Adrenaline & Noradrenaline

1. Adrenaline & noradrenaline Dr Nida Fatima jawaharlal nehru medical college , AMU ALIGARH
2. adrenaline • Catecholamine, sympatho-mimetic monoamine, derived - phenylalanine and tyrosine. • C9H13NO3 • MOL WT:183.20442 g/mol
3. Biosynthesis HO NH2 CO2H L-Tyrosine Tyrosine hydroxylase HO NH2 CO2H Levodopa HO HO NH2 Dopamine HO Dopa Decarboxylase Dopamine -hydroxylase HO HO NH2 OH Norepinephrine (Noradrenaline) HO HO NHMe OH Epinephrine (Adrenaline) N-methyl transferase (in Adrenal medulla)
4. Mechanism of action
5. Types of -adrenergic receptor Receptor Sites of action Effects 1 smooth muscle, heart, and liver vasoconstriction, intestinal relaxation, uterine contraction and pupillary dilation, 2 platelets, vascular smooth muscle, nerve termini, and pancreatic islets platelet aggregation, vasoconstriction, and inhibition of NE release and of insulin secretion.
6. Types of β-adrenergic receptor Receptor Sites of action Effects β1 Heart tachycardia β2 lungs, gastrointestinal tract, liver, uterus, vascular smooth and skeletal muscle Bronchodilatation Smooth muscle relaxation, sphincter constriction β3 Fat cells
7. Receptors and signal transduction in the ANS Adrenergic Receptors 1A 1 2 1B 1D 2A 2B 2C 1 2 3
8. Classification of Adrenergic Hormone Receptors Receptor Agonists Second Messenger G protein alpha1 (1) NE > E IP3/Ca2+; DAG Gq alpha2 (2) E > NE  cyclic AMP Gi beta1 (1) E = NE  cyclic AMP Gs beta2 (2) E >> NE  cyclic AMP Gs E = epinephrine; NE = norepinephrine
9. Cardiovascular effects of adrenergic agonists
10. PHARMACODYNAMICS
11. ADRENALINE PREPARATIONS • Clear solution conc. of 1:1000 (1ml amp) or 1:10 000 (10 ml mini-jet for resuscitation). • Along with L.A- conc. of 1:200 000, upto 1:80 000 (Lignocaine 2% for dental inj). • Auto-injectors for use in anaphylaxis • 0.3 mg and 0.15 mg (EpiPen®) for i.m inj.
12. SIDE EFFECTS • Exaggerated effects of adrenaline, overdosage, inadvertent i.v injection , inappropriate use. • palpitations, tremor, light headedness • tachycardia, arrhythmias, hypertension • cerebral haemorrhage ,acute pulmonary edema • lactic acidosis
13. Effects of adrenaline on organs and tissues in the body ORGAN EFFECT RECEPTOR TYPE Heart Increase heart rate Increased contractility β1 β1 Blood vessels Vasoconstriction Vasodilation α1 β2 Lungs Bronchodilation β2 Uterus Relaxation β2
14. ORGAN EFFECT RECEPTOR Metabolism Inhibits pancreatic insulin secretion α2β2 Glycogenolysis in liver and muscle α1β2 Glycolysis in muscle α1β2 Gluconeogenesis α1β2 Glucagon secretion in pancreas α2 ACTH secretion by pituitary β Lipolysis in adipose tissue β2β3 Renin secretion from kidney β1β2
15. RESUSCITATION • Adrenaline - DOC -cardiac arrest. • Main action - ↑ vascular resistance via α1 vasoconstriction → improves perfusion pressure to the myocardium and brain. • Adrenaline -greatest effect when given i.v intraosseous route if i.v route not patent.
16. ADR IN ACLS • VF/VT cardiac arrest -1mg ,in the third cycle after 2 shocks and then every 3-5 minutes (alternate CPR cycles). • PEA arrest -1 mg, and then every 3-5 minutes (alternate cycles). • Children-10 micrograms ( 0.1 mL of the 1:10,000 solution) per kg i.v ,repeated every 3-5 minutes.
