrease in PVR lead to ABP

Inject ATROPINE & then test the effect of ACETYLCHOLINE

ACETYLCHOLINE REVERSAL

1. Inject a test dose of Ach2. Inject atropine 3.Inject the same dose of acetylcholine4.Inject a dose of Ach which is 10 times the test dose

Explanation for acetylcholine reversalAtropine injection A parasympatholytic blocks muscarinic receptors. It blocks the effect of small dose of Ach.Ach injection [big dose] Stimulates nicotinic receptors Nn after muscarinic receptors have been blocked by atropine ABPDue to activation of Nn at : Adrenal medulla release epinephrine BPAutonomic ganglia release of catecholamines from post-synaptic adrenergic nerve endings BPThe BP by Ach [big dose] after muscarinic receptor block [by atropine] Ach reversal

Ach reversal by : Nn receptorsEPI reversal by : 2 receptors

Reversible anticholinesteraseSo Ach augment Ach effect NEOSTIGMINE

prove the mechanism of action of neostigmine