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Antidepressants  /certified fixed orthodontic courses by Indian dental academy
 

Antidepressants /certified fixed orthodontic courses by Indian dental academy

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Welcome to Indian Dental Academy
The Indian Dental Academy is the Leader in continuing dental education , training dentists in all aspects of dentistry and offering a wide range of dental certified courses in different formats.


Indian dental academy has a unique training program & curriculum that provides students with exceptional clinical skills and enabling them to return to their office with high level confidence and start treating patients

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  • High correlation particularly among kin <br /> Reserpine, a drug used in the treatment o hypertension and schizophrenia can cause depression because it depletes the vesicular storage of amine neurotransmitters (NE, 5-HT, DA). <br /> Depression could be relieved by isoniazid, a drug used in the treatment of tuberculosis. <br /> TCAs, MAOIs, SSRIs, and all the new drugs. <br /> ECT causes a massive release of NTs and is a very effective antidepressant. <br />

Antidepressants  /certified fixed orthodontic courses by Indian dental academy Antidepressants /certified fixed orthodontic courses by Indian dental academy Presentation Transcript

  • ANTIDEPRESSANTS INDIAN DENTAL ACADEMY Leader in continuing dental education www.indiandentalacademy.com www.indiandentalacademy.com
  • Classification of Major Affective Disorders M a jo r A ffe c tiv e D is o rd e rs E p is o d a l D e p re s s io n M a jo r/ Endogenous D e p re s s io n M a n ia Seasonal A ffe c tiv e D is o rd e r A ty p ic a l D e p re s s io n www.indiandentalacademy.com B ip o la r d e p re s s io n
  • Episodal (reactive) Depression ♦Adverse life events. ♦Physical illness. ♦Hormonal steroids. ♦Drugs. ♦Other psychiatric disorders. www.indiandentalacademy.com
  • Reactive (episodal) Depression ♦More than 60% of all depressions. ♦Core depressive syndrome: feelings of misery, apathy, inadequacy, pessimism, anxiety, tension, guilt. ♦Bodily complaints ♦May respond spontaneously or to a variety of administrations. www.indiandentalacademy.com
  • Major Endogenous Depression • Recurrent, Cyclic, Seasonal. • Degree of depression is not adequate for precipitating event. • Automaton (unresponsive). www.indiandentalacademy.com
  • Major Endogenous Depression Core Symptoms: • Feeling of misery, apathy and pessimism. • Withdrawn. • Low self –esteem, feelings of guilt, inadequacy and ugliness. • Loss of interest in pleasurable activities. • Indecisiveness, loss of motivation. • Retardation of thought and action. Sleep disturbance and significant weight change (without dieting or changes in appetite). www.indiandentalacademy.com • Psychomotor agitation or retardation.
  • Major Endogenous Depression Core Symptoms (con’t): • In severe cases, it is accompanied by hallucinations and delusions. • Recurrent suicidal ideation, a suicide attempt or a specific suicide plan. www.indiandentalacademy.com
  • Mania • Mania alone is rare (10%) and most frequently cycles with Major/endogenous depression (ManicDepressive Disease, Bipolar Disorder). www.indiandentalacademy.com
  • Mania Core Symptoms: • It is characterized by an elevated “high” mood. • Talkative, go on-and-on about the things they will do. • Increased self-esteem. • Auditory hallucinations. • Decrease need to sleep. • Lack judgement, indiscrete. • SuperME www.indiandentalacademy.com
