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Amphetamine et al   Back Bookmark and Share

Author : O'Shea Brian

Various addictive behaviours (alcohol, other substances, overeating, gambling, stealing) may have similar effects on specific brain reward areas, such as the ventral tegmental area, the locus ceruleus and the nucleus accumbens.

Amphetamine, synthesized by Gordon Alles in 1927 as a substitute for ephedrine in asthma therapy, directly releases neuronal dopamine and blocks nor-adrenaline reuptake, especially in the reward pathways. Tricyclic antidepressants potentiate these actions. The sulphate form of amphetamine can be snorted. Some users take sedatives when coming off amphetamines in order to sleep off fatigue and depression. Amphetamine abuse increased in Britain to become second only to cannabis in the early 1990s.1 Legitimate uses of amphetamines include attention-deficit hyperactivity disorder and narcolepsy, and, in America, refractory depression. Patients with a family history of Tourette's syndrome are at increased risk of (sometimes permanent) motor and vocal tics when given psychostimulants (dextroamphetamine, methylphenidate, pemoline).

The classic amphetamines are dextroamphetamine (Dexedrine) and metamphetamine. Methylphenidate (Ritalin), ephedrine and propanolamine are related to the amphetamines. Phenylpropanolamine (PPA) and ephedrine can cause hypertension, a toxic psychosis and death. Amphetamine sulphate can sometimes cause disseminated intravascular coagulation (DIC), hyperthermia, and renal failure.2 Amphetamines can also cause seizures.

'Designer drugs' (vide infra) are an illegal group of cheaply synthesized chemicals that mimic the effects of structurally similar compounds, such as the amphetamines or the opiates; the dosage required to produce euphoria is often close to the toxic dose; and they commonly cause psychosis, seizures, brain damage (as with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine or MPTP which mimics Parkinson's disease), and death. Designer amphetamines release catecholamines and serotonin, mimicking a mix of amphetamine and hallucinogen.

'Ice' ('crystal', 'crank', 'speed', 'meth', 'poor man's cocaine'), a pure form of metamphetamine that spread from South Korea to America via Hawaii toward the end of the 1980s, can be smoked using certain paraphernalia or injected intravenously. Euphoria with this drug lasts 10 to 12 hours (20-30 minutes with cocaine), followed by a "downside".

Amphetamine-induced psychosisusually disappears when the drug taking ceases, but it may persist for some considerable time. Patients are mentally over-responsive rather than emotionally blunted, thought disorder is rare, and tactile and olfactory hallucinations are less common than in schizophrenia. Amphetamine is one cause of secondary mania.3

Ephedrine

The ancient Chinese used 'Ma Huang', a herb containing ephedrine. The active chemical was extracted toward the end of the 19th century and was used to treat asthmatics during the 20th century. There have been a number of reports of psychosis following its use, with persecutory delusions, auditory and visual hallucinations, clear consciousness, insomnia, and agitation.4,5

'Ecstasy'(3,4-methylenedioxymetamphetamine; MDMA; 'E'; 'XTC', 'Adam')

This popular, synthetic, oral (tablets/capsules), low potency, hallucinogenic amphetamine which combines the effects of lysergic acid diethylamide (LSD) and amphetamine was patented in 1914 as an appetite suppressant (Not to be confused with 'liquid ecstasy' or gamma-hydroxybutyrate, GHB, a breakdown product of GABA, a dangerous anaesthetic abused in the UK.6 Having been taken up into the cell by the serotonin transporter, 'E' blocks neuronal serotonin uptake and induces its release from nerve cells, as well as inhibiting serotonin-producing enzymes. Europeans use it in dance halls, whereas Americans use it when alone. It can cause a paranoid psychosis.7 Regular use leads to tolerance and increased intake. Other problems include flashbacks, anxiety, agitation, panic, confusion, insomnia, anorexia, nausea, mydriasis, sweating, tachycardia, trismus, bruxism, muscle aches, and stiffness. Acute effects usually resolve within two days. Severe cases may have asthma, seizures, collapse, high followed by low blood pressure. fever (especially if ambient temperature is high: heatstroke), thrombotic stroke, DIC (thrombocytopenia, abnormal coagulation profile, low fibrinogen), rhabdomyolysis and acute renal failure, or ventricular arrhythmias. Regular users may chew gum to overcome effects on the jaw muscles, and they may present with weight loss, exhaustion, jaundice and hepatomegaly, flashbacks, irritability, paranoid delusions, depression, or some other psychotic state.8-11 Biochemically there may be raised creatine phosphokinase, elevated liver enzymes, and hypoglycaemia.12 Excessive fluid intake with 'E' leads to raised antidiuretic hormone (ADH) levels and reduced renal function. Ecstasy may leave one tired for hours to days, yet unable to sleep. Road traffic accidents have been caused by 'E'.13 Irreversible damage to serotonergic neurones in animals and probably in humans may follow use of ecstasy.14,15 Users coming down from 'E' may use benzodiazepines, heroin or methadone. To complicate matters, several other drugs are sold as 'E': MDEA (n-ethyl-3,4-methylenedioxyamphetamine; 'Eve'), DOM (2,5-dimethoxy-4-methylamphetamine; 'STP') and MMDA (5-methoxy-3,4-methylenedioxyamphetamine), the 'designer' amphetamines.

Withdrawal from 'E' can be associated with anxiety, tremor, severe dysphoria, fatigue, lethargy, rebound of REM sleep with nightmares, headache, sweating, muscle and stomach cramps, and an insatiable appetite for food; these peak in 2-4 days and resolve in up to a week.

Management

Adolescents often ignore medical and other warnings about the dangers of drug abuse.16 Amphetamine abusers may be refused treatment in favour of heroin users.17 Urine for analysis should be collected promptly because amphetamines are eliminated quickly by the body. We should monitor changes in the pattern of drug misuse, e.g. sildefanil (Viagra) added to 'E' is 'sextasy'! Severe ecstasy toxicity is treated with intravenous fluids and dantrolene.13 'E' users should drink less than a pint of fluid to avoid ADH increases, and preferably fruit juices or isotonic drinks rather than water. Specific serotonin reuptake inhibitors (SSRIs) inhibit MDMA uptake and block the experience of euphoria.

Other causes of hyperthermia must be considered in every case: severe infection, heatstroke, neuroleptic malignant syndrome, serotonin syndrome (antidepressant combinations, e.g. an SSRI and an MAOI), malignant hyperthermia (anaesthetics), and overdose (anticholinergics, salicylates, amphetamine and analogues, cocaine).

B O'Shea
Newcastle Hospital,
Greystones,
Co. Wicklow

References:

  1. Richards T. Drug abuse increasing. Br Med J 1991; 302: 132.
  2. Ginsberg MD, Herzman M, Schmidt-Nowara W. Amphetamine intoxication with coagulopathy, hyperthermia, and reversible renal failure. Ann Intern Med 1970; 73: 81-85.
  3. Cummings JL. Clinical Neuropsychiatry. Orlando: Grune & Stratton, 1985.
  4. Herridge CF, A'Brook MF. Ephedrine psychosis. Br Med J 1968; ii: 160.
  5. Whitehouse AM, Duncan JM. Ephedrine psychosis rediscovered. Br J Psychiatry 1987; 150: 258-261.
  6. Williams H, Taylor R, Roberts M. Gamma-hydroxybutyrate (GHB): a new drug drug of misuse. Ir Med J 1998; 91: 56-57.
  7. McGuire P, Fahy T. Chronic paranoid psychosis after misuse of MDMA ("ecstasy"). Br Med J 1991; 302: 697.
  8. Peroutka SJ, N
   
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