Psychoactive DrugsPsychoactive Drugs

Dr. KlineDr. Kline

Part IPart I

I.  How drugs are handled by the I.  How drugs are handled by the body?body?

1.     1.     Absorption Absorption –into the body.–into the body.

  2.     2.     DistributionDistribution – of the drug through the body, including the – of the drug through the body, including the fetus, at time drug is taken.fetus, at time drug is taken.

  3.     3.     MetabolismMetabolism – the detoxification of the drug by the body (liver). – the detoxification of the drug by the body (liver).

Most drugs are broken down into metabolites (by-products or Most drugs are broken down into metabolites (by-products or waste) that no longer exert an effect.waste) that no longer exert an effect.

  4.     4.     Elimination Elimination – of the drug, usually excreted through urine. – of the drug, usually excreted through urine.   

Six routes of drug entry into body:Six routes of drug entry into body:

1.     Orally 1.     Orally (tablets, capsules, liquid)(tablets, capsules, liquid) 2.     2.     Rectally Rectally (suppositories)(suppositories) 3.     3.     Intravenous Intravenous (injected in liquid form through a (injected in liquid form through a

needle into the skin)needle into the skin) 4.     4.     Inhaled through the lungs Inhaled through the lungs (as gases, vapors, or (as gases, vapors, or

particles)particles) 5.     5.     Through skin Through skin (patches on skin)(patches on skin) 6.     6.     Through mucous membranes Through mucous membranes (snorting or (snorting or

sniffing; under tongue)sniffing; under tongue)  

How drugs act on the systemHow drugs act on the system

The pharmacological, physiological, or The pharmacological, physiological, or behavioral effects induced by a drug follow behavioral effects induced by a drug follow their interaction with receptors. their interaction with receptors.

This is called pharmacodynamics & This is called pharmacodynamics & involves the mechanisms of drug action that involves the mechanisms of drug action that occur at the occur at the molecular levelmolecular level. .

Drugs produce effects by:Drugs produce effects by:

binding to & interacting with specialized binding to & interacting with specialized receptors, located on the synapses of receptors, located on the synapses of neurons.neurons.

What are receptors?What are receptors?

A A receptor receptor is a large molecule on the cell’s is a large molecule on the cell’s surface where endogenous compounds surface where endogenous compounds (neurotransmitters) induce their normal (neurotransmitters) induce their normal effects. effects.

Usually only 1-2 neurotransmitters is Usually only 1-2 neurotransmitters is specific enough to fit or bind to a specific specific enough to fit or bind to a specific receptor. receptor.

Binding to receptorsBinding to receptors

1.    1.    A drug that binds to a receptor normally occupied A drug that binds to a receptor normally occupied by a given transmitter can initiate a cellular response by a given transmitter can initiate a cellular response similar or identical to that exerted by the similar or identical to that exerted by the transmittertransmitter. .

The drug mimics the action of the transmitter. Here, The drug mimics the action of the transmitter. Here, the drug is an the drug is an agonistagonist for that transmitter.   for that transmitter.  

2.  2.  A drug that binds to a receptor & blocks the A drug that binds to a receptor & blocks the neurotransmitter from stimulating the cell is called an neurotransmitter from stimulating the cell is called an antagonistantagonist. .

II. II. Dose-Response RelationshipsDose-Response Relationships

A dose-response curve may be plotted as:A dose-response curve may be plotted as: the dose of a drug given as a function of the dose of a drug given as a function of

the % of people who show an effect at a the % of people who show an effect at a given dosage.given dosage.

Drug EffectivenessDrug Effectiveness The dose of a drug that produces the desired The dose of a drug that produces the desired

effect in 50 % of subjects tested is called effect in 50 % of subjects tested is called the the EDED50.

The lethal dose for 50% of subjects (animals) is called the LD50.

