Clinical Pharmacology

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Clinical Pharmacology

• Jeff Baker, Ph.D.
• Associate Professor Chief Psychologist
• Adopted from Kaplan and Sadock (2003) Drs.
  Brazeal, Piggot, Kraus, Schneider
• This is a limited lecture designed to introduce
  you to clinical psychopharmacology to assist in
  the management of psychological and behavioral
  problems

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Psychopharmacology

• Drug an exogenous chemical that effects one or
  more biological processes.

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Clinical Pharmacology

• Pharmacokinetics (quantitative)
• Movement of drugs through the body
• Pharmacodynamics
• Study of qualitative effects of drugs
• Actions
• Agonism facilitates normal functioning of
  synapse
• Antagonism hinder

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Effective Pharmacological Treatments

• Efficacy
• How good is the drug in diminishing the
  manifestations of the disorder
• Percent of patients responding to a medication in
  a controlled study
• Double-blind placebo controlled
• Relative efficacy
• One treatment vs. another

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Effective Pharmacological Treatments

• Effectiveness
• How in the real world is this treatment effective
• Ease of administration
• Side effects
• Patient compliance
• Usefulness with real patients

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Effective Pharmacological Treatments

• Clinical Response
• Pharmacologic effect
• Placebo response
• Spontaneous remission

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Goals of Pharmacotherapy

• Acute Treatment
• Used to alleviate the symptoms of an actively
  occurring disorder
• Continuation Treatment
• Goal To prevent a relapse into the same episode
  for which treatment began
• Maintenance Treatment
• Goal To prevent recurrences by the ongoing
  maintenance use of a medication

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Compliance

• Defined as Adherence to the recommended
  treatment plan of a health care professional

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Strategies to Increase Compliance

• Encourage active patient participation
• Adequate communication
• Empathetic approach/Trusting relationship
• Family and community involvement and support
• Emphasis on positive effects of medication
• Use the most simplified drug regimen

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Various Reasons for Noncompliance

• Stigma of disorder
• Denial of illness
• Disruption of cognitive process
• Side effects of medication
• Slow onset of beneficial effects
• Cost

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Clinical Characteristics to Suggest
Pharmacological Treatment

• Psychiatric Symptoms
• Sleep or Appetite Disturbance
• Fatigue
• Panic Attacks
• Ritualistic Behavior
• Cognitive Symptoms
• Psychosis such as Delusions or Hallucinations

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Clinical Characteristics to Suggest Psychiatric
Referral

• Prominent Physical Symptoms or Significant
  Medical Disorder Resulting in Significant
  Behavioral Changes
• Significant Suicidality
• Family History of Major Psychiatric Disorder
• Marked Mood Lability
• Intense Rage or Depressive Symptoms
• Nonresponse to Psychotherapy

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Brain Neurotransmitters

• Amines
• Serotonin
• Dopamine
• Norepinephrine
• Epinephrine
• Acetylcholine
• Amino Acids
• GABA
• Glycine
• Glutamic Acid

• Neuropeptides
• CRH, CRF
• TRH, LHRH
• GH, somatostatin
• Opioid Peptides
• Dynorphin
• ß-endorphin
• Gut hormones
• CCK, secretin
• Substance P

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Neurotransmission

• The receptor sites are specifically structured to
  bind with neurotransmitters.
• Soon after the neurotransmitter is released, it
  must quickly be inactivated in order for the
  postsynaptic neuron to be able to receive new
  messages.

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Most common means of inactivation

• Enzymatic degradation
• Reuptake
• Neurotransmitter is transported back into the
  presynaptic neuron where it is repackaged into
  the vesicles.

