Psychopharmacology Exam 1

Front 1

What is a drug?

Back 1

A substance administered for a specific purpose with intent to alter some bodily/brain structure and/or function.

Front 2

Psychopharamcology is…

Back 2

Study the effect of drugs on the brain or nervous system and the resulting effects on behavior, cognition, and emotion

Front 3

How have food, supplements, pharmafoods, and turaceuticals muddied the definition of a drug

Back 3

Some foods can be drugs, contains precursors for neurotransmitters (e.g., Triptofan). Self medicating with carbs. Supplements (e.g., vitamins) are used with the intent to alter. Pharmafoods: Cinamon Toast Crunch with Ca. Neutraceuticals: spinach in a capsule.

Front 4

How is the field interdisciplinary?

Back 4

Academics (research/teaching), Psychiatry/clinical psychology, Medical field (all personnel), Pharmacy (preparing, dispensing),Pharmaceutical industry (Big Business-Pfizer, Lilly, etc.), Federal organizations (FDA, NIH, NIDA, DEA, etc.)

Front 5

Differentiation between drug abuse, recreational use, and therapeutic use

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Recreational (& more) is an effect on behavior, therapeutic has an effect on cognition, abuse has an effect on emotions.

Front 6

Prehistoric time/earliest humans (early days, 6000-500BC)

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Drug use has always existed, abudunance of drugs in nature, innate need to experience change in consciousness.

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Sumerians, Egyptians (5000 BC) early days, 6000-500BC)

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Herbal meds + prayer, Ebers & Smith papyri/Imhotep-900+ prescriptions. Use of alcohol, opium, psychedelics, MJ

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Imhotep early days, 6000-500BC)

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Phsycian god, came up with over 900 prescriptions.

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Asian, Arabic, African cultures (3000 BC) early days, 6000-500BC)

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Improved records! "Herbals." Advanced drug processing, texts. Belief in balance, holistic medicines.

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Classical Age: 500BC-AD500

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A time of cultural development and exchange of ideas, religions, art, science, achievements, and inventions.

Front 11

Greece- Hippocrates (first monist?)

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Health=balance of 4 humours via… blood (Sanguine), yellow bile (Choleric), black bile (Melancholic), brain (phlegmatic). Herbs, temples, spas. Rest (sedatives), restore, rejuvenate

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Roman Empire- Galen

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Shared Hippocrates’ views, plus a special role for just about every organ in body (brain, heart, ventricles). Physicians are gods-separation of western and eastern medicine begins. Precise drug “recipes”, many steps Galen was influential but arrogant

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AD 500-700: Middle Ages

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Little progress. Fall of Roman Empire, terrible diseases (plague). Use of magic, prayer, ritual, amulets, herbs-mandrake to ward off evil/disease. Healing by clergy vs. secular doctors. Best bet-monasteries, cloisters. Result: religion influenced medical practice for years.

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AD 500-700: renaisssance & Reformation

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End of religious. suppression of arts/science. Paracelsus-challenged ideas of Hippocrates and Galen. Age of Reason-advances in math, science, astronomy, philosophy. Trade/exploration brought new meds, goods, ideas, plus disease (Ex.-Crusades).

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Trephination

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Hole in scalp. Evil spirits out of head.

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Paracelsus (16th cent)

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Father of chemical pharmacology. “Boy genius”, Swiss physician, viewed as brilliant but immature. Trained in surgery, medicine, alchemy, worked with minerals, magnets, homeopathy, etc. Prepared tinctures from plants-the 5th essence, said dosage was key, differentiated drug from poison. Went against teachings of H&G and burned books of medical “experts” in class, considered a heretic and banished twice. Hung around with “bad crowd” (witches, gypsies, sorcerers…)

Front 17

Physician vs. Shaman: A Split Evident for much of Recorded History

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Allopathic view-western view, Spiritual/holistic/natural view, now people seeking both in US

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Allopathic view-western view

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Physicians role: diagnose, treat (esp meds). Reactive not preventative. Individual (often impersonal) not community based. Linear not holistic

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Spiritual/holistic/natural view

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Healers, shamans, witches, etc. Preventative not reactive Personal, social, rejuvenating. Multifaceted, complex, holistic.

