CENTRAL STIMULANTS
Amphetamines are abused for their stimulant properties, which
are related acutely to the release of dopamineandnoradren-
aline. Their therapeutic use is limited to specialist treatment of
narcolepsy and hyperactivity in children. They should not be
prescribed in the management of depression or obesity. Acutely
they may alleviate tiredness and induce a feeling of cheerfulness
and confidence, and because of their sympathomimetic effects
they raise blood pressure and heart rate. With high doses, partic-
ularly after intravenous use, a sensation of intense exhilaration
may occur. Users tend to become hyperactive at high doses,
especially if these are repeated over several days. Repeated use
of amphetamines can produce ‘amphetamine psychosis’, which
is characterized by delirium, panic, hallucinations and feelings
of persecution, and can be difficult to distinguish from acute
schizophrenia. Anxiety, irritability and restlessness are also com-
mon. Prolonged use leads to psychological dependence, toler-
ance and hostility, as well as irritation due to lack of sleep and
food. The most commonly used amphetamine is amphetamine
sulphatein oral or injectable forms, which are only available
illegally. More recently, free-base amphetamine has become
available (‘ice’), which can be smoked, and this has pharmaco-
kinetic and subjective effects similar to those of injected amphet-
amine sulphate. There are no specific drug treatments for
amphetamine dependence, and the mainstay of therapy
involves counselling and social management. MDMA is
described under drugs that alter perception.
Cocaineis derived from the Andean coca shrub. It has
powerful stimulant properties which are related to its action
in blocking synaptic re-uptake of dopamine, and to a lesser
extent noradrenaline and serotonin. As the salt it is most com-
monly sniffed up the nose, although it can also be injected. In
the USA, the free base of cocaine (‘crack’) is widely available.
The pharmacokinetics of smoked crack cocaineare almost
identical to those of intravenous cocaine.
Acutelycocainecauses arousal, hypertension, exhilaration,
euphoria, indifference to pain and fatigue, and the sensation
of having great physical strength and mental capacity.
Repeated large doses commonly precipitate an extreme surge
of agitation and anxiety. Myocardial infarction or arterial
dissection can occur acutely. In contrast to alcohol and opi-
oids, which addicts tend to use on a regular basis, cocaineis
used in binges, where doses may be taken several times an
hour over a day or several days until exhaustion or lack of
money prevents this. Tolerance of the euphoric effects occurs.
However, upon stopping a cocainebinge, withdrawal symp-
toms including excessive sleep, fatigue and mild depression,
may occur. Repeated cocaineuse may produce adverse effects
including anorexia, confusion, exhaustion, palpitations, dam-
age to the membranes lining the nostrils and, if injected,
blood-borne infections. Use of cocainein pregnancy is associ-
ated with damage to the central nervous system of the fetus.
‘Crack babies’ can usually be cured of their ‘addiction’ by
abstinence over a few weeks. Currently, there are no specific
drug treatments for cocainedependence. Counselling and
social management of patients have been shown to be of only
modest benefit in maintaining abstinence.
Nicotineis an alkaloid present in the leaves of the tobacco
plant. The only medical use of nicotineis as an aid in smoking
cessation. Its importance relates to its addictive properties and
its presence in tobacco. The smoke of a completely burned cig-
arette usually contains 1–6 mg and that of a cigar contains
15–40 mg of nicotine. Acute administration of 60 mg of nico-
tineorally may be fatal. Nicotinefirst stimulates the nicotinic
receptors of autonomic ganglia and then blocks them. Thus
smoking can accelerate the heart via sympathetic stimulation,
or slow it by sympathetic block or parasympathetic stimula-
tion. Adrenaline and noradrenaline are secreted from the
adrenal medulla. The motor end-plate acetylcholine receptors
are initially stimulated and then blocked, producing a paraly-
sis of voluntary muscle. The results of extensive central stimu-
lation include wakefulness, tremor, fits, anorexia, nausea,
vomiting, tachypnoea and secretion of antidiuretic hormone
(ADH).Adverse effects of smoking
Smoking is a potent risk factor for malignant and cardiovascu-
lar disease. Some of the specific causes of death which are
related to smoking are listed in Table 53.5.
Chronic obstructive pulmonary disease including chronic
bronchitis and emphysema are also associated with smoking
as is peptic ulcer disease. Smoking during pregnancy is asso-
ciated with spontaneous abortion, premature delivery, small
babies, increased perinatal mortality and an increased inci-
dence of sudden infant death syndrome (cot death). In house-
holds where the parents smoke, there is an increased risk
of pneumonia and bronchitis in preschool and school-age
children, which is most marked during the first year of life.Pharmacokinetics
About 90% of nicotinefrom inhaled smoke is absorbed, while
smoke taken into the mouth results in only 25–50% absorp-
tion. As well as being absorbed via the gastro-intestinal (GI),
buccal and respiratory epithelium, nicotine is absorbed
through the skin. A high concentration of nicotinemay be
present in the breast milk of smokers. Around 80–90% of circu-
latingnicotineis metabolized in the liver, kidneys and lungs.
The plasma elimination t1/2is 25–40 minutes. Nicotineand its
metabolites are excreted in the urine. The metabolite cotinine
can be used to quatitate exposure.438 DRUGS AND ALCOHOL ABUSE
Table 53.5:Principal causes of death associated with smokingIschaemic heart disease (strongest correlation)
Cancers of the lung, other respiratory sites and the oesophagus,
lip and tongue
Chronic bronchitis and emphysema, respiratory tuberculosis
Pulmonary heart disease
Aortic aneurysm