Anti-Depressant Drugs PDF

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Anti-Depressant Drugs I 418191 w 410351 DR. TALHA JAWAID PH.D ASSISTANT PROFESSOR DEPARTMENT OF PHARMACOLOGY IMSIU, RIYADH MAO Monoamineoxidase wow 1 F whatwewanttoinhibit so impulsecome MAOA serotonine nor epiepi onedrug selegilinéedopamine MAOB itsedation disfuncless thanSSRI sexual BlockReuptaketransporters vision M drymouth constipation blurred was norepitransporter retention urine tgo gg.gg Serotonine transporter other and E blockboth no hypotention uggs chronicpainsyndrome ofmigraine Prophylaxis can'tbegiventoPt with glaucoma eletary SSRI selectiveSeton SNR sereto Not SIElessthantricyclic Reuptakeinhibitors 9 It M Metabolite have long yzlife q ago greatersexualdisfund civic try bit alwaysmentorfespiinchildren ifyouwanttogiveotherdrugstopyaoiforatleast2weekstoclearitfromsystem 2 non.si Majority MicrosomalEnzymeinhibitors j.fi jjjjjj thenstart thenewdrug DDinteraction don't givewith Mai m serotonensyndrome don'tworkonchronicpain myo mao selegiline indepre used astransdermalpatch chronicpain syndrome eithercaused bydepressionorother vtrydiaittitentititioodcontainthyramincegcheese Cheesereaction Typical like neurolagia hypertention crisis workon amines whatamines Atypical dopamine serotonin e other action norepi Most commonlyused Rightnow SSRIs uses depresstion Biogenicaminetheory ECD neurosis phopia eatdisorder etc give Medicationto 4levelsof serotonine need 2 4 week to seeeffect orand norepi LEARNING & OBJECTIVES At the end of lecture students must know the following: 1)Define Depression? Explain the causes of depression. 2)Explain the different types of Depressive disorder & their hypothesis. 3)Classify Anti- Depressant drugs? 4)Explain the pharmacodynamics of TCAs in detail with the role & synthesis of amines. Explain the pharmaco kinetics of TCAs drug with clinical application & doses. Depression "Depression" is a very common psychiatric disorder that is related to the "mood" (affective disorder). Changes in mood are associated with depression and/or mania. Disorders of mood rather than disturbance in thought or cognition. Clinical depression: feeling sad for more than two weeks. Symptoms of Depression 1- Emotional Symptoms Intense feelings of sadness, hopelessness and despair Inability to experience ordinary pressure or to cope with ordinary life events Feeling of guilt and ugliness Indecisiveness and loss of motivation Loss of energy and interest Biological symptoms 1- Retardation of thought and action 2- Loss of libido 3- Loss of appetite and sleep disturbance *** DEPRESSION IS THE MOST COMMON CAUSE OF SUICIDE Symptoms opposite: of "mania" are exactly the Happy, excited, euphoric , self-confidence, lack of judgment Sudden odd decisions of disastrous consequences that are mostly Excessive rapid talking , moving quickly from one to another (Flight of ideas) Hyperactive & full of energy, unable or unwilling to sleep Sudden irritability, rage or paranoia Impatience, Aggression Classification of Depression Classification of Depression A) According to severity of symptoms: 1. Mild depression---------self-limiting 2. Moderate depression -------difficulties at home and work 3. Severe depression --------serious, associated with suicidal thoughts B) According to type 1- Unipolar depression (major depression): mood swings are always in the same direction about 75% of cases non-familial accompanied by symptoms of anxiety and agitation Associated with stressful life events 25% familial unrelated to external stresses endogenous depression antidepression 1,6164 lithium 2- Bipolar depression (manic-depressive): In which depression alternates with mania enthusiasm and self-confidence, accompanied by impulsive actions antidepression Mania 121 The patient swings between "mania" and "depression“ (manic-depressive illness) - It is mainly hereditary and appears in early adult life. - Alternating depression and mania What are the possible mechanisms of depression? Depression is associated with insufficient central release of NA and 5-HT Led to development of the