Biological Basis for Understanding Psychotropic Drugs (Chapters 3, 4, & 5)

What are some things that could interact and produce a psychiatric disorder? No matter the cause, what happens to the brain?

• Genetics

• Neurodevelopment factors

• Substances

• Infections

• Traumatic experiences

All interact and can produce a psychiatric disorder. No matter the cause, physical changes in the brain can result in disturbances in the patient’s mood and behavior

What are some of the responsibilities of the brain?

1. Maintenance of homeostasis

2. Regulation of the autonomic nervous system and hormones

3. Control of biological drives and behavior

4. Cycle of sleep and wakefulness

5. Circadian rhythms

6. Conscious mental activity

7. Memory

8. Social skills

Describe how the brain is responsible for the maintenance of homeostasis

• The brain directs and coordinates the body’s response to internal and external changes

• Various sensory organs relay information about the external world to the brain by peripheral nerves (sensations can be altered in psychotic disorders)

• The brain controls skeletal muscles to respond to the external world; including the ability to initiate the contraction of muscles (including the diaphragm)

• The brain also monitors internal functions

• Receives information about blood pressure, body temperature, blood gases, and chemical composition of body fluids

Describe how the brain regulates the autonomic nervous system and hormones.

• The autonomic nervous system and the endocrine system serve as links between the brain and cardiac muscle, smooth muscle, and glands of which the internal organs are composed

• The brain influences internal organs by regulating hormonal secretions of the pituitary gland (master gland) which in turn regulates other glands

• The hypothalamus secretes hormones called releasing factors which act on the pituitary gland to inhibit or stimulate the synthesis and release of pituitary hormones

Describe the hypothalamic pituitary adrenal axis (HPA axis).

1. Hypothalamus secretes corticotropin-releasing hormone (CRH)

2. CRH stimulates the pituitary gland to release adrenocorticotropic hormone

3. Adrenocorticotropin stimulates the cortex of each adrenal gland (located on top of the kidneys) to secrete the stress hormone cortisol

This is done in response to a variety of mental and physical stressors

How does the brain control biological drives and behavior?

• Responsible for basic drives such as sex and hunger

• Disturbances of these drives can be an indication of underlying psychiatric disorders such as depression

How does the brain control the cycle of sleep and wakefulness?

Various regions of the brain regulate and coordinate the entire cycle of sleep and wakefulness

• Sleep pattern disturbances can occur in every psychiatric disorder

• Psychotropic medications may interfere with the normal regulation of sleep and alertness (can cause drowsiness)

What is the circadian rhythm?

Fluctuation of various physiological and behavioral patterns over a 24-hour cycle, which influences:

• Changes in sleep

• Body temperature

• Secretion of hormones such as corticotropin and cortisol

• Secretion of neurotransmitters such as norepinephrine and serotonin

How does the brain control conscious mental activity?

All aspects of conscious mental experience and sense of self orientate in the activity of the brain

• Conscious activity can be stream of consciousness, or can be more complex when applied to problem solving or interpretation

• Can be distorted in psychiatric disorders

How does the brain influence memory?

Memory is the ability to retain and recall past experiences

When is the most common time for men and women to have a psychotic break?

Men: 18-25

Women: 26-32

Describe the composition of the brain and the three main functions:

• Composed of 100 billion neurons

• Neurons are nerve cells that conduct electrical impulses

• 3 main types of physiological actions:

1. Responding to stimuli

2. Conducting electrical impulses

3. Releasing chemicals called neurotransmitters

What is a neurotransmitter? What process are they apart of?

A chemical substance that functions as a neuro-messanger

• Released from the axon terminal of the presynaptic neuron on excitation, then crosses the space (synapse) to the adjacent postsynaptic neuron where it attaches to receptors on the neuron surface

• → This interaction allows the activity of one neuron to influence the activity of other neurons (THIS IS WHAT MEDS TRY TO TARGET!)

What happens after the neurotransmitter attatches to a receptor and exerts its influence on postsynaptic cells? What are the 2 ways that this happens?

Neurotransmitter is destroyed in one of 2 ways:

1. Enzymes: break down the neurotransmitter

2. Reuptake: taken back into the presynaptic cell from which they were originally released

Describe sodium and potassium in relation to neurons

• Inward flow of sodium

• Outward flow of potassium

What are the 3 main properties of neurotransmitters?

