Pharm Lecture 3 Notes

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Pharm Lecture 3 Notes
2012-04-21 01:42:43

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  1. What is psychosis?
    • -Gross impairment in reality testing and creation of a new
    • unique reality that is not shared by others

    • -Impairment in reality testing is manifested by:
    • Disturbances in perception, thinking and speech including experiences not shared by others that occur in
    • the absence of any external stimulus

    • -Delusions
    • False fixed beliefs

    • -Disturbances in behavior
    • Bizarre and inappropriate behavior may include doing something irrational or dangerous to accomplish a desired goal
  2. Which psychotic problems are treated with antipsychotics? (6)
    • 1. Schizophrenia
    • 2. Schizophreniform disorder
    • 3. Schizoaffective disorder
    • 4. Delusional disorder
    • 5. Brief reactive psychosis
    • 6. Psychotic disorder, NOS
  3. Which disorders other then psychotic DOS are treated with antipsychotics?
    • .Bipolar Disorder
    • -Atypicals
    • §Most are on-label now for acute mania
    • .Mood disorders with psychotic features
    • -Bipolar Disorder
    • -MDD
    • .Parkinson’s disease
    • -L-Dopa-induced psychotic disorder (build more DA in cortex.. Cause psychotic features)
    • -Idiopathic Parkinson’s
    • -Developmental disorders
    • -Tourette’s
  4. Explanation of substance use that can give rises to psychotic features?
    • .Substance induced psychotic disorders
    • -Typcially result of acute intoxication with or withdrawal from a drug or substance
    • *Withdrawal from chronic alcohol abuse/dependence
    • *Intoxication with or sustained use of
    • >Stimulants or sympathomimetics
  5. Major classes of differential diagnoses for psychotic disorders?
    • Important rule-outs or differential diagnoses
    • -Endocrine Disorders:
    • *Addison’s disease
    • *Cushing’s disease
    • *Grave’s Disease (thyrotoxicosis or hyperthyroidism)
    • *Myxedema (hypothyroidism)
  6. Examples of substances that cause intoxication?
    • Intoxication with or sustained use of:
    • -Hallucinogens: LSD
    • -Dissociative anesthetics: PCP
    • -Opiods:
    • heroin, morphine, Vicodin, OxyContin
    • -Anti-inflammatory drugs such as steroids
    • -Anticholinergic drugs:
    • used to treat Parkinson-like side effects of antipsychotic drugs
    • -Withdrawal from chronic alcohol abuse/dependence
  7. Negative symptoms of schizophrenia?
    • Correlated with more problems
    • Higher rates of permanent disability
    • Affective flattening
    • Alogia
    • Avoiltion
    • Apathy
    • Anhedonia
    • Asociality
  8. Positive and negative symptoms of schizophrenia?
    • 1. Hallucinations
    • 2. Delusions
    • 3. Formal thought disorder
    • 4. Bizarre behavior
    • 5. Better response to medications
    • Less permanent disability
  9. Weak vs. potent antipsychotics?
    • 1.Potent = use low doses
    • Higher rate of extrapyramidal symptoms (EPS)

    • 2. Weak = use in high doses can be longer lasting
    • Dopamine antagonists (DA blockers)
    • Have potent side effects (all have side effects)
  10. Mechanisms of action of the dopamine blockers?
    Neuroleptic drugs modify several neurotransmitter systems.

    Despite this, a drugs efficacy in alleviating psychotic symptoms is best correlated with their effects on DA

    • Effective antipsychotics interfere with DA transmission by:
    • 1. Blocking post-synaptic DA receptors, and/or by
    • 2. Ultimately inhibiting DA release

    • Evidence for actions on DA comes from
    • 1. Their molecular structure
    • 2. Their side effects
    • Receptor binding and DA turnover
    • Neuroendocrine changes
  11. Effects and efficacy classic antipsychotic medications?
    • -Classic neuroleptics have widespread effects on numerous receptor systems
    • -Even looking at a single receptor type (e.g., D2), neuroleptics will have differing effects in different areas of the brain
    • -The relationship between therapeutic benefit and side effect profiles may depend on actions at different receptor subtypes within different brain pathways
  12. Side effects of antipsychotic medications on neuroendocrine systems – particularly prolactin?
    • 1. Neuroleptic Malignant Syndrome (rare):
    • Fatal in 20% of cases, High fever, Catatonia (bradykinesia) brady slow, taki fast. Stupor Unstable blood pressure and pulse

    • 2. Anticholinergic effects: (regonize!!!!)
    • Ataxia (loss of coordination), Burred vision, Confusion,
    • Dry mouth, Dry skin, Constipation, Delayed urination,
    • Weight gain, Sexual dysfunction

    • 3. Extrapyramidal (EPS) Side Effects:
    • Acute dystonia, Spasms of tongue, face, neck, back
    • Akathesia, Restlessness with anxiety or agitation,
    • Akinesia, Apathy, indifference in initiating activities, paucity of movement, lack of speech initiation, Parkinsonism (With longer term use: Motor slowing, retarded facial movement, muscular rigidity (catalepsy), gait disturbance, resting tremor, High speed jitters more anxiety.)