The ratio of the LD50 to the ED50 is used The ratio of the LD50 to the ED50 is used as an index of the relative safety of the drug as an index of the relative safety of the drug & is called the therapeutic index& is called the therapeutic index

III. DrugsIII. Drugs

A. ALCOHOL (ethanol)A. ALCOHOL (ethanol)

Alcohol is found in different concentrations in liquid:Alcohol is found in different concentrations in liquid:

-12% in wine-12% in wine

-3.5-5% in beer-3.5-5% in beer

-40-50% in liquors-40-50% in liquors

It is most often expressed as “proof” which is twice the It is most often expressed as “proof” which is twice the percent concentration (i.e., 80 proof = 40 % ethanol). percent concentration (i.e., 80 proof = 40 % ethanol).

Alcohol absorption:Alcohol absorption: Alcohol readily diffuses across all biological Alcohol readily diffuses across all biological

membranes & is completely absorbed by the entire membranes & is completely absorbed by the entire GI tract.GI tract.

Alcohol usually takes 30-90 minutes to reach peak Alcohol usually takes 30-90 minutes to reach peak levels in the blood. levels in the blood.

About 20% of a single dose of alcohol is absorbed About 20% of a single dose of alcohol is absorbed directly via the directly via the stomachstomach. .

The remaining 80% is absorbed rapidly by the large The remaining 80% is absorbed rapidly by the large intestine. intestine.

Alcohol metabolism:Alcohol metabolism:

85% by liver85% by liver 5%-by lungs (can be detected by breath)5%-by lungs (can be detected by breath) 15%- broken down by stomach enzymes.15%- broken down by stomach enzymes.

A full stomach reduces a person’s blood A full stomach reduces a person’s blood alcohol level, because the enzymes have alcohol level, because the enzymes have longer time to metabolize the alcohol. longer time to metabolize the alcohol.

Who has the higher blood alcohol level, Who has the higher blood alcohol level, men or women?men or women?

Women!!!Women!!!

1.  Women --50% less gastric metabolism of alcohol, 1.  Women --50% less gastric metabolism of alcohol, because they have lower levels of gastric enzymes. because they have lower levels of gastric enzymes.

2.  Since men have greater ratio of muscle to fat than do 2.  Since men have greater ratio of muscle to fat than do women, alcohol is more diluted in their blood (fat has women, alcohol is more diluted in their blood (fat has little blood supply in contrast to muscle).little blood supply in contrast to muscle).

  

What are the effects of alcohol?What are the effects of alcohol?

1. 1. Physiological effectsPhysiological effects--

Slows Respiration (CNS depressant)Slows Respiration (CNS depressant) Sedative effects are additive when combined with other Sedative effects are additive when combined with other

depressants (e.g., barbituates).depressants (e.g., barbituates). Dilates blood vessels in skin (Dilates blood vessels in skin (decreases body tempdecreases body temp; blushing).; blushing). Lowers cholesterol (low doses) by lowering LDL & increasing Lowers cholesterol (low doses) by lowering LDL & increasing

HDL.HDL. May cause heart damage (high doses-5 drinks per day).May cause heart damage (high doses-5 drinks per day). May cause liver damage (high doses over time)May cause liver damage (high doses over time)

2. 2. Psychological effectsPsychological effects

Behavioral disinhibition (low doses)Behavioral disinhibition (low doses) Euphoria (low to moderate doses)Euphoria (low to moderate doses) Violent or irascible mood (moderate to high Violent or irascible mood (moderate to high

doses)doses) Memory, concentration, & insight are impairedMemory, concentration, & insight are impaired Reaction time is impairedReaction time is impaired Motor system is impaired (cerebellum)Motor system is impaired (cerebellum)

  

How does alcohol produce its effects?How does alcohol produce its effects? 1. Alcohol is a GABA agonist, it facilitates expression 1. Alcohol is a GABA agonist, it facilitates expression

of GABA (inhibitory transmitter). Contributes to of GABA (inhibitory transmitter). Contributes to behavioral disinhibition, motor slowing. behavioral disinhibition, motor slowing.

2. Alcohol inhibits glutamate (excitatory system). 2. Alcohol inhibits glutamate (excitatory system).

Receptors, which may cause cognitive effects of alcohol Receptors, which may cause cognitive effects of alcohol intoxication, such as slurred speech & memory loss. intoxication, such as slurred speech & memory loss.

