Download 11. DRUGS OF ABUSE

DRUGS OF ABUSE
By: Jeffrey L. Leal, MD, DPBA
Drug Abuse
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§
§
use of an illicit drug or
the
excessive or nonmedical
use of an
illicit drug
denotes the deliberate
use of
chemicals that generally
are not
considered drugs by the
lay public
but may be harmful to
the user
primary motivation for
drug abuse appears to
be the anticipated
feeling of pleasure
derived from the CNS
effects of the drug
Dependence
§ A state characterized by signs and symptoms, frequently the opposite of
those caused by a drug, when it is withdrawn from chronic use or when
the dose is abruptly lowered.
§ formerly termed physical or physiologic dependence
Addiction
§ Compulsive drug-using behavior in which the person uses the drug for
personal satisfaction, often in the face of known risks to health
§ formerly termed psychological dependence
THE DOPAMINE HYPOTHESIS OF
ADDICTION
§ Dopamine in the ventral tegmental area and the nucleus accumbens of
the mesolimbic system appears to play a primary role in the expression
of “reward”
§ excessive dopaminergic stimulation may lead to reinforcement such that
the rewarded behavior may become compulsive—a common feature of
addiction
§ most addictive drugs have actions that include facilitation of the effects
of dopamine in the CNS
SEDATIVEHYPNOTICS
Benzodiazipine and Barbiturate
Effects
§ reduce inhibitions, suppress anxiety, and produce relaxation thus
encourage repetitive use
§ enhance brain dopaminergic pathways leading to the development
of addiction
§ enhanced by concomitant use of opioid analgesics, antipsychotic
agents, marijuana, and any other drug with sedative properties
Acute Overdose
§ result in death through depression of the medullary respiratory and
cardiovascular centers.
Treatment
•
•
Flumazenil: reverse the CNS depressant effects of benzodiazepines
No antidote for barbiturates or ethanol
Flunitrazepam
(Rohypnol)
a potent rapid-onset
benzodiazepine with marked
amnestic properties, has
been used in “date rape”
Chloral hydrate
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•
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•
aka: f-hydroxybutyrate (GHB; sodium oxybate)
added to alcoholic beverages
renders the victim incapable of resisting rape
used as a “club drug,” causes euphoria, enhanced sensory
perception, and amnesia
Withdrawal Treatment
§ Long-acting sedative-hypnotic (eg, Chlordiazepoxide or Diazepam) to
suppress the acute withdrawal syndrome, followed by gradual dose
reduction
§ Clonidine or Propranolol may be used to suppress sympathetic
overactivity.
Treatment of Alcoholism
§ Naltrexone: opioid receptor antagonist
§ Acamprosate: N-methyl-d-aspartate (NMDA) glutamate
receptors antagonist
OPIOID
ANALGESICS
Primary targets underlying
the actions of the opioid
analgesics:
μ, κ, and δ receptors
Commonly abused
Drugs
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§
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Heroin
Morphine
Codeine
Oxycodone
Meperidine
Fentanyl
Effects
§ IV admin: rapid development of tolerance, dependence, and
addiction
e.g. Heroin IV: “rush” or orgasmic feeling followed by
euphoria and then sedation
§ Oral admin or smoking of opioids: causes milder effects, with
a slower onset of tolerance and dependence
Overdose
§ respiratory depression progressing to coma and death
Management:
§ Naloxone or Nalmefene
§ Ventilatory support
Withdrawal
Abstinence syndrome
lacrimation
rhinorrhea
yawning
sweating
weakness
gooseflesh (“cold turkey”)
nausea and vomiting
tremor
muscle jerks (“kicking the habit”)
hyperpnea
Treatment
§ Methadone
§ Buprenorphine
§ a partial agonist at μ opioid receptors
§ longer acting opioid (half-life >40 h)
§ suppress withdrawal symptoms and
as substitution therapy for opioid
addicts
Treatment
§ Neonates born to mothers physiologically dependent on
opioids require special management of withdrawal
symptoms.
