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Psychopharmacology

8 min read

References:

  1. Course Module

Antipsychotics

Also termed as “Neuroleptics”, these drugs block dopamine receptors in the post-synaptic membrane and reduces dopaminergic activity. There are two general types: typical (first generation; “conventional”) and atypical (second generation) antipsychotics. There is also a new generation termed as Dopamine System Stabilizers.

  • For Schizophrenia, Bipolar Disorder, Autism, Psychosis, Tourette’s Syndrome, and Severe Aggression.

Typical Antipsychotics

Used to treat positive symptoms of psychosis, serving as a potent D2 blocker: delusions, hallucinations, disorganized thinking and behavior. Incidence of EPSs are high, also with high rates of Tardive Dyskinesia.

  1. Phenothiazines
    • Thorazine (Chlorpromazine)
    • Trilafon (Perphenazine)
    • Prolixin (Fluphenazine)
    • Mellaril (Thioridazine)
    • Serentil (Mesoridazine)
    • Stelazine (Trifluphenazine)
  2. Thioxantene
    • Navane (Thiothixine)
  3. Butyrophenones
    • Haldol (Haloperidol)
    • Inapsine (Droperidol)
  4. Dibenzazepine
    • Loxitane (Loxapine)
  5. Dihydroindolne
    • Moban (Molindone)

Atypical Antipsychotics

Treats both positive and negative symptoms of psychosis, being both a weak D2 receptor and a serotonin inhibitor: anhedonia, avolition, asociality, alogia, anergia, apathy, affective disturbances.

  • Clozaril (Clozapine)
  • Risperdal (Risperidone)
  • Seroquel (Quetiapine)
  • Zyprexa (Olanzapine)
  • Geodon (Ziprasidone)

Dopamine System Stabilizers

The latest generation of antipsychotic drugs that stabilize dopamine production, reducing the hyperdopaminergic activity associated with psychosis. It is also associated with reduced incidence of EPSs and TD.

  • Aripiprazole (Abilify)
  • Palliperidone (Invega)
TypicalAtypicalDopamine System Stabilizer
Conventional; Traditional (1950)New Generation (1994)Newest Generation (2002)
Treats (+) symptoms of psychosisTreats (+) and (-) symptoms of psychosisStabilizes dopamine output
Potent D2 receptor blockerWeak D2 receptor blockerWeak D2 receptor blocker
High incidence of EPS and TDLow incidence of EPS and TDRare incidence of EPS and TD

Side Effects

  1. Extrapyramidal Side Effects (EPSs):
    • Akinesia, Pseudoparkinsonism: motor retardation, reduced arm swinging, shuffling and festinating gait, mask-like face, salivation, tremors, bradycardia.
      • Treatment: Amantadine (Symmetryl) 100 mg b.i.d., an anticholinergic/dopamine agonist.
    • Akathisia: motor restlessness, pacing, tremors, rigid posture and gait.
      • Treatment:
        • Anticholinergics: Cogentin (Benztropin), Akineton (Biperiden), Kemadrin (Procyclidine), Artane (Trihexaphenidyl)
        • Beta Blockers: Inderal (Propanolol)
        • Benzodiazepine: Ativan (Lorazepam)
        • Changing prescribed antipsychotic drug
    • Dystonia: acute muscular rigidity and cramping with a stiff or thick tongue, torticollis, opisthotonos, oculogyric crisis. This may result in laryngospasms and respiratory distress. It is likely to occur within the first week of treatment for male clients younger than 40 years old who are receiving high potency antipsychotic medications.
      • Treatment:
        • Cogentin Mesylate (Benztropine) 1 to 2 mg IM, an anticholinergic
        • Benadryl (Diphenhydramine) 25 to 50 mg IM, an antihistamine
    • Tardive Dyskinesia: long-lasting, irreversible side effect of antipsychotics, involving eye-blinking, lip smacking, teeth grinding, tongue protrusion, cheek puffing, and body rocking behaviors. Prevention is applied by using the minimal therapeutic dosage possible, changing medications as necessary, and monitoring for signs of TD using the Abnormal Involuntary Movement Scale (AIMS).
  2. Anticholinergic Side Effects: xerostomia (dry mouth), urinary retention, constipation, blurred vision.
    • Treatment and Management:
      • Xerostomia: offer sugarless candies or ice chips.
      • Urinary Retention: measure I&O, assess for bladder distention or sensation of bladder fullness.
      • Constipation: increase fluid intake, dietary fiber, and exercise.
      • Blurred Vision: provide a well-lit environment.
  3. Endocrine Side Effects: gynecomastia, sexual dysfunction, amenorrhea, risk for breast cancer.
    • Treatment and Management:
      • Gynecomastia: breast examinations; encourage discussion of effect on body image.
      • Sexual Dysfunction and Amenorrhea: report any changes of sexual desire and functioning.
  4. Cardiovascular Side Effects: tachycardia, arrhythmias, dysrhythmias.
    • Causes: Serentil (Mesoridazine), Inapsine (Droperidol), Mellaril (Thioridazine)
    • Management: assess radial and apical pulses, report feelings of lightheadedness and dizziness.
  5. CNS Side Effects: headache, dizziness, sedation, decreased alertness.
    • Treatment and Management: headaches may abate with accustomization to antipsychotics. Medication may also be taken at bedtime (as advised by the physician) to minimize effects. Caution the client when performing activities that require mental alertness.
  6. Dermatologic Side Effects: photosensitivity, dermatitis
    • Treatment and Management: avoid sunlight, utilize sunscreen, and supervise personal hygiene.
  7. Serious Side Effects
    • Agranulocytosis: fever, sore threat and mouth, body malaise. WBC count is <2,000 from halted production in the bone marrow.
      • Treatment and Management: notify physician, monitor WBC count, withhold further medication, and place the patient in reverse isolation.
    • Hepatotoxicity: fever, nausea, jaundice, abdominal pain, and an abnormal liver function test.
      • Treatment and Management: notify physician, monitor liver function test, withhold further medication, ensure adequate rest and diet.
    • Neuroleptic Malignant Syndrome: diaphoresis, change in mental alertness (from stupor to comatose), hyperthermia, labile blood pressure, agitation, tachycardia, tachypnea, muscle-rigidity (board-like arms and abdomen), pallor.
      • Treatment and Management:
        • Psychopharmacology: dopamine receptor antagonist e.g. Parlodel (Bromocriptin), beta blockers e.g. L-dopa (Levodopa), benzodiazepam e.g. Ativan (Lorazepam)
        • Notify physician, withhold further medication, admit client to ICU, administer IVF and anti-arrythmics, maintain body temperature.

