drug of abuse
DESCRIPTION
DRUG OF ABUSE. By: Dr. Israa Omar. DRUG DEPENDANCE. It refers to the state of affairs when administration of drug is sought compulsively, leading to disturbed behavior if necessary to secure its supply. - PowerPoint PPT PresentationTRANSCRIPT
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DRUG OF ABUSEBy: Dr.Israa Omar
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DRUG DEPENDANCE
• It refers to the state of affairs when administration of drug is sought compulsively, leading to disturbed behavior if necessary to secure its supply.
• It comprises physical dependence, which there is distinct symptoms of withdrawal, and psychological dependence, which is craving for the drug .
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PHYSICAL DEPENDANCE
• (tolerance and withdrawal syndrome) • Tolerance: The decrease in a pharmacological effect
on repeated administration of the drug
• Withdrawal symptoms: may be experienced upon discontinuation. Some of these symptoms are generally the opposite of the drug's direct effect on the body.
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PHYSICAL DEPENDANCE
•Withdrawal symptoms( abstinence syndrome) can vary significantly among individuals and among drugs, but there are some commonalities. It is often characterized by depression, anxiety and dysphoria
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PHYSICAL DEPENDANCE
• In general, the longer the half-life of the drug, the longer the acute abstinence syndrome is likely to last. However, with drugs with a longer half-life, the acute abstinence syndrome will be much milder than that of those with shorter half-lives.
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DRUG ADDICTION
• It is not clearly defined but generally it refers to the state of severe psychological dependence that outlasts the physical withdrawal syndrome.
• Drug abuse and substance abuse are more general terms, meaning recurrent use of illicit substances
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REWARD PATHWAYS• virtually all dependence-inducing drugs so far tested,
activate the REWARD PATHWAY - mesolimbic dopaminergic pathway, which runs from the ventral tegmental area (VTA) of the midbrain to the nucleus accumbens and limbic region positive reinforcing effect.
• addictive drugs increase the release of dopamine in the nucleus accumbens even though primary sites of action are generally elsewhere in the brain
• the hedonic effect of dependence-producing drugs results from activation of this pathway, rather than from a subjective appreciation of the diverse other effects (e.g. alertness or stimulation)
• Importance for drug-seeking behaviour
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• MAJOR GROUPS OF DRUGS THAT ARE SUBJECT TO ABUSE:
1. Opioids analgesics: Morphine and Heroin2. General CNS depressant: Ethanol,
Barbiturates , Anesthetics and solvents3. Anxiolytics drugs: Benzodiazepines4. Psychomotor stimulant : Amphetamines,
Cocaine, Caffeine and Nicotine 5. Psychotomimetic: LSD, Cannabis, Mescaline
and Phencyclidine
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Nicotine and tobacco• It appear to be the only pharmacologically active
substancesin tobacco smoke• One cigarette contain about 9-17mg of nicotine,
of which 10% is normally absorbed • In the brain it causes neuronal excitation that can
be blocked by mecamyline• In the spine it inhibits spinal reflex and thus
causing muscle relaxation • In the peripheral tissues, nicotine stimulates the
receptors at the ganglion and causes tachycardia, hypertension and reduced GI motility
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Main health risks
• Cancer: lung mouth, throat, esophagus pancreas and kidney
• Coronary heart disease and peripheral vascular disease
• Chronic bronchitis • Deleterious effects in pregnancy: growth
retardation, low birth weight, increased abortion rate and perinatal mortality
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Adverse effects• Tolerance: to peripheral (not central)
ganglionic stimulation, perhaps due to desensitization of receptors
• Physical dependence craving : increased irritability, anxiety, impaired performance of psychomotor tasks, aggressiveness and sleep disturbances, headache increased appetite lasts for 2-3 weeks :
• Psychological dependence and addiction
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TREATMENT OF NICOTINE DEPENDENCE
• Nicotine replacement therapy–Nicotine in patches (controlled release),
chewing gums, nasal sprays several times daily (short effect)
• Adjunct therapy–Bupropion, TCAs and MAOI –Clonidine – rarely used due to the side-effects
(hypotension, drowsiness…)–Mecamylamine–Counselling the patients is very important
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ETHANOL
• Most commonly taken substance leading to physical dependence (it is legal for adults!)• Rapid absorption after oral administration
(measurable concentration after 5 min), immediately from the stomach• Wide distribution to the whole body fluids• More than 90% of ethanol is metabolised,
less than 5-10% excreted unchanged in expired air and in urine • Saturation character of metabolism
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METABOLISM OF ETHANOL• Main metabolism via 2 subsequent oxidations:
a) cytoplasmic alcoholdehydrogenase →acetaldehyde b) aldehydedehydrogenase →acetic acid this enzyme can be inhibited by various substances →‘disulfiram effect’ (disulfiram but also chlorpropamide, nitrofurantoin etc.) Symptoms: nauzea, flushing, tachycardia, hyperventilation, panic
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Limiting factor for ethanol metabolismis a NAD+ availability
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PHARMACOLOGICAL EFFECTS OF ETHANOL
1. CNS EFFECTS- mainly depressant action at the cellular levelsymptoms of acute intake:- slurred speech, euphoria, motor incoordination, increased self-confidence, decreased concentration and learning ability.- higher plasma levels lead to mood lability, later ataxia, stupor and coma, death from respiratory failure2. effect on peripheral systems
-cutaneous vasodilatation ‘warm feeling’ and tachycardia,↑salivary and gastric secretion,↑ hydrocortisone, oxytocin secretion and ADH
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TOLERANCE AND DEPENDENCE• Tolerance – it develops over 1-3 weeks of continuing
administration = 2-fold decrease in alcohol potency. There is a cross-tolerance with many anaesthetics .
