week 9 pharm

Antipsychotics and anxiolytics

neurotransmitters

Mood & emotion are communicated through central nervous system

Synthesized in presynaptic neurons and stored in vesicles

Impulse triggers release into synaptic cleft

Impulse is communicated by traveling through the presynaptic neuron across the synaptic cleft and binding to receptor on the postsynaptic neuron

Gamma-aminobutyric acid (GABA)

Aids in regulation of anxiety; inhibitory: decreases stimulation of nerve cells (benzos, gabapentin)

serotonin

Affects mood, sleep, and movement

dopamine

Aids in regulation of cognition, emotional responses, and motivation

norepinphrine

Involved in stress response, aids in memory, attention, and regulation of emotions

acetylcholine

Plays a role in memory, learning, attention, arousal and involuntary muscle movement

Faulty release, uptake, or elimination of neurotransmitters may lead to disorders that affect individual's thoughts, feelings, and behaviors

psychosis

Loss of contact with reality

• Thought to be caused by an imbalance of neurotransmitter dopamine in the brain

• Characteristics (usually > 1 symptom)

• Difficulty in processing information

• Disorganized thoughts, incoherence

• Distortion of reality

• Delusions, hallucinations, catatonia

• Aggressive or violent behavior

schizophrenia

Chronic psychotic disorder

Occurs in adolescence or early adulthood

Three groups of symptoms: cognitive, positive, and negative

cognitive

Disorganized thinking

Memory difficulty

Decreased ability to focus attention

positive

Exaggeration of normal function

incoherent speech

Hallucinations

Delusions

Paranoia

negative

Decrease or loss in function and motivation

Simplicity of speech

Blunted affect

Poor self-care

Social withdrawal

antipsychotics

Largest group of medications used to treat mental illness

Improves thought process and behavior of patients with psychotic symptoms

Psychotic symptoms thought to be result from imbalance in dopamine

antipsychotics MOA

Block dopamine receptors in the brain and reduce psychotic symptoms

Also block CTZ and vomiting center

May result in EPS or Parkinson's like symptoms

typical antipsychotics

Dopamine (D2) receptor antagonists 

Phenothiazines 

Block norepinephrine causing sedative and hypotensive effects early in treatment 

Non-phenothiazines 

Block dopamine

atypical antipsychotics

Block dopamine and serotonin receptors

Treat schizophrenia and other psychotic disorders in patients unresponsive to or intolerant of typical antipsychotics

antipsychotic effects

Typical > Atypical

CNS: Confusion, dizziness

Anticholinergic: Blurred vision, dry mouth, urinary retention

Extrapyramidal syndrome: Akathisia (restlessness), Tardive dyskinesia, Acute dystonia

Cardiovascular: ECG changes, Orthostatic hypotension

Neuroleptic malignant syndrome

Weight gain

phenothiazines (typical)

Utilized for the treatment and management of schizophrenia and psychosis

MOA: Blocks dopaminergic receptors in the brain

3 groups: aliphatic, piperazine, piperidine

Pharmacokinetics: Absorbed oral, IM/IV metabolized in the liver excreted in the urine, not commonly used

aliphatic

Chlorpromazine

Side effects - Strong sedation, orthostatic hypotension, moderate EPS

piperazine

Fluphenazine, perphenazine

Side effects - Dry mouth, blurred vision, weight gain, severe EPS

piperidine

Thioridazine

Side effects - Strong sedation, low to moderate effect on blood pressure, few EPS

pheno/non pheno effects

Adverse Events 

• Drowsiness/Dizziness

• Tremor

• Headache 

• Life-threatening arrhythmias

• Hypotension 

• Weight gain

• CNS depression

• Extrapyramidal symptoms 

• Photosensitivity

• Blurred vision/Ocular effects

Caution

• CNS depression

• Narrow angle glaucoma

• Renal impairment

Drug interactions

• CNS depressants

• Agents that prolong QTc

• Anti-cholinergic agents

• Parkinson agents

Haloperidol (non phenothiazines)

