Drugs of Abuse Flashcards
What is Drug Abuse?
• Abuse is the excessive self-administration of
any substance for nonmedical purposes.
• Some drugs of abuse do not lead to addiction.
• This is the case of substances that alter
perception without causing sensations of reward
and euphoria, such as the hallucinogens.
What behaviors indicate addiction?
Behaviors that include one or more of the following: • impaired control over drug use • compulsive use • continued use despite harm • craving
What is physical dependence and how can withdrawal syndrome be reproduced?
• State of adaptation manifested by drug class
specific withdrawal syndrome.
• The withdrawal syndrome can be produced by:
• abrupt cessation
• rapid dose reduction
• administration of an antagonist.
What is withdrawal syndrome?
• Physiological and behavioral changes directly
related to sudden cessation or reduction in use of a drug to which the body has become adapted.
What is considered tolerance?
• A state of adaptation in which exposure to a
drug induces changes that result in a diminution
of one or more of the drug’s effects over time.
• Tolerance may occur to both the desired and
undesired effects of drugs, and may develop at
different rates for different effects.
Physical dependence and Tolerance
• Normal responses that often occur with the
persistent use of certain medications.
Mechanisms of Addiction?
• The mesolimbic dopamine system is the prime
target of addictive drugs.
• As a general rule, all addictive drugs activate
the mesolimbic dopamine system.
Types of drugs of abuse?
- CNS DEPRESSANTS
- PSYCHOSTIMULANTS
- NICOTINE
- OPIOIDS
- MARIJUANA
- PSYCHEDELIC AGENTS
- INHALANTS
- ANABOLIC STEROIDS
list 3 cns depressants?
- Ethanol
- Benzodiazepines
- Barbiturates
Ethanol classification and moa?
• Ethanol is classed as a depressant because it
produces sedation and sleep.
• The initial effects of ethanol are often perceived
as stimulation due to suppression of inhibitory
systems.
• Ethanol influences several cellular functions:
• GABAA receptors
• Kir3/GIRK channels
• Adenosine reuptake
• Glycine receptors
• NMDA receptors
• 5-HT3 receptors.
Describe ethanol withdrawal syndrome?
• Heavy consumption of ethanol leads to acquired
tolerance and physical dependence.
• Withdrawal syndrome may include tremor, nausea, vomiting, sweating, agitation and anxiety.
• This may be followed by hallucinations.
• Generalized seizures may appear after 24-48 h.
• After 48-72 h delirium tremens may appear.
• Delirium tremens is associated with 5-15%
mortality.
TREATMENT OF ALCOHOL WITHDRAWAL?
• Long half-life benzodiazepines are the preferred agents: Diazepam and chlordiazepoxide.
• Because of their long half-life, withdrawal is smoother, and rebound withdrawal symptoms are less likely.
• Lorazepam and oxazepam are intermediateacting drugs.
• They may be preferable in the elderly and
those with liver failure.
Treatment of alcohol addiction?
• Three drugs are FDA-approved for treatment of alcoholism: • Disulfiram: Aldehyde dehydrogenase inhibitor. Used to create aversion to drinking. • Naltrexone: Orally available opioid antagonist. Reduces craving for alcohol. • Acamprosate: NMDA receptor antagonist. Prevents relapse. Topiramate • Facilitates GABA function, antagonizes glutamate receptors. • May reduce cravings. • Not FDA-approved.
Benzodiazepine overview, withdrawal syndrome, and management of withdrawal?
• Can cause physical dependence and addiction.
• Addiction is rare.
• Signs and symptoms include: tremors, anxiety,
perceptual disturbances, dysphoria, psychosis,
and seizures.
• The syndrome can be life-threatening.
• If the patient is on a short-acting drug, they are
switched to a long-acting drug.
• Diazepam is the most used agent.
• Then the dose is gradually reduced.
What does barbiturate abuse resemble?
• Abuse problems with barbiturates resemble those seen with benzodiazepines.
List three psychostimulants?
- Methylxanthines
- Cocaine
- Amphetamines
List 3 methylxanthines and moa?
• Caffeine, theophylline & theobromine.
• Caffeine is the most widely consumed stimulant.
• Methylxanthines block presynaptic adenosine
receptors.
• Activation of adenosine receptors inhibits
norepinephrine release.
• Therefore blockade of adenosine receptors
increases norepinephrine release.
Actions of caffeine dose on CNS?
CNS
• 100–200 mg caffeine (1 - 2 cups of coffee) cause decrease in fatigue and increased mental
alertness.
• 1.5 g caffeine (12 to 15 cups of coffee) produces
anxiety and tremors.
• The spinal cord is stimulated only by very high
doses (2–5 g) of caffeine.
METHYLXANTHINES:
TOLERANCE AND WITHDRAWAL
• Tolerance can rapidly develop to the stimulating
properties of caffeine.
