Schizophrenia and ADHD PDF

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Schizophrenia Mesolimbic pathway and the Mesocortical Pathway are the Dopaminergic Pathways affected in Schizophrenia Overstimulation of the mesolimbic pathway accounts for the positive symptom’s “hallucinations” Under stimulation of the mesocortical accounts for the negative and cognitive symptoms “hypoactivity” Piperidine: thioridazine (Mellaril; Millazine) is a first generation (low potency) First generation Antipsychotics: D2 Antagonists (D2 Receptors): Blocks dopamine  Causes a Parkinson’s like syndrome (affects the Nigrostriatal Pathway) They can also block H1, M1 and Alpha1 receptors Dopamine goes down, prolactin goes up Increase in Prolactin is an indicator of D2 receptor antagonism* ADR/SE: Hyperprolactinemia, EPS, orthostatic hypotension, constipation, urinary retention, GI Issues, confusion, sedation, potentiation of other CNS depressants, impotence, altered thermoregulation, dyscrasias, CV Drugs that increase dopaminergic (amphetamine, cocaine) activity either aggravate schizophrenia, psychosis or produce psychosis in some patients Second Generation Antipsychotics: Higher affinity for the serotonin receptor and less affinity for the D2 receptor “Atypical antipsychotic drugs reduced effect on D2 receptors” Action at 5HT Work largely by blocking or mitigating the activity of dopamine at D2 receptors Extrapyramidal symptoms: From 1st generation antipsychotics Glutamate – suggested that hypofunction “inadequate activity of Glutamate” of NMDA receptors leads to diminished inhibitory influences on neuronal function, and contributes to schizophrenia NMDA antagonists exacerbates schizophrenia Activation of AMPA receptor may be effective Cariprazine (Vraylar) – D2/D3 partial agonist 2nd Generation “Atypical” are 5HT2A/D2 Antagonists are associated with lower risk of EPS, are associated with higher risk of metabolic side effects

ADR/SE Metabolism, NVS, increase BW, insulin resistance (Type2 Diabetes) Obesity, Akathisia, induce weight gain, hyperglycemia, hypercholesterolemia, If D2 is high, EPS is high and vice versa D1 antagonist might impair cognitive function D2 antagonist “FGA”, antipsychotic, relieves positive symptoms; EPS, increases prolactin 5HT2A/D2 antagonist “SGA”– improve negative symptoms; cognitive impairment, decrease in EPS There is no evidence that SGAs are significantly more effective than FGAs in the treatment of cognitive and negative symptoms of schizophrenia ADHD (Attention Deficit Hyperactive Disorder) Dopaminergic activity (inadequate D receptor, low dopamine levels) Abnormal adrenergic activity Catecholamines: NEPI, Dopamine, Serotonin Stimulants increase (Dopamine) and NEPI Non-stimulants increase (NEPI and Serotonin) MOA: Modulate dopamine and NEPI in brain; perhaps 5HT results in improved executive functioning; regulation of arousal Anti-depressants: increase level of catecholamines in the brain in order to suppress the symptoms of depression [can be used in ADHD] TX: ADHD Stimulants: block reuptake of dopamine and NEPI Methylphenidate (Ritalin): increases levels of the dopamine’s and NEPI in the cleft by blocking reuptake, doing good things in the cortex ADR/SE Appetite suppression, weight loss, interruption of sleep patterns Amphetamines does the same thing Nonstimulants (Atomoxetine Strattera) Blocks NEPI reuptake

Doesn’t block DA level Clonidine Alpha 2 adrenergic Agonist Acts at the locus coeruleus affecting NEPI function, inhibits NEPI function ADR/SE Sedation, decreased appetite, irritability, anticholinergic (dry mouth, GI, etc…) decreased seizure threshold Stimulants: increase DA and NEPI Increased attention, decreased motor activity and improvement on learning tasks Stimulants have been shown to: Inhibit the reuptake of dopamine and NEPI Enhance release of these transmitters from presynaptic neuron Inhibit enzyme monoamine oxidase Amphetamines promote the release of catecholamines such as DA and NE nerve endings The major action of these drugs is in the CNS. These agents produce a feeling of well-being and euphoria. Tachyphylaxis or tolerance to the stimulating actions of these agents can develop. Clinical Therapeutics of CNS Stimulants Appetite suppression - amphetamine analogs Narcolepsy - methylphenidate, amphetamine analogs ADHD: methylphenidate, amphetamine analogs ADHD TX: amphetamines Methylphenidates Inhibits DA reuptake Biotransformation-de-esterification Ritalinic Acid Atomoxetine ADR/SE NVD, Abdominal pain, anorexia, insomnia, agitation, nervousness, fever, increase seizure frequency (epileptics and ADD) Second line therapy for patients with ADHD unresponsive to stimulants or those with comorbid anxiety or depression, or a history of substance abuse Imipramine Bupropion Desipramine Drug therapy for patients with ADHD and Tourette syndrome or those with comorbid anxiety or preschool age children with severe hyperactivity and impulsivity Clonidine

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