Trade Name: ANQUIL TABLET 7.5 MG
Generic Name: Midazolam INN

What is ANQUIL?
Anquil is a preparation of Midazolam which is indicated as a sedative and/Hypnotic agent (causes natural sleep).

Presentation :
Anquil 7.5 : Each tablet contains 7.5 mg of Midazolam BP as Midazolam maleate.
Anquil 15 : Each tablet contains 15 mg of Midazolam BP as Midazolam maleate.

Indication & uses :
Anquil is used for the short term treatment of sleep disturbances. Disturbances of sleep rhythm and all asleep either initially or after premature awakening. Sedation in premedication before surgical or diagnostic procedures.

Dosage & adnimistration : Standard dosage
The usual adult dose is 7.5 - 15 mg.
Because of the short duration of Midazolam in the body, Midazolam can be taken at any time of day, provided the patient is subsequently assured of at least four hours undisturbed sleep. There then hardly any fear of residual effects. Owing to the rapid onset of action, Midazolam should be taken immediately before retiring and be swallowed whole with fluid.

Special dosage instructions :
In elderly and debilitated patients, the recommended dose is 7.5 mg. This dosage applies also to patients with imparied liver and or kidney function.
In premedication, 15 mg of Midazolam should be given orally 30 to 60 minutes before the operation, unless the parenteral route is preferred.

Mode of Action :
Binding of g-amino butyric acid (GABA) to its receptor on the cell membrane triggers and opening of a chloride channel, which leads to an increase in chloride conductance. The influx of chloride ions causes a small hyper polarization that moves the post synaptic potential away from its firing threshold and thus inhibits the formation of action potentials. Midazolam binds to specific high affinity sites on the cell membrane, which are separate from but adjacent to the receptor for GABA. The Midazolam receptors are found only in the central nervous system, and their location parallels that of the GABA neurons. The binding of Midazolam enhances the affinity of GABA receptors for this neurotransmitter, resulting in a more frequent opening of adjacent chloride channels. This is in turn results in enhanced hyper polarization and further inhibition of neuronal firing.

Note : Midazolam and GABA mutually increase the affinity of their binding sites without actually changing the total numbers of sites.

Pharmacokinetics :

• Absorption of Midazolam is rapid. peak plasma concentration being achieved with in 20 to 60 minutes of administration.
• Extensive first pass metabolism results in a low systemic bioavailability after oral administration.
• Midazolam is extensively binds to plasma protein.
• Midazolam has short elimination half life of about 2 hours. The elimination half is prolonged in neonates, in elderly and in patients with liver disorder.

Advantages of Anquil (Midazolam) over Diazepam :

• Midazolam was 3.4 times more potent than diazepam.
  Ref. : Gastrointest-Endosc. 1999 Jun, 49(6) : 684-9

• It has a more rapid onset of action and often used in preferences to intravenous Diazepam.

• It has a shorter duration of action and Diazepam, second period of drowsiness~ does not occur after its administration. (Alprazolam, Bromazepam, Chlordiazepoxide, Clobazam and Clorazepate have a sustain action.)

SOME ADVANTAGES OF ANQUIL OVER OTHER BENZODIAZEPINES :

• At indentical plasma concentration, the oral dose produces more marked effects than the intravenous dose because of the activity of the a-hydroxy metabolite. Patients with normal metabolism wake at plasma midazolam concentrations of 100mg/L and a-hydroxymidazolam levels of about 30mg/L.

• The a-hydroxymidazolam is biologically active but has a short half-life than midazolam. It may contribute to the pharmacological acitivty of the drug after oral administration.

• Midazolam 15 mg orally at night is an effective hypnotic, increasing the total duration of sleep and decreasing the number of awakening. There is no carryover of sedation to the morning and it is most useful as a hypnotic inpatient in whom absence of daytime sedation is important.
  Ref. : Therapeutic Drug P-M176;

• Midazolam 15 mg may be given for premedication before general anesthesia or to provide sedative cover for minor surgical or investigative procedures.
  Ref. : Martindale p-681;