• Withdrawal consists of feelings of fatigue and
sedation.
• Addiction is rare.
• Caffeine is not listed in the category of addicting
stimulants.
Cocaine overview and moa?
• Due to its abuse potential, cocaine is classified
as a Schedule II drug by the DEA.
• Cocaine inhibits dopamine, norepinephrine and
serotonin reuptake.
• The prolongation of dopaminergic effects in the
brain’s limbic system produces the intense
euphoria that cocaine initially causes.
Cocaine’s action on the cns?
CNS
• Stimulation of cortex and brainstem.
• Increases mental awareness and produces a
feeling of well-being and euphoria.
• Paranoia may occur after repeated doses.
• At high doses: tremors and convulsions, followed by respiratory and vasomotor
depression
Cocaine action on the SNS?
SYMPATHETIC NERVOUS SYSTEM
• Peripherally, cocaine potentiates the action of
norepinephrine resulting in adrenergic
stimulation.
• Adrenergic stimulation produces tachycardia,
hypertension, mydriasis, and diaphoresis
Describe cocaine withdrawal syndrome?
• Dysphoria, depression, sleepiness, fatigue, cocaine craving and bradycardia.
• Cocaine withdrawal is generally mild.
• Treatment of withdrawal symptoms is usually not
required.
• Many agents, mainly antidepressants and
dopamine agonists have been tested as treatments for cocaine abuse.
• None have demonstrated clear efficacy
Amphetamines overview and moa?
• Amphetamines are classified as Schedule II
drugs by the DEA.
• Amphetamines increase release of catecholamines.
• They are also weak inhibitors of MAO.
• They are also possible direct catecholaminergic
agonists in the brain.
AMPHETAMINES: ACTIONS on CNS and SNS?
CNS
• Behavioral effects similar to those of cocaine.
• Due to release of dopamine.
• Increased alertness, decreased fatigue,
depressed appetite and insomnia.
• At high doses, psychosis and convulsions.
SYMPATHETIC NERVOUS SYSTEM
• Activate receptors through norepinephrine
release.
Amphetamine uses?
• Attention deficit syndrome: Amphetamine and
methylphenidate.
• Narcolepsy: Amphetamine and methylphenidate.
Describe amphetamine tolerance and withdrawal?
• Tolerance can be marked. • An abstinence syndrome can occur upon withdrawal. • Symptoms include increased appetite, sleepiness, exhaustion, and mental depression. • Antidepressants may be indicated.
Nicotine overview and moa?
• Second only to caffeine as the most widely used
CNS stimulant.
• Second only to alcohol as the most abused drug.
• Full agonist of the nicotine receptor.
• The rewarding effect of nicotine requires
involvement of the ventral tegmental area ,
where nicotinic receptors are expressed on
dopamine neurons.
• When nicotine excites these neurons, dopamine
is released.
Nicotine actions?
• In low doses: ganglionic stimulation by
depolarization.
• At high doses: ganglionic blockade.
CNS
• Cigarette smoking or administration of low doses
of nicotine produces some degree of euphoria
and relaxation.
• Improves attention, learning, problem solving,
and reaction time.
• High doses of nicotine result in central
respiratory paralysis and severe hypotension
caused by medullary paralysis.
• Nicotine is an appetite suppressant.
Describe nicotine withdrawal symptoms?
• Nicotine withdrawal is mild.
• Involves irritability and sleeplessness.
• However, nicotine is among the most addictive
drugs.
• Relapse is very common.
Treatment for nicotine addiction?
NICOTINE REPLACEMENT THERAPY
• Nicotine can be administered by transdermal
patch, gum, nasal spray, vapor inhaler or by
lozenge for buccal absorption.
SUSTAINED-RELEASE BUPROPION
• MOA unclear.
VARENICLINE
• Partial agonist at nicotinic receptors in the CNS.
• Reduces the reward of smoking.
4 most common opioids and describe opioid tolerance, dependence, and addiction?
• All opioids induce strong tolerance and dependence.
• Addiction to heroin or other short-acting opioids
produces behavioural disruptions and usually is
incompatible with a productive life.
• The withdrawal syndrome is unpleasant but not
life-threatening.
• It includes dysphoria, lacrimation, rhinorrhea and
yawning.
OPIOIDS: TREATMENT OF OPIOID WITHDRAWAL?
DETOXIFICATION USING OPIOID AGONISTS
• The illicit agent is replaced by a long-acting opioid.
• The dose is slowly reduced.
• Drugs used: Methadone or buprenorphine.
• Methadone is a useful drug for detoxification and
maintenance of the chronic relapsing heroin addict.
Describe DETOXIFICATION USING OPIOID ANTAGONISTS?
