Principles of Psychopharmacology

What are part of the agonist spectrum ranging from agonist to inverse agonist?

1. Agonist

2. Partial agonist

3. Antagonist

4. Partial inverse agonist

5. Inverse agonist

1. What do agonists do?

1. Fully open the ion channel

2. Stabilizes the active form of receptor

1. What do antagonists do?

1. Retain the resting state between open and closed states

2. By itself can make no change

   1. With agonist of inverse agonist can stop those effects

1. What do inverse agonists do?

1. Close the ion channel

2. Stabilizes the inactive form 

   1. Or shuts down active receptors

3. Does opposite of agonist 

1. What are partial agonists?

1. Partially open the ion channel

2. Not a good stabilizer

1. What are partial inverse agonists?

1. Partially close the ion channel

What can return the ion channel to the resting state in each instance?

Antagonists which can block anything in the agonist spectrum

1. What do the agonist and inverse agonist do to each other?

1. Compete based on concentration and affinity

1. What do agonists and partial agonists do to each other?

1. Partial agonist will act as antagonist to take agonist to partiality

1. Why would partial agonist be favored over antagonist?

1. The function of the receptor might be necessary but levels needs to be lower but not 0

2. Also to prevent the danger of upregulation of receptors that is caused by antagonist

Neurotransmitters have multiple ______________ that interact for drug specificity.

1. Receptor subtypes

1. The most selective drugs are capable of ___________ the natural neurotransmitter’s action at just one receptor lock.

1. Mimic

1. Each drug is selective for a ________ of the neurotransmitter receptors.

1. Different single subtype

1. When a neurotransmitter binds to receptors making up an ion channel, the channel opens. However, what occurs when both the neurotransmitter and a second chemical are bound to the receptor (allosteric modulator)?

1. The channel opens further allowing more ions into the cell

1. Where does the allosteric modulator bind?

1. Not on the active site

What is an example of a positive allosteric modulator?

1. Alcohol 

   1. Binds to GABA receptor 

   2. Increases affect on amygdala

1. What are included in the principles of psychopharmacology?

1. Pharmacokinetics

2. Drug effectiveness

3. Effects on repeated administration

4. Placebo effects

1. What is psychopharmacology?

1. The study of the effects of drugs on the nervous system and on the behavior

1. What is the drug effect?

1. The changes a drug produces in an animal’s physiological processes and behavior

1. What are the sites of action?

1. The locations at which molecules of drugs interact with molecules located on or in cells of the body, thus affecting some biochemical processes of these cells

1. What is pharmacokinetics?

1. The process by which drugs are absorbed, distributed within the body, metabolized, and excreted

1. What are some routes of administering drugs?

1. Intravenous (IV) 

2. Intraperitoneal (IP)

3. Intramuscular (IM)

4. Subcutaneous (SC)

5. Oral 

6. Sublingual

7. Intrarectal 

8. Inhalation

9. Insufflation

10. Topical

11. Intracerebral 

12. Intracerebroventricular (IVC)

1. Describe intravenous (IV) injection as a route of administration.

1. Injection of a substance directly into a vein

1. Describe Intraperitoneal (IP) injection as a route of administration.

1. injection of a substance into the peritoneal cavity- the space that surrounds the stomach, intestines, lives, and other abdominal organs

   1. Relatively fast (area next to blood vessels)

   2. Can cause cramping

1. Describe Intramuscular (IM) injection as a route of administration.

1. Injection of a substance into a muscle

1. Describe Subcutaneous (SC) injection as a route of administration.

1. Injection of a substance into the space beneath the skin

   1. Not as fast as IV

   2. Where a lot of blood supply

1. Describe oral administration as a route of administration.

1. Administration of a substance into the mouth, so that is swallowed

   1. Most common

   2. Safer, doesn’t need to be sterile

   3. Needs to be able to sustain acidity of stomach

1. Describe sublingual administration as a route of administration.

1. Administration of a substance by placing it beneath the tongue

   1. Doesn’t need to sustain acidity

1. Describe intrarectal administration as a route of administration.

1. Administration of a substance into the rectum

   1. Drugs meant for rectum because drug or disease causes vomiting and can sustain acidity 

1. Describe inhalation as a route of administration.

1. Administration of vaporous substance into lungs

   1. Relatively safe

   2. Full of blood vessels

1. Describe Insufflation as a route of administration.

1. Administration of powdered drugs into the mucous membrane of the nasal passages

   1. One of the fastest

   2. Used when taking crack

1. Describe topical administration as a route of administration.

1. Administration of a substance directly onto the skin or mucous membrane

   1. Partial and slow

1. Describe intracerebral administration as a route of administration.

1. Administration of a substance directly into the brain

   1. Least safest

   2. For drugs that don’t pass the BBB

Describe intracerebroventricular (IVC) administration as a route of administration.