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Drug Development Treatment for Psychiatric Issues

• 1845 Hashish
• 1875 Cocaine
• 1892 Morphine, alcohol, ether
• 1903 Barbiturates
• 1927 Insulin Shock
• 1936 Frontal Lobotomies
• 1938 ECT
• 1949 Lithium Introduced
• 1950 Chlorpromazine (Thorazine)
• 1955 Tricyclics MAOs
• 1990s SSRIs SNRIs
• 2000 ER CR

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Classes of Psychotropics

• Antipsychotics
• Antidepressants
• Mood Stabilizers Anxiolytics
• Anti-Abuse

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Schizophrenia

• 1 get it approximately 10 million in the world
• Not sure as to why it occurs
• DA (dopamine) theory is best guess

• Positive effects
• delusions
• hallucinations
• inappropriate affect
• cognitive disorders
• Negative effects
• flattened affect
• social withdrawal
• catatonia

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Schizophrenia Drug Treatment

• Dopamine Receptor Antagonists
• Chlorpromazine (Thorazine)
• Haloperidol (Haldol)
• Dopamine and Serotonin Receptor Antagonists
• Clozapine
• Works on - and effects
• Serious side effect - 1-2 develop agranulocytosis

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Dopamine Receptor Antagonist Side Effects

• Vegetative disorders
• decrease in blood pressure, acceleration of pulse
  rate, modification of myocardial activity,
  sweating, dry mouth, constipation, impotence,
  ejaculation disorders, anorgasmia
• Extrapyramidal disorders
• Early dyskinesia
• Spasms of tongue, visual spasms, grimacing,
  gyratory and rotatory movements of the upper
  extremities

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Dopamine Receptor Antagonist Side Effects

• Extrapyramidal disorders cont.
• Neuroleptic Parkinsonoid
• akinesia (restriction of motor movement),
  hypomimia (loss of facial expression), rigor and
  tremor (in muscles)
• Akathisia
• Restlessness, urge to move continuously
• Tardive dyskinesia
• Involuntary chewing, smacking of lips, swallowing
  and rolling movements of the tongue
• Gyratory and flailing movements of the extremities

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Antipsychotics (Neuroleptics)

• Typical Neuroleptics
• High potency (Haldol)
• Medium potency (Stelazine)
• Low potency (Thorazine)
• Depot/Decanoate (Prolixin-D or Haldol-D/LA)
• Atypical Neuroleptics
• Clozaril (Clozapine)
• Risperidol Pisperidone)
• Zyprexa (Olanzapine)
• Seroquel (Quetiapine)
• Geodon (Ziprasidone)

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Typical Neuroleptics
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Neuroleptics Indications

• Schizophrenic disorders
• Mania
• Acute Psychotic reactions
• Mood d/o with psychotic symptoms
• Delirium/dementia

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Atypical Neuroleptics
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Depression Who Needs Meds?

• Depressed mood with neurovegetative symptoms gt 4
  weeks
• Previous episodes
• Severe, disabling, or presence of Sx Increase
• Comorbid anxiety d/o
• Psychotic symptoms
• Family history of suicide

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Depression

• During any 1 year period, 17.6 million American
  adults suffer from a depressive illness.
• Cost an estimated 44 billion a year.
• Nearly two-thirds of depressed people do not get
  appropriate treatment.
• 80 of those with depression can feel better with
  proper treatment.
• Antidepressants used
• Neurotransmitters involved NE, DA,
  5-Hydroxytryptamine

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Antidepressant Classes

• TCA (Elavil)
• MAOI (Nardil)
• Monoamine oxidase inhibitors
• Selective Reuptake Inhibitors
• SSRI (Prozac)
• SDRI (Wellbutrin)
• SNRI (Effexor)
• Serotonin Modulators
• Desyrel
• Remeron

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Common Tricyclic Antidepressants
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TCA-Common Side Effects

• Weight gain
• Anticholinergic
• Dry mouth, cavities
• Blurred vision
• constipation
• Urinary retention
• Tachycardia
• Sedation, fatigue
• Tremor, dizziness
• Impotence

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TCA-Efficacy

• Depression
• Anxiety
• Panic
• OCD (Anafranil Only)
• PTSD
• Bulimia
• Chronic Pain
• Headaches

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Depression Tricyclics and Tetracyclics

• Non-Selective Monomic Reuptake Inhibitors
• Fairly effective but side-effects
• Therapeutic Lag Drug starts working immediately,
  but doesnt have any effect for a couple weeks
  sometimes 6 weeks

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Depression SSRIs

• Other treatments
• Biploar I disorder, dysthymic disorder, eating
  disorders, panic disorders, obsessive-compulsive,
  and borderline personality disorder.
• Prozac has been used for Anxiety, panic attacks,
  phobias, obsessive compulsivenss, anorexia and
  bulimia, seasonal affective disorder, obesity,
  PMS, chronic pain.

