Amylobarbitone
A white crystalline powder.
Very slightly soluble in water; freely soluble in alcohol and in
ether; soluble in dichloromethane. Forms water-soluble com-
pounds with aqueous solutions of alkali hydroxides and car-
bonates and with ammonia.
Amylobarbitone Sodium
A white, odourless, hygroscopic, friable, granular powder.
Very soluble in carbon dioxide-free water, sometimes leaving
a small insoluble residue; practically insoluble in chloroform
and in ether. The Ph. Eur. states freely soluble, and the USP
soluble in alcohol. Solutions decompose on standing: decom-
position is accelerated by heat. The Ph. Eur. specifies that a
10% solution in water has a pH of not more than 11.0; the
USP specifies a pH between 9.6 and 10.4. Store in airtight
containers.
Amylobarbitone may be precipitated from preparations con-
taining amylobarbitone sodium, depending on the concentra-
tion and pH. Amylobarbitone sodium has, therefore, been
reported to be incompatible with many other drugs, particu-
larly acids and acidic salts.
Dependence and Withdrawal
The development of dependence is a high risk with amylobar-
bitone and other barbiturates and may occur after regular use
even in therapeutic doses for short periods. Barbiturates
should not therefore be discontinued abruptly, but should be
withdrawn by gradual reduction of the dose over a period of
days or weeks. A long-acting barbiturate such as phenobarbi-
tone may be substituted for a short- or intermediate-acting
one, followed by gradual reduction of the phenobarbitone
dose.
Withdrawal symptoms are similar to those of alcohol with-
drawal and are characterised after several hours by apprehen-
sion and weakness, followed by anxiety, headache, dizziness,
irritability, tremors, nausea and vomiting, abdominal cramps,
insomnia, distortion in visual perception, muscle (witching,
and tachycardia. Orthostatic hypotension and convulsions
may develop after a day or two, sometimes leading to status
epilepticus. Hallucinations and delirium tiemens may devel-
op after several days followed by coma before the symptoms
disappear or death occurs.
Adverse effects :
Drowsiness, sedation, and ataxia are the most frequent ad-
verse effects of amylobarbitone and other barbiturates and are
a consequence of dose-related CNS depression. Other ad-
verse effects include respiratory depression, headache, gas-
tro-intestinal disturbances, skin reactions, confusion, and
memory defects. Paradoxical excitement and irritability may
·occur, particularly in children, the elderly, and patients in
acute pain. Hypersensitivity reactions occur rarely and in-
clude skin rashes (erythema multiforme and exfoliative der-
matitis, sometimes fatal* have been reported), hepatitis and
cholestasis, and photosensitivity. Blood disorder, including
megaloblastic anaemia after chronic use of barbiturates, have
also occurred occasionally.
Neonatal intoxication, drug dependence ,and symptoms re-
sembling vitamin-K deficiency have been reported in infants
born to mothers who received barbiturates during pregnancy.
Congenital malformations have been reported in children of
women who took barbiturates during pregnancy, but the caus-
al role is a matter of some debate.
Nystagmus, miosis, slurred speech, and ataxia may occur
with excessive doses of barbiturates. The toxic effects of
overdosage result from profound central depression and in-
clude coma. respiratory and cardiovascular depression, with
. hypotension and shock leading to renal failure and death. Hy-
pothermia may occur with subsequent pyrexia on recovery.
Erythematous or haeroorrhagic Misters reportedly occur in
about 6% of patients, but are not characteristic solely of bar-
biturue poisoning.
Solutions of the sodium salts of barbiturates are extremely al-
kaline. and necrosis has followed subcutaneous injection. In-
travenous injection maybe hazardous, hypotension, shock.
laryngospasm. and apnoea have occurred particularly after
rapid administration. Gangrene has resulted from intra-arteri-
al injection into an extremity.
Barbiturates are abused for their euphoriant effects.
PRECAUTIONS :
Following recent ingestion of an overdose of barbiturate the
stomach may be emptied by lavage. Oral administration of
activated charcoal may be useful. Patients should be managed
with intensive supportive therapy, with particular attention
being paid to the maintenance of cardiovascular, respiratory,
and renal functions. and to the maintenance of the electrolyte
balance.
The value of measures aimed at the active removal of barbit-
urates is questionable, except perhaps for charcoal haemoper-
fusion which can be life-saving in the most severe cases.
Precautions
Amylobarbitone and other barbiturates are best avoided in
elderly and debilitated patients, young adults, in children, and
in those with mental depression.
Amylobarbitone is contra-indicated in patients with pulmo-
nary insufficiency, sleep apnoea. pre-existing CNS depression
or coma. and severe hepatic impairment, and should be given
with caution to those with renal insufficiency. Barbiturates
given to patients in pain may provoke a paradoxical excitatory-
reaction. unless an analgesic is given concomitantly. With
continued administration, tolerance develops to the sedative
or hypnotic effects of the barbiturates to a greater extent than
to their lethal effects. Barbiturates may cause drowsiness; af-
fected patients should not drive or operate machinery.
See under Adverse Effects, above, for the hazards of admin-
istration of barbiturates during pregnancy. Small amounts of
barbiturates are distributed into breast milk: they should not.
therefore, be given to nursing mothers.
Dependence readily develops after use of barbiturates with a
withdrawal syndrome on abrupt discontinuation (see under
Dependence and Withdrawal, above).
Porphyria : Barbiturates including amylobarbitone have
been associated with acute attacks of porphyria and are con-
sidered unsafe in patients with acute porphyria.
Interactions :
Sedation or respiratory depression may be enhanced by drugs
with CNS-depressant properties; in particular alcohol should
be avoided. Barbiturates generally induce liver enzymes, and
thus increase the rate of metabolism, and decrease the activi-
ty of many other drugs as well as endogenous substances.
Continued use may result in induction of their own metabo-
lism. MAOls may prolong the CNS depressant effects of
some barbiturates, probably by inhibition of their metabo-
lism. However. MAOls like other antidepressants also reduce
the convulsive threshold and thereby antagonise the anticon-
vulsant action of barbiturates. For some further interactions
involving barbiturates see under Phenobarbitone.
Pharmacokinedci
Amylobarbitone is readily absorbed from the gastro-intesti
tract and following absorption some 60% is bound to plas
proteins. It has a half-life of about 20 to 25 hours which
considerably extended in neonates. It crosses the placenta af
small amounts are distributed into breast milk. Amylobart
tone is metabolised in the liver, up to about 50% is excrete
in the urine as 3'-hydroxyainylobarbitonc and up to abo
30fb as A/-hydroxyamylobaibitone, less than 1% appearing
unchanged: up to about 5% is excreted in the faeces.
Uses and Administration.
Amylobarbitone is a barbiturate that has been used as a hyp
notic and sedative. It’s use can no longer be recommended be-
cause of its adverse effects and risk of dependence, although
continued use may occasionally be considered necessary for
severe intractable insomnia in patients already taking
it. The usual dose by mouth at bedtime was 100 to 200 mg of
the base or 60 to 200 mg of the sodium salt. A more rapid
onset of effect was obtained with the sodium salt.
Barbiturates with a longer action such as phenobarbitone
are still used in epilepsy and those with a shorter ac
tion such as methohexitone or thiopentone for anaesthesia .
Cerebro—vascular ddisorders: For reference to the use of
barbiturate-induced coma in the management of patients with
cerebral ischaemia .
Epilepsy : Amylobaibitone sodium in the assessment of
memory function prior to surgery for temporal lobe epilepsy.