1. Administration of a substance into one of the cerebral ventricles

1. How are drugs slowly distributed within the body and helpes to maintain the NTs composition from metabolism?

1. Depot binding

2. Albumin

1. What is depot binding

1. Binding of a drug with various tissues of the body or with proteins in the blood

   1. When drugs are bound, they are protected from metabolism (slower)

What is albumin?

1. A protein found in the blood; serves to transport free fatty acids and can bind with some lipid-soluble drugs

1. When does inactivation of a drug occur?

1. When metabolized

1. When does excretion of a drug occur?

1. Drug goes into body then gets metabolized (drug can sometimes be active still or become more active) and gets to to half-life of 50%

1. What does cytochrome P450 Superfamily (CYP) do?

1. Mediates how the body metabolites drugs

2. The CYP enzyme in the gut wall converts the drug into a biotransformed product in the bloodstream. After passing through the gut wall and liver, the drug will exist partly as unchanged drug and partly as transformed drug

3. Metabolizes alcohol

   1. Increased levels in males 

4. Carries 3 allele

   1. Individualized half life of drug

      1. Important for dosing

1. How is drug effectiveness determined?

1. Dose response curve

2. Affinity

1. What is the dose-response curve?

1. A graph of the magnitude of an effect of a drug as a function of the amount of drug administration

1. What is affinity

1. The readiness with which two molecules join together

1. What is the therapeutic index?

1. The ratio between the dose that produces the desired effect in 50% of the animals and the dose that produces toxic effects in 50% of the animals

1. What are the effects of repeated administration?

1. Tolerance

2. Sensitization

3. Withdrawal symptoms

1. What is tolerance?

1. A decrease in the effectiveness of a drug that is administered repeatedly

1. What is sensitization?

1. An increase in the effectiveness of a drug that is administered repeatedly

1. What are withdrawal symptoms?

1. The appearance of symptoms opposite to those produced by a drug when the drug is administered repeatedly and then suddenly no longer taken

1. What is the placebo effect?

1. An inert substance that is given to an organism in lieu of a physiologically active drug; used experimentally to control for the effects of mere administration of a drug

What is penetration?

1. The statistical term for the percentage of people/animals that have the gene and have disease?

1. How does penetration occur?

1. 1st abnormal gene

2. Then abnormal gene product

3. Then inherited disease

1. What does 100% penetration mean?

1. 100% will develop the inherited disease 

   1. Classical autosomal dominant pattern

1. Psychiatric disorders are developed via multiple genes that are considered …?

1. Risk factors

1. What would be some things that a hypothetical gene for a subtle molecular abnormality can affect?

1. Selection

   1. Migration

   2. Differentiation

   3. Synaotogenesis

2. Enzymes for monoamine degradation

3. Serotonin transporter

4. Signal transduction pathway

5. Synaptic plasticity machinery

6. Axonal and dendritic protein synthesis and internal transport

1. What is the hypothetical path from gene to behavior?

1. Genotype

2. Subtle molecular abnormality

3. Abnormal information processing

   1. Biological endophenotype

4. Behavior with complex functional interactions and emergent phenomena

   1. Symptom endophenotype

1. What are the properties of endophenotypes

1. Associated with illness in the population

2. Heritable

3. Primarily state-independent

   1. Manifests in an individual whether or not illness is active

4. Within families, endophenotype and illness co-segregate. Subsequently, an additional criterion that may be useful for identifying endophenotypes of disease that display complex inheritance patterns were suggested

5. Found in affected family members is found in nonaffected family members at a higher rate than in the general population

1. Describe when a gene is activated.

1. Gene activating which eventually gives acetyl group

   1. Histone acetyl transferase

   2. DNA demethylase

   3. Histone demethylase

2. DNA is not tightly packed; thus, transcription factors are able to access DNA

3. Translated to mRNA

   1. Which created gene product

4. Gene is activated

1. Describe gene silencing.

1. After gene activating

   1. Histone acetyl transferase

   2. DNA demythlase

   3. Histone demethylase

2. Transcription accesses loosely packed DNA

3. Gene silencing

   1. Histone deacetylase

   2. DNMT

   3. Histone methyltransferase

4. Then L-MF which eventually gives methyl groups 

   1. SAMe

   2. Me

   3. DNMT

5. Coils the DNA closer together to 

Which part of the stress diathesis has no gene and has normal function?