17. ADR IN ACLS • Bradycardia: 1mg ADR with 500ml of NS or D5W. Infusion @ 2-10 µg/min (titrated to effect). • ROSC hypotension: 0.1-0.5 mcg/kg/min • Endotracheal Tube: 2-2.5mg ADR is diluted in 10cc NS and given directly into ET tube.
18. ANAPHYLAXIS • Adrenaline is the drug of choice. • α1-agonist, reverses -peripheral vasodilation by inflammatory mediator release,↓ oedema. • β activity dilates bronchial airways, ↑myocardial contractility, ↓ histamine and LT release and ↓ severity of IgE-mediated allergic reactions.
19. Management of acute anaphylaxis AGE IM DOSE (micrograms) (ml of 1:1000 solution) IV DOSE (micrograms) (ml of 1:10 000 solution) Adult 500 micrograms (0.5 ml) 50 micrograms (0.5 ml) titrated to effect Child > 12 years 500 micrograms (0.5 ml) 50 micrograms (0.5 ml) titrated to effect Child 6-12 years 300 micrograms (0.3 ml) 1 microgram/kg titrated to effect Child < 6 years 150 micrograms (0.15 ml) 1 microgram/kg titrated to effect
20. ANAPHYLAXIS DOSES • Adults-initial dose is 100 to 500 microgram (0.1 to 0.5 mL of the 1:1,000 sol) SC or IM. • repeated at 20 minute to 4 hour intervals • severe anaphylactic shock, slow and cautious IV administration-100 to 250 microgram • Children-10 microgram per kg SC repeated at intervals of 20 min to 4 hrs
21. INOTROPIC SUPPORT • Continuous infusion in ICU- via CVP line, with invasive blood pressure monitoring. • Indications : • profoundly low blood pressure, • shock, • low cardiac output states and • status asthmaticus.
22. • There is no single appropriate concentration. • 4 mg Adrenaline diluted to 50 ml in saline or 5% dextrose, infused by means of a syringe driver. • Rate of infusion -titrated to effect, to achieve target blood pressure.
23. AIRWAY OBSTRUCTION • Severe croup-m/c airway indication for Adr. • angio-oedema- life threatening obstruction. • racemic adrenaline -nebulized route. • MOA-reduce the local inflammatory process and to provide local vasoconstriction- reducing obstruction caused by oedema.
24. DOSAGE • L-Adrenaline-0.5 ml/kg of a 1:1000 solution (maximum of 5 ml) placed undiluted into the chamber of the nebulizer for children. • Racemic -0.05 ml/kg (max 1.5 ml) of 2.25% sol diluted to 4 ml NS.
25. Topical or local vasoconstriction • Local vasoconstricting action- adrenaline used as a topical application or combined with local anaesthetic to be infiltrated. • Prolongs its action, reduces bleeding at the site of injection or topically (nasal mucosa as part of Moffat’s solution)
26. CONTRA-INDICATIONS • Known hypersensitivity • Shock (other than anaphylactic shock) • Cardiac dilatation and insufficiency • Hypertension • Ischaemic heart disease • Arrhythmias • Cerebral arteriosclerosis
27. • Diabetes mellitus· • Hyperthyroidism • Narrow angle (congestive) glaucoma • Organic brain damage • Phaeochromocytoma / thyrotoxicosis • halogenated hydrocarbons or cyclopropane • L.A in fingers, toes, ears, nose or genitalia • Labour
28. NORADRENALINE Mol formula C8H11NO3 Catecholamine with multiple roles: •Hormone •Neurotransmitter.
29. BIOSYNTHESIS
30. ACTIONS • Stress hormone • Fight-or-flight response • Increases heart rate • Triggers the release of glucose • Increases blood flow to skeletal muscle. • Suppress neuro-inflammation.