Alcohol increases levels of dopamine & serotonin, Alcohol increases levels of dopamine & serotonin, likely providing both euphoric & sedative effects. likely providing both euphoric & sedative effects.

B. MARIJUANAB. MARIJUANA Dried & crushed leaves & flowering tops of the Dried & crushed leaves & flowering tops of the

hemp plant, hemp plant, Cannabis sativaCannabis sativa. .

Major ingredient-- delta-9-tetrahydrocannabinol Major ingredient-- delta-9-tetrahydrocannabinol (THC) (THC)

Marijuana has 2-5 % THCMarijuana has 2-5 % THC

May be smoked, chewed, or eaten (in baked May be smoked, chewed, or eaten (in baked goods). goods).

What are effects of marijuana?What are effects of marijuana?

1. Physiological effects1. Physiological effects Produces analgesia Produces analgesia Has antiemetic properties (decreases nausea Has antiemetic properties (decreases nausea

& vomiting)& vomiting) Increased HR & blood pressureIncreased HR & blood pressure Dilated blood vessels in eyes (bloodshot eyes)Dilated blood vessels in eyes (bloodshot eyes) Sedative effectsSedative effects

2. Psychological effects2. Psychological effects

Shifts in emotionShifts in emotion Disrupted attentionDisrupted attention Impaired STMImpaired STM Altered sensory perceptionAltered sensory perception Time distortions (time moves more slowly)Time distortions (time moves more slowly) Motor activity impairedMotor activity impaired Hallucinations (with heavy doses)Hallucinations (with heavy doses) Panic (with heavy doses)Panic (with heavy doses)

How does marijuana produce its effects?How does marijuana produce its effects?

We have cannabis receptors in the brain. These We have cannabis receptors in the brain. These receptors are found in the:receptors are found in the:

1. basal ganglia (fine motor system)1. basal ganglia (fine motor system) 2. cerebellum 2. cerebellum 3. cortex (especially the frontal lobe)3. cortex (especially the frontal lobe) 4. hippocampus 4. hippocampus

We don’t have any cannabis receptors in the We don’t have any cannabis receptors in the brainstem. THC does not affect basal body brainstem. THC does not affect basal body functions. functions.

Do we have a transmitter substance like Do we have a transmitter substance like THC in our brains?THC in our brains?

Yes!!! Yes!!! We have anandamide which binds to We have anandamide which binds to cannabinoid receptors & produces cannabinoid receptors & produces cannabinoid-like pharmacological effects. cannabinoid-like pharmacological effects.

C. HALLUCINOGENSC. HALLUCINOGENS 1. 1. LSDLSD

First synthesized in 1938, as a compound of ergot (a fungus that grows on rye) by Hoffman.

Hoffman accidentally ingested the drug & noticed its unusual effects.

During 1950s, LSD was used as a model for examining & treating psychosis; was also used in therapy.

LSD administration:LSD administration: Is taken Is taken orallyorally. .

ED50 is 25 micrograms to 300 micrograms. ED50 is 25 micrograms to 300 micrograms.

Usually is found on sugar cubes, stamps, candy Usually is found on sugar cubes, stamps, candy dotsdots

Is absorbed within 1 hour; peaks in 3 hours.Is absorbed within 1 hour; peaks in 3 hours. Duration: 6-8 hours. Duration: 6-8 hours.

What are the effects of LSD?What are the effects of LSD? 1. Physiological Effects1. Physiological Effects

Slight increase in body temperature pupil dilation slightly increased HR & blood pressure dizziness; nausea

2. Psychological Effects2. Psychological Effects 1.     Altered perception, thinking, emotion, arousal1.     Altered perception, thinking, emotion, arousal 2.     time distortions (slowed)2.     time distortions (slowed) 3.     Intense visual & auditory hallucinations 3.     Intense visual & auditory hallucinations

(trasers)(trasers) 4.     Cross-sensing (hearing colors; seeing sounds)4.     Cross-sensing (hearing colors; seeing sounds) 5.     emotions shift rapidly (happiness to pit of 5.     emotions shift rapidly (happiness to pit of

despair)despair) 6.     tension & anxiety make lead to panic6.     tension & anxiety make lead to panic 7.     psychotic experience7.     psychotic experience

How does LSD produce its effects?How does LSD produce its effects?

