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

2. Dog Blood Pressure Experiment

3. Introduction Following induction of surgical anesthesia (typically by IV pentobarbital) catheters are placed as followsFollowing induction of surgical anesthesia (typically by IV pentobarbital) catheters are placed as follows 1.One for IV injection of drugs on the one hand (femoral vein) 2.The other for intra-arterial monitoring of arterial blood pressure on the other hand (femoral artery).

5. B.P. = C.O. X P.R. Stroke volumeHeart Rate Preload Force of contraction Blood volumeVeins capacity Blood vessel β2(-) α1(+) M3(-) β1β1 β1(+)M2(-) Endothelium β1(+)

6. Parasympahtetic acting drugs

7. 1.Acetylcholine(Ach) Direct acting Parasympathomimtics Effect:↓ B.P. Short duration of actionEffect:↓ B.P. Short duration of action Receptors involved: ↑ M receptors  agonistic effect (stimulation)Receptors involved: ↑ M receptors  agonistic effect (stimulation) Hemodynamic mechanism: agonist on (M 3 ) receptors on blood vessels endothelium releasing NO  V.D.  ↓ TPR  ↓ B.P.Hemodynamic mechanism: agonist on (M 3 ) receptors on blood vessels endothelium releasing NO  V.D.  ↓ TPR  ↓ B.P. Short duration of action due to rapid metabolism by CHEShort duration of action due to rapid metabolism by CHE

9. 2.Carbachol ↑ M & N receptors Direct acting parasympathomimeticsDirect acting parasympathomimetics Same as Acetylcholine, but longer duration of action due to resistance to hydrolysis by plasma cholinesterase (CHE).Same as Acetylcholine, but longer duration of action due to resistance to hydrolysis by plasma cholinesterase (CHE). 3. Pilocarpine Typical muscarinic agonist acting as Ach or Carbachol

12. Sympathetic acting drugs

13. 1. Epinephrine 1. Epinephrine Effect: ↑ B.P., short duration of actionEffect: ↑ B.P., short duration of action Receptors involved: ↑ β1& α1 >>> β2 receptorsReceptors involved: ↑ β1& α1 >>> β2 receptors Hemodynamic mechanism:Hemodynamic mechanism: Stimulation of β1  ↑ SV & ↑ contractility  ↑ HR  ↑CO  ↑ B.P.Stimulation of β1  ↑ SV & ↑ contractility  ↑ HR  ↑CO  ↑ B.P. CO = SV X HR CO = SV X HR the capacity for vasoconstriction mediated by α- receptor is much higher than that of the β - receptors at high doses  ↑ TPR  ↑ B.P.the capacity for vasoconstriction mediated by α- receptor is much higher than that of the β - receptors at high doses  ↑ TPR  ↑ B.P. At therapeutic dose stimulation of β receptors >> α1 Short duration of action due to rapid metabolism.Short duration of action due to rapid metabolism.

15. 2. Norepinephrine ↑ α1 >>>>>> β2 ↑ α1  generalized V.C. & ↑ BP.↑ α1  generalized V.C. & ↑ BP. No affinity to β2No affinity to β2 Destroyed by COMT.Destroyed by COMT. No effect on CO ( ↑ β1  ↑ SV & ↑ HR  ↑ CO with reflex bradycardia  ↓ CO)

16. 3. Phenylephrine Selective ↑ α1 Same effects of NESame effects of NE Not desteroyed by COMT  ↑ duration of actionNot desteroyed by COMT  ↑ duration of action

19. 5. Isoproterenol 5. Isoproterenol Effect: Initial ↑ B.P. followed by huge dec. in BPEffect: Initial ↑ B.P. followed by huge dec. in BP Receptors involved: ↑ β1 & β2Receptors involved: ↑ β1 & β2 Hemodynamic mechanism:Hemodynamic mechanism: Stimulation of β1  ↑ contractility  ↑ HR  ↑CO  ↑ B.P. followed by huge depressor effect due to ↑ β2 on blood vessels "generalized vasodilation”  ↓ TPR  dec. in BP

21. You are provided with a tracing of dog blood pressure. Decide each of the following: 1. Describe the type of observed effect on BP 2. Mention the type of autonomic receptors involved and the type of action (agonist or antagonist) 3. Explain the hemodynamic mechanism involved in the drug-induced effect on BP

22. Drugs acting on the rabbit eye

23. Anatomy of the eye M3M3 α1α1 Miosis Mydriasis

24. Innervation of iris muscle

25. Drugs acting on rabbit eye Mydriatics Phenylephrine Atropine Miotics Pilocarpine Eserine (Physostigmine)

26. Phenylephrine (active) Phenylephrine (active) acts on α1 on radial pupillae muscle  contraction of muscle  dilatation of pupil  Active mydriasis indicated by presence of light reflex α1α1

27. Atropine (passive) Anticholinergic drug block M3 on circular constrictor muscle  leaving sympathetic unopposed  Passive mydriasis indicated by loss of light reflex M3M3 α1α1 Mydriasis even in presence of light

28. Pilocarpine “direct cholinomimetics” Acts on M3 on circular constrictor muscle  contraction of the muscle  constriction of pupil  miosis. M3M3

29. Eserine “Physostigmine” indirect cholinomimetics Inhibit Ch.E  accumulation of Ach on M3 on circular constrictor muscle  contraction of the muscle  constriction of pupil  miosis.Inhibit Ch.E  accumulation of Ach on M3 on circular constrictor muscle  contraction of the muscle  constriction of pupil  miosis. M3M3 Ch. E Eseri ne ↑Ac h

30. You are provided with two photos of rabbit's eye, one control and another after treatment with an autonomic nervous system drug. Determine each of the following: You are provided with two photos of rabbit's eye, one control and another after treatment with an autonomic nervous system drug. Determine each of the following: 1.Type of effect and name of inducing drug 2.Type of receptor involved, and whether the drug is agonist or antagonist 3.Pharmacological mechanism involved in drug induced effect (pupillary muscle)

31. توزيع مجموعات الطلاب في امتحان نظري العملي اليومالمكانأرقام الطلابالساعة الإثنين 12/22 مـــــدرج منصور خليفة 640 - 511 3:00 – 3:10 770 – 641 3:30 – 3:40 900 - 771 4:00 – 4:10 للآخر- 901 4:30 – 4:40 الخميس 12/25 1 - 13011:00 – 11:10 131 - 26011:30 – 11:40 261 - 39012:00 – 12:10 391 - 51012:30 – 12:40 على الطلبة الباقون للإعادة حضور امتحان نظري العملي في مجموعتهم (901 – للآخر)