Psychopharmacology

Excitatory Neurotransmitters

• Dopamine

• Norepinephrine

• Epinephrine

• Acetylcholine

• Glutamate

Inhibitory neurotransmitters

• Serotonin

• Gamma-Aminobutyric Acid (GABA)

GABA

Counterpart of glutamate

Modulating Neurotransmitters

• histamine

• Neuropeptides

Dopamine

Controls complex movements, motivation, cognition; regulates emotional response

Norepinephrine

Causes changes in attention, learning and memory, sleep and wakefulness, mood

Epinephrine

Controls fight-or-flight response

Acetylcholine (ACH)

Also inhibitory NT, controls sleep and wakefulness cycle; signals muscles to become alert

Glutamate

Most abundant excitatory. Results in neurotoxicity if levels are too high

<10%

The drug is considered significant lowness potently after 4 half-lifes

Serotonin

Controls food intake, sleep and wakefulness, temperature regulation, pain control, sexual behaviors, regulations of emotions

Gamma-Aminobutyric Acid (GABA)

Most common Inhibitory. Modulates other neurotransmitters. Controls mood, anxiety and muscle spasticity

Anxiolytics

All drugs except ___ takes months for the effects. Side effects are first before therapeutic effects

Lowest dosage

Dosage of the medication is adjusted effective for the client

Histamine

Controls alertness, gastric secretions, cardiac stimulation, peripheral allergic responses

Neuropeptides

Enhance, prolong, inhibit, or limit the effects of principal neurotransmitters

Drug efficacy

Maximal therapeutic effect that can be achieved by a drug

Drug potency

Amount of drug needed to achieve that maximum effect

Half life

Amount of time it takes for half of the drug to be removed from the bloodstream

Tapering

Decreasing gradually to avoid rebound and withdrawal symptoms

Antipsychotic

• aka Neuroleptics

• Symptoms of psychosis, such as delusions and hallucinations

• M.O.A. Blocking the receptors of the neurotransmitter dopamine

1st Generation / typical / conventional / older

• dopamine antagonist

• For positive symptoms

2nd generation / atypical / modern / newer

• dopamine antagonist and serotonin reuptake inhibitors

• For positive and negative symptoms

3rd generation / atypical / modern / newer

• dopamine stabilizers

• Same as 2nd gen but fewer s/e

• Best indicated if with mood disorder

Novel / 4th Gen

• reduce dopamine production by reduction ACH production (positive sx)

• Increase in GABA, and decrease in Glutamate (negative sx)

Extrapyramidal Symptoms (EPS)

• Side effects of antipsychotic drugs (APAT, in order)

  • Acute dystonia

  • Pseudoparkinsonism

  • Akathisia

  • Tardive Dyskinesia

Acute dystonia

Acute muscular rigidity and cramping

• Torticollis

• Opisthotonus

• Oculogyric crisis

• A stiff or thick tongue with difficulty of swallowing

• In severe cases, laryngospasm and respiratory difficulties

Anticholinergic (Benztropine) IM

Diphenhydramine IM/IV

Medication for acute dystonia

Tortocollis

Neck deviation

Opisthotonus

Arching of back

Oculogyric crisis

Eyes rolling back

Pseudo Parkinsonism

– A stiff, stooped posture

– Masklike facies

– Decreased arm swing

– A shuffling gait (with small steps)

– Drooling

– Tremor

– Bradycardia

– Pill-rolling movements of the thumb and fingers while at rest

Anticholinergic (Amantadine) PO

Antidote of Pseudo Parkinsonism

Akathisia

• intense need to move about

• Appears restless or anxious and agitated, often with a rigid posture or gait and a lack of spontaneous gestures

• This feeling of internal restlessness and the inability to sit still or rest often leads clients to discontinue their antipsychotic medication

Beta-blockers (Propanolol)

Anticholinergics

Benzodiazepine

Antidote of akathisia

Tardive Dyskinesia

• Most commonly caused by the long-term use of typical antipsychotics

• Irreversible once developed

  • Involuntary movements of the tongue, facial and neck muscles, upper and lower extremities, and truncal musculature

  • Tongue-thrusting and protrusion, lipsmacking, blinking, grimacing and other excessive, unnecessary facial movements

Vesicular monoamine transporter 2 inhibitors (Valbenazine)

Antidote of tardive dyskinesia

Metabolic Syndrome

Caused by 2nd generation antipsychotic drugs

• obesity

• Hyperglycemia

• BP increase

• Cholesterol Increase

Lifestyle changes

Solution to metabolic syndrome

Agranulocytosis

Caused by Clozapine (antipsychotic drugs)

• WOF: signs of infection

• Monitor: WBC count

Dysrhythmias or cardiac arrest

Caused by Thioridazine or Mesoridazine

• WOF: Tachycardia

• Monitor: ECG QT Intervals

Neuroleptic Malignant Syndrome (NMS)

Emergency

• potentially fatal, idiosyncratic reaction to an antipsychotic drugs. Autonomic instability:

