anti depressant drugs
TRANSCRIPT
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Dr. RAGHU PRASADA M SMBBS,MDASSISTANT PROFESSOR DEPT. OF PHARMACOLOGYSSIMS & RC.
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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 condition Types of Depression - Two types
Unipolar Exogenous / Reactive Depression
Endogenous/Major Depression (MDD)
Bipolar
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1. Selective Serotonin Reuptake Inhibitor (SSRI)
• Sertraline, Fluoxetine
• Paroxetine, Citalopram, Escitalopram2. Tricyclic Antidepressant (TCA)
• Amitriptyline, Nortriptyline
• Imipramine, Desipramine
• Doxepine, Trimipramine
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MAO Inhibitors Phenelzine, moclobemide TranylcypromineAtypical Antidepressants Bupropion, nefazodone, mianserin, Trazodone, venlafaxine Mirtazepine
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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
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Depression is due to deficiency of nor-epinephrine & serotonin
Normally action of released NE & serotonin is terminated by active reuptake into the nerve terminal from the synapse via specific transporters.
TCAs block the amine transporters (uptake pumps) for nor-epinephrine (NET) & serotonin (SERT) in brain.
Facilitation of NE & serotonin transmission ---- improves symptoms of depression .
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Imipramine Stimulant Anticholinergic ++ 150 mg/ day
Dothiepin Sedative Same side effects as
amitryptyline. By far and away the
most toxic antidepressant.
150 mg / day
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antimuscarinic effects postural hypotension tachycardia, arrhythmias sedation weight gain jittery feeling sexual dysfunction (ejaculatory)
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Citalopram Few interactions
Most expensive
20 mg /day
Fluoxetine Sedation –
Skin s/e
Anxiety +
Cheapest
20-80 mg /day
Fluvoxamine Gut s/e + Insomnia - 200 mg /day
Paroxetine Sedation + Withdrawal problems ?
20 mg /day
Sertraline Diarrhoea 50 mg /day
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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 to titrate dose upwards.
?
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MOA: Inhibit Serotonin& NE reuptake at all doses by
binding to NET & SERTVenlafaxine: Potent inhibitor of serotonin reuptake & at
medium to high doses. Inhibitor of NE reuptake.Weak Dopamine re-uptake inhibitor at higher
doses.No effect on muscarinic, adrenergic or histaminic
receptors. So they are preferred over TCAs for MDD & pain syndromes.
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The old ones block peripheral MAOI ( B ) and central MAOI (A) so a low tyramine diet is needed. ? Obsolete.
Moclobemide. Only MAOI-A. Special place in anxiety disorder. 300-600mg / day.
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Trazodone. Unique structure. Low cardiotoxicity, few anticholinergic side
effects. Drowsiness +. Nausea. 150 mg /day.
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Mirtazapine : Blocks 5HT2 , & presynaptic α2 receptors.
Enhances release of Serotonin & NEAmoxapine: Potent Nor-Epinephrine uptake inhibitor but
mild inhibition of Serotonin reuptake. Blocks D2 receptors
Bupropion: Inhibitor of NE reuptake, Weak Inhibitor of dopamine reuptake
Maprotiline: Potent Nor-Epinephrine uptake inhibitor.
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All are useful in Major depression, in combination with other drugs.
Bupropion is useful in ADHD Bupropion also helps in reducing craving &
attenuating the withdrawal symptoms for Nicotine in tobacco users trying to quit smoking.