• Mechanism: not well explained, changes in CNS neurons – down-regulation of GABAA-receptors, up-regulation of voltage-gated Ca channels and NMDA receptors?
• Physical abstinence syndrome ( in 24-36h): tremor, nausea, sweating, fever, occasionally hallucinations and epilepsy-like seizures!
• ‘delirium tremens’ over few following days: confusion, agitation, aggression, unpleasant hallucinations
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TREATMENT OF ALCOHOLISM• Disulfiram – blockade of aldehydedehydrogenase
cummulation of acetaldehyde - nausea, flushing, tachycardia, hyperventilation, panic…Aim: to make alcohol consumption unpleasant and intolerable
• Naloxone and naltroxone – reduces alcohol-induced reward (unclear mechanism)
• The drugs used to alleviate the acute abstinence syndrome: benzodiazepines, clonidine (inhibits exaggerated neurotransmitter release) and propranolol (blocks excessive sympathetic activity).
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CANNABIS AND CANNABINOIDS• Extracts of the hemp plant;originally from
Himalaya and Kashmir• Marijuana - dried leaves and flower heads• Hashish - extracted resin• Active substances: cannabinoids (lipophilic non-
alkaloid natural compounds)• Routes of administration: mainly inhaled in
cigarette smoke
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PHARMACOLOGICAL EFFECT OF CANNABISOn CNS: combination of psychotomimetic, depressant
effect– a feeling of relaxation, well-being and euphoria -
without accompanying aggression– Uncontrolled laughing without reason– a feeling sharpened sensory awareness– impairment of motor coordination (driving), short-
term memory and judgement. Feeling of time passing slowly, depersonalisation; increased appetite
– Analgesia, antiemetic action– In high doses: hallucination, paranoia, anxiety
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PHARMACOLOGICAL EFFECT OF CANNABIS
peripheral effects:– vasodilatation (obvious on conjunctive
vessels)– tachycardia–Bronchodilation (but opposite may appear
during smoking)– reduction of intraocular pressure
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MECHANISM OF ACTION• Through cannabinoid receptors (GPCR type)– CB1- brain – highly abundant in: hippocampus
(memory), cerebellum (loss of coordination), and substantia nigra (motor disturbances), hypothalamus (appetite) and mesolimbic dopaminergic pathway (reward) and cortex.
– Mostly localised presynaptically – their activation inhibits neurotransmitter release
Their paucity in the brain stem lack of serious respiratory and cardiovascular toxicity.
• Endogenous agonist: anandamide– CB2- periphery - immune system
(immunosuppressive effects?!)
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PHARMACOKINETICS
- lipophilic compound - well absorbed, highly bound to plasma proteins, widely distributed and partially sequestrated in body fat → excretion lasts for days (can still be detected in urine) - liver metabolism to mostly inactive metabolites
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HARMFUL EFFECT
- Relatively safe from the viewpoint of acute drug overdose - Problems are rather with chronic use: -Somatic effects: decreased testosterone and sperm count -Long-term psychological changes: apathy, impaired memory and decision ability, may promote schizophrenia in pre-disposed patients
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TOLERANCE AND DRUG DEPENDENCE
• Tolerance and physical dependence occur only to a minor degree in heavy users
• Withdrawal syndrome: weak and usually mild irritability, restlessness, confusion, sweating tremor and sleep disturbances
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THERAPEUTIC USE OF CANNABINOIDS?
• Synthetic analogues– Nabilone and dronabilone
• Potential indications– Antiemetic therapy in cancer chemotherapy– Analgesia– Glaucoma– Multiple sclerosis
• Therapeutic values and utility?• Legal limitations
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PSYCHOTOMIMETIC DRUGS (HALLUCINOGENS)
• affect thought, perception and mood without causing psychomotor stimulation or depression
• Effects: thoughts and perceptions tend to become distorted and dream-like, colours and sounds are more sharp. Induction of euphoria and happiness.
• Different kind of hallucination (visual, auditory, tactile and olfactory appear). Thought process tend to be illogical and disconnected but subject mostly retain insight that these effects are drug-induced. Increased sense of empathy.