Biogenic Amine Hypothesis The Monoamine Theory of Depression Proposed in 1965 and states that DEPRESSION is caused by a functional deficit of Monoamine transmitter at certain sites in the brain, while MANIA results from functional excess. The Theory is based on the ability of known antidepressat drugs (TCAs and MAOIs) to facilitate monoaminergic transmission and of drugs as Reserpine to cause depression. Pharmacological evidence supporting The Monoamine Theory of Depression Drug 0W Ask NovepiD serosa 2k Principal action Effect in depressed patients TCA Block NA and 5-HT reuptake Increase MOOD MAO Inhibitors Increase stores of NA Increase MOOD and 5-HT Reserpine Inhibits NA and 5-HT storage Methyldopa Inhibits NA synthesis Decrease MOOD ECT Increase CNS response to NA and 5-HT Increase MOOD Tryptophan Increase 5-HT synthesis Increase MOOD Decrease MOOD Monoamine nerves: Neurotransmission Treatment of Depression Anti depressant drugs is not to cure the depressant, but it is used to reduce the symptom of depression. 1. Psychological treatment 2. Pharmacological treatment 70 % of depressed patients respond to antidepressants 3. ECT ( electroconvulsive therapy) for very severe depression, which has not responded to other treatments or for patients who cannot take antidepressants Three rules of Anti depressant drugs ( Patient Safety). Increased suicidal tendency: Antidepressant drugs increase suicidal thought in first few week of treatment (1824 years). Start with low dose then increase Slow Onset & slow taper off. So never stop abruptly. Ptdepressed again Never Mix : SSRI+St.John’s Wort DDinteraction MAOI + Antidepressant (TCA,SSRI,SNRI) Antidepressants wait at least a week to see if drug is working Antidepressants do not act immediately (show clinical effects after 2 weeks) indicating that secondary adaptive changes in the brain are important. The most consistent adaptive change seen with antidepressant drugs is the downregulation of beta-, alpa2 and 5-HT2 receptors. Alpha-1 is not affected. 0 19411 i Wiebe d Metabolismfrom one Affect only people who are depressed. P to anotherisdiff Effect does not increase with increasing doses. inhighdosestheylowertheseziur thresholdsobecareful d narrowtherapeuticindex Antidepressants are not habit-forming. no SSRIs cardie arrythmia Antidepressants differ widely in side effects. addiction Classification of Antidepressants 1) Tricyclics (TCAs) and Tetracyclics hort HT 5 andgothe Imipramine( Tofranil) , Desipramine (Norpramin) Amitriptyline (Elavil) 2) Monoamine Oxidase Inhibitors (MAOIs) Tranylcypramine Phenelzine Moclobemide spea.fi MOAA 3) Selective Serotonin Reuptake Inhibitors (SSRIs) Fluoxetine MOAB Sertraline dopal seregalin Paroxetine Classification of Antidepressants 4) Serotonin and Norepinephrine Reuptake Inhibitor (SNRI) Venlafaxine Duloxetine 5) Serotonin-2 Antogonist and Reuptake Inhibitors (SARIs) Nefazodone Trazodone 6) Norepinephrine and Dopamine Reuptake Inhibitor (NDRI) Bupropion help to quit smoking 7) Serotonin Reuptake Enhancer Tianeptine gym d Mechanism TRICYCLIC ANTI-DEPRESSENT DRUGS A ImipraminePro drug Clomipramine Nortriptyline Trimipramine Desipramine Amitriptyline Doxepin DISADVATAGE: Almost all type of TCAs start showing action afer one week. Tricyclic Antidepressants (TCAs) represents the class (Prototype) Inhibit monoamine reuptake (serotonin and noradrenalin) Imipramine Serotonin and NA at Increase the concentration of synapse and potentiate the action (therapeutic effects) Other receptors acted (Adverse effects) Muscarinic- Anticholinergic side effects (dryness etc.) # Alpha- alpha blocking actions (postural hypotension etc.) # Histamine-Antihistaminic (sedation) # Dopamine- antipsychotic (amoxapine, EPS maprotiline) also block DopamineR MECHANISM OF ACTION of TCAs: All tricyclics block reuptake pumps for both 5HT and NE in nerve terminals by competing for binding site of the transport protein ØSo ↑ conc. of NE & serotonin in the synaptic cleft & at the receptor site SIEdrymouth so wedon'tgiveto Ptwithbenginprostatic hypertrophy ØFacilitation of NE & serotonin