1. The chemical must be found in the pre-synaptic vesicles and must be released when the neuron is stimulated

2. The chemical must be inactivated after release (the most common mechanism of action is the re-uptake of the chemical by the pre-synaptic membrane, or the second being destruction by an extracellular enzyme)

3. If the chemical is applied exogenously (through medication) at the post-synaptic membrane, the effect will be the same as when the pre-synaptic neuron is stimulated

Describe the cholinergic neurotransmitter acetylcholine

• Found in the cerebral cortex, hippocampus, limbic structures, and basal ganglia

• More widespread in peripheral NS than CNS

• Involved in sleep, arousal, pain perception, movement and memory

Decrease in acetylcholine can cause what diseases?

• Alzheimers (decrease in acetylcholine-secreting neurons)

• Huntington’s disease

• Parkinson’s

• Myasthenia Gravis (decrease in acetylcholine receptors)

What enzyme eats away at acetylcholine?

Acetylcholinesterase

• Axons normally have slippery outer part, but this is destroyed by the enzyme

• Causes the neurons to stick together and get all twisted up

• Body forgets how to do things because signals aren’t fully sending

Describe the monoamine neurotransmitter norepinephrine

• Found in the thalamus, hypothalamys, limbic system, hippocampus, cerebellum and cerebral cortex

• Influences mood, cognitiion, perception, locomotion, sleep, arousal, cardiovascualr functioning

• Plays a role in anxiety disorders

• Antidepressants block the reuprake of norepinphring into the pre-synaptic cell or inhibit monoamine oxidase from metabolizing it

What disorders are associated with a decrease in norepinephrine?

• Depression

What disorders are associated with an increase in norepinephrine?

• Mania

• Anxiety states

• Schizophrenia

Describe the monoamine neurotransmitter dopamine

• Found in the frontal cortex, limbic system, basal ganglia, thalamus, posterior pituitary and spinal cord

• Involved in the control of complex movements, motivation, cognition, and regulating emotional responses

• Many drugs of abuse (cocaine, amphetamine) cause dopamine release, suggesting a role in what makes things pleasurable *inside the brain, there is a development of more receptors that NEED to be filled = make it hard to come off of them)

Disorders associated with decreased dopamine

• Parkinson’s disease

• Depression

Disorders associated with increased dopamine

Schizophrenia

Mania

Describe the amine neurotransmitter serotonin (5-HT)

• Found in the hypothalamus, thalamus, limbic system, basal ganglia, cerebral cortex, cerebellum, and spinal cord

• Influences sleep and arousal, libido, appetite, mood, aggression, pain perception, coordination, and judgement

• Plays a role in mood and probably delusions, hallycinations and withdeawl of schizophrenia

• Involved in temperature regulation and pain control system

• LSD acts as a serotonin receptor sites

• Anitdepressants block its reuptake at the presynamtic cell

Disorders associated with decreased serotonin

Depression

Describe the amine neurotransmitter melatonin

• Further synthesis of serotonin that is produced in the pineal gland

• Induces pigment lightening effect on skin cells and regulates reproductive function in animals

• Role in humans unclear

• Implicated in the sleep-wake cycle and seasonal affective disorder

What is the most amount of melatonin that a person needs?

0.5 mg!!!!! That’s it!

Describe the neurotransmitter amino acid gamma-aminobutyric acid (GABA)

• Found in the hypothalamus, hippocampus, cortex, basal ganglia, spinal cord and retina

• A major transmitter for post-synaptic inhibition in the CNS

• Involved in the slow down of body activity

• Drugs that increase GABA, such as benzodiazepines, are used to treat anxiety and sleep

Diseases associated with decreased GABA

• Anxiety

• Schizophrenia

• Mania

• Hunington’’s disease

Describe the neurotransmitter amino acid glutamate

• Found in all cells of the body and in the CNS where it si stored in synaptic vesicles and used as a neurotransmitter

• Implicated in schizophrenia and may cause cell death in strokes and Hungington’s disease

Diseases that result from increase in glutamate

• Psychosis

Diseases that result from decrease in glutamate

• Prolonged increased neurotoxic

• Neurodegeneration in Alzheimer’s disease

• Improvement of cognitive performance in behavioral tasks! (which is good!)

• Depression

• Schizophrenia

• PTSD

Describe the peptide neurotransmitters: endorphins and enkephalins

• Distributed in the CNS

• Their effect is generally inhibitory

• The opiates morphine and heroin bind to endorphin and enkephalin receptors on pre-synaptic neurosn, blocking th erelease of neurotransmitters and thus reducing the pain

Describe the peptide neurotransmitter Substance P

• Found in the spinal cord, brain, and sensory neurons associated with pain

• Generally excitatory

• Blocking the release of substance P by morphine, leads to a reduction in pain

• Involved in the regulation of pain and possibly mood and anxiety

Describe the brainstem

• Most primitive area of the brain

• Connects directly to the spinal cord

• Central to the survival of all animals by controlling heart rate, breathing, digestion, and sleeping

• Ascending pathways that prokect to the cerebrum are known as the limbic system

What is the limbic system?

Plays a crucial role in the emotional status and psychological function using norepinephrine, serotonin, and dopamine as its neurotransmitters

Describe the hypothalamus and its function

Small area above the brainstem that plays a vital role in:

• Controlling basic drives, such as hunger, thirst and sex

• Linking higher activities (thought and emotion) to the functioning of internal organs

• Processing sensory information that is then sent to the cerebral cortex

• Regulating the sleep and wakefulness cycle and the ability of the cerebrum to carry out conscious mental activity

Describe the cerebellum and its function

• Located behind the brainstem where the spinal cord meets the brain

• Receives information from the sensory systems, the spinal cord, and other parts of the brain then regulates voluntary motor movements of skeletal muscles

• Plays a crucial role in coordinating contractions so movement is smooth and directed

• Involved in balance and equilibrium

Describe the cerebrum and its function s

• On top of surrounding brainstem

• Responsible for mental activities and a consious sense of being

• Responsible for consious perception of the external world, our body, emotional status, memroy, and control of skeletal muscles

• Responsbble for lanugage and communication

• Surface of the cerebrum is the cerebral cortex, which has 4 major lobes

  • Consicous sesnsation and initiation of movemnt = frontal lobe

  • Sensation of touch = parietla lobe

  • Sounds = temporallobe

  • Vision = occipital lobe

What are the pockets of gray matter deep within the cerebrum?

• Basal ganglia: involved in movement regulation

• Amygdala and hippocampus (part of limbic system): involved in emotions, learning, memory, and basic drives

How can we visualize the brain?

Structured imaging techniques

• Computed tomography (CT)

• Magnetic resonance imaging (MRI)

Functional imaging techniques

• Positron emission tomography (PET)

• Single photon emission computer tomography (SPECT)

What does pharmacodynamics refer to?

Biological and physiological effects of the drug on the body

• Drug action

• Responses

*Dose related!

What does pharmacokinetics refer to?

Movement of a drug through the body (actions of the body on the drug!) ADME

• Absorption

• Distribution (how it’s distributed through the body)

• Metabolism (liver transformation)

• Excretion (kidney excretion)

*Also includes the half-life and dosing of medications

Benzodiazepines

Anti-anxiety and hypnotic medications

• GABA is the major inhibitory (calming) neurotransmitter in the CNS

• Benzos promote the activity if GABA

• Possess anti-anxiety, hypnotic (sleep inducing, anticonvulsant, amnestic (loss of memory) and muscle relaxant properties

5 examples of Benzodiazepines

“-PAM”

1. Diazepam (Valium)

2. Clonazepam (Klonopin)

3. Alprazolam (Xanax)

4. Loreazepam (Ativa)

5. Temazepam (Restoril) - helps with sleep!

What is important to remember about benzodiazepines?

• High risk for addiction

• Short term use only to calm down

• Do not use for more than 2 weeks

Side effects of benzodiazepines

• Sedation

• Ataxia

• Anterograde amnesia

• If combined with other CNS depressants, can cause respiratory depression and death

Z-Hypnotics

Short-Acting Sedative-Hypnotic Sleep Agents

• Selectivity for GABA receptors

• Possess hypnptic and amnestic effects without the antianxiety, anticonvulsant, or muscle relaxant effects of benzodiazepines

Examples of Z-hypnotics

• Zolpidem (Ambien)

• Zalepon (Sonata)

• Eszopiclone (Lunesta)

What is important to remember about Z-hypnoics?

