General Pharmacology

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ANTIDEPRESSANTS/MOOD STABILIZERS

Tricyclic Antidepressants (TCAs)

  • Common TCAs
    • imipramine (Tofranil)
    • clomipramine (Anafranil)
    • amitriptyline (Elavil)
  • Mechanism of Action
    • NE and 5-HT receptors
  • Uses
    • Somatic and vegetative symptoms of depression, panic attacks, agoraphobia, and obsessive states
  • Side Effects
    • Anticholinergic (e.g., dry mouth, blurred vision, pupil dilation, urinary retention, nasal congestion, skin rash, cardiovascular effects, memory, confusion, and insomnia)

Selective Serotonin Reuptake Inhibitors (SSRIs)

  • Common SSRIs
    • fluoxetine (Prozac)
    • sertraline (Zoloft)
    • paroxetine (Paxil)
  • Mechanism of Action
    • 5-HT
  • Uses
    • Depression, obsessive compulsive disorder, and eating disorders
  • Side Effects
    • Sexual problems, gastrointestinal symptoms, headache, and dizziness
    • Less severe side effects than TCAs
    • Less potential for a lethal dose
    • In combination with other serotonergic compounds, can result in central serotonin syndrome that can be fatal

Other

  • Types
    • bupropion (Wellbutrin)
    • nefazodone (Serzone)
    • venlafaxine (Effexor)
  • Side Effects
    • Less anxiety and sexual side effects than SSRIs

Monoamine Oxidase Inhibitors (MAOIs)

  • Common MAOIs
    • phenelzine (Nordil)
    • tranylcypromine (Parnate)
  • Mechanism of Action
    • NE
  • Uses
    • Atypical depression, hostility, anxiety, and hypochondriasis
  • Side Effects
    • Tremor, hypotension, dizziness, dry mouth, upset stomach, weight gain, blurred vision, and headache
    • Must avoid foods with tyramine due to possibility of developing hypotensive crisis

Mood Stabilizers

  • Types
    • lithium (Lithobid)
    • divalproex sodium(Depakote)
  • Mechanism of Action
    • Unknown
  • Uses
    • Mania and mood swings
  • Side Effects
    • Hand tremor, gastric distress, weight gain, fatigue, and mild cognitive impairment
    • Vomiting, abdominal pain, diarrhea, severe tremor, ataxia, and coma can appear at toxic levels

ANTIPSYCHOTICS

  • Types
    • chlorpromazine (Thorazine)
    • thioridazine (Mellaril)
    • haloperidol (Haldol)
    • clozapine (Clozaril)
    • risperidone (Risperdal)
  • Mechanism of Action
    • Dopamine
  • Uses
    • Positive symptoms of schizophrenia and psychotic reactions
  • Side Effects
    • Anticholinergic and extrapyramidal effects (Parkinsonian symptoms) and tardive dyskinesia
    • Risk of agranulocytosis with clozapine
    • Neuroleptic Malignant Syndrome (e.g., high fever, severe muscle rigidity, altered consciousness, and ANS dysregulation)

SEDATIVES, HYPNOTICS, ANXIOLYTICS

Benzodiazepines

  • Types
    • diazepam (Valium)
    • alprazolam (Xanax)
    • clonazepam (Klonipin)
    • lorazepam (Ativan)
    • Triazolam (halcion)
  • Mechanism of Action
    • GABA
  • Uses
    • Anxiety, seizure disorder, and sleep
  • Side Effects
    • Sedation/drowsiness, confusion, disorientation in the elderly, disturbed sleep, potential for a withdrawal syndrome

Barbiturates

  • Types
    • thiopental (Pentothal)
    • amobarbital (Amytal)
    • secobarbital (Seconal)
  • Mechanism of Action
    • Reticular Activating System
  • Uses
    • Acute agitation
  • Side Effects
    • Addictive
    • Synergistic effects with alcohol consumption

Beta-Blockers

  • Types
    • propanolol (Inderal)
  • Mechanism of Action
    • Beta-adrenergic
  • Uses
    • Physical manifestations of anxiety (anticipatory)
  • Side Effects
    • Gastric distress, hypotensive episodes, sexual dysfunction, numbness, and some memory impairment

OPIOIDS

  • Types
    • Morphine
    • Percodan
    • Darvon
    • Methadone
  • Mechanism of Action
    • Enkephalin receptors
  • Uses
    • Pain relief
  • Side Effects
    • Pupil constriction, decreased visual acuity, perspiration, gastric distress, respiratory suppression, constipation, and addictive

PSYCHOSTIMULANTS

  • Types
    • methylphenidate (Ritalin)
    • pemoline (Cylert)
    • Dexedrine
  • Mechanism of Action
    • Catecholamines (i.e., DA, NE, Epinephrine)
  • Uses
    • ADHD, narcolepsy, and treatment resistant depression
  • Side Effects
    • Anorexia and dry mouth
    • Overdose can lead to paranoid state, tachycardia, and anxiety

