Labetalol
Class
Antihypertensives: β1 and β2 and alpha 1 antagonist
Indications
- All grades of HTN, hypertensive emergencies
- To produce controlled hypotension during anaesthesia
- Control of reflex cardiovascular response to intubation
- Mx of acute MI
Pharmaceutics
Synthetic salicyclamide derivative
Presentation
Clear solution for injection 5mg/ml
Tablets 50-400mg
Dose
Hypertensive emergency: IV 20mg then give 40mg after 10-20 minutes if needed
Further doses of up to 80mg may be given at 10-20min intervals
Max 300mg in 24 hours
Consider IV infusion 2mg/min until desired BP (usual dose 50-200mg)
PO 100-800mg bd
Route
IV/PO
Onset
IV: 5 – 30mins
DoA
50 mins
MoA
Selective antagonism of alpha 1, beta 1 and 2 adrenoreceptor
Ratio of alpha:beta effect is 1:3 ( oral) ; 1:7 (IV)
Intrinsic sympathomimetic activity at beta 2 adrenoreceptor and cause vasodilatation directly by stimulation of beta 2 receptor in vascular smooth muscle
PD
CVS
IV cause 20% ¯ in systolic and diastolic BP, HR and CO may by 10%. ¯ SVR by 14%, limb blood flow and coronary vascular resistance may ¯. Inhibit plt aggregation in vitro
Resp
Single dose no effect on lung function test, or affect pt with COPD. Chronic use – no clinical significant effect on resp function
CNS
No effect on cerebral blood flow, autoregulation is well maintained
GU
↓ Renal vascular resistance by 20%, leading to ↑ blood flow. EGFR unchanged.
Metabolic
Adrenaline, norad, prolactin ↑ when given IV. ↓ Plasma renin activity and angiotension II. ESR and transaminase may ↑
PK
A
PO. Well absorbed. Significant 1st pass. Variable OBA 11-80%
D
50% protein bound. Vd 2.5 – 15.7 L/kg
M
Extensive liver metabolism to inactive conjugates
E
Renal. T1/2b – 8hrs
Renal impairment has no effect on kinetics; reduced dose if there is liver impairment
AE
S/E of beta blockade – occur less frequently as compared to
S/E of alpha blockade (dizziness, formication [insect crawling], nasal congestion. GI disturbance
Contraindications
Shock
Author: Huiling Tan