- Adrenaline is a natural catecholamine with alpha and beta effects. At low doses, beta 1 and beta 2 effects predominate. At high doses alpha 1 effect predominate.
- Alpha1- GqPCR → stimulates phospholipase C → increased IP3/DAG → increased intracellular calcium and smooth muscle constriction
- Beta1 and 2 → GsPCR → increased adenylate cyclase → increased cAMP → increased phosphorylation

i) ↑myofilament Ca sensitivity by binding to Cardiac trop C in Ca-dependent manner.
ii) Vasodilation through opening of ATP-sensitive K channels
iii) selective PDE-III inhibition at higher conc - inotropy

lower doses: β2 - vasodilatory, bronchodilation
Higher doses β1 agonism: ↑ino+chronotropy
Highest doses: primarily a
vasoconstrictor.

Detail:
CVS:
- At low dose infusions (beta predominates), beta 2 effects lead to skeletal muscle vasculature vasodilation, leading to a decrease in DBP and SVR. It also causes coronary artery vasodilation.
- Beta-1 leads to increased inotropy, increased chronotropy (increases phase 4 gradient), and increased dromotropy. It increases myocardial oxygen consumption and lowers arrhythmia threshold
- At higher doses, alpha 1 effects predominate. This causes arteriolar vasoconstriction, which may increase aortic diastolic BP and therefore increase coronary perfusion pressure (e.g. arrest). At these doses it also increases coronary artery vasoconstriction. Venous return may be enhanced as capacitance vessels constrict
- Extravasation may cause tissue necrosis and injection into end arteries may lead to digital ischaemia

CNS:
- May cause anxiety, tremor and raises pain threshold. Causes mydriasis

Resp:
- Small increase in MV. Potent bronchodilator
- PVR increased

Renal:
- Decreased renal blood flow. Renin stimulation → increased aldosterone and potassium secretion
- Decreases plasma volume
- Increased bladder sphincter tone, may lead to difficulty of micturition

GIT:
- Decreased hepatosplanchnic flow. May lead to decreased lactate clearance
- Relaxation of gastrointestinal smooth muscle, leading to increased transit times

Haem: Coagulation is accelerated by adrenaline. Induces platelet aggregation and increases factor V activity

Metabolic
- Increases BMR
- Increases glycolysis (liver and skeletal muscle) and gluconeogenesis. Alpha1 effects suppress insulin secretion. Causes hyperglycaemia and lactic acidosis.
- Lipase activity is augmented, leading to increased lipolysis and keto-acidosis
- B2 stimulates Na/K/ATPase, lowering K+. B1 activates RAAS, which leads to aldosterone increasing K+ secretion

CVS:
- Increased cardiac output without increasing MVO2
- Causes coronary and peripheral vasodilation → anti-ischaemia and anti-stunning effects

GU:
Increased GFR and UO secondary to increased CO

IV, IM, SC, Inhaled, ETT
1mg arrest, 0.1mg anaph. Inf: β effects: 0.1-0.3mcg/kg/min
α: >0.3 (vasocon). on/dur imm/1-2min

IV only

doesn’t cross the BBB

small vd

98% protein binding.
Peak concentration after 48 hrs

0.2 L/kg

Taken up into adrenergic neuron – Metabolized by MAO and COMT

Circulating drug hepatically metabolized

Intestinal bacteria OR1896 active metabolite

Hepatic conjugation

Urine as inactive metabolites

excretion renal and fecal. Cardiac Effects 2-7 days

2 minutes

1 hour (70hr for active metabolite)

High doses: HTN+++, tachyarrhythmias, deranged metabolic
States: ↑ glucogenolysis, lipolysis, gluconogenesi
Insulin Prodxn: initial ↑ (β2) → ↓ (α) limiting use in DM.
Can worsen PHTN. Avoid in glaucoma. Peripheral necrosis.

Interference with potassium channels causes an increase in the QTc- theoretical ↑risk of arrhythmias. May cause hypotension. Caution should be exercised in
patients with renal or hepatic impairment.

ADRENERGIC

NON-ADRENERGIC

1. Anaphylaxis
2. Cardiac arrest
3. Low cardiac output states (including complete heart block)
4. Severe asthma
5. Glaucoma
6. Local vasoconstriction
7. Adjunct to local anaesthetic to prolong duration of action

short term management of severe acute heart failure

Is a naturally occurring catecholamine released in the adrenal medulla

Ca sensitizer and PDE-III inhibitor
selectively

Level 1

Level 3

Level 1

It is a non selective adrenergic agonist.

Mast cell stabilizer (anaphylaxis)

Increases Myofilament Ca sensitivity, vasodilation

IV,Neb. in clear sol, Vials 1mg/mL in 5 and 50 mL,
Minijets with 1mg in 10mL(1:10000).
With Lignocaine (1:80000-200000). In acidic sol as turns pink in alk(oxid to
Adrenochrome)

in IV form only - clear yellow solution 2.5mg/mL in 5 and 10ml vials

1. 1mg in PEA arrest IV
2. Infusion of 0.01-0.1micrograms/kg/min
3. 10mcg/kg (up to 500mcg) IM
4. Nebulizer or MDI

IV, loading dose of 6 to 24 mcg/kg over 10 minutes
then continuous infusion of 0.05-0.2 mcg/kg/min