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 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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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