ANTICONVULSANTS

  • Types
    • carbamazepine (Tegretol): Can also be a mood stabilizer
  • Side Effects
    • CNS (i.e., drowsiness, confusion, ataxia, hyperreflexia, clonus, tremor)
    • GI (i.e., n/v, diarrhea, constipation, anorexia)
    • Blood dyscrasia (rare)
    • Cardiovascular
    • Dermatologic problems

AGENTS FOR COGNITIVE DEFICITS (NOOTROPICS)

  • Cholinergic Therapies
    • tacrine (Cognex)
    • donepezil (Aricept)
    • eldepryl (Selegiline)
    • Estrogen
    • Ibuprofen
    • Vitamin E (&C) nerve growth enhancers
  • Rationale
    • Cholinergic deficit has been the most commonly observed neurotransmitter deficits in Alzheimer’s Disease and is hypothesized to underlie the cognitive deficits; although the precise relationship remains unknown
    • Cholinesterase inhibitors approved for use are Cognex and Aricept
    • Aricept has less hepatotoxicity than Cognex

SPECIAL CONSIDERATIONS IN AN AGING POPULATION

  • Growing Population
    • Individuals > than 6 comprise 12% of the population but receive 33% of all prescription drugs
    • Elderly patients take on average of 3-4 prescription drugs per day
    • The > 65 age group is growing
  • Physiology of Aging
    • Diminished Physiologic Reserve
      • Changes in CNS function may not become apparent until patient confronts a physiologic challenge (acute illness or medical intervention)
    • Aging Impacts the Pharmacokinetics of Drugs
      • Absorption is influenced by gastric pH, intestinal blood flow, GI motility, # of cells to absorb
      • Altered nutritional status in the elderly, consumption of other drugs can also affect absorption
      • Distribution: 3 compartments (fat tissue, body water, binding to plasma proteins)
      • Increased proportion of body fat to water with age
      • Increased total body fat which increases the volume of distribution of lipid soluble drugs which can impact the ½ life
      • Intravascular protein levels drop in the elderly and this impacts distribution
      • Psychotropics generally bind extensively to plasma proteins
      • Malnutrition, protein wasting, and concomitant administration of other drugs that compete for protein binding sites leads to drop in amount of circulating proteins
      • Metabolism (liver is principal site of metabolism)
      • Decreased hepatic blood flow, competing drugs may impact metabolism
      • Excretion (kidney is major organ for excretion)
      • Renal clearance is a problem with dehydration which is common in the elderly
    • Pharmacodynamics and the Elderly
      • Age related alteration in neuronal cell # and neurotransmitter production and break down
      • Selective alteration in pre or post-synaptic receptors e.g., decrease in # and sensitivity of serotonin receptors may impact sleep/appetite in the elderly
      • Age related alterations in receptor binding
      • Less efficient blood brain barrier
      • Decreased cerebral circulation and metabolism
      • Autonomic neurodegenerative changes, predisposing to orthostatic hypotension and thermal dysregulation
    • Specific Risks
      • AD: Degeneration of the cholinergic system where anticholinergic drugs have amplified negative effect on an already compromised memory system
      • PD: Profound DA depletion
  • Drug Induced Neuropsychiatric Disorders in the Elderly
    • Seven categories of adverse effects of commonly encountered agents used with geriatric patients (e.g., Coffey & Cummings, APA Textbook of Geriatric Neuropsychiatry, 1994)
      • Depression
      • Mania
      • Anxiety or agitation
      • Delirium
      • Psychosis
      • Visual hallucinations
      • Dementia-like syndrome
  • Medical Conditions Producing Psychiatric Symptoms
    • Cognitive
      • Delirium may arise from intracranial or extracranial causes
      • Dementia: Must involve cerebral dysfunction, whether primary or secondary, may have treatable causes (e.g., neurosyphilis, thyroid disease, vitamin deficiencies, medication-induced)
    • Mood
      • Neurological (e.g., Parkinson’s, MS, Huntington’s, dementia, hydrocephalus, infections, trauma)
      • Cerebrovascular disease (MID)
      • Endocrine (e.g., thyroid, adrenal, menses or post-partum related)
      • Infections or inflammatory disorders (e.g., HIV, mono, chronic fatigue syndrome, pneumonia, lupus, rheumatoid arthritis, etc.)
      • Miscellaneous (e.g., cancer, uremia, nutritional deficiencies)
    • Psychotic Symptoms
      • Neurological (e.g., epilepsy, neoplasm, trauma, hydrocephalus, HD, herpes encephalitis, neurosyphilis)
      • CBVS Disease
      • Many other disease states (e.g., nutritional deficiencies, delirium syndromes, heavy metal poisoning, lupus, acute intermittent porphyria)
    • Anxiety
      • Neurological (see above)
      • Hypoxia due to cardiovascular disease, pulmonary disease, anemia
      • Endocrine (e.g., thyroid, pituitary, adrenal, virilization disorders in females)
      • Inflammatory disorders (e.g., lupus, rheumatoid arthritis)
      • Nutritional deficiencies
      • Miscellaneous (e.g., hypoglycemia, cancer, mono, etc.)