31. Noradrenergic system • Amygdala • Cingulate gyrus • Cingulum • Hippocampus • Hypothalamus •Neocortex • Spinal cord • Striatum • Thalamus
32. VESICULAR TRANSPORT • Between the decarboxylation and final β- oxidation, norepinephrine is transported into synaptic vesicles. • Accomplished by vesicular monoamine transporter (VMAT) in the lipid bilayer. • This transporter has equal affinity for norepinephrine, epinephrine and isoprenaline
33. PHARMACODYNAMICS • Potent action-both a1 & b1 receptors –Little action on b2 –Causes potent vasoconstriction (α) –Lacks bronchodilating effect –↑ systolic, diastolic & MAP –Reflex bradycardia –Metabolic acidosis
34. PHARMACOKINETICS Onset- 1-2 min Duration- 1-2 min Metabolism- by COMT and MAO Distribution • Sympathetic nervous tissue. • Crosses the placenta not blood-brain barrier. Excretion- mainly urine (84-96%)
35. HYPOTENSIVE STATES • First-line therapy for maintenance of B.P and tissue perfusion in septic shock. • adjunct to correct hemodynamic imbalances • Start:8-12 µg/min IV infusion; titrate to effect • Maintenance: 2-4 mcg/min IV infusion • Septic shock: 0.01-3 mcg/kg/min IV infusion
36. Cardiac Arrest • Adjunctive Treatment in Cardiac Arrest • Infusions of noradrenaline given during cardiac arrest to restore and maintain an adequate blood pressure after an effective heartbeat and ventilation have been established by other means. • Initial: 8-12 mcg/min IV infusion; titrate to effect • Maintenance: 2-4 mcg/min IV infusion
37. DOSAGE • The usual dose range is 0.01-0.1 m/kg/min • Avg. adult maintenance dosage: 2–4 µg/min • May require 8–30 mcg/minute in cases of refractory shock • Drug is diluted with 5% dextrose or dextrose normal saline
38. • administered through central venous line to minimize the risk of extravasation and subsequent tissue necrosis • control rate and strict monitoring • must not be stopped suddenly, gradually withdrawn to avoid disastrous falls in blood pressure Noradrenaline infusion
39. Noradrenaline infusion • 4mg = 4mL of 1:1000 • Add 4mL of 1:1000 Noradrenaline to 46mL 5% Glucose to make 50mL • Starting dose- 0.025microgram/kg/minute • the rate in mL/hour
40. INFUSION TABLE
41. ADVERSE EFFECTS  Hypertension , bradycardia, arrhythmias, palpitations  Ischemic injury -potent vasoconstriction.  Anxiety, insomnia, confusion,  Headaches, psychosis  Weakness, tremor  Anorexia, nausea and vomiting.
42. Extravasation • Infusion site-checked frequently for free flow. • Avoid extravasation of noradrenaline • Local necrosis -vasoconstrictive action • Blanching- change infusion site • Extravasation-infiltrate area → 10 ml-15 ml of saline solution containing 5 mg to 10 mg of phentolamine.
43. Comparison Features Adrenaline Noradrenaline Heart rate ↑ ↓ Cardiac output ↑↑ -- Blood pressure-systolic ↑↑ ↑↑ diastolic ↑↓ ↑↑ mean ↑ ↑↑ Bronchial muscle ↓↓ -- Intestinal muscle ↓↓ ↓ Blood sugar ↑↑ --, ↑
44. Drug interaction • Non-selective MAO inhibitors • selective MAO inhibitors • Linezolid • Thyroid hormones • Cardiac glycosides • Ergot alkaloids or oxytocin # enhance the vasopressor and vasoconstrictive effects.
45. CONTRA-INDICATIONS • Known hypersensitivity • hypotensive from blood volume deficits • mesenteric or peripheral vascular thrombosis • Cyclopropane and halothane anesthetics

