PHARMACOLOGY

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PHARMACOLOGY

• Psychiatric drugs

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OBJECTIVES

• Identify the classes of drugs that alter
  psychogenic behavior and promote sleep.
• Identify the uses and varying actions of these
  drugs.
• Identify how these drugs are absorbed,
  distributed, metabolized, and excreted.
• Identify drug interactions and adverse reactions
  to these drugs.

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DRUGS AND PSYCHIATRIC DISORDERS

• Drugs that are used to treat various sleep and
  psychogenic disorders are classified according to
  the following categories
• Sedative and hypnotic drugs
• Antidepressant and antimanic drugs
• Antianxiety drugs
• Antipsychotic drugs

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SEDATIVE AND HYPNOTIC DRUGS

• Sedatives reduce activity or excitement resulting
  in drowsiness.
• Are considered hypnotics when given in large
  doses.
• Three main classes of synthetic drugs include
  benzodiazepines, barbiturates, and
  nonbenzodiazapine-nonbarbiturate drugs.
• Also includes alcohol and OTC sleep aids.

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BENZODIAZEPINES

• Produce many therapeutic effects including
  daytime sedation sedation before anesthesia
  sleep inducement relief of anxiety or tension
  skeletal muscle relaxation anticonvulsant
  activity.
• Flurazepam (Dalmane), lorazepam (Ativan),
  temazepam (Restoril), and triazolam (Halcion) are
  commonly used for their sedative/hypnotic
  effects.

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BENZODIAZEPINES

• Alprazolam (Xanax), chlordiazepoxide (Librium),
  chlorazepate (tranxene), diazepam (Valium), and
  oxazepam (Serax) are commonly used for their
  antianxiety effects.
• Pharmacokinetics
• Absorbed well orally and parenterally
  distributed widely metabolized in the liver
  excreted in the urine.

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BENZODIAZEPINES

• Pharmacodynamics
• Work by stimulating gamma-aminobutyric receptors
  in the ascending reticular activating system of
  the brain.
• At low doses they decrease anxiety by acting on
  the limbic system and other areas of the brain
  that help regulate emotional activity.

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BENZODIAZEPINES

• At higher doses they induce sleep by depressing
  the RAS of the brain.
• Pharmacotherapeutics
• Clinical indications include producing preop
  relaxation treating insomnia producing IV
  anesthesia treating alcohol withdrawal treating
  anxiety and seizure disorders producing skeletal
  muscle relaxation.

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BENZODIAZEPINES

• Drug interactions
• Few interactions.
• Increased sedation when taken with alcohol and
  other CNS depressants.
• Adverse reactions
• Potential for abuse, tolerance, and physical
  dependence.

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BARBITURATES

• Reduce overall CNS alertness.
• Phenobarbital is the prototype drug in this
  class.
• Pharmacokinetics
• Absorbed well from the GI tract distributed
  rapidly metabolized by the liver excreted in
  the urine.

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BARBITURATES

• Pharmacodynamics
• Depress the sensory cortex of the brain, decrease
  motor activity, alter cerebral function, and
  produce drowsiness, sedation, and hypnosis.
• Pharmacotherapeutics
• Clinical indications include daytime sedation
  insomnia preop sedation and anesthesia anxiety
  relief anticonvulsant.

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BARBITURATES

• Drug interactions
• Interact with many other drugs.
• Phenytoin and valproic acid may increase toxic
  effects.
• Adverse reactions
• Tolerance, psychological and physical dependence

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NONBENZODIAZEPINES-NONBARBITURATES

• Act as hypnotics for short-term treatment of
  simple insomnia.
• Include chloral hydrate, ethchlorvynol
  (Placidyl), and zolpidem (Ambien).
• Pharmacokinetics
• Absorbed rapidly from the GI tract metabolized
  in the liver excreted in the urine.

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NONBENZODIAZEPINES-NONBARBITURATES

• Pharmacodynamics
• Mechanism of action not known but similar to
  barbiturates. Lose their effectiveness in 2 - 4
  weeks.
• Pharmacotherapeutics
• Used for short-term treatment of simple
  insomnia preop sedation pre-EEG sedation.

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NONBENZODIAZEPINES-NONBARBITURATES

• Drug interactions
• Additive CNS depression when taken with other CNS
  depressants.
• Adverse reactions
• Gastric irritation, N V, and hangover effects.

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ANTIDEPRESSANT AND ANTIMANIC DRUGS

• Used to treat affective disorders which are
  disturbances in mood characterized by depression
  or elation.
• Unipolar disorders (depression) are treated with
  MAO inhibitors, tricyclic antidepressants, or
  other antidepressants.
• Bipolar disorders (depression and mania) are
  treated with lithium.

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MAO INHIBITORS

• Divided into two classifications
• Hydrazines - phenelzine sulfate (Nardil)
• Nonhydrazines - tranylcypromine sulfate (Parnate)
• Pharmacokinetics
• Absorbed rapidly from the GI tract metabolized
  in the liver into metabolites excreted mainly by
  the GI tract.

