antidepressants 2013

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  • AntidepressantsPrajogo Wibowo

  • What are antidepressants???Drugs that are used to relieve or prevent psychic depression.Work by altering the way in which specific chemicals, called neurotransmitters, work in our brains (i.e. in the case of depression, some of the neurotransmitter systems dont seem to be working properly).They increase the activity of these chemicals in our brains

  • HistoryAntidepressants were first developed in the 1950s and have been used on a regular basis since then.There are many different types, for example, the older tricyclics and the newer SSRIs (Selective Serotonin Reuptake Inhibitors). These two types account for about 95% if the antidepressants prescribed.Now there are newer, more popular types, such as SNRI (Dual Serotonin and Norepinephrine Reuptake Inhibitor) and NDRI (Norepinephrine and Dopamine Reuptake Inhibitor)

  • Antidepressants Classification1) Tricyclics and Tetracyclics (TCA)Imipramine Doxepin Desipramine AmoxepineTrimipramineMaprotiline Clomipramine Amitriptyline NortriptylineProtriptyline2) Monoamine Oxidase Inhibitors (MAOIs)TranylcypraminePhenelzineMoclobemide3) Serotonin Selective Reuptake Inhibitors (SSRIs)FluoxetineFluvoxamineSertralineParoxetineCitalopram4) Dual Serotonin and Norepinephrine Reuptake Inhibitor (SNRI)Venlafaxine Duloxetine5) Serotonin-2 Antogonist and Reuptake Inhibitors (SARIs)NefazodoneTrazodone6) Norepinephrine and Dopamine Reuptake Inhibitor (NDRI)Bupropion7) Noradrenergic and Specific Serotonergic Antidepressant (NaSSAs)Mirtazapine8) Noradrenalin Specific Reuptake Inhibitor (NRI)Reboxetine9) Serotonin Reuptake EnhancerTianeptine

  • Tricyclic Antidepressants (TCAs)Between 1960 and 1980 tricyclic antidepressants (TCAs) represented the major pharmacological treatment for depression.They have been considered a homogeneous group of drugs differing mostly in their potency to inhibit presynaptic norepinephrine or serotonin uptake and in their propensity for causing variety of unwanted effects. The TCAs induce anticholinergic, antihistaminergic, and cardiotoxic side effects which are related to their action on muscarinic (mainly M1), histamine (H1), adrenergic (1) receptors and cardiac Na+ and Ca2+ channels.

  • TCA DrugsThe first tricyclic antidepressant discovered was imipramine, which was discovered accidentally in a search for a new antipsychotic in the late 1950s. Imipramine hydrochloride is a member of the dibenzazepine group of compounds. It is designated 5-[3-( Dimethylamino)propyl]-10,11- ihydro-5H-dibenz [b,1-azepine] Monohydrochloride. Imipramine (Tofranil)

  • Imipramine (Tofranil)Imipramine is the prototypic tricyclic antidepressant utilized in the treatment of major depression and exerts its therapeutic efficacy only after prolonged administration. The mechanism of action of imipramine hydrochloride is not definitely known. However, it does not act primarily by stimulation of the central nervous system. The clinical effect is hypothesized as being due to potentiation of adrenergic synapses by blocking uptake of norepinephrine at nerve endings.

  • Amitriptyline (Elavil, Tryptanol, Endep)Amitriptyline HCl is 3-(10,11-dihydro-5H-dibenzo [a,d] cycloheptene-5-ylidene)-N,N-dimethyl-1-propanamine hydrochloride. Its empirical formula is C20H23NHCl.Amitriptyline

  • AmitriptylineAmitriptyline HCl is an antidepressant with sedative effects. Its mechanism of action is not known. It is not a monoamine oxidase inhibitor and it does not act primarily by stimulation of the central nervous system.Amitriptyline inhibits the membrane pump mechanism responsible for uptake of norepinephrine and serotonin in adrenergic and serotonergic neurons. Pharmacologically this action may potentiate or prolong neuronal activity since reuptake of these biogenic amines is important physiologically in terminating transmitting activity. This interference with the reuptake of norepinephrine and/or serotonin is believed by some to underlie the antidepressant activity of amitriptyline.

  • Side Effects of TCAsThe side effects of tricyclic antidepressant may include drowsiness, anxiety, restlessness, dry mouth, constipation, urinary retention or difficulty with urination, cognitive and memory difficulties, weight gain, sweating, dizziness, decrease in sexual ability and desire, muscle twitches, weakness, nausea, increased heart rate and irregular heart rhythms (rare). Some of these side effects relate to their anticholinergic properties.

