Pharmacology Flashcards
What is the monoamine hypothesis?
- This states that depression results from a functional deficit of monoamine transmitters in particular serotonin (5-HT) and noradrenaline
- This was based off the evidence that drugs that deplete stores of monoamines e.g. resperine can induce low mood
- Also, CSF from depressed patients have reduced levels of monoamines or metabolites
- Most drugs that treat depression act to increase monoaminergic transmission
- But it’s not that simple, these are just parts of a complex pathway that are modifiable
List 4 SSRIs?
fluoxetine, citalopram, sertraline, paroxetine
MOA of SSRIs?
selectively inhibit reuptake of serotonin (5-HT) from the synaptic cleft
Common side effects of SSRIs?
Common side effects: nausea, headache, worsened anxiety, transient increase in self harm in adolescents and young people, sweating, vivid dreams, sexual dysfunction, hyponatraemia (important in the elderly), discontinuation effects
Which SSRIs have longest and shortest half life? What is the clinical relevance of this?
- Paroxetine has the shortest half life and produces the most pronounced withdrawal effects, it can be really difficult to get people off this, so best avoided
- Fluoxetine has the longest half life and produces the fewest withdrawal symptoms
What SSRI increases QT interval?
citalopram
Give 4 examples of tricyclic antidepressants?
imipramine, dosulepin, amitriptyline, lofepramine
MOA of tricyclic antidepressants?
block the uptake of monoamines serotonin and noradrenaline into presynaptic terminals equally
Common side effects of tricyclic antidepressants?
most are due to their anticholinergic effect as the drugs also block muscarinic receptors, these effects include blurred vision, dry mouth, constipation, urinary retention, sedation, weight gain, postural hypotension, tachycardia, arrhythmias, cardiotoxicity in overdose
Are monoamine oxidase inhibitors prescribed as antidepressants much now?
no
What is an example of a NRI?
reboxetine
What are 2 examples of dual reuptake inhibitors (SNRIs)?
venlafaxine and duloxetine
side effects of SNRIs and NRIs are similar to?
side effects of SSRIs
9 clinical uses of antidepressants?
- Moderate to severe depression
- Dysthymia
- Generalised anxiety disorder
- Panic disorder
- OCD
- PTSD
- Premenstrual dysphoric disorder
- Bulimia nervosa
- Neuropathic pain
What is serotonin syndrome caused by?
- Uncommon but can be serious
- Usually triggered when taking SSRI/ SNRI with another medication that increases serotonin e.g. St John’s Wort
Symptoms and severe symptoms of serotonin syndrome?
- Symptoms include: agitation, confusion, muscle twitching, sweating, shivering, diarrhoea
- Severe symptoms: seizures, arrhythmias and unconsciousness
SSRIs and NSAIDS combine _____
increase risk of GI bleeding so should give a PPI
What is mirtazipine?
tetracyclic antidepressant - noradrenergic and specific serotonergic antidepressant
When checking lithium levels samples should be taken ________
12 hours post dose
Rough MOA of antipsychotics ?
- Schizophrenia is thought to be partially due to the firing of aberrant dopaminergic neurons
- So, if you can block the receptors are reduce the effect of firing you will treat the symptoms (there are other factors that contribute to schizophrenia but this is just a known part of the pathway we can treat)
Antipsychotic structure is based on the ____
triple benzene ring
An ideal antipsychotic would be a pure ______ only active in _____
D2 agonist only active in the mesocortical and mesolimbic pathways (respsonible for cognitive function, reward and motivation)
List 5 brain pathways that involve dopamine
mesocortical
mesolimbic
nigrostriatal
tuberoinfundibulnar
spinothalamic
What other receptors minus dopamine do antipsychotics act on (not desired)?
dopamine receptors, Ach, histamine, 5HT, NA and potentially other receptors that haven’t even been discovered yet
List 1st generation (typical) and 2nd generation (atypical) antipsychotics
- 1st generation (typical): haloperidol, chlorpromazine
- 2nd generation (atypical): clozapine, olanzapine, quetiapine, risperidone. apiprazole
Generally first generation antipsychotics are thought to ______ and second generation are _______
- Generally, first generations are thought to cause more extrapyramidal side effects
- Second generation thought to be worse for weight gain, central adiposity and type 2 diabetes
- Theoretically lower risk of neuroleptic malignant syndrome in second generation drugs
Why do you get extrapyramidal side effects when using antipsychotics?
disruption of substantia nigra and nigrostriatal pathways
List three EPS that can get from antipsychotics?
acute dystonia
tardive dyskinesia
parkinsonism
Presentation of acute dystonia?
- Acute dystonia results in increasing muscle tone occurring in minutes from starting the drug
- The increased muscle tone uses a lot of energy
- There is torticollis (head tilted and rotated at odd angle), oculogyric crisis (prolonged upwards gaze of the eyes) and tongue protrusion
What can be used to treat acute dystonia?
benzotropine
Presentation of tardive dyskinesia?