Stress Diathesis Model Part 1

Which part of the stress diathesis has one risk gene and normal function?

Stress diathesis part 2

Which part of the stress diathesis has two risk genes, slowing of function by compensation and no breakdown?

Stress Diathesis part 3

Which part of the stress diathesis has multiple risk genes, slowing of function with mild stressor, but decompensation and breakdown with severe stressor?

Stress Diathesis part 4

What might take only relatively minor or usual stressors for the set of __________ vulnerability genes of a vulnerable individual to be activated into producing a disease.

Schizophrenia

Since fewer individuals with postulated genetic potential for depression or bipolar disorder may actually, it may take ___________ for the vulnerable individual to have his or her set of bipolar disorder vulnerability genes activated into producing a disease.

Moderate or more unusual stressors

Even those with apparently normal DNA, with no known predisposition to any given psychiatric disorder, may decompensate under _________________ (such as rape or combat or natural disasters) to produce a breakdown of cellular functioning through the breakdown of normal DNA to produce yet other psychiatric disorders.

Major or overwhelming stressors

What is behavioral neuroscience

The study of the brian and neuronal functioning

1. What is the approach used in behavioral neuroscience?

1. Studies using experimental animals

2. Use of drugs to probe neurobiological and molecular regulatory mechanisms

1. What are the recent findings in behavioral neuroscience relevant to pharmacology?

1. Discovery of neurotransmitters and their enzymes and receptors

2. Principles of neurotransmission

3. Genetic and molecular regulation of neuronal functioning

4. Neurobiological regulation of animal behaviors

1. What is biological psychiatry?

1. The study of abnormalities in brian neurobiology associated with the causes or consequences of mental illness

1. What is the approach of biological psychiatry?

1. Studies using patients with psychiatric disorders

2. Taking direction from psychopharmacological studies indicating that drugs with known mechanisms of action on receptors or enzymes predictably alter symptoms in a specific psychiatric disorder

3. Search for abnormalities in receptors, enzymes, neurotransmitters, genes, or gene products that correlate with the diagnosis of particular mental illness

4. Biochemical measurements using blood, urine, cerebrospinal fluid, peripheral tissues such as platelets or lymphocytes, postmortem brain tissues, or plasma hormones after provoking hormone secretion by drugs

5. Measurements of structural abnormalities using CT or MRI brain scans

6. Measurements of functional or physiological abnormalities using PET, EEG, evoked potentials or magnetoenecephalogrpahy

1. What are the findings in biological psychiatry relevant to biological psychiatry?

1. Few strong biological findings demonstrating lesions in specific psychiatric disorders

   1. Example

      1. Discovery of changes in serotonin receptors and metabolites in depression schizophrenia, and suicidal behavior

   2. Search for the genetic basis of specific neurological and psychiatric illnesses

1. What is psychopharmacology?

1. The use of drugs to treat symptoms of mental illness

2. The science of drug recovery, targeting enzymes and receptors

1. What is the approach to psychopharmacology?

1. Studies in patients with psychiatric disorders

2. Serendipitous clinical observations

3. In clinical investigations, the use of drugs with known mechanisms of action to provoke biological or behavioral response that would provide clues where abnormalities in brain functioning may exist in specific psychiatric disorders

4. In drug discovery, theory-driven targeting of enzymes and receptors hypothesized to regulate symptoms in a psychiatric disorder

1. What are the psychopharmacological results?

1. In clinical investigations, the first observation is often a serendipitous discovery of clinical efficacy, after which the biochemical mechanisms of action is discovered

2. In drug discovery, specific enzymes or receptors are first targeted for drug action. The earliest experiments use chemistry to synthesize drugs; experimental animals to test the biochemical, behavioral, and toxic actions of the drugs; and human subjects, both normal volunteers and patients, to test the safety and efficacy of the drugs

3. Discovery and use of antidepressants, anxiolytics, antipsychotics, and cognitive enhancers as well as drugs of abuse