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Four reasons people use both allopathic and holistic tx

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Chronicity/willing to buy into new approach, seeking help- not just absence of disease, media- has promoted alternative approach, insurance is now covering alter approaches

Front 21

Modern Pharmacology (AD 1800-1900)

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Drugs are scrutinized in labs; Drug discovery, use, abuse;Drugs and mental illness (as treatment of MI, not cause)

Front 22

Drugs are scrutinized in labs

Back 22

Isolation, ID, purification, synthesis; Increased potency/discovery ; Mid-1800s: syringe developed (increase people taking drugs and addiction).

Front 23

Drug discovery, use, abuse

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Opium Wars (China vs. Britain); Morphine (1805) & heroin (1898); Anesthetics, sleep aids, barbiturates; Cocaine isolated (1844)

Front 24

Drugs and mental illness (as treatment of MI, not cause)

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Moreau: Hashish and Mental Alienation; Freud: “Uber Coca”; Pavlov (bromide), James (NO).

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Major Episodes (USA): late1800s & early 1900s

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Temperance movement; first cocaine epidemic; pure food & drug act; harrison Narcotic Act; Marijuana Tax Act; Tobacco Use Unchecked

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Temperance movement (alcohol)

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Key players: Role of women (Carrie A. Nation). Prohibition favoring women, children, patriots, religious people… Against men, sinners. Suffrage movement physically destroyed alcohol. WWI and Prohibition victory. Alcohol was coming from enemies, grains needed for food. Probibition. 18th Amend-1919 (repealed in 1933): repealed because it caused crime, deaths, bath tub gin- potent or use too much, increased consumptoin. Afterwards, still dry/wet states.

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First cocaine epidemic (1885-1920+)

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From harmless tonic to hysteria.

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Pure Food & Drug Act (1906)

Back 28

Labeling.

Front 29

Harrison Narcotic Act (1914)

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Regulation of cocaine and opiates- by prescription.

Front 30

Marijuana Tax Act (1937)

Back 30

Reefer Madness hysteria,“evil weed." Still reflected in our laws/beliefs. Taxing to restrict. Considered classification 1, highest caution. Use increased.

Front 31

Tobacco use unchecked

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Prescribed by docs

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Drug Abuse 1960s

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Heavy drug use/experimentation. Especially hallucinogens, MJ. Triggered research on addiction/tx. Precipitated resarch on drug use and facilities for drug use.

Front 33

Drug abuse- 70s

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Use peaked, then stabilized. War veterens and the middle class junkie. Identifying and classifying drugs, CSA. Addiction and therapeutic potential. War veterens, used it foreign, came back, didn't…

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Drug Abuse: 80s

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1/3 MJ, 1/3 cocaine, 1/3 mixed. Designer drugs. Second cocaine epidemic.

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Drug Abuse: 90s

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Comeback drugs: Ecstasy, heroin. Concern about potent MJ, link to schizophrenia, suicide. Frozen addict: trying to make stronger opiate; side product, less dopamine.Increased use by young: self-medicating.

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Therapeutic Drug Explosion (1950-present)

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Antipsychotics, anti-depressants/antimanics, anxiolytics

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Antipsychotics (1950s+)

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From antihistamines to Thorazine. 1954: 600K to 100K inpatients.

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Antidepressants/antimanics

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1957: MAOis & TCAs; 1959: Lithium (actually 1870!)

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Anxiolytics

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benzodiazepines (1970s-Valium & Librium)

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1980s and 1990s (psychoth..)

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SSRIs et al. New antipsychotics (Clozaril, Risperdal). Pharmaceutical industry: trying for “better drugs” = safer, increased efficacy, more lucrative?

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Enduring favorite drugs, modern time USA

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Nicotine, Alcohol, Caffeine. Legal drugs kill 20-30x as many people as illegal drugs.