  • Unstable BP

  • Diaphoresis

  • Pallor

  • Delirium

  • Elevated CPK

• Due to constant constriction of muscle → breakdown (creatine phosphokinase) → increased temp, dilated blood vessels (water leaves plasma) → decreased volume → decreased bp

IV Fluids and electrolytes; Paracetamol

• Intervention for Neuroleptic Malignant Syndrome

Calorie-free beverages and candy. Avoid calorie-laden

For dry mouth due to anticholinergic side effects of EPS medication

• Increase exercise

• Water intake

• Bulk-forming foods

• Stool softeners

• Avoid Laxatives (may cause Dysrhythmias)

For constipation due to anticholinergic side effects of EPS medication

• Use sunscreen

• Avoid long periods of time under the sun

• Wear protective covering

For photosensitivity (dry eyes) due to anticholinergic side effects of EPS medication

Rising slowly from a sitting or lying position

For orthostatic hypotension due to anticholinergic side effects of EPS medication

Missed dose can be taken within 3-4 hours late

Can omit if more than 4 hours

Dementia-related psychosis

Atypical Antipsychotics increases risk of death

Antidepressants

Primarily used in the treatment of:

• Major depressive illness

• Panic disorder

• Other anxiety disorders

• Bipolar depression

• Psychotic depression

Tricyclic Antidepressants (TCA)

• MOA: block the reuptake of both norepinephrine and serotonin

• The oldest antidepressants (mid-1950s)

• First choice of drugs to treat depression

• For hopelessness, helplessness, anhedonia, inappropriate guilt, suicidal ideation, and daily mood variations

• Dry mouth

• Constipation

• Urinary hesitancy or retention

• Dry nasal passages

• Blurred near vision

• Severe anticholinergic side effects: agitation, delirium, and ileus (common in elders)

Tricyclic antidepressants (anticholinergic side effects) side effects

• Severe liver impairment

• Myocardial infarction

• MAOI antidepressants

• Conditions that must take caution with anticholinergic effects

Tricyclic antidepressants contraindications

Monoamine Oxidase inhibitors (MAOI)

• Found to have a positive effect on depressed persons during 1950s

• Have a low incidence of sedation and anticholinergic effects

• MOA: interfere with enzyme metabolism of Monoamines:

  • Serotonin

  • Norepinephrine

  • Dopamine

• Used to treat sleep problems, nightmares, intrusive daytime thoughts in individuals with Post Traumatic Stress Disorder

• Enemy of TCA

• Hypertensive crisis - when taken within Tyramine (preservatives, processed, fermented) rich foods (onset 20-60 mins)

• Day-time sedation and insomnia

• Weight gain

• Dry mouth

• Orthostatic hypotension

• Sexual dysfunction - difficult to treat and may necessitate a change in medication

Monoamine Oxidase Inhibitors Side Effects

• Tricyclic antidepressants

• Meperidine

• CNS Depressants

• Many antihypertensives

• General Anesthesia

Medications fatal with Monoamine oxidase inhibitors

Phentolamine Mesylate

Antidote for sexual dysfunction of MAOIs

Selective Serotonin Reuptake Inhibitors (SSRI)

• Replaced the cyclic drugs as the first choice in treating depression when Fluoxitine was released in 1987

• Produce fewer troublesome side effects

• In combination with clomipramine (cyclic antidepressant), are effective in the treatment of Obsessive-Compulsive Disorder

• Anxiety → suicide

• Agitation

• Akathisia or motor restlessness

• Nausea - drink meds with food; if already with nausea no food

• Insomnia - give morning to 12 NN

• Sexual dysfunction

Side effects of SSRIs

Beta-blocker (propranolol or benzodiazepine)

Antidote of sexual dysfunction of SSRIs

Serotonin Syndrome (Storm)

SSRI overdose or drug interaction with MAOI

• Change in mental state: confusion and agitation

• Neuromuscular excitement: muscle rigidity, weakness, sluggish pupils, shivering, tremors, myoclonic jerks, collapse, and muscle paralysis

• Autonomic abnormalities: hyperthermia, tachycardia, tachypnea, hypersalivation, and diaphoresis

Selective Norepinephrine Reuptake inhibitors (SNRI)

• Used the classification of Atypical Antidepressant

• Used when the client has an inadequate response to or side effects from SSRIs

• MOA: Blocks reuptake of norepinephrine and serotonin; weakly blocks dopamine (Duloxetine)

• Loss of appetite, nausea, and constipation

• Dry mouth

• Drowsiness, sedation, insomnia - except Venlafaxine

• Agitation

• Increase BP

• Headache

• Sexual dysfunction

• Alters lab test - for Venlafaxine only

  • Particularly AST ALT

Take daily doses in the morning; remain out of bed and be active during the day; avoid alcohol; give sleep medication as indicated

Reduce insomnia caused by SSRI & SNRI

Cheeking

To ensure clients are not saving up pills in attempt to commit overdosing from potentially fatal antidepressants:

