antipsychotics and antidepressants

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  • Dr. Dua Al-ZoubiPharmacistMaster degree in pharmacology

  • The symptoms of depression are feelings of sadness and hopelessness, as well as the inability to experience pleasure in usual activities, changes in sleep patterns and appetite, loss of energy, and suicidal thoughts. Mania is characterized by the opposite behavior: enthusiasm, anger, rapid thought and speech patterns, extreme self-confidence, and impaired judgment.

  • Major depression and dysthymia (minor): pure depression syndrome.

    Bipolar disorder

  • Biochemicals are necessary for normal mental function

    GABAAcetylcholine (ACh)Sodium, potassium, magnesiumDopamine, norepinephrine, serotonin and histamine

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  • Is the treatment of mental disorders

    Pharmacologic treatment.Non-pharmacologic treatment.

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  • -Older generation:Tricycles. (imipramine, Clomipramine, Amitriptyline).Tetracycles (Mirtazapine: Remeron) Monoamine oxidase inhibitors MAOIs-Newer generation: SSRIs (Citalopram, Escitalopram, Fluoxetine, Paroxetine, Sertraline, Fluvoxamine)SNRIs (Duloxetine, Venlafaxine)

  • The MAOIs are indicated for depressed patients who are unresponsive or allergic to TCAs and SSRIs or who experience strong anxiety.

    These drugs are well absorbed after oral administration. Enzyme regeneration, when irreversibly inactivated, varies, but it usually occurs several weeks after termination of the drug.

    a minimum of 2 weeks of delay must be allowed after termination of MAOI therapy and the initiation of another antidepressant from any other class

  • Considered second-line

    For patients who fail with newer-generation antidepressantsAs adjunct therapy with newer-generation antidepressants

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  • Amitriptyline (Elavil, Endep)Doxepin (Sinequan)Imipramine (Tofranil)Chlomipramine.Desipramine (Norpramin)Nortriptyline (Aventyl, Pamelor)

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  • Elevates mood and increase interest in social and daily relationships.Improve mental alertness.Increase physical activity.Block alpha, histamine and M receptors.

  • DepressionChildhood enuresis (imipramine)Obsessive-compulsive disorders (clomipramine)Trigeminal neuralgic pain

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  • TCAs are well absorbed upon oral administration. Because of theirlipophilic nature, they are widely distributed and readily penetrate into the CNS. As a result of their variable first-pass metabolism in the liver, TCAs have low and inconsistent bioavailability. These drugs are metabolized by the hepatic microsomal system (and, thus, may be sensitive to agents that induce or inhibit the CYP450 isoenzymes) and conjugated with glucuronic acid. Ultimately, the TCAs are excreted as inactive metabolites via the kidney.

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  • Blockade of muscarinic receptors leads to blurred vision, xerostomia (dry mouth), urinary retention, sinus tachycardia, constipation, and aggravation of angle-closure glaucoma These agents affect cardiac conduction similarly to quinidine and may precipitate life-threatening arrhythmias in an overdose situation. The TCAs also block -adrenergic receptors, causing orthostatic hypotension, dizziness, and reflex tachycardia. Imipramine is the most likely, and nortriptyline the least likely, to cause orthostatic hypotension. Sedation may be prominent, especially during the first several weeks of treatment (block histamine H1 receptors). Weight gain is a common adverse effect of the TCAs.

  • The atypical antidepressants are a mixed group of agents that have actions at several different sites.

    This group includes bupropion , mirtazapine, nefazodone, trazodone,vilazodone, and Vortioxetine.

  • Mirtazapine enhances serotonin and norepinephrine neurotransmission by serving as an antagonist at presynaptic 2 receptors.Additionally, some of the antidepressant activity may be related to antagonism at 5-HT2 receptors. It is sedating because of its potent antihistaminic activity, but it does not cause the antimuscarinic side effects of the TCAs, or interfere with sexual function like the SSRIs.

  • Fewer adverse effects than older

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  • SSRIs

    sertraline (Zoloft)fluoxetine (Prozac)citalopram (Celexa) escitalopram (Lexapro)paroxetine (Paxil)fluvoxamine (Luvox)

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  • venlafaxine (Effexor)duloxetine (Cymbalta)

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  • All of the SSRIs are well absorbed after oral administration. Peak levels are seen in approximately 2 to 8 hours on average. Food has little effect on absorption (except with sertraline, for which food increases its absorption).The majority of SSRIs have plasma half-lives thatrange between 16 and 36 hours. Metabolism by cytochrome P450 (CYP450)dependent enzymes and glucuronide or sulfate conjugation occur extensively. Fluoxetine differs from the other members ofthe class by having a much longer half-life (50 hours).

