DRUGS OF ABUSE

EVELYN B. YUMIACO M.D.DEPARTMENT OF PHARMACOLOGY

SCHOOL OF MEDICINEANGELES UNIVERSITY FOUNDATION

HISTORY

3500 BC EGYPTIAN RITUALS1600 BC ANALGESIC AND PAIN KILLER1869 COCAINE1898 HEROIN (BAYER)

1930 MARIJUANA

DANGEROUS DRUGS ACT OF 1972 (RA 6425 )

PROHIBITS THE • IMPORTATION• SALE, ADMINISTRATION, DELIVERY, DISTRIBUTION

AND TRANSPORTATION OF PROHIBITED DRUGS• MAINTENANCE OF DEN, DIVE, RESORT FOR USERS

– EMPLOYEES AND VISITORS OF DRUG DEN– MANUFACTURE OF PROHIBITED DRUGS

• POSSESSION OR USE OF PROHIBITED DRUGS• CULTIVATION OF PLANTS WHICH ARE SOURCES OF

PROHIBITED DRUGSRECORDS OF PRESCRIPTION, SALES, PURCHASE,

ACQUISITION AND DELIVERY OF PROHIBITED DRUGS– UNLAWFUL PRESCRIPTION OF PROHIBITED DRUGS– UNNECESARY PRESCRIPTION OF PROHIBITED DRUGS– POSSESSION OF OPIUM PIPE AND OTHER PARAPHERNALIA

DANGEROUS DRUGS BOARD• POLICY MAKING, STRATEGY FORMULATING BODY IN THE

PLANNING AND FORMULATION OF POLICIES AND PROGRAMS ON DRUG PREVENTION AND CONTROL

• COMPOSITION– SECRETARY OF DEPT OF JUSTICE– DOH– DND– DF– DOLE– DILG– DSWD– DFA– DEPED– CHAIR NATIONAL YOUTH COMMISSION– DIRECTOR GENERAL PHIL DRUG ENFORCEMENT AGENCY– CABINET SECRETARIES– PRESIDENT OF IBP– NGO– NBI– CHIEF PNP

DEFINITION• DANGEROUS DRUGS REFERS TO:• PROHIBITED DRUGS

– OPIUM AND ITS ACTIVE COMPONENTS AND DERIVATIVES SUCH AS HEROIN AND MORPHINE

– COCA LEAF AND ITS DERIVATIVES PRINCIPALLY COCAINE, ALPHA AND BETA EUCAINE

– HALUCINOGENIC DRUGS– MESCALINE, LYSERGIC ACID DIETHYLENEAMIDE (LSD)– INDIAN HEMP AND DERIVATIVES

• REGULATED DRUGS– SELF INDUCING SEDATIVES SUCH AS SECOBARBITAL,

PHENOBARBITAL, PENTOBARBITAL, BARBITAL, AMOBARBITAL AND OTHER DRUGS CONTAINING BATBITURIC ACID AND SALT OR ISOMER OF AMPHETAMINE SUCH AS BENZEDRINE OR DEXBENZEDRINE AND HYPNOTIC DRUGS SUCH AS METHAQUALONE, NITRAEPAN

• INDIAN HEMP• MARIJUANA• EVERY KIND, CLASS , GENUS OR SPECIES

OF THE PLANT CANNABIS SATIVA INCLUDING C. AMERICANA, HASHISH, BHANG, GUAZA, CHURRUS, CANJAB WHETHER DRIED, FRESH, FLOWERING OR FRUITING TOPS, SEEDS

• NARCOTIC DRUGS REFERS TO:– ANY DRUG WHICH PRODUCES

INSENSIBILITY, STUPOR, MELANCHOLY OR DULLNESS OF MIND WITH DELUSION , MAY BE HABIT FORMING SHALL INCLUDE OPIUM, DERIVATIVES AND SYNTHETIC OPIATES

