Psychopharmacology Exam 4

Inhalants & Herbs, Hormones/Steroids, Psychotherapeutic Medications, Treatment & Prevention

Broad classes of Inhalants

Solvents, Anesthetics

What are inhalants?

Breathable chemicals that produce psychoactive vapors

• Usually: volatile, hydrocarbon, or organic solvents

Inorganic exceptions for inhalants?

• Nitrous oxide (laughing gas)

• Nitrites: amyl, butyl, isopropyl nitrite

Volatile agent classes?

• Glue

• Aerosols: paint, hairspray

• Cleaning agents

• Gases: butane, gasoline

• Solvents: nail polish remover, paint thinner, correction fluid

Main effects of inhalants?

Produce dizziness & euphoria - acutely

Some are “true sedatives”

Who uses/abuses inhalants?

Youth: young males 8-16 years old

20% of youth have experienced by 8th grade

How are inhalants administered?

Huffing: enclosed spaces/rooms

Bagging: spraying into bag and inhaling

Chemical makeup of inhalants?

Most are lipid-soluble

• absorbed rapidly and stays in tissues

Length of effect of inhalants?

Absorbed rapidly, effects are fast and also dissipate fast

Metabolism & Excretion of inhalants?

1. Most through lungs (exhaled)

2. Some via liver and kidneys

3. Complete elimination takes time bc product stays in fatty tissue

What are the effects of Inhalants similar to?

Alcohol, Sedatives, Hypnotics

Behavioral effects of inhalants?

(similar to alcohol)

• low dose = euphoria

• high dose = depressant

• Slurred speech

• Disorientation

• Coughing, Wheezing

• Acute use causes:

  • loss of smell

  • hearing is impacted

• Chronic use leads to:

  • dependence, emotional instability, depression

  • short-term memory loss, damage to brain

  • damage to liver, kidneys

Inhalants Mechanism of Action?

• Enhances GABA - think alcohol as a depressant: GABA is wide inhibitory

• Reduces glutamate at NMDA receptors

• Taken up by myelin white matter: TOXIC

What type of drug is absorbed by myelin white matter?

Inhalants (lipid-soluble)

Toxic effects of inhalants?

• Nervous system

  • Headache, cortical/cerebellar damage

  • Peripheral nerve damage, numbness

  • Parkinson-like syndrome

• Organ damage

• Reproductive damage

• Death: asphyxiation, cardiovascular-related

Date & explanation? - Dietary Supplement Health & Education Act

1994

• Extended definition of supplement beyond vitamins

• Reduced FDA authority to regulate supplements

• Led to increased # of health food shops, grocery, drugstores

Precursor of testosterone in body?

Dehydroepiandrosterone (DHEA)

Ephedra/ Ma Huang

• originally from Asia

• Marketed for: ↑energy, ↓drowsiness, appetite

  • “herbal ecstasy”

Ephedra/Ma huang: side effects on physiology

Sympathomimetic

• ↑heart rate, ↑blood pressure

• insomnia

• short term tremor

Ephedra legality?

Banned by FDA in 2004 after a high-profile death due to ephedra use

Gingko Biloba

Cognitive and learning capacity enhancement - not real evidence

• “the smart drug”

HAS been shown to have effect in:

• early Alzheimer’s patients - helps mitigate some cognitive decline, but not prevention

• Helps: Dizziness, Inflammation, Memory impairment

What is Gingko Biloba rumored to help?

dementia, Alzheimers.

it does not slow cognitive decline in normal adults

Kava

• root is crushed and made into tea

• traditionally used in South Pacific, Fiji

• produces sedative, relaxant effects (like alcohol)

• Marketed to relieve anxiety + stress

Active chemical in Kava?

Kavalactones: enhance GABA transmission

• Causing: drowsiness, blurred vision…

• Too much: GABA agonistic effects - can overdose

Toxicity of Kava

• Faster liver toxicity than alcohol (chronic)

• In this way, riskier than alcohol

What exactly is melatonin (biologically)

Serotonin in the pineal gland

Melatonin

Clock genes stimulate the pineal gland to produce melatonin

• restores normative sleep patterm,

• ↑length of sleep, ↓time to fall asleep

• wrongly advertized to treat heart disease, cancer

Melatonin side effects

Nonrestorative sleep, grogginess, disorientation

Irritability, depressive symptoms (mood changes)

Altered menstrual cycle

Vasoconstriction to heart and brain

St John’s Wort

• Antidepressant properties

• Active chemicals: hypericum, pseudohypericum

  • Thought to block serotonin & norepinephrine reuptake

St John’s Wort side effects

• GI tract irritation, reactions

• May worsen depressive condition when stopped (expectations)

• Serotonin Syndrome: Body temp regulation, etc.

Use of what herb can cause Serotonin Syndrome?

St John’s Wort - because of targeting serotonin reuptake

When is St. John’s Wort effective

effective in treating mild cases of depression eg. seasonal

Ginseng

Drank in tea or chewed root - widespread medicinal use in Asia

Reports are largely anecdotal

• Regulate stress

• Regulate blood pressure

• Combat cancer - no studies support

• Fatigue

Ibogaine

Discovered in Africa, from rootbark of Tabernathe iboga

• Reduces withdrawal and craving symptoms - promising addiction treatment?