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Drug use trends in 21st century

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Recreational drugs: Alcohol, nicotine, caffeine: HIGH. Illegal drugs? Typical approach emphasizes control over education/treatment. DEA: Border patrol/stop trafficking,. incarceration, anti-gang violence (high % prisoners are drug users) The new administration’s approach? Therapeutic drugs: Continued growth of psycho-pharmaceuticals. Genetic prediction of what drugs work best. New routes of administration, personalized drugs, etc. Pragmatics: cost (Medicare mess, Canadian issue, heath care bill?)

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Controlled Substances CSA

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Narcotics (opium, morphine, heroi, etc.); Depressants (benzo's); Stimulants (cocaine, ritalin, etc.); Hallucinogens (LSD, Ectasy, etc); Cannibis. I= most dangerous. Functional clas, Cannibis most dangerous?! Benzo's last?!

Front 44

Ineffective Classifications

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Legal v. Illegal; Abused v. Non-Abused; Therapeutic vs. Non-Therapeutic; Grouped by molecular structure; Groupwed by NT affected; Classified by the synapse affected… All ineffective

Front 45

Functional approach

Back 45

Based on the effects of drugs on the nervous system and behavior. Accounts for most drugs of abuse, recreational drugs, and some therapeutic drugs. Basic four: NS depressants; NS stimulants; Opiates/Analgesics; Hallucinogens/Psychedelics/Psychotherapeutics belong in a separate class.

Front 46

Therapeutic Drugs for Mental & Neurological Disorders

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Treatments for mental disorders: Antipsychotics; Antidepressants; Antimanics; Anxiolytics. Treatments for neurological dis.: Anti-seizure meds; Anti-dementia drugs (AD); Anti-Parkinsonian drugs; Anti-migraine drugs; Anti-MS drugs.

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Misc Categories

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Cognitive enhancers; Food; Herbal; Prescription-approved for other conditions; Performance enhancers; Herbal; Steroids

Front 48

Legal Version: The Controlled Substance Act

Back 48

Schedules determine punishment/fines for possession and trafficking. Det. by med use, abuse potential.

Front 49

Sched. I

Back 49

(no med use, high abuse) Guess what is in this group?

Front 50

Sched. II

Back 50

(med use, high abuse)

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Sched. III

Back 51

(med use, mod abuse)

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Sched. IV

Back 52

(med use, low abuse). Check out the drugs here!

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Sched. V

Back 53

(med use, no abuse)

Front 54

Alternative: UK. See slide

Back 54

Physical criteria (acute, chrnoic, intravenous harm); dependence (intensity of pleasure, psychological dependence, physiological dep); social harm (intoxication, other social harm (ex. Family), health care costs).

Front 55

Personal Harm

Back 55

Drug use. Drug dependence. Drug abuse. Addiction. Toxicity-TD. Fatality-LD vs. ED

Front 56

Harm to others/society

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Family disruption; effects on fetus (Fetal Alcohol Syndrome, tobacco, effects birth process: abruption of placenta, cocaine, withdrawal of baby); link to violence (pharmacological violence, economically compulsive violence, systemic violence)

Front 57

Pharmacological violence

Back 57

Cocaine, meth, alcohol. Drug induced aggression & violence. Not causal, correlated. Person type may lead to taking certain kind of drugs. Not marijuana, opiates, sedatives- except for alcohol.

Front 58

Economically compulsive rage

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Occurs when the person is trying to get the drug.

Front 59

Systemic violence

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Trafficking; gangs.

Front 60

Abstinence

Back 60

"Just say no," Dare; zero tolerance.

Front 61

Harm reduction

Back 61

Goal is to reduce drug use or harmful effects. E.g., provision of clean neddles. Decriminalization?

Front 62

Legalization

Back 62

Access to methadone, med MJ. LEAP: Law enforcement against prohibition.

Front 63

Where do our tax dollars go?

Back 63

Decrease supply-expensive!!! Enforcement side (DOJ). Patrol borders (Mexico and yes, Canada too). Target supply areas (Columbia, Afghanistan, etc). Decrease demand: Severe penalties for drug-use and drug-possession? Drug-related crimes are very common, jails are full, $$$! Scare tactics? (Ads-at end) Prevention via education? Treatment of drug addiction. Very little $ allocated here

Front 64

Tax dollars

Back 64

Mainly to decrease supply, rather than decreasing demand or treatment of drug addiction.

