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WĂƌŬŝŶƐŽŶ͛Ɛ ĚŝƐĞĂƐĞ ‡ Paralysis Agitans ‡ Dr. James Parkinson - ͞ƐŚĂŬŝŶŐƉĂůƐLJ͟;ϭϴϭϳͿ WĂƌŬŝŶƐŽŶ͛Ɛ ĚŝƐĞĂƐĞ ‡ neurodegenerative disease associated with depigmentation of the substantia nigra and the loss of dopaminergic input to the basal ganglia (extrapyramidal system); ‡ it is characterized...

WĂƌŬŝŶƐŽŶ͛Ɛ ĚŝƐĞĂƐĞ ‡ Paralysis Agitans ‡ Dr. James Parkinson - ͞ƐŚĂŬŝŶŐƉĂůƐLJ͟;ϭϴϭϳͿ WĂƌŬŝŶƐŽŶ͛Ɛ ĚŝƐĞĂƐĞ ‡ neurodegenerative disease associated with depigmentation of the substantia nigra and the loss of dopaminergic input to the basal ganglia (extrapyramidal system); ‡ it is characterized by distinctive motor disability. ^LJŵƉƚŽŵƐ ŽĨ WĂƌŬŝŶƐŽŶ͛Ɛ ŝƐĞĂƐĞ ‡ Tremors (shaking usually starts on one side of the body, often in the hand or finger) ‡ Rigidity ‡ Akinesia (difficulty in initiating movement and slowness of movement) ‡ Postural instability  Classification of Drug Therapy for WĂƌŬŝŶƐŽŶ͛Ɛ ŝƐĞĂƐĞ ‡ Two major categories 1. Dopaminergic agents : ‡ Promote activation of dopamine receptors 2. Anticholinergic agents : ‡ Prevent activation of cholinergic receptors Mechanisms of Action ‡ Promotion of dopamine synthesis ‡ Direct activation of dopamine receptors ‡ Prevention of dopamine degradation ‡ Promotion of dopamine release ‡ Blockade of muscarinic cholinergic receptors in the striatum ANTIPARKINSONIAN DRUGS 1. LEVODOPA + CARBIDOPA 2. DOPAMINE RECEPTOR AGONISTS - Bromocriptine, Pergolide, Pergolidee, Pramipexole, Pram mipexole, Ropinirole Ro opinirole 3. MAO-B INHIBITORS - Selegiline, Rasageline 4. COMT INHIBITORS - Entacapone, Entacap pone, Tolcapone 5. AMANTADINE 6. ANTICHOLINERGICS - Benztropine mesylat mesylate, te, Biper Biperiden, riden, Trihexyphenidyl Trihexyphen nidyl ͞WƐLJĐŚŽƐŝƐΗ ‡ denotes a variety of mental disorders  clear sensorium but a marked thinking disturbance The Course of Schizophrenia ‡ Prodromal phase: ‡ Onset and buildup of schizophrenic symptoms The Course of Schizophrenia ‡ Active phase: ‡ Full-blown symptoms: severe disturbances in thinking, deterioration in social relationships, and flat or inappropriate affect The Course of Schizophrenia ‡ Residual phase: ‡ Symptoms no longer prominent ‡ Complete Com mplete recovery recoveery is rare,, but sch schizophrenics hizophrenics can caan lead lead productive lives. The Symptoms of Schizophrenia ‡ Characteristic symptoms: ‡Two or more of the following, each persisting for a significant portion of at least a 1- month period: ‡ Positive symptoms ‡ Disorganized speech ‡ Grossly disorganized or catatonic behavior ‡ Negative symptoms The Symptoms of Schizophrenia ;ĐŽŶƚ͛ĚͿ ‡ Positive symptoms: ‡ Symptoms which are not present in the normal individual but are added to the schizophrenic person. ‡ hallucinations and delusions Positive Symptoms ‡ Distortions or excesses of normal functioning ‡ Delusions: ‡ False beliefs firmly and consistently held despite disconfirming evidence or logic Positive Symptoms ‡ Delusions: ‡ Delusions of grandeur Delusions of control Delusions of thought broadcasting Positive Symptoms ‡ Delusions: Delusions of persecution Delusions of reference ± ³FHQWHURIDWWHQWLRQ´ Positive Symptoms ‡ Delusions: ‡ Thought withdrawal &DSJUDV¶V\QGURPH ± ³GRXEOH´ WŽƐŝƚŝǀĞ ^LJŵƉƚŽŵƐ ;ĐŽŶƚ͛ĚͿ ‡ Perceptual distortion (hallucinations): Sensory perceptions not directly attributable to environmental stimuli (appear real to the schizophrenic): ‡ Auditory Audiitory (hearing) (hearing) ‡ Visual Visuaal (seeing) ‡ Olfactory Olfacctory (smelling) ‡ Tactile Tactiile (feelings) ‡ Gustatory Gustattory (tasting) The Symptoms of Schizophrenia ;ĐŽŶƚ͛ĚͿ ‡ Negative symptoms: ‡ Symptoms involving characteristics, behavior or abilities that are present in a normal person but missing in the schizophrenic in individual. ndividual. ‡ Associated with inferior premorbid social functioning The Symptoms of Schizophrenia ;ĐŽŶƚ͛ĚͿ ‡ Negative symptoms: ‡ Flat affect ‡ (little or no emotion in situations in which strong reactions are expected) ‡ alogia (poverty of speech) ‡ The failure to respond to questions or comments ‡ Can also take the form of slow or delayed responses The Symptoms of Schizophrenia ;ĐŽŶƚ͛ĚͿ ‡ Negative symptoms: ‡ Avolition ‡ (inability (inab bility to take action or to become becom me goal oriented) oriennted) ‡ Inactivity Inacttivitty or or early loss of interest ntereest in ongoin in ongoing ng aactivity ctivity ‡ ***May ***MMay indicate indicaate irreversible ble neuronal irreversib neuronaal loss loss in a structurally abnormal brain Negative symptoms: ‡ Asociality ‡ Inability to form close cllose personal relationships relationship ps ‡ Anhedonia: ‡ Inability Inabilitty tto o feel pleasure Disorganized Symptoms ‡ Disorganized speech (Formal thought disorder) ‡ Incoherence ‡ Inability to organize ideas ‡ Loose associations (derailment) ‡ Rambles, difficulty difficculty stickingg to one topic to opic Disorganized Symptoms ‡ Disorganized behavior ‡ Odd or peculiar behavior ‡ Silliness, agitation, unusual dress ‡ e.g., wearing several heavy coats in hot weather Other symptoms ‡ Catatonia ‡ Motor ab abnormalities bnormalities ‡ Repetitive, com complex mplex gestures ‡ Usually of the fingers or hands ‡ Excitab Excitable, ble, wild flailing of limbs lim mbs ‡ Catatonic immobility ‡ Ma Maintain aintain unusual posture possture for long period of timee e.g., e.g., stand on one leg Other symptoms ‡ Waxy flexibility ‡ Limbs can be mani manipulated ipulated and posed posed by another an nother person perso on Other symptoms ‡ Inappropriate affect ‡ Emotional responses responsses inconsistent inconsisteent with situation situaation PATHOPHYSIOLOGY ‡ NEUROTRANSMITTER CHANGES ‡ Dopamine ‡ Glutamate ‡ Serotonin ANTIPSYCHOTICS Phenothiazine ‡ Aliphatic ‡ Chlorpromazine ‡ Promazine ‡ Trifluoropromazine Triflu uoropromazine ‡ Piperidine ‡ Thioridazine ‡ Mesoridazine Mesooridazine ‡ Piperacetazine Piperracetazine Phenothiazine ‡ Piperazine ʹ more potent, more selective ‡ Fluphenazine ‡ Perphenazine ‡ Acettophenazine Acetophenazine ‡ Triflu uoroph henarine Trifluorophenarine ‡ Procchlorperazinee Prochlorperazine  Antipsychotic/Neuroleptics Piperazine P iperazine e Piperazine>Piperidine>Aliphatic Piperidine Pip peridine Aliphatic Alipha atic Which is the MOST POTENT? [Drug dose] Atypical Anti-psychotics ‡ Dibenzoxazepine ʹ Loxapine ‡ Dibenzodiazepine ʹ Clozapine ‡ Benzisoxazole ʹ Risperidone ‡ Thienobenzodiazepine ʹ Olanzapine ‡ Fluorophenylindole ʹ Sertindole ADRs - ANTIPSYCHOTICS ‡ Seizures ʹ Clz, Chlorpromazine ‡ Agranulocytosis ʹ Clozapine ‡ Cardiotoxicity