  • III. Biological Correlates of Depression 1. Hypersecretion of cortisol. 2. Escape from dexamethasone suppression. 3. Blunted TSH response to TRH. 4. Blunted GH response to hypoglycemia. 5. Altered 24hr rhythm of prolactin secretion. 6. Decreased 5-HT metabolites in plasma. 7. Decreased REM latency. www.indiandentalacademy.com
  • IV. Biological Basis for Depression 1. Has a genetic component. 2. Depression can be drug-induced. 3. Depression can be drug-repressed. 4. Depression can be treated with drugs. 5. Depression can be treated with Electroconvulsive Therapy (ECT). www.indiandentalacademy.com
  • V. Biogenic Theory of Depression • The precise cause of affective disorders remains elusive. • Evidence implicates alterations in the firing patterns of a subset of biogenic amines in the CNS, Norepinephrine (NE) and Serotonin (5-HT). ↓ Activity of NE and 5 -HT systems?. www.indiandentalacademy.com
  • VI. NE System Almost all NE pathways in the brain originate from the cell bodies of neuronal cells in the locus coereleus in the midbrain, which send their axons diffusely to the cortex, cerebellum and limbic areas (hippocampus, amygdala, hypothalamus, thalamus). • Mood: -- higher functions performed by the cortex. • Cognitive function: -- function of cortex. • Drive and motivation: -- function of brainstem • Memory and emotion: -- function of the hippocampus and amygdala. • Endocrine response: -- function of hypothalamus. α and β receptors.ww.indiandentalacademy.com w
  • VII. Serotonin System As with the NE system, serotonin neurons located in the pons and midbrain (in groups known as raphe nuclei) send their projections diffusely to the cortex, hippocampus, amygdala, hypothalamus, thalamus, etc. --same areas implicated in depression. This system is also involve in: • • • • • • Anxiety. Sleep. Sexual behavior. Rhythms (Suprachiasmatic nucleus). Temperature regulation. CSF production. www.indiandentalacademy.com
  • Antidepressants S S R Is TCAs s www.indiandentalacademy.com V enfl axine I SSR Venflaxine Is SSR • dox SSRIs TC TCAs epi MAOIs As n Is MAO O Is A TCAs M MAOIs ide az Is box O TCAs car A iso M MAOIs maprotiline MAOIs MAOIs SSRIs Am ox ep Venflaxine ine e MAOIs rtriptylin No
  • Antidepressants 1. Tricyclic anti-depressants (TCAs). Imipramine, desipramine, nortriptyline, protryptyline, amytriptiline, doxepin. 2. Monoamine oxidase inhibitors (MAOIs). Isocarboxacid, phenelzine, tranylcypromine. 3. Selective serotonin reuptake inhibitors (SSRIs) Fluoxetine, sertraline, paroxetine, trazodone. 4. Atypical anti-depressants (Others) New TCAs, amoxapine, bupropion, alprazolam, maprotiline, nomifensine, mianserin. www.indiandentalacademy.com
  • Mechanism of Action 1. Inhibition of NE and 5-HT reuptake. (TCAs, SSRIs, Newer TCAs). 2. Inhibition of MAO enzymes. (MAOIs). 3. 5-HT2A and 5-HT2C antagonists. (Nefazodone, trazodone, mirtazapine) 4. Alteration of NE output . (Bupropion) 5. Stimulation of 5-HT1A receptors. ( 6. α2–AR antagonists. www.indiandentalacademy.com (mirtazapine)
  • Tricyclic Antidepressants (TCAs) • amytriptiline • imipramine • desipramine • nortriptyline • protryptyline • doxepin. www.indiandentalacademy.com
  • Tricyclic Antidepressants (TCAs) • Characteristic three ring nucleus. • Most are incompletely absorbed, all are metabolized in liver => High first pass effect: 1) Transformation of the tricyclic nucleus => hydroxylation => conjugation => glucoronides. 2) Alteration of aliphatic side chain => demethylation of the nitrogen => active metabolites. • High protein binding, high lipid solubility. www.indiandentalacademy.com
