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Chapter 4

Biological Basis for Understanding

Psychopharmacology

Psychotropic Drugs

Psychiatric illness is related to a number of factors (e.g., genetics, neurodevelopmental factors, drugs, infection, psychosocial experience).

Psychiatric illness results in an alteration in neurotransmitters.

These alterations are the targets of psychotropic drugs.

Psychotropic Drugs (Cont.)

All mental activity has its locus in the brain.

The primary goals of psychiatric mental health nursing is to:

Understand the biological basis of both normal and abnormal brain functions.

Apply this understanding to the care of individuals treated with psychotropic drugs.

Objective 1: Identify at least three major brain structures and eight major brain functions that can be altered by mental illness and psychotropic medications.

Figure 4-1 in text.

Functions of the Brain

Maintenance of homeostasis

Regulation of autonomic nervous system (ANS) and hormones

Control of biological drives and behavior

Cycle of sleep and wakefulness

Circadian rhythms

Conscious mental activity

Memory

Social skills

Objective 2: Describe how evidence-based neuroimaging is helpful in understanding abnormalities of brain function, structure and receptor pharmacology.

Positron-emission tomography (PET) and single-photon emission computed tomography (SPECT)

Localize brain regions associated with perceptual, cognitive, emotional, and behavioral functions.

Provide evidence of metabolic changes in unmedicated individuals with depression, schizophrenia, or obsessive-compulsive disorder (OCD).

Functional magnetic resonance imaging (fMRI)

Demonstrates cognitive function.

Maps effects of psychotropic medications.

Antipsychotic medications are now prescribed at a fraction of the dosages that were once considered standard, in large part because of imaging studies.

PET Scan

Identical Twins (31-year-old men) Note reduced brain activity in frontal lobes of twin with schizophrenia.

Figure 4-4 in text.

Objective 3: Explain the basic process of neurotransmission and synaptic transmission.

An essential feature of neurons is their ability to initiate signals and conduct an electrical impulse from one end of the cell to the other called neurotransmission.

The brain is composed of a vast network of more than 100 billion interconnected nerve cells (neurons) and supporting cells. An essential feature of neurons is their ability to initiate signals and conduct an electrical impulse from one end of the cell to the other called neurotransmission.

Once an electrical impulse reaches the end of a neuron, a neurotransmitter is released, crossing the synapse to attach to receptors on the postsynaptic cell to inhibit or excite it.

Activities of Neurons

Electrical signals within neurons are then converted at synapses into chemical signals through the release of molecules called neurotransmitters, which then elicit electrical signals on the other side of the synapse. Once an electrical impulse reaches the end of a neuron, the neurotransmitter is released from the axon terminal at the presynaptic neuron and diffuses across a synapse to a postsynaptic neuron. Here it attaches to specialized receptors on the cell surface and either inhibits or excites the postsynaptic neuron.

Insufficient Transmission

An insufficient degree of transmission may be caused by a deficient release of neurotransmitters from the presynaptic cell or by a decrease in receptors.

Excessive Transmission

Excessive transmission may be due to excessive release of a transmitter or to increased receptor responsiveness, as occurs in schizophrenia.

A. Normal transmission

B. Deficient neurotransmitter

C. Deficient receptors

Transmission of Neurotransmitters

Figure 4-7 in text.

Destruction of Neurotransmitters

After attaching to a receptor and exerting its influence on the postsynaptic cell, the transmitter separates from the receptor and is destroyed.

First way: Immediate inactivation of the neurotransmitter at the postsynaptic membrane.

Destruction of Neurotransmitters (Cont.)

Second way: After interacting with the postsynaptic receptor, the neurotransmitter is released and taken back to the presynaptic cell. The action is called the reuptake of the neurotransmitter.

Transmission of Neurotransmitters Concept

All activities of the brain involve actions of neurons, neurotransmitters, and receptors. These are the targets of pharmacologic intervention.

Thought disorders such as schizophrenia are physiologically associated with the excess transmission of the neurotransmitter dopamine.

Most psychotropic drugs act by either increasing or decreasing the activity of certain neurotransmitter-receptor systems.

