G7i / 21A01: Describe the pharmacology of adrenaline

21A01: Exam Report

Describe the pharmacology of adrenaline

90% of candidates passed this question.

Adrenaline is a level 1 drug and is commonly used in intensive care. A comprehensive explanation of the drugs MOA, PK, PD and side effect were expected. Candidates who scored well generally provided a factually accurate, detailed and well-structured answer. Overall, the quality of answer provided for this question was of a high standard.

G7i / 21A01: Describe the pharmacology of adrenaline

Adrenaline

Adrenaline

Chemical

Naturally occurring catecholamine with mixed direct α & β activity, produced by adrenal medulla

The prototype sympathomimetic

Use

Inotropy

Cardiac arrest

Anaphylaxis

Vasoconstrictor

Presentation

Clear solution

100mcg – 1mg/mL

Brown ampoule → deteriorates on exposure to air/light

Excipients: sodium metabisulphite, sodium chloride, sodium hydroxide, hydrochloric acid, water

Dose

Inotropy (IV)

1 – 2mcg/min = β2 receptors

2 – 6mcg/min = β1 & β2 receptors

>10mcg/min = β & α receptors

Cardiac arrest = 1mg (IV)

Anaphylaxis = 100mcg – 1mg (IV)

Vasoconstriction = 1:200,000 diluted with lignocaine

Route

IV

ETT

Subcut

Epidural space

Onset

Immediate, effect lasting 1 – 5 mins

MoA

Agonist of adrenergic receptors; β2 > β1 > α1 = α2

  • β2 → GS → activates AC → ↑cAMP
      • Cardiac = ↑Ca++
      • Smooth muscle = inhibits MLC CK
      • Liver = activates glycogen phosphatase
      • NB: MAST CELL stabilisation by β2 agonism of MC
  • β1 → GS → activates AC → ↑cAMP
      • Cardiac = +ve inotropy, +ve chronotropy, +ve dromotropy
      • Metabolic = lipolysis
      • ↑RENIN → ↑AII → VC
  • α1 → Gq → stimulates phospholipase C → ↑IP3 & DAG
      • IP3: smooth muscle VC
      • IP3: cardiac → weak +ve Inotropy
      • DAG: metabolic → ↑BSL
  • α2 → Gi → inhibits AC → ↓cAMP
      • CNS : ↓symp. outflow
      • Peripheries : inhibits NA release by –ve feedback
      • Platelets : ↓platelet aggregation

PD

CVS

+ INOTROPY, + CHRONOTROPY, + DRONOTROPY

↑CO

↑Myocardial O2 consumption

Coronary dilatation

VC peripherally

RESP

↑MV

Bronchodilation

↑PVR

Mast cell stabilisation

RENAL

↑Bladder sphincter tone = difficulty voiding

↓Renal blood flow

METABOLIC

↑BMR

↑Plasma glucose

Gluconeogenesis

↑FFA

CNS

Pupil dilatation

GI

↓Secretions & ↓ tone

PK

A

Slow after IM/SC injection

Good tracheal mucosal absorption

Inactivated PO

D

M

Metabolised by mitochondrial MAO & COMT in liver, kidneys, blood

ADRENALINE

Metanephrine & VMA are conjugated with glucuronic acid

E

Inactive metabolites excreted in urine

Adverse Effects

Arrhythmias

Myocardial ischaemia

Cerebral bleed

Lactaemia (from aerobic glycolysis) ; ↑glycolysis, ↑glycogenolysis, ↑release of sk & lactate reserves → all for ENERGY

Tremor

Author: Krisoula Zahariou