Utilized for the treatment and management of schizophrenia and psychosis, attention-deficit/hyperactivity disorder, Tourette’s syndrome

MOA: Blocks dopaminergic receptors in the brain

Pharmacokinetics: Absorbed oral, IM/IV metabolized in the liver excreted in the urine

pheno nursing

Monitor vital signs

Remain with patient while medication is taken and swallowed

Observe for EPS

Inform patients that medication may take 6 weeks or longer to achieve full clinical effect

Caution patients not to consume alcohol or other CNS depressants such as opioids

atypical antipsychotics

Effective in treating both positive and negative symptoms of schizophrenia

Less likely to cause EPS or tardive dyskinesia

Action: Block serotonin and dopaminergic D4 receptors

Side Effects: Drowsiness, headache, unsteady gait 

• Depression, insomnia 

• Weight gain, dyslipidemia, diabetes mellitus

clozapine (atypical)

Utilized for severe schizophrenic patients unresponsive to traditional antipsychotics

 MOA: block serotonin and dopaminergic D4 receptors

Effects:

• Dizziness, sedation, constipation

• Neutropenia (check WBC count, ANC)

• Tachycardia, orthostatic hypotension

• Tremors, occasional rigidity

• Seizures, low possibility of EPS

risperidone (atypical)

Utilized for management of symptoms of psychosis and to treat positive and negative symptoms of schizophrenia

MOA: block serotonin and dopaminergic receptors

Higher affinity for D2 than clozapine, but lower affinity than typical antipsychotics

Effects:

• Dizziness, sedation, headache, photosensitivity

• Dry mouth, urinary retention, constipation

• Tachycardia, orthostatic hypotension

• Weight gain, sexual dysfunction, seizures

• Low possibility of EPS and tardive dyskinesia

aspirazole (atypical)

Used for management of symptoms of schizophrenia, bipolar disorder, autism, depression, Tourette syndrome

MOA: block serotonin and dopaminergic (D2) receptors

Can be taken IM to last a month for non-compliant patients, long-acting

Effects:

• Drowsiness, dizziness, headache, dry mouth

• Anxiety, agitation, memory impairment

• Blurred vision, weight gain/loss, insomnia

• Urinary retention, GI distress, constipation

• Tachycardia, orthostatic hypotension, erectile dysfunction

• Low possibility of EPS and tardive dyskinesia

primary anxiety

Caused by a medical condition or drug use

Managed with short-term anxiolytics

secondary anxiety

Related to selected drug use, medical, or psychiatric conditions

Medications are not usually given for secondary anxiety

anxiolytics (benzos)

Lorazepam, diazepam, chlordiazepoxide, alprazolam

MOA: Enhance the inhibitory effects of GABA in the CNS. Bind to benzodiazepine receptors on the postsynaptic GABA neuron

Use: Generalized anxiety, antiseizure, sedation-induction, status epilepticus

Controlled substance schedule IV

anxiolytic effects

Adverse effects:

• Sedation, drowsiness, dizziness, ataxia

• Headache, confusion, blurred vision

• Bradycardia, hypotension

• Seizures, erectile dysfunction

• Anterograde amnesia

• Tolerance, dependence

Discontinuation: Gradually decrease dose

withdrawal syndrome

Develops slowly (2 to 10 days) and may last several weeks

Paranoia, delirium, agitation

Tremor, muscle cramps

Sweating

Hypertension

Seizures, status epilepticus

benzo toxicity

​​Reversal agent: Flumazenil

MOA: competitively inhibits activity of benzodiazepine and non-benzodiazepine substances that interact with benzodiazepine receptors site on the GABA/benzodiazepine receptor complex

Adverse effects:

• Dizziness, headache

• Anxiety, insomnia, agitation

• Vomiting, dry mouth

• Ataxia, tremor

benzo nursing

Encourage patient to avoid alcohol (inhibits GABA) other CNS depressants to avoid respiratory depression​/excessive sedation

Advise patients to report adverse reactions.​

Determine patient’s support system, Encourage family to be supportive of patient

Teach patient that benzodiazepines should be gradually withdrawn.​

buspirone (anxiolytic)