STIMULANTS
Nicotine
§ tobacco products
§ Withdrawal:
§ anxiety and mental discomfort (major impediments to
quitting the habit)
Smoking Cessation
§ Varenicline
§ partial agonist at the α4β2 subtype nicotinic receptors
§ occludes the rewarding effects of nicotine
§ Rimonabant
§ an agonist at cannabinoid receptors
§ approved for use in obesity
Caffeine
§ in beverages
§ Withdrawal:
§ lethargy,
irritability, and
headache
Acute Toxicity from Overdosage of
Caffeine or Nicotine
§ excessive CNS stimulation with tremor, insomnia and
nervousness
§ cardiac stimulation and arrhythmias
§ respiratory paralysis (nicotine)
Amphetamines
§ alter transporters of CNS amines including
dopamine, norepinephrine, and
serotonin, and increase their release
• cause a feeling of euphoria and selfconfidence that contributes to the rapid
development of addiction
• Chronic high-dose abuse leads to a
psychotic state (with delusions and
paranoia) that is difficult to differentiate
from schizophrenia
Amphetamines
• Example:
• Dextroamphetamine
• Methamphetamine
(“speed”): a crystal form of
which (“ice”) can be
smoked
Tolerance
and
Withdrawal
§ Abstinence Syndrome:
– characterized by increased appetite,
sleepiness, exhaustion, and mental
depression, can occur on withdrawal
– Antidepressant drugs may be
indicated
Congeners of Amphetamines
§ hallucinogenic
properties
§ 2,5-dimethoxy-4methylamphetamine
(DOM [STP])
§ Methylene
dioxyamphetamine
(MDA)
§ Methylene
dioxymethamphetamin
e (MDMA)/ “ecstasy”
Cocaine
§ inhibitor of the CNS
transporters of
dopamine,
norepinephrine, and
serotonin
§ marked a amine-like
effects (“super-speed”)
§ euphoria, selfconfidence, and mental
alertness
§ Overdose:
§ result in fatalities from
arrhythmias, seizures,
or respiratory
depression
Cocaine
• Cardiac toxicity: due to
blockade of norepinephrine
reuptake
• Local anesthetic action:
production of seizures
• vasoconstrictive action:
severe hypertensive
episodes, resulting in
myocardial infarcts and
strokes
• No specific antidote
HALLUCINOGENS
Psychedelic and mind revealing
Phencyclidine
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PCP
“angel dust”
most dangerous of the hallucinogenic agents
Psychotic reactions, impaired judgment and reckless behavior
classified as a psychomimetic
Overdosage
§ horizontal and vertical nystagmus, marked hypertension and seizures
Ketamine
§ “special K”
§ NMDA receptor antagonist
Other Hallucinogens
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Lysergic acid diethylamide (LSD)
Mescaline
Psilocybin
Scopolamine
MARIJUANA
§ plant Cannabis sativa
(hemp)
§ Marijuana (“grass”): a
collective term for the
psychoactive constituents
in crude extracts
MARIJUANA
Active principles:
§ Tetrahydrocannabi
nol (THC)
§ Cannabidiol (CBD)
§ Cannabinol (CBN)
Endogenous cannabinoids in the CNS
1.
2.
MARIJUANA
Anandamide
2-arachidonyl glycerol
§ released postsynaptically
§ act as retrograde messengers to
inhibit presynaptic release of
conventional transmitters including
dopamine
§ receptors for these compounds are
the targets for exogenous
cannabinoids present in marijuana
CNS
Effects
a feeling of being “high”
euphoria
disinhibition
uncontrollable laughter
changes in perception
achievement of a dream-like state
mental concentration may be difficult
Vasodilation
Increased pulse rate
Others
reddened conjunctiva for
habitual users
impairment of judgement
and reflexes
Therapeutic Effects
1.
2.
Decrease intraocular pressure
Antiemesis
INHALANTS
provide a feeling of euphoria or disinhibition
Anesthetics
§ they affect judgment and induce loss of consciousness
1.
Nitrous oxide
§ asphyxia and death if with no Oxygen
2. Chloroform
3. Diethylether
§ highly flammable
Industrial Solvents
§ most frequently abused by children in early adolescence
§ gasoline, paint thinners, aerosol propellants, glues, rubber cements, and
shoe polish
§ Active ingredients:
§ benzene, hexane, methylethylketone, toluene and trichloroethylene
Organic Nitrites
§ “poppers”
§ mainly used as sexual
intercourse enhancers
§ Amyl nitrite
§ Isobutyl nitrite
Organic Nitrites
• causes dizziness,
tachycardia,
hypotension, and
flushing
• methemoglobinemia
STEROIDS
§ anabolic steroids are
controlled substances
based on their
potential for abuse
§ increase in muscle
mass and strength
STEROIDS
Adverse Effects:
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Severe acne
premature closure of the
epiphyses
masculinization in females
hepatic dysfunction
increased risk of myocardial
infarct
increase in libido
aggression (“roid rage”)