Front 65

Does Rehab Work?

Back 65

If you can afford it (insurance?) If you can find it (programs closing). If you stay in it (revolving door phenomenon). Recovery/rehab is a process not a cure.

Front 66

PDFA Ads

Back 66

The meth ads seem to be similar to culture jamming (a tactic used by consumer social movements to disrupt or subvert mainstream cultural institutions- including corporate advertising…). Seem to be like Calvin Klein ads. They seem to be ineffective, especially in the way that they even try to make the pictures, in some way, visually attractive. Overall, they seem silly!

Front 67

Drug’s Path” through Body: Pharmaceutical phase

Back 67

drug formulation

Front 68

2) Route of administration

Back 68

drug entry; pill vs. liquid (PK- somach, circulatory system, blood to all organs. Muscles, smooth (relaxes) strided (strengthens).

Front 69

3) Absorbtion

Back 69

Through cell membranes of tissues (PK)

Front 70

4) Distribution

Back 70

via blood to body and brain (PK).

Front 71

5) Binding to receptors in target tissues (PD)

Back 71

PD= pharmacodynamic

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6) Biotransformation

Back 72

Inactiviation of the drug (PK)

Front 73

7) Excretion of drug

Back 73

PK; peeing. ** See slide

Front 74

Routes of administration: Oral- pros

Back 74

Easy to do, so patients like it. Economical for pharm companies

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Oral- cons

Back 75

Unpredictable abosrption in GI tract, interacts with food, nausea, destroyed

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IV inj - pro

Back 76

Fast in to circulatory system. Precise dosage using syringe

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IV inj - con

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Can't "recall" dose, OD, allergic rx? Chance of infection.

Front 78

IM inj- pro

Back 78

Moderate to slow release. Depot injections inconvenient.

Front 79

IM inj- con

Back 79

Hurts! Not all drugs can be IM

Front 80

SC Inj- pro

Back 80

Slow release from implants-months! Very easy to do.

Front 81

SC Inj - con

Back 81

May damage skin. May be too slow, incomplete absorbtion.

Front 82

Inhalation pro

Back 82

Fast route to brain (lungs to brain). Large surface area for drug impact.

Front 83

Inhalation con

Back 83

Increases addiction due to above. Damages lung.

Front 84

Transdermal- pro

Back 84

May irritate skin. May be too slow.

Front 85

Mucous mem- pro

Back 85

Fast if near BV's. Multiple sites- intranasal, sublingual, rub on gums, chewing gum, vaginal, rectal.

Front 86

Mucous Mem- con

Back 86

If too much, too fast can be dangerous

Front 87

Absorbtion and Distribution

Back 87

Absorption depends on route of administration. Factors affecting A & D: membranes that drug must cross and how permeable they are. Cell membrane, special barriers: blood brain barrier, placenta. Lipid bilayer, lipid soluable- bbb. Lipid solubility. Ionization of the drug. pH of the body fluids. The PCP sink: illustration of the importance of these factors.

Front 88

Other influences of A & D

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Volume of blood flow to tissue, surface area of tissue.

Front 89

PCP Sink

Back 89

See slide

Front 90

Typical cell membrane

Back 90

Lipid bilayer. Drugs that are lipid soluble can go through the membrane. Possibilities for movement of drugs- diffusion (if lipid soluble)- most common for psychotropic drugs- A. Diffusion through pore size- dep-B. Carrier mediated transport-C. (See slide).

Front 91

Blood brain barrier

Back 91

Special capillaries & astrocytes, selectively permeable. Barrier between blood vessels and brain tissue. Advantages: keeps somethings out of the brain. Disadvantages: sometimes needs to get across, e.g., cancer, psychotropics (increase dose).

Front 92

Placenta is not a barrier

Back 92

Historically viewed as a lifeline and protective filter. Description of mom-fetus interface. 1) Necessarily a place of exchange not a barrier – Exposes vulnerable fetus to many toxic agents/drugs-teratogens. 2) Drug effects during pregnancy: First trimester (severe effects on organs or miscarriage), 2nd trimester (development of brain: schizophrenia and autism), 3rd trimester (oxygen delivery, smaller babies), Drug exposure: labor & nursing.