Neurotransmitters (Monoamines)

SEROTONIN Decrease: Depression

Increase: Anxiety states

HISTAMINE High levels associated with anxiety and depression

NOREPINEPHRINE Decrease: Depression

Increase: Anxiety states

DOPAMINE Decrease: Parkinson disease, depression

Increase: Schizophrenia, mania

Neurotransmitters (Amino Acids)

GLUTAMATE:

Is the major mediator of excitatory signals in the central nervous system

Is involved in most aspects of normal brain function, including cognition, memory, and learning

GAMMA-AMINO BUTYRIC ACID (GABA):

Decrease: Anxiety disorders, schizophrenia, mania, Huntington chorea

Increase: Reduction of anxiety, schizophrenia, mania

Neurotransmitters (Cholinergics)

ACETYLCHOLINE:

Increase: Depression

Decrease: Alzheimer disease, Huntington chorea, Parkinson disease

Neurotransmitters (Peptides-Neuromodulators)

Substance P

Regulation of mood and anxiety

Somatostatin

Decrease: Alzheimer disease

Increase: Huntington disease

Neurotensin

Decreased levels in spinal fluid of patients with schizophrenia

Role in pain management

Psychotropic

Drugs

Antianxiety

Hypnotics

Anti-depressants

Alzheimer Agents

Herbal Treatments

ADHD Agents

Anti-psychotics

Anti-convulsants

Mood Stabilizers

Antidepressant Drugs— Monoamine Oxidase Inhibitors

Monoamines: Organic compound, including neurotransmitters that are further divided into subgroups

Catecholamines (e.g., norepinephrine, epinephrine, dopamine)

Indolamines (e.g., serotonin)

Many drugs and food substances

Monoamine oxidase (MAO): Enzyme that destroys monoamines

Monoamine oxidase inhibitors (MAOIs): Drugs that increase concentrations of monoamines by inhibiting the action of MAO

Antidepressant Drugs— Monoamine Oxidase Inhibitors (Cont.)

phenelzine (Nardil)

tranylcypromine (Parnate)

EMSAM (selegiline transdermal system) delivers monoamine oxidase inhibitors (MAOIs) through the skin.

Hypertensive crisis: Occurs if patient ingests tyramine found in some over-the-counter (OTC) medications, beer, wine, aged cheese, organ meats, avocadoes, and other foods (see Slide 25).

Dietary restriction of tyramine must be maintained for 2 weeks after stopping MAOIs.

Objective 4: Explain the relevance of pharmacokinetic and pharmacodynamic drug interactions in the delivery of safe, effective nursing care.

Psychotropic Drug Interactions

Drug interactions alter and modify the effects of psychotropic drugs.

Pharmacokinetic interactions:

Are the effects of drugs on the plasma concentrations of each other.

Pharmacodynamic interactions:

Are the combined effects of drugs.

Objective 5: Discuss the rationale for special dietary and drug restrictions with MAOIs.

Hypertensive crisis: Occurs if patient ingests tyramine found in some OTC medications, beer, wine, aged cheese, organ meats, avocadoes, and other foods (see Slide 23).

Dietary restriction of tyramine must be maintained for 2 weeks after stopping MAOIs.

For a more detailed description of how MAOIs work, visit the Evolve web site at: http://evolve.elsevier.com/Varcarolis/ essentials

Antidepressant Drugs

Tricyclic (cyclic) antidepressants (TCAs): amitriptylene (Elavil), nortriptyline (Pamelor)

Increase norepinephrine.

Side effects include anticholinergic effects.

Selective serotonin reuptake inhibitors (SSRIs): fluoxetine (Prozac), sertraline (Zoloft), paroxetine (Paxil)

Increase serotonin.

Side effects include fewer anticholinergic effects than tricyclic agents; N/V.

Serotonin-norepinephrine reuptake inhibitors (SNRIs): venlafaxine (Effexor), duloxetine (Cymbalta)

Increase serotonin and norepinephrine.

Side effects include fewer anticholinergic effects.

Serotonin-norepinephrine disinhibitors (SNDIs): mirtazapine (Remeron)

Increase serotonin and norepinephrine. Combined with SSRIs to augment efficacy or counteract serotonergic side effects.

NOTE: Because MAOIs block the enzyme that metabolizes monoamines, they may occasionally be used to increase the levels of serotonin and norepinephrine in intractable depression. However, selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) are the more commonly used antidepressants because of the vasopressor effects that occur when MAOIs are combined with other sympathomimetics (amines that stimulate the sympathetic nervous system).