MOA: binds to serotonin and dopamine receptors

May not see effect for 1 to 2 weeks

Max effect takes 2 to 4 weeks

Effects:

• Drowsiness, dizziness

• Headache, excitement

• Nausea, nervousness

• Fewer side effects of sedation and physical and psychological dependency

depression

 Most common mental illness

• < 50% of individuals seek treatment

• More common in women

Characterized by mood changes and loss of interest in normal activities 

depression causes

Etiology

• Genetic predisposition

• Social and environmental factors

• Biologic conditions 

Pathophysiology theories

• Decreased levels of monoamine neurotransmitters 

• Norepinephrine, serotonin, dopamine

depression symptoms

Depressed mood, despair

Weight loss or gain

Loss of interest in most activities

Fatigue, insomnia, oversleeping

Decreased ability to think or concentrate

Suicidal thoughts

reactive depression

Sudden onset after a precipitating event (example: loss of a loved one)

Usually lasts for months

deep depression

May be primary or secondary to a health problem

Loss of interest in work or home

Inability to concentrate and complete tasks

Difficulty sleeping or excessive sleeping

Feelings of fatigue and worthlessness

bipolar disorder

Mood swings between manic and depressive

Ginkgo biloba/St. John’s wort

Have been suggested for management of mild depression

Should not be taken with prescription antidepressants 

Discontinue herbal products 1 to 2 weeks before surgery

Check with the health care provider before taking herbal treatments

major antidepressants

Tricyclic antidepressants (TCAs)

Selective serotonin reuptake inhibitors (SSRIs)

Serotonin-norepinephrine reuptake inhibitors (SNRIs)

Atypical antidepressants

Monoamine oxidase inhibitors (MAOIs)

tricyclic antidepressant

Use: Major depression

MOA: Blocks uptake of neurotransmitters norepinephrine and serotonin in brain

• Elevates mood, increases interest in ADLs, decreases insomnia

• Blocks histamine receptors which leads to sedation

• Blocks cholinergic receptors which leads to anticholinergic effects

Clinical response occurs in 2-4 weeks

tricyclic effects

Adverse effects:

• Sedation, drowsiness, dizziness, seizures

• Blurred vision, constipation, urinary retention

• Sexual dysfunction

• Weight gain

• Suicidal ideation

• Cardiotoxicity

• Orthostatic hypotension

• Blood dyscrasias

• EPS

• Neuroleptic malignant syndrome (Clomipramine)

Drug Interactions

• Alcohol and other CNS depressants 

• MAOIs may lead to toxic psychosis, cardiotoxicity

• Antithyroid drugs may increase dysrhythmias

selective serotonin reuptake inhibitors (SSRI)

MOA: blocks reuptake of neurotransmitter serotonin into the nerve terminal of the CNS

Use: Major depression

• Decrease premenstrual tension syndrome

• Eating/substance use disorders

• Prevention of migraine headaches       

• Anxiety disorders (OCD, panic/phobias, PTSD)

More commonly used to treat depression than TCAs

Fewer side effects, reduced risk of toxicity in overdose

May improve compliance

Take 1 to 3 weeks to see effect

• Citalopram (celexa)

• Fluoxetine (prozac)

• Paroxetine (paxil)

• Sertraline (zoloft)

SSRI effects

Interactions

• Alcohol and other CNS depressants 

• Grapefruit juice with SSRIs can lead to toxicity

Adverse effects:

• Side effects often decrease over 1 to 4 weeks

• Confusion, dizziness, drowsiness 

• Insomnia

• Headache, blurred vision, dry mouth

• Nausea, vomiting, diarrhea 

• Weight loss early in treatment, but eventual weight gain

• Sexual dysfunction

• Suicidal ideation

serotonin norepinepherine reuptake inhibitors (SNRI)

MOA: block the reuptake of serotonin and norepinephrine

Use: Major depressive depression 

• Generalized anxiety disorder 

• Social anxiety disorder

• Desvenlafaxine (Pristiq)

