DRUGS – PSYC 179

DRUGS – PSYC 179 9/24/09 9:30 AM

Professor George Koob [email protected] http://courses.ucsd.edu/gkoob experimentrix – 1 pt class participation – 1 pt Drug Nomenclature Drug Classification – Schedules Drug Classification – Behavioral

Definitions Drug – any chemical agent that affects an organism (even some vitamins) Psychotropic – drug effect on mind and behavior

Drug Nomenclature3 ways to name a drug Chemical – chemical structure, describes its structure,

Librium – 7 chloro-2 menthylamino-5-phenyl 3-11-1,4 benzodiazapine-4 oxide

Don’t often use chemical name, too complicated Nonproprietary (generic name) – given when a drug has demonstrated

therapeutic use Librium – generic name is Chlordiazepoxide

Proprietary (trade name) – given what a drug is patented by a drug company

Librium

Differences in the compound, the making of the pill Trade name advantage it is ensured, not sitting out too long, trade name

is also cheaper A variety of different trade names for a drug, but only one generic name

Drug Classification- prescription and non-prescription (get most of them right in supermarket)- Legal & illegal, some drugs like medical marijuana legal in some states- Abuse potential has to deal with schedule classification - (LOOK ON WEBSITE FOR THIS SLIDE – US DRUG SCHEDULES SLIDE)- Drug schedule classification

o Began with controlled substances act (1970) drugs need to be put in safe, schedule 1 schedule 2 need to have license for

o Five schedules createdo Determination of which drugs are on which schedule made by

Department of Justice (DEA and FBI) and the department of health and human services (FDA)

o Classification decisions made on criteria of potential for abuse, accepted medical use in ……..

o Schedule 1: no accepted medical use in the US *** High abuse potential *** Heroin, marijuana, LSD, peyote, mescaline, psilocybin,

MDMA (E)o Schedule II: high abuse potential with severe psychological or

physical dependence, also reasonable medical use Aderol is a schedule 2 drug

o Schedule III: abuse potential less than those in schedules 1 and 2, and include compounds containing limited qualities of certain narcotic drugs and non- narcotic drugs

Need prescriptiono Schedule IV: milder drug, abuse potential less than those in III

and include drugs such as barbital, phenobarbital, meprobamate (Equanil, Miltown), chloriazepoxide (Librium), diazepam (valium)…..

Need prescriptiono Schedule V: lowest abuse potential, consist of preparations

containing limited quantities of certain narcotic drugs such as codeine generally for antitussive (codeine) and antidiarrheal purposes, which may be distributed without a prescription order, don’t get into the brain very well??

Don’t need prescriptiono ONLY PSYCHOPETIC DRUGS With abuse potential fall in these

scheduleso Pharmacy keep off schedule or keep as low on schedule as

possible Behavioral Classification

Stimulants: caffeine, nicotine, cocaine, methamphetamineo Drugs increase arousal, sustain performance

Opiates: analgesics .. (anally), morphine, meperidine (Demerol)o Relieve pain…has medical uses

Sedative-Hypnotics: alcohol, diazepam (valium): (antianxiety drugs)o

Antipsychotics: haloperidol (haldol) Antidepressants: Fluoxetine (prozac)

o Treat effective disorder, depression, major depressive episode,

Psychedelics: hallucinogens, lysergic acid (LSD), psilocybin (magic mushrooms), marijuana (high dose has psychedelic actions, but at moderate doses, it relaxes you…)

DEFINITIONS Pharmacology: study of the interaction of chemical reagents with

living organisms Toxicology: study of the harmful effects of drugs Pharmacotherapeutics: study of the diagnostic/therapeutic effects

of drugso Take test to see if you are actually dependent withdrawal or

just trying to spam opius Pharmacokinetics: Study of the factors which determine amount of

drug at sites of actiono How much gets out

Pharmacodynamics: study of how drugs produce their biological effect

o Where it goes and what it does when it gets there One absect of pharmacokinetics

o Absorption: movement of a drug into the blood streamo Assumption made, if its in your blood stream, its in your braino Different ways to get drug in there

Method: IV Advantage: titratable (regulate the amount) Disadvantage: no turning back, once its in there

its in there Method: IM

Advantage: rapid onset, good distribution, relatively safe

Disadvantage: discomfort, tissue damage, hit a blood vessel

Method: Oral Advantage: safe, reversible, induce vomiting, get

stomach pumped, there’s ways to get rid of drugs from your stomach

Disadvantage: absorption is poor and slow, varies tremendously with whether you have food or no food in your stomach

o Smoking a drug distributes to your blood stream as quickly

maybe even more quickly***

9/24/09 9:30 AM

Lungs, heart, brain Heart lung heart brain? Snorting a drug is through your nose Im – intermuscular Po – oral

IV. Drug Elimination: how do we get rid of it two ways: break down the drug, eliminate it through the kidney (1st

order kinetics: constant rate removed)o Half-life: time it takes to remove 50% of drug from

bloodstream… Independent of drug concentration Constant rate: doesn’t matter if you take a big dose or a

small dose, the half-life is the sameo Examples:o Generally about 3 half life,

long half life, longer duration of action half life doesn’t change small dose or big dose, but duration of

action does **** HALFLIFE Occurs in kidney – most other drugs; 1st order kinetics Liver – alcohol metabolism; 0 order kinetics (no half life ) alcohol is

broken down in the liver and that’s how it is eliminated, so there is no half life, so constant AMOUNT