Antidepressant Drugs (Cont.)

Norepinephrine-dopamine reuptake inhibitors (NDRIs): bupropion (Wellbutrin)

Do not act on serotonin system.

Inhibit nicotin acetylcholine receptors to reduce addictive effects.

Serotonin antagonist/reuptake inhibitors (SARIs): trazodone (Desyrel):

Not the first choice for antidepressant treatment, but useful for insomnia. Can cause priapism.

Selective norepinephrine reuptake inhibitors (NRIs): atomoxetine (Strattera):

Treat ADHD when stimulants are not tolerated, but no significant antidepressant benefits.

Antianxiety or Anxiolytic Drugs: Benzodiazepines

Anxiety: diazepam (Valium), clonazepam (Klonopin), alprazolam (Xanax)

Lorazepam (Ativan) and alprazolam (Xanax) reduce anxiety without being as soporific (sleep producing) at lower therapeutic doses.

Insomnia: flurazepam (Dalmane), triazolam (Halcion)

Benzodiazepines promote activity of GABA by binding to a specific receptor on the GABAA receptor complex.

Antianxiety and Hypnotic Drugs: Nonbenzodiazepines

buspirone (Buspar): An anxiolytic agent with less potential for dependence

“Z-hypnotics” (nonbenzodiazepine agents): Short-acting sedative and hypnotic sleep agents

Provide sedative effects without the antianxiety, anticonvulsant, or muscle relaxant effects of benzodiazepines:

zolpidem (Ambien)

zaleplon (Sonata)

eszopiclone (Lunesta)

Melatonin-Receptor Agonist

ramelteon (Rozerem): A hypnotic drug that acts similar to melatonin; is thought to regulate circadian rhythms

Mood Stabilizers

lithium (Eskalith, Lithobid):

Stabilizes depression and mania (bipolar disorder).

Narrows the therapeutic index.

Has a potential for toxicity.

Toxic effects can include tremor, ataxia, confusion, convulsions, and N/V.

Anticonvulsant Mood Stabilizers

valproate (Depakote/Depakene)

Is very effective in managing impulsive aggression.

carbamazepine (Tegretol)

Is administered for acute mania.

lamotrogine (Lamictal)

Is administered for maintenance therapy.

Watch for rash; may indicate Stevens-Johnson syndrome.

Off-Label Mood Stabilizers

oxcarbazepine (Trileptal)

gabapentin (Neurontin)

topiramate (Topamax)

Antipsychotic Drugs/ First-Generation Agents (FGA)

chlorpromazine (Thorazine)

fluphenazine (Prolixin)

haloperidol (Haldol)

Positive Symptoms Schizophrenia

Antipsychotic Drugs/ First-Generation Agents (FGA) (Cont.)

Also called dopamine receptor agonists (DRAs)

Bind to dopamine type 2 (D2) receptors

Reduce dopamine transmission

Extrapyramidal Side Effects and Adverse Reactions

Conventional antipsychotic drugs

Dystonia (muscle stiffness)

Akathisia (restlessness)

Tardive dyskinesia (TD)

Drug-induced parkinsonism

Neuroleptic malignant syndrome (NMS); rare but life-threatening

Orthostatic hypotension

Specific Adverse Reactions

Blocking muscarinic cholinergic receptors

Blurred vision, dry mouth, constipation, and urinary hesitancy

Antagonism of the histamine1 receptors

Sedation and weight gain

Blocking α1 receptors for norepinephrine

Drop in blood pressure, or orthostatic hypotension

Antagonism of either α1 receptors or 5-HT2 receptors

Ejaculatory dysfunction

Blocking muscarinic cholinergic receptors can result in blurred vision, dry mouth, constipation, and urinary hesitancy. Antagonism of the histamine1 receptors causes sedation and weight gain. Blockage at the α1 receptors for norepinephrine can affect vasodilation and a consequent drop in blood pressure, or orthostatic hypotension. Antagonism of either α1 receptors or 5-HT2 receptors may result in ejaculatory dysfunction.

Audience Response Question

Blocking muscarinic cholinergic receptors may result in which one of the following?

Sedation

Weight gain

Blurred vision

Orthostatic hypotension

Answer

Blocking muscarinic cholinergic receptors may result in which one of the following?