• OPIUM REFERS TO – THE COAGULATED JUICE OF PAPAVER

SOMNIFERUM

• HALLUCINOGENIC DRUGS– DRUGS THAT PRODUCE PERCEPTUAL

DISTORTION– ILLUSION– HALLUCINATION– PARANOIA– MINIMAL EFFECT ON MEMORY AND

ORIENTATIONGOODMAN GILMAN

CLASSIFICATION

• DRUGS THAT ACTIVATE Gio COUPLED RECEPTOR

• DRUGS THAT MEDIATE EFFECTS VIA IONOTROPIC RECEPTOR

• DRUGS THAT BIND TRANSPORTER OF BIOGENIC AMINE

DRUGS THAT ACTIVATE Gio COUPLED RECEPTOR

• OPIOIDS• CANNABINOIDS• GHB• HALLUCINOGEN

– LSD– MESCALINE– PSILOCYBIN

OPIOID

• REFERS TO ALL COMPOUNDS RELATED TO OPIUM

• OPOS= JUICE• DERIVED FROM JUICE OF OPIUM

POPPY (PAPAVER SOMNIFERUM)

CAPSULE OF PAPAVER SOMNIFERUM WITH LATEX

POPPY CULTIVATION

OPIATES• DRUGS DERIVED FROM OPIUM• ENDOGENOUS OPIOID PEPTIDES

– ENKEPHALINS (LEU ENKEPHALIN, MET ENKEPHALIN)– ENDOPHIN 1,2– DYNORPHIN A,B

• NATURAL PRODUCTS– MORPHINE– CODEINE– THEBAINE

• SEMISYNTHETIC DERIVATIVE– BUPRENORPHINE– CODEINE– DIHYDROCODONE– HEROIN (MOST WIDELY USED)

• JUNK, H, SMACK, SKAG, HORSE, – DIPIPANONE– FENTANYL– METHDONE– NALBUPHINE– OXYCODONE– PENTAZOCINE– PETHIDINE– TRAMADOL

ABSORPTION

• CODEINE• OXYCODONE

– LOWER FIRST PASS EFFECT • MORPHINE

– HIGH FIRST PASS EFFECT

• ROUTES OF ADMIN• NASAL ROUTE

– BYPASS THE FIRST PASS EFFECT– BUTORPHANOL

• BUCCAL – FENTANYL LOZENGE

• TRANSDERMAL– STABLE BLOOD LEVEL, BETTER PAIN CONTROL– FENTANYL

• RECTAL• PAIN CONTROLLED ANALGESIA (PCA)

POLISH MAKOWEIC CAKE

DISTRIBUTION

• DRUG CONCENTRATION IN THE SKELETAL MUSCLE IS LOW

• HIGH CONCENTRATION IN HIGHLY PERFUSED AREAS– BRAIN– LUNGS– KIDNEYS– LIVER – SPLEEN

METABOLISM

• CONVERTED TO POLAR METABOLITES IN THE LIVER

• HEROIN HAS NO INTRINSIC ACTION AT OPIOID RECEPTOR– METABOLITES

• 6 MONO ACETYL MORPHINE • MORPHINE

EXCRETION

• POLAR METABOLITES ARE EXCRETED IN THE URINE

MECHANISM OF ACTION1. RECEPTORTYPES

– MU 1,2– DELTA 1,2– KAPPA 1,2,3– ORPHANIN OPIOID RECEPTOR LIKE SUBTYPE( ORL1)

