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Pharmacology of Psychotherapeutic Drugs By : Dr Seddigh HUMS.
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Transcript of Pharmacology of Psychotherapeutic Drugs By : Dr Seddigh HUMS.
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Pharmacology of Psychotherapeutic Drugs
By : Dr SeddighHUMS
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Psychiatric Diagnoses
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Diagnoses of Concern Mood Disorders Substance abuse related Somatoform Disorders Anxiety Disorders Psychotic Disorders Personality Disorders Impulse Control Disorders Factitious Disorders (Munchausen’s) Malingering
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Critical Situations
Suicide risk v. accidental overdose Potential for violence toward others Multi-substance abuse Undiagnosed depression Opioids and benzodiazepines Poor impulse control
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What is Multi-Axial Diagnosis? Axis I: Clinical Disorders & other conditions that
may be focus of attention Axis II: Personality Disorders, Mental
Retardation Axis III: General Medical Conditions Axis IV: Psychosocial and Environmental
Problems Axis V: Global Assessment of FunctioningAm Psychiatric Association, 2000. Quick Reference to the Diagnostic Criteria from DSM-IV-TR.
Washington, DC: APA Press.
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Mood Disorders
Major Depressive Disorder Dysthymic Disorder Depressive Disorder (NOS) Bipolar
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Psychotic Disorders
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Psychotic Disorders
Schizophrenia Schizophreniform Schizoaffective Disorder Delusional Disorder Brief Psychotic Disorder
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Pharmacology Basics
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Classes of Psychiatric Drugs
Tricyclics & Tetracyclics
Selective Serotonin Reuptake Inhibitors
Monoamine Oxidase Inhibitors
“Atypical” antidepressants
Benzodiazepines
Nonbenzodiazepine anxiolytics
Antipsychotics “Atypical”
antipsychotics Lithium Antiepileptic drugs Stimulants Anti-EPS agents
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Cyclic Antidepresants
Imipramine (Tofranil)
Desipramine (Norpramin)
Amitriptyline (Elavil) Nortriptyline
(Pamelor) Clomipramine
(Anafranil)
Trimipramine (Surmontil)
Doxepin (Sinequan) Protriptyline
(Vivactil) Amoxapine
(Asendin) Maprotiline
(Ludiomil)
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Cyclic Antidepressant Indications
Generalized Anxiety Disorder Obsessive-Compulsive Disorder Panic Disorder with Agoraphobia Anorexia Nervosa &Bulimia Cataplexy & narcolepsy Depression Childhood enuresis Migraine & pain Urticaria & itching
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Cyclic Adverse Effects
Weight gain Inducing mania Anticholinergic
dry mouth, constipation, blurred vision, urinary retention Sedation Autonomic
orthostatic hypotension, profuse sweating, palpitations, hypertension
Cardiac tachycardia, flattened T waves, prolonged QT intervals, depressed
ST segments Neurological
delirium, psychomotor stimulation, myoclonic twitches, tremors, paresthesias, peroneal palsies, ataxia
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Selective Serotonin Reuptake Inhibitors
Citalopram (Celexa) Escitalopram (Lexapro) Fluoxetine (Prozac) Fluvoxamine (Luvox) Paroxetine (Paxil) Sertraline (Zoloft)
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SSRI Indications
Depression & suicidality Obsessive-Compulsive Disorder Panic Disorder Eating Disorders Alcoholism Obesity
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Features of Serotonin Syndrome Diarrhea Diaphoresis Tremor Ataxia Myoclonus Hyperactive reflexes Disorientation Rigidity
Uncontrollable shivering Hyperthermia Delirium Coma Status epilepticus Cardiovascular collapse Death
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MAO Inhibitors
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MAOI Indications
Atypical depression Major depression Dysthymia Melancholia Panic disorder Bulimia Atypical facial pain Parkinson’s Disease
Obsessive-compulsive
Narcolepsy Headache Chronic pain
disorder Generalized anxiety
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MAO Inhibitor Drugs MAO A
Nonselective inhibitors Phenelzine (Nardil) Tranylcypromine (Parnate) Avoid tyramine-containing foods
MAO B Selective inhibitor Selegiline [deprenyl] (Eldepryl) Avoid tyramine and SSRIs Lose selectivity at high doses
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MAO Inhibitor drug interactions Antidepressants
SSRIs
Tricyclic antidepressants
Sympathomimetics
Ephedrine
Some opioids
Meperidine
Pentazocine
Dextromethorphan
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MAOI Dietary Interactions
Contain Tyramine Cheese Overripe aged fruit Fava beans Sausage, salami Sherry, liquors Sauerkraut MSG (glutamate)
Pickled fish Brewer’s yeast Beef & chicken liver Fermented products Red wine Caffeinated
beverages Chocolate
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Medications to Avoid with MAOIs
Antiasthmatics Antihypertives (methyldopa, guanethidine) Buspirone Levodopa Opioids Cold, allergy or sinus medications with
dextromethorphan or sympathomimetics SSRIs, clomipramine, venlafaxine, sibutramine Sympathomimetics L-Tryptophan
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Medications to Use Carefully with MAOIs
Anticholinergics Antihistamines Disulfiram Bromocriptine Hydralazine Sedative-hypnotics Terpin hydrate with codeine Tricyclics & tetracyclics
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Atypical Antidepressants
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Atypical Antidepressants
Buproprion (Wellbutrin, Zyban) Duloxetine (Cymbalta) Mirtazapine (Remeron) Nefazodone (Serzone) Trazodone (Desyrel) Venlafaxine (Effexor)
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Atypical Antidepressant Indications
Depression Generalized Anxiety Disorder Obsessive-Compulsive Disorder Smoking Cessation Panic Disorder Agoraphobia Chronic pain
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Atypical Antidepressant Adverse Effects and Problems
Buproprion: headache, insomnia, upper respiratory complaints, nausea, restlessness, agitation & irritability
Duloxetine: nausea, dry mouth, fatigue, dizziness, constipation, somnolence & sweating
Mirtazapine: somnolence, dizziness, increased appetite, increased cholesterol and triglycerides, orthostatic hypotension
Nefazodone: postural hypotension, activation of mania, liver dysfunction
Trazodone: sedation, orthostatic hypotension, dizziness, headache, nausea, priapism
Venlafaxine: nausea, somnolence, dry mouth, hypertension, dizziness, nervousness, constipation, etc.
