Psychopharmacology Flashcards
How long should you continue anti-depressants treating a SINGLