class 1 antidepressants
TRANSCRIPT
Dr. RAGHU PRASADA M SMBBS,MDASSISTANT PROFESSORDEPT. OF PHARMACOLOGYSSIMS & RC.
1
They are among the most commonly prescribed drugs .Depression: It is a the most commonly serious disorder of
mood, ranges from mild to very serious conditionTypes of Depression - Two types Unipolar Exogenous / Reactive Depression Endogenous/Major Depression (MDD) Bipolar
Tricyclic Antidepressant (TCA)AMITRIPTYLINE, NORTRIPTYLINEIMIPRAMINE, DESIPRAMINEDOXEPINE, TRIMIPRAMINE
Selective Serotonin Reuptake Inhibitor (SSRI)SERTRALINE, FLUOXETINEPAROXETINE, CITALOPRAM, ESCITALOPRAM
SNRI-Serotonin and Noradrenaline reuptakeinhibitorsDULOXETINE, VENLAFAXINEReversible inhibitors of MAO-A(RIMA)MOCLOBEMIDE, CLORGYLINEAtypical AntidepressantsBUPROPION, NEFAZODONE, MIANSERIN,TRAZODONE, MIRTAZEPINE
Depression is due to deficiency of nor-epinephrine &serotonin
Normally action of released NE & serotonin is terminatedby active reuptake into the nerve terminal from thesynapse via specific transporters.
TCAs block the amine transporters (uptake pumps) fornor-epinephrine (NET) & serotonin (SERT) in brain.
Facilitation of NE & serotonin transmission ---- improvessymptoms of depression .
Amitryptyline Potent sedative Weight gain ++ Anticholinergic ++ Most researched 150mg / day(Therapeutic in 95% of
adults)
Clomipramine Similar side effects to
amitryptyline. Said to be best for
obsessionalsymptoms.
150mg / day
Dothiepin Sedative Same side effects as
amitryptyline. By far and away the
most toxicantidepressant.
150 mg / day
Imipramine Stimulant Anticholinergic ++ 150 mg/ day
Antimuscarinic effectsPostural hypotensionTachycardia, arrhythmias-TCAs potentiate the effect ofdirectly acting sympathomimetics but inhibit the effect ofindirectly acting sympathomimetics
SedationWeight gainJittery feelingSexual dysfunction (ejaculatory)Demerits-anticholinergic, cardiovascular and neurologicalside effectsRelatively low safety margin, lag time of 2-4wks beforeaction
Anticholinergic drugs aggravative the toxicity of TCAsT3 and T4 potentiate CNS stimulant effects of TCAsPhenytoin, chlorpromazine and aspirin displace TCAsFrom lprotein binding sitesMOAs and TCAs show synergistic action leading toserious toxicitiesTCAs reverse the antihypertensive effect of alfa2receptor agonist clonidine
Citalopram Fewinteractions
Mostexpensive
20 mg /day
Fluoxetine Sedation –Skin S/E
Anxiety +Cheapest
20-80mg/day
Fluvoxamine Gut S/E + Insomnia - 200 mg /day
Paroxetine Sedation + Withdrawalproblems ?
20 mg /day
Sertraline Diarrhoea 50 mg /day
First choice in elderly. First choice if heart
disease. First choice if suicide
risk. More expensive.
Side effects Like TCA reduce with
time. Gut problems
predominate. Flat dose response
curve – so no need totitrate dose upwards.
MOA: Inhibit Serotonin & NE reuptake at all doses by
binding to NET & SERTVenlafaxine: Weak Dopamine re-uptake inhibitor at higher
doses. No effect on muscarinic, adrenergic or histaminicreceptors. They are preferred over TCAs for MDD & painsyndromes
ADR-sweating, anxiety, dizziness, impotenceDuloxetine-used fro panic attacks, diabetic neuropathic pain,
fibromyalgia and stress urinary incontinence in womenADR-agitation, insomnia and rise in BP
MAO –mono amino oxide is a mitochondrial enzymeinvolved in oxidative deamination of biological amines(Adr, NA, DA, 5-HT)MAO-A inhibitor posses antidepressant acitvityMoclobemide-Reversible and selective MAO-A inhibitorBecause of competitive enzyme inhibition, tyramine isable to displace it from the enzymeIt lacks anticholinergic, sedative, cognitive, psychomotarand cardiovascular side effectsWell tolerated alternative to TCAs150mg BD max-600mg / day.ADR- dizziness, insomnia, headache
With non-selective MAO inhibitorscheese wine, pickled meat, fish, yeast extractContain large quantities of tyramine, dopaIndirectly acting sympathomimetics escapedegradation in gut reach systemic circulation anddisplace large amount of NA hypertensive crisis,cerebrovascular accidentsTreatment-phentolamine, chlorpromazine, prazocin
MOIs +TCAs- hypertension, arrhythmias and seizuresMOIs inhibit degradation of dopamineNEhypertensionMOIs are enzyme inhibitorsMOIs+morphine severe respiratory depressionMOIs+sulfonylureas hypoglycemic comaMOIs+ chloroquine increased toxicity
Trazodone-first atypical antidepressant, blocks5-HT uptake and has prominent α adrenergic andweak 5HT2 antagonistic propertyBeneficial to OCD (Obsessive Compulsive Disorder)Low cardiotoxicity, few anticholinergic side effects.Drowsiness, Nausea.150 mg /day.
BUPROPION -The inhibitor of DA and NA uptake hasexcitant propertyIts metabolite is amphetamine like presynapticrelease of DA and NAUsed as an aid for smoking cessationMay be acting by augmenting the dopamine rewardpathwayAdverse effects- insomnia, agitation, dry mouthC/I- bipolar disorders
Mirtazapine : Blocks 5HT2 , & presynaptic α2 receptors.Enhances release of Serotonin & NEAmoxapine: Potent Nor-Epinephrine uptake inhibitor but
mild inhibition of Serotonin reuptake. Blocks D2receptors so has neuroleptic property also
Maprotiline: Potent Nor-Epinephrine uptake inhibitor.
All are useful in Major depression, in combination withother drugs.Bupropion is useful in ADHD
Bupropion also helps in reducing craving & attenuatingthe withdrawal symptoms for Nicotine in tobacco userstrying to quit smoking.Panic attacks, post traumatic stress disorderObsessive compulsive disorderNocturnal enuresisPremenstrual syndromeChronic alcoholism