LSD exerts its effects by interacting with LSD exerts its effects by interacting with serotonin receptors (5-HT receptors). serotonin receptors (5-HT receptors).

Most researchers argue it’s a serotonin Most researchers argue it’s a serotonin agonist.agonist.

2. MESCALINE2. MESCALINE Comes from the crown or “button” of the peyote cactus.Comes from the crown or “button” of the peyote cactus.The crown is dried into a hard brown disk that softens when The crown is dried into a hard brown disk that softens when

ingested.ingested.

Is absorbed in 1-2 hours.Is absorbed in 1-2 hours.

Effects occur between 3.5 & 4 hours after ingestion. Effects occur between 3.5 & 4 hours after ingestion. Vivid hallucinations most salient.Vivid hallucinations most salient.

--trip is long (10 hours)--trip is long (10 hours)

Right frontal activity seems to be high in people on Right frontal activity seems to be high in people on mescaline. Agonistic for norepinephine & serotonin.mescaline. Agonistic for norepinephine & serotonin.

3. 3. PSILOCYBINPSILOCYBIN Found in Found in mushroomsmushrooms (genera Psilocybe). (genera Psilocybe). Mushrooms are eaten raw.Mushrooms are eaten raw.

mushrooms grow through out world, including mushrooms grow through out world, including northwestern US. northwestern US.

It peaks in about 2 hours, & effects It peaks in about 2 hours, & effects last 6-10 hours. last 6-10 hours.

How does it produce its effects?How does it produce its effects?

It appears to exert its effects as a serotonin It appears to exert its effects as a serotonin agonist that stimulates 5-HT receptors agonist that stimulates 5-HT receptors especially in the frontal areas. especially in the frontal areas.

4. 4. MYRISTIN & ELEMICINMYRISTIN & ELEMICIN

Are agents found in Are agents found in nutmeg & macenutmeg & mace, two common , two common household spices. household spices.

ED50--1-2 teaspoons—usually brewed in teaED50--1-2 teaspoons—usually brewed in tea

Within 2-5 hours, you get symptoms similar to LSD Within 2-5 hours, you get symptoms similar to LSD (euphoria, visual hallucinations, psychosis, etc.) (euphoria, visual hallucinations, psychosis, etc.)

However, most people experience vomiting, nausea, & However, most people experience vomiting, nausea, & tremors prior to the “trip” making it a one time event for tremors prior to the “trip” making it a one time event for many. many.

D. STIMULANTSD. STIMULANTS

In general these drugs:In general these drugs: increase behavioral activityincrease behavioral activity elevate moodelevate mood increase alertnessincrease alertness allay sleepallay sleep increase brain’s metabolic & neuronal increase brain’s metabolic & neuronal

activity.activity.

1. COCAINE:1. COCAINE: Comes from the coca plant (Erythroxylon coca) found in Comes from the coca plant (Erythroxylon coca) found in

South America. South America.

The active alkaloid in E. coca was isolated in 1855, purified The active alkaloid in E. coca was isolated in 1855, purified in 1860, & named cocaine. in 1860, & named cocaine.

In late 1800s, cocaine was used as an anesthetic (spinal, In late 1800s, cocaine was used as an anesthetic (spinal, local), was added to medicines & Coca-Cola. local), was added to medicines & Coca-Cola.

It was banned from use in medicines & beverages in 1914 in It was banned from use in medicines & beverages in 1914 in the Harrison Narcotic Act. the Harrison Narcotic Act.

COCAINE (history):COCAINE (history):

By 1930s, amphetamines replaced the popularity of By 1930s, amphetamines replaced the popularity of cocaine. cocaine.

1960s- cocaine makes a comeback when 1960s- cocaine makes a comeback when amphetamines become pricey. amphetamines become pricey.

