1. 1

2.  It is the major constituent of the adrenal medulla secretion (80%).  Hydrochloride aqueous solutions are hydrolyzed rapidly in alkaline or neutral media but are stable at low pH and in the presence of reducing agents (ascorbic acid). 2

3. Absorption and Fate:  It is not effective orally because: A.Poor absorption from the GIT B.Rapid destruction by digestives juices C.Rapid metabolism by the liver 3

4. Absorption and Fate:  It is absorbed slowly from s.c. tissues due to local vasoconstriction (α-effect).  It is more rapidly absorbed from i.m. sites (β 2 -mediated vasodilatation).  Inhaled solutions have a restricted action to the respiratory tract.  Intracardiac: emergency.  Infusion: adrenaline and noradrenaline. 4

5. Pharmacological actions: I.Local actions: 1.On mucous membranes or abraded surfaces  vasoconstriction  A.Added to local anesthetics to prolong their duration of action. B.A haemostatic action when applied to bleeding surface. C.A delay in the absorption of associated drugs when injected subcutaneously 5

6. 2.Local application of adrenaline to the eye:  It has a limited effect on the size of the pupil because: A.It is partly destroyed by the alkalinity of tears. B.It causes v.c. of the conjunctival blood vessels  hinders its own absorption.  In patients with open angle glaucoma, it helps to  the formation of the A.H. &  its drainage   the IOP. 6

7. Adrenaline causes mydriasis in the following conditions: Adrenaline causes mydriasis in the following conditions: 1.Acute hemorrhagic pancreatitis. 2.Postganglionic sympathetic denervation of the dilator pupillae muscle. 3.Some cases of glaucoma. 4.Hyperthyroidism. 5.Diabetic coma. 7

8. II.Systemic actions: 1.Cardiovascular system: A.Heart (β 1 receptors) i.  Heart rate (+ve chronotropic action, tachycardia). ii.  Force of contraction (+ve inotropic action). iii.  Cardiac output. iv.  Heart work and O 2 consumption. 8

9. B.Blood vessels (α and β 2 ) i.α-Stimulation  v.c. of the blood vessels of the skin, mucous membrane and kidney. ii.β 2 -Stimulation  v.d. of the skeletal muscle and coronary blood vessels. 9

10. C.Blood pressure (B.P.):   SBP (due to  COP) while DBP changes up or down depending on the final effect on the PVR.  Therapeutic doses   PVR due to the dominant action on β 2 receptors   DBP.  Experimentally, epinephrine (low dose)   B.P. because of its β effects. Gradual  epinephrine doses   B.P. (marked α effects) and ergotamine (α-adrenergic blocker) administration   B.P. (epinephrine reversal) as epinephrine would act only on β-receptors. 10

11. The pressor effect of phenylephrine (a selective α 1 -stimulant) is abolished by ergotamine. The pressor effect of NE is partially blocked by ergotamine [the pressor effect of NE is partly due to its v.c. (α 1 -receptors) and partly due to a cardiac stimulant action (β 1 - receptor) that remains in effect after α- receptors blockade]. 11

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13. 2.Effect on Eye:  Active mydriasis (α 1 -receptors )!!!  No loss of light reflex & accommodation. 13

14. 3.Effect on bronchi:  It stimulates β 2 -receptors in the bronchioles  bronchodilatation.  Adrenaline acts also on α-receptors of blood vessels  v.c.   bronchial mucosal congestion. 14

15. 4.Gastrointestinal tract:  The GIT contains both α and β receptors.  Stimulation of either types of receptors leads to inhibition of tone and motility. 15

16. 5.Urinary bladder  Adrenaline relaxes the detrusor muscle (β 2 -receptors) and contracts the sphincter (α 1 -receptors)  urine retention. 16

17. 6.Uterus:  Adrenaline relaxes the pregnant human uterus (β 2 ). 17

18. 7.Metabolic Actions: A.  Blood glucose through: i.Enhancement of hepatic glycogenolysis (β 2 ). ii.  Glucose uptake by peripheral tissues. B.  Blood lactate (  breakdown of glycogen to lactate in skeletal muscles). 18

19. 7.Metabolic Actions: C.  Blood concentration free fatty acids (due to lipolysis β 1 & β 3 ). (  Breakdown of TGs in adipose tissues) D.  O 2 consumption (20-30%) due to  metabolism. E.A transient  in plasma K + level followed by a prolonged fall. 19

20. 8.Action on the CNS:  Adrenaline has a weak stimulant effect  restlessness, headache & tremors. 20

21. 9.Skeletal muscle action:  It facilitates neuromuscular transmission by sensitization of the motor endplate and hastens recovery from fatigue by increasing blood flow to the muscles. 21

22. 10.Antihistamine and antiallergic action.  Adrenaline is the physiological antagonist of histamine. 22

23. Therapeutic Uses: 1)Acute bronchial asthma  bronchodilatation &  bronchial mucosal congestion and edema. 2)Allergy, urticaria, edema and anaphylactic shock. 3)Insulin hypoglycemia. 4)Cardiac resuscitation (intracardiac injection of adrenaline in cardiac arrest). 23

24. 3)Adrenaline is given with local anesthetics (s.c.)  v.c.  A.Prolong their durations of action. B.  Bleeding from the operation sites. 6)Local hemostatic (stop hemorrhage from the nasal mucosa, epistaxis). 7)As eye drops in some cases of glaucoma. 24

25. Contraindications: 1.Coronary heart diseases (  anginal attacks) 2.Hypertension (  cerebral hemorrhage). 3.Cardiac arrhythmias. 4.During anesthesia with halogenated inhalational anesthesia. 5.In patients receiving digitalis 6.Hyperthyroidism. 7.With local anesthetics in fingers and toes. 25