PRACTICAL PHARMACOLOGY-1 (303) Third Year FACULTY OF PHARMACY Department of Pharmacology & Toxicology CAIRO UNIVERSITY Pharmacology staff.

PRACTICAL PHARMACOLOGY-1 PRACTICAL PHARMACOLOGY-1 (303)(303)

Third YearThird Year

FACULTY OF PHARMACY

Department of Pharmacology & Toxicology

CAIRO UNIVERSITY

Pharmacology staffPharmacology staff

Dog Blood Pressure Dog Blood Pressure ExperimentExperiment

IntroductionIntroduction

• Following induction of surgical anesthesia Following induction of surgical anesthesia (typically by IV pentobarbital) catheters are (typically by IV pentobarbital) catheters are placed as followsplaced as follows

1.1. One for IV injection of drugs on the one One for IV injection of drugs on the one hand (femoral vein)hand (femoral vein)

2.2. The other for intra-arterial monitoring of The other for intra-arterial monitoring of arterial blood pressure on the other hand arterial blood pressure on the other hand (femoral artery).(femoral artery).

B.P. = C.O. X P.RB.P. = C.O. X P.R..

Stroke volume

Heart Rate

PreloadForce of

contraction

Blood volumeVeins

capacity

Blood vess

elβ2(-)

α1(+)

M3(-)

β1

β1(+)

M2(-)

Endothelium

β1(+)

Parasympahtetic Parasympahtetic acting drugsacting drugs

11..Acetylcholine(Ach)Acetylcholine(Ach)Direct acting ParasympathomimticsDirect acting Parasympathomimtics

• Effect:↓ B.P. Short duration of action Effect:↓ B.P. Short duration of action

• Receptors involved: ↑ M receptors Receptors involved: ↑ M receptors agonistic effect agonistic effect

(stimulation)(stimulation)

• Hemodynamic mechanism: agonist on (MHemodynamic mechanism: agonist on (M33) receptors ) receptors

on blood vessels endothelium releasing NO on blood vessels endothelium releasing NO V.D. V.D. ↓ ↓

TPR TPR ↓ B.P. ↓ B.P.

• Short duration of action due to rapid metabolism by Short duration of action due to rapid metabolism by

CHECHE

22..CarbacholCarbachol ↑ ↑ M & N receptorsM & N receptors

• Direct acting parasympathomimeticsDirect acting parasympathomimetics

• Same as Acetylcholine, but longer duration Same as Acetylcholine, but longer duration of action due to resistance to hydrolysis by of action due to resistance to hydrolysis by plasma cholinesterase (CHE).plasma cholinesterase (CHE).

3. Pilocarpine3. PilocarpineTypical muscarinic agonist acting as Ach or Typical muscarinic agonist acting as Ach or

CarbacholCarbachol

Sympathetic Sympathetic acting drugsacting drugs

11 . .EpinephrineEpinephrine • Effect:Effect:↑↑ B.P. , short duration of action B.P. , short duration of action

• Receptors involved: Receptors involved: ↑ ↑ ββ1& 1& αα1 >>>1 >>> β β2 receptors2 receptors• Hemodynamic mechanism:Hemodynamic mechanism:• Stimulation of Stimulation of ββ1 1 ↑↑SV &SV &↑ ↑ contractility contractility ↑ HR ↑ HR ↑CO↑CO

↑ B.P. ↑ B.P.

CO = SV X HRCO = SV X HR• the the capacity forcapacity for vasoconstriction mediated by αvasoconstriction mediated by α--receptor is receptor is

much highermuch higher than that of than that of the the β β --receptorsreceptors at high doses at high doses ↑↑ TPR TPR ↑↑ B.P. B.P.

At therapeutic dose stimulation of At therapeutic dose stimulation of ββ receptors >> receptors >> αα11• Short duration of action due to rapid metabolism.Short duration of action due to rapid metabolism.

22 . .NorepinephrineNorepinephrine ↑↑ α α1 >>>>>> 1 >>>>>> ββ22

• ↑↑ αα1 1 generalized generalized V.C. & V.C. & ↑ ↑ BP. BP.

