1.Adrenaline (Epinephrine)

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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).

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• Absorption and Fate: It is not effective orally because:

A.Poor absorption from the GITB.Rapid destruction by digestives

juicesC.Rapid metabolism by the liver

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• 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 (β2-mediated vasodilatation). Inhaled solutions have a restricted

action to the respiratory tract. Intracardiac: emergency. Infusion: adrenaline and noradrenaline.

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• 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

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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.

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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.

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II.Systemic actions: 1.Cardiovascular system:A.Heart (β1 receptors)

i. Heart rate (+ve chronotropic action, tachycardia).

ii. Force of contraction (+ve inotropic action).

iii. Cardiac output.iv. Heart work and O2 consumption.

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B.Blood vessels (α and β2)

i. α-Stimulation v.c. of the blood vessels of the skin, mucous membrane and kidney.

ii.β2-Stimulation v.d. of the

skeletal muscle and coronary blood vessels.

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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 β2 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. 1

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The pressor effect of phenylephrine (a selective α1-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. (α1-receptors) and partly due to a cardiac stimulant action (β1-receptor) that remains in effect after α-receptors blockade].

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2.Effect on Eye: Active mydriasis (α1-receptors )!!! No loss of light reflex &

accommodation.

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3.Effect on bronchi: It stimulates β2-receptors in the

bronchioles bronchodilatation. Adrenaline acts also on α-receptors

of blood vessels v.c. bronchial mucosal congestion.

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4.Gastrointestinal tract: The GIT contains both α and β

receptors. Stimulation of either types of

receptors leads to inhibition of tone and motility.

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5.Urinary bladder Adrenaline relaxes the detrusor

muscle (β2-receptors) and contracts

the sphincter (α1-receptors) urine retention.

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6.Uterus: Adrenaline relaxes the pregnant

human uterus (β2).

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7.Metabolic Actions:A. Blood glucose through:

i. Enhancement of hepatic glycogenolysis (β2).

ii. Glucose uptake by peripheral tissues.

B. Blood lactate ( breakdown of glycogen to lactate in skeletal muscles).

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7.Metabolic Actions:C. Blood concentration free fatty

acids (due to lipolysis β1 & β3). ( Breakdown of TGs in adipose

tissues)

D. O2 consumption (20-30%) due to metabolism.

E. A transient in plasma K+ level followed by a prolonged fall.

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8.Action on the CNS: Adrenaline has a weak stimulant

effect restlessness, headache & tremors.

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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.

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10.Antihistamine and antiallergic action.

Adrenaline is the physiological antagonist of histamine.

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• 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).

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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 digitalis6.Hyperthyroidism.7.With local anesthetics in fingers and toes.

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