• Duloxetine (Cymbalta)

SNRI effects

Adverse effects:

• Drowsiness, dizziness

• Insomnia

• Headache, blurred vision, dry mouth

• Nausea, vomiting

• Weight loss

• Sexual dysfunction  

• Tachycardia, hypertension

• Seizures

• Suicidal ideation

serotonin syndrome

Can start 2 to 72 hrs after starting treatment (SSRI,SNRI, TCA)

Can be lethal: Stop medication and notify provider

Symptoms

• Confusion, agitation, poor concentration

• Disorientation, hallucinations

• Seizures, status epilepticus

• Tachycardia

• Fever

• Nausea, vomiting, diarrhea

• Coma 

Amoxapine (Asendin)

MOA: Atypical antidepressant that affects neurotransmitters serotonin, norepinephrine, and dopamine

Use: Major depression

• Reactive depression

• Anxiety 

Adverse effects

• Dry mouth, blurred vision, orthostatic hypotension

• Constipation, erectile dysfunction

MAOI interactions

Drug interactions: Vasoconstrictors, Cold medications containing phenylephrine and pseudoephedrine

Food containing tyramine

• Some cheeses, cream, yogurt, coffee, chocolate, bananas, raisins, Italian green beans, liver, pickled foods, sausage, soy sauce, yeast, beer, and red wines 

Patients must avoid these foods and medications when taking MAOIs

MAOI effects

Adverse effects:

• Agitation, restlessness, insomnia

• Anticholinergic effects

• Orthostatic hypotension

• Hypertensive crisis from food/drug interactions

• Suicidal ideation

Monoamine oxidase inhibitors (MAOI)

MOA: Monoamine oxidase enzyme inactivates norepinephrine, dopamine, epinephrine, tyramine and serotonin

• By inhibiting MAO levels of neurotransmitters rise

Use: Depression not controlled by TCAs and second-generation antidepressants

An increase in tyramine can lead to an increase in blood pressure

Avoid interactions to reduce risk of a hypertensive crisis

last line, many side effects and can contribute to serotonin syndrome

lithium (mood stabilizer)

Use: Bipolar disorder/Manic episodes

• Therapeutic serum range: 0.8 to 1.2 mEq/L

• Levels > 1.5 mEq/L may lead to toxicity

Monitor: Biweekly until therapeutic level obtained

• Every 1-2 months for maintenance dose

• Narrow therapeutic serum range- must monitor levels

MOA: Alteration of ion transport in muscle and nerve cells, increased receptor sensitivity to serotonin

Adverse effects: Hyponatremia

lithium toxicity (mild)

1.5-2 mEq/L; mild symptoms

GI distress: nausea, vomiting, diarrhea

Mental confusion

Poor coordination

Coarse tremors

Sedation

lithium toxicity (severe)

> 2 mEq/L

Extreme polyuria

Tinnitus

Involuntary extremity movements

Seizures

Kidney failure

Severe hypotension

lithium interactions

Increased with Thiazides, methyldopa, haloperidol, NSAIDs, antidepressants, phenothiazines, carbamazepine, spironolactone, sodium bicarbonate, ACE inhibitors, calcium channel blockers

Decreases level with caffeine, loop diuretics, theophylline

antidepressant nursing

Baseline assessment of depressive symptoms; continue during antidepressant therapy

Monitor for suicidal thoughts, especially during the first few weeks

Take medication exactly as prescribed

• Inform patients they may not see the full effect of medication for several weeks

• Do NOT abruptly stop taking these medications

Medication can be taken at bedtime to decrease danger of sedating effects

May take with food to avoid GI upset

Monitor food/drug and drug/drug interactions

lithium caution

Serum sodium levels need to be monitored in patients

Tends to deplete sodium, must be used with caution, if at all, by patients taking diuretics.

Monitor serum drug level

Signs of lithium toxicity- nausea, vomiting, blurred vision, confusion, and tremors

anticonvulsants

Antidepressants can lower the seizure threshold