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MAO INHIBITORS

• Pharmacodynamics
• Appear to work by inhibiting monoamine oxidase,
  the enzyme that normally metabolizes
  norepinephrine and serotonin, making these
  neurotransmitters more available to the receptors.

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MAO INHIBITORS

• Pharmacotherapeutics
• Treatment of choice for atypical depression
  (signs opposite of typical depression - weight
  gain, lacks suicidal tendencies, increased sexual
  drive).
• Also used to treat typical depression when other
  treatments are unsuccessful phobic anxieties,
  neurodermatitis hypochondriasis and refractory
  narcolepsy.

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MAO INHIBITORS

• Drug interactions
• Interact with a wide variety of drugs.
• Tyramine-rich foods (red wines, aged cheese,
  sympathomimetic drugs) can produce severe
  reactions if taken with MAO inhibitors.
• Adverse reactions
• Many including hypertensive crisis and
  orthostatic hypotension.

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TRICYCLIC ANTIDEPRESSANTS

• Used to treat depression.
• The following drugs are the most commonly used in
  this class imipramine hydrochloride (Tofranil),
  amitriptyline hydrochloride (Elavil), amoxapine
  (Asendin), and nortriptyline hydrochloride
  (Aventyl Pamelor).

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TRICYCLIC ANTIDEPRESSANTS

• Pharmacokinetics
• Absorbed completely when taken orally but undergo
  the first-pass effect metabolized in the liver
  excreted in the urine extremely fat-soluble
  leading to a longer half-life.
• Pharmacodynamics
• Increase the amount of norepinephrine and
  serotonin by preventing their reuptake and
  storage in the presynaptic nerves.

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TRICYCLIC ANTIDEPRESSANTS

• Pharmacotherapeutics
• Used to treat episodes of major depression.
• Less effective in patients with hypochondriasis,
  atypical depression, or depression with
  delusions.
• Also being investigated for use with migraine
  headaches, phobias, urinary incontinence,
  attention deficit disorder, ulcers, and diabetic
  neuropathy.

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TRICYCLIC ANTIDEPRESSANTS

• Drug interactions
• Interact with several commonly used drugs.
• Cimetidine impairs metabolism.
• Adverse reactions
• Orthostatic hypotension and sedation

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SELECTIVE SEROTONIN REUPTAKE INHIBITORS

• Developed to treat depression with fewer adverse
  effects.
• Chemically different from tricyclic
  antidepressants and MAO inhibitors.
• Include fluoxetine hydrochloride (Prozac),
  paroxetine hydrochloride (Paxil), and sertraline
  hydrochloride (Zoloft).

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SELECTIVE SEROTONIN REUPTAKE INHIBITORS

• Pharmacokinetics
• Almost completely absorbed after oral
  administration highly protein-bound metabolized
  in the liver excreted in the urine.
• Pharmacodynamics
• Inhibit neuronal reuptake of the neurotransmitter
  serotonin.

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SELECTIVE SEROTONIN REUPTAKE INHIBITORS

• Pharmacotherapeutics
• Used to treat major depressive episodes as well
  as obsessive-compulsive disorders.
• Paxil is also used to treat social anxiety
  disorder Zoloft is also used to treat
  posttraumatic stress disorder.
• Useful in treating panic disorders eating
  disorders personality disorders impulse control
  disorders and PMS.

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SELECTIVE SEROTONIN REUPTAKE INHIBITORS

• Drug interactions
• Interactions are associated with their ability to
  competitively inhibit a liver enzyme that is
  responsible for oxidation of numerous drugs.
• Use with MAO inhibitors can cause serious and
  potentially fatal reactions.
• Adverse reactions
• Anxiety, insomnia, sleepiness, palpitations

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MISCELLANEOUS ANTIDEPRESSANTS

• Include maprotiline hydrochloride (Ludiomil),
  mirtazapine (Remeron), bupropion hydrochloride
  (Wellbutrin), venlafaxine hydrochloride
  (Effexor), trazodone hydrochloride (Desyrel), and
  nefazodone hydrochloride (Serzone).
• Pharmacokinetics
• Properties vary by drug.

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MISCELLANEOUS ANTIDEPRESSANTS

• Pharmacodynamics
• Much about how these drugs work has yet to be
  fully understood.
• Pharmacotherapeutics Used to treat depression.
• Drug interactions May have serious and
  potentially fatal reactions when combined with
  MAO inhibitors
• Adverse reactions various.

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LITHIUM

• Lithium carbonate and citrate are the drugs of
  choice to prevent or treat mania and bipolar
  disorders.
• Pharmacokinetics
• Absorbed rapidly and completely when taken
  orally distributed to body tissues not
  metabolized excreted unchanged.

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LITHIUM

• Pharmacodynamics
• Mania - excessive catecholamine stimulation.
• Bipolar disorder - swings between excessive
  catecholamine stimulation (mania) and diminished
  catecholamine stimulation (depression).

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LITHIUM

• Regulates catecholamine release in the CNS by
  increasing norepinephrine and serotonin uptake
  reducing the release of norepinephrine from the
  synaptic vesicles in the presynaptic neuron
  inhibiting norepinephrines action in the
  postsynaptic neuron.