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Depression Commonly Used SSRIs

• Side Effects
• mostly involved the central nervous system and
  the gastrointestinal system
• sexual dysfunction or allergic reactions
• some adverse symptoms can disappear or lessen
  with time.
• Fluoxetine (Prozac, Lilly) (Selective for 5-HT)
• Paroxetine (Paxil)
• Sertraline (Zoloft)
• Escitalopram (Lexapro)
• R-Fluoxetine (Mirror of Prozac, 2004)

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Selective Serotonin Reuptake Inhibitors
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SSRI-Efficacy

• Depression
• Panic
• OCD
• PTSD
• Social Phobia
• Bulimia
• PMS, BDD
• Chronic Pain
• Kids Meds

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SSRI-Common Side Effects

• Insomnia, headache
• Nausea, anorexia
• Diarrhea
• Constipation (Paxil)
• Sexual dysfunction
• Decreased libido
• Anorgasmia
• Nervousness, tremor
• Myoclonus
• Teeth-clenching

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DRI, SNRI, and SMA Antidepressants
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Wellbutrin-Tolerability

• Excitation effects
• Insomnia
• Anxiety
• Tremor
• Menstrual irregularity
• Seizures linked to
• Single dose gt 150 mg.
• Daily dose gt 450 mg.
• Bulimia or eating disorders

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Wellbutrin- Special Factors

• Pro
• No sexual dysfunction
• No weight gain
• Smoking Cessation
• Preference in Bipolar depression?
• Con
• Poor anxiolytic not anti-panic
• Can worsen psychosis
• Seizure issue

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Effexor-Tolerability

• Nausea (lt7 days)
• Agitation, insomnia
• Anticholinergic effects
• Dry mouth, sweating
• Ur. Retention
• Constipation
• HTN linked to
• Doses gt225 mg/day
• Dose changes

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Effexor- Special Factors

• Pro
• Energizing
• Rapid onset
• Severe depression
• Anti-panic?
• No weight gain
• Con
• Side Effexor
• Hypertension issue

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Serzone- Special Factors

• Pro
• Sleep enhancing
• No sexual dysfunction
• Anxiolytic anti-panic
• Con
• Taken off the market Nov 2003
• Important dangerous drug interactions

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Remeron-Special Factors

• Pro
• Sleep enhancing at 15 mg.
• limited sexual dysfunction
• Anti-nausea
• IBS improved?
• Chronic pain
• Anxiolytic anti-panic
• Con
• Weight gain

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SSRI Other Indications

• Anxiety/Panic
• Bulimia Nervosa
• PMDD
• OCD-Spectrum
• Impulse Control

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Increase in Prescription Meds 9/11/2001
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Eating Disorders

• Bulimia Nervosa
• SSRI
• All antidepressants
• Anorexia Nervosa
• SSRI

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Impulse Control SSRI-Responsive?

• Kleptomania
• Trichotillomania
• Compulsive D/O
• Paraphilias
• Pyromania
• Gambling

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Chronic Pain States

• TCA
• Toxicity/Intolerance
• Alcohol synergism
• Alternatives
• Remeron
• SSRI
• Potential Advantages
• Safe Well-tolerated
• Preserve sleep architecture

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Insomnia

• Trazodone
• Males priapism
• Safe, not abusable, cheap
• Remeron
• 15 mg dose
• Safe
• TCA
• Low dose
• Toxicity issues

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Anxiety Disorders Differentiation

• Disorder Core Fear Common Triggers
• OCD Obsession Obsession or
  Tension
• Panic Disorder Dying Crowds, bridges,
  etc.
• Agoraphobia Being Trapped Open spaces,
  crowds
• GAD Everything Anything
  stressful
• Social Phobia Public Public speaking,
• Embarrassment Performance anxiety
• PTSD Recurrence of Trauma-related
  places
• Traumatic Event or experiences

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Anxiolytics

• Antidepressants
• Benzodiazepines
• Buspirone
• Antihistamines
• over-rated
• tolerance develops fast
• Neuroleptics
• bad idea