- This comes on within weeks to months and lasts a long time even if treated
- It involves involuntary, repetitive oro-facial movement, blinking, grimacing, pouting, lip smacking, may involve limbs and/or trunk
Presentation of parkinsonism in antipsychotic use?
- This comes on within weeks to months
- It presents like Parkinson’s disease with tremor, rigidity, bradykinesia, gait disturbance
Treatment of EPS in antipsychotic use?
- Acute dystonia can be treated with benzotropine
- EPS of antipsychotics can also be treated with anti-cholinergics which reduce Ach and balance the system
- It’s fine to have less of dopamine and Ach, it just needs to be balanced (there’s a lot of redundancy in the system)
- Anticholinergics e.g. procyclidine, trihexyphenidyl, orphenadine
- If side effects are very bad, might need to switch antipsychotics
Explain what neuroleptic malignant syndrome is, how it presents and treatment?
- This is a rare but important side effect as it is fatal in 20-30% of cases
- [side note: neuroleptic means a drug that depresses nerve function- antipsychotics are neuroleptic]
- Symptoms occur a few days to a few weeks after starting treatment
- Symptoms: Increasing muscle tone, hyperthermia, changing pulse
- This progresses to rhabdomyolysis which can cause AKI leading to coma and death
- Treatment involves stopping the antipsychotic, rapid cooling, renal support, skeletal muscle relaxants, may need induced coma, dopamine agonists e.g. bromocriptine
Prolactin side effects in antipsychotics is caused by disruption of ______
- Caused by disruption of the tuberoinfundibular pathway
- Prolactin release is inhibited by dopamine so antipsychotics cause an increase in prolactin
Prolactin related symptoms in antipsychotics?
- In men: gynaecomastia, erectile dysfunction, oligospermia
- In women: amenorrhoea, galactorrhoea
- In both: decreased libido, infertility, osteoporosis (prolactin plays a role in bone mineralization)
Treatment of prolactin side effects in antipsychotics?
Management may involve changing antipsychotic or reducing dose, occasionally may give dopamine agonists but that can worsen psychosis
Describe akathisia as an antipsychotic side effect?
- 1/5 patients report symptoms of this
- It comes on in days to weeks
- There is a feeling of inner restlessness which causes pacing, rocking from foot to foot, inability to stand still, poor sleep
Treatment of akathisia as an antipsychotic side effect?
1st line treatment is usually propranolol and 2nd line benzodiazepines e.g. clonazepam
Other side effects of antipsychotics?
- Anticholinergic side effects
- Action on 5HT receptor causes weight gain
- Antiadrenergic side effects causes postural hypotension
- Hepatotoxicity
- Prolonged QT interval;
- Photosensitivity
Treatment pathway for choosing an antipsychotic in schizophrenia?
- Clozapine works best out of all the antipsychotics by far but causes significant side effects including agranulocytosis so needs very strict monitoring and is therefore not first line but used for resistant cases
- Usually start with second generation antipsychotics and titrate up to an adequate dose
- If that isn’t working there is the option to switch to 1st or 2nd generation drugs
- If that doesn’t work then needs to consider diagnosis, compliance and psychological input and can try clozapine
- Sometimes doctors may use of a combination if getting partial responses from some drugs
- Long acting depot medication good for compliance issues and gives better plasma level stability (deltoid or gluteal)
What are clozapine specific side effects and what does this mean for monitoring?
- Clozapine carries risk of agranulocytosis and myocarditis (risks about 1/1000 for both)
- This means monitoring needs done, risks drop with time on drug, generally every week for set time, then fortnightly, then monthly life long
- ECG every 3 months
- May also measure plasma clozapine levels to check in expected ranges
- There is a risk of seizures at very high doses
- Also risk of severe constipation as a side effect which can cause bowel obstructions
- Hypersalivation (sialorrhea) is another common side effect, sometimes hyoscine can be helpful for this
- Tend to get a large amount of weight gain with clozapine
What antipsychotics cause sedation? What is this good for?
- Olanzapine, quetiapine and clozapine all cause sedation
- This can be particularly good for management of manic psychosis where patients will not be sleeping
What is a disadvantage of a depot antipsychotic?
cant take it back once injected it so if have side effects stuck with it
hence always want to trial someone on an oral first
Important side effect of haloperidol?
prolongs QT interval
In general most antidepressants and antipsychotics have been linked to?
prolonged QT interval
What atypical antipsychotic has been found to cause the least weight gain?
aripiprazole
What complementary medicine when used with an SSRI may cause serotonin syndrome?
St Johns wort
After changing lithium dose check ______ until levels are stable
weekly
Triptans should be avoided _______
in those on a SSRI as increases risk of serotonin syndrome
Common cause of serotonin syndrome?
tramadol plus SSRIs
