risks of psychotropics
Download
Skip this Video
Download Presentation
Risks of Psychotropics

Loading in 2 Seconds...

play fullscreen
1 / 32

Risks of Psychotropics - PowerPoint PPT Presentation


  • 137 Views
  • Uploaded on

Risks of Psychotropics. The Risks. Antidepressants Antipsychotics Adverse Effects Toxicity Significant Interactions. Tricyclic antidepressants. Mechanism of action Block reuptake of noradrenaline seratonin . Dose dependent increase in seratonin, noradrenaline and dopamine.

loader
I am the owner, or an agent authorized to act on behalf of the owner, of the copyrighted work described.
capcha
Download Presentation

PowerPoint Slideshow about 'Risks of Psychotropics' - delores


An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript
the risks
The Risks
  • Antidepressants
  • Antipsychotics
  • Adverse Effects
  • Toxicity
  • Significant Interactions
tricyclic antidepressants
Tricyclic antidepressants
  • Mechanism of action
    • Block reuptake of noradrenaline seratonin.
    • Dose dependent increase in seratonin, noradrenaline and dopamine.
    • Also alpha blockade antihistamine actions and anticholinergic actions.
  • Pharmacokinetics
    • Highly lipid soluble
    • large volume of distribution
    • rapid absorption
    • Polymorphic hepatic metabolism.
tcas pharmacokinetic interactions
Elevated [TCAs]

Cimetidine

Ethanal acute ingestion

Haloperidol

Phenothiazine

Propoxyphene

Fluoxetine

Lower [TCAs]

Chronic ethanol

Barbiturates

Carbamazepine

TCAs: Pharmacokinetic Interactions

Elevated

[Interacting Drugs]