Panic attacks, post traumatic stress disorder Obsessive compulsive disorder Nocturnal enuresis Premenstrual syndrome Chronic alcoholism
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ManiaEuphoriaGrandiosityPressured speechImpulsivityExcessive libidoRecklessnessDiminished need for sleep
DepressionDepressionAnxietyIrritabilityHostilityViolence or suicide
Manic, depressed
or mixed
Psychosis
•Delusions
•Hallucinations
•Sensory hyperactivity
Cognition
•Racing thoughts
•Distractability
•Poor insight
•Disorganization
•Inattentiveness
•Confusion16
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Mood Disorders:Therapeutic Options
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Lithium* (A, M)
Anticonvulsants
Valproate* (A)
Lamotrigine* (M)
Carbamazepine (A)
Oxcarbazepine*
Topiramate
Gabapentin
Psychotherapy
Cognitive behavioral therapy Marital/family counseling
Interpersonal therapy Group therapy
Pharmacological/Somatic
Antidepressants; OLZ/FLU* (D)
Quetiapine* (D)
Electroconvulsive therapy
Possibly:» Bright light therapy
» Transcranial magnetic stimulation
» Vagal nerve stimulation
» Sleep deprivation
First generation
antipsychotics
Second
generation
antipsychotics
Clozapine
Olanzapine* (A, M)
Risperidone* (A)
Quetiapine* (A)
Ziprasidone* (A)
Aripiprazole* (A)
* FDA approved© Janicak 17
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Drug Desired
Cp
Distribution Metabolism Elimination
Lithium 0.6-1.0
mEq/L
No PB
kidneys,
thyroid
None Renally,
18-20
hours
CBZ 6-12
mcg/ml
Complete Hepatic,
Auto
inducer
10,11
epoxide
15-28
hours
VPA 50-120
mcg/ml
Rapid in
CNS
Hepatic,
Inhibitor or
Inducer
8-17 hours
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Narrow therapeutic index Slow onset of action Numerous adverse effects
DISADVANTAGES
BIPOLAR DISORDER
© Janicak 19
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Impaired Renal Function Pregnancy Sodium balance Medications
Diuretics → Na depletion → Li reabsorption
Caffeine ↓ lithium levels
ACE Inhibitors → ↓ GFR → increase Li concentration
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Organ System Clinical Presentation Comments
Cardiovascular ECG changes T wave suppression, delayed or irregular rhythm, increase in PVCs
Sick sinus node syndrome (SSNS)
Myocarditis
Dermatologic Acne
Psoriasis
Rashes
Worsens
Treatment-refractory worsening
Maculopapular and follicular
Endocrine Hypothyroid state About 5% goiter; about 4% clinically significant hypothyroidism
Hyperparathyroid state Clinically nonsignificant
Fetus (teratogenic) Tricuspid valve malformation
Atrial septal defect
Ebstein’s anomaly
Gastrointestinal Anorexia
Nausea (10-30%)
Vomiting
Diarrhea (5-20%)
Usually early in treatment and usually transient; may be early sign
of toxicity
Slow release preparations may help
Hematological Granulocytosis May be useful in disorders such as Felty’s syndrome, iatrogenic
neutropenia. May counter CBZ-induced leukopenia
Renal Polyuria-polydipsia
(Nephrogenic diabetes
insipidus)
May be an indication of morphologic changes
Requires adequate hydration
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Neurological Cognitive; tremors
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Usually inhibits hepatic metabolism Occasionally induces hepatic metabolism
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Adverse effects
Weight gain
Tremors
Hyperammonemia
PCOS (?)
DISADVANTAGES
BIPOLAR DISORDER
© Janicak 23
Pancreatitis
Hepatotoxicity
Teratogenicity
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Oxidation to CBZ-10,11-epoxide Potent enzyme inducer
antidepressants, anticonvulsants, antipsychotics
Autoinduction
serum level should stabilize within 4 weeks
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Slow titration to avoid rash Adverse effects
Serious rashes
▪ SJS
▪ TEN
BIPOLAR DISORDER
DISADVANTAGES
© Janicak 25
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Have predominantly stimulant effect onthe central nervous system
Convulsants and respiratory stimulants Psychomotor stimulants Hallucinogens
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Little effect on mental function
Act mainly on the brain stem and spinal cord
Higher dosage causes convulsions
Sometimes called analeptics
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Obtained from the fishberry also blocks the action of GABA on chloride channels
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Similar to the above drugs Bigger margin of safety between
respiratory stimulation and convulsions Causes nausea, coughing and restlessness,
which limit its usefulness Occasionally used as an intravenous
infusion in patients with acute respiratory
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Cause excitement and euphoria Decrease feelings of fatigue Increase motor activity
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Methylxnthines Nicotine Methylphenidate Cocaine Amphetamine Vareneciline
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Theophylline (tea)Theobromine (cocoa)Caffeine
Caffeine, the most widely consumed stimulant in theworld,is found in highest concentration in coffee
Also present in tea, cola drinks, chocolatecandy, and cocoa.
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Translocation of extracellular calcium
Increase in CAMP and CGMP caused by inhibition of phosphodiesterase
Blockade of adenosine receptors
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Cocaine has a local anesthetic Applied topically as a local anesthetic during eye,
ear, nose, and throat surgery Local anesthetic action due to a block of voltage-
activated sodium channels Only local anesthetic that causes vasoconstriction.
This effect is responsible for necrosis Perforation of the nasal septum is seen with chronic
inhalation of cocaine powder
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