Transcript Psychoactive Drugs

Psychoactive Drugs
Dr. Kline
Part I
I. How drugs are handled by the
body?
1.
Absorption –into the body.
2. Distribution – of the drug through the body, including
the fetus, at time drug is taken.
3.
Metabolism – the detoxification of the drug by the body
(liver). Most drugs are broken down into metabolites (byproducts or waste) that no longer exert an effect.
4.
Elimination – of the drug, usually excreted through
urine.
Six routes of drug entry into body:
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1. Orally (tablets, capsules, liquid)
2. Rectally (suppositories)
3. Intravenous (injected in liquid form through a
needle into the skin)
4. Inhaled through the lungs (as gases, vapors, or
particles)
5. Through skin (patches on skin)
6. Through mucous membranes (snorting or
sniffing; under tongue)
How drugs act on the system
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The pharmacological, physiological, or
behavioral effects induced by a drug follow
their interaction with receptors.
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This is called pharmacodynamics &
involves the mechanisms of drug action that
occur at the molecular level.
Drugs produce effects by:
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binding to & interacting with specialized
receptors, located on the synapses of
neurons.
What are receptors?

A receptor is a large molecule on the cell’s
surface where endogenous compounds
(neurotransmitters) induce their normal
effects.
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Usually only 1-2 neurotransmitters is
specific enough to fit or bind to a specific
receptor.
Binding to receptors

1. A drug that binds to a receptor normally occupied
by a given transmitter can initiate a cellular response
similar or identical to that exerted by the
transmitter.
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The drug mimics the action of the transmitter. Here, the
drug is an agonist for that transmitter.
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2. A drug that binds to a receptor & blocks the
neurotransmitter from stimulating the cell is called an
antagonist.
II. Dose-Response Relationships

A dose-response curve may be plotted as:
 the dose of a drug given as a function of the
% of people who show an effect at a given
dosage.
Drug Effectiveness

The dose of a drug that produces the desired
effect in 50 % of subjects tested is called the
ED50.
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The lethal dose for 50% of subjects
(animals) is called the LD50.
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The ratio of the LD50 to the ED50 is used
as an index of the relative safety of the drug
& is called the therapeutic index
III. Drugs
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A. ALCOHOL (ethanol)
Alcohol is found in different concentrations in liquid:
-12% in wine
-3.5-5% in beer
-40-50% in liquors
It is most often expressed as “proof” which is twice the
percent concentration (i.e., 80 proof = 40 % ethanol).
Alcohol absorption:
Alcohol readily diffuses across all biological
membranes & is completely absorbed by the entire
GI tract.
Alcohol usually takes 30-90 minutes to reach peak
levels in the blood.
About 20% of a single dose of alcohol is absorbed
directly via the stomach.
The remaining 80% is absorbed rapidly by the large
intestine.
Alcohol metabolism:
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85% by liver
 5%-by lungs (can be detected by breath)
 15%- broken down by stomach enzymes.
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A full stomach reduces a person’s blood
alcohol level, because the enzymes have
longer time to metabolize the alcohol.
Who has the higher blood alcohol level,
men or women?
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Women!!!
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1. Women --50% less gastric metabolism of alcohol,
because they have lower levels of gastric enzymes.
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2. Since men have greater ratio of muscle to fat than do
women, alcohol is more diluted in their blood (fat has
little blood supply in contrast to muscle).
What are the effects of alcohol?
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1. Physiological effects-
Slows Respiration (CNS depressant)
 Sedative effects are additive when combined with other
depressants (e.g., barbituates).
 Dilates blood vessels in skin (decreases body temp; blushing).
 Lowers cholesterol (low doses) by lowering LDL & increasing
HDL.
 May cause heart damage (high doses-5 drinks per day).
 May cause liver damage (high doses over time)
2. Psychological effects
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Behavioral disinhibition (low doses)
Euphoria (low to moderate doses)
Violent or irascible mood (moderate to high doses)
Memory, concentration, & insight are impaired
Reaction time is impaired
Motor system is impaired (cerebellum)
How does alcohol produce its effects?
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1. Alcohol is a GABA agonist, it facilitates expression
of GABA (inhibitory transmitter). Contributes to
behavioral disinhibition, motor slowing.
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2. Alcohol inhibits glutamate (excitatory system).
Receptors, which may cause cognitive effects of alcohol
intoxication, such as slurred speech & memory loss.