2. CELLULAR ACTION– CLOSE CA CHANNELS ON PRESYNAPTIC NERVE

TERMINAL LEADING TO DECREASE RELEASE OF NEUROTRANSMITTERS

– OPEN K CHANNELS LEADING TO HYPERPOLARIZATION AND INHIBITION OF POST SYNAPTIC NEURONS

MECHANISM OF ACTION

TOLERANCE– GRADUAL LOSS OF EFFECT WITH

REPEATED USE

PHYSICAL DEPENDENCE– WITHDRAWAL SYNDROME DEVELOPS

WHEN A DRUG IS STOPPED OR AN ANTAGONIST IS ADMINISTERED

TOLERANCE AND DEPENDENCE

• PERSISTENT ACTIVATION OF MU RECEPTORS

• UPREGULATION OF CAMP?• DOWN REGULATION OF MU

RECEPTORS• DYSFUNCTION BETWEEN THE

RECEPTOR, G PROTEIN, 2ND MESSENGER

OPIOID RECEPTORSANALGESIA

SUPRASPINAL M,K,D ANALGESIC

SPINAL M,K,D ANALGESIC

PSYCHOMIMETIC K INCREASE

RESPIRATORY M DEC

GIT M,K DEC TRANSIT

FEEDING M,K,D INC FEEDING

SEDATION M,K INC

DIURESIS K INC

OPIOID RECEPTORSHORMONE REGULATIONPROLACTIN M INCREASE RELEASEGH M,D INCREASE RELEASENEUROTRANSMITTERACH M INHIBITDOPAMINE M,D INHIBITISOLATED ORGAN BIOASSAY GUINEA PIG ILEUM M

DECREASE CONTRACTION

MOUSE VAS DEFERENS D DECREASE CONTRACTION

EFFECTS

CNS

• ANALGESIA– REDUCE THE SENSORY AND AFFECTIVE

COMPONENT• EUPHORIA

– PLEASANT FLOATING SENSATION WITH LESS ANXIETY AND DISTRESS

• SEDATION– DROWSINESS AND CLOUDING OF MENTATION

• RESPIRATORY DEPRESSION– INHIBIT BRAINSTEM RESPIRATORY MECHANISM– INCREASE ALVEOLAR PCO2– DOSE RELATED– C/I– ASTHMA– COPD– COR PULMONALE– INC ICP

• COUGH SUPPRESSION– INCREASE THRESHOLD FOR STIMULATION OF NEURON

IN THE MEDULLARY COUGH CENTER– DIRECT INHIBITION OF COUGH REFLEX IN THE

MEDULLARY CENTER– DEPRESS THE CNS AND INHIBIT THE COUGH CENTER– MAY LEAD TO ACCUMULATION OF SECRETION AND

OBSTRUCTION

• MIOSIS– CONSTRICTION OF PUPILS

• TRUNCAL RIGIDITY– DECREASE THORACIC COMPLIANCE

AND VENTILATION• NAUSEA /VOMITING

– ACTIVATE CRTZ• TEMPERATURE

– M= HYPERTHERMIA– K=HYPOTHERMIA

PERIPHERALCVS• BRADYCARDIA• NO MAJOR EFFECT ON RHYTHM• HYPOTENSION

– DUE TO PERIPHERAL AND VENOUS DILATATION– DUE TO RELEASE OF HISTMINE

• CNS DEPRESSION OF VASOMOTOR MECHANISM• MEPERIDINE

– TACHYCARDIAGIT

– CONSTIPATION– DECREASE TONE AND HCL

• BILIARY– CONTRACT SM LEAD TO BILIARY COLIC– CONTRACTION OF SPHINCTER OF ODDI

LEADING TO REFLUX OF BILIARY AND PANCREATIC SECRETION

• RENAL– DECREASE RENAL PLASMA FLOW– ENHANCE TUBULAR NA REABSORPTION

• UTERUS– PROLONG LABOR– REDUCE UTERINE TONE

• NEUROENDOCRINE– STIMULATE ADH– PROLACTIN– SOMATOTROPIN– INHIBIT LH

• PRURITUS– FLUSHING AND WARMING– HISTAMINE RELEASE

SPECIFIC AGENTS

STRONG AGONIST• PHENANTRENE

– MORPHINE– HYDROMORPHONE– OXYMORPHONE– HEROIN (DIACETYL MORPHINE)