  • Tricyclic Antidepressants (TCAs) / CH3 / H N N CH3 CH3 tertiary amine secondary amine 3o => 2o www.indiandentalacademy.com
  • Tricyclic Antidepressants (TCAs) 3°Amines: 2°Amines: Selectivity Imipramine, Amitriptyline ⇓⇓ Desipramine, Nortriptyline 2o Amines -- NE > 5-HT 3o Amines -- 5-HT > NE www.indiandentalacademy.com
  • Tricyclic Antidepressants (TCAs) Mechanism of Action: - Inhibition of NT reuptake. - Immediate action = >↑ NE and 5-HT in synapse. - After chronic treatment (2 - 4 weeks) = > ↓ β NE-R and ↓5-HT2R. ↓ NE release and turnover. ↓ NE-stimulated cAMP in brain. ↑ Sensitization of 5-HT receptors. * Adaptive Responses * - Takes up to 4 weeks for all TCA antidepressants to have an effect. www.indiandentalacademy.com
  • Tricyclic Antidepressants (TCAs) Side Effects: • Atropine-like side effects: dry mouth, paradoxical excessive perspiration, constipation, blurred vision, mydriasis, metallic taste, urine retention => muscarinic blockade. • Orthostatic hypotension => α1-AR and possibly α2-AR blockade. • Drowsiness, sedation and weight gain => Histamine-Receptor blockade. www.indiandentalacademy.com
  • Tricyclic Antidepressants (TCAs) Side Effects (con’t): • Most serious side effect is cardiac toxicity => Palpitations, tachycardia, dizziness => excessive CNS stimulation => ↑NE in Heart. • Sexual dysfunction, including loss of libido, impaired erection and ejaculation and anorgasmia . …↓ COMPLIANCE www.indiandentalacademy.com
  • Tricyclic Antidepressants (TCAs) Other effects (con’t): • Metabolism is affected by: Smoking, Barbs, estrogens, neuroleptics and anticonvulsants. • Can lower seizure threshold. • All TCAs can cause: vagal block, postural hypotension, arrythmias, sinus tachycardia. • All potentiate CNS depressants (BZDs, Barbs, ETOH) => coma and death. • TCA administration in bipolar disorder may precipitate acute mania or rapid cycling. • Fatal in overdosewww.indiandentalacademy.com can kill anyone). (a 2 wk supply
  • X. MAO INHIBITORS • Isocarboxacid • Phenelzine • Tranylcypromine. www.indiandentalacademy.com
  • X. MAO INHIBITORS • Developed for the treatment of tuberculosis (iproniazid derivatives) - 1951. • These drugs are not widely used today, although a small number of patients appear to do better in MAOIs than TCAs or the newer drugs. • Are readily absorbed from GI tract and widely distributed throughout the body. • May have active metabolites, inactivated by acetylation. • Effects persist even after these drugs are no longer detectable in plasma (1-3 weeks). www.indiandentalacademy.com
  • X. MAO INHIBITORS Mechanism of action: Inhibit MAO enzymes (non-selective): 1) Irreversible MAO inhibitors Phenelzine and isocarboxazid => hydrazides. 2) Reversible MAO Inhibitors. Tranylcypromine => non-hydrazide, prolonged blockade, but reversible within 4hr. Decrease metabolism of most biogenic amines (NE, 5HT, DA, www.indiandentalacademy.com tyramine, octopamine).
  • X. MAO INHIBITORS Mechanism of action (con’t): Acute administration causes: ↑ NE and 5-HT in synaptic terminals in brain but ↓NE in PNS. ↓NE synthesis. – Acute euphoria – Suppressed REM sleep. Chronic administration causes: ↓ NE-stimulated cAMP in brain. – Down regulation of β receptors. www.indiandentalacademy.com – Down regulation of 5-HT2 receptors.
