CLINICAL TOXICOLOGY

1. CNS STIMULANTS-
AMPHETAMINES

2. INTRODUCTION
• Amphetamine is a strong central nervous system (CNS) stimulant that is used in the
treatment of attention deficit hyperactivity disorder (ADHD), narcolepsy, and obesity
• It is also commonly used as a recreational drug.
• Amphetamine belongs to the phenethylamine class.
• Some of the amphetamines are amphetamine phosphate, amphetamine
sulphate,benzophetamine,clobenzorex
hydrochloride,dextroamphetamine,methoamphetamine,4-methylthioamphetamine.
• Long-term amphetamine exposure at sufficiently high doses in is known to produce
nerve damage
• In some cases with humans with ADHD, pharmaceutical amphetamines at
therapeutic dosages may improve brain development and nerve growth.

3. USES
. Some amphetamines have therapeutic uses and are still available as
prescription drugs in western countries

4. MODE OF ACTION
• Release of Monoamines from storage site at axon terminal which leads to
increased monoamine concentration in synaptic cleft.
• Cardiovascular effects results from stimulation of release of Noradrenaline.
• Dopamine release in nucleus causes mood elevating effects.
• The dopamine release into the cytoplasm of neurons undergoes oxidation
resulting in production of several toxic chemicals(oxygen
radicals,peroxides,hydroxyquinones)

5. Psychological effects Physiological effects
Euphoria Increased BP
Excitement Decreased HR
Mood elevation Increased alertness
Increased speech activity Psychomotor stimulant
Feeling of power Loss of appetite

6. TOXICOKINETICS
➢In general peak plasma level are seen in 30 minutes after IV or IM .
➢About 2-3 hours after oral amphetamine ingestion .
➢Metabolised in Liver but much is excreted unchanged in the urine.
➢Lipophilic and can cross blood brain barrier easily.
➢Protein binding -16% for amphetamine,15% methylphenindate,less than 40% for
pemoline.
➢Amphetamines have large volume of distribution.
➢Half live -7-30 hours.
➢Half life is shortened when urine is acidic.Excretion of unchanged amphetamine
is dependant on pH and at urine pH less than 6.6, a range of 67 to 73 % of
unchanged drug is excreted in the urine.
➢At urine pH greater than 6.7,17 to 43% is reported to be excreted unchanged in
the urine.

7. CLINICAL MANIFESTATIONS
Acute poisoning
• CNS effects in moderate to severe include
euphoria,agitation,headache,anorexia,hyperthermia,convulsions and coma.
• CVS effects like
tachycardia,hypertension,arrhythmias,cardiomyopathy,myocardial
ischaemia.
• Sympathetic effects are sweating,tremors,nausea,tachypnoea and mydriasis.
• Other effects like muscle rigidity, pulmonary
oedema,Rhabdomyolysis,hyperthermia & metabolic acidosis.

8. Chronic poisoning
• Amphetamines can be taken orally,by injection by absorption or by heating,Inhalation of
vapours.
• Inhaled amphetamines are absorbed immediately with a rapid onset of effects .
• Chronic users of amphetamines tends to fail into one or other of following categories:
1)Intermittent low dose misuse:
• Amphetamines are consumed periodically to overcome fatigue, prolong wakefulness or elevate
mood.
• They usually do not develop dependence.
2)Sustained oral misuse:
• Some individuals who have been using these drugs illicitly continue to ingest them in relatively
large daily doses ( 40 to 100mg or more).
3)High dose IV abuse:
 Individuals who relish euphoria induced by amphetamines quickly progress to IV injections in
order to enhance the "rush or flash".
4)Inhalant abuse:
 When Benzedrine inhalers were available a significant proportion of users became addicted.

9. HOSPITAL MANAGEMENT
ACUTE POISONING-
⮚ Airway is stabilized by using oxygen and ventilatory support.
⮚Mannitol diuresis is used to promote myoglobin clearance in order to prevent
renal failure.
⮚Activated charcoal is used for gastric decontamination with appropriate
tracheal protection.
⮚Anxiety agitation and hyper reactivity can usually be controlled with
benzodiazepines.diazepam is the drug of choice with dose of 10mg IV at
intervals(max 100mg)
⮚Neuroleptics are generally not preferred. Extreme agitation and
hallucinations may require the administration of IV droperidol (upto
0.1mg/kg).
⮚Convulsions can be managed with benzodiazepines(iv diazepam) phenytoin
or barbiturates

10. ⮚Hyperthermia should be tackled aggressively with hypothermic blankets,
icebaths and dantrolene infusions.Large doses of benzodiazepines can help.
⮚Tachycardia can be managed with beta-blockers (Eg:Atenolol&Labetolol).
⮚For ventricular arrhythmias:Lignocaine and Amiodarone are generally first
line agents for stable monomorphic ventricular tachycardia.
⮚Amiodarone and Sotalol should be used if QT interval prolonged or
torsades de pointes is involved in the overdose.
⮚Atropine may be used when severe bradycardia is present.
⮚Diazepam and Chlorpromazine have been effective in treating
Amphetamine induced chorea.
⮚The clinical efficacy of peritoneal dialysis and haemodialysis
have not been proven and they are rarely indicated for elimination
of amphetamine.

11. CHRONIC POISONING-
⮚ Most casual users of amphetamines do not need treatment.
⮚ Strategies range from residential and ambulatory detoxification to day
treatment,multiple activities and case management.
⮚ It is preferable to provide a structured and manualized cognitive
behavioural treatment,making use of combination of group and
individual counselling.
⮚ In some European countries, low-dose amphetamines are administered
to addicts as part of the detoxification programme.

12. THANK YOU