• PHENYLHEPTYLAMINE– METHADONE

• PHENYLPIPERIDINE– FENTANYL

• MORPHINAN– LEVORPHANOL

MILD TO MODERATE AGONIST

• PHENANTRENE– CODEINE– OXYCODONE

• PHENYLHEPTYLAMINE– PROPOXYPHENE

• PHENYLPIPERIDINE– DIPHENOXYLATE– DIFENOXIN– LOPERAMIDE

MIXED RECEPTOR ACTION

• PHENANTRENE– NALBUPHINE– BUPRENORPHINE

• MORPHINANS– BUTORPHANOL

• BENZOMORPHAN– PENTAZOCINE

MISCELLANEOUS

• TRAMADOL– BLOCKADE OF SEROTONIN REUPTAKE– WEAK MU RECEPTOR AGONIST– MAY CAUSE SEIZURE

• ANTITUSSIVE– DEXTROMETHORPHAN

• DERIVATIVE OF LEVORPHANOL• NO ADDICTIVE PROPERTY

– LEVOPROPOXYPHENE• DERIVATIVE OF DEXTROPOPOXYPHENE• NO OPIOID EFFECT

– CODEINE

HEROIN

• 1 MIL ADDICTS IN THE USA• 1 OUT OF 4 USERS BECOME

ADDICTED• NO LEGAL SUPPLY FOR CLINICAL

USE• AS PURITY INCREASES LEVEL OF

DEPENDENCE IS HIGH• IV, SMOKED, NASAL (SNORTED)

HEROIN

• INJECTION• WARMTH, HIGH INTENSE PLEASURE

(RUSH = SEXUAL ORGASM)• ONSET = LESS THAN 1 MIN• DURATION OF EUPHORIA= LESS THAN 45

SEC – MINUTES• FOLLOWED BY SEDATION AND

TRANQUILITY= 1 HOUR• TOTAL DURATION OF EFFECT 3-5 HRS

HEROIN

• AFTER INJECTION• MALE = DOCILE, COMPLIANT • WITHDRAWAL= AGGRESSIVE ,

IRRITABLE• HEROIN + FENTANYL• HEROIN + COCAINE (SPEEDBALL)

HEROIN

MORTALITY• INVOLVEMENT IN CRIME• INFECTION

• NON STERILE NEEDLE• SHARING OF PARAPHERNALIA

– SKIN ABSCESS– ENDOCARDITIS– PULMONARY INFECTION (TB)– HEPATITIS C– AIDS

HEROINMETHODS TO DETOXIFY1. GIVE PRESCRIPTION OPIOID THEN

GRADUAL TAPER2. CLONIDINE ALPHA ADRENERGIC AGONIST

(DECREASE ADRENERGIC NEUROTRANSMISSION)

3. ACTIVATION ENDOGENOUS OPIOID WITHOUT MEDICATION (ACUPUNCTURE, CNS ELECTRICAL STIMULATION)

4. RAPID ANTAGONIST UNDER GA

HEROIN

• CHARACTERISTICS OF WITHDRAWAL– PUPILLARY DILATION– SWEATING– PILOERECTION– TACHYCARDIA– VOMITING, DIARRHEA– INCREASE BP– YAWNING– FEVER

CANNABINOIDS

• MOST COMMONLY USED ILLEGAL DRUG IN THE USA

• REFERS TO – INDIAN HEMP– CANNAVIS SATIVA

• MAJOR ACTIVE CONSTITUENTS– CANNABINOIDS ( >60)– DELTA 9 TETRAHYDROCANNABINOL (THC)

• MOST IMPORTANT

CANNAVIS SATIVA

• MARIJUANA (HERB FORM)– GRAY GREEN DRIED AND CRUSGHED FLOWER HEADS AND

SMALL LEAVES OF CANNABIS PLANT• MARIHUANA• GRASS• DOPE• BLOW• SKUNK• WEED• POT• HEMP• BHANG• GANJA• 5% THC

• HASHISH (RESIN FROM)– REFER TO THE CANNABIS RESIN ALONE AFTER REMOVAL

FROM THE PLANT– HASHISH AL KIEF = HERB OF PLEASURE– 20% THC

• HASH OIL– CONCENTRATED RESIN EXTRACT– MOST POTENT FORM OF CANNABIS– 60% THC

MARIJUANA HASHISH

• MARIJUANA HERB ROLLED INTO CIGARETTES OR MIXED WITH TOBACO ALSO CALLED– SPLIFFS, JOINTS, REEFERS

• SYNTHETIC CANNABINOID DERIVATIVE– DRONABINOL– NABILONE

PROVIDES LOW DOSE SERVINGS

SMOKING PIPE

SMOKING PIPE

JOINT

KINETICS• THC DISSOLVES IN PULMONARY SURFACTANT• HIGHLY LIPID SOLUBLE PENETRATES CNS• ONSET MINUTES• PEAKS IN 1-2 MIN• T1/2 4 HRS• ORAL DOSE EXTENSIVE FIRST PASS EFFECT• DISTRIBUTES INTO ADIPOSE TISSUE THEN

