PSYCHOPHARMACOLOGY ANTI-PSYCHOTICS ANTI-SCHIZOPHRENICSPsychiatric IllnessImpairment of thinking process, mood, behavior and perceptionPsychiatric Illness:-Neurosis: Psychosis Mild Problem serve problem Comprehension to accept reality that he is ill and exaggerate his condition. Patient lives in imagination Neurosis include anxiety states Anxiety Phobic states: fear of places, persons or situations Obsessive compulsive states even can’t stop himself voluntary, he compel to do it. Post traumatic stress disorder Hysteria: having severe physical sufferings, Rxn in response to severe disease, loss of some relative or some hard situation etc. Reactive depression.Psychosis: Schizophrenia Split mind Thought disorder Affective disorders Depression Mania Bipolar depressive illness Organic Psychosis Mentally disturb caused by Alcoholism Org - disease Head injureSchizophrenia: Most important and highly disabling Large portion of patients in mental hospitals Affect in early young adult lifeIncidence: 1 % of total population
Ac episode ____ 20 % cured by treatment Rest follows a chronic cause Suicide is about 10% casesEtiology: Not known Strong but incomplete genetic pre-disposition (1st degree relatives – 10%) (2nd monozygotic twin – 50%) Genetic predisposition but not complete.Hypothesis:1. Environmental Factors: Maternal viral infection associated with autoimmune process & high B.P duringpregnancy2. Neurodevelopmental Factors: Involving mainly cerebral, cortical neurons & limbic systemSymptoms:1.Positive symptom: (result from Neurochemical Abnormality) Increase do paminergic transmission Respond well to Rx a) Delusions often paranoid in nature: (persecuting type pt. feeling everybody conspirating against him, laughing at them) in nature. These delusions cant be rectified by reasoning. b) Hallucinations: (usually auditory often exhortatory in their message) They may be • Visual • Auditory • Tactile (CD Canine bugs)Usually threatening, harsh types and pt. responding to those hallucinations. c) Thought disorder Wild train of thoughts and garbled sentences. Draw irrational conclusion with the feeling that thoughts are inserted or withdrawn by an outside agency. Usually not like to be interfered, flight of ideas from one thought to other thought. Broadcast of ideas. d) Abnormal stereotypical behavior, usually aggressive.
e) Defectiveness in selective attention unnecessary voices are ignored but he can’t ignore unnecessary voices.2. Negative Symptoms: • Result from brain atrophy • Don’t respond / less responsive to Rx a) Emotional blunting (flattening of emotional responses) he likes to remain alone. b) Poor Socialization (withdrawal of social contacts) c) Cognitive deficit (Dementia) Irritability more irritable.Neurochemical Basis:1) Dopamine Theory (Hypothesis by Carlson awarded noble prize in year 2000) Dopamine hyperactivity in mesolimbic and mesocortical pathway & amygdalepositive symptoms of schizophrenia. Proof: • Dopamine agonists – produce these symptoms of schizophrenia e.g. central sympatholytics Amphetamines) • Block Dopamine recap Improve the symptoms2) Glutamate Theory Glutamate and DA exert excitatory and inhibitory effects respectively on GABA ergic striatal neurons which project to thalamus and constitute “sensory Gate” Glutamate or DA disables the gate and uninhibited sensory input reaches the cortex. Glutamate NMDA (N-methyl deaspartate) recep antagonists: Phencyclidine Katamine Produce Psychotic Symtoms Dizoclipine3) 5 – HT Theories: • 5 – HT dysfxn • LSD & 5-HT2 Receptors agonists produced schizophrenia like syndrome. Mostly of Anti-psychotics in addition to affect dopamine also back serotonin receptors.4) Current views: Combination of DA hyperactivity with 5-HT & glutamate dysfxn.DA – Recognized as NT 1959