Liver is CONSTANT amount removed, kidney is CONSTANT rate *** Half-life – time to remove half drugs from the blood

Dose Response Curve****** Effectiveness: Percent of maximum response (Y-axis on DRC) Potency: Dose required to produce an effect relative to a standard

(X-axis on DRC)

Relationship between dose and whatever effect your looking at (the effectiveness of the drug)

Ex. Opiates have same effectiveness but different potency Less potent shifts curve to the right, more potent shifts to the left*** Potent (take less to get the same effect)

V. Therapeutic Ratios Therapeutic ratio = lethal dose (LD50)/effective dose (ED50) Effective dose depend Examples:

o Morphine = 80 mg(LD50)/10mg(ED50) = 8.0

“… you take drugs to make yourself feel better, to fill a hole.” – Ricky Williams

Classes of Abused Drugs All drugs that produce a positive change in mood state tend to be

drugs of abuse Sedative Hypnotics: Alcohol (high abuse potential), Quaaludes

(high), Barbiturates (low), benzodiazepines (lowest) Stimulants: Nicotine (high), Cocaine (high), Amphetamines (high) Opiates: Heroin (high), Morphine (high) Psychodelics are not on this. They have dangerous effects, but

rarely do they meet the criteria for addiction

Physical Dependence – Definition “an adaptive state that manifests itself by intense physical

disturbances when the administration of a drug is suspended…these disturbances, i.e., the withdrawal or abstinence syndromes, are made of specific arrays of symptoms and signs of psychic and physical nature that are characteristic for each drug type.”

Can drugs which are not addictive produce withdrawal?

Psychic (psychological) dependence – definition “a condition in which a drug produces ‘a feeling of satisfaction and a

psychic drive that require periodic or continuous administration of the drug to produce pleasure or to avoid discomfort’…”

Starbucks?? Different from alcoholic?

Don’t use these two definitions anymore.

Definitions of addiction Drug abuse versus drug dependence – usually drugs are abused

first, and dependence comes later DRUG ABUSE

o DSM (American Psychiatric Association)o A. Drug Abuse (substance abuse)

*maladaptive pattern of substance use with significant adverse consequences related to repeated use

o ICD (World Health Organization)o A. Harmful use (substance abuse)

*a pattern of use that is damaging to overall health ***Substance abuse Worksheet!!

Definitions of addiction Drug Dependence

o Substance Dependence – “with a capital D” equivalent to addiction***

Compulsive drug use with LOSS OF CONTROL over intake and (emergence of a negative emotional state upon cessation of chronic drug use- Koob)

o Dependence – “with a little d” The manifestation of a withdrawal syndrome; you can

have abstinence syndrome without addiction ***memorize substance abuse worksheet (left side dependence)

Dependence DSM-IV** MEMORIZE (do not have to learn ICD-10)

1. Tolerance2. Withdrawal3. The substance is often taken in large amounts or over a longer period

than was intended4. Any unsuccessful effort or a persistent desire to cut down or control

substance use (loss of control)5. A great deal of time is spend in activities necessary to obtain the

substance or recover from its effects (activity to get the drug)6. Important social, occupational, or recreational activities given up or

refused because of substance abuse7. Continued substance use despite knowledge of having had a persistent

or recurrent physical or psychological problem that is likely to be caused or exacerbated by the substance (persistent psychological problems)

You can have psychological dependence without physical dependenceSubstance dependence = addictionAbuse is different than dependent

Earlier you start, most likely to be a problem.

9/24/09 9:30 AM

Sources and Names of drugs Drugs mostly come from plants and the plants mutate over time to

develop these chemical reactions when animals for example eat them as a possible defense mechanism

In large doses, these plants are dangerous, but in small doses they may alter the biochemistry just enough to produce interesting or useful effects

Those who used these plants effectively were usually important figures in their communities: pharmacists, religious figures in tribes

Names of Drugs Brand, generic, and chemical

o Generic official (legal) names of drugs Usually refers to specific chemical, but shorter and

simpler than chemical name Names in public domain, so cannot be trademarked

o Brand name specifies a particular formulation and manufacturer

Copyrighted and protected by trademark laws

CATEGORIES of DRUGS Any scheme for categorizing drugs has meaning only if it serves the

purpose for which the classification is being made Stimulants and depressants do not counteract one another Regular use of depressant drugs can lead to a withdrawal

syndrome: restlessness, shakiness, hallucinations, convulsions Opioids: group of analgesic (pain killing) drugs that produce a

relaxed, dreamlike states aka narcoticso Opioids there is a clouding of consciousness w/out reckless

abandon, staggering, and slurred speech produced by alcohol and other depressnants

o Regular use of opioids can lead to withdrawal of diarrhea, cramps, chills, and sweating

Hallucinogens produce altered perceptions Psychoterapeutic drugs include a variety of drugs prescribed by

psychiatrists and other physicians for the control of mental problems

The antipsychotics are also called neuroleptics

o Can calm psychotic patients and over time help them control hallucinations and illogical thoughts.