Phenytoin

Warfarin

tcas pharmacodynamic interactions
TCAs: Pharmacodynamic Interactions
  • Decreased antihypertensive effect.
    • Methyldopa Clonidine
    • Disulfiram - acute organic brain syndrome
  • Classic monoamine oxidase inhibitors increase therapeutic and toxic effects of both drugs. Hypertension, delirium, seizures.
toxicity in overdose
Toxicity in overdose
  • Not all are equipotent
  • CNS
    • Sedation & coma
    • Seizures
    • Anticholinergic delirium
  • Cardiovascular
    • Supraventricular and ventricular arrhythmias
    • Conduction defects
    • Sinus tachycardia
    • Hypotension
mao a inhibitors moclobemide
MAO-A inhibitors: Moclobemide
  • Mechanism
    • reversible competitive blockade of monoamine oxidase A enzymes decreasing breakdown of monoamines.
  • Pharmacokinetics
      • polymorphic P450 hepatic metabolism - active metabolites
      • half life 1 - 1½ hours
      • low volume of distribution
      • 50% protein bound
      • high bioavailabilty 90% with repeated doses
      • Inhibition of monoamine oxidase 12 to 16 hours.
mao a inhibitors moclobemide1
MAO-A inhibitors: Moclobemide
  • Dosage
    • 300 to 600mg per day.
  • Side effects
    • Nausea (for possibly 5%)
  • Drug interactions
    • No clear evidence for dietary restrictions.
    • Reduced clearance by cimetidine.
mao a inhibitors moclobemide2
MAO-A inhibitors: Moclobemide
  • Toxicity
    • Minimal toxicity in overdose
    • CNS depression and confusion, nausea, hyperreflexia, hypotension and occasional hyperthermia.
fluoxetine
Fluoxetine
  • Mechanism
    • Inhibition of presynaptic seratonin reuptake plus probably altering sensitivity to serotonin.
fluoxetine1
Fluoxetine
  • Pharmacokinetics
    • High bioavailability and volume of distribution
    • High protein binding.
    • P450 hepatic metabolism, less than 5% renal metabolism.
    • Half life of fluoxetine approximately 70 hours.
    • Half life of active metabolite desmethylfluoxetine 330 hours, therefore steady state concentrations take 2 to 4 weeks.
fluoxetine2
Fluoxetine
  • Efficacy
    • In moderate depression similar to tricyclic antidepressants
    • some analgesic and anorectic effects, no sedative effects or alpha effects.
  • Not proarrhythmic.
  • No evidence of psychomotor changes subjectively or objectively
fluoxetine3
Fluoxetine
  • Side effects
    • Approximately 20% of patients experience nervousness, insomnia or nausea. Treatment failure due to side effects approximately 5%.
  • Drug interaction
    • Kinetic: Increased concentration of TCA, carbamazepine, haloperidol, metoprolol & terfenadine
  • Toxicity
    • Minimal cardiotoxicity, ataxia, CNS depression, occasional seizures.
antipsychotics phenothiazines and butyrophenones
Antipsychotics:Phenothiazines and butyrophenones
  • Mechanism
    • Antipsychotic effect probably due to dopamine blockade.
    • Dirty drugs with alpha effects, antihistamine effects, anticholinergic effects (except haloperidol) direct membrane stabilising effects.
antipsychotics phenothiazines and butyrophenones1
Antipsychotics:Phenothiazines and butyrophenones
  • Metabolism
    • Predominantly Polymorphic hepatic P450 enzyme metabolism.
    • Conjugation
    • High volume of distribution, long half life
antipsychotics phenothiazines and butyrophenones2
Antipsychotics:Phenothiazines and butyrophenones
  • Side effects
    • Similar to those of tricyclic antidepressants
    • Attributed to dopamine blockade
      • Parkinsonian states
      • Tardive dyskinesia
      • Neuroleptic malignant syndrome
      • Acute dystonia (early)
      • Akathesia
antipsychotics phenothiazines and butyrophenones3
Antipsychotics:Phenothiazines and butyrophenones
  • Lowered seizure threshold
  • Hypersensitivity reactions
  • Hyperpigmentation
  • Retinal toxicity (especially thioridazine >800mg/day)
  • Lowered seizure threshold for phenothiazines
  • Endocrine
antipsychotics phenothiazines and butyrophenones4
Antipsychotics:Phenothiazines and butyrophenones
  • Drug interactions
    • Enzyme inducers some self induction.
    • Heavy smoking may decrease levels.
    • Antipsychotics may inhibit antidepressant metabolism.
    • Inhibits phenytoin metabolism.
neuroleptic malignant syndrome
Neuroleptic Malignant Syndrome
  • ESSENTIAL CRITERIA (need 1 of the following)
    • Receiving or recently received a neuroleptic drug
    • Receiving other dopamine antagonist (eg metoclopramide)
    • Recently stopped therapy with a dopamine agonist (eg levodopa)
neuroleptic malignant syndrome1
Neuroleptic Malignant Syndrome
  • MAJOR
    • Fever > 37.5OC (no other cause)
    • Autonomic dysfunction
    • Extrapyramidal syndrome
neuroleptic malignant syndrome2
Neuroleptic Malignant Syndrome
  • MINOR CRITERIA
    • CPK rise
    • Altered sensorium
    • Leucocytosis >15000
    • Other possible cause for fever (delete leucocytosis)
    • Low serum iron
    • Therapeutic response (Sequence)
neuroleptic malignant syndrome3
Neuroleptic Malignant Syndrome
  • TREATMENT
    • Withdrawal
    • Specific
    • Bromocriptine.
    • L-Dopa
    • Dantrolene.
    • Anticholinergics and benzodiazepines
    • ECT
    • Nifedipine
neuroleptic malignant syndrome4
Neuroleptic Malignant Syndrome
  • Recommencement of Neuroleptics.
    • with caution after complete recovery from NMS
clozapine
Clozapine
    • A Diebenzodizepine Antipsychotic
    • A Low Affinity Dopamine Antagonist
    • A High Affinity Serotonin Antagonist
  • Indications
    • Treatment Resistant Schizophrenia
clozapine1
Clozapine
  • Pharmacokinetics
    • Bioavailability 50%
    • Protein Binding 95%
    • Half Life 12 Hours
    • Hepatic Metabolism
clozapine2
Clozapine
  • Adverse Effects
    • Neuroleptic Malignanct Syndrome
    • Seizures 5% of Patients > 600 Mg a Day
    • Hypersalivation
    • Agranulocytosis
      • 0.8% In One Year (95% in First Six Months)
      • Increased Risk in the Elderly and Female
      • Increased Risk in Ashkenazi Jews
clozapine3
Clozapine
  • Drug Interactions
    • Enhance Sedation With Other Sedatives
    • Metabolism Inhibited by Cimetidine Leading to Clozapine Toxicity
    • Clozapine Metabolism Induced by Phenytoin
clozapine4
Clozapine
  • Overdose
    • Delirium, Coma, Seizures
    • Tachycardia, Hypotension
    • Respiratory Depression
    • Hypersalivation
risperidone a benzisoxazole derivative
Risperidone - a benzisoxazole derivative
  • Indications
    • schizophrenia
      • Negative symptoms
      • Movement disorders on conventional therapy
  • Mechanism
    • Low affinity D2 antagonism
    • High affinity 5H2 antagonism
    • Some alpha 1 and antihistamine effect
risperidone a benzisoxazole derivative1
Risperidone - a benzisoxazole derivative
  • Pharmacokinetics
    • rapid absorption and high bioavailability
    • risperidone metabolised to 9 hydroxy resperidone
    • P450 to D6 half life of risperidone (fast acetylators 2-4 hours)
    • Half life hydroxyrisperidone (fast acetylators 27 hours)
    • Protein binding (albumin and alpha glycoprotein)
      • risperidone 88%, 9 hydroxyrisperidone 77%
risperidone a benzisoxazole derivative2
Risperidone - a benzisoxazole derivative
  • Side effects
    • postural hypotension
    • weight gain
    • hyperprolactinaemia asthaenia
  • Drug interactions
    • pharmacodynamic
      • dopamine
      • augmented affect of TCAs and phenothiazines
selectivity of antidepressants

Selectivity of antidepressants

Nisoxetine

1000

Nomifensine

Maprotiline (approx)

100

NA-

selective

Desipramine

10

Imipramine

Nortriptyline

Amitriptyline

Non-

selective

1

Ratio NA: 5-HT uptake inhibition

Clomipramine

Trazodone

Zimelidine

0.1

5-HT-

selective

0.01

Fluoxetine

Citalopram (approx)

0.001

ad