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Alcohol increases levels of dopamine & serotonin,
likely providing both euphoric & sedative effects.
B. MARIJUANA
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Dried & crushed leaves & flowering tops of the
hemp plant, Cannabis sativa.
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Major ingredient-- delta-9-tetrahydrocannabinol
(THC)
 Marijuana has 2-5 % THC
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May be smoked, chewed, or eaten (in baked
goods).
What are effects of marijuana?
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1. Physiological effects
 Produces analgesia
 Has antiemetic properties (decreases nausea
& vomiting)
 Increased HR & blood pressure
 Dilated blood vessels in eyes (bloodshot eyes)
 Sedative effects
2. Psychological effects
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Shifts in emotion
 Disrupted attention
 Impaired STM
 Altered sensory perception
 Time distortions (time moves more slowly)
 Motor activity impaired
 Hallucinations (with heavy doses)
 Panic (with heavy doses)
How does marijuana produce its effects?
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We have cannabis receptors in the brain. These
receptors are found in the:
1. basal ganglia (fine motor system)
2. cerebellum
3. cortex (especially the frontal lobe)
4. hippocampus
We don’t have any cannabis receptors in the
brainstem. THC does not affect basal body
functions.
Do we have a transmitter substance like
THC in our brains?
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Yes!!! We have anandamide which binds to
cannabinoid receptors & produces
cannabinoid-like pharmacological effects.
C. HALLUCINOGENS
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1. LSD
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First synthesized in 1938, as a compound of
ergot (a fungus that grows on rye) by Hoffman.
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Hoffman accidentally ingested the drug &
noticed its unusual effects.
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During 1950s, LSD was used as a model for
examining & treating psychosis; was also used
in therapy.
LSD administration:
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Is taken orally.
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ED50 is 25 micrograms to 300 micrograms.
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Usually is found on sugar cubes, stamps, candy
dots
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Is absorbed within 1 hour; peaks in 3 hours.
 Duration: 6-8 hours.
What are the effects of LSD?
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1. Physiological Effects
Slight increase in body temperature
 pupil dilation
 slightly increased HR & blood pressure
 dizziness; nausea
2. Psychological Effects
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1. Altered perception, thinking, emotion, arousal
2. time distortions (slowed)
3. Intense visual & auditory hallucinations
(trasers)
4. Cross-sensing (hearing colors; seeing sounds)
5. emotions shift rapidly (happiness to pit of
despair)
6. tension & anxiety make lead to panic
7. psychotic experience
How does LSD produce its effects?
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LSD exerts its effects by interacting with
serotonin receptors (5-HT receptors).
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Most researchers argue it’s a serotonin
agonist.
2. MESCALINE
Comes from the crown or “button” of the peyote cactus.
The crown is dried into a hard brown disk that softens
when ingested.
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Is absorbed in 1-2 hours.
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Effects occur between 3.5 & 4 hours after ingestion.
Vivid hallucinations most salient.
--trip is long (10 hours)
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Right frontal activity seems to be high in people on
mescaline. Agonistic for norepinephine & serotonin.
3. PSILOCYBIN
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Found in mushrooms (genera Psilocybe).
 Mushrooms are eaten raw.
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mushrooms grow through out world, including
northwestern US.
It peaks in about 2 hours, & effects
 last 6-10 hours.
How does it produce its effects?
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It appears to exert its effects as a serotonin
agonist that stimulates 5-HT receptors
especially in the frontal areas.
4. MYRISTIN & ELEMICIN
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Are agents found in nutmeg & mace, two common
household spices.
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ED50--1-2 teaspoons—usually brewed in tea
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Within 2-5 hours, you get symptoms similar to LSD
(euphoria, visual hallucinations, psychosis, etc.)
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However, most people experience vomiting, nausea, &
tremors prior to the “trip” making it a one time event for
many.
D. STIMULANTS
In general these drugs:
 increase behavioral activity
 elevate mood
 increase alertness
 allay sleep
 increase brain’s metabolic & neuronal
activity.
1. COCAINE:
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Comes from the coca plant (Erythroxylon coca)
found in South America.
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The active alkaloid in E. coca was isolated in 1855,
purified in 1860, & named cocaine.
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In late 1800s, cocaine was used as an anesthetic
(spinal, local), was added to medicines & Coca-Cola.
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It was banned from use in medicines & beverages in
1914 in the Harrison Narcotic Act.
COCAINE (history):
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By 1930s, amphetamines replaced the popularity
of cocaine.