70s-80s – cocaine becomes “chic” with jetset.70s-80s – cocaine becomes “chic” with jetset. & cheap “crack” cocaine becomes hit in poor areas. & cheap “crack” cocaine becomes hit in poor areas.   

Forms of cocaineForms of cocaine Cocaine can be snorted, smoked, taken Cocaine can be snorted, smoked, taken

orally, or injected intravenously.orally, or injected intravenously.

Powdered cocaine (cocaine hydrochloride) Powdered cocaine (cocaine hydrochloride) 25 mg per “line.”25 mg per “line.”

Crack cocaine- (250 mg-1 gm) per smoke. Crack cocaine- (250 mg-1 gm) per smoke.

Physical Effects:Physical Effects:

VasoconstrictorVasoconstrictor Increases norepinephrine & dopamineIncreases norepinephrine & dopamine TachycardiaTachycardia Stroke, seizure, heart attackStroke, seizure, heart attack Increased blood pressureIncreased blood pressure

Local anesthetic Local anesthetic

Psychological EffectsPsychological Effects

EuphoriaEuphoria Elevated moodElevated mood AgitationAgitation Flight-of-ideasFlight-of-ideas Grandiose thoughtsGrandiose thoughts

How does it produce its effects?How does it produce its effects?

Cocaine blocks reuptake of dopamine, Cocaine blocks reuptake of dopamine, norepinephrine, & serotonin, thereby norepinephrine, & serotonin, thereby increasing them in the CNS.increasing them in the CNS.

Increasing dopamine levels in dopaminergic Increasing dopamine levels in dopaminergic reward system results in euphoric/addictive reward system results in euphoric/addictive effects of drug.effects of drug.

2. AMPHETAMINES- Effects2. AMPHETAMINES- Effects

VasoconstrictionVasoconstriction HypertensionHypertension TachycardiaTachycardia Increased motor activityIncreased motor activity Loss of appetiteLoss of appetite Restlessness/tremors Restlessness/tremors  hallucinations (amphetamine psychosis) hallucinations (amphetamine psychosis) Paranoid delusions Paranoid delusions

Amphetamines-todayAmphetamines-today

1.  Therapeutic use in the treatment of 1.  Therapeutic use in the treatment of narcolepsy & ADHD.narcolepsy & ADHD.

2.  To treat compulsive misuse of 2.  To treat compulsive misuse of methamphetamine (amphetamine methamphetamine (amphetamine derivative). derivative).

How do amphetamines cause their How do amphetamines cause their effects?effects?

They cause release of norepinephrine & They cause release of norepinephrine & dopamine from presynaptic storage sites in dopamine from presynaptic storage sites in nerve terminals. nerve terminals.

Peripheral NS activity --increased Peripheral NS activity --increased norepinephrine norepinephrine   

ICE- form of methamphetamineICE- form of methamphetamine Was originally used to treat ADHD, not mostly a an Was originally used to treat ADHD, not mostly a an

illegal street drug.illegal street drug.

Street names of drug– Speed, crystal, crank, go, & ICE. Street names of drug– Speed, crystal, crank, go, & ICE.

Methamphetamine--orally, by IV injection, & snorted. Methamphetamine--orally, by IV injection, & snorted. The base form (ICE) can be smoked. The base form (ICE) can be smoked.

ICE-methamphetamine, crack-cocaine. It’s the free-ICE-methamphetamine, crack-cocaine. It’s the free-base, smokable form of the parent compound. base, smokable form of the parent compound.

NONAMPHETAMINE NONAMPHETAMINE BEHAVIORAL STIMULANTSBEHAVIORAL STIMULANTS

Does not have the same nucleus structure of Does not have the same nucleus structure of amphetamines, but shares same action of amphetamines, but shares same action of increasing SNS activation.increasing SNS activation.

One of the most common of these is:One of the most common of these is: Methylphenidate (Ritalin)Methylphenidate (Ritalin)

Methylphenidate (Ritalin)Methylphenidate (Ritalin)

Has a short half life (2-4 hours). Has a short half life (2-4 hours).

Concerta--A new sustained-release Concerta--A new sustained-release formulation of methylphenidate--taken in formulation of methylphenidate--taken in the early AM, it is good through the day.the early AM, it is good through the day.

