7.2: Antipsychotic & Antidepressants Flashcards
A study of the drugs that affect cognition, affect, and behavior of an individual.
Psychopharmacology
Inability to distinguish between what is real and what is not real such as:
- Delusions
- Hallucinations
- Disorganized thinking with clear sensorium
Psychosis
What is the most common psychotic disorder?
Schizophrenia
This disorder has a structural and functional changes in the brain, and dysregulated neurotransmitters.
Schizophrenia
3 Neuronal Networks of Psychosis
- Dopamine theory
- NMDA theory
- Serotonin theory
Identify this neuronal network of psychosis:
A classic and one of the most enduring ideas in psychopharmacology.
Dopamine hypothesis of psychosis
Identify this neuronal network of psychosis:
Increasing evidence implicates both serotonin and glutamate
networks.
dopamine hypothesis of psychosis
- Reduce psychotic symptoms
- Improve mood and reduce anxiety
- Neuroleptic
Antipsychotic drugs
It is an antipsychotic drug with high incidence of EPS.
Neuroleptic
Typical / Classic Drugs of Antipsychotic drugs
Phenothiazine
Thioxanthine
Butyrophenone
Mnemonic: PettyBoo (PheThiBu)
Atypical / Newer Agents of Antipsychotic drugs
Clozapine
Olanzapine
Risperidone
Quetiapine
Ziprasidone
Aripiprazole
Mnemonic: CROQZA >:( !!
What are the receptors of Typical / Classic Drugs?
D2»_space; 5-HT2 receptors
What are the receptors of Atypical / Newer Agents?
5-HT2»_space; D2 receptors
Pharmacokinetics:
Well absorbed when administered _____?
orally
Pharmacokinetics:
Antipsychotic drugs are extensively bound to ____?
plasma proteins
[ Modified T or F ]
Antipsychotic drugs are lipid soluble and short half-lives.
First statement is true, Second statement is false.
Should be LONG half-lives
Parenteral forms of Antipsychotic drugs
- Fluphenazine
- Haloperidol
- Ziprasidone
- Olanzapine
- Aripiprazole
For rapid initiation of tx, uncooperative patients, or depot.
Identify this neuronal network of psychosis:
Schizophrenia is due to excess of functional DA in mesocortical tracts in the brain.
Dopamine hypothesis
Dopamine receptors
- GPCR, D1-D5
- D2
- Blockade of D2 - EPS
Identify what dopamine receptors:
Located in the caudate, putamen, cortex, hypothalamus – negatively coupled to adenylyl cyclase.
D2
[Dopamine receptors]
EPS (tremor, slurred speech, akathisia, dystonia)
Blockade of D2
Affinity for other receptors:
Atypical antipsychotics
True or False:
Atypical antipsychotics has less EPS than first generation drugs.
True
All antipsychotic drugs block H1 receptor to some degree except:
- Haloperidol
- Iloperidone
- Lurasidone
What are the effects of first generation drugs?
dopamine receptor blockade
Effects of Mesocortical-mesolimbic pathway
Antiemetic effect due to blockade of the chemoreceptor trigger zone
Common adverse effects of First generation drugs
Extrapyramidal symptoms, hyperprolactinemia (1st Generation)
Treatment of schizophrenia
- Hyperactivity, bizarre thoughts, delusions and hallucinations
- Effects take several weeks to develop
Clinical use of 1st generation
lower cost, EPS
Clinical use of 2nd generation
- Improves negative symptoms
- emotional blunting, social withdrawal, lack of motivation)
Treatment for mania
- Lithium
- Second generation drugs, with benzodiazepenes
Prevention of manic phase of bipolar disorder
- Aripiprazole
- lanzapine
- Asenapine
What are the drugs used to prevent bipolar depression?
- Quetiapine
- Lurasidone
- Olanzapine
- Carizapine
Treatment for Tourette syndrome
Molindone
Treatment for Psychotic symptoms in Alzheimers and Parkinsonism
Molindone
Reversible neurologic effects
Toxicity
Parkinson-like symptoms
Dose-dependent EPS
Dose-dependent EPS, which can resemble Parkinson-like symptoms, are common with __________. However, they are less frequent with _____________
• high-potency first-generation antipsychotics like Haloperidol, Fluphenazine, and Trifluoperazine
• second-generation drugs like Clozapine.
True or False:
Dose-dependent EPS management typically involves increasing the dose and using antimuscarinic agents to alleviate symptoms.
False
Should be reducing the dose.
Dose-dependent EPS movement problems such as akathisia (restlessness) and dystonias (involuntary muscle contractions) are also observed and can be managed with _______?
antimuscarinic agents or diphenhydramine
Endocrine effects of antipsychotic medications can include primarily __________. These effects are particularly prominent with medications like __________.
• hyperprolactinemia, gynecomastia, and infertility ( due to the blockade of dopamine D2 receptors in the pituitary gland )
• Risperidone
Toxicity of Neuroleptic malignant syndrome
hyperthermia
Neuroleptic malignant syndrome treatment typically involves medications such as
dantrolene, diazepam, and dopamine agonists.
marked with chlorpromazine
Sedation
Among the antipsychotics, ______ & _______ are among the least sedating options, while aripiprazole and lurasidone are also known for causing less sedation.
fluphenazine and haloperidol
Visual toxicity
retinal deposits with thioridazine
Cardiac rhythm abnormalities toxicity
- Thioridazine
- Quetiapine
- Ziprasidone
Agranulocytosis toxicity
Clozapine
Commonly used for manic phase of bipolar disorder
Lithium
MOA of lithium
inhibits enzymes for recycling neuronal membrane phosphoinositides → depletion of PIP2 , IP3, DAG →
prevents amine neurotransmission
[ T or F ]
It is important to monitor plasma level to establish effective and safe dosage for lithium
True
Used in bipolar disorder to decrease manic behavior and reduces frequency and magnitude of mood swings.