transmission ----leadtoI acut improves symptoms of depression retentionof otherwaytocalcifythem urine Some have more potency for inhibition of 5HT uptake pump; clomipramine, imipramine, amitryptyline Others have more potency for inhibition of NE uptake pump: nortriptyline, desipramine it. at SIE Postoralhypotention Wightgain d Both O PHARMACOLOGICAL ACTIONS 1- Elevate mood allsymptoms ofdepression willimprove 2- Improve mental alertness 3- Increase physical activity # The antidepressant effect may develop after several weeks of continued treatment ( 2 - 3 weeks) 4- In non-depressed patients àThey cause sedation, confusion & motor incoordination sax PHARMACOKINETICS of TCAs Peak levels: 2-6 hours post ingestion TCAs are "lipophilic" inu nature, therefore they are well orally absorbed from the GIT and readily cross the blood brain barrier to penetrate the CNS. Elimination: hepatic oxidation activemetabolitethatlater will be excreated in urine g(Imipramine to Desipramine, Amitriptyline to Nortriptyline) TCAs are metabolized in the liver by demethylation and by hydroxylation into metabolites that retain the biological activity of the parent compounds. PHARMACOKINETICS of TCAs TCAs are strongly bound to plasma proteins. DDinteraction Average t1/2: 24 hours Up to 72 hours in overdose Large T1/2 and large VD because TCA extensively bound to plasma protein (90-95 %) Therapeutic uses of TCAs m not bipolar Endogenous (Major) Depression -- moderate to severe. Panic attack /acute episode of anxiety. Passurinewhile a sleep But Imipramine is used for treatment of nocturnal enuresis in Btc children and geriatric patients as it constricts internal urethral sphincter ( anti-muscarinic effect). Generalized Anxiety Disorder (GAD). Obsessive Compulsive Disorder (OCD) Attention Deficit Hyperkinetic Disorder (ADHD). Chronic neuropathic pains or Unexplained body pains. Prophylaxis of maigrane Side Effects of TCAs Side Effects of TCAs Side effects of TCAs Four major toxic effects (A, C, S, D) A = Anticholinergic( dryness of mouth, Difficulty in swollening) C = Cardiovascular arrythmias narrow tharapaticrange S = Seizures Mowtheirthreshold D = Death ANTICHOLINERGIC EFFECTS Sedation, Delirium, coma Tachycardia Mydriasis Dry mucous membranes and skin Dry mouth Decreased or absent bowel sounds Constipation Urinary retention Interaction of TCA with other drugs q TCA are strongly bound to plasma protein, therefore their effect can be potentiated by drugs that compete for their plasma protein binding site ( Aspirin and Phenylbutazone). q TCAs are metabolized by liver microsomal enzymes, therefore their effect can be reduced by inducers of liver microsomal enzymes (Barbiturates), or potentiated by inhibitors of liver microsomal enzymes (Oral contraceptives, Antipsychotics, and SSRIs). q TCA (inhibitors of monoamine reuptake) should not be given with MAOIs (inhibitors of monoamine degradation) "hypertensive crisis". serotonine syndrome hypothermia Contraindications qTCAs should not be used in patients with Glaucoma or with enlarged prostate because of I their atropine-like action. espinarrowngleglaucoma qTCAs (given alone) are contraindicated in manicdepressive illness, because they tend to "switch" the depressed patient to the "manic" phase, therefore, they should be combined with "lithium salts". Anti-Depressant Drugs -2 LEARNING & OBJECTIVES Anti-Depressant Drugs2: At the end of lecture students must know the following: 1) Explain the mechanism of action of Selective serotonin reuptake inhibitors. 2) Explain the detail Pharmacokinetic profile including drug interaction of SSRIs. 3) Explain the uses of SSRIs in detail. 4) Explain the pharmacodynamics of Mono aminooxidase inhibitors & Atypical Anti- depressant drugs. 