  • Selective Serotonin Reuptake Inhibitors (SSRIs)The SSRIs are currently the most widely utilized class of antidepressants in clinical practice.They act within the brain to increase the amount of the neurotransmitter, serotonin (5-hydroxytryptamine or 5-HT), in the synaptic gap by inhibiting its re-uptake. Instead of being discovered by accident, SSRIs were specifically designed while considering the biological causes of depression. SSRIs are described as 'selective' because they affect only the reuptake pumps responsible for serotonin, as opposed to earlier antidepressants, which affect other monoamine neurotransmitters as well. Because of this, SSRIs lack some of the side effects of the more general drugs.

  • SSRI DrugsSSRI drugs include many of the popular drugs on the market todayThey include Fluoxetine (Prozac) and Sertraline (Zoloft).FluoxetineSertraline

  • Fluoxetine (Prozac)Fluoxetine, also known as Prozac, was initially approved for treatment of depression in Belgium in 198617, and then Eli Lilly's Prozac was approved by the FDA on December 27th 1987 and introduced in the United States at the beginning of 1988. Prozac was the first of a new class of drugs, called selective serotonin reuptake inhibitors (SSRIs), to be approved for use in the United States.Fluoxetine hydrochloride is an antidepressant for oral administration. It is chemically unrelated to tricyclic, tetracyclic, or other available antidepressant agents. It is designated ()-N-methyl-3-phenyl-3-[(a,a,a-trifluoro-p-tolyl)-oxy]propylamine hydrochloride and has the empirical formula of C17H18F3NOHCl.

  • Fluoxetine (Prozac)Fluoxetine is a racemic mixture (50/50) of R-fluoxetine and S-fluoxetine enantiomers, where both enantiomers are specific and potent serotonin uptake inhibitors with essentially equivalent pharmacologic activity. But, the S-fluoxetine enantiomer is eliminated more slowly and is the predominant enantiomer present in plasma at steady state. The body eliminates Fluoxetine very slowly. The half-life of fluoxetine after a single dose is 2 days and after multiple dosing 4 days. The liver then metabolizes fluoxetine into norfluoxetine, a desmethyl metabolite, which is also a serotonin reuptake inhibitor; norfluoxetine has an even longer half-life, i.e. 8.6 and 9.3 days for single and repeated dosage respectively.Because fluoxetine's metabolism involves the P450IID6 system, concomitant therapy with drugs also metabolized by this enzyme system (such as the tricyclic antidepressants) may lead to drug interactions. Hence, the complexity of the metabolism of fluoxetine has several consequences that may potentially affect fluoxetine's clinical use.

  • Fluoxetine Dosage and Side EffectsIt is marketed in capsules containing 10, 20, or 40 mg of active ingredient or in tablets containing 10 mg. Dosages in the range of 20-60 mg per day are standard, with 80 mg considered a maximum. Fluoxetine has a wide range of published interactions, notably with monoamine oxidase inhibitors. Common side-effects include anxiety, restlessness, trembling, weakness, skin rash, anorgasmia, itching, and a decrease in sexual drive.

  • Sertraline (Zoloft)Sertraline HCl is a selective serotonin reuptake inhibitor (SSRI) for oral administration. It is chemically unrelated to other SSRIs, tricyclic, tetracyclic, or other available antidepressant agents. Sertraline hydrochloride has the following chemical name: (1S-cis)-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-N-methyl-1-nanphthalenamine hydrochloride. The empirical formula is C17H17NCl2HCl.

  • Sertraline (Zoloft)The mechanism of action of sertraline is presumed to be linked to its inhibition of CNS neuronal uptake of serotonin (5HT).In vitro studies have shown that sertraline has no significant affinity for adrenergic (alpha1, alpha2, beta), cholinergic, GABA, dopaminergic, histaminergic, serotonergic (5HT1A, 5HT1B, 5HT2), or benzodiazepine receptors; antagonism of such receptors has been hypothesized to be associated with various anticholinergic, sedative, and cardiovascular effects for other psychotropic drugs. Sertraline does not inhibit monoamine oxidase. Sertraline undergoes extensive first pass metabolism. The principal initial pathway of metabolism for sertraline is N-demethylation. N-desmethylsertraline has a plasma terminal elimination half-life of 62 to 104 hours.

  • Sertraline Dosage and Side EffectsSertraline is manufactured by Pfizer as small green 25 mg tablets, blue 50 mg tablets, or off-yellow 100 mg tablets. It is used in dosages of between 25 mg and a maximum of 200 mg per day. It has a number of adverse effects including insomnia, asthenia, gastrointestinal complaints, tremours, confusion, and dizziness; it can induce mania or hypomania in around 0.5% of patients. One property of sertraline is that it appears to be also a minor inhibitor of dopamine reuptake.

  • Serotonin and Noradrenaline Reuptake Inhibitors (SNRIs)Serotonin norepinephrine reuptake inhibitors (SNRIs) are a class of antidepressant used in the treatment of clinical depression and other affective disorders.They act upon two neurotransmitters in the brain that are known to play an important part in mood, namely, serotonin and norepinephrine. This can be contrasted with the more widely-used selective serotonin reupt