Is much more expensive than regular Is much more expensive than regular Ritalin.Ritalin.

How does Ritalin exert its effects?How does Ritalin exert its effects?

Thought to increase norepinephrine & dopamine, Thought to increase norepinephrine & dopamine, by blocking reuptake in the presynaptic neuron. by blocking reuptake in the presynaptic neuron. Also stimulates the release dopamine. Also stimulates the release dopamine.

Once thought to exert its behavioral effects Once thought to exert its behavioral effects (calming) via increased dopamine, it is now (calming) via increased dopamine, it is now thought that effects may be result of increased thought that effects may be result of increased serotonin activity (or balance of both). serotonin activity (or balance of both).

3. CAFFEINE3. CAFFEINE The most common psychoactive drug in world. The most common psychoactive drug in world.

Consumed -80% of adult population. Consumed -80% of adult population.

1 cup of coffee---50-150 mg of caffeine. 1 cup of coffee---50-150 mg of caffeine. Caffeine content of chocolate--25 milligrams per Caffeine content of chocolate--25 milligrams per

ounce. ounce.

Average intake – 3-5 cups of coffee every day. Average intake – 3-5 cups of coffee every day.

AbsorptionAbsorption

Significant blood levels of caffeine are reached Significant blood levels of caffeine are reached in 30 to 45 min; with complete absorption in 90 in 30 to 45 min; with complete absorption in 90 min.min.

Peaks in about 2 hrs & decreases thereafter.Peaks in about 2 hrs & decreases thereafter.

The half-life is about 3.5 to 5 hours in most The half-life is about 3.5 to 5 hours in most adults. adults.

Effects Effects

   tachycardiatachycardia Increased Blood pressureIncreased Blood pressure VasoconstrictionVasoconstriction DiurecticDiurectic Increased mental activity; alertnessIncreased mental activity; alertness Increased wakefulnessIncreased wakefulness AgitationAgitation TremorsTremors AnxietyAnxiety InsomniaInsomnia

   HOW DOES CAFFEINE EXERT ITS HOW DOES CAFFEINE EXERT ITS

EFFECTS?EFFECTS?

Caffeine exerts its effects by blocking adenosine Caffeine exerts its effects by blocking adenosine receptors.receptors.

Adenosine is a neuromodulator that influences the Adenosine is a neuromodulator that influences the release of several neurotransmitters in the CNS. release of several neurotransmitters in the CNS.

It appears to exert sedative, depressant, & It appears to exert sedative, depressant, & anticonsulsant actions. Thus, blocking adenosine anticonsulsant actions. Thus, blocking adenosine causes anxiogenic effects. causes anxiogenic effects.

E. OPIATESE. OPIATES A group of addictive sedatives that inA group of addictive sedatives that inmoderate doses relieve pain & induce sleep.moderate doses relieve pain & induce sleep.

The original principle opiate was opium, which is The original principle opiate was opium, which is extracted from poppy seeds of the poppy plant (papaver extracted from poppy seeds of the poppy plant (papaver somniferum). somniferum).

The psychoactive ingredient in opium is morphine, The psychoactive ingredient in opium is morphine, named for Morpheus—the Greek God of dreams. named for Morpheus—the Greek God of dreams.

Two drugs are found in the exudate of the poppy: Two drugs are found in the exudate of the poppy: morphine & codeine. morphine & codeine.

OPIATES-HistoryOPIATES-History Opium--has been used for thousands of years to Opium--has been used for thousands of years to

produce euphoria, analgesia, sleep, & relief from produce euphoria, analgesia, sleep, & relief from diarrhea & cough.diarrhea & cough.

Ancient Greece & Rome-- through the 16Ancient Greece & Rome-- through the 16 thth- & - & 1717thth-centuries, opium’s medicinal & recreational -centuries, opium’s medicinal & recreational uses were well established.uses were well established.

A mixture of opium and alcohol, called A mixture of opium and alcohol, called laudanum, was used to treat practically every laudanum, was used to treat practically every disease known during the 1800s. disease known during the 1800s.

