Drug Abuse

Self administration of drug or drugs in manner not in accord

with accepted medical or social patterns

Psychological Dependenc (Habituation) addiction. Drug necessary to maintain user’s sense of

well-being Physical Dependence, dependence

Physical symptoms if intake is reduced

Addiction Compulsive, relapsing drug use

despite negative consequences, at times triggered by cravings. Includes

Tolerance (dose has to be progressively increased to maintain rewarding or analgesic effect)

Psychological dependence Physical dependence Compulsive use

Mesolinbic dopamine system is the prime target of addictive drugs.

The system originates in the ventral tegmental area (VTA).

Drug of abuse are rewarding and reinforcing.

Drugs that activate G Protein-Coupled Receptors

Opioids Cannabinoids γ-hydroxybutyric acid (GHB) LSD, mescaline Drugs that bind to ionotropic receptors

and ion channels Nicotine Alcohol Benzodiazepines Phencyclidine, ketamine

Drugs that bind to transporters of Biogenic Amines

Cocaine Amphetamine Ectasy

OPIATESOPIATES

Opiates are drugs that are derived from the Poppy Opiates are drugs that are derived from the Poppy Plant and are Central Nervous System (CNS) Plant and are Central Nervous System (CNS) depressants.depressants.

The most common opiates are:The most common opiates are:OpiumOpiumHeroinHeroinMorphineMorphineCodeineCodeine

Opiates are known by several different names:Opiates are known by several different names: SmackSmack SmackSmack ChivaChiva ChivaChiva

MorfMorf MorfMorf HH HH

SoapiumSoapium SoapiumSoapium FlowerFlower FlowerFlower

PoppyPoppy PoppyPoppy HazelHazel HazelHazel

Examples Opium Morphine Heroin Codeine

Oxycodone (Percodan)

Meperidine (Demerol)

Propoxyphene (Darvon)

Talwin Fentanyl

Acts on μ, κ and delta opioid receptors

Effects Analgesia CNS depression

Euphoria Drowsiness Apathy

Antidiarrheal action Antitussitive action

Nausea/VomitingNausea/Vomiting

ConstipationConstipation

Itchy SkinItchy Skin

SleepinessSleepiness

Loss of Sex DriveLoss of Sex Drive

Altered Mental ProcessAltered Mental Process Absence of StressAbsence of Stress

Overdose/DeathOverdose/Death Impaired VisionImpaired Vision

Collapsed VeinsCollapsed Veins

Menstrual IrregularitiesMenstrual Irregularities

Liver DamageLiver Damage

Kidney DamageKidney Damage

Lung DamageLung Damage

Brain DamageBrain Damage

Immune System Immune System DamageDamage

Overdose Mild to

Moderate Lethargy Pinpoint pupils Bradycardia Hypotension Decreased

bowel sounds Flaccid muscles

SevereSevere Respiratory depressionRespiratory depression ComaComa AspirationAspiration Seizures with certain Seizures with certain

compounds (meperidine, compounds (meperidine, propoxyphene, tramadol)propoxyphene, tramadol)

Overdose Management Naloxone

Treatment of opioid addiction Long acting opioids

Withdrawal Insomnia Restlessness Irritability Anorexia Tremors Back, extremity

pain

Watery eyes Yawning Rhinorrhea Sneezing Diarrhea Diaphoresis

Resembles Severe Influenza

Marijuana (Tetrahydrocannabinol (THC) Endogenous cannabinoids (Anandamide) Act on CB1 receptors, presynaptically and

inhibit the release of glutammate or GABALeading to disinhibition of dopamine neurons.Onset of effects: within minutes Effects: Euphoria, relaxation, visual

distortions, drowsiness, diminished coordination and memory impairment.

LSD Mescaline Psilocybin

Produce altered/enhanced sensation Increased dose does not intensify

effect Mechanism of action Act on 5HT2A receptor------G proteins

------ IP3 ---intracellular calcium-------- increase glutamate release.

Signs and symptoms Anxiety, excitement Nausea, vomiting Tachycardia, tachypnea

Moderate Intoxication Tachycardia Mydriasis Diaphoresis Short attention span Tremor Hypertension Hyperreflexia Fever

Life-threatening toxicity (rare) Seizures Severe hyperthermia Hypertension, arrhythmias Agitated Diaphoretic, hyperreflexic Untreated hyperthermia can lead to

hypotension, coagulopathy, rhabdomyolysis and multiple organ failure

Nicotine Smoking of tobacco through different

routes. Agonist of nicotinic acetylcholine receptor

(nAChR),role in cognitive processes. Rewarding effect of nicotine requires

involvement of VTA in which (nAChR) are expressed on dopamine neurons.

Nicotine withdrawal : irritability, sleep problems.

Slowly absorbable form of nicotine. Cytisine, varenicline (partial agonists) Act by occupying nAChRs on dopamine

neurons of the VTA. Bupropion + behavioural therapy

Anxiolytic and sleep medications Abused for their EUPHORIC effects GABAA receptors on interneurons,

disinhibition of mesolimbic dopamine system-----rewarding effects.

Withdrawal symptoms include Irritability, insomnia, photophobia,

depression, muscle cramps and even seizures.

General anesthetic Non-competitive antagonism of NMDA

receptor. Increased blood pressure, impaired

memory function & visual alterations. ‘Club drugs’ and sold as ‘angel dust’

Street names Angel dust Peace Pill Hog Krystal Animal tranquilizer

Used as veterinary anesthetic

Examples Nitrates , ketones , aliphatic and

aromatic hydrocarbons Gases (freon, halon fire extinguishing

agent) Metallic paints Sniffing Huffing Bagging

Examples Cocaine Amphetamines

Benzedrine (bennies) Dexedrine (dexies, copilots) Methamphetamine (ice, black beauties)

Ephedrine Caffeine Ritalin

Cocaine local anesthetic used to treat depression Block of dopamine transporter, by

increasing conc in nucleus accumbens Increased risk of intracranial haemorrhage,

ischemic stroke, myocardial infarction and seizures.

Produce euphoria hyperactivity alertness sense of enhanced energy anorexia

Overdose signs/symptoms Euphoria, restlessness, agitation, anxiety Paranoia, irritability, delirium, psychosis Muscle tremors, rigidity Seizures, coma Nausea, vomiting, chills, sweating, headache Elevated body temperature Tachycardia, hypertension Ventricular arrhythmias

Withdrawal Drowsiness Profound depression (“cocaine blues”) Increased appetite Abdominal cramps, diarrhea, nausea Headache

Include derivatives of amphetamine related compound methylene-dioxymethaamphetamine (MDMA)

Increases extracellular concentration of serotinin

Long term cognitive impairement in heavy users of MDMA.

Withdrawal lead to depression

Transdermal nicotine patches for smoking

Baclofen is a GABAB receptor agonist Rimonabant is inverse agonist of CB1

receptors