RELEASED SLOWLY• METABOLISM CCUR IN THE LIVER• URINE TEST POSITIVE FROM 31.5- 95 DAYS

DYNAMICS

• CB1 (CNS) AND CB2 (PERIPHERAL TISSUES)

• INHIBIT THE RELEASE OF GLUTAMATE AND GABA THROUGH PRESYNAPTIC INHIBITION

EFFECTS• EUPHORIA• RELAXATION• WELL BEING• GRANDIOSITY• ALTERED PERCEPTION OF TIME PASSAGE• PERCEPTUAL CHANGES• “HIGH”= 2 HRS= IMPAIRMENT OF

COGNITIVE FXN, PERCEPTION, MEMORY, LEARNING , IMPAIRMENT OF COORDINATION

ACUTE ADVERSE EFFECTS• ANXIETY, CONFUSION, DROWSINESS, PANIC

REACTION, PSYCHOSIS• PSYCHOMOTOR IMPAIRMENT, ATAXIA, MEMORY

LOSS• TACHYCARDIA, PALPITATION, POSTURAL

HYPOTENSION, FLUSHING• COUGH, SORETHROAT, BRONCHOSPASM• DELAY GASTRIC EMPTYING, NAUSEA, DRY

MOUTH, INCREASE APETITE (HUNGER)• RED EYES• CAN PPT RECURRENCE OF SCHIZOPRENIA• “AMOTIVATIONAL SYNDROME”= DROP OUT

FROM SOCIAL ACTIVITY AND SHOW LITTLE INTEREST IN SCHOOL

LONG TERM USE

• BRONCHITIS• CANCER• OLIGOSPERMIA• GYNECOMASTIA, DECREASE LIBIDO• INSOMIA, DEPRESSION, SOCIAL

WITHDRAWAL, DECREASE MENTAL PERFORMANCE, REDUCE DRIVE, DEPENDENCE, WITHDRAWAL SYMPTOMS

• NO EVIDENCE OF BRAIN CELL DAMAGE

• BENEFITS– ANTICONVULSANT– MUSCLE RELAXANT– DECREASE IOP

MARIJUANA

• WITHDRAWAL (THOSE WHO ARE USING DAILY THEN SUDDEN STOP)– RESTLESSNESS– IRRITABILITY– MILD AGITATION– INSOMNIA– SLEEP EEG DISTURBANCE– NAUSEA– CRAMPING

LSD

• OTHER NAMES– ACIDS– TRIPS– LYSERGIC ACID DIETHYL AMIDE – LYSERGIDE

• FROM ERGOT (CLAVICEPS PURPUREA)• MOST POTENT HALLUCINOGENIC DRUG• SOLD ILLEGALLY AS STAMP SIZE PAPER

WITH LSD

CLAVICEPS

BLOTTER PAPER IMPREGNATED WITH LSD

KINETICS

• ABSORBED BY MOUTH RAPIDLY• EFFECTS SEEN IN 30-90 MIN• LAST 3-12 HRS, T1/2 3 HRS• ELIMINATED VIA THE LIVER

MECHANISM

• INTERACT WITH SEROTONIN RECEPTOR IN THE CNS (5 HT2A)

• COUPLES WITH Gq WITH IP3

EFFECT

• INDUCE PERCEPTUAL SYMPTOMS– SHAPE AND COLOR DISTORTION

• PSYCHOSIS LAST 2 DAYS• SCHIZOPRENIC EPISODES• SOMATIC SYMPTOMS• TOLERANCE• DOES NOT INDUCE DEPENDENCE OR

ADDICTION

SIGNS OF INTAKE• PUPILLARY DILATION• INCREASE BP• INCREASE HR• FLUSHING • SALIVATION• LACRIMATION• HYPERREFLEXIA• “BAD TRIP”= SEVERE ANXIETY, INTENSE