OPIATES-HistoryOPIATES-History

During the civil war, opium addiction was a During the civil war, opium addiction was a widespread problem. widespread problem.

By 1914, the Harrison Narcotic Act was By 1914, the Harrison Narcotic Act was passed and the use of most opioid products passed and the use of most opioid products was controlled. was controlled.

Opiates vs. OpioidsOpiates vs. Opioids OpiateOpiate-- is a drug that is extracted from the -- is a drug that is extracted from the

exudates of the poppy. exudates of the poppy. E.g., E.g., morphine and codeinemorphine and codeine. .

An An opioidopioid is any exogenous drug (natural is any exogenous drug (natural or synthetic) that binds to an opiate receptor or synthetic) that binds to an opiate receptor & produces agonist or morphine-like & produces agonist or morphine-like effects. effects.

E.g., E.g., heroinheroin

Endorpins (“morphine-within”)Endorpins (“morphine-within”)

  Endorphins --any endogenous substance Endorphins --any endogenous substance (naturally occurring in the body) that (naturally occurring in the body) that exhibits pharmacological properties of exhibits pharmacological properties of morphine. morphine.

We have 3 families of endorphins—We have 3 families of endorphins—enkephalins, dynorphins, & beta-enkephalins, dynorphins, & beta-endorphins. endorphins.

MORPHINEMORPHINE Is still the most potent pain reliever available (no other Is still the most potent pain reliever available (no other

drug has its clinical effectiveness).drug has its clinical effectiveness).

Is administered orally, rectally, or by injection. Is administered orally, rectally, or by injection. Absorption is slow & only 20% of the drug reaches Absorption is slow & only 20% of the drug reaches the CNS. the CNS.

Is broken down by liver & produces metabolites Is broken down by liver & produces metabolites (morphine t-glucoronide) that are 10 to 20-fold more (morphine t-glucoronide) that are 10 to 20-fold more potent that morphine itself. These continue exerting potent that morphine itself. These continue exerting analgesic effects.analgesic effects.

Morphine’s half-life: 3 to 5 hours. Morphine’s half-life: 3 to 5 hours.

MORPHINE-DRUG TESTINGMORPHINE-DRUG TESTING For 2 to 4 days following opiate use, urine For 2 to 4 days following opiate use, urine

screening tests can be used to detect codeine & screening tests can be used to detect codeine & morphine as well as their metabolites. morphine as well as their metabolites.

Heroin use can be tested for indirectly. Heroin is Heroin use can be tested for indirectly. Heroin is metabolized to morphine & also often contains metabolized to morphine & also often contains acetylcodeine (metabolized form of codeine).acetylcodeine (metabolized form of codeine).

Although the tests cannot accurately determine Although the tests cannot accurately determine which drug (heroin, codeine, morphine) was which drug (heroin, codeine, morphine) was present. present.

WHAT ARE EFFECTS OF WHAT ARE EFFECTS OF MORPHINE?MORPHINE?

Analgesia Analgesia RelaxationRelaxation EuphoriaEuphoria SedationSedation Sense of transquilitySense of transquility Reduced anxiety Reduced anxiety Respiratory depressionRespiratory depression Cough suppressionCough suppression

HOW DOES MORPHINE EXERT ITS HOW DOES MORPHINE EXERT ITS EFFECTS?EFFECTS?

Morphine, like other opiates & opioids, Morphine, like other opiates & opioids, exert its effects by stimulating opiate exert its effects by stimulating opiate receptors widely distributed through the receptors widely distributed through the CNS (brain, brain stem, spinal cord).CNS (brain, brain stem, spinal cord).

  CODEINECODEINE Is usually combined with aspirin or acetaminophen for Is usually combined with aspirin or acetaminophen for

the relief of mild to moderate pain. the relief of mild to moderate pain.

Half-life--3 to 4 hours. Half-life--3 to 4 hours.

Codeine is metabolized by hepatic cytochrome Codeine is metabolized by hepatic cytochrome CYP2D6 enzymes to morphine, & many of its effects CYP2D6 enzymes to morphine, & many of its effects may be the result of morphine actions.may be the result of morphine actions.

