Antidepressant Drugs
Antidepressant Drugs *Symptoms of depression: Intense feelings of sadness, hopelessness as well as changes in sleep patterns and appetite, loss of energy and suicidal thoughts.*Most clinically useful antidepressant drugs potentiate either directly or indirectly, the action of norepinephrine(NE) and ? or serotonin(5-HT) in the brain.*Types of depression:-(1) "reactive" or "secondary" depression(most common), occurring in response to real stimuli such as grief, illness, etc (2) "endogenous" depression, a genetically determined biochemical disorder manifested by inability to experience ordinary pleasure or to cope with ordinary life events*The amine hypothesis of mood: -Brain amines particularly NE and 5HT are neurotransmitter in pathway that function in the expression of mood. -Functional decrease in activity of such amines result in depression while functional increase in activity result in mood elevation. *Difficulties with amines hypothesis include: 1-Although antidepressants may cause changes in brain level of NE and 5-HT within hrs, weeks may required for clinical effects. 2-Most antidepressants ultimately cause down-regulation of amines receptors necessitating increasing the dose of the antidepressant drug.Tricyclic Antidepressants (TCAs)-Imipramine, Clomipramine, Amitriptyline and Nortryptilin are the prototypical drugs of the class as mixed norepinephrine and serotonin uptake inhibitors .*Mechanism of action:-The TCAs have affinity for both receptors and transporters of monoamine transmitters and behave as antagonistsin both respects. Thus, the neuronal reuptake of norepinephrine and serotonin is inhibited, with a resultant increase in activity.*TCAs action:--Elevate mood, improve mental alertness, increase physical activity.-The onset of mood elevation is slow, requiring 2 wks or longer.*Therapeutic uses of TCAs:-- depression.-Enuresis –bed wetting in children-(imipramine)-Chronic pain (neuropathic pain) (amitriptyline).*Adverse effects:--Blockade of Ach receptors lead to blurred vision, urinary retention, constipation, and aggravation of glaucoma .-Increased catecholamine activity results in cardiac over stimulation.-Blockade of -adrenoceptors, causing orthostatic hypotension and reflex tachycardia.-Imipramine is the most likely and nortriptyline is the least likely to cause orthostatic hypotension.-Blockade of histamine 1 receptors lead to sedation.-Sexual dysfunction in minority of patients.*Drugs interaction with TCAs:-1-Pronounced sedation with drugs which have sedative effects e.g. opioid analgesics, antihistamines, anxiolytics and alcohol3-Potentiate the effect of catecholamines and other direct acting sympathomemetics*Selective serotonin re-uptake inhibitors(SSRIs)-300-3000 fold greater selective for serotonin transporter than for norepinephrine transporter(in contrast to TCAs that non-selectively inhibit uptake of norepinephrine and serotonin).-SSRIs have little blocking activity at muscarinic, -adrenoceptors, and histaminic 1 receptors (much less adverse effects than TCAs)-SSRIs include fluxetine(prototype), citalopram, escitalopram, fluvoxamine, paroxetine, and sertraline-Take 2wks to start improvement in mood(12 wks for full effect)*Pharmacokinetics of SSRIs:--The majority of SSRIs have half-life (16-36 hrs)-Fluxetine differs in 2 respects: A-it has longer half-life (50 hrs) B-it has active metabolite (S-norfluxetine) with 10 days h?-Fluxetine and paroxetine are potent enzyme inhibitors (TCAs, ?-adrenergic antagonists)-Excretion of SSRIs is through kidneys (in paroxetine and sertraline there is also fecal excretion)*Therapeutic uses:--Depression(as effective as TCAs)-Pre-menstrual dysphoric disorder.-SSRIs are generally free of sedative effects and remarkably safe in overdose. Combined with the ease of once-a-day dosing, these qualities may explain why they have become the most widely prescribed antidepressants.*Adverse effects of SSRIs; -Generally side effects are less than in TCAs and MAO inhibitors. -Paroxetine is sedating, fluxetine is not. -Sexual dysfunction (which is less in bupropion, mitrazepine) -Used cautiously in children and teenagers because of increased risk of suicide -Over dose not causing arrhythmia, but fluxetine over dose may cause epilepsy (therapeutic dose is 20mg-day) -weight gain *Drugs interaction with SSRIs:-1-Serotonin syndrome(hyperthermia, muscular rigidity, and changes in mental status and vital signs) if MAO inhibitors is co-administered .2-CNS toxicity if given with dopaminergic drugs e.g. selegiline (anti Parkinson drug).*Monoamine oxidase inhibitors (MAOIs)-They includes:A-Non-selective inhibitors of MAO:Phenelzine and isocarboxazide (no longer marketing), they bound irreversibly to MAO (A and B) with prolonged duration of action .Tranylcypromine which bound reversibly to MAO(A and B) with long duration of action. B-Selective inhibitors of MAO: -Selegiline is selective for MAO-B at low doses, but at high doses it is less selective, used in Parkinson's disease and has been approved in major depression. -Moclobemide is selective for MAO-A *Pharmacokinetic of MAOIs -Readily absorbed from GIT-Duration of action is about 7 days in tranylcypromine, and 2-3 wks in Phenelzine and selegiline after drug discontinuance.*Mechanism of action of MAOIs-Increase the availability of amines (serotonin) by preventing their destruction by MAO enzyme in pre-synaptic terminal-Increased synaptic dopamine is also relevant to the efficacy of MAOIs *Adverse effects of MAOIs:--Severe and unpredictable side effects limit the use of MAOIs e.g .food containing tyramine- reaction Tyramine contained in some foods e.g. aged cheeses, chicken liver and beer normally inactivated by MAO-B in the gut. Individuals receiving MAOIs are unable to degrade tyramine which will cause release of large amount of stored catecholamines from nerve terminal resulting in headache, tachycardia, hypertension, cardiac arrhythmias and stroke. . *Treatment of mania and bipolar disorders*Lithium *Possible mechanism of action of lithium: lithium Inhibit synthesis of phosphatidylinositol biphosphate(PIP2) (chemical mediator responsible for mania) leading to its relative depletion in neuronal membrane of the CNS*Pharmacokinetic of lithium:--Absorbed rapidally and completely from gut-Distributed throughout the body-Excreted through kidneys -lithium is very toxic with very low therapeutic index.*Clinical uses:--Lithium carbonate continue to be the standared treatment of bipolar disorders.*Toxicity of lithium:--Ataxia, tremor, confusion and convulsion.-Dry mouth, polyurea.-Decreased thyroid function. ................
................
In order to avoid copyright disputes, this page is only a partial summary.
To fulfill the demand for quickly locating and searching documents.
It is intelligent file search solution for home and business.
Related searches
- list of blood pressure drugs being recalled
- new drugs for rsd
- drugs for erectile dysfunction price
- blood pressure drugs recalled 2019
- length of drugs in urine
- names of drugs for blood pressure recalled
- drugs a to z
- roman drugs review
- drugs for autoimmune disease
- drugs used for erectile dysfunction
- new ed drugs coming soon
- buy prescription drugs online without