- 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

Via selective PDE3 inhibition which causes
decreased cAMP breakdown intracellularly
and hence increased Ca

This improves myocardial contractility and improves cAMP-dependent protein phosphorylation leading to vascular smooth muscle relaxation.

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
- Positive inotrope, leading to increased cardiac output. CI increases 30%
- PCWP decreases 20%, with improved lusotropy
- SVR and MAP decrease
- May increase AV nodal conductance, accelerating arrhythmias in atrial fibrillation or flutter

Resp: Decreased PVR

GU: UO and GFR may increase in response 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

0.4 L/kg

Taken up into adrenergic neuron – Metabolized by MAO and COMT

Circulating drug hepatically metabolized

minimally hepatic

Urine as inactive metabolites

excretion is in the urine, mostly as
unchanged drug, dose adjustment
in renal failure

2 minutes

2 hours

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.

may be proarrhythmogenic causing SVT and
VT. Have been shown to worsen outcomes
in acute on chronic heart failure

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

used in severe refractory heart failure and
for short periods post cardiac surgery

Is a naturally occurring catecholamine released in the adrenal medulla

selective phosphodiesterase inhibitor

Level 1

Level 1

It is a non selective adrenergic agonist.

Mast cell stabilizer (anaphylaxis)

PDEIII Inhibition: Improves myocardial contractility, 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)

is a yellow solution, stored at room temperature, should not be given with HCO3 or frusemide

pKA of 9.67 and pH of 6.35

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
50mcg/kg loading dose over 10min (optional)
0.375mcg/kg/min-0.75mcg/kg/min