Drugs in Health and Disease 1: Antipsychotics Flashcards
Describe chlorpromazine
- Group of drugs it belongs to
- Indication
- Side effects
- State 2 other drugs in class
- Phenothiazine
- Used to treat psychosis, anti-emetic; strong sedative
- Moderate extapyramidal side effects
- Promazine, levomepromazine, perphenazine, fluphenazine
How do agonist work?
- Lock and key hypothesis: drug fits within receptor forming drug-receptor complex
Describe the dose response curve for agonist
How does the presence of a competitive anatagonist work?
- Log linear dose response curve
- Causes a parallel shift, there is no change in max response
- Greater shift with increased concentration of antagonist
- In the presence of naloxone, you need a greater amount of opioid for same “hit’
How does non-competitive inhibition effect the dose-response curve
- Causes the maximum response to decrease
- As the concentration of the antagonist increases, the maximum response decreases further
How does chlorpromazine exert its effects in the brain?
Describe its chemical properties and MOA
- Contains benzene rings that make it lipid soluble and able to pass BBB
- Antipsychotic effects by blocking postsynaptic dopamine receptors in limbic and cortical areas
- Same MOA to exert antiemetic activity but in the chemical trigger zone
- Side effects are directly related to dopamine blockade
Why might a patient on choropromazine present as if they are drunk?
- Side effects can make one appear so
- Strong sedation effects
- In combination with alcohol can be confusing presentation
What are antipsychotics used for generally speaking?
- In the short term they are used to calm disturbed patients despite underlying psychopathology
- Prevent harm to self and other
- Anxiolytic (should only be used in short term)
What are the physical characteristic features of choropromazine?
- White crystalline powder
- Soluble in water and alcohol
- Bitter taste
- Decomposes on exposure to air and light
- Melts at 196 degrees
Consider use of antipsychotics
How does dosing vary with route of administeration?
How should it be reviewed?
- IM doses should be less than PO doses as there is no first pass hepatic metabolism
- IM doses should also reflect activity level of patients, those who are active will have high blood flow to area which will increase the absorption rate
- Prescriptions should clearly. state dose for each route
- If antipsychotic used in emergency it should be reviewed daily
Which conditions might require use of neuroleptics?
- Schizophrenia
- Brain damage
- Mania
- Toxin derlirium
- Agitated depression
- Bipolar
Why are neuroleptics used in schizophrenia?
Alleviate the positive psychotic symptoms
- thought disorder
- hallucinations
- delusions
Prevent relapse
Poor at treating negative symptoms
How are neuroleptics used in long term for schizophrenic patients?
- Required to prevent relapses
- Doses effective in acute episodes should be continued prophylaxis
State the four dopaminergic pathways
- Mesolimbic- pleasure and reward
- Mesocortical- cognition, working memory and decision making
- Nigrostriatial- purposeful movement
- Tuberinfundibular- dopamine inhibits prolactin release
Why do first generation anti-psychotics have an extensive side effect profile?
- Not selective for any of the 4 dopamine pathways –> side effect
- Extrapyramidal symptoms and hyperprolactinaemia
Describe the side effect profile of the group 1 phenothiazines. Give an example
Group 1
- pronounced sedative effects
- moderate antimuscarinic effects (caused by blockade of cholinergic receptors)
- EP side effects
- Chlorpromazine, levomepromazine, promazine
Describe the side effect profile of the group 2 phenothiazines. Give an example
- Moderate sedative effect
- Fewer EP side effects than Group 1 and 3
- Pericyazine
Describe the side effect profile of the group 3 phenothiazines. Give an example
- Fewer sedative and antimuscarinic effects
- Pronounced EP side effects (> group 1 and 2)
- Fluphenazine decanoate, perphenazine, prochlorperazine, trifluoperazine
What side effects does blockade of the following receptors lead to
(1) cholinergic
(2) alpha-adrenergic
(3) histaminergic
(4) serotonergic
(1) Leads to antimuscarinic side effects: dry mouth, constipation, blurred vision
(2) sexual dysfunction (erectile and ejaculation problems), cardiac abnormalities, nasal congestion
(3) sedation/drowsiness
(4) headache, dizziness, insomnia, temperature distubrances, hypotension
Side effects as a result of D2 receptor blockade :
Give any details about particular susceptible patients
Extrapyramidal symptoms:
1- Parkinsonism inc. tremor
2- Dystonia (abnormal face and body movements) and dyskinesia. Frequent in children/young adults after few doses
3- Akasthisia (restlessness) after large initial doses
4- Tardive dyskinesia (rhythmic involuntary movements of tongue, face and jaw): develops long term/high dosage. Short term TD may arise after withdrawal (in kids). Especially in elderly. Irreversible
Which antipsychotics are most likely to cause hyperprolactinaemia?
What are the symptoms?
Risperidone, amisulpride, first generation APs
- Sexual dysfunction
- Reduced bone mineral density
- Menstrual disturbances
- Breast enlargement
- Galactorrhoea
Particular risks/side effects when using antipsychotics in elderly
- In dementia, associated with small increase risk of mortality, stroke and TIA
- Increased susceptibility to postural hypotension, hyper- and hypothermia in hot and cold weather
How should you approach prescribing antipsychotics in the elderly population?
- avoid in mild or moderate psychotic symptoms
- initial doses should be lower, reflect weight, comorbidity, concomitant medication
- review regularly
How should you approach continuous antipsychotics in the learning disabilities population with no psychotic symptoms?
- reduce dose/discontinue
- review condition after this
- refer to specialist LD and MH services
- if you maintain the same dose you should document annually the reason why
Factors affecting onset of extrapyramidal symptoms:
- dose
- type of drug
- individual susceptibility