5) Explain the clinical uses, adverse effect, doses & drug interaction of SSRIs. Monoamine Oxidase Inhibitors Amongst the first Antidepressants Include: - Phenelzine( Nardil) Elective - Tranylcypromine (Parnate) - Isocarboxazid N- Moclobemide(Aurorix) only NOAA - Pargyline (Eutonil) ØOnset of antidepressant effect is delayed for 2-4 weeks. Monoamine Oxidase Inhibitors (MAOIs) MAO Enzyme MAO exists in tow forms coded by separate genes MAO-A: Metabolizes norepinephrine, serotonin and tyramine. Inhibition of MAO-A produces Antidepressant effect. MAO-B: specific for dopamine. Inhibition of MAO-B produces Anti-parkinsonian um effect. Monoamine Oxidase Inhibitors (MAOIs) 1- Irreversible and nonselective MAOIs (Classic MAOI) Phenelzine Tanylcypromine Isocarboxazid pargyline - Can not distinguish between the two isoenzymes - MAO-A and B enzyme activity can not be restored unless new enzyme is synthesized, therefore the effect of MAOIs persists for a period of 2-3 weeks after stopping treatment, where a new (fresh) enzyme has to be synthesized. II IT stg 2-Reversible and selective inhibitors of MAO-A: - Moclobemide (antidepressant action, Short acting) 3- Selective inhibitor of MAO-B: - Deprenyl (neurodegenerative disorder) - Selegiline (used in the treatment of I Parkinsonism) also fordepression as trandermalPatch Side Effects of MAOIs 1- Hypertensive crisis: After MAO inhibition, other amines such as dopamine are able to accumulate in peripheral sympathetic nerve terminals and displace vesicular NA, thus increase NA release and sympathetic activity. 2- Antimuscarinic effects (atropine-like sideeffects): Dry mouth blurred vision Urinary retention Side Effects of MAOIs 3- CNS stimulation: Insomnia Tremors Excitement Convulsions 4- Weight gain: associated with increased appetite Drug interactions of MAOIS 1- Pethidine: MAOIs interact with the opioid receptor agonist (pethidine) which may cause severe hyperpyrexia, restlessness, coma, hypotension. The mechanism still unclear – but it is likely that an abnormal pethidine metabolite is produced because of inhibition of normal demethylation pathway. 2- Levodopa: precursor of dopamine can interact with MAOIs leading to hypertensive crisis. selective we give in PA selective MAOB if g Drug interactions of MAOIs 3- Amphetamine and Ephedrine: Indirectly acting sympathomimetics can interact with MAOIs causing the liberation of accumulated monoamines in neuronal terminals leading to hypertensive crisis. 4-TCAs (inhibitors of monoamine reuptake) can interact with MAOIs (inhibitors of monoamine degradation) leading to hypertensive crisis. ANI 5- MAOIs & SSRIs ------- Serotonin syndrome. 49HIS d Items qThis occurs when Tyramine rich foods are taken with MAOIs. qTyramine rich foods include Old cheese , Concentrated yeast products, Pickled or smoked fish, Red beans, Red Wine, Chicken liver, Sausages. qTyramine in food is normally degraded in the gut by MAO-A. Pt give list of food to he can't eat qSince the enzyme is inhibited by MAOIs, tyramine from ingested food is absorbed, and then taken up into adrenergic neurons where it is converted into octopamine - a false transmitter which causes massive release of NE and may result in hypertensive crisis ; severe hypertension, severe headache and fatal intracranial haemorrhage. qTreatment : Prazocin or phentolamine q N.B. At least 10 mg tyramine needs to be ingested to produce this reaction. q The special advantage claimed for Moclobemide. is that, less cheese reaction occurs with its use. Therapeutic uses of MAOIs Considered to be the last –line agents due to Drug / Food interactions 1. In endogenous depression, specially patients non responsive / allergic to TCAs 2. Atypical depression 3. Phobic states Ien times Selective 5-HT reuptake inhibitors (SSRIs) i - Fluoxetine (prozac) 20-80 mg/d - Fluvoxamine (luvox) 50-300 mg/d - Paroxetine (paxil) 20-50 mg/d - Sertraline (zoloft) 50-200 mg/d Maryases PTSD ADHD depression - Citalopram Aff Initiate with 10-20 mg/d Phopia panic attack OCD Selective 5-HT reuptake inhibitors (SSRIs) - Fluoxetine (prozac) - Fluvoxamine - Paroxetine - Sertraline - Citalopram - Escitalopram Selective Serotonin Reuptake Inhibitors 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 in synaptic cleft. (5-hydroxytryptamine or 5-HT), in the synaptic gap by inhibiting its re-uptake. 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. 