ʹ Thioridazine ‡ Prolong QT interval ʹ Ziprasidone, Sertindole ‡ Cornea/Lens deposit ʹ Chlorpromazine ‡ Retinal deposits ʹ Thioridazine ‡ Neuroleptic Malignant Syndrome Extrapyramidal symptoms (EPS) ƒ aka neuroleptic-induced parkinsonism ƒ most common (15%) ƒ coarse tremors, rigidity, bradykinesia ƒ Risk: high potency TX: lower dose, anticholinergics These symptoms include dystonia (continuous spasms and muscle contractions),akathisia (motor restlessness), parkinsonism (characteristic symptoms such asrigidity), bradykinesia (slowness of movement), and tremor, and tardive dyskinesia (irregular, jerky movements). AFFECTIVE DISORDERS ‡ mental illnesses characterized by pathological changes in MOOD Unipolar disorders Bipolar disorder Depression (manic-depressive illness) ± Mania ³F\FOLQJPRRG³ MAJOR DEPRESSIVE DISORDER (MDD) ‡ Characterized by a DEPRESSED mood most of the time for at least 2 weeks or loss of interest or pleasure in most activities MAJOR DEPRESSIVE DISORDER (MDD) ‡ SYMPTOMS ‡ feelings of guilt or low low self-worth, self-wortth, ‡ appettite, disturbed sleep or appetite, ‡ energy low energy ‡ poorr concen ntration concentration ‡ Suiciidal attempts Suicidal attemptts Therapy of depression ‡ Non-pharmacological treatment ‡ Psychotherapy Psychoth herapy (cognitive b behavior eh havior therapy therap py ) ‡ Electroconvulsive Electtroconvulssive therapy ((ECT) ECT) TREATMENT PHASES FOR DEPRESSION TREATMEN TREATMENT NT DURATION G GOAL OAL PHASE Acute § 6 w eeks eeks s Resolve Reso symptoms olve sympto oms Continuation Continu uation months 6-9 mont ths Prevent nt relapse Preven relapse Maintenance 3-5 years of Prevent recurrence in lifelong lifel long high hig gh risk risk patie patients ents* ANTIDEPRESSANTS y SSelective electiive Serotonin Re-uptake Inhibitors (SSRI) y FLUOXETINE, FLUOXETTINE, SSERTRALINE, ERTRALINE, CCITALOPRAM ITALOPRAM y Tricyclic antidepres ssants (TCA) antidepressants y IMIPRAMINE, AMOXA APINE, AMYTRIPTYLINE, AMOXAPINE, AMYYTRIPTYLINEE, D ESIPRAM MINE DESIPRAMINE y Monoami Monoamine ine oxidase inhibitorss (MAOI) y PHENELZINE, PHENEELZIINE, ISOCARBOXAZID, ISOCARBOXAZZID, TRANYLCYPROMINE, TRANYLCYPR ROMINE, MOCLLOBEMID MOCLOBEMIDE DE y Serotonin Serotonin-2 n-2 Antagonist Antagonists/Reuptake ts/Reupptake In Inhibitors nhibitors (SA (SARI) ARI) y TRAZODONE, TRAZO NEFAZODONE ODONE, NEFAZODON NE y NE and Dopamine Reuptake Inhibitors (NDRI) y BUPROPION N yN Noradrenaline Reuptake oradrenaline Reupt (NaRI) take Inhibitors (N NaRI) yRREBOXITINE EBOXITINE Other antidepressants: 1. Venlafaxine (Effexor) ƒ Serotonin and NE reuptake reuptake inhibitor (SNRI) (SSNRI) 2. Mirtazapine (Remeron) ƒ noradrenergic and specific serotonergic antidepressant (NaSSA) Antimanic Agents/Mood Stabilizers Lithium carbonate (Eskalith, Quilonium) ‡ DOC ‡ unknown unknnown mechanism ‡ Narrow therapeutic Narrrow the erapeutic index ‡ Therapeutic Therrapeutic range: rangge: 0.6-1.2 2 mEq/L Adverse Effects Minor: tremor, polyuria, gastrointestinal distress, memory problems, acne exacerbation, weight gain Long-term: hypothyroidism Toxicity: ataxia, coarse tremor, confusion, coma, sinus arrest, and death Interactions: ƒ Diuretics - dec. NaÆ inc. Li; ƒ excessive Na intake Æ dec.Li ƒ Other mood stabilizers: valproic acid, carbamazepine