2. Course contents Lab1 : Introduction to Pharmacology and Concept of ( Dose - Response Curve ). Lab2 : Effect of cholinergic Drugs on intestine and % of antagonism. Lab3 : Effect of Adrenergic Drugs on intestine and Identification of Unknown. Lab 4 : Effect of Nm blockers on frog rectus abdominis muscle. Lab 5 : Spasmogens and their specific Antagonist on Guinea-Pig Ileum. Lab6 : Influence of Drugs on Isolated Rabbit’s Heart. Lab 7 : Influence of Drugs on Blood Pressure.

3. Marks Lab. 30 10 attendance and Reports 20 Final Exam 30 Mid-term Exams 40 Final Exam

4. Lab Coat Scrub Lab. requirements

5. Pharmacology : Drug : Any material which can alter biological function May be Synthetic or Natural Agonist : Has affinity and efficacy Antagonist : Has affinity but no efficacy Partial Agonist : Affinity and low efficacy. Inverse Agonist : Bind to the same receptor as the agonist but gives reverse response Pharmacology

6. Receptors Receptor : Structure which interacts with a drug to initiate chain of events leading to the response Receptor exhibit : 1 - Sensitivity. 2 - Selectivity : Response only elicited by a narrow range of chemical response. 3 - Specificity : Always elicit the same response. Response : Observable change in the state of the organ or organism : Contraction. Change in blood pressure. Behavioral change.

7. Lab. 1 Introduction to CNS Pharmacology & Concept of ( Dose - Response Curve )

8. P.N.S C.N.S Brain Brain stem cerebrum Spinal Cord White matter Gray matter Meninges Efferent ( Ventral horn ) Afferent ( Dorsal horn ) Somatic Voluntary muscle e.g. : Skeletal muscle Autonomic Involuntary muscle e.g. : Cardiac muscle Glands

9. Acetylcholine transmitter. - Long preganglionic neurons, short postganglionic neurons - Vagus nerve innervates heart, lungs, esophagus, stomach, small intestine, proximal colon, liver, gallbladder, pancreas, kidneys, upper ureters Acetylcholine transmitter. - Long preganglionic neurons, short postganglionic neurons - Vagus nerve innervates heart, lungs, esophagus, stomach, small intestine, proximal colon, liver, gallbladder, pancreas, kidneys, upper ureters Acetylcholine ( Ganglionoic ) Catecholamine ( Effector – cell ) -Short preganglionic neurons, long postganglionic neurons. - Adrenal medulla functions by releasing epinephrine & nor epinephrine into the systemic circulation Acetylcholine ( Ganglionoic ) Catecholamine ( Effector – cell ) -Short preganglionic neurons, long postganglionic neurons. - Adrenal medulla functions by releasing epinephrine & nor epinephrine into the systemic circulation

10. PreganglionicPostganglionic Ach

12. 25 ml Intestine part Oxygen Supply Valve (wash) Valve Physiograph

13. Tyroide’s Solution : To keep Intestine part a live contains : 1- Na Cl :Isotenicity 2- CaCl2 :Contraction of muscle 3- Glucose :Energy 4- NaHCO3 :PH 5- MgCl2 :Relaxation

14. It is a relationship between ( Dose ) and Response %. From this curve we can see :  Potency.  Efficacy.  Therapeutic Index.  ED 50.  Threshold.

15. 0.2ml0.4ml0.6ml0.8ml 1.6ml MaximumSub Maximum cm D + R DR complex Response

17. 0.10.20.30.70.60.5 ED 50 = 0.4 mL Dose mL 0.4 Response % 10 20 30 40 50 60 70 80 90 100

18. Lab. 2 Effect of cholinergic Drugs on intestine and % of antagonism.

19. M1 : CNS, Intestine M2 : Heart, Presynaptic Ganglia M3 : Exocrine gland M4 & M5 : CNS Nn Nm e.g. Ganglia e.g. Skeletal muscle

20. 1- Direct acting : e.g. Ach, Caracoled, Bethanechol, Pilocarpine 2- Indirect acting : A - Reversible : e.g. Physostigmine, Neostigmine, Pyridostigmine B – Irreversible : e.g. Organophosphate compounds : ( Isoflurophate, Echothiophate )

21. 1- Antimuscarinic Agents : e.g. Atropine, Ipratropium, Scopolamine 2- Ganglionic Blockers ( Non Selective ) : e.g. Pentamethonium, Hexamethonium, 3- Neuromuscular Blockers : A - Non-depolarizing ( Competitive ) : e.g. D-tubocurarine, …. etc B- Depolarizing Agents : e.g. Suxamethonium, Decamethonium

22. X1X1 X 1 – X 2 * 100 Dil Nic C 6 -Blocker Wash Dil Nic No Wash X1X1 X2X2

23. X1X1 X 1 – X 2 * 100 Ach Atropine Wash Ach No Wash

24. Bacl 2 C 6 -Blocker Wash Bacl 2 No Wash Atropine Wash No Wash Bacl 2 X1X1 X 1 – X 2 * 100

25. Lab. 3 Effect of Adrenergic Drugs on intestine and Identification of Unknown.

26. α1α1 β1β1 α2α2 β2β2  Negative feed-back Inhibit Release of ( Nor - Epi. )  Heart rate.  Force of contraction.  Blood pressure Vasoconstriction  Vasodilatation  Bronchodilatation  Glycogenolysis  Release of glucagons.