• NNo affinity to βo affinity to β2 2

• Destroyed by COMT.Destroyed by COMT.

No effect on CONo effect on CO

((↑↑ ββ1 1 ↑ ↑SV & SV & ↑ ↑ HR HR ↑ ↑CO withCO with

reflex bradycardia reflex bradycardia ↓↓COCO ) )

33 . .PhenylephrinePhenylephrine Selective ↑ Selective ↑ α α11

•Same effects of NESame effects of NE

•Not desteroyed by COMT Not desteroyed by COMT

↑↑duration of actionduration of action

55 . .IsoproterenolIsoproterenol

• Effect: InitialEffect: Initial↑↑ B.P. followed by B.P. followed by huge dec. in BP huge dec. in BP • Receptors involved: Receptors involved: ↑ ↑ ββ1 & 1 & ββ22• Hemodynamic mechanism:Hemodynamic mechanism:

Stimulation of Stimulation of ββ1 1 ↑ contractility ↑ contractility ↑↑ HR HR ↑CO↑CO ↑↑ B.P. B.P. followed by huge depressor effect due to followed by huge depressor effect due to

↑ ↑ ββ2 on blood vessels "generalized 2 on blood vessels "generalized vasodilation”vasodilation” ↓ TPR ↓ TPR dec. in BP dec. in BP

You are provided with a tracing of You are provided with a tracing of

dog blood pressure. Decide each of dog blood pressure. Decide each of

the following:the following:

1.1. Describe the type of observed Describe the type of observed

effect on BPeffect on BP

2.2. Mention the type of autonomic Mention the type of autonomic

receptors involved and the type of receptors involved and the type of

action (agonist or action (agonist or

antagonist)antagonist)

3.3. Explain the hemodynamic Explain the hemodynamic

mechanism involved in the drug-mechanism involved in the drug-

induced effect on BP induced effect on BP

Drugs acting Drugs acting on the rabbit on the rabbit

eyeeye

Anatomy of the eyeAnatomy of the eye

M3α

1

MiosisMydriasis

Innervation of iris Innervation of iris musclemuscle

Phenylephrine (active)Phenylephrine (active)acts on acts on αα1 on radial pupillae muscle 1 on radial pupillae muscle contraction of muscle contraction of muscle dilatation of pupil dilatation of pupil Active mydriasis Active mydriasis indicated by presence of light indicated by presence of light reflexreflex

α1

Atropine (passive)Atropine (passive)Anticholinergic drug block M3 on circular Anticholinergic drug block M3 on circular constrictor muscle constrictor muscle leaving sympathetic leaving sympathetic unopposed unopposed Passive mydriasisPassive mydriasis indicated by indicated by loss of light reflexloss of light reflex

M3

α1

Mydriasis even in

presence of light

Pilocarpine “direct Pilocarpine “direct cholinomimeticscholinomimetics””

Acts on M3 on circular constrictor muscle Acts on M3 on circular constrictor muscle contraction of the muscle contraction of the muscle constriction of pupil constriction of pupil miosis. miosis.

M3

Eserine “Physostigmine”Eserine “Physostigmine”indirect cholinomimeticsindirect cholinomimetics

• Inhibit Ch.E Inhibit Ch.E accumulation of Ach on M3 on accumulation of Ach on M3 on circular constrictor muscle circular constrictor muscle contraction of contraction of the muscle the muscle constriction of pupil constriction of pupil miosis. miosis.

M3

Ch.E

Eserine

↑Ach

You are provided with two photos of You are provided with two photos of rabbit's eye, one control and rabbit's eye, one control and another after treatment with an another after treatment with an autonomic nervous system drug. autonomic nervous system drug. Determine each of the followingDetermine each of the following::

1.1. Type of effect and name of inducing drugType of effect and name of inducing drug

2.2. Type of receptor involved, and whether Type of receptor involved, and whether the drug is agonist or antagonistthe drug is agonist or antagonist

3.3. Pharmacological mechanism involved in Pharmacological mechanism involved in drug induced effect (pupillary muscle)drug induced effect (pupillary muscle)

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