1) Nigrostriatal Pathway: 75% of dopamine in brain Co-ordination of motor movements activity: Parkinsonism activity auntingtons chorea2) Mesolimbic mesocortical pathway: Projects from neurons near S.N to limbic system & Neocortex Behaviorial effects Hyperactivity leads to schizophrenia.3) Tuberoinfundibular (Tubrohypophy Scal) Pathway: Connects arcuate nuclei & prevent nuclei hypothalamus and post pituitary.Regulation endocrine control – control MSH, GH, Prolactin.4) Medullary Perventricular Pathway: From neurons of Motor Nucleus of Vagus ___ Periventricular nuclei Eating behavior Satiety center ____ Bolimia Nervosa Appetite Cetre _____ Anorexiz Nervosa5) Incertohypothalamic Pathway: From medial zone incerta to hypothalamus & Amygdala. Sexual drive, Microvasculatory function and temperature regulation.6) Many local Dopaminergic Neurons in olfactory cortex & retina:7) Dopaminergic transmission in periphery:- Renal Vasculatory- Mesenteric pathway- CVSDOPAMINE TRANSMISSION INVOLVED:a- Motor Effect: Deficient in nigrastriatal system ___ Parkinsonism Excess of DA ___ Huntigtonb- Behavior Effect: DA hyperactivity in mesolimbic & mesocortex pathway ___ schizophreniac- Endocrine Effects: i) Agonists (Ergot & Non-Ergot) Decrease in Prolactin & MSH Increase in GH (in N individuals, in acromegaly patients opposite effects)
ii) Antagonists (Anti-Psychotics) Increase in prolactin ____ Infertilityd- CTZ & Vomiting: StimulatedDA Receptors & Their Location: D1 Family: Increase in CAMP Increase in PIP2 hydrolysis Cat2 mobilization PKc activation Distribution:D1 Striatum Neocortex Nucleus accustoms Olfactory tubercle Periphery Fxn: 1. CNS 2. Horizontal cell coupling in retina 3. Dilation or renal & mesentreric 4. Increase in force of myocardial contractionDS: Hippocampus HypothalamusD2 Family: (D2, D3 & D4) Decrease in CAMP Post Synaptic Increase in K conductance Decrease in voltage gated Cat2 currents (pre-synaptic) Distribution:D2 Striatum (caudate & Putamen) Substantia nigra pars compacta (SNPC) ____ Pre & post synaptic inhibition Olfactory Tubercle Nucleus accumbans Pituitary
D3 Olfactory tubercle Nucleus accumbanes Hypothalamus Frontal cortex & medulla & mid brainD4 Frontal Cortex Medulla Mid brain PSYCHOTROPIC DRUGS: Drugs which effect mood & behavior.1) Anxiolytics, sedatives, hypnotics, Minor tranquillizers: (Psychorelaxants): Reduce anxiety and induce sleep2) (Anti-psychotics, Anti-Schizophrenics, Major tranquillizers, psycholeptic, ataractic) Neuroleptics: ___ Neuron seize Seize those neurons which are hyperactive effectively relieve symptoms of schizophrenia.3) (Thymoleptics, psychoenergisers) Anti-depressants: Depress depressive idealization No Anti-depressant is CNS stimulant Alleviate symptoms of depressive illness.4) Psychomotor stimulants (Psychostimulants) Cause wakefulness & Euphoria5) Psychodysleptics, psychotomumetic, psychedelics: (Hallucinogens) Cause disturbance of perception & behavior _____ Psychosis like illness.6) Antimaniacs (Mood Stabalizers)Control mania7) Neurotropic drugs: Enhance mental performance NEUROLEPTICS (ANTI-PSYCHOTICS)A) Classical Typical Nemoleptics: 1. Phenothiazines: a) Aliphatic Comp: Chloropromazine (Largactil) Promazine Triflupromazine
Promethazine (Phanergen)---got important anti-histaminic actions, so, commonly placed in H1 blockers Chlorpromazine: discovered by surgeon, trying to find that relief person in surgery. b) Piperidine Derivative: Thioridazine (Melleril) Polent Anti-Cholinergic Mesoridazine (metabolite of thioridazine) Action Mepozine Piperacetazine All Anti-psychotics cause parkinsonism by blocking DA receptors in Nigrostriatal system so drug having Anti-muscarinic effect neutralize this effect. c) Piperazine Derivative: Fluphenazine (I/V preparation, slowly, release, Perphenazine Adv. Trifluperazine 1) Long DOA Prochlorperazine 2) Patient Compliance becomes Thioperazine better as in schizophrenia. Acctophenazine Carphenzaine So, to overcome compliance problem as schizophrenia patients never accept that he is sick, so longer acting DEPOT Preparation made to over come this problem. DEPOT preparation ____ slowly release2. Thioxanthines: (also available as DEPOT preparation) Thiothixene Clopenthixol ___ inj. ____ for false thoughts Flupenthixol Zuclopenthixol Chlorprothixine3. Butyrophenones: Haloperiodol Properidol Benperidol Triflupeidol4. Rauwalfia alkaloids:
Reserpine ___ useful as deplete DA ___ Not used as induce suicidal thoughts None of alkaloids are used now-a-days.B) Atypical Neuroleptics: Their mechanism of action is different from anti-psychotics Loxapine Clozapoine (Clozanl) ___ A/E: Cause agranulocyctosis ___ Bone marrow depression Risperidone ____ commonly used D2 5HT2 selective activity for D4 receptors Olanzapine __ Disadv: cause agranulocytosis Ziprasidone Treatment patients who are resistant to other drugs. Also R x of negative effects Sulpirdie (D2 selective) Remazopride Remoxipride Primozide (D2 selective) long acting indole Quetiapine Aripiprazole (partial agonist at D & SHT a antagonist at x