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1960s- cocaine makes a comeback when
amphetamines become pricey.
70s-80s – cocaine becomes “chic” with jetset.
 & cheap “crack” cocaine becomes hit in poor
areas.
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Forms of cocaine
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Cocaine can be snorted, smoked, taken
orally, or injected intravenously.
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Powdered cocaine (cocaine hydrochloride)
25 mg per “line.”
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Crack cocaine- (250 mg-1 gm) per smoke.
Physical Effects:
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Vasoconstrictor
 Increases norepinephrine & dopamine
 Tachycardia
 Stroke, seizure, heart attack
 Increased blood pressure
Local anesthetic
Psychological Effects
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Euphoria
 Elevated mood
 Agitation
 Flight-of-ideas
 Grandiose thoughts
How does it produce its effects?
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Cocaine blocks reuptake of dopamine,
norepinephrine, & serotonin, thereby
increasing them in the CNS.
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Increasing dopamine levels in dopaminergic
reward system results in euphoric/addictive
effects of drug.
2. AMPHETAMINES- Effects
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Vasoconstriction
 Hypertension
 Tachycardia
 Increased motor activity
 Loss of appetite
 Restlessness/tremors
 hallucinations (amphetamine psychosis)
 Paranoid delusions
Amphetamines-today
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1. Therapeutic use in the treatment of
narcolepsy & ADHD.
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2. To treat compulsive misuse of
methamphetamine (amphetamine
derivative).
How do amphetamines cause their
effects?
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They cause release of norepinephrine &
dopamine from presynaptic storage sites in
nerve terminals.
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Peripheral NS activity --increased
norepinephrine
ICE- form of methamphetamine
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Was originally used to treat ADHD, not mostly a an
illegal street drug.
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Street names of drug– Speed, crystal, crank, go, & ICE.
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Methamphetamine--orally, by IV injection, & snorted.
The base form (ICE) can be smoked.
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ICE-methamphetamine, crack-cocaine. It’s the freebase, smokable form of the parent compound.
NONAMPHETAMINE
BEHAVIORAL STIMULANTS
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Does not have the same nucleus structure of
amphetamines, but shares same action of
increasing SNS activation.
One of the most common of these is:
 Methylphenidate (Ritalin)
Methylphenidate (Ritalin)
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Has a short half life (2-4 hours).
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Concerta--A new sustained-release
formulation of methylphenidate--taken in
the early AM, it is good through the day.
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Is much more expensive than regular
Ritalin.
How does Ritalin exert its effects?
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Thought to increase norepinephrine & dopamine,
by blocking reuptake in the presynaptic neuron.
Also stimulates the release dopamine.
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Once thought to exert its behavioral effects
(calming) via increased dopamine, it is now
thought that effects may be result of increased
serotonin activity (or balance of both).
3. CAFFEINE
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The most common psychoactive drug in world.
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Consumed -80% of adult population.
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1 cup of coffee---50-150 mg of caffeine.
 Caffeine content of chocolate--25 milligrams per
ounce.
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Average intake – 3-5 cups of coffee every day.
Absorption
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Significant blood levels of caffeine are reached
in 30 to 45 min; with complete absorption in 90
min.
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Peaks in about 2 hrs & decreases thereafter.
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The half-life is about 3.5 to 5 hours in most
adults.
Effects
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tachycardia
Increased Blood pressure
Vasoconstriction
Diurectic
Increased mental activity; alertness
Increased wakefulness
Agitation
Tremors
Anxiety
Insomnia
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HOW DOES CAFFEINE EXERT ITS
EFFECTS?
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Caffeine exerts its effects by blocking adenosine
receptors.
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Adenosine is a neuromodulator that influences the
release of several neurotransmitters in the CNS.
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It appears to exert sedative, depressant, &
anticonsulsant actions. Thus, blocking adenosine
causes anxiogenic effects.
E. OPIATES
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A group of addictive sedatives that in
moderate doses relieve pain & induce sleep.
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The original principle opiate was opium, which is
extracted from poppy seeds of the poppy plant
(papaver somniferum).
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The psychoactive ingredient in opium is morphine,
named for Morpheus—the Greek God of dreams.
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Two drugs are found in the exudate of the poppy:
morphine & codeine.
OPIATES-History
 Opium--has been used for thousands of years to
produce euphoria, analgesia, sleep, & relief from
diarrhea & cough.
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Ancient Greece & Rome-- through the 16th- &
17th-centuries, opium’s medicinal & recreational
uses were well established.