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Anxiety Pharmacotherapy

• Disorder Acute/Situational Chronic
• GAD Buspirone or BZD AD
• Panic D/O BZD AD AD
• Social Phobia BZD or b-blocker AD
• OCD SSRI same
• PTSD BZD AD
• BZDbenzodiazepine ADantidepressant
• GADgeneralized anxiety disorder
• OCDobsessive-compulsive disorder
• PTSDpost-traumatic stress disorder

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Benzodiazepines

• Short-term use or situational anxiety
• Tolerability
• Cognitive effects
• Enhanced effects
• gender
• age
• alcohol

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Common Benzos Dosing
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Benzodiazepine Side Effects

• Behavioral Disinhibition
• hostility, aggressiveness, rage reactions
• paroxysmal excitement, irritability
• Psychomotor Impairment
• synergistic effects with ETOH
• Cognitive Impairment
• impaired visuospatial ability sustained
  attention tasks
• Withdrawal Phenomena
• flu-like symptoms (mild), psychotic s(x)s or
  seizures (severe

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Mood Stabilizers

• Used for Bipolar or Manic-Depressive to
  regulate mood
• Side Effects
• constipation, nausea, dry mouth, headache,
  fatigue
• occasionally hyperactivity, Akathisia, and
  Parkinsonism
• Lithium (naturally occurring mineral)
• Carbamazepine (Tegretol)
• Valporic Acid (anticonvulsant)

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Medication-Induced Movement Disorders

• Anti-parkinsonsism, anticonvulsant,
  anticholinergic
• Include beta-blockers, L-dopa, and others
• Side Effects
• hypotensions, nausea, vomiting, etc
• abuse potential, depression, anxiety, psychosis
• Atenolol (Tenormin),Metoprolol (Lopressor),
  Nadolol (Corgard), Propranolol (Inderal)

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Miscellaneous

• Alcohol withdrawal
• Disulfiram (antabuse)
• Side effects
• if alcohol used in conjunction - possible
  respiratory depression and even death
• w/o alcohol fatigue, impotence, mental changes,
  hepatic damage

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Anti-Abuse Medications

• Anti-Alcohol
• Revia
• Antabuse
• Buprenex
• Catapres
• Narcan
• Anti-Narcotic
• Methadone
• LAAM
• Buprenorphine
• Nicotine
• Habitrol
• Nicotrol
• Zofran
• Orlaam
• Nircorette Gum

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Miscellaneous

• Opioid withdrawal
• Methadone and Clonodine
• Side effects
• tolerance, psychological and physical dependence,
  dizziness, depression, euphoria, agitation

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Miscellaneous

• Alzheimer
• Aerocept
• Still being studied for AD, early results are
  hopeful.
• Memantine
• Approved for release Jan 2004, first med approved
  for mod to severe Alzheimers disease. Early
  reports suggest help with symptoms AND slows
  neruodegenerative process.
• Tacrine
• Studies are still being reviewed Pfizer claims
  no harm and some benefits have been documented.
• Side effects
• elevations in hepatic transaminase levels (can
  cause liver damage), nausea, vomiting, diarrhea

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Miscellaneous

• Autism
• Fenfluramine (Not used very often)
• Side Effects
• drowsiness, diarrhoea, dry mouth, dizziness,
  confusion, headache, fatigue, agitation

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Miscellaneous

• Sexual dysfunction
• Yohimbine
• Commonly used but major side effects Elevated
  blood pressure and heart rate, nausea, vomiting,
  sweating, urinary frequency Recent 2003 Studies
  show no effect on sexual performance.
• Sildenafil Citrate (Viagra) (2001)
• Originally developed to tx cardiovascular
  disease. Side Effects Combination with
  nitroglycerin might cause death (severe
  hypotension). Blurred vision, blue vision, temp
  color blindness, breast enlargement, priaprism.
  1 study showed 40 of men with heart disease
  using Viagra with ED had a serious reaction.
• Vardenafil (Levitra) (2003)
• Newly released by Bayer/SmithGlaxoKline for the
  tx of ED (similar side effect), similar
  effectiveness (80).

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ADHD ADD
Perhaps ADHD kids are starting here and the drug
pushes them over the edge.

• In .1 to 6 of school population
• Treatment
• Ritalin (methylphenidate)
• Adderall (Dexedrine Amphetamine)
• from the amphetamine family
• No clinical proof one is better than the other
  (Dulcan, 1986)

Locomotive Activity
Dose