Using serotonin-specific antidepressants can block the Using serotonin-specific antidepressants can block the pain relief of codeine, because they block the pain relief of codeine, because they block the conversion of codeine to morphine.conversion of codeine to morphine.

HEROINHEROIN (diacetylmorphine) (diacetylmorphine) Is produced by a slight modification of the chemical Is produced by a slight modification of the chemical

structure of morphine. structure of morphine.

It cross the blood-brain barrier very rapidly, leading to It cross the blood-brain barrier very rapidly, leading to an intense rush when it is either smoked or injected an intense rush when it is either smoked or injected intravenously. intravenously.

It is metabolized to monoacetylmorphine &morphine. It is metabolized to monoacetylmorphine &morphine.

Clinical use of heroin is legal in Great Britain & Clinical use of heroin is legal in Great Britain & Canada. Canada.

F. ANTIDEPRESSANTSF. ANTIDEPRESSANTS A broad class of drugs used to treat depression.A broad class of drugs used to treat depression.

What is depression???What is depression??? A state of great sadness characterized by feelings A state of great sadness characterized by feelings

of despair, worthlessness, hopelessness, & of despair, worthlessness, hopelessness, & withdrawal from other.withdrawal from other.

It’s the “common cold” of psychopathology—It’s the “common cold” of psychopathology—we’ve all had symptoms at some point.we’ve all had symptoms at some point.

Major depression: DSM diagnosis made Major depression: DSM diagnosis made if:if:

Person has 5 of the following symptoms Person has 5 of the following symptoms (next slide) for at least 2 weeks. (next slide) for at least 2 weeks.

Depressed mood or Depressed mood or loss of interest loss of interest & pleasure in enjoyable & pleasure in enjoyable activities (anhedonia) must activities (anhedonia) must be included in symptoms. be included in symptoms.

Symptoms of major depression:Symptoms of major depression: 1. Depressed mood.1. Depressed mood. 2. Loss of interest and pleasure.2. Loss of interest and pleasure. 3. Significant weight loss or weight 3. Significant weight loss or weight gain.gain.

4. Difficulty in sleeping-Insomnia or4. Difficulty in sleeping-Insomnia or hypersomnia.hypersomnia. 5. Shift in activity level, psychomotor 5. Shift in activity level, psychomotor retardation, or agitated.retardation, or agitated.

6. Fatigue or loss of energy.6. Fatigue or loss of energy. 7. Negative self-concept.7. Negative self-concept. 8. Difficulty concentrating.8. Difficulty concentrating. 9. Recurrent thoughts of death or 9. Recurrent thoughts of death or suicide.suicide.

1. Tricyclics1. Tricyclics

E.g., imipramine (Tofranil) and amitriptyline (Elavil).E.g., imipramine (Tofranil) and amitriptyline (Elavil).

These prevent reuptake of both norepinephrine & These prevent reuptake of both norepinephrine & serotonin by the presynaptic neuron.serotonin by the presynaptic neuron.

2. 2. Monoamine oxidaseMonoamine oxidase (MAO) inhibitors - (MAO) inhibitors - tranylcypromine (Parnate) tranylcypromine (Parnate)

Keeps enzyme monoamine oxidase from Keeps enzyme monoamine oxidase from deactivating neurotransmitters, thereby increasing the deactivating neurotransmitters, thereby increasing the levels of both serotonin and norepinephrine.levels of both serotonin and norepinephrine.

3. 3. Selective serotonin reuptake inhibitors Selective serotonin reuptake inhibitors (SSRIs): fluoxetine (Prozac) & (SSRIs): fluoxetine (Prozac) & sertraline (Zoloft).sertraline (Zoloft).

   Selectively blocks reuptake of serotonin.Selectively blocks reuptake of serotonin.

Efficacy of all three classes of drugs about Efficacy of all three classes of drugs about the same (50-70% effective). the same (50-70% effective).

Side effects fewer in SSRI’s. Tricyclics can Side effects fewer in SSRI’s. Tricyclics can be dangerous.be dangerous.