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Benzodiazepines
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Benzodiazepines
Triazolam (Halcion) Alprazolam (Xanax) Lorazepam (Ativan) Oxazepam (Serax) Temazepam
(Restoril) Chlordiazepoxide
(Librium) Clonazepam
(Klonopin)
Diazepam (Valium) Clorazepate
(Tranxene) Halazepam
(Paxipam) Prazepam (Centrax) Flurazepam
(Dalmane) Estzolam (ProSom) Midazolam (Versed)
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Benzodiazepine Indications
Sedative-hypnotics Muscle relaxants Anticonvulsants Alcohol withdrawal Anxiety disorders Agitation control
Nocturnal myoclonus
Tic douloureux Tetanus Cerebral malaria Chloroquine toxicity Maternal eclampsia
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Nonbenzodiazepine Anxiolytics
Meprobamate (Miltown) Buspirone (Buspar) Gepirone (Ariza) Ipsapirone Tandospirone
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Antipsychotics
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Antipsychotics
Phenothiazines: Chlorpromazine (Thorazine), Fluphenazine (Prolixin), Mesoridazine (Serentil), Trifluoperazine (Stelazine), Perphenazine (Trilafon), Thioridazine (Mellaril)
Butyrophenones: Haloperidol (Haldol) Thioxanthenes: Thiothixene (Navane) Dihydroindolones: Molindone (Moban, Lidone) Dibenzoxazepines: Loxapine (Loxitane) Diphenylbutylpiperidines: Pimozide (Orap)
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Antipsychotic Mechanisms D2 receptor antagonists 5HT2 receptor antagonists Older agents generally have higher
5HT/DA binding ratios The atypical antipsychotics have less
potential for extrapyramidal side effects (EPS)
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Antipsychotic Indications
Acute Schizophrenia Chronic Schizophrenia Schizoaffective Disorders Depression with Psychotic Features Agitation Mania Chorea
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Antipsychotic Adverse Effects Cardiac toxicity &
sudden death Orthostatic hypotension Hematological toxicity Increased secretion of
prolactin Sexual dysfunctions Weight gain Jaundice Dermatitis and
photosensitivitySadock BJ & Sadock VA, 2003. Kaplan & Sadock’s
Synopsis of Psychiatry 9th Ed. Philadelphia, PA: Lippincott Williams & Wilkins.