  • Acts on serotonergic 2A receptors - LSD-like effect

  • Sigma receptors - novel therapeutic uses

What herb/supplement causes LSD-like effects? Why?

Ibogaine, because of its targeting of serotonergic 2A receptors

3rd Revolution in Pharmacology

Psychotherapeutics

US, Europe, Italy

US alone: 250 million prescriptions in a given year

Psychotherapeutic med use trends

2x higher in women than men - this gap is closing

Use increases with age - increase most dramatic in men

Highest use in individuals who:

• Live alone (agoraphobia?)

• ↑ Education (cognizance?)

• ↑ Income (more likely to seek treatment)

When was the Pre-Chlorpromazine Era

Before development of Chlorpromazine - 1950

Pre-Chlorpromazine Era (pre 1950)

Kraeplin, Pinel, Esquirol and the question: How to categorize?

• Van de Grace Hospital: patients treated w. Chlorpromazine showed:

  • successful anesthetic/subduing agent w/o loss of consciousness

  • rapid worldwide spread

  • reduction in psych cases needing hospitalization

  • Deinstitutionalization

Psychosis vs Neurosis

Psychosis: disorganized thought process + abnormal behavior

Neurosis: Non-psychotic emotional disturbance + abnormal discomfort

Post-Chlorpromazine Era

Advances in antidepressant + antianxiety Rx

• Reserpine used for hypertension (1954), but not as successful

Hormone definition?

Substance released from one type of cell and exerts its influence on another type of cell

• eg. Interstitial fluid to activate other neurons

• BBB to body

Major brain structures involved in producing sex hormones?

Hypothalamus: releases gonadotropin-releasing factor (GnRF)

Pituitary gland: Stimulated by GnRF, releases follicle-stimulating hormone (FSH), lutenizing hormone (LH)

Whats special about bloodflow to pituitary?

Particularly enhanced with blood flow

Female hormones?

Estrogen

Progesterone

State of birth control for women in 1960s?

Too much estrogen and progestin (100-150mg)

State of birth control for women in 1990s

Optimal balance of estrogen & progestin achieved

What is Mifepristone?

Progesterone antagonist - terminates pregnancy

Oral Contraceptives side effects?

Mimic those of early pregnancy

• Nausea, vomitting

• Headaches, dizziness

• Breast discomfort

• Weight gain

May result in depressive phenotypes, change in mood

Oral contraceptives effects on mood?

May cause depressive phenotypes, change in mood

Caveat: for those w/ mood swings on natural cycle, they can help regulate mood

Oral contraceptives biological side effects?

Low dose: risks minimal

High dose: worsens preexisting conditions - Cardiovascular, cancer risk, diabetes, adverse effects on fetus

• increased risk of blood clots —>heart attack, stroke

What are male hormones/steroids used for?

• Delayed puberty

• Burn victims: initiation of healing factors

• Wasting victims: stimulate appetite, maintenance of BW

Who tends to abuse steroids?

• Athletes, bodybuilders

• Muscle Dysmorphia Disorder

they enhance athletic performance and increase muscle mass

Timeline of steroid use and legality in sports?

1960: Use rampant, semi-accepted in sports world

1970: 50-90% of football players were on steroids

1980: Olympic testing begins, US boycotted Olympics

1990: Anabolic Steroid Act: moved to Schedule III drug

Synthetic steroid examples?

Oral: Anadrol, Oxandrin, Dianabol, Winstrol

Injectable: Deca-Durabolin, Durabolin, Depo-Testosterone, Equipoise

Toxic side effects of steroids

• Liver damage (tumors, hepatitis from sharing needles)

• Cardiovascular - ↑Low-density cholesterol

  • LDL leads to ↑blood pressure=↑risk of heart attack and stroke

• Reproductive

  • testicular shrinkage and ↓sperm count

  • women: loss of period

Psychological effects of steroids?

Anhedonia

Irritability/aggression

Depression

Sleep problems, insomnia

Loss of appetite

Premenstrual dysphoric disorder

Effect of steroids on mood?

• too little = depressive

• too much = anxiety, agitation

Effect of steroids on cognition?

• enhances some - working memory, spatial memory

• impairs learning, influences cog. control under stress

Mechanism of action of steroids

Passes bilayer easily —>steroid receptor in cell —>translation of DNA in nucleus

• Alters GABA and Glutamate receptors

Classes of psychotherapeutic drugs?

• antipsychotics

• antidepressants

• antianxiety agents

• mood stabilizers

State of psychotherapeutics in 19th century?

little understanding of psychiatric disorders

no treatments, methods used were cruel

• Kraeplin, Pinel, & Esquirol develop classifications of disorders

• 1840s: Jacques Moreau proposes cannabis as psych treatment

State of psychotherapeutics in 20th century

amphetamines and CO gas used to treat conditions

psychoses treated with antihistamines, insulin shock, psychosurgery

What was discovered in 1949 as a treatment?