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Receptors

Back 93

Ionotropic, Metabotropic

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Ionotropic receptors

Back 94

Direct opening of ion channels. Tell you about nature- receptor is protein subunits of ions. Passes trhough.

Front 95

Metabotropic receptors

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Indirect effects on the next cell. Chain of amino acids through the membrane, drug or NT attaches to chain. Causing opening of more channeles (e.g., protein syntehsis). More complicated with downstream receptors, more common. Drugs may affect all or some subset.

Front 96

Function of receptors

Back 96

Ligand (drug/NT) interacts with receptors: affinity (fit: agonist vs. antagonist, both may fit receptor...) and efficacy (action) rec – Dynamic characteristics of rec. are impt. for tolerance, addiction (Unit II) – Silent/depot binding can alter effect (Ex. MJ)… A drug that hides in fat/blood proteins. A drug hides, stays in "system." See slide

Front 97

Biotransformation

Back 97

Liver, etc. metabolizes to active and inactive forms. -First-pass metabolism (oral meds)

Front 98

Biotransformation Phase 1 Metabolism

Back 98

Liver. More ionized and water soluble. Drugs go through this, sometimes Phase II as well. • Oxidation, reduction, hydrolysis (make drug more water soluble, more ionized, go out by fluid; urine) • P-450 enzyme system (non-specific)

Front 99

Biotransformation Phase 2 Metabolism

Back 99

Sometimes drugs go through this, some only go through this. Conjugation of drug with another substance • Usually detoxifies drug • Increases water solubility

Front 100

Biotransformation drug effects on metabolism

Back 100

Enzyme induction, enzyme inhibition, drug competition, genetic varaiation. See slide. Increase enzyme induction (if you have more, break down faster, less drug effect-- tolerance). Enzyme inhibition (if you have less, increase effect of the drug). Alcohol, broken down into intermediary... 40% of Asians, flushing response. Certain enzyme not present. Nicotine- African Americans less affected by nicotine, smoke less- connected to enzymes. Enzyme inhibition due to drugs, food, etc. E.g., MAO and Cheese. Enzyme that breaks down food is the same.

Front 101

Excretion and Drug Clearance: Kidneys

Back 101

Most of the fluid is filtered is reabosrbed (99%). Some leaves as urine w/ metabolites.

Front 102

Excretion and Drug Clearance: Kidneys (Other routes out)

Back 102

Sweat, saliva, lungs, bile, feces. Breast milk! (nursing moms beware)

Front 103

Drug clearance from body

Back 103

Definition of half-life: period of time it takes for 50% of drug to leave the body. Why important, which determines the dosing intervals. Switching drugs (washout, may have to wait like 2 weeks). Note: first-order kinetics (50% drug removed each interval, curve) v. zero-order kinetics (amount removed is constant, 1 drink per hr). See slides.

Front 104

Dose response curves

Back 104

Provides key information: 1) Efficacy (maximum effect), 2) Potency: dose, position on x-axis, 3) Safety: slope, 4) Compare DRCs for desired, side, and lethal effects. Median dose levels: 50 Effective Dose (ED), Toxic Dose (TD50), Lethal Dose (LD50. 50% affected or maximal effect. TD: 50% people getting side effects. 50% people dying.

Front 105

Thereapeutic Index (TI)

Back 105

LD50/ED50 for each drug. TD50/ED50 (humans).

Front 106

Therapeutic Window

Back 106

Index for the estimation of drug dosage which can treat disease effectively while staying withint he safety range (TD50/ED50).

Front 107

TDM

Back 107

compliance and efficacy ck. Monitor drug levels, effectiveness. Therapeutic drug monitoring (Lithium).