DEPRESSION, SUICIDAL THOUGHTS

ADVERSE EFFECTS

• COMMON– ADRENERGIC FLIGHT OR FIGHT– EXHAUSTION, TIREDNESS, WEAKNESS– HEADACHE , DISORIENTATION,

CONFUSION– ANXIETY, PSYCHOSIS, HALLUCINATION

ADVERSE EFFECT

• RARE ACUTE– ATAXIA, CONVULSION– HYPERPYREXIA

POST EXPOSURE– FLASHBACKS– DEPRESSION, INSOMINA

INCREASE

GAMMA HYDROXYBUTYRIC ACID

• OTHER NAMES– GBH– LIQUID X– LIQUID ECSTASY– FANTASY– GCLUB DRUGDATE RAPE DRUGGRIEVOUS BODILY HARM

• USED FOR DRUG FACILITATED SEXUAL ASSAULT

• ODORLESS WHITE POWDER• SOLUBLE IN WATER• T ½ 30 MIN

MECHANISM

• 2 BINDING SITES– GHB– GABA B

• INHIBIT DOPAMINE RELEASE

ADVERSE EFFECTS• DROWSINESS, HYPNOSIS, CONFUSION,

COMBATIVENESS• HEADACHE, TUNNEL VISION, DEPRESSION, COMA• ATAXIA, MYOCLONIC MOVEMENTS, SEIZURE ,

TREMORS• BRADYCARDIA, CARDIAC ARREST,

HYPOTENSION• NAUSEA, VOMITING, DIARRHEA• URINARY AND FECAL INCONTINENCE• HYPOTHERMIA

MEDIATE EFFECTS VIA IONOTROPIC RECEPTOR

• NICOTINE• BENZODIAZEPINE• ALCOHOL• KETAMINE • PCP• INHALANTS

ETHANOL

• DEPRESSANT– SLEEP – SEDATION

• LOW DOSE – SUPPRESSION OF INHIBITORY SYSTEM– IMPAIRS RECENT MEMORY– BLACKOUT– RELIEVE ANXIETY

KETAMINE/ PHENCYCLIDINE

• OTHER NAMES– ANGEL DUST– PCP– HOG– SPECIAL K– CLUB DRUG

• BLOCK ACTION OF NMDA AND GLUTAMATE RECEPTORS

• PRODUCE VIVID DREAMS AND HALLUCINATION• PRODUCE LONG LASTING PSYCHOSIS LIKE

SCHIZOPHRENIA• DOES NOT CAUSE DEPENDENCE OR ADDICTION

ADVERSE EFFECTS

• HYPERTENSION• TACHYCARDIA• SWEATING• BRONCHOSPASM• BIZARRE AND DANGEROUS

(ASSAULTIVE) BEHAVIOR

• OVERDOSE IS TREATED WITH LIFE SUPPORT

• NO ANTAGONIST TO PCP EFFECT

INHALANTS• NITRATES• KETONES• HYDROCARBON• SNIFFING

– INHALATION FROM AN OPEN CONTAINER• HUFFING

– SOAKING CLOTH IN VOLATILE SUBS• BAGGING

– BREATHING IN /OUT OF PAPER OR PLASTIC BAG

• ALTERED FUNCTION OF IONOTROPIC RECEPTORS AND ION CHANNELS THROUGHOUT THE CNS

• MOST HAVE UNKNOWN MECHANISM• NITRATES

– BIND TO NMDA RECEPTORS• AMYL NITRATE

– SMOOTH MUSCLE RELAXATION– ERECTION

NMDANa

Ca Ca

VDCC

Depolarization

Ca Na

(-) GLU

K Na

CaATP

N methyl d aspartateVoltage activated Ca chanAminomethylisoxazole propionic acid

AMPA

GLUTAMATE

M

Ca

Activation PROTEASE/LIPASE/NO

FREE RADICAL

ER

BIND TRANSPORTER OF BIOGENIC AMINE

• COCAINE• AMPHETAMINE• ECSTACY

COCAINE

• ERYTHROXYLON COCA• T1/2 COCAINE= 50 MIN• URINARY METABOLITE = FOUND IN URINE

AFTER 2-5 DAYS (UP TO 10 DAYS)• BLOCK THE UPTAKE OF

– NE (TACHYCARDIA, HYPERTENSION, ARRYTHMIA

– SEROTONIN (HALLUCINOGEN, ANORIXIGENIC, HYPERTHERMIA)