• Controlled substances but less tolerance and dependence than benzodiazepines

• Short half lives and no active metabolites compared to benzodiazepines

• Start dosage low then slowly increase for best effect

Side effects of z-hypnotics

• Bitter taste upon awakening

• Complex sleep-related behaviors (sleepwalking, driving, cooking, etc)

• CNS depressant use can increase side effects

Melatonin receptor agonists

Anti-anxiety and Hypnotic drugs (relax and sleep)

• Melatonin is a naturally excreted hormone by the pineal gland at night as part of the normal circadian rhythm

Examples of melatonin receptor agonists

• Ramelteon (Rozerem) is a melatonin receptor agonist and acts similar to endogenous melatonin

Buspirone

• Treatment of generalized anxiey disorder

• Side effects: dizziness, headache, nausea

• Buspirone (BuSpar): people want fast results, but takes 2-3 weeks for it to work; people won’t get addicted!

• Best anti-anxiety med because the least amount of side effects

Doxepin

• Doxepin (Silenor) is the low dose formulation of a tricyclic antidepressant (TCA)

• Approved for insomnia characterized by difficulty falling alssep

• DO NOT TAKE IF ON A MONOAMINE OXIDASE INHIBITOR

Orexin Receptor Antagonists

• Orexins (neuropeptide procied in the hypothalamis) promote wakefulness

• Suvorexant (Belsomra) and Lemborexant (Daybigo) are orexin receptor antagonists

• Used for insomnia

• CONTRAINDICATEDIN NARCLEPSY

• Controlled substance

What are the irst line drugs for longterm treatment of anxiety and depression disorders

Antidepressant medications, NOT benzodiazepines (these should be short term only)

How do SSRIs work?

Selective Serotonin Reuptake Inhibitors

• Block the reuptake of serotonin by makign the meurotransmitter availabel in synapse

• Examples:

  • Fluoxetine (Prozac) - people will take this for a long time, then it will stop working

  • Sertaline (Zoloft)

  • Paroxetine (Paxil)

  • Citlopram (Celexa)

  • Escitlopram (Lexapro)

  • Fluvoxamne (Luvox)

BOLDED MEDS ARE BEST ONES! BUT MOST EXPENSIVE

First line medications for treatment of major depressive disorder and anxiety disorders

Common side effects: nausea, restlessness, jitterieness, sleep disturbances, sexual dysfinction

What are the most common side effect of psychotropic medications:

• Nausea

• Vomiting

• Weight gain

• Low libido

• Dizziness

• Constipation

• Blurred vision

Norepinephrine and Serotonin Specific Antidepressants

• Mirtaxapine (Remeron)

• Engnaces norepinpehrine and serotonin neurotransmission

• Side effects: sedation, appetite stimulation, weight gain

• Commonly given for insomnia

Serotonin-norepinephrine reuptake inhibitors

• Increase both serotonin and norepinephirine in the synapse by reuptake

• Venlafaxine (Effexor)

• Desvenlafaxine (Pristiq)

• Duloxetine (Cymbalata)

• Levomilnacipran (Fetzima)

• Treatment of major depssive disorder and anxiety disorders

• More likely to ause sweating

• Dose depednet increased in BP and hR due to norepinephine reuptake blockade - MONITOR BP AND HR!!!

• Pain reduction

Monoamine Oxidase Inhibitors

• Class of antidepressants that are rarely used today

• Last-line agents

• Phenelzine (Nardil)

• Isocarboxazid (Marplan)

• Tranylcypromine (Parnate)

• Selegiline (Emsam)

Metabolized monoamines, including serotonin, norepinpehinr, and dopamine → Inhibit MAO, and increase synaptic levels of these neurotransmitters → antidepressant effects

What medications should be avoided if a patient is taking an MAOI?

SSRI & Busprione & Psychostimulants

Can lead to serotonin syndrome!!!!!!! Patient will become vasoconstrictive → HIGHER BLOOD PRESSURE BAD CAN DIE BC OF HYPETENSIVE CIRSIS

What food should someone taking an MAOI not consume?

• Tyramine in protein-based foods: aged cheeses, pickled or smoked fish, wine ALL BAD!!!

What is the gold standard mood stabilizer for bipolar disorder?

Lithium

• Narrow therapeutic index

• Must monitor levels regularly

• Dehydration, med interactions, decreased renal function can all increase lithium levels

What are some anticonvulsant medications that are also mood stablizers?