John Cade discovered Lithium as a successful treatment of mania in Bipolar

• medical use was approved by 1970

What supports the Dopamine Hypothesis of Schizophrenia?

• Amphetamines trigger psychosis - LSD used as “model psychosis”

  • This is best treated w/ chlorpromazine

  • Chlorpromazine blocks D2 receptors more than norepi, serotonin, etc.

What is NCS-R and its findings?

National Comorbidity Survey Replication - on 9000 adults in US

• ¼ have a diagnosable disorder in a given year

  • ¼ of these are “severe”

• 18% anxiety, 10% mood, 10% impulse control, 15% substance…

• ½ adults meet criteria during lifetime

• less than 50% who need treatment, receive it

Main areas affected by Antipsychotics?

• Reticular activating system: decrease reactivity

• Limbic system: blunt emotional arousal

• Hypothalamus: alter metabolism, alertness, muscle tone

Antipsychotics Side Effects

Extrapyramidal tract: blocks receptors in the basal ganglia

• affects motor coordination and planning

  • Dyskinesia/Akinesia - Parkinsonian syndrome

Tardive Dyskinesia?

involuntary movement of the mouth, tongue, trunk, extremities

• Effect of long-term antipsychotic use - can develop 2+ yrs after

Side effects of Antipsychotics?

a “dirty" drug blocking acetylcholine receptors = biological inactivity

• Dry mouth, dry eyes

• Constipation

• Loss of sexual desire+function

Goals of 2nd Gen Antipsychotics?

• Reduce side effects of phenothiazines, namely tardive dyskinesia

• Additionally reduce less obv symptoms (eg. emotional withdrawal)

How are 2nd gen antipsychotics different from 1st

Reduced affinity for D2, but reduced receptor blockade at NSP = just enough to reduce side effects

2nd generation antipsychotics egs.

Clozapine, Risperadone - non phenothiazines

Even newer antipsychotics (past 2nd gen)

eg. Aripiprazole (Abilify)

• “stabilizes” dopamine, acting as partial agonist - restores dopaminergic tone

Side effects of 2nd gen antipsychotics?

Substantially reduced

• Weight gain

• Agranulocytosis (low white blood cell ct)

• ‘probable’ tardive dyskinesia

What does the antipsychotic Reserpine do?

depletes concentrations of norepinephrine - individuals display depressed appearance

2nd gen antipsychotics egs.

Clozapine, Risperadone

Depression statistics

• 20% of US has depressive episode within lifetime

• 10% have one in a given year

Common symptoms of depression

• Dysphoric mood

• Loss of interest, withdrawal

• Sleep disturbance

• Difficulty concentrating

Order of depression medication through history

1. Stimulants

2. Tricyclics and MAOIs (1950s)

3. 2nd gen (SSRIs, SNRIs, Heterocyclics)

Tricyclics

• One of oldest antidepressants (1950s)

• Block reuptake of multiple NTs (dirty drug) by binding to receptors

Monoamine Oxidase Inhibitors (MAOIs)

• One of oldest antidepressants (1950s)

• Increase # of monoamine NTs available in brain by blocking degradation

Selective Serotonin Reuptake Inhibitors (SSRIs)

• Newer

• Decreased side effects for many people

• Specific targeting for serotonin

SSRI specific side effect

increased risk for bone fractures, decreased hip-bone density in older women

Tricyclic, MAOIs side effects

• Most common: Drowsiness

• Anticholinergic effects: dry mouth, constipation, ↓libido, ↓urination

• Blurred vision, dizziness, weight gain, tachycardia

MAOI side effects

• All same as Tricyclics (drowsy, anticholinergic, adverse effects)

• + Temporary low BP when moving

• Dietary restrictions, can’t pair with tyramine (in cheese, Chianti wine)

Overdose threat for antidepressants?

Major concern for all (cyclics, SSRIs, SNRIs) except MAOIs, for which overdose is not a concern

What are Mood Stabilizers used to treat?

Mania in Bipolar disorder. To a lesser extent, for depression when Lithium fails

Symptoms of Mania?

• Elation

• ↑ Talkativeness

• Flights of ideas

• Racing thoughts

• Grandiosity

• ↓ need for sleep

Typical onset and duration of Mania?

Onset: 20-30 years old

Untreated course: couple months

Lithium

• 1st line treatment for Mania

• Therapeutic properties discovered by John Cade in 1940s

• Approved in the US for treatment in 1970s

Lithium mechanism of action?

Modulates GABA, glutamate, and dopamine

Limitations for Lithium medication

• Diet - high sodium decreases efficacy

• Must be monitored closely - requires consistency

• Doesn’t cross the BBB

Side effects of Lithium?

GI tract: nausea, diarrhea, hand tremor, dry mouth, ↑ urination

• Most side effects stop in a matter of weeks

Safety concerns for Lithium? Toxic effects?

Small therapeutic window: toxic effects are easy to reach

• Toxic effects: Drowsiness, Blurred vision, Ataxia, Confusion, Arrythmia, Seizure, Coma