邢唷> bdc( /00DArialngs埞埞&鸱0z[ 0D媅SOalngs埞埞&鸱0z[ 0 DTahomags埞埞&鸱0z[ 00DWingdings埞埞&鸱0z[ 0 A. @n?" dd@ @@``鸢PJ 0咥臕@83簱蚌蕷;斍蕷;g4[d[d z[ 0揀ppp@<4ddddL 0埞&80___PPT10 ppAntidepressant drugs Overview Affecting energy, sleep, appetite, libido and the ability to function. Different from schizophrenia Due to a deficiency of monoamines such as norepinephrine and serotonin at certain key sites in the brain. 3%Tricyclic /polycyclic antidepressants Block norepinephrine, and serotonin uptake into the neuron. Imipramine, amitriptyline, desipramine All have similar therapeutic efficacy, and the choice of drug depends on tolerance of side effects and duration of action.P) |Mode of actionInhibition of neurotransmitter uptake: TCA inhibit the neuronal reuptake of norepinephrine, and serotonin into presynaptic nerve terminals. Blocking of receptors: The TCAs also block serotonergic, alpha-adrenergic, histamine, and muscarinic receptorsbL-# actionsTCAs elevate mood, improve mental alertness, increase physical activity, and reduce morbid preoccupation in 50 to 70% of individuals with major depression. Therapeutic uses The tricyclic antidepressants are effective in treating severe major depression. Some panic disorders also respond to TCAs. Imipramine has been used to control bed-wetting in children (older than 6 years) by causing contraction of the internal sphincter of the bladder. H i Pharmacokinetics Absorption and distribution: The TCAs are well absorbed upon oral administration, are widely distributed and readily penetrate into the CNS. 4 to 17 hours for imipramine. 6!z Adverse effectsAntimuscarinic effects: Cardiovascular: Increased catecholamine activity results in cardiac overstimulation Orthostatic hypotension: TCAs block alpha-adrenergic receptors, causing orthostatic hypotension and reflex tachycardia. Sedation@OdPrecautionsThe tricyclic antidepressants should be used with caution in manic-depressive patients, since they may unmask manic behavior. The tricyclic antidepressants have a narrow therapeutic index6 u 0 (SELECTIVE SEROTONIN-REUPTAKE INHIBITORS (,The selective serotonin-reuptake inhibitors (SSRI) are a new group of chemically unique antidepressant drugs that specifically inhibit serotonin reuptake. This contrasts with the tricyclic antidepressants that nonselectively inhibit the uptake of norepinephrine, and serotonin, and block muscarinic, -Z-Z Fluoxetine Actions: Fluoxetine is the prototype of antidepressant drugs that selectively inhibit serotonin reuptake. Fluoxetine is as effective in the treatment of major depression as tricyclic antidepressants. The drug is free of most of the troubling side effects of tricyclic antidepressantsZ W 9 L Therapeutic uses<The primary indication for fluoxetine is depression. Fluoxetine is effective in treating bulimia nervosa and obsessive-compulsive disorder. The drug has been used for a variety of other indications, including anorexia nervosa, panic disorder, pain associated with diabetic neuropathy, and for premenstrual syndrome. =Z=6 Pharmacokinetics8Fluoxetine and norfluoxetine are slowly cleared from the body, with a 1 to 10 day half-life for the parent compound, and 3 to 30 days for the active metabolite. Fluoxetine is administered orally; with a constant dose, a steady-state plasma concentration of the drug is achieved after several weeks of treatment. 9Z9X Adverse affectsLoss of libido, delayed ejaculation and anorgasmia are probably under-reported side effects often noted by clinicians but are not prominently featured in the list of standard side effects. Overdoses of fluoxetine do not cause cardiac arrhythmias but can cause seizures. 6( :Test aList some routes of drug administration, and their important features (8) What is bioavailability? And how to determine it? The factors that influence bioavailability. (7) How to determine Vd if the drug is not eliminated from the body?(4) What are the two types of kinetics of metabolism for most drugs? And how to calculate their velocity simply? 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