Sedation

Weight gain

*C. Blurred vision

Orthostatic hypotension

Audience Response Question

Extrapyramidal side effects are the result of which one of the following?

A. Too much serotonin

B. Dopamine blocking

C. Too little serotonin

D. Too few receptors

Answer

Extrapyramidal side effects are the result of which one of the following?

A. Too much serotonin

*B. Dopamine blocking

C. Too little serotonin

D. Too few receptors

Second-Generation (AGA) Atypical Antipsychotic Drugs

Produce fewer extrapyramidal side effects (EPS)

Target negative and positive symptoms of schizophrenia

clozapine (Clozaril)

risperadone (Risperdal)

quetiapine (Seroquel)

olanzapine (Zyprexa)

iloperidone (Fanapt)

lurasidone HCl (Latuda)

ziprasidone HCl (Geodon)

aripiprazole (Abilify)

paliperidone (Invega)

Adverse effects of receptor blockage of antipsychotic agents

Figure 4-13 in text.

Objective 6: Compare and contrast the side effect profiles of conventional antipsychotic drugs with the side effect profiles of the atypical antipsychotic drugs.

Conventional

EPS:

Dystonic reaction

Akathisia

Drug-induced parkinsonism

Tardive dyskinesia

Orthostatic hypotension

NMS

Atypical

Risk of metabolic syndrome:

Increased weight

Increased blood glucose

Increased triglyceride levels

Insulin resistance

Lower risk of EPS

Objective 7: Identify the main neurotransmitters affected by the following psychotropic drugs and their subgroups (see below):

NOTE: Ask students to identify one neurotransmitter for each group listed here. (Answers in next screen.)

ANTIDEPRESSANT

ANTIANXIETY

SEDATIVE HYPNOTIC

MOOD STABILIZER

ANTIPSYCHOTIC

ANTICHOLINESTERASE

Objective 7: Identify the main neurotransmitters affected by the following psychotropic drugs and their subgroups (see answers below) (Cont.):

ANTIDEPRESSANT: serotonin

ANTIANXIETY: GABA

SEDATIVE HYPNOTIC: histamine

MOOD STABILIZER: norepinephrine

ANTIPSYCHOTIC: dopamine

ANTICHOLINESTERASE: acetylcholine

Objective 8: Discuss the relationship between the immune system and the central nervous system in mental health and mental illness.

Psychoneuroimmunology (PNI)

Research:

Focuses on the relationship between the immune system and central nervous system

Investigates the role in psychiatric disorders

Examples:

Cytokine-induced depression and stress-related disorders

Neuroinflammatory processes

Cognitive deficits in Alzheimer disease

Sleep-wake cycles

Objective 9: Describe how genes and culture affect an individual’s response to psychotropic medication.

Cultural and ethnic beliefs:

Mental illness and pharmacotherapy

Cross-cultural psychopharmacology:

Effects and responses that exist among ethnic groups

Pharmacogenetics:

How genes influence drug metabolism

Audience Response Question

Genetics play which role in response to psychotropic drugs?

Different ethnic groups have different responses.

Genetics are not associated with drug response.

Response to psychotropic drugs may be related to genetics.

Genetics are related to the disease process and not the drug response.

Answer

Genetics play which role in response to psychotropic drugs?

Different ethnic groups have different responses.

Genetics are not associated with drug response.

*C. Response to psychotropic drugs may be related to genetics.

Genetics are related to the disease process and not the drug response.

Audience Response Question

Psychogenetics may one day lead to which of the following? (Select all that apply.)

Personalized medications

Safer drugs

Targeted pharmacologic therapies determined by genetically inherited factors

Increased number of receptors

Answer

Psychogenetics may one day lead to which of the following? (Select all that apply.)

*A. Personalized medications

*B. Safer drugs

*C. Targeted pharmacologic therapies determined by genetically inherited factors

Increased number of receptors

ReceptorNorepinephrine

A Normal

B Deficient neurotransmitter

C Deficient receptor

Dopamine receptorDopamine

A Normal

B Excess neurotransmitter

C Excess receptors

GABA receptor

Benzodiazepine receptorBenzodiazepine

GABA

DopamineDA

Presynaptic cell Postsynaptic cell Dopamine receptor

Antipsychotic drug

DADA