LABETALOL

“” oil on canvas, Evelyn De Morgan, 1903

“Sir Knight, the four Queens said, thou must understand thou art our prisoner, and we here know thee well that thou art Sir Lancelot du Lake, King Ban’s son, and because we understand your worthiness, that thou art the noblest knight living, and we know well there can no lady have thy love but one, and that is Queen Guinevere, and now thou shalt lose her forever, and she thee, and therefore there behoveth now to choose one of us four. I am the Queen , queen of the land of Gore, and here is the Queen of Northgalis, and the Queen of the Eastlands, and the Queen of the Outer Isles; now choose one of us which thou wilt have to thy paramour, for thou mayest not choose or else in this prison to die.”

“Le Morte D’Arthur”, Sir Thomas Mallory, 1485.

Morgan le Faye, (also known as Morgane, Morgaine, and Morgana) was a mysterious and ethereal figure of the middle ages. The earliest references to her are merely as a “fay” from the French “la fée”, meaning fairy, and establish her as somewhat of a supernatural being. She gains greatest prominence in the Arthurian legends as the half sister of King Arthur. She appears as the villainous femme fatale to Arthur as well as to his Knights of the Round Table. In the Arthurian tradition she becomes a powerful sorceress, having studied under the greatest wizard in history, Merlin himself. The antagonism towards Guinevere stems from an early encounter with her; when Guinevere had had her expelled from court on account of her ungovernable promiscuity. She alternately tries to seduce and then to bring about Lancelot’s fall by exposing him as Guinevere’s adulterous lover. In the Tristan and Iseult legend she delivers to Arthur’s court an enchanted drinking horn from which no unfaithful lady can drink without spilling. By this trickery she hoped to reveal to Arthur, Guinevere’s unfaithfulness.

In the Age of King Arthur and the Knights of the Round Table many powerful wizards and sorceresses existed. By their armory of magical potions, they could heel, poison or bewitch. These potions could be used for both good and for evil, but they required great skill in their administration. In the current age we can no longer bewitch, but we can certainly still poison, and occasionally heal. By the skillful administration of the potion, labetalol, we to heal the malady of the “hypertensive crisis”.

LABETALOL

Introduction

Labetalol is dual alpha and beta adrenoceptor blocker.

This agent therefore provides additional arteriolar vasodilating action over and above the action of the traditional beta-blocking agents.

It is primarily used in the management of hypertension, both as maintenance oral therapy or as urgent IV therapy in cases of hypertensive emergencies.

Preparation

Tablets:

● 100mg; 200mg.

IV Preparation:

● Ampoules 100mg/20ml

Therefore 10mg = 2ml

Mechanism of Action

Labetalol competitively antagonises alpha1-adrenoceptors and non-selectively antagonises beta-adrenoceptors

It lowers the blood pressure primarily by blocking alpha-adrenoreceptors in peripheral arterioles and thereby reducing the peripheral resistance.

The concurrent beta-blockade protects the heart from the reflex sympathetic drive normally induced by peripheral vasodilation.

It has no intrinsic sympathomimetic activity and less pronounced membrane stabilizing activity than propranolol.

Pharmacokinetics

Absorption:

● Is well absorbed orally.

● Can be administered IV

Maximum effect after IV injection occurs at about 5 minutes.

● Bioavailability is about 35-40%

Distribution:

● At therapeutic concentrations, the active drug binds to albumin (52%).

Metabolism and excretion:

● Labetalol has a short plasma half life of about 4 hours.

● It is extensively metabolized by the liver

Indications

Labetalol administered orally is used for the treatment of hypertension.

It is also useful in IV form for the urgent management of hypertensive emergencies, including:

● Hypertension in patients who require stroke thrombolysis or who have undergone this therapy.

♥ Generally aim for 185/110 in this setting.

● Preeclampsia

● Eclampsia

● Aortic dissection:

♥ Labetalol has a dual effect of decreasing blood pressure and cardiac contractility which is important in this condition.

Contraindications/ Precautions

● Asthma

● Peripheral vascular disease (relative)

● Cardiac conduction abnormalities (Second or third degree AV block)

● Cardiac failure, including (as for all beta blockers) right ventricular failure secondary to pulmonary hypertension.

● Significant bradycardia (<50)

● Hypotension

● Caution with concurrent calcium channel blockers

● Caution with other class I or class III antiarrhythmic agents.

Adverse Effects

Labetalol in appropriate therapeutic doses is generally well tolerated and side effects are usually minor and transient.

Principle adverse reactions can include:

● Bradycardia

● Hypotension (including postural hypotension)

● Bronchospasm (in at risk patients).

Dosing

In general terms:

Oral dosing:

● Labetalol 100 to 600 mg orally, twice daily.

IV Dosing:

● Labetalol 10mg IV bolus (undiluted) over 1-2 minutes.

♥ This dose can be repeated at 10 minute intervals, as required.

♥ Maximum dose is considered to be 150mg

References

1. Cardiovascular Therapeutic Guidelines, 6 (1) ed 2012.

2. MIMMs November 2012

Dr J. Hayes November 2012