Front 108

Drug variability: genetics

Back 108

Asians "flushing," African Americans- Nicotine

Front 109

Age

Back 109

Older/younger more affected

Front 110

Gender

Back 110

Females: more impacted by alcohol, more fat

Front 111

Handedness

Back 111

Left-handed people more affected

Front 112

Drug/diet interactions

Back 112

Bloack metabolism of certain drugs (grapefruit)

Front 113

Placebo affects

Back 113

Psychotropics

Front 114

Environmental conditions

Back 114

Cleanliness of bedding, L/D cycle

Front 115

Neuron

Back 115

Dendrites (receiving), cell body, axon (sending), terminal buttons. Synapse- where most of the psychotropic drug effects occur.

Front 116

Soma: Protein Synthesis

Back 116

Drugs exert their effects on proteins like receptors, chanels, transporters, enzymes. (Some effects on protein synthesis may be mediated by drug modification of transcription factors). Some drugs effect nucleus- by protein synthesis, imp because drugs act on this.

Front 117

Axonal transport

Back 117

NT synthesis may require transport of precursors/enzymes. See slide.

Front 118

Types of channels involved in neural function

Back 118

Ligand-gated channel. Ionotropic receptor: when it opens, ions move through receptor. Fast, local. Ligand= NT, drug- a voltage-gated channel. Action potential: phosphorylation of channel. Is the message of the NT. Deppends on ion channels in the axon. Drugs can affect these channels. E.g., cocaine affects transmission. Downstream effects of NT, drug. Have to have a NT acintg on receptor sites, can open a channel --> can affect next cell. Has more effects, slower, more diffuse. See slide.

Front 119

Excitatory neurotransmitters

Back 119

Bind to receptors opening ligand-gated NA+ channels producing Excitatory postsynaptic potential in postsynaptic neuron.

Front 120

Inhibitory neurotransmitters

Back 120

Bind to receptors opening ligand-gated K+ or Cl- channels producing Inhibatory postsynaptic potential in postsynaptic neuron.

Front 121

Glial cells & Myelin Sheath

Back 121

Drugs affect glial cells. Myelin sheath protects neuron.

Front 122

CNS

Back 122

Brain, spinal cord

Front 123

PNS

Back 123

Somatic NS (sensory, motor, voluntary), Autonomic (internal, organs, involuntary)

Front 124

Review of NS

Back 124

Review slides

Front 125

Synapse

Back 125

Terminal button (pre-synaptic membrane + cleft + dendrite/soma of the next cell (post-synaptic membrane)

Front 126

Drug effects occur at…

Back 126

Multiple sites-presynaptic & postsynaptic receptors, reuptake pumps, enzymes, etc.

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Net effect of drug activity is to

Back 127

increase or decrease the effects of neurotransmitter released at synapse.

Front 128

Presynaptic Phase

Back 128

Movement of vesicles, NTs, precursors, enzymes, etc. via microtubules to TB. Synthesis of NTs and storage in vesicles via vesicle transporters. AP arrives at TB, Ca++ channels open, vesicles move to active zone and “dock." Fusion pore opens &  profile forms. Vesicle membrane merges with TB membrane* Exocytosis/NT diffuses-->post SM.

Front 129

Postsynaptic phase

Back 129

Two major types of receptors on PSM. Ionotropic receptors: directly open ion channels to produce IPSPs or EPSPs. Metabotropic receptors: activate G-proteins to cause changes in PS cell. (Don't memorize... Open ion channels. Have cascade effects via activating 2nd messengers (amplifiers) Ex. Open many ion channels. 2nd mess=cyclic nucleotides (cAMP, cGMP, etc.). Even 3rd messengers! Protein kinases . Various kinase enzymes phosphorylate substrates to cause structural changes. Change gene expression (transcription factors), alter receptor number, affect synthesis & release, play a role in addiction… Note: the NT=the “1st messenger."*)

Front 130

Deactivation and Regulation

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Diffusion into ECF • Reuptake via pumps/transporters – Removes NT from cleft/receptors – May recycle some NTs – Many drugs block reuptake • Glialuptake(ions,NTs...) •Enzymes – AChE for ACh – MAO for monoamines – Second and third messenger enzymes – Many drugs block these enzymes •Regulation is accomplished by autoreceptors

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Drug Mechanisms: Presynaptic

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Synthesis – Provide (limit) precursor – Block synthesizing enzyme • Storage – Block vesicle transporter • Release of NT – Block release (blocks docking proteins-vAMP2) – Increase release (↑ Ca2+ channels)

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Drug Mechanisms: Postsynaptic

Back 132

Postsynapticreceptors – Block receptor: false NT • Antagonist • Examples? – Stimulate receptor: mimic • Agonist • Examples? • Other PS drug effects involve 2nd messenger components (neurogenesis?) – Ex. Lithium, caffeine?