206 Polenta a obis's 5551 Blocked by Blocked antidepressants by antidepressants Fluoxetine (Prozac) long Yz life ad The body eliminates Fluoxetine very slowly. The half-life of fluoxetine after a single dose is 2 days and after multiple dosing 4 days. It is a prodrug. Contraindicated with epilepsy patient. The liver then metabolizes fluoxetine into norfluoxetine, a desmethyl metabolite, which is also a serotonin reuptake inhibitor. metabolite Norfluoxetine has an even longer half-life, i.e. 8.6 and 9.3 days for single and repeated dosage respectively. Very few anticholinergic side effect (Advantage ) Fluoxetine is approved for use in children & adolescence, is relatively safe in pregnancy. d ADHD 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. The mechanism of action of sertraline is presumed to be linked to its inhibition of CNS neuronal uptake of serotonin (5HT).It is a prodrug. One property of sertraline is that it appears to be also a minor inhibitor of dopamine reuptake. Individual compounds Fluoxetine nFluvoxamine Prototype of SSRIs Longest acting Less cholinergic side effect like dryness of mouth,constipation etc nShort acting nCommonly used in indoor patients nSertraline Paroxetine not block of Short acting More GI side effects qCitalopram Hi i Similar to sertraline but should be avoided in patients attempting suicide nLess chances of drug interactions due to low potency to cause cytochrome enzyme depression qEscitalopram Active enantiomer of citalopram side effects are less Selective Serotonin Reuptake Inhibitors No Chease reaction Advantages - The Most commonly prescribed antidepressants - Lacks cardiovascular and anticholinergic side effects compared to TCA - In contrast to MAOI, they do not cause ‘cheese’ reaction - Safer (low risk of overdose) - Acute toxicity is less than that of MAOI or TCA SSRIs ski MAID 1521 IM 1 washout peroid pit Adverse effects of SSRIs: GIT symptoms: Nausea vomiting & diarrhea. Changes in appetite ---weight loss/ gain. Sleep disturbances: Drowsiness with Fluvoxamine. ME Anxiety & Tremors. Sexual dysfunction: Loss of libido , delayed ejaculation. Coz SIADH syndromy All antidepressant drug produce hyponatremia due to induction of ADH but it is reported more frequently with SSRI in compare to other drugs. Discontinuation syndrome: apruptydroping Symptoms are headache ,malaise & flu like symptoms, agitation , irritability & nervousness Therapeutic Uses of SSRIs Same as for TAC, in addition effective in the following conditions Depression. Anxiety Disorder. Eating disorders- bulimia nervosa (fluoxetine). Post traumatic stress disorder. Premenstrual dysphoric disorder. Attention Deficit Hyperkinetic Disorder. Treatment of premature ejaculation. Drug interactions of SSRIs SSRIs are potent inhibitors of liver microsomal enzymes. Therefore they should not be used in combination with TCAs because they can inhibit their metabolism increasing their toxicity. SSRIs should not be used in combination with MAOIs because of the risk of life-threatening "serotonin syndrome" (tremors, hyperthermia, cardiovascular collapse and death). Both drugs require a "washout" period of 6 weeks before the administration of the other. and at least sweet NE Selective Reuptake Inhibitors (NRIs) New group Reboxetine Tomoxetine Selective to NE uptake May be more effective in noradrenaline deficiency syndrome (e.g., depression associated with fatigue, apathy, cognitive disturbances), or non responders to SSRIs. Also act at presynaptic α2, postsynaptic α1, α2 and β adrenergic receptors (tremor, agitation, blood pressure). Advantages Lacks antagonistic activity at histamine H1, muscarinic & adrenergic receptors or Na+ pump as with TCA. Fewer unwanted cardiovascular effects than TCA’s. TCR act on other receptor 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, 5HT and NE. This can be contrasted with the more widely-used selective serotonin reuptake inhibitors (SSRIs), which act only on serotonin. Serotonin and Noradrenaline Reuptake Inhibitors (SNRIs) SNRIs were developed more recently than SSRIs, and there are relatively few of them. Their efficacy as well as their