Ch29: Antipsychotic & Lithium (Textbook)
What is the mechanism of classic antipsychotic drugs?
Block Dopamine Receptor (D2)
What is the mechanism of new antipsychotic drugs?
Block Serotonin Receptor (5-HT2)
What is an example of a classic Bipolar drug?
What is an example of a New Bipolar drug?
Olanzapine (also 5-HT2 blocker)
What is the mechanism of heterocyclic antidepressants?
Inhibit reuptake of NE & (5-HT)
Antipsychotic Pharmacokinetics: Half-life?
Lipid soluble: ready to enter CNS
Metabolized by Liver before elimination
What prolongs Antipsychotic half-lives?
Inhibition of CYP450 or other liver enzymes
Drugs blocking D2 Receptor causes what side effect?
Extrapyramidal Dysfunction: Dyskinesia, Tremor, Rigidity
What other receptor has an antipsychotic effect besides dopamine & (5-HT)?
What are the two hypothesis for cause of Schizophrenia?
- Too much Serotonin
- Too much Dopamine
All Antipsychotic drugs block what receptors?
H1 & alpha1 Receptors
What do Atypical drugs do to Extrapyramidal Dysfunction?
Decreases Extrapyramidal Dysfunction
What Is Dopamine pathway in the brain affected by Antipsychotic drugs?
Block this pathway on antipsychotics
Receptor blocking drugs have what ADR?
What are the positive symptoms of Schizophrenia?
- Bizarre Ideation
What type of symptoms do antipsychotics treat in Schizophrenia?
How long does it generally take for antipsychotics to work?
Clozapine: old or new drug? What receptor affected?
Effective in what type of pt's?
Lessons symptoms of what disease?
New Drug. (5-HT2) receptor blockade
Effective in antipsychotic resistant pt's.
Lessons Parkinson Symptoms
What side effects do Older Antipsychotic Drugs cause? (Think about what older drugs do and whats affected)
Block D2 receptors --> Parkinson's symptoms
Akathisia: Feeling of inner restlessness & inability to stay still
Dystonias: involuntary muscle contraction causing repetitive or twisting motion
What other psychiatric neurological Indications are involved with Antipsychotic drugs?
Mania: (new antipsychotic) + (Lithium)
Acute Mania & Bipolar Disorder: Aripiprazole & Olanzapine
Tourette's: Molindone (Antipsychotic)
Alzeihmers & Parkinson's: Atypical Antipsychotics
OD on CNS Stimulants
What types of effects do H1 receptor blocking drugs have?
- Antipruritics (Anti-Itch)
- Antiemetic effect
What is an example of a reversible and irreversible neurologic Side Effect of antipsychotic drugs?
Reversible: Extrapyramidal Effects (tremor, dyskinesia,
Irreversible: Tardive Dyskinesia (Choreanthetoid movements of the muscles of the lips & buccal cavity
Tx for Reversible Extrapyramidal Effect?
Tx for Irreversible Tardive dyskinesia?
Tx for Reversible Extrapyramidal Effect: Lower Antipsychotic dose or give Antimuscarinic Drug
Tx for Irreversible Tardive dyskinesia: Increase neuroleptics (Antipsychotics) --> reduce s/s Temporarily
What do Antimuscarinic drugs do to both Extrapyramidal effects and Tardive dyskinesia?
Relieves Extrapyramidal effects (lowers Dopamine)
Worsens Tardive dyskinesia
In what way do antipsychotics have autonomic effects?
- Antimuscarinic receptor drugs (ACh) - Parkinson's
- Block alpha-Adrenoceptors (NE)- Antipsychotic
- Atropine-Like Effects (dry mouth, constipation, urinary retention, visual problems)
- Block muscarinic receptors causing: confusion similar to atropine & tricyclic antidepressants
- Postural hypotension: By alpha blockade, common in Older drugs
In what way do antipsychotics have Endocrine & Metabolic Effects?
Effects: Hyperprolactinemia, Gynecomastia, Amenorrhea-Galactorrhea Syndrome, Infertility
Cause: D2 receptor blocker in the pituitary & Dopamine inhibits prolactin secretion (By not having dopamine causes lactation)
What Endocrine & Metabolic Effects do Clozapine & Olanzapine have?
Hyperglycemia due to diabetogenic action
very problematic in pregnancy
Malignant Hyperthermic Syndrome: What is it?
Symptoms? Big issue?
What: Hypermetabolism of skeletal muscle & hyperthermia
Symptoms: Muscle Rigidity, Cant Sweat, Hyperpyrexia(fever), Autonomic instability
Malignant Hyperthermic Syndrome Tx?
- Dopamine Agonist
What does lithium treat?
Bipolar & Mania
Pharmacokinetics of Lithium: What is dependant on its distribution? Metabolised by what organ? Half-life?
Distribution dependent of body water.
Things that increase lithium blood toxic levels
- Loop Diuretics
- Angiotensin Converting Enzyme Inhibitor (ACEI)
Lithium mechanism of action: Not Well Defined
Inhibits many enzymes
Decrease 2nd Messengers:
Why are 2nd messengers important?
Important in Amine (dopamine & Serotonin) Neurotransmission
Clinical use of Lithium:
- Tx bipolar disorder
- lowers mood swings
- Monotherapy for mania (Olanzapine & Quetiapine)
At the beginning of Lithium treatment, what must you do? Why?
Must combine Lithium w/ an Antipsychotic or Benzodiazepine
Because Lithium has a slow onset of action (Lithium & Valproic)
Lithium Protective effects:
- Suicidal & self-harm
- Antidepressants --> for maintanance
Ebstein's Anomaly is a toxic effect of what drug?
Pregnancy: congenital cardiac anomaly
What is Valproic equivalent to?
What drugs are used to treat bipolar disorder?
- Antipsychotic drugs (Olanzapine & Quetiapine)
- Antiseizure Drugs (Carbamazapine & Lamotrigine for acute mania & to prevent depressive phase)