Psychopharmacology Flashcards
What factors predict poor adherence to medication?
▪️ Psychological problems and/or cognitive impairment
▪️ Complexity of treatment
▪️ Inadequate follow up
▪️ Poor insight
▪️ Side effect profile
▪️ Barriers to care
▪️ Culture, religion, stigma
How can we check for and improve adherence?
▪️ Blood tests - check for metabolites
▪️ Check pill bottle
▪️ Use injections when at high risk of non-adherence (LAI)
▪️ Depot = special preparation for slow release
What are orodispersible tablets?
Tablets that disintegrate in the mouth within a minute in the presence of saliva due to super disintegrants in formulation
May improve compliance
When can antipsychotic long acting injections NOT be used and why?
When antipsychotic-naïve:
▪️ Plasma levels will increase over several weeks without increasing dose due to accumulation
▪️ Increased risk of AE
What do you need to enquire about when deciding on the right medication?
▪️ Allergies
▪️ Vitamins and herbs
▪️ Old and OTC drugs
▪️ Interactions
▪️ Dependence
▪️ Use of street drugs
▪️ Family history
What happens when a tablet is swallowed?
▪️ Sits for ~45 minutes in stomach
▪️ Absorbed into bloodstream from small intestine
▪️ Transferred to liver through portal vein
What happens to a medication in the liver?
▪️ Chemically processes it into active and inactive metabolites
▪️ Ratio determines bioavailability of the drug (duration and intensity)
▪️ Mediated through cytochrome 450 (system of enzymes)
What happens when rate of metabolism of active metabolites in the liver is increased (e.g., enzyme induction)?
Decreased duration and intensity
(Unless metabolising a pro-drug into a drug)
What factors might affect drug metabolism?
▪️ Age (slower in foetal, neonatal, and elderly)
▪️ Genetic variation
▪️ Ethnicity and sex
▪️ Enterohepatic circulation
▪️ Nutrition
▪️ Intestinal flora
▪️ Diseases such as liver, kidney or heart
What factors are known to affect clozapine metabolism and why is it important to consider these?
▪️ Some SSRIs such as fluoxetine (increased seizure risk)
▪️ Smoking - induces metabolism
If metabolism is increase, e.g. by smoking, may be at risk of toxicity is smoking ceased
What is the key consideration when creating a drug for the CNS?
That it can cross the blood-brain barrier
What is the difference between an antagonist and an inverse agonist?
Antagonists prevent action of agonists/block receptors BUT have no activity of their own
(An inverse agonist blocks the action of an agonist AND exerts its own opposite effect)
What was the first typical antipsychotic developed in the 50s?
Chlorpromazine (Thorazine)
(Saw big decrease in no. of inpatients)
Malfunction of which neurotransmitter system is primarily implicated in depression?
The monoaminergic neurotransmitter system
(serotonin?)
What is typically the first line of treatment for depression of at least moderate severity?
SSRIs (e.g., fluoxetine, paroxetine, sertraline)
(Effective in ~50%, after as quickly as 1-2 weeks)
(Best com
What are the main side effects associated with SSRIs?
▪️ Headaches
▪️ Sexual dysfunction
▪️ Hyponatraemia
▪️ Gastrointestinal bleeds
▪️ Increased risk of suicidal thoughts in younger people?
What are discontinuation symptoms?
▪️ Symptoms experienced after stopping a drug, often explained by ‘receptor rebound’
▪️ Usually within 5 days but depends on half-life
▪️ Usually mild and self-limiting
(E.g., diarrhoea on discontinuation of antidepressant with potent anticholinergic effects)
When is risk of discontinuation symptoms the greatest?
With short half-life drugs (e.g., paroxetine), thus just missing doses may be enough to trigger symptoms
(If severe, taper off gradually)
What are NaSSAs?
Noradrenergic and Specific Serotonergic Antidepressants (e.g. mirtazapine)
What do NaSSAs do?
▪️ Alpha 2 antagonism (adrenergic)
▪️ Blocks 3 serotonin receptors and histamine 1
▪️ Leads to increased release of noradrenaline and serotonin
What are the benefits of NaSSAs?
▪️ As effective as SSRIs
▪️ Anxiolytic and sleep-restoring
▪️ No sexual dysfunction
▪️ Improves appetite (may make weight gain more likely
What are SNRIs?
Serotonin and Noradrenaline Re-uptake Inhibitors (e.g., Venlafaxine)
Low dose = inhibition of serotonin uptake
Higher dose = inhibition of noradrenaline re-uptake
When should SNRIs be used and why?
▪️ Reserved for 2nd line treatment
▪️ Risk of hypertension so blood pressure should be checked regularly
When are pharmacological interventions typically considered for anxiety?
As a second option is psychological therapy is not effective
What are benzodiazepines and when/how should they be used?
▪️ GABA enhancers - inhibition!
▪️ Only for when anxiety is severe, disabling or causing extreme distress
▪️ At the lowest effective dose for as short as possible due to potential physical dependence and withdrawal
What should you do when prescribing SSRIs and SNRIs for generalised anxiety?
Start at half the normal starting dose and titrate upwards as tolerated
What is pregabalin licensed for?
Generalised Anxiety Disorder
What interventions should be considered for panic disorder?
