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Adrenaline (Epinephrine)

Adrenaline (Epinephrine)

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Adrenaline (Epinephrine)

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  1. Adrenaline (Epinephrine)

  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).

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

  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 (β2-mediated vasodilatation). • Inhaled solutions have a restricted action to the respiratory tract. • Intracardiac: emergency. • Infusion: adrenaline and noradrenaline.

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

  6. Local application of adrenaline to the eye: • It has a limited effect on the size of the pupil because: • It is partly destroyed by the alkalinity of tears. • 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.

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

  8. Systemic actions: • Cardiovascular system: • Heart (β1 receptors) •  Heart rate (+vechronotropic action, tachycardia). •  Force of contraction (+veinotropic action). •  Cardiac output. •  Heart work and O2 consumption.

  9. Blood vessels (α and β2) • α-Stimulation  v.c. of the blood vessels of the skin, mucous membrane and kidney. • β2-Stimulation  v.d. of the skeletal muscle and coronary blood vessels.

  10. 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.

  11. 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].

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

  13. 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.

  14. Gastrointestinal tract: • The GIT contains both αand βreceptors. • Stimulation of either types of receptors leads to inhibition of tone and motility.

  15. Urinary bladder • Adrenaline relaxes the detrusor muscle (β2-receptors) and contracts the sphincter (α1-receptors)  urine retention.

  16. Uterus: • Adrenaline relaxes the pregnant human uterus (β2).

  17. Metabolic Actions: •  Blood glucose through: • Enhancement of hepatic glycogenolysis (β2). •  Glucose uptake by peripheral tissues. •  Blood lactate ( breakdown of glycogen to lactate in skeletal muscles).

  18. Metabolic Actions: •  Blood concentration free fatty acids (due to lipolysisβ1 & β3). • ( Breakdown of TGs in adipose tissues) •  O2 consumption (20-30%) due to  metabolism. • A transient  in plasma K+ level followed by a prolonged fall.

  19. Action on the CNS: • Adrenaline has a weak stimulant effect  restlessness, headache & tremors.

  20. 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. Antihistamine and antiallergic action. • Adrenaline is the physiological antagonist of histamine.

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

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

  24. Contraindications: • Coronary heart diseases ( anginal attacks) • Hypertension ( cerebral hemorrhage). • Cardiac arrhythmias. • During anesthesia with halogenated inhalational anesthesia. • In patients receiving digitalis • Hyperthyroidism. • With local anesthetics in fingers and toes.