Antidepressants help some ppl recover more rapidly from seriously depressed mood states

Lithium is used to control manic episodes and to prevent mood swings in bipolar disorder

Nicotineo Thought of as mild stimulant, but have some relaxant

properties of a low dose depressant Marijuana

o Relaxant, depressive type of drug, but does not share features of that class

o Sometimes hallucinogens because high doses can alter perceptions

DRUG IDENTIFICATION Physicians Desk Reference published color photographs of legally

manufactured pharmaceuticals Markers of illicit tablets Cocaine heroin powder wrapped and labeled in a consistent way.

DRUG EFFECTS Effects of a drug don’t depend only on chemical interactions with

the body Sometimes it depends on the mood and feelings of the user Nonspecific effects are those that come from the user’s unique

background and perception of worldo Anything except the chemical activity and direct effects of the

activityo “placebo effects”, because they can often be produced by an

inactive chemical that user believes to be drug Specific effects Placebo many times work Studies show depressed people feel better after unknowingly taking

a “placebo Dose-response curve

o Threshold: at some low dose, an effect on the response system being monitored is observed

o In some interactions, effect of drug is all of noneo Look at post it

Ataxia (staggering or inability to walk straight) Comatose (pass out and cannot be aroused)

Estimating safety margino To determine effective dose (ED) on animals ED sub 50 or

effective dose for 50 % of animals Toxicity is usually measured in one early animal studying by seeing

how many mice die LD sub 50 (lethal dose for 50% of mice) THERAPEUTIC INDEX (TI) is LD50/ED50 Thus, if the new drug has a greater TI than existing drugs, it is likely

to be safer when given to humans Safety margin: dosage difference b/w an acceptable level of

effectiveness and the lowest toxic dose Side effects: unintended effects that accompany therapeutics

effects Selection of a drug for therapeutic use should be made on the basis

of effectiveness in treating the symptoms w/ minimal side effects Potency: measured by the amount of drug required to produce an

effecto The smaller the amount needed to get a particular effect, the

more potent the drug Time Dependent Factors in drug actions

o Time course: timing of the onset, duration, and termination of a drug’s effect

o When the maximum possible therapeutic effect has been reached, increasing the dose primarily adds to the number of side effects

o Cumulative effects: effects of giving multiple doses of the same drug

o Time release preparations: large amount drug is made available for absorption then smaller amounts are released continuously for a long period.

Make measured highest effect of drug longer without increasing concentration of drug in blood

Getting the Drug to the Brain

Lipid solubility: tendency of a chemical to dissolve in fat, as opposed to in water

o Most psychoactive drugs dissolve to some extent in either water or lipids

Reach brain through bloodstream: mouth, injection, inhalationo Oral

Easiest to get in body, but most complicated to get in bloodstream

Has to survive actions of stomach acid and digestive enzymes

o Injection IV (intravenous injection): put directly in bloodstream;

injection directly into a vein Bad and good: deliver high concentrations fast But vein wall loses some strength and elasticity around

injection sight Bacteria can get in…shared needles

o Subcutaneous and intramuscular injections Similar characteristics Subcutaneous: injection under the skin Intramuscular: injection into a muscle Absorption more rapid from intramuscular injection Less chance of irritation if intramuscular injection and

larger volumes BUT side of injection might die and be shed the skin

“skin popping”o Inhalation

Efficient Rapid drug onset Blood circulation from lungs moves directly to brain BAD: material must not be irritating to mucuous

membranes and lungs AND control of dose is more difficult

When drug admin is stopped, effect rapidly decreases Transport in the blood

o When a drug enters bloodstream, its molecules will attach to one of the protein molecules in the blood

o As long as there is protein-drug complex, drug is inactive and can’t leave the blood; drug is protected from inactivation by enzymes

o BUT release of protein-bound drug to maintain the proportion of bound to free molecules

o Alcohol: flow through blood easilyo THC in marijuana bound to blood proteins, w/ only a small

fraction free to enter brain o If two drugs were identical in every respect except protein

binding, the one w/ greater affinity for blood proteins would require a higher dose to reach an effective tissue concentration

o But the effect would be longer because of “storage” on blood proteins

o Drugs w/ high affinity would displace drugs w. weak protein bonds

Blood- brain barriero Blood brain barrier: structure that prevents many drugs from

entering braino Capiillaries in brain contain no poreso Even water soluble molecules can’t leave the capillaries in

brain, only lipid-soluble substances can pass the lipid capillary wall???????????????????????????

o Then if pass that, glial cells; there is little extracellular space next to blood vessel walls

o With no pores and close contact b/w capillary walls and glial cells, an active transport system is needed to move chemicals in and out of brain

MECHANISMS of DRUG ACTIONS Semipermeable characteristic of cell membrane Each type of psychoactive drug interacts in a different way w. the

various neurotransmitter systems in the brain

DRUG DEACTIVATION Urine or chemically changed so it has no effect on the body

Metabolite: product of enzyme action on a drug CYP450 enzymes seem to be specialized for inactivating various

general kids of foreign chemicals that the organism might ingest Active metabolites: metabolites that have drug actions of their own Prodrugs: drugs that are inactive until acted on by enzymes in the

body

MECHANISMS OF TOLERANCE AND WITHDRAWAL SYMPTOMS Tolerance

o drug disposition tolerance: tolerance caused by more rapid elimination of the drug

o increased elimination: pH (acidity) of urineo behavioral tolerance: tolerance caused by learned adaptation

to the drugo Pharmacodynamic tolerance: tolerance caused by altered

nervous system sensitivity Many times amount drug reaching brain doesn’t

change, but sensitivity of the neurons to the drug’s effect does change

Withdrawal reactions Body aims for homeostasis

Grapefruit-juice effect Raise concentrations of the drug beyond what dosage calls for

