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Section IVOther important drugs
Central effects – excitation, seizures (correlating with a QRS duration of more than
0.1 seconds) and then depression. Mydriasis is a feature, as is hyperthermia.
Anticholinergic effects.Treatment
This includes gastric lavage followed by activated charcoal. Supportive care may
require supplementation with specific treatment. Seizures may be treated with ben-
zodiazepines or phenytoin and ventricular arrhythmias with phenytoin or lidocaine.
Inotropes should be avoided where possible as this may precipitate arrhythmias.
Intravascular volume expansion is usually sufficient to correct hypotension. The
anticholinergic effects may be reversed by an anticholinesterase, but this is not rec-
ommended as it may precipitate seizures, bradycardia and heart failure.Selective serotonin re-uptake inhibitors – SSRIs (fluoxetine, paroxetine,
sertraline, venlafaxine)
As their name suggests, SSRIs selectively inhibit the neuronal re-uptake of 5-HT. They
are no more effective than standard antidepressants but do not have their associated
side-effect profile. SSRIs are less sedative, have fewer anticholinergic effects and
appear less cardiotoxic in overdose although they are associated with gastrointestinal
side-effects (nausea and constipation).
Despite their side-effect profile, when combinations of serotonergic drugs are
used the potentially fatal serotonergic syndrome may result, which is characterized
byhyper-reflexia, agitation, clonus and hyperthermia. The commonest combination
is an MAOI and SSRI – however, the phenylpiperidine opioids (particularly pethi-
dine) have weak serotonin reuptake inhibitor properties and can also precipitate the
syndrome.
Fluoxetineis an effective antidepressant causing minimal sedation. It is a 50:50
mix of two isomers that are equally active. It is well absorbed and metabolized in the
liver by cytochrome P450 enzymes. In addition, there are non-saturable enzymes
that prevent an unchecked rise in levels. However, the dose should be reduced in
renal failure as accumulation may result. Side effects include nausea and vomiting,
headache, insomnia, reduced libido and mania or hypomania in up to 1%.
Venlafaxineappears to block the re-uptake of both noradrenaline and 5-HT (and
to a lesser extent dopamine) while having little effect on muscarinic, histaminergic
orα-adrenoceptors.Monoamine oxidase inhibitors – MAOIs
This group of drugs is administered orally for the treatment of resistant depression,
obsessive compulsive disorders, chronic pain syndromes and migraine.
MAO is present as a variety of isoenzymes within presynaptic neurones and is
responsible for the deamination of amine neurotransmitters. They have been clas-
sified as types A and B. Following their inhibition there is an increase in the level of