• Naltrexone is an antagonist with a high affinity for the μ opioid receptor.
• Naltrexone will not satisfy craving or relieve withdrawal symptoms.
• Naltrexone can be used after detoxification for
patients with high motivation to remain opioidfree.
Overview of Marijuana?
• The smoke from burning cannabis contains 61
different cannabinoids.
• D9-tetrahydrocannabinol (D9-THC, THC,
dronabinol) produces most of the effects.
MARIJUANA: MECHANISM OF ACTION?
• Two cannabinoid receptor subtypes:CB1 & CB2.
• Both are G protein-linked receptors.
• Both couple to Gi.
• CB1 receptors are found primarily in the brain
and mediate the psychological effects of THC.
• CB2 receptors are present mainly on immune
cells.
MARIJUANA: ACTIONS? Tolerance and dependence?
• THC can produce euphoria, followed by
drowsiness and relaxation.
• Affects short-term memory and mental activity.
• Impairs highly skilled motor activity.
• Other effects: appetite stimulation, xerostomia,
visual hallucinations, delusions, enhancement of
sensory activity.
• At high doses: toxic psychosis.
• Tolerance and mild physical dependence occur
with continued, frequent use of the drug.
MARIJUANA: USES?
• Therapeutic THC is called dronabinol.
• Dronabinol is FDA-approved for:
• Anorexia associated with weight loss in
patients with AIDS.
• Nausea and vomiting associated with cancer
chemotherapy (second line).
List 5 PSYCHEDELIC AGENTS
• LSD • MESCALINE • PSILOCYBIN • PHENCICLIDINE • MDMA • Psychedelic drugs affect thought, perception and mood. • They don’t cause marked psychomotor stimulation or depression.
3 lsd like group of drugs?
The LSD-like group of drugs include:
• LSD
• Mescaline
• Psilocybin
LSD moa?
• The hallucinogenic actions of LSD appear to be
mediated by agonist effects at 5-HT2 receptors
in the CNS.
LSD: CLINICAL PRESENTATION?
• Patients who have taken LSD generally present
with a combination of somatic and psychomimetic symptoms.
• Somatic symptoms are usually due to sympathomimetic effects.
• Somatic symptoms include: mydriasis, hypertension, tachycardia, increased body
temperature, flushing, sweating, tremors and
piloerection.
LSD: PHYSICAL DEPENDENCE AND
WITHDRAWAL and AE?
• LSD does not cause addiction.
• There is no withdrawal syndrome.
• Users may require medical attention because of
“bad trips”.
• Severe agitation may require medication:
diazepam is effective.
Overview and actions of Phencyclidine?
• Dissociative anesthetic.
• Blocks reuptake of norepinephrine and
dopamine.
• Causes cholinergic and anticholinergic effects.
• Has actions at nicotinic and opioid receptors.
• The dissociative properties of PCP are believed
to be due to non-competitive antagonism at
NMDA receptors.
PHENCYCLIDINE: CLINICAL PRESENTATION?
• Clinical manifestations include violent or bizarre
behavior, psychosis, nystagmus, tachycardia,
hypertension, diaphoresis, miosis, anesthesia,
and analgesia.
• An important diagnostic clue is nystagmus.
PHENCYCLIDINE: TREATMENT?
- There is no specific antidote for PCP.
- Extreme violent psychotic behavior requires sedation with parenteral benzodiazepines.
- Seizures should be treated with benzodiazepines.
Overview of MDMA(ecstasy)?
• MDMA fosters feelings of empathy and intimacy
without impairing intellectual capacities.
• MDMA causes release of biogenic amines.
• It most strongly increases the concentration of
serotonin in the synaptic cleft.
• Withdrawal is characterized by depression, lasting up to several weeks.
• MDMA produces degeneration of serotonergic
neurons in rats.
Name 3 inhalants?
- NITROUS OXIDE
- VOLATILE ORGANIC SOLVENTS
- ORGANIC NITRITES
Effects of Nitrous oxide?
NITROUS OXIDE
• Produces euphoria and analgesia and then loss
of consciousness.
• Usually taken as 35% N2O mixed with O2.
• Administration of 100% N2O may cause
asphyxia and death
What are categorized under volatile organic solvents, effects, and toxicities?
VOLATILE ORGANIC SOLVENTS
• Include gasoline, paint thinner, lighter fluid, glue
and degreasers.
• Produce sense of exhilaration and lightheadedness.
• Toxicity depends on the properties of individual
solvents.
• Implicated in cancer, cardiotoxicity, neuropathies
and hepatotoxicity.
Describe organic nitrites?
ORGANIC NITRITES
• Amyl nitrite and butyl nitrite are used to enhance
erection.
• They are not addictive.
What are anabolic steroids used for?
• Used to increase muscle size by body-building
competitors.