    • 4. EPS effects treated with other medications:
    • Titrate dose of medication
    • 5. Tardive Dyskenesia (parkinsonian)
    • Permanent, late developing movement disorder
    • Behavioral indications
    • Slow twisting of hands
    • Involuntary rhythmic movement in mouth and face
    • Spastic movement in limbs
    • Can cause tremendous social embarrassment
  13. EPS (and treatment), NMS, anticholinergic effects?
    • Extrapyramidal (EPS):
    • Acute dystonia
    • Spasms of tongue, face, neck, back
    • Akathesia
    • Restlessness with anxiety or agitation
    • Akinesia
    • Apathy, indifference in initiating activities, paucity of movement, lack of speech initiation
    • Parkinsonism
    • With longer term use
    • Motor slowing, retarded facial movement, muscular rigidity (catalepsy), gait disturbance, resting tremor
    • High speed jitters more anxiety.
    • EPS effects treated with other medications
    • -Titrate dose of medication
    • -Treated with anticholinergics.
    • 2. Neuroleptic Malignant Syndrome (rare):
    • Fatal in 20% of cases, High fever Catatonia (bradykinesia) brady slow, taki fast. Stupor, Unstable blood pressure and pulse.

    3. Anticholinergic effects (regonize!!!!) Ataxia (loss of coordination), Burred vision, Confusion, Dry mouth, Dry skin, Constipation, Delayed urination, Weight gain, Sexual dysfunction.
  14. TD rates, predictors and its treatment
    • -Permanent, late developing movement disorder
    • -Behavioral indications
    • Slow twisting of hands
    • Involuntary rhythmic movement in mouth and face
    • Repetitive sucking or blinking
    • Spastic movement in limbs
    • Can cause tremendous social embarrassment
    • Class of neuroleptic and specific drug
    • All antipsychotic drugs but clozapine
    • Newer atypicals present less risk than older typical anti-psychotics
    • Dosage of neuroleptic (how fast it will happen)
    • The higher the dose, the greater the risk
    • Potency of neuroleptic
    • Low potency (more meds) anti-psychotics present greater risk than high potency drugs

    lDiscontinuing medication not effective (can even make worse)

    lEPS drugs will make it worse

    • lNo known medical treatment to cure, some possibilities for
    • help


    • lWater soluble B vitamin may be
    • helpful

    lStill unclear if helpful


    lPossibly helpful, but not clear

    lVitamin E

    Not effective

    lDrug free intervals

    • Patients who stop taking their neuroleptics, with or without consent of their physician, appear to be at higher risk than those who do not take “drug
    • holidays”
    • Age
    • Older adults are at higher risk than younger adults
    • Gender
    • Women are at higher risk for TD than men
    • Smoking tobacco appears to increase risk of TD
    • Drinking alcohol increases the risk of TD

    lDuration of treatment

    lThe longer a person takes an anti-psychotic, the more likely s/he is to develop TD

    • lOnly 4-6% of patients taking neuroleptics for one year develop TD (classics, lower potency higher dose)
    • However, if a patient takes the neuroleptic continuously for 10 years, s/he will have a 49% probability of developing TD.
    • Drugs will cause it. Atypicals are the first lining drugs.
  15. Common interactions with the classic antipsychotic medications (induction and inhibition effects).

    • lSome drugs can elevate blood and tissue levels of neuroleptics by inhibiting the
    • action of liver enzymes (cytochrome P450 system) cause more EPS effects.

    lBecause the metabolism of the neuroleptic is slowed down, more of the drug stays in the bloodstream for longer times

    • lThus, a patient on a normal moderate dose of a neuroleptic may be at risk for overdose,
    • toxicity, or at minimum, increased occurrence of side effects like sedation,
    • EPS, and anticholinergic symptoms
    • 2.

    lInhibiting the action of liver enzymes (cytochrome P450 system)

    lThe following drugs interact with the older typical neuroleptics to raise blood levels of the neuroleptic


    • lInducing (speeding up) the action of
    • liver enzymes (cytochrome P450 system)
    • Because the metabolism of the neuroleptic is speeded up, less of the drug reaches the bloodstream and less is available for use at the brain receptor sites
    • Patient taking a usual dose of a neuroleptic may not get relief of psychotic symptoms
    • Neuroleptic dosage may need to be increased
    • to compensate for the increased metabolism of the drug by the interacting medication
    • 4.