Front 133

Drug Mech: Deactivation, Regulation

Back 133

Enzyme blockers – MAO inhibitors – AChE inhibitors •Reuptake – Block pump/transporter – Increase pump’s activity • Autoreceptors – Block A, “we lack NT”, make more! – Stimulate A, “we have plenty of NT”, stop making/releasing!

Front 134

NT: ACh

Back 134

In Nervous System: Neuro Muscular Junction, Autonomic Nervous System (glands), brain-BFCS (basal forebrain..). Affects normal functioning of: Motor fx, organs, Learning &Memory, REM. Disorders: MG, Alzheimer’s disease. Key drugs: Aricept, nicotine, curare, Botox, nerve gases-Sarin, VX. Receptors: Nicotinic and muscarinic rec

Front 135

NT: DA

Back 135

Where in NS: Nigrostriatal, mesolimbic, mesocortical. Normal functioning: Motor, reward, attention/exec. fx. Disorders: Parkinson’s disease, addiction, AD/HD, schizophrenia. Key drugs: L-DOPA, cocaine, Ritalin, amphetamine, Thorazine. Receptors: D1 type (D5) and D2 type (D3 and D4)

Front 136

NT: NE/NA

Back 136

Where in NS: Sympathetic NS, LC to forebrain, sc, cerebellum. Normal functioning: Fight/flight R-act, arousal, stress, mood, appetite. Disorders: Anxiety, PTSD, depression, BD, eating disorders. Drugs: Anxiolytics Antidepressants, Lithium. Receptors: 1 and 2 rec, 1 and 2 rec

Front 137

NT: S or 5-HT

Back 137

Where in NS: Most in GI, blood; small % in brain-in raphe nuclei Normal Fx: You name it-mood, arousal, sleep, appetite, pain….. Disorders: Depression, anxiety, OCD, PMS, eating disorders, etc. Drugs: SSRIs, BuSpar, LSD, Ecstasy, weight loss drugs. Receptors: At least 15 rec, focus on 5-HT1A and 5-HT2A rec

Front 138

NT: Glutamate

Back 138

Where in NS: Everywhere-esp. CNS. Normal fx: Major excitatory NT of the CNS, L&M, LTP, plasticity, cell death. Disorders: Seizures, strokes, many neurological disorders like AD, PD, ALS-LG dis (excitotoxicity). Drugs: PCP, ketamine, Provigil, Namenda. Receptors: NMDA, kainate & AMPA rec; mGluR1-mGluR8

Front 139

NT: Gaba

Back 139

Where in NS: Everywhere! CNS: brain/ cortex & spinal cord. Normal fx: Major inhibitory NT of the CNS; important in development (w/ glutamate). Disorders: Seizure disorders, anxiety, Huntington’s chorea. Drugs: Benzodiazepines (Valium, Xanax..), anesthetics, barbiturates, alcohol, GHB. Receptors: GABAA and GABAB receptors

Front 140

NT: End. Opiates

Back 140

Where in NS: Spinal cord, limbic system, brain stem. Normal Fx: Analgesia, euphoria, etc. Disorders: Addiction, PTSD, eating disorders, autism, depression…. Drugs: Morphine, heroin, codeine, Oxy & Vic. Receptors: , ,  receptors

Front 141

NT: Nitric Oxide

Back 141

Where in NS: Everywhere! NS, CVS, IS. Unique Fx: Synthesized via NOS when needed, released as gas, retrograde messenger from post-syn cell. Disorders: Excitotoxicity, Addiction, Erectile Dysfunction Disorder. Drugs: NOS inhibitors block excitotox damage, used to treat drug addiction (l-NAME), EDD drugs block NO pathway . Receptors: Linked to NMDA receptor (glut)