Animal Toxicity Tests PETA (people for the ethical treatment of animals) fight

Avoiding Withdrawal Symptoms Dependence may be less of a problem when he is allowed to take

the drug as needed

Drugs in Depth Respiratory depression, slow breathing……people stop breathing Stimulants and antidepressants

Stimulants and depressantso Behaviors don’t counteract one another

Cocaine + alcohol = cocathyleneo Produce cocaethylene – stimulant that animal studies indicate

20x as toxic as cocaine

OPIATES 9/24/09 9:30 AM

Cont. The earlier you start doing drugs, the more likely you’ll have

problems later on Brain at adolescence altered that way makes you more vulnerable

to addiction later on

Drugs as Reinforcers Reinforcement: process by which an event increases the probability

of a given response Positive reinforcement: presentation of an event increases the

probability of a responseo Ex. Work hard and get praise from your braiseo Ex. Drink alcohol to feel good, attract opp. Sex, and be more

outgoing Negative reinforcement: termination of an event increases the

probability of a responseo Take drug to avoid withdrawalo Ex. Work hard to avoid getting laid offo Drink alcohol to avoid severe withdrawal effects

Punishment: presentation of an event decreases the probability of a response

o Behavior rebound Addiction is a process, uses both type of reinforcement, move from

positive reinforcement into negative reinforcement so you have both reinforcements, when cross that line, cross into “addiction”

Shift in reinforcement Associated with Development of addiction Addiction combination of two types of disorders

o Impulse control disorders Ex. Kleptomania …lobster man Tension/arousal to impulsive acts to pleasure/relief

gratification……………

More positive reinforcemento Compulsive disorders

Ex. OCD Anxiety/stress to negative behaviors to relief of

anxiety/relief of stress to obsessions to anxiety/stess….. More negative reinforcement

Stages of the Addiction Cycle Preoccupation Anticipation: not actively participant, but really want

drug Binge intoxication: take lots of drug Withdrawal negative affect: motivational withdrawal.. need to feel

normal

DSM IV criteria as a function of addiction stage A. Preoccupation/Anticipation: a lot of time is spent procuring drugs.

Continued use despite negative consequences B. Binge/intoxication: take more than intended. Decreased social

and occupational functioning C. Withdrawal/Negative Affect: Tolerance, Withdrawal

Active Reinforcement/Social Drinking escalating/compulsive use binge drinking dependence withdrawal (can go to relapse) protracted withdrawal (can go relapse) recovery

All of these influenced by genetic variables, environmental factors, stress, conditioning effects

OPIATES (classic drug of abuse) Poppy: grows in south east asia When you cut it, white substance comes out, and that is Opium Opium Poppy (papaver somniferum)

o 20 alkaloids (rebase, needs to put in alkaloid solution): morphine*: pain reliever Codeine******** natural opiuds in the opium poppy Thebaine

o Opium can be smokedo Opium used as a pain reliever

Heroin: semi synthetic derivative of morphineo Not a natural product of opium poppyo Developed to shift morphine in a more purified formo Gets into brain faster than morphine so more potent

Opioids SLIDE! http://courses.ucsd.edu/gkoob/PSYCH179/opioids2009.pdf

Methadone (drug used to treat addiction but it is an opiates itself)****

Endogenous opioid peptides: we have opiods in our brain..endorphins . produce pain relief

Definitions Opiate = any drug derived from opium that has morphine-like

effectso Naturalo Semi-synthetic

Opioid = any drug natural or synthetic that has morphine-like effects

o Naturalo Endorphinso Semi-synthetic and synthetic

Narcotic = any drug of abuse Analgesia:

o Raising of pain thresholdso Lowering of pain

Hyperalgesiao Lowering of pain thresholdso Increased paino Are withdrawal like reactions

Allodyniao Painful response to non painful stimuluso Are withdrawal like reactions

Anesthesiao Analgesiao Loss of consciousnesso Loss of memory

Narcotic Analgesics Table (in book in opiods chapter) Drugs not asked about oxymorphone, hydromorphone,

dihydrocodeine, and pentazocine***

Medical Uses

Opioids widely used for diarrhea Produce constipation if your normal, but if you have diarrhea, they’ll

stop diarrhea Ioperamide (Imodium) 4 mg (2-2mg tablets) not ask dosages on test

o Does not cross the blood brain barriero Half life around 11 hours

Diphenoxylate (lomotil) with atropineo Crosses the blood brain barrier but atropine (gives dry mouth)

prevents abuseo Trick of adding drug helps prevents abuseo Half life of 13 hours

Drugs used to treat diarrhea have no abuse potential and are affective

EFFECTS OF OPIOIDS ON PAIN*** Powerful, relieve enormous amount of pain, Analgesia selective to pain

o Raising of pain thresholdso Lowering of paino Other sensory modalities such as tough, vibration, vision,

hearing are not altered Type of pain

o Continuous dull pain is relieved more effectively than sharp intermittent pain

Ex. The hammer on hand example pain Type of analgesia:

o Pain is present but patient feels more comfortable Lets find opioid that relieves pain, but not cause addiction, but

never happened!