• Cyclic

• MAOI

SSRI & SNRI - does not cause death only serotonin storm

3-6 months

Necessary months for medication adherence of antidepressants

18-24 months

Months for Antidepressant therapy to avoid relapses

Years or lifetime

How long should antidepressants be taken

Mood stabilizers

Primarily used in the treatment of:

• Bipolar affective disorder

• Avoid or minimize the highs and lows that characterize bipolar illness

• Acute phases of mania

Lithium

The most established mood stabilizer

• not for maintenance

• For 1st and short period of time

• Manic episodes

• Decreases Norepinephrine and dopamine by:

  • Hastens destruction

  • Inhibits release

  • Decrease the sensitivity of postsynaptic receptors

• Normalizes reuptake of Serotonin, Norepinephrine, ACH, and Dopamine

5 to 14 days

Onset of action for Lithium

20 to 27 hours

Half-life for lithium

900 - 3,600 mg

Daily dosage of lithium

0.5 - 1.0 meq/L

Serum lithium levels

1.5 meq/L

Toxic Serum lithium levels

No need to discontinue

1.5 meq/L serum lithium level but no signs of dehydration

• Severe diarrhea

• Vomiting

• Drowsiness

• Muscle weakness

• Fine hand tremors

• Lack of coordination

*Untreated, these symptoms worsen and can lead to renal failure, coma and death.

Toxic effects of lithium

3 meq/L

Discontinue immediately before serum lithium level reach

Carbamazepine (Tegretol)

Anticonvulsant drugs that are effective mood stabilizers

• Mode of action:

  • Inhibits kindling (brain seizure) by raising the brain’s threshold for dealing with stimulation, by:

    • Decrease firing of AP

    • Decrease Glutamate release (calm)

Valproic Acid (Depakene, Depakote)

Anticonvulsant drugs that are effective mood stabilizers

• MOA: inhibit kindling by raising the brain’s threshold for dealing with stimulation, by:

  • Increasing GABA

12 hours

Serum drug levels are obtained how many hours after the last dose of these medications

50 - 125 ug/mL

Serum drug levels of Valproic Acid

4 - 12 ug/mL

Serum drug levels of Carbamazepine

2-3 days, weekly, monthly, less frequently

Lithium serum levels are monitored periodically

Persistent thirst (frequent swallowing) and diluted urine

Watch out for what and call a physician and check lithium serum levels

water intake within normal range

Avoid heavy sweating

Monitoring fluid balance

To avoid increase in lithium blood levels

Kidney and thyroid function tests

Monitor for patients taking lithium

Beta-blocker (Propranolol)

For the fine hand tremors

Lifetime regimen

Medication compliance of mood stabilizers

Antianxiety (aka anxiolytics)

• Outpatient usually

• Anxiety and anxiety disorders

• Insomnia

• Obsessive-Compulsive Disorder

• Depression

• Post-Traumatic Stress Disorder

• Alcohol withdrawal

• Symptomatic relief only

• Does not treat the underlying problems that cause the anxiety

Benzodiazepines (Gamma-Aminobutyric Acid agonist)

Modulates other neurotransmitters, particularly Acetylcholine by slowing action potential

• Have proved to be the most effective in treating anxiety

• GABA agonist

Buspirone (Serotonin)

• Non-benzodiazepine that is often used for relief of anxiety

• MOA: Serotonin Agonist

• Controls food intake, sleep and wakefulness, temperature regulation, pain control, sexual behaviors, regulations of emotions

• Drowsiness - no driving, heavy machinery, heavy things

• Dizziness

• Sedation

• Poor coordination

• Impairment of memory or clouded sensorium

• Next-day sedation or a hangover effects - when used for sleep

Side effects of Anxiolytics

Alcohol and other CNS depressants

Do not drink/take ___ when taking anxiolytics

• Decreased response time

• Slower reflexes

• Possible sedative effects

Side effects of benzodiazepines

Follow the exact prescription

Intervention for anxiolytics because it is prone for overdose or to be overused

Stimulants (MOA: CNS stimulation)

Amphetamine and Methylphenidate

• Indirectly acting amines

  • Norepinephrine

  • Dopamine

  • Serotonin

• Release from presynaptic nerve

terminals and prevent reuptake

Pemoline

• Same MOA, but only for Dopamine

SNRI

Atomoxetine

• The only non-stimulant drug for ADHD

• Blocks reuptake of norepinephrine,

leaving more neurotransmission in the

synapse

• Anorexia, weight loss, nausea, and irritability

• Dizziness

• Dry mouth

• Blurred vision

• Palpitations

• Long term problem: growth and weight suppression in Children

Stimulants side effects

Decreased appetite, N/V, tiredness, and stomach upset

Side effects of stimulants SNRI to children

Insomnia, Anticholinergic SE, N/V, dizziness, decreased sexual functions

Side effects of stimulants SNRI to adults