  • X. MAO INHIBITORS MAO-A  NE, 5-HT, Tyramine MAO-B  DA Selective MAOIs: Inhibitors MAO-A Moclobemide, Clorgyline Inhibitors of MAO-B. Deprenyl, Selegiline www.indiandentalacademy.com
  • X. MAO INHIBITORS Wine-and-Cheese Reaction - Fatal interaction with tyraminecontaining foods (fermented foods in particular, such as wine and cheese). - ↓ MAO-A => ↑ Tyramine in the body =>↑NE in circulation => induces hypertensive crisis => can lead to intracranial bleeding and other organ damage. www.indiandentalacademy.com
  • X. MAO INHIBITORS Negative drug interactions with: Any drug metabolized by MAOs* including SSRIs, TCAs and meperidine, alcohol, CNS depressants, sympathomimetics, phenylephrine (O/C nasal decongestants), ampetamines, and other indirect-acting adrenergic drugs. * Interaction with drugs metabolized by MAOs (e.g. Meperidine (opioid analgesics) => hyperpyrexia or “hyperexcitation syndrome” involving high fever, delirium and hypertension). www.indiandentalacademy.com
  • X. MAO INHIBITORS Other side effects: • Hypotension • Hepatotoxicity. • Sedation. www.indiandentalacademy.com
  • XI. SSRIs • Fluoxetine • Sertraline • Paroxetine • Fluvoxamine (Labeled for obsessive-compulsive disorder) www.indiandentalacademy.com
  • XI. SSRIs • Most widely prescribed drugs for depression. • They have few side effects and seem to be rather safe. More rational prescribing and better patient compliance. • Adverse effects include: nausea, decreased libido, decrease sexual function. • Low threat for overdose. Suicide may be considered in severe depression. www.indiandentalacademy.com
  • XI. SSRIs Mechanism of action: • Specific serotonin uptake inhibitors increase 5-HT by inhibiting reuptake. Current theory holds that: • Enhanced stimulation or responsiveness of postsynaptic 5-HT1A receptors is particularly important in the action of antidepressants. www.indiandentalacademy.com
  • XI. SSRIs Fluoxetine is the prototype. • Approximately 70% of depressed patients will respond to an SSRI therapy at the end of 6 weeks (4 to 6 weeks before effects are evident to patient). • T1/2 of 16 – 24 hrs. except for fluoxetine’s metabolite norfluoxetine (T1/2 = 8 days). • Fluoxetine and paroxetine inhibit liver enzymes, particularly P450-2D6. • Paroxetine and Sertraline have PK parameters similar to TCAs. www.indiandentalacademy.com
  • XI. SSRIs Drug-drug interactions: dangerous with other antidepressant drugs, MAOIs in particular. ”Serotonin Syndrome”: – hyperthermia, muscle rigidity, myoclonus, rapid changes in mental status and vital signs. Thus it is important to wait up to 6 weeks after medication is stopped, before starting with another drug. www.indiandentalacademy.com
  • XII. Heterocyclics 2nd Generation heterocyclics • amoxapine • maprotiline • trazodone • bupropion Third Generation heterocyclics • mirtazapine • venlafaxine • nefazodone www.indiandentalacademy.com
  • XII. Heterocyclics • The second and third generation antidepressants are by no means a homogeneous group. • As with the TCA's , they all have variable bioavailability. • High protein binding. • Some have active metabolites. • Trazodone and Venlafaxine have the shortest plasma half-lives, which mandates divided doses during the day. • Nefazodone and fluvoxamine cause inhibition of CYP3A4. www.indiandentalacademy.com
  • XII. Heterocyclics Mechanism of Action: 1) NT reuptake inhibition. maprotiline. 2) 5-HT receptor antagonism (for 5-HT2A or 2C receptors). nefazodone, mirtazapine, and trazodone 3) Alteration of NE Output. bupropion, amoxapine, and trazodone. www.indiandentalacademy.com
  • XII. Heterocyclics Amoxapine. Metabolite of Loxapine (an antipsychotic) -- retains some antipsychotic activity and DA receptor antagonism => parkinson's-like symptoms. May be useful if psychosis is present. NE output. Maprotiline. A tetracyclic drug, resembles desipramine with less sedative and antimuscarinic side effects. Evokes seizures at high doses. Blocks NT reuptake. www.indiandentalacademy.com
  • XII. Heterocyclics Trazodone. Antagonist of 5-HT2A or 2C receptors. Unpredictable efficacy. Highly sedative (hypnotic), but minimal antimuscarinic action. Bupropion. Resembles amphetamine. Blocks DA reuptake (not important in depression). Causes CNS stimulation. Inhibits appetite. Aggravates psychosis. NE output. www.indiandentalacademy.com