▪️ SSRI = first line
▪️ Encourage self-help based on CBT
▪️ AVOID benzodiazepines
What interventions should be considered for generalised anxiety disorder?
▪️ SSRI = first line
▪️ SNRIs and pregabalin = alternative choices
▪️ Benzos not beyond 2-4 weeks
▪️ High intensity psychological intervention and self-help
What interventions should be considered for cases of OCD with moderate-severe functional impairment?
▪️ SSRI and/or intensive CBT
▪️ Clomipramine if SSRIs fail
▪️ Add antipsychotic if still suboptimal response, or combine clomipramine with citalopram
What should you consider when prescribing medication for sleep?
▪️ Behavioural strategies to improve sleep hygiene (e.g, alcohol, pain, caffeine, other medications)
▪️ Intermittent and short-term dosing at lowest effective dose if necessary
What might you prescribe someone who has difficulties falling asleep?
Zolpidem because it has a short-half life
Temazepam also has a short half life but has increased risk of dependence
What might you prescribe someone who has difficulties maintaining sleep?
Zopiclone because of its long half-life so longer lasting
What is promethazine?
An antihistamine with sedative properties
What is melatonin?
A hormone produced by the pineal gland in a circadian manner
▪️ Rises in evening ~2 hours before sleep, enabled by darkness
▪️ Involved in induction of sleep and synchronisation of circadian system
What are the main dopamine pathways in the brain that antipsychotics act on?
▪️ Mesolimbic (delusions and hallucinations)
▪️ Mesocortical (cognitive and affective symptoms)
▪️ Tuberoinfundibular (prolactin secretion)
▪️ Nigrostriatal (movements
(Latter two both NORMAL in SCZ)
(5th = thalamic?)
What do typical, first generation antipsychotics do?
D2 receptor antagonism to improve positive symptoms in psychosis
BUT block reward circuits leading to apathy, anhedonia, and EPSEs
(e.g., haloperidol, chlorpormazine)
What are atypical, second generation antipsychotics?
▪️ Rapid dissociation from dopamine receptors
▪️ 65-75% D2 blockade
▪️ Additional properties such as serotonin antagonism, D2 partial agonism, and serotonin partial agonism
(e.g., olanzapine, risperidone, quetiapine, aripiprazole)
What are the pros and cons of atypical antipsychotics?
▪️ Reduced extrapyramidal symptoms
▪️ Increased effectiveness for negative symptoms
▪️ Last longer
BUT more metabolic side effects such as weight gain and diabetes
What can be used for refractory schizophrenia?
Clozapine
(Must have already tried 2 different antipsychotics)
What should you consider when prescribing clozapine?
▪️ Dose-dependent adverse effects
▪️ Most common and severe at the beginning
▪️ Monitor blood levels to ensure still in therapeutic range
▪️ Monitor white blood cell count to avoid fatal side effects such as agranulocytosis
▪️ Increased risk of seizures
What should you take baseline measurements of when starting antipsychotics?
▪️ Full blood count (FBC)
▪️ Urea and electrolytes (U&Es)
▪️ Liver function tests (LFTs)
▪️ Electrocardiogram (whenever dose increases)
▪️ Blood pressure
What additional factor should you monitor if prescribing risperidone, amisulpiride or sulpiride?
Prolactin
What additional factors should you monitor if prescribing olanzapine?
Plasma glucose and blood lipids
What is the mainstay treatment for bipolar disorder?
▪️ Antipsychotics (e.g., olanzapine)
▪️ Mood stabilisers (incl lithium, sodium valproate, carbamazepine)
▪️ Possibly sedatives/anxiolytics in addition (e.g., benzodiazepines)
What is the first line treatment for rapid cycling type bipolar disorder?
Lithium, either with or without valproate
▪️ If neither, try alternative antipsychotics such as lamotrigine
(Lithium = second messenger systems and gene regulation, valproate = boosts GABA)
What might partly explain the association between epilepsy and depression?
Depletion of serotonin
What should be considered when using pharmacological interventions for psychiatric symptoms in neurological illness?
▪️ Psychiatric side effects (e.g., with ASM)
▪️ Pharmacokinetic interactions (e.g., fluoxetine may increase ASM plasma levels, causing toxicity)
▪️ Pharmacodynamic interactions (may overlap with psychotropic adverse effects)
▪️ Dose-related risk of seizures in some psychotropics
What percentage of people with PD experience depression and what should be considered when treating this?
▪️ ~25%, predicts greater decline
▪️ SSRIs = first line
▪️ BUT when combined with selegiline may risk serotonin syndrome
How might you treat someone with PD-related psychosis?
▪️ Typically secondary to dopaminergic meds
▪️ If have insight and not distressed by hallucinations, don’t treat with additional psychotropics
▪️ Consider adjusting dopamine agonist
▪️ Consider cholinesterase inhibitor or atypical antipsychotic with low affinity - most evidence for clozapine
What are the main considerations when treating NPS in MS?
▪️ Depression = most common
▪️ SSRIs or Neudexta (dextromethorphan and quinidine)
▪️ Steroid treatment might cause affective disorder
▪️ Modafinil or amantadine for sleep?
▪️ Be careful not to worsen cognition