Opioid preparations widely used for pain management ???????????????????? Meperidine (Demerol) Hydrocodone (vicodine) + acetaminophen decrease dose of opiod

Oxycodone (percocet) + acetaminopheno DO NOT EXCEED 4 GRAMS ACETOMINOPHEN PER DAY)****

Oxycodone (percodan) + aspirin Oxycodone (oxycontin) comes in high concentration so controlled

release dose rangeo 80 and 160 MG ONLY USE IN OPIOID TOLERANT PATIENTS

Pain management with opioids outpatient analgesia:

o oralo patch-transdermal: transdermal adminstration of drug,

chronic drug, some people can’t take opiuis orally, makes then nauseus

Impatient analgesiao Intravenous-titration possible

Pump press nurse Patient controlled analgesia:

o Procedure allows self-administered opioido Doses less than oralo Greater relief of pain?

People don’t get addicted in the hospital when theyre being treated for pain

Opioids as Adjuncts in Anesthesia Opioids as adjuncts in anesthesia reduce preoperative pain, lower

requirements for inhaled anesthetics and provide immediate postoperative analgesia

Opioids are often used to relieve pain during general anesthesia Opioids are a key component of “balanced anesthesia” where

different agents are use to produce: analgesia, amnesia, muscle relaxation, and abolition of autonomic reflexes

Drug of choice for anesthesia is fentanyl (very potent, a lot more than morphone.. the highest abusive opiod is fentanyl…anesthesia’s overdose on fentanyl) and its derivatives

Fentanyl is 80x more potent than morphone Opioids are used as adjuncts in anesthesia, the part theyre used for

is for pain

Drugs for General Anesthesia Parental (injectable) anesthetics- induction and maintenance

o Propofol-iv inductiono Desflurane-inhaled (volatile) anesthetics-maintenance

Anesthetic adjunctso Opioids

Opioids widely used for control of cough Dextromethorphan

o Over the countero 30mg every 6 hours as needed not to exceed 120mg/dayo very high dose (3000mg) produces psychedelic-like

experience (hallucinations) Codeine

o Presciptiono 7.5 mg-60mg per dayo schedule V drug as a liquido Schedule II drug as tableto Schedule III drug when combined with acetominopheno

Full antagonist knock off receptor cause its repetitive

NEED TO GET NOTES 9/24/09 9:30 AM

Opiate Abuse + dependence

Euphorific effects Tolerance Withdrawal – dependence

Opiates use: Patterns Junkies Chippers

Long term withdrawal-conditioning

Euphoric effects Heroin – most commonly used

Heroin/morphine effects 1-3 mg heroin:

1. Rush, kic, thrill nod (sleepiness) 3. High 4. Being straight

3-15 mg morphine 45 seconds

high – feeling of general well-being accompanied by either:

o a feeling of boundless energy and strength

o or a pleasant dreamlike state

4. Being straight

o normal – not sick, not suffering from withdrawal symptoms

you don’t die from opioid withdrawal but you feel like you do its like getting the “flu” flu like state

opiate usepatterns

1. Drug use can begin with medical treatment *minor contribution) 2. Recreational drug use – primarily adolescents 3. Oral opiates – methadone from treatment methadone – very synthetic opioid, prevents withdrawal for 24-48

hours after you take it but could still be abuse

types of opiate usrs1. junkie – a classic addict

a. longtime (chronic) user who cares more about where and when next “fix” will come than other ties to reality (e.g. family, friends, bills and responsibility)

b. geatest fear is not death but the intense sickness associated with withdrawal that he or she will pay if he or she does not get the next injection

c. 96% of users inject drugs 2. Chipper – occasional opiate user; nondependent

evidence that occasional use may go on for years most likely to have rules:

o refuse to inject

o plan for their use

o exercise caution when getting drug

o budget money to be spent on opiates

able to defer use when opiates are not available

o drug use involves complex social relations

o little evidence of physiological pathology associated with

opiate use; does not lead to mental deterioration or psychological disorders

can skip a weekend, whereas drug addict can’t opiates don’t rot brain, liver, or heart but others have effect on body its easy for nicotine to transit from chipping to dependent chippers don’t generally bring in much withdrawal they use drug in manner in which they don’t produce withdrawal

interview with an opioiod addict (on website)

ocygontin and potential for abuse

Oxycontin and potential for abuse oxycontin

o dosage forms: 10mg, 20mg, 40mg, 80mg, and 160 mg tablets

o administered every 12 hours

abuse potential:

o abuse potential tends to increase based upon route of

administration: oral vs. snorting vs. i.v.

o large amount of active ingredient compared to other opioid

pain relievers

o marketed as have less addicting potential, less abuse and

diversion, less likely to interact with other medications is abused for chronic pain, but before made in strong, so that’s why

people abuse it

tolerance 1. Tolerance to opiates is characterized by a shortened duration and

decreased intensity of action 2. What becomes tolerant: analgesia, euphoria, sedative effects,

respiratory depression, lethal affects (5g of morphine per day!) 3. What does not become tolerant : papillary constriction and

constipation 4. Onset

o depends on route of administration

o significant tolerance only when administration is daily

high gets less and the duration gets shortened if can condition a high can also condition a withdrawal constipation is resistant to tolerance as well as papillary constriction

differential tolerance rapid

o analgesia

o euphoria

o respiratory depression

slow

o constipation

o papillary constriction

withdrawal time course chart (on website) 6-8 anxiety and craving for drug, restlessness, irritability 8-16 hours of withdrawal starting to get physical effects: running

nose, teary eyes, yawning, restless sleep, miserable feelings

16-24: papillary dilation, goose bumps, tremors, hot and cold, aching bones and muscles, loss of appetite, flu like state