  • XII. Heterocyclics Third Generation Mirtazapine. A derivative of mianserin. Antagonist of 5-HT2A or 5-HT2C receptors. Also antagonizes α 2adrenergic receptors, thus increasing NE and 5-HT release. Very sedating. Venlafaxine. Short plasma half-live, thus needs to be given in divided doses. Potent inhibitor of 5-HT uptake and weaker at NE reuptake (at low concentrations it acts like an SSRI). Nefazodone. Antagonist of 5-HT2A or 5-HT2C receptors. Moderately sedating. Potent inhibitor of www.indiandentalacademy.com CYP3A4, so cannot be given with cisapride
  • XII. Atypical/Heterocyclic 2nd Generation heterocyclics • Amoxapine Similar to TCAs ⇑NE output • Maprotiline α2-AR antagonist • Trazodone 5-HT antagonists • Bupropion SSRI-like Third Generation heterocyclics • Mirtazapine • Venlafaxine • Nefazodone www.indiandentalacademy.com
  • Noradrenergic Control of Serotonergic Release Receptors α 2-AR NE 5-HT α 1-AR 5-HT1 5-HT2 5-HT3 NE 1 2 www.indiandentalacademy.com 3 Mianserin
  • XIV. Alternative Therapies No way of a priori knowing which therapy will be best for a patient. • • • • Light Therapy Psychological Treatment ECT St. John’s Wort www.indiandentalacademy.com
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  • XVI. Anti-Manic Drugs Lithium (Li+) remains the drug of choice for the treatment and prophylaxis of mania. • Acute manic episodes are managed with lithium salts (carbonate or citrate) alone, or in combination with: 1) Antipsychotics (carbamazepine, similar in structure to TCAs but not effective in depression). 2) Valproic acid 3) Calcium-channel blockers (nifendipine, diltiazem, verapamil). www.indiandentalacademy.com
  • XVI. Anti-Manic Drugs + Li • Small monovalent cation (between H+ and Na+). • Distributed in total body water, similar to sodium. • May partially inhibit Na+-K+ ATPase. • Inhibits ADH => diuresis. • May decrease thyroid function. • Teratogenic (tricuspid valve malformation). • Excreted by kidney. www.indiandentalacademy.com
  • XVI. Anti-Manic Drugs + Li • Not to be taken with thiazide diuretics (e.g. chlorthiazide). • Lithium clearance is reduced by 25%. • All neuroleptics (with the exception of clozapine), produce more severe extrapyramidal syndromes when combined with lithium. www.indiandentalacademy.com
  • XVI. Anti-Manic Drugs + Li • Helps alleviate the depressive phase of bipolar illness. • Useful in refractory depression when added to SSRIs or TCAs, but not a good antidepressant alone. www.indiandentalacademy.com
  • XVI. Anti-Manic Drugs Li + Mechanism of action: • Does not alter receptor numbers but alters the coupling of the receptors with their second messengers by reducing coupling of G-proteins. • Regulation of β-AR and DAR. • Can reduce release of NTs (5-HT) and affinity of binding to receptor. www.indiandentalacademy.com
  • XVI. Anti-Manic Drugs Li + Mechanism of action (Con’t): Inhibits breakdown of IP2 to IP1 (during PIP hydrolysis) => depletion of DAG and IP3 and ↓ [Ca2+] in response to receptor activation (i.e. from 5-HT2R, α1-AR, muscarinic receptors and others). • Alterations in adenylate cyclase and phospholipase C. www.indiandentalacademy.com
  • XVI. Anti-Manic Drugs G PLC PIP2 DAG IP3 Ca 2+ IP2 X Li PIP IP1 PI Inositol www.indiandentalacademy.com +
  • XVI. Anti-Manic Drugs Valproic Acid A well known antiepileptic has been found to have antimanic effects. Shows efficacy equivalent as that of lithium during the early weeks of treatment and is being evaluated for maintenance treatment. Titrated well, the sedation can be controlled. Nausea being the only limiting factor in some patients. May be used as first line treatment for mania, although it may not be as effective in maintenance treatment as lithium for some patients. www.indiandentalacademy.com Mechanism of action: ???
  • XVI. Anti-Manic Drugs Carbamazepine Effective as an antimania medication Mechanism of action (Con’t): May be due to decrease overexcitability of neurons (anticonvulsive effect). www.indiandentalacademy.com
  • XVI. Anti-Manic Drugs Ca2+ Channel blockers Nifedeipine Verapamil Mechanism of action (Con’t): NT Release? www.indiandentalacademy.com
  • www.indiandentalacademy.com Leader in continuing dental education www.indiandentalacademy.com