Lithium
Lithium toxicity
- Tremor, ataxia, sedation, aphasia [ TASA ]
- Thyroid enlargement
- Cardiac abnormalities in the fetus
Other drugs for Bipolar Disorder
Antiseizure drugs:
• Valproic acid
• Carbamazepine and lamotrigine
Prolongs inactivation of voltage gated Na channels, GABAA agonist
Valproic acid
antimanic effects when failed to respond to lithium
Valproic acid
Prolongs inactivation of voltage gated Na channels
Carbamazepine and lamotrigine
for mania and prophylaxis of depressive phase
Carbamazepine and lamotrigine
Feelings of sadness and or loss of interest in normally pleasurable activities, leading to emotional and physical problems, with resulting impairment in social, occupational and other areas of functioning for 2 weeks.
Depression
Depression symptoms
- Depressed mood
- Changes in appetite
- Sleeping problems
- Fatigue
- Feeling of guilt and worthlessness
- Concentration problems
- Suicidal thoughts
Monoamine hypothesis
• noradrenaline
• dopamine
• serotonin
Hyperactive dopamine in the mesolimbic pathway
Dopamine theory
Identify what neuronal network of psychosis:
NMDA receptor hypofunction
NMDA theory
5-HT2A receptor hyperfunction in the cortex
Serotonin theory
Depression is associated with loss of neurotrophic support
Neurotrophic hypothesis
Identify what pathopsyiology:
For neural plasticity, resilience, and neurogenesis.
Brain-derived neurotrophic factor (BDNF)
Tricyclic antidepressants examples
- Amitryiptyline
- Clomipramine
- Imipramine
Related to phenothiazine antipsychotics
Tricyclic antidepressants
Identify this antidepressant:
Well absorbed orally, but undergo first-pass effect
Tricyclic antidepressants (TCA)
• Excessive hepatic metabolism required
• Forms active metabolites
Tricyclic antidepressants
Long half life (OD dosing)
Tricyclic antidepressants
Selective serotonin reuptake inhibitors example
- Paroxetine
- Escitalopram
- Fluoxetine
- Fluvoxamine
- Sertraline
PEFFS
Require hepatic metabolism
Selective serotonin reuptake inhibitors
half life of several days – once a week dosing
Fluoxetine
Heterocyclics examples
- Bupropion
- Amoxapine
- Mirtazapine
HETERO BAM!
Pharmacokinetics similar to TCA
Heterocyclics
Identify this antidepressant based on its pharmacokinetics:
Short half lives
(BID to TID dosing)
Nefazodone and trazodone
5-HT2 antagonist
5-HT-NE reuptake inhibitors
- Duloxetine
- Venlafaxine
5-HT antagonists
- Nefazodone
- Trazodone
Monoamine Oxidase Inhibitors examples
- Phenelzine
- Selegiline
- Tranylcypromine
PST MOA !
Related to amphetamines and orally active
Monoamine Oxidase Inhibitors
metabolizes NE, Epinephrine, Serotonin
MAO-A
metabolizes Dopamine, Tyramine
MAO B
fastest in onset, short duration of action and Inhibitors of hepatic drug metabolizing enzymes
Tranylcypromine
Other drugs with antidepressant action
Ketamine
Brexanolone
NMDA antagonist
Ketamine
modulator of GABA A receptors
Brexanolone
What drug is used for postpartum depression?
Brexanolone
Anesthetic agent that has antidepressant action as long as 1 week
Ketamine
• Inhibit the reuptake transporters that terminate the actions of NE and 5-HT
• Blocks H receptors and α-adrenoceptors
Tricyclic antidepressants
Identify this antidepressant:
- Highly selective on Serotonin Transporter (SERT) - allosterically inhibit the transporter
- Minimal inhibitory effects on NE
SSRI
Bind to transporters for both serotonin and NE
SNRI
• Nefazodone and trazodone – blocks 5HT2A receptor in
the neocortex
• Anti-anxiety and anti-depressant
5-HT2 Receptor Antagonist
• Increase brain amine levels, interfering with metabolism
→ increase in vesicular stores of NE and 5-HT
MAO Inhibitor
increase amine release by antagonism
of α-2 receptors
Mirtazapine
no effect on 5-HT or NE amine ransporters
Bupropion
Clinical Uses of Major depressive disorders
- Primary indication of antidepressants
- Newer drugs more tolerable side effects (SSRI, SNRI, 5-HT
antagonists, certain heterocyclics)
Identify this pharmacologic effects:
- Sympathomimetic effects - Increase NE
- Chronic use - low BP
Amine uptake blockage
Identify this pharmacologic effects:
Common in TCA and heterocyclic (mirtazapine) and 5-HT2 blockers (nefazodone and trazodone)
Sedation
Identify this pharmacologic effects:
- Occurs with all TCA except amitryptaline and doxepine
- Atroine like effects - minimal with SSRI and buproprion
Muscarinic blockade
Identify this pharmacologic effects:
- Common with TCA: hypotension, arrhythmias
- Cardiotoxicity: venlafaxine
Cardiovascular effects
Identify this pharmacologic effects:
- TCA and MAOIs lower consulsive threshold
- Overdoses of maprotiline and SSRI’s
Seizures