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LITHIUM

• Pharmacotherapeutics
• Used primarily to treat acute episodes of mania
  and to prevent relapses of bipolar disorders.
• Other uses include preventing unipolar
  depression migraine headaches treating
  depression alcohol dependence anorexia nervosa
  syndrome of inappropriate ADH and neutropenia.

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LITHIUM

• Drug interactions
• Serious drug interactions with other drugs can
  occur because lithium has a narrow therapeutic
  margin of safety.
• Adverse reactions
• Patients on a severe salt-restricted diet are
  susceptible to toxicity.

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ANTIANXIETY DRUGS

• Also called anxiolytics.
• Are one of the most commonly prescribed drugs in
  the US.
• Used primarily to treat anxiety disorders.
• Three main types are benzodiazepines,
  barbiturates, and buspirone.

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ANTIANXIETY DRUGS

• Buspirone hydrochloride (BuSpar) is the first
  anxiolytic in a class of drugs known as
  azaspirodecanedione derivatives.
• Structure and mechanism differs from other
  antianxiety drugs.
• Has several advantages less sedation no
  increase in CNS depressant effects when taken
  with alcohol or sedative-hypnotics lower abuse
  potential.

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ANTIANXIETY DRUGS

• Pharmacokinetics
• Absorbed rapidly undergoes intensive first-pass
  effect metabolized in the liver eliminated in
  the urine and feces.
• Pharmacodynamics
• Mechanism of action isnt known.
• Pharmacotherapeutics
• Used to treat generalized anxiety states not
  useful in panic attacks.

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ANTIANXIETY DRUGS

• Drug interactions
• Hypertensive reaction may occur when given with
  MAO inhibitors.
• Adverse reactions
• dizziness and lightheadedness

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ANTIPSYCHOTIC DRUGS

• Can control psychotic symptoms such as delusions,
  hallucinations, and thought disorders that can
  occur with schizophrenia, mania, and other
  psychoses.
• Drugs used to treat psychoses have several
  different names - antipsychotic, major
  tranquilizer, and neuroleptic.

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ANTIPSYCHOTIC DRUGS

• All antipsychotic drugs belong to one of two
  major groups
• Typical antipsychotics - phenothiazines and
  nonphenothiazines.
• Atypical antipsychotics - clozapine, olanzapine,
  and risperidone

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TYPICAL ANTIPSYCHOTICS

• Include phenothiazines and nonphenothiazines.
• Can be broken down into three smaller
  classifications
• Aliphatics - cause sedation and anticholinergic
  effects - chlorpromazine hydrochloride (Thorazine)

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TYPICAL ANTIPSYCHOTICS

• Piperazines - cause extrapyramidal reactions -
  fluphenazine decanoate (Prolixin)
• Piperidines - cause sedation - mesoridazine
  besylate (Serentil) and thioridazine
  hydrochloride (Mellaril)

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TYPICAL ANTIPSYCHOTICS

• Nonphenothiazine antipsychotics can be divided
  into several drug classes
• Butrophenones - haloperidol (Haldol)
• Dibenzoxazepines - loxapine succinate (Loxitane)
• Dihydroindolones - molindone hydrochloride
  (Moban)
• Diphenylbutylpiperidines - pimozide (Orap)
• Thioxanthenes - thiothixine (Navane)

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TYPICAL ANTIPSYCHOTICS

• Pharmacokinetics
• Absorbed erratically very lipid-soluble and
  protein-bound distributed to many tissues
  highly concentrated in the brain metabolized in
  the liver excreted in the urine and bile.
• Phenothiazines may produce their effect up to 3
  months after they are no longer taken.

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TYPICAL ANTIPSYCHOTICS

• Pharmacodynamics
• Mechanism of action not fully understood.
• Pharmacotherapeutics
• Used primarily to treat schizophrenia calm
  anxious or agitated patients improve a patients
  though processes alleviate delusions and
  hallucinations.
• Many other therapeutic uses have been found.

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TYPICAL ANTIPSYCHOTICS

• Drug interactions
• Interact with many different types of drugs that
  may produce serious effects.
• Nonphenothiazines interact with fewer drugs than
  phenothiazines.
• Adverse reactions
• Neurologic reactions are the most common.

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ATYPICAL ANTIPSYCHOTICS

• New agents designed to treat schizophrenia.
• Include clozapine (Clozaril), olanzapine
  (Zyprexa), and risperidone (Risperdal).
• Pharmacokinetics
• Absorbed after oral administration metabolized
  by the liver highly protein-bound eliminated in
  the urine/feces.

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ATYPICAL ANTIPSYCHOTICS

• Pharmacodynamics
• Block the dopamine and serotonin receptor
  activity.
• Pharmacotherapeutics
• Indicated for schizophrenic patients who are
  unresponsive to typical antipsychotics.
• Because of the decreased instance of
  extrapyramidal effects are becoming more widely
  prescribed.

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ATYPICAL ANTIPSYCHOTICS

• Drug interactions
• Counteract the effects of levodopa and other
  dopamine agonists.
• Adverse reactions
• Have less extrapyramidal effects than typical
  antipsychotics.