Editor's Notes

Adrenaline acts non-selectively at all the adrenergic receptors (α1, α2, β1, β2, β3) to produce a ‘flight or fight’ response. Its mechanism of action is via membrane receptors, which trigger a second messenger response

Both of these formulations contain 1 mg of adrenaline

once chest compressions have restarted
is given as soon as intravascular access is achieved
Epinephrine should not be used in cardiogenic shock because it increases myocardial oxygen demand, nor should it be used in hemorrhagic or traumatic shock

(for example a 70kg adult: 7-35 mcg/min would be given).
Epinephrine should be used with caution in patients suffering from myocardial infarction since epinephrine increases heart rate and raises blood pressure. This increase in HR and BP can increase myocardial oxygen demand and worsen ischemia.

The preferred route is intramuscular (IM)
For IM use, the anterolateral aspect of the middle third of the thigh is the best site for injection
The dose can be repeated at 5 minute intervals if there is no improvement and according to the patient’s response.

, and the local ICU policies and guidelines should be observed.
microgram per minute (mcg/min) microgram per kilogram per minute (mcg/kg/min).

Anaphylaxis Agent, Anesthetic Adjunct, Antiglaucoma, Bronchodilator, Decongestant, Vasopressor
generally as alternatives to inhaled, short-acting beta2-adrenergic agonists, as bronchodilators in the symptomatic treatment of bronchial asthma and reversible bronchospasm that may occur in association with chronic bronchitis, emphysema, and other obstructive pulmonary diseases.
The ophthalmic preparations are used to decrease conjunctival and scleral inflammation and edema and to treat primary open-angle glaucoma.

Smaller doses are described for conditions other than croup, but these may be increased or repeated until the desired effect is achieved. All the anticipated side effects of systemic adrenaline may occur (described above), so the patient should be carefully monitored in a high care environment.

Epinephrine has been administered intra-arterially via the celiac artery, inferior mesenteric artery, or superior mesenteric artery to control hemorrhage in patients with severe GI bleeding and via the renal artery to control hemorrhage in patients with renal arterial bleeding. Epinephrine also has been injected into one renal artery prior to and during irradiation of the abdominal area involving both kidneys. The drug may protect the kidney from radiation nephritis by causing vasoconstriction which results in hypoxia. /Use not currently included in US product label/
Epinephrine has been given intra-arterially in conjunction with radiographic contrast media in arteriography. Epinephrine may improve visualization by causing vasoconstriction thereby reducing dilution of the contrast media in the blood. In addition, some tumors (especially if highly vascularized) may be better defined, apparently because epinephrine causes constriction and reduced filling of normal arteries surrounding the tumor while having minimal effect on the tumor vasculature. /Use not currently included in US product label

Known hypersensitivity to sympathomimetic amines

norepinephrine affects parts of the brain where attention and responding actions are controlled
Along with epinephrine, norepinephrine also underlies the fight-or-flight response
triggering the release of glucose from energy stores
suppress neuroinflammation when released diffusely in the brain from the locus ceruleus.

The noradrenergic neurons in the brain form a neurotransmitter system, that, when activated, exerts effects on large
areas of the brain. The effects are alertness and arousal, and influences on the reward system.
noradrenergic neurons originate both in the locus coeruleus and the lateral tegmental field. The
axons of the neurons in the locus coeruleus act on adrenergic receptors in:On the other hand, axons of neurons of the lateral tegmental field act on adrenergic receptors in hypothalamus, for
example

Causes potent vasoconstriction (α) as well as a less pronounced increase in cardiac output
May decrease tissue blood flow leading to metabolic acidocis

Orally ingested noradrenaline is destroyed in the GI tract and the drug is poorly absorbed after subcutaneous injection.

It causes rise in systolic ,diastolic and mean arterial pressure
adjunct to correct hemodynamic imbalances in the treatment of shock that persists after adequate fluid volume therapy

Dilution-
Drug is diluted with 5% dextrose or dextrose normal saline
Should not be mixed with alkaline solution

ischemic injury due to potent vasoconstrictor action may result in coldness and paleness in periphery

phentolamine, an adrenergic blocking agent

Also noradrenaline decreases blood flow to skin mucous membranes and kidneys but increases coronary circulation along with adrenaline

Known hypersensitivity to sympathomimetic amines

hypotensive from blood volume deficits except as an emergency measure to maintain coronary and cerebral artery perfusion until blood volume replacement therapy can be completed.
continuously administered to maintain blood pressure in the absence of blood volume replacement, the following may occur: severe peripheral and visceral vasoconstriction, decreased renal perfusion and urine output, poor systemic blood flow despite “normal” blood pressure, tissue hypoxia, and lactate acidosis
Cyclopropane and halothane anesthetics increase cardiac autonomic irritability and therefore seem to sensitize the myocardium to the action of intravenously administered epinephrine or norepinephrine.- ventricular tachycardia or fibrillation.

Adrenaline & Noradrenaline

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Adrenaline & Noradrenaline

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