tolerability appears to be somewhat better than the SSRIs, owing to their compound effect. These new drugs, because of their specificity for the serotonin and norepinephrine reuptake proteins, lack most of the adverse side effects of TCAs and MAOIs. Serotonin and Noradrenaline Reuptake Inhibitors (SNRIs) Venlafaxine It is used primarily for the treatment of depression, generalized anxiety disorder, and social anxiety disorder in adults. Venlafaxine is the first and most commonly used SNRI. Selective 5HT and NE uptake blockers Combines the action of SSRI and NRI. Causes dual action on serotonin and adrenergic systems, thus amplifying these two systems synergistically. But without α1, M1 cholinergic or H receptor blocking properties. Venlafaxine Venlafaxine Side Effects Because of its relatively short half-life of 4 hours, it should be administered in divided dosages throughout the day. common in all Side effects may include nausea, dizziness, sleepiness, abnormal ejaculation, sweating, dry mouth, gas or stomach pain, abnormal vision, nervousness, insomnia, loss of appetite, constipation, confusion/agitation, tremors, and drowsiness. for chronic pain syndrome good very neuropathy 1.581 w sb Norepinephrine and Dopamine Reuptake w I Inhibitor (NDRI) nThese are a class of antidepressants that are not really categorized as a special group of antidepressants. nThe only antidepressant in this group is Bupropion (Wellbutrin), which is an antidepressant of the aminoketone class, chemically unrelated to tricyclics or SSRIs. Quit smoking counding nicotine Patch Gum Bupropion or clonidine tocurving of Bao Bupropion Bupropion is a selective catecholamine (norepinephrine and dopamine) reuptake inhibitor. It has only a small effect on serotonin reuptake. It does not inhibit MAO. Bupropion is metabolised in the liver. It has at least three active metabolites; hydroxybupropion, threohydrobupropion and erythrohydrobupropion. These active metabolites are further metabolised to inactive metabolites and eliminated through excretion into the urine. Partial agonist at 5-HT type IA receptors (decrease 5HT activity ) but enhances dopaminergic and noradrenergic activity Bupropion Advantages and Side Effects Advantages Sexual side effects normally accompanying SSRI's do not accompany bupropion. Interestingly, patients commonly report increased libido, perhaps evidence of its dopaminergic properties. No weight gain, loss of appetite. Common side effects Dry mouth, tremors, anxiety, agitation, dizziness, headache, excessive sweating, increased risk of seizures and insomnia. d almost all anti depressant Therapeutic Uses of Bupropion Major depression. Bupropion is useful in ADHD. Bupropion also helps in reducing craving & attenuating the withdrawal symptoms for Nicotine in tobacco users trying to quit smoking. Atypical Antidepressants nTianeptine / and Amineptine nVenlafaxine / Duloxetine nIncreases rather inhibiting 5-HT uptake nNeither sedative nor stimulant nEffective in anxiodepressive states nSNRI selective in action nFaster onset of action nIncreases BP Ly nDuloxetine increases uretheral tone used in urinary incontinence ( over active bladder) my to go on details Mirtazapine (NaSSA) Noradrenergic and specific serotonergic antidepressant Blocks alpha 2 auto receptor (on NA neuron) and hetero- (on 5HT neuron) receptors increasing both NA and serotonin release. i typical Bupropion Inhibits DA and NA uptake has excitant effect Used to reduce smoking Special Groups 1. Epilepsy: No currently used antidepressive is entirely safe in epilepsy, but SSRIs are likely to cause fits thean the amityptyline group, mianserin or maprotiline. The Elderely: Depression is a common in the elderly in whom it tend to be chronic and has rate of recurrence. Treatment with drugs became more difficult because of slow metalbolism of drugs. Lofepramine and SSRIs cause fewer problem in patients with proststism or glucoma than to do with TCAs because they have less anticholinergic effect. Miaserin has fewer anticholinergic effect, but blood dyscriasis occurs about one in 400 patients.