• Carbamazepine (Tegretol, Equetro): second line agent for manic or mized episodes

• Lamotrigine (Lamictal): maintencance therapy for bippoalr disprder, used for bipolar depression

• Valproate (Depakote): manic episodes with biplar disorder, useful for rapid cycling

Anticonvilsant properites derive from the lareration of electrical conductivity in menbranes

First generation antipsychotics

• Strong antagonists (blocking agents)

• Bind to D2 receptors

• Block attatchement of dopamine

• Reduce dopaminergic transmission

Agnists of receptors for:

• Acetylcholine

• Norepinephrine

• Histamine

Second generation antipsychotics

• Bind to dopamine receptors in the limbic system

• Preferntially over dopamine receptors in neostrital areas of the basal ganglia

• Decreased motor side effects

• Target both the psotive nd negative symptoms of schizophrenia

• Antangoisnts for serotninin and dpaine receeptors

Common second-generation antipsychotic drugs

• Clozapine (Clozaril)

• Risperidone (Risperdal)

• Olanzapine (Zyprexa)

• Ziprasidone (Geodon)

• Aripiprazole (Abilify) - MOST COMMON

• Paliperidone (Invega)

Medication treatment for Alzheimer’s disease

• Prevent or slow strucutral degeneration

• Cholinestease inhibitors slwo the rate of memory loss

• NMDA receptor agntagnonists

• Examples:

  • Tacrine (Cognex)

  • Donepezil (Aricept)

  • Galantamaine (Razadyne)

  • Revastigmine (Exelon)

  • Memantine (Namenda)

Medication treatment for attention-deficit.hyperactivity disorder

• Psychostimulants are first line treatment

• Sympathomimetic amines that act by blocking the reuptake of norepinephrine and dopamine

• Examples:

  • Methylphenidate (Ritalin)

  • Dextrosmphetamine (Adderall)

  • Atomoxetine hydrochloride (Strattera)

Major concerns of herbal medicine

Potential long-term effects

• Nerve damage

• Kidney damage

• Liver damage

• Possibility of adverse chemical reactions with other substances and conventional medications

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CORRECT ANSWER: D

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CORRECT ANSWER: D

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Name and describe six functions of the brain

1. Circadian rhythm: regulating sleep and wake cycle

2. Motor functioning: regulate skeletal muscle coordination and contraction

3. Vital functioning: heart rate, respirations, blood pressure

4. Emotions, learning, memory

5. Basic drives and regulates hormones

6. Cognitive functioning

What is a neurotransmitter?

A chemical substance that functions as a neuromessenger, interacts with other neurons to release chemicals and conduct electrical impulses, and respond to stimuli.

How does the neurotransmitter dopamine affect mental illness?

Dopamine: Involved with the integration of emotions and thoughts. Involved in decision making.

• Decrease → Parkinson’s and depression

• Increase → mania and schizophrenia

How does the neurotransmitter serotonin affect mental illness?

Serotonin: Involved in sleep regulation, hunger, mood states, pain perception, aggression, and sexual behavior

• Decrease → depression

• Increase → serotonin syndrome

Give two examples of SSRIs. When are they used? What are some of the side effects?

1. Lexapro: used to treat depression and generalized anxiety

   • Side effects: GI upset, weight gain, decreased libido, constipation

2. Zoloft: used to treat depression and generalized anxiety

   • Side effects: dry mouth, weight gain, decreased libido

Describe mood stabilizers.

Class of drugs used to treat symptoms associated with bipolar disorder.

What are two examples of mood stabilizers, and when are they used?

1. Lithium: for bipolar disorder

2. Seroquel: for mood stabilizer and anti-psychotic

Describe first and second-generation antipsychotics. What are their side effects?

• First generation: decrease dopamine activity in CNS; reduce positive symptoms - have more side effects than second generation!

• Second generation: dopamine and serotonin antagonists - reduces positive and negative symptoms - fewer and better-tolerated side effects!

A nurse administers a medication that potentiates the action of GABA. What effect would you expect?

a. reduced anxiety

b. improved memory

c. more organized thinking

d. fewer sensory perceptual alterations

Correct answer: A!!

GABA receptors = related to anxiety!!!

What is a possible side effect of Buspirone?

Dizziness

If psychotropic drug block muscarinic receptors, what will the patient complain of?

• Dry mouth

• Blurred vision

• Urinary retention

• Constipation

• Tachycardia