    • lInducing
    • (speeding up) the action of liver enzymes (cytochrome P450 system)

    • lThe following drugs/substances interact with the older
    • typical neuroleptics to lower blood levels of the neuroleptic
    • 5.

    • lSome drugs may interact with neuroleptics and cause increased sedation (CNS
    • depression and CNS depression= more sedation). Low BP CNS.

    • lCNS depressants (narcotic
    • analgesics, anesthetics, anti-anxiety
    • drugs, sleep medicines, antihistamines),



    lOther drug interactions with neuroleptics may put the patient at risk for very low blood pressure (hypotension; orthostasis)
  16. General principles of how atypical antipsychotic medications work
    Multiple Receptor Antagonists

    lDesigned to block D2 and one or more other receptors (e.g., 5-HT2, α1-adrenergic, or D1).


    lFor example: clozapine (NOTICE atypical hit a lot)…

    lRelatively weak D1 and D2 affinities

    lSubstantial serotonergic, α-adrenergic, muscarinic, and histaminergic affinities

    lAlso, high affinity for recently cloned D4 receptor

    • lEffective for positive & negative symptoms and low
    • incidence of EPS and TD
  17. Clozapine and agranulocytosis?

    lClozaril (clozapine)

    lPrototypic atypical antipsychotic

    • lMore effective than traditional
    • antipsychotics

    • lEspecially good for refractory
    • patients and severe psychosis

    lGood with negative symptoms

    • lHelps promote gains in social and
    • occupational functioning
    • lUsed to treat BD and Schizoaffective disorder
    • lUsed to treat Parkinson’s disease
    • related problems (D1 to go after D4 as a blocker for Park.
    • No effect on prolactin
    • Low EPS
    • 2. Agranulocytosis NB! (rare!)
    • high fever and a sharp drop in circulating granular white
    • blood cells
  18. Risperdal and dose related EPS and TD
    §Risperdal (risperidone)

    §Chemically unrelated to any other antipsychotic

    §Potent 5-HT2A, 5-HT7, α1- and α2 adrenergic, and histamine H1 receptor antagonist

    §Also, D2 antagonist comparable to haloperidol


    §Possesses many of the benefits of clozapine without the risk of blood disorders (e.g., agranulocytosis)

    §Less catalepsy than Haldol

    §Interactions with other drugs likely

    lRisperdal (risperidone)

    • lGood for positive and negative
    • symptoms

    • lGood for treatment refractory
    • patients

    • lUsed for mood disorders with
    • psychotic features

    • lOne study showed increase in
    • mania for shizoaffectives

    lMay lead to emergence of OCD behaviors & thinking

    Used for Tourette’s and DD


    lSide effects

    • lDefinitely has dose-related EPS
    • (inside dosing range pretty safe but if not can be dangerous)

    • lDon’t want patients dosed over
    • 10mg


    lOrthostatic hypotension


    • lIncreases prolactin
    • 3.

    lRecently developed long lasting injectable form

    lUses microspheres – injected into skin

    lNo greater association with EPS and TD

    lWill see these though

    lMay have advantages for compliance
  19. Issue of weight gain and diabetes with newer antipsychotic medications. Name two?
    • Zyprexa (olanzapine): Weight Gain <-know!
    • Abilify (aripiprazole): Minimal Weight Gain
  20. General issues for pharmacotherapy with antipsychotic medications?
    • -Has the patient been treated successfully in the past with an anti-psychotic drug?
    • -Is sedation needed to help manage this patient’s symptoms?
    • -The side effect profile of the drugs, the patient’s unique
    • characteristics, and medical conditions
    • -Certain antipsychotic medications have more severe side effects than others
    • -The goal is to limit, minimize, and manage side effects so that the patient is able to tolerate the drug’s side effects
  21. Increasing compliance for antipsychotic medications
    • 1. Asking a patient to monitor their medication-taking behavior is often enough to improve compliance
    • -Ask a person to carry a little card in their pocket that
    • lists all the days/times for medication administration
    • -When they take a dose, they put a check mark next to the
    • correct day/time
    • -When the patient comes to see the clinician or physician, thecan share this info from card
    • -It provides an opportunity for the clinician to review
    • medication taking behavior, highlight problems, and provide praise, support and
    • encouragement, as appropriate, and simple monitoring like that increases compliance

    • 2.Clinicians can also help the patient set up contingencies, positive rewards for appropriate medication administration:
    • -This approach helps patients take control over their
    • medication compliance by using behavioral techniques; it helps them help
    • themselves
    • -Support from family and friends is also crucial in
    • maintaining medication compliance

    • 3. Psychoeducation
    • -Need to involve families and
    • other social support-Need to explain importance of being asymptomatic
    • -Not cured, but getting better
    • - Need to help anticipate triggers for problems
    • -Not taking medications is a big one!