– DOPAMINE (EUPHORIA, ABNORMAL MOVEMENTS, PSYCHOTIC EPISODES)

ERYTHROXYLON COCA

LEAVES AND BERRIES

• OTHER EFFECTS– AROUSAL – INCREASE ALERTNESS– SELF CONFIDENCE AND WELL BEING– IRRITABILITY– PARANOIA– INCREASE VIOLENCE

• HIGH ADDICTION POTENTIAL (23 MIL AMERICANS)

• TOXICITY– PROLONGED AND INTENSE ORGASM– ASSOCIATED WITH PROMISCUOUS SEXUAL ACTIVITY– LONG TERM USE = DECREASE SEXUAL DRIVE– ANXIETY– DEPRESSION– PSYCHOSIS

• INCREASE RISK– ISCHEMIC STROKE– MI– SEIZURE, CEREBRAL VASOCONSTRICTION– ARRYTHMIA– MYOCARDITIS– AORTIC DISSECTION

• OVERDOSE– HYPERTHERMIA– COMA– DEATH

COCAINE

• WITHDRAWAL– DYSPORIA– DEPRESSION– SLEEPINESS– FATIGUE– COCAINE CRAVING– BRADYCARDIA

DAT

COCAINE

DOPAMINE

DAT

AMPHETAMINE

DOPAMINE

VMATA

DAT= DOPAMINE TRANSPORTERVMAT = VESICLE MONOAMINE TRANSPORTER

AMPHETAMINE AND OTHER AGENTS

• AMFETAMINE (AMPHETAMINE)• METAMFETAMINE = ICE• METHYLENEDIOXYAMFETAMINE=MDA• METHYLENEDIOXYMETAMFETAMINE=

MDMA ( ECSTASY)

MECHANISM

• AMPHETAMINE– DEPLETE VESICULAR TRANSMITTERS

• MDMA– HIGH AFFINITY TO SEROTONIN TRANSPORTER– INCREASE EXTRACELLULAR CONC OF

SEROTONIN– REPETITIVE ADMINISTRATION MAY LEAD TO

DEPLETION– MAY BE NEUROTOXIC

AMFETAMINE METAMFETAMINE ECSTASY

ADMIN INJ, NASAL INJ, NASAL INJ, NASAL

FORM POWDER POWDERCRYSTALTABLETS

TABLETS

HALF LIFE 12-13 HRS 10-12 HRS 8-9 HRS

ALL PURPOSE STIMULATION

CNS STIMULANTS EMOTIONALMYSTICAL EFFECTS

PERIPHERAL ACTION

MOST POWERFUL CNS STIMULANT ACTION

SEROTONINERGIC EFFECT

DEPENDENCE POTENTIAL

HIGH HIGH LOWER

MDMA PILLSMDMA FACTORY

ADVERSE EFFECT• MINOR ADVERSE EFFECT• MYDRIASIS, PHOTOPHOBIA, BLURRED

VISION, HEADACHE, NUMBNESS• ANOREXIA, SWEATING• TACHYCARDIA, PALPITATION• TREMOR, ATAXIA• CONFUSION, ANXIETY• SEIZURE• MAY CAUSE IRREVERSIBLE BRAIN

DAMAGE

• KHAT– PLANT FROM YEMEN, EAST AFRICA– ALKALOIDAL CATHINONE SIMILAR TO AMPHATAMINE

• CAFFEINE– MILD STIMULANT– INCREASE NE AND DOPAMINE RELEASE– ENHANCE NEURAL ACTIVITY– COMPETITIVE ANTAGONIST OF ADENOSINE– CAN LEAD TO CAFFEINE WITHDRAWAL

• FATIGUE, SEDATION• HEADACHE• NAUSEA

–

REFERENCES

• PHARMACOLOGY BY KATZUNG• DRUGS OF ABUSE BY SIMON WILLS• COMPREHENSIVE DRUG EDUCATION

BY SORIANO• GOODMAN GILMAN