Antidepressants

These drugs operate by blocking the re-uptake of serotonin and norepinephrine, increasing their levels in the brain and thus affecting mood and emotion. Used for clients with major depressive disorder, type 2 bipolar disorder, or depression secondary to other disorders such as in OCD, panic attacks, phobias, etc. It is prescribed for adults and the elderly, used in children and adolescents, but not recommended for pregnant and lactating individuals.

Tricyclic Antidepressant Drugs (TCA)

These may take from 2 to 6 weeks to take effect. “Save Mr. Tan” may be used as a mnemonic for memorizing the medications

  • Sinequan (Doxepin)
  • Anafranil (Clomiframin)
  • Vivactil (Protriptylline)
  • Elavil (Amitriptylline)
  • Tofranil (Imipramine)
  • Ascendin (Amoxapine)
  • Norpramin (Despramine)

Monoamine Oxidase Inhibitor

These may take 2 to 4 weeks to take effect. Patients should be warned to avoid tyramine-rich food in order to avoid a hypertensive crisis.

  • Marplan (Isocarboxazid)
  • Nardil (Phenelzine)
  • Parnate (Tranylcypromine)

Selective Serotonin Reuptake Inhibitor (SSRI)

These may take 2 to 3 weeks to take effect.

  • Prozac (Fluoxetine)
  • Paxil (Paroxetine)
  • Zoloft (Sertraline)
  • Luvox (Fluvoxamine)

Norepinephrine Reuptake Inhibitors (NRI)

AKA Noradrenaline Reuptake Inhibitors or Adrenergic Reuptake Inhibitors (ARI). These block norepinephrine and epinephrine re-uptake in the brain by blocking their transporters. This leads to increased extracellular concentration, increasing adrenergic neurotransmission.

  • Dyserel (Trazadone)
  • Effexor (Venlafaxine)
  • Wellbutrin (Bupriopion)
  • Strattera (Atomoxetine)

Contraindications

  1. Cardiovascular Disease
  2. Glaucoma
  3. Benign Prostatic Hypertrophy
  4. Liver and Renal Disease

Side Effects

Common:

  1. Anticholinergic Effects
  2. Photosensitivity
  3. CNS Effects (sedation and fatigue)
  4. Cardiovascular Effects
  5. GIT Effects (anorexia and nausea)

Serious:

  1. Agranulocytosis
  2. Serotonin Syndrome: Diaphoresis, Mental Status Changes (confusion, restlessness, agitation), Hypertension, Rigor, Acidosis, Respiratory Failure, Myoclonus (twitching), Tremors
    • Treatment and Management: serotonin receptor antagonist; Sansert (Methysergide), Periactin (Cyproheptadine).
      • Notify physician, withhold further medication, admit client to ICU, administer IVF and antiarrhythmic drugs, and hyperthermic measures.
  3. TCA Overdose: sedation, stupor, convulsion, coma, agitation, ataxia, respiratory depression.
    • Treatment and Management:
      • Monitor Vital Signs and ECG Tracing
      • Maintain a patent airway
      • Catharsis or gastric lavage
      • Cholinergic stimulants e.g. Antilirium (Physostigmine)