Neuroleptic-induced Parkinsonism
Neuroleptic-induced Acute Dystonia
Neuroleptic-induced Tardive Dyskinesia
Neuroleptic Malignant Syndrome
Lowered seizure threshold
Sedation Anticholinergic effects
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Atypical Antipsychotics
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Atypical Antipsychotics
Aripiprazole (Abilify) Clozapine (Clozaril) Olanzapine (Zyprexa) Quentiapine (Seroquel) Risperidone (Risperdal) Ziprazadone (Geodon)
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Advantages of Atypical Antipsychotic Agents
These are serotonin-dopamine antagonists (except aripiprazole which is partial agonist for D2 receptors, but behaves as functional antagonist in hyper DA states & agonist in hypo DA states)
Lower risk for Extrapyramidal Side Effects (EPS) than DA antagonists
Effective for positive & negative symptoms Effective for treatment of mood disorders with
psychotic or manic features & for behavioral disturbances with dementia
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Toxicities of Atypical Antipsychotic Agents
Aripiprazole: Too new to be fully known (mild nausea & vomiting, wt. loss, lowered prolactin levels, low levels of EPS)
Clozapine: sedation, dizziness, syncope, tachycardia, hypotension, ECG changes, leukopenia (aplastic anemia), wt. gain
Olanzapine: Somnolence, dry mouth, dizziness, constipation, dsypepsia, increased appetite & wt. gain, tremor
Quetiapine: somnolence, postural hypotension, dizziness, modest wt. gain
Risperidone: dose-dependent EPS, wt. gain, anxiety, nausea, erectile and orgasmic dysfunction
Ziprasidone: somnolence, headache, dizziness, nausea, QT prolongation (fatal in pts with Hx of cardiac arrhythmia)
Many cause abnormalities with glucose & lipid metabolism leading to DM & hyperlipidemias
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Risk Factors Leading to Acute Dystonic Reactions
Male gender Younger age Previous dystonic reaction Using higher doses of medication Giving higher potency antipsychotics Intramuscular route of administration
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Drugs to Treat ExtrapyramidalSide Effects
Benztropine (Cogentin) Trihexyphenidyl (Artane) Procyclidine (Kemadrin) Diphenhydramine (Benadryl) Biperiden (Akineton) Amantadine (Symmetrel)
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Strategies for Extrapyramidal Side Effects (EPS) Reduce antipsychotic medication dose Substitute lower-potency antipsychotic Add an anticholinergic agent, titrate up Add amantadine to anticholinergic agent Add a benzodiazepine or beta-blocker Stop antipsychotic medication Substitute an atypical agent
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Antimania Medications
Lithium Benzodiazepines Anticonvulsants
Carbamazepine (Tegretol)
Gabapentin (Neurontin)
Lamotrigine (Lamictal) Topiramate (Topamax) Valproate (Depakote);
valproic acid (Depakene)
Calcium Channel Antagonists
Amlodipine Isradipine Nicardipine Nifedipine Nimodipine Nisoldipine Verapamil
Atypical antipsychotic agents
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Anticonvulsant Issues Carbamazepine: blood dyscrasias, hepatitis, exfoliative
dermatitis, GI upset, acute confusional state, decreased cardiac conduction, SIADH, birth defects
Gabapentin: somnolence, dizziness, ataxia, fatigue, nystagmus
Lamotrigine: decreased valproic acid level, increased carbamazepine epoxide metabolite, life-threatening skin rashes
Topiramate: increased phenytoin and valproic acid levels, psychomotor slowing, speech & language problems, dizziness, ataxia, fatigue, poor concentration, wt. loss, tremor
Valproate: GI distress, sedation, tremor, wt. gain, hair loss, elevated transaminases, fatal hepatotoxicity, platelet dysfunction
Sadock BJ & Sadock VA, 2003. Kaplan & Sadock’s Synopsis of Psychiatry 9th Ed. Philadelphia, PA: Lippincott Williams & Wilkins.
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Responsiveness to Lithium Unfavorable
Borderline features Neuroticism Rapid cycling Mixed
manic/depressive Sx Substance abuse Psychosis Depression followed
by maniaSadock BJ & Sadock VA, 2003. Kaplan & Sadock’s
Synopsis of Psychiatry 9th Ed. Philadelphia, PA: Lippincott Williams & Wilkins.
Favorable Prior long-term response
to Lithium Classic euphoric or pure
mania Family history of bipolar
disorder Secondary mania Family history of
response to lithium Obsessional features Mania followed by
depression
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Recognizing Lithium Toxicity GI (mild)
Vomiting Abdominal pain Dryness of mouth
Neurological (mild) Ataxia Dizziness Slurred speech Nystagmus Lethargy or excitement Muscle weakness
GI (moderate-severe) Anorexia
Neurological (mod-sev) Muscle fasciculations Clonic limb movements Hyperactive DTRs Choreoathetoid
movement Convulsions Delirium Stupor Coma Death
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Stimulants
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Stimulants
Cocaine Amphetamines
Amphetamine (Adderall) Dextroamphetamine (Dexedrine) Methamphetamine (Desoxyn)
Methylphenidate (Concerta, Ritalin) Modafinil (Provigil) Pemolin (Cylert)
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Stimulant Indications
Narcolepsy Attention Deficit Hyperactivity Disorder Enhanced alertness and combat
readiness (military only) Unofficial uses:
Reversing opioid induced sedation Refractory depression Chronic pain Stroke
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Psychopharmacological Treatment of Agitation Anticonvulsants Antipsychotics Benzodiazepines Beta-blockers Buspirone Lithium Serotoninergic antidepressants
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Impediments to Adherence to Recommended Treatment
Excessively complex regimens Early onset & persistence of side effects Slow onset of beneficial effects Low apparent relapse risk experienced if
treatment is interrupted Psychosis, confusion, dementia, low
intelligence, impaired hearing or vision Lack of information & need for education Involvement of multiple clinicians
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Conclusions
Medications play a vital role in the management of mental illness.
There is still a role for therapy, and working with families.
There is much to still learn about drug therapy for mental illness.
Keep studying and asking questions.
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ReferencesSadock BJ & Sadock VA. Kaplan & Sadock’s
Synopsis of Psychiatry 9th Ed. Philadelphia, PA: Lippincott Williams & Wilkins. 2003
Am Psychiatric Association Quick Reference to the Diagnostic Criteria from DSM-IV-TR. Washington, DC: APA Press. 2000
Drugs for Pain. Hanley & Belfus, Philadelphia. Misc. chapters. 2003.