27. A) Adrenergic agonist : α-adrenergic agonist e.g. Nor-epinephrine β-adrenergic agonist e.g. Isoprenaline B) Adrenergic antagonist : α-adrenergic antagonist e.g. Phentolamine β-adrenergic antagonist e.g. Propranolol. B)Direct Relaxant : e.g. Papaverine

28. If the Unknown Produce contraction of the tissue,it may be nicotinic agonist,Muscarinic agonist or direct acting drug 1 - 0.2 ml of dil Nicotine, Record & wash 2 - 0.3 ml of C6-blocker,leave 2 min,add 0.2ml of dil Nic. (must block) without wash add 0.2ml of Unk,. Block,,,,,,,,,,,,,,,, Nicotine-like drug. Agonist no effect Muscarinic or Direct 3 - 0.2 ml of Ach, Record & wash 4 - 0.3 ml of Atropine,leave 2 min,add 0.2ml of Ach. without wash add 0.2ml of Unk,. Block, Muscarinic. No effect may be Direct stimulant.

29. Lab. 4 Effect of Nm blockers on frog rectus abdominis muscle

30.  Voluntary muscle which receive motor somatic innervations, (lack the ganglia)  Receptor is Nm which is different from receptors in the autonomic ganglia.  It contains Ach-esterase for destruction of Ach

31. Neuromuscular Agent : A - Direct acting : e.g. Ach, carbacol B – Indirect Acting : 1 - Choline-esterase inhibitors : e.g. Prostigmine 2 - Non-depolarizing blocker (Competitive ) : e.g. D-tubocurarine, Atracurium 3 - Depolarizing Agents blocker : e.g. Succinylcholine

32.  Frog-Ringer solution - No Mg+2 ( no relaxation) - ( Ca,K,PO4, Na, HCO3 ) - Glucosse  Tension 0.5-4 gm  Temp. 25 C

33. 1 - Add 0.2ml of Ach, Record, Wash. 2 - Add 0.2ml of Prostigmine,wait 2 min, Add 0.2ml Ach, Record,Wash. 3 - Add0.2ml Ach, Record, Wash, Add 0.2ml Carbacol,Record, Wash 4 - Add 0.2 ml Ach,Record, Wash, Add 0.2ml. Succinylcholine,Record, No wash,Add 0.2ml of Ach 5 - Add 0.2ml Ach,Record, Wash,Add 0.2ml Atracurium

34. Lab. 5 Effects of drugs on Isolated Perfused Rabbit’s Heart ( Langendroff’s Preparation )

35. Na for depolarization K for repolarization Glucose for energy Ca to prevent arrhythmias HCO3 for adjust PH Temp. 37 Oxygenation

36. Heart rate : Beats/Min Force of contraction Coronary Flow Rate: ml/min

37. A) Adrenergic Drugs - Epinephrine ( adrenaline ) Heart Rate Force of contraction of cardiac Muscle (β- Receptor) (--) Flow Rate - Norepinephrine ( noradrenaline ) Heart Rate less effect on Force of contraction (more on α) (--) Flow Rate - Isoproterenol ( Isoprenaline non selective β-Agonist ) Heart Rate Force of contraction (β - Receptor) (--) Flow Rate

38. B) Cholinergic Drugs : - Acetylcholine Heart Rate and cardiac output (--) Force of contraction of cardiac Muscle (Beta2- Receptor) (--) Flow Rate - Atropine ( ) Heart Rate (--) Flow Rate C) Calcium channel blockers - Verapamil Heart rate Force of Contraction (--) Flow rate - Amlodipine Heart rate Force of Contraction (--) Flow rate

39. D) C.H.F : - Digoxin Heart rate Force of Contraction Flow rate - Bretylium ( Adrenergic Neuronal Blocker ) Heart rate Force of Contraction - Amiodarone ( Adrenergic Neuronal Blocker ) Heart rate Force of Contraction - β 1 - agonist ( Dobutamine) Heart rate Force of Contraction

40. E) Vasodilator Drugs : - Isosorbide (Isordil) Heart rate Force of Contraction (--) Flow rate F) Anti-arrhythmic : - Procainamide Heart rate Force of Contraction (--) Flow rate - Lidocaine Heart rate Force of Contraction (--) Flow rate - β- blocker ( Propranolol ) Heart rate Force of Contraction (--) Flow rate