24-36 all sighs worse – insomnia, increased BP, respiratory rate, nausea and body temperature

36-48 peak of syndrome, worsen, vomiting, diarrhea, weight loss, weakness depression

46-68 dissipation of syndrome, diminishing of all symptoms 7-10 days most signs of withdrawal gone

withdrawal in short vs. long acting drugs short acting drugs

o short onset withdrawal

o short duration

o very intense

long acting drugs

o long onset withdrawal

o long duration

o milder-less intense

methadone withdrawal withdrawal slow in onset and generally less severe:

o first signs 24-48 (-72) hours

o peak 3rd day

o more prolonged

however, nix can precipitate a severe withdrawal (displacing drug from receptor)

o over by 10-14 days

substituting synthetic for the illegal one

9/24/09 9:30 AM

substance dependence – addiction

treatment detoxification

o methadone

o bupremophine

o cold turkey: stop taking the drug

o Opioid antagonist can have two dif affects

Can block effect of opioids Precipitate drug

o

Methadone Maintenance:

o No illicit drug use

o Substitute of oral methadone for IV heroin

o Synthetic opioid substitute for the heroin and it prevents illicit

drug use and it prevents withdrawal

o Opioid agonist

o High affinity, high intrinsic activity

o Long half life : 35 hours

o Detoxification: prevents opioid withdrawal at doses of 40-60

mg/day p.o

o Maintenance: blunts opioid actions at doses of 60-80 mg/day

p.o Buprenorphone Maintenance:

o No illicit drug use

o Partial agonist

o New medication, been approved last 5 years, become

increadily popular and seems to be working very well

o Partial agonist, has properties of agonist and antagonist

o If have drugs on top of it, have no effect….

Just getting off the drug, doesn’t solve addiction Drug addiction is not treated by detoxification

Methadone Detoxification Way you use the drug, decrease the amount 5 mg a day, FDA requires

you do be finished by 21 days, This is for someone who wants to get off the drug completely Methadone. Take away their methadone will go into withdrawal Methadone: WHAT ARE THE EFFECTS OF IN METHADONE

MAINTAINED OPIOID:…….(get chemical)…

o Answer: blocked the effects of opioid and precipitate

withdrawal immediately******* This is a way of substituting for the heroin

Buprenorphone Opioid partial agonist High affinity, moderate intrinsic activity Getting effect of opioid actions Long half-life: 37 hours Withdrawal modest; delayed Detoxification & maintenance (15 mg/day, sublingual)

o Burprenex- buprenorphine injetion for analgesia 0.3mg= 10mg

morphine

o Subutex- buprenprphine:

o Suboxone-buprenorphine + naloxone

ALCOHOL Drinking: major social nightmare

o Abuse of alcohol, leading to DUI,

o Rotting brain when you overindulge in alcohol

Stats

120 million drink 18 million alcoholics 20% binge drinkers Driving: 40,000 fatalities; 17,500 alcohol related Cost: $180 billion/year

Ethanol CH3CH2OH 200% solution trace amounts of benzene

Denatured Ethanol Has methanol added Toxic

Isopropyl Ethanol CH3CH-OHCH3 Solvent and disinfectant Consisteng of rubbing alcohol and antifreeze Causes serious CNS depression Severe poisoning, deep coma, respiratory depression Metabolized to acetone

Ethanol comes in many different forms and anything with glucose or any carbohydrate can change it into alcohol solution by fermentation (where you create alcohol where you convert sugar into alcohol as a byproduct)

Proof 2x Percent*** 200 proof = 100% 100 proof = 50% 40% = 80 proof 50% = 100 proof Beer – 4% Wine – 10% Whiskey 40-50% Gin – 40-50% Vodka – 40-50%

Blood Alcohol Level 0.08 grams percent 0.08 grams alcohol in 100ml blood x1,000 = 80 mg% 0.08 g % = 80 mg % 1g 100ml = 1% that will kill all of us . in our blood

table in book*** table 9.2, pg 207***great table to memorizeboth females and malesmight ask how many drinks if you weighed 100lbs??? *****