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HALLUCINOGENS
• Major groups/drugs (different classification in literature)–LSD and related compounds–MDMA and related compounds–Phencyclidine and ketamine
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LSD (LYSERGIC ACID DIETHYLAMIDE)
Originally produced as a drug candidate in Sandoz Labs in 1938 by Albert Hoffman It is among the most potent drugs known so far
Mechanism of action: acting on different 5-HT receptors in CNS
• mainly as agonist on 5-HT2A autoreceptors in CNS firing of 5-HT neurons in Raphe N• Somatic effects: sympathomimetic (↑blood p
and HR, neurological (tremor, ataxia)• Tolerance: develops quickly (on CNS effects)• Adverse effects and dangers: persistent mental
disorder, schizophrenia, injury due to violent behaviour
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OTHER HALLUCINOGENS• MDMA (MethylenDioxyMethAmphetaminem, ecstasy)– Dance-floor drug– Stimulant and hallucinogenic effects (related to
amphetamines)– Danger in acute overdose: exhaustions, dehydratation,
hyperpyrexia, arrhythmias
• Phencycline („angel dust“, PCP)– Chemically related to ketamine (anaesthetic drug) and
originally also developed as a drug with this indication– Not so frequent among abusers, unpleasant vegetative
effects – Some delusions and/or hallucination may turned into
the violent behaviour
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PSYCHOMOTOR STIMULANTS
1)AMPHETAMINES AND RELATED DRUGS
2)COCAINE
3)METHYLXANTINES (CAFFEINE )
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AMPHETAMINES AND RELATED COMPOUNDS
• substances: amphetamine, methamphetamine and other drugs like ephedrine, phentermine, methylphenidate and MDMA.
• Routes of administration: oral, nasal, inhalation and parenteral
• Mechanism of action: indirect CNS „sympathomimetic“ effect – release of monoamines (noradrenaline, dopamine, or 5-HT) from nerve terminals in the brain
• Main effects on CNS: locomotor stimulation, euphoria and excitement, increased self-confidence,
stereotyped behaviour, resistance to fatigue, decreased appetite, anorexia
• Peripheral effects: tachycardia and palpitations, ↑blood pressure, ↓GIT motility
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AMPHETAMINES AND RELATED STIMULANTS• Tolerance develops rapidly to the peripheral
sympathomimetic and anorexic effects, but more slowly to the central effects
• no clear-cut physical withdrawal syndrome → dependence seems to be a consequence of the unpleasant after-effects (i.e. fatigue, lethargy, anxiety, depression, hunger) and the effort to avoid them
• full-blown dependence occurs in 5% of users – characterized by strong craving, increased doses, and common uncontrolled ‘runs’)
• Amphetamine psychosis – closely resembles the Schizophrenic attack – incoherent thought, hallucinations, paranoia, aggression.
• Therapeutic use: minimal e.g., narcolepsia ,hyperkintic syndrome and treatment of obesity)
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COCAINE• the most expensive drug illegally sold• Routes of administration: salt - nasal or i.v. , free base:
smoking-inhalation • MECHANISM OF ACTION:
inhibition of catecholamine Re-uptake increase noradrenaline and dopamine transmissionindirect „sympathomimetic“ agentPharmacological effects: very similar to those of amphetamines yet less prone to cause stereotyped behaviour, paranoia, delusions
• Duration of effect is much more shorter (30 min, i.v.) than in amphetamines, rapid metabolism – liver and plasma esterase (hair deposit of metabolites).
• no clear-cut physical dependence syndrome but depression, tiredness and dysphoria coupled with very intensive craving for the drug (strong psychological dependence
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COCAINE • Tolerance: in most abusers is to euphoria• Intoxication (overdose): tremor, hypertension,
tachycardia, arhythmias, cardiac pain, hyperpyrexia, convulsions and shock even with fatal consequencesLong term abuse
• Characteristic behavioural changes: paranoia, anxiety, aggression, loss of social contacts
• Increased risk of coronary and cerebral thrombosis• slowly developing damage to myocardium leading to
heart failure may appear• Therapeutic use: rarely as a local anaesthetic drug in
ophthalmology (event. nose/throat surgery)
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METHYLXANTHINES• natural alkaloids occurring in various beverages, namely tea,
coffee, cocoa and cola-flavored drinks• substances: caffeine, theophylline, theobromine• a cup of coffee or strong tea contains 50-100 mg of caffeine Pharmacological effects:• CNS stimulation • diuresis (vasodilatation of the afferent glomerular arteriole)• stimulation of cardiac muscle• relaxation of smooth muscle, especially bronchial.MECHANISMS:1) inhibition of phosphodiesterase, responsible for intracellular
metabolism of cAMP2) antagonism on both A1 and A2 adenosine receptorstolerance and habituation develop to a small extent and withdrawal
effects are very slight (headache, fatigue)
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THANK YOU Reference:RANG AND DALE PHARMACOLOGY