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A mixture of opium and alcohol, called
laudanum, was used to treat practically every
disease known during the 1800s.
OPIATES-History
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During the civil war, opium addiction was a
widespread problem.
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By 1914, the Harrison Narcotic Act was
passed and the use of most opioid products
was controlled.
Opiates vs. Opioids
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Opiate-- is a drug that is extracted from the
exudates of the poppy.
 E.g., morphine and codeine.
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An opioid is any exogenous drug (natural or
synthetic) that binds to an opiate receptor &
produces agonist or morphine-like effects.
 E.g., heroin
Endorpins (“morphine-within”)
Endorphins --any endogenous substance
(naturally occurring in the body) that
exhibits pharmacological properties of
morphine.
We have 3 families of endorphins—
enkephalins, dynorphins, & betaendorphins.
MORPHINE
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Is still the most potent pain reliever available (no
other drug has its clinical effectiveness).
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Is administered orally, rectally, or by injection.
Absorption is slow & only 20% of the drug
reaches the CNS.
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Is broken down by liver & produces metabolites
(morphine t-glucoronide) that are 10 to 20-fold
more potent that morphine itself. These continue
exerting analgesic effects.
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Morphine’s half-life: 3 to 5 hours.
MORPHINE-DRUG TESTING
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For 2 to 4 days following opiate use, urine
screening tests can be used to detect codeine &
morphine as well as their metabolites.
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Heroin use can be tested for indirectly. Heroin is
metabolized to morphine & also often contains
acetylcodeine (metabolized form of codeine).
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Although the tests cannot accurately determine
which drug (heroin, codeine, morphine) was
present.
WHAT ARE EFFECTS OF
MORPHINE?
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Analgesia
Relaxation
Euphoria
Sedation
Sense of transquility
Reduced anxiety
Respiratory depression
Cough suppression
HOW DOES MORPHINE EXERT ITS
EFFECTS?
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Morphine, like other opiates & opioids,
exert its effects by stimulating opiate
receptors widely distributed through the
CNS (brain, brain stem, spinal cord).
CODEINE
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Is usually combined with aspirin or acetaminophen for
the relief of mild to moderate pain.
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Half-life--3 to 4 hours.
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Codeine is metabolized by hepatic cytochrome
CYP2D6 enzymes to morphine, & many of its effects
may be the result of morphine actions.
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Using serotonin-specific antidepressants can block the
pain relief of codeine, because they block the
conversion of codeine to morphine.
HEROIN (diacetylmorphine)
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Is produced by a slight modification of the chemical
structure of morphine.
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It cross the blood-brain barrier very rapidly, leading to
an intense rush when it is either smoked or injected
intravenously.
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It is metabolized to monoacetylmorphine &morphine.
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Clinical use of heroin is legal in Great Britain &
Canada.
F. ANTIDEPRESSANTS
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A broad class of drugs used to treat depression.
What is depression???
 A state of great sadness characterized by feelings
of despair, worthlessness, hopelessness, &
withdrawal from other.
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It’s the “common cold” of psychopathology—
we’ve all had symptoms at some point.
Major depression: DSM diagnosis made
if:
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Person has 5 of the following symptoms
(next slide) for at least 2 weeks.
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Depressed mood or loss of interest
& pleasure in enjoyable
activities (anhedonia) must
be included in symptoms.
Symptoms of major depression:
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1. Depressed mood.
2. Loss of interest and pleasure.
3. Significant weight loss or
weight gain.
4. Difficulty in sleeping-Insomnia
or
hypersomnia.
5. Shift in activity level,
psychomotor retardation, or
agitated.
6. Fatigue or loss of energy.
7. Negative self-concept.
1. Tricyclics
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E.g., imipramine (Tofranil) and amitriptyline
(Elavil).
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These prevent reuptake of both norepinephrine &
serotonin by the presynaptic neuron.
2. Monoamine oxidase (MAO) inhibitors tranylcypromine (Parnate)
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Keeps enzyme monoamine oxidase from
deactivating neurotransmitters, thereby increasing
the levels of both serotonin and norepinephrine.
3. Selective serotonin reuptake inhibitors
(SSRIs): fluoxetine (Prozac) &
sertraline (Zoloft).
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Selectively blocks reuptake of serotonin.
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Efficacy of all three classes of drugs about
the same (50-70% effective).
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Side effects fewer in SSRI’s. Tricyclics can
be dangerous.