Elimination 90-95% metabolism 5-10% directly (urine, breath)

alcohol doesn’t have a half life (in this class) Zero Oder Kinetics (concentration non-dependent) = constant

amount eliminated over time Rate of elimination: 0.01% per hour (not completely accurate, this is

average) Alcohol is broken down

Alcohol acetaldehyde CO2 + water Females have less alcohol dehydrogenase Females have larger amount of body fat/kg Disulfiram to building up Acetaldehyde dehydrogenasse which is

toxic, ****** Disulfiram (antabuse): when your on this and drink alcohol, you get

really sick . flushlight reaction: intense reddening, heat on face, dizzy, nauseous, vomit

o Asians 30-50% are missing one of the allele so its like they

have disulfiram on board

o If you have more body fat you have less water and alcohol

hangs out in water Behavioral Effects

0.05g %

o euphoria

o personality changes

o “social lubricant”

o release of inhibitions

0.08 g %

o release of inhibitions

o impairment in judgment

o motor impairment

o binge to reach 0.08

o 5 for male, 4 for female in two hours

0.20 g %

o ataxia – inability to move

o decreased motor

o decreased sensory

o decreased pain = analgesic

o “blackouts”- loss of memory, don’t remember events that take

place when your intoxicated 0.30 g %

o stuporous but conscious

0.40-0.50 g %

o unconscious

o lethal dose = 50%

o alcohol can be used as anesthetic but risk lethal toxicity

drug relaxation induces sleep it will disrupt your sleep, alcohol makes you sleepy but later brain will relapse and you will be awake don’t sleep well alcohol increases motivation for sexual activity probably through release of

inhibitions but limit performance in males, and females delayed orgasm

Blackouts loss of memory for events that took place while intoxicated*** blackouts are not loss of consciousness blackouts do not cause permanent memory loss blackouts represent “gap in the tape”

blackouts may be similar to “traveler’s amnesia” produced by a combination of benzodiazepines and alcohol

one of the dangers of alcohol, when combined with any other ..hynotic will increase the alcohol level, make each others effects bigger.???

Chart alcohol continues through whole sequence of events

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slide on alcoholTolerance

Tolerance = increasing amounts of drug required to produce same effect. Same drug, less effect over time

Dispositional (metabolic)- removal of alcohol from blood stream 0.01/hr non-alcoholics 0.02/hr alcoholics in a sense, alcoholics can obtain twice as much with same blood level induce an enzyme start losing liver functions Pharmacodynamic (functional) – neuroadaptive response Running around with a blood alcohol .6 Normally kills us doesn’t kill them ??????? (ask why) Alcohol is filtered through the liver Subjective intoxication graph

o How much drunk they think they are graphs compared to how

drunk they really are

o Chronic tolerance ….. ???

o Differential tolerance: while your high, your intoxication … that

blind spot…. ????

o Tolerance subjective

o If intoxicated with alcohol, you’ll be slowed down. Response

slower******

o Describe a question like intoxication parallel: which part of the

alcohol proof, ascending, ascending, descending… ONLY ASCENDING!!! **********

o Behavioral tolerance: learning to drive a car under the

influence Don’t account for reaction time, sensory

Binge: consuming 5 or more drinks male or 4 or more drinks female in about 2 hours is considered binge drinking (in handout)****

Alcohol abuse when our age doesn’t necessary believe we’re going to go on to alcoholism (not a strong correlation), but it could determine whether you go on or not

Alcoholism Alcohol Dependence = addiction = alcoholism

Loss of control over intake Compulsive drug taking Impairment in social and occupational functioning Negative emotional state upon withdrawal Alcoholism is a disease and substance dependent on alcohol as

defined DSM IV Alcoholism is very genetically determined

Alcoholism Risk Factors

o Family history positive 4x likelihood of becoming alcoholic

o Decreased sensitivity to alcohol****

Protective factors – positive

o Asians 30-50% heterozygote for gene deletion of Acetaldehyde

dehydrogenase

o 5-10% homozygous

Alcoholic case: David (on website)

Alcohol Withdrawal 1. Somatic

o early 24-48 hours

insomnia; CNS hyperexcitability

tremor sympathetic response increased

increased heart rate increased blood pressure increased body temperature

Seizures

o Late 2-4 days

Delirium tremens Hallucination High fever

II. Motivational

o Anxiety

o Dysphoria – negative mood state

o Everything is gray

Treatment Benzodiazepine: Chlordiazepoxide (Librium): treatment of acute

withdrawals of alcohol, it’s a sedative hypnotic, sedative

Employee Behavioral Pattern Early Stage: drinking to relieve tension, increase in tolerance,

memory lapses Middle stage: sneaking drinks, feeling guilty, tremors, loss of interest Late middle stage: unable to discuss problems, efforts for control fail,

neglect of food, drinking alone Terminal stage: not thinks “my job interferes with my drinking”

Toxic Effects of Alcohol

Cirrhosis of the Body

o Liver

o Heart

o Pancrease

Cirrhosis of the brain

o Wernicke’s/Korsakoff’s Syndrome

Fetal Alcohol Syndrome Alcohol Abuse- harmful use Alcohol Dependence = addiction = alcoholism

Alcohol and Brain Wernicke-Korsakoff syndrome

o With thiamine deficiency damages mammillary bodies and

thalamus and hippocampus***

o 12% of patients

o 10-20% mortality

o early, reversible – confusion, visual problems

o late, irreversible – anterograde amnesia (can’t remember new

things)

o neurological syndrome

o reversible with proper nutrition

Fetal alcohol syndrome

o Mild to moderate mental retardation (only fetal alcohol effect,

need all 3 to be called SYNDOME)

o Hyperactivity in childhood

o Growth deficiency

o Characteristic facial abnormalities

o Dose dependent and can be observed even with doses as low

as 2 drinks per dayDefinition

Absorption: movement of a drug into the blood steam

o Metabolism is 0.01 gm%/hour

o Alcohol: if you drink on a full stomach, absorption is blunted

o Full stomach, go up less dramatically strung out longer* will

blunt the high cause blunt the absorption

Treatment Framework Phases

o Detoxification

o Short-term treatment – Rehab

o Long term – after care

Detox- reduce excessive behavior (until behavior normalizes) Short-term abstinence (3-6 months) Reconstruction Long-term- prevent relapse (6 months- 2 years)