  • Depression (main use)Bipolar disorderEating disordersObsessive-compulsive disorder

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  • Severe emotional disorder that impairs the mental function of the affected individual to the point that the individual cannot participate in activities of daily livingHallmark: loss of contact with realityPrimary types:

    SchizophreniaMania.Bipolar disorder.

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  • Schizophrenia is a type of chronic psychosis characterized by delusions, hallucinations (often in the form of voices), and thinking or speech disturbances.

    The onset of illness is often during late adolescence or early adulthood. It occurs in about 1% of the population and is a chronic and disabling disorder.

    Schizophrenia has a strong genetic component and probably reflects some fundamental biochemical abnormality, possibly a dysfunction of the mesolimbic or mesocortical dopaminergic neuronal pathways.

  • Hallucinations (distortions or exaggeration of perception) Most frequently auditory, can also be visual, olfactory, gustatory, and tactile. Can be voices or thoughts that feel distinct from the persons mind. Voices may be threatening or commanding (eg, commanding the person to perform a particular action). Delusions (fixed false beliefs) Beliefs despite invalidating evidence May be bizarre in nature Often paranoid in nature which may cause suspiciousness Thought disorder (illogical thought and speech) Loosening of associations Tangentiality Thought blocking Concreteness Circumstantiality Perseveration Thinking and speech may be incomprehensible and illogical

  • Impoverished speech and thinking Lack of social drive (avolition) Flatness of emotional expression Apathy May be primary or occur secondarily to medication side effects, mood disorder, environmental understimulation, or demoralization The best strategy for differentiating primary from secondarynegative symptoms is to observe for their persistence over time despite efforts at resolving the other causes

  • Attention Processing speed Verbal, visual memory, and working memory Problem solving There is a loss of, on average, one standard deviation ofpreillness IQ, with the average IQ between 80 and 84.

  • Mood stabilizers: lithium carbonate, antiepileptics

    Antipsychotics:Older generation

    Newer generation

  • Older generation: Phenothiazines (thioridazine, trifluoperazine, chlorpromazine).Phenylbutylpiperidines (Haloperidol) Newer generation: Dibenzodiazepines (Clozapine, Olanzapine, Quetiapine)Benzisoxazoles (Risperidone)Quinolinone (Aripiprazole)

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  • Most are readily but incompletely absorbed.Many of these drugs undergo first pass effect.Most are lipid soluble.Protein binding (92-99)%Volume of distribution more than 7L/Kg since sequestered in lipid compartments of the body.Most are completely metabolized.

  • Some matabolites are active but parent drug is more potent except for thioridazones metabolite is more active than the parent.Very little parent of drugs excreted unchanged.

  • Five dopaminergic systems or pathways are important for understanding schizophrenia and the mechanism of action of antipsychoticdrugs. The first pathwaythe one most closely related to behavior and psychosisis the mesolimbic-mesocortical pathway, which projects from cell bodies in the ventral tegmentum in separate bundles of axons to the limbic system and neocortex.

  • The second systemthe nigrostriatal pathwayconsists of neurons that project from the substantia nigra to the dorsal striatum, which includes the caudate and putamen; it is involved in the coordination of voluntary movement. Blockade of the D 2 receptors in the nigrostriatal pathway is responsible for EPS.

  • third pathwaythe tuberoinfundibular systemarises in the arcuate nuclei and periventricular neurons and releases dopamine into the pituitary portal circulation.

    Dopamine released by these neurons physiologically inhibits prolactin secretion from the anterior pituitary

  • . The fourth dopaminergic system the medullary-periventricular pathwayconsists of neurons in the motor nucleus of the vagus whose projections are not well defined.

    This system may be involved in eating behavior. The

  • fifth pathwaythe incertohypothalamic pathwayforms connections from the medial zona incerta to the hypothalamus and the amygdala. It appears to regulate the anticipatory motivational phase of copulatory behavior in rats.

    Receptrs blocker by antipsychotics:dopamine, serotonine, alpha, muscarine and histamine.

  • Antipsychotic effectsExtrapyramidal effects.Increased prolactine release.Anttiemetic effect.Antimuscarinic effect.Orthostatic hypotension.Alter tempretureregulatory mechanism.Antipruritic effects.

  • Treatment of serious mental illnesses

    Bipolar affective disorderDepressive and drug-induced

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