Antimanics

Drugs that normalize the re-uptake of serotonin, norepinephrone, dopamine, and acetylcholine. These are used for:

  • Manic period of those with bipolar disorder
  • Prevention of recurrent episodes of mania and depression
  • Schizo-affective disorder

The most common medication used as an antimanic is lithium. Lithium is a salt contained in the human body. 70% to 80% of clients in acute mania respond to lithium therapy. Lithium therapy decreases the range of bipolar behaviors and can also stabilize bipolar disorder by reducing the degree and frequency of cycling or eliminating manic episodes.

  • Lithium competes for salt receptor sites, and also affects calcium, potassium, magnesium, and glucose.
  • The mechanism of action of lithium is unknown, but is thought to destroy catecholamines, inhibit neurotransmitter release, and decrease sensitivity of postsynaptic receptors.
  • Lithium’s action peaks in 30 minutes to 4 hours or regular forms and in 4 to 6 hours for slow-release forms. It crosses the blood-brain barrier and placenta and is distributed in sweat and breast milk. Lithium use during pregnancy is not recommended because it can lead to first-trimester developmental abnormalities.
  • Onset of action is 5 to 14 days; with this lag period, antipsychotic or antidepressant agents are used carefully in combination with lithium to reduce symptoms in acutely manic or accurately depressed clients. The half-life of lithium is 20 to 27 hours.

Contraindications

Lithium levels, even at therapeutic ranges (0.6 - 1.2 mEq/L) may result in toxicity. It should be checked every two to three days during the first month of therapy, then weekly and monthly or more when stable.

  1. Hypersensitivity response to Lithium
  2. Renal Disease
  3. Thyroid Disease
  4. Pregnancy

Side Effects

  1. Common:
    • GIT Effects: nausea, anorexia, diarrhea
    • Weight Gain
    • A “metallic taste”
    • Fatigue and lethargy
    • Polyuria
    • Tremors
  2. Serious:
    • Thyroid Impairment: thyroid function studies are done every 3 to 6 months for clients on long-term lithium therapy.
    • Renal Impairment
  3. Toxic:
    • Muscle Weakness
    • Nausea
    • Slurred Speech
    • Agitation, Ataxia
    • Vomiting
    • Diarrhea, Drowsiness
  4. Severely Toxic:
    • Coma
    • Altered Level of Consciousness
    • Arrhythmia
    • Seizure
    • Stupor
    • Spastic Muscles
    • Hypotension
    • Renal Failure
  • Treatment of Lithium Toxicity: monitor lithium levels, VS, electrolytes, BUN and Creatinine (renal function). Withhold any further doses. Prepare for hemodialysis if indicated for severe toxicity (>3 mEq/L).
  • Prevention of Lithium Toxicity:
    • Regular appointments for blood studies should be held. Advise the patient about the signs of and to report for toxicity.
    • Maintain adequate fluid and electrolytes (sodium; 2g/d) intake.
    • Restrict caffeine intake.
    • Be cautious of patients who have diarrhea, polyuria, vomiting, diaphoresis, and a low salt diet as these may increase incidence of lithium toxicity.

Anxiolytics

Drugs used for anxiety, anxiety disorders, post-traumatic disorders, depression, OCD, and alcohol withdrawal.

Non-Benzodiazepines

These act as a partial agonist for serotonin receptors which decrease serotonin turnover.

  • BusPar (Buspirone)
  • Ambient (Zolpidem)

Side Effects

  • Sedation
  • Headache
  • Nausea
  • Dizziness

Benzodiazepines

These mediate/boost the action of gamma amino butyric acid (GABA) as they bind to receptors on the GABA-A receptor. They have a muscle-relaxant, anticonvulasant, sedative, hypnotic, and anxiolytic effect.

  • Dalmane (Flurazepam)
  • Librium (Chlordiazepoxide)
  • Ativan (Lorazepam)
  • Serax (Oxazepam)
  • Tranxene (Chlorazepate)
  • Valium (Diazepam)
  • Inderal (Propanolol)
  • Vistaril (Hyroxyzine)
  • Equanil (Propanolol)
  • Klonopin (Clonazepam)
  • Halcion (Triazolam)
  • Restoril (Temazepam)
  • Xanax (Akprazolam)

Side Effects

  • Drowsiness
  • Impaired Memory
  • Poor Motor Coordination
  • Sedation

Administration Guidelines

  1. Dependence: monitor dependence on the drug.
  2. Driving and other hazardous activities should be avoided.
  3. Drowsiness and sedation should decrease with time.
  4. Don’t stop benzodiazepines abruptly
  5. Don’t drink alcohol when taking anxiolytics.

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