Medications for Alcohol Dependence Disulfiram (Antabuse)

o FDA approved 1954

o Just makes u sick

o

Naltrexone (ReVia)

o Opioid antagonist, orally active, absorb through stomach,***

unfortunately blocking brains endorphines isn’t always fun

o Blocks opioid peptide that’s released by alcohol

Acamprosate

o Medication

o Help track abstinence

o Reduce blooming responses

o Blocks glutomate

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II medical uses Cocaine:

o Topical anesthetic

o Vasoconstrictor

o Local anesthetic

Cocaine Doses:

o 20-50 mg

o 1-4% solution (not to exceed 10%)

o Maximum dose: 200 mg

o No systemic side effects on cardiovascular function

Amphetamines

o Narcolepsy (excessive daytime sleepiness)

o Attention Deficit Hyperactivity Disorder (Adderal)

o Weight control (appetite suppressant)

III Behavioral Effects Euphoria Improves performance Alleviates fatigue Decreases appetite (anorexic) Increases violence Increases sexual motivation (sexual motivation decreases with

chronic stimulant use) Euphoria

-20 mg cocaine snorted increased talkativeness and confidence

fatigue reduction restlessness “it gives me a hilarious exhilarating feeling” “produces an illusion of supreme well being. Supreme well being and

soaring overconfidence” “one thing you do get a lot of energy” intravenous injection of cocaine produces an intense “rush” increases dopamine produces pleasurable effect Locomotor activity vs. stimulant dose ..bell curve normal

Behavioral Pathology Stereotyped behavior

o Repetitive thoughts or actions

o Decreased amounts of response categories

o “punding” – goal directed but meaningless activity

o catatonia – immobility caused by rigidity

Paranoia

o Psychosis – paranoia; unable to recognize reality

o Cognitive stereotyped behavior

High abuse potential

o Substance dependence or addiction

Stereotyped Behavior Def: integrated behavioral sequences that acquire a stereotyped

character being performed at an increasing rate in a repetitive manner

Theory: increasing rate of behavior in a decreasing number of response categories

Behavior not only physical form but also cognitive form

Shift to left of dose effect curve with complex task These drugs have most dramatic effect when tired and worn out that’s why

they are called stimulants Paranoid Behavior

IV. Physical Effects Autonomic nervous system activation:

o Increased heart rate

o Increased blood pressure

o Increased body temperature (hyperthermia)

o Dilated bronchi

o Stimulants can deregulate our body temperature

Physical Pathology:

o Akathisia – urge to be in motion

o Akinesia – lack of movement

o Tremors

Dyskinetic movements:

o Abnormal, involuntary movements

Skin Picking – “crank bugs”

o Associated with stereotyped behavior

Midterm40 QuestionsNo history, no doses, no graphsBut focus on HINTS, relative potency, and know your drug category

Extra office hours TA office hours

First practice exam question on website Name patented name of the drug which allowsA) chemicalB) non proprietaryC) Generic D) Proprietary ****

V Addiction – Psychostimulant Addiction Cycle Euphoria , Dysphoria paranoia psychosis

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Prevalence of caffeine Most ubiquitious psychoactive substance -possibly 6,000bc America’s drug of choice 1 billion Kg coffee annually 40 gallons of soda per person energy drinks- newest, fastest growing

Coffee bush (>90 species, Rubia case) tropical Africa & Asia

o Each coffee cherry yields 2 coffee beans

o Beans dried and groupd

Arabica (coffee Arabica ) w. Africa, latin America high attitudes

Delicate plant, milder flavor, lower caffeine: ~1 percent

Robusta (coffee canephora ) Africa, Brazil, southeast Asia Hardier plan, harsher flavor 2x caffeine: ~2

percent Instant coffees and blends

Tea Bush (Carmellia Sinensis) Asia

SourcesCacao tree (theobroma cacao, sterculiciacease) Central America

Theo=god …broma = drink/exlier Kernels from pods roasted and ground Fat and powder separated

Cola tree (cola acuminate, sterculiacee) East Africa

Seeds from cola nut Synthetic forms used in US

Guarana (Paulinia cpana, Spaindaceee) Amazon South America Berries crushed, seeds extracted for a pate

Mate (liex para gueriensus, Aquifoliaee) Sotuh America Relative of holly

Leaves dried, chopped, and ground to powder (yerba) Agonist fits in the receptor and activates it, binds Most of the drugs are agonist Bind to site in the neuron and activate it At a site on the neuron Receptor on neuron, agonist Antagonist binds to receptor, binds to receptor doesn’t activate it, blocks it So agonist can’t get in Heroin and morphine are short acting drugs so they produce faster high

and fast intense withdrawal Methadone long acting drug agonist, but because long acting drug it gives

you more gradual affect, last longer, so withdrawal is a lot less severe Seriously addicted and can’t get off, because methadone maintained,

take methadone to keep them from going through withdrawal, so get to point where u take drug and not get high normal. Take methadone to make them feel normal. So before withdrawal, they take it again, so always taking it so that they feel normal