Propranolol

Chemical

Aromatic amine

→ Weak base pKa 7.4

→ 99% ionised at 7.4

→ but the 1% is highly lipid soluble

Use

  1. Hypertension
  2. Arrhythmias
  3. Tremor
  4. Anxiety
  5. Migraine
  6. Oesophageal varices
  7. Phaeochromocytoma prophylaxis

Dose

High 1st pass metabolism ∴ PO & IV doses very different

PO: 10-80mg tablets

IV: 1-10mg

Presentation

IV: 1mg/mL clear solution

Tablets: 10/40/80/160mg

Route

PO/IV

Onset

2 mins (IV)

DoA

4 hrs

MoA

Competitive antagonist of β1 & β2 adrenoreceptors

ECG: ↓HR

PD

CVS: β1: -ve inotropy, -ve chronotropy, -ve dromotropy

  • (weak) ↑SVR by β2 block

Resp: ↑airway resistance

CNS: insomnia, depression, fatigue, lethargy

Renal: ↓RENIN release

GU: ↓uterine tone

Metabolic:

  • ↓plasma FFA
  • ↓BSL
  • Prevents peripheral conversion of LEVOTHYROSINE → TRIIODOTHYRONINE

Skeletal m: stops tremor

PK

A

Rapid & complete

D

HIGH LIPID SOLUBILITY

PPB 99%

Crosses placenta & BBB

M

High hepatic ER

High 1st pass metabolism

Liver → active metabolite

4 – HYDROXYPROPANOLOL

E

Renally excreted

Active metabolite accumulates in renal failure

t ½ B 3hrs

NB: β-blocking activity is greater after PO cf. IV dose

Because ↑production of active metabolite due to 1st pass clearance

NOT REMOVED BY DIALYSIS

Adverse Effects

  • Bronchospasm/asthma
  • Masks sympathetic of hypoglycaemia
  • May precipitate HF
  • Sleep disturbance, nightmares