Core pharmacology

Class Group

ADRENERGIC

Legacy Cicm Level

Level 1

Introduction

Is a naturally occurring catecholamine released in the adrenal medulla

Indications Uses

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

Presentation

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)

Main Action

It is a non selective adrenergic agonist.

Mast cell stabilizer (anaphylaxis)

Mechanism of action

- 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

Physiological effects

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

Adverse Effects Toxicity

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.

Absorption

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

Distribution

doesn’t cross the BBB

Metabolism

Taken up into adrenergic neuron – Metabolized by MAO and COMT

Circulating drug hepatically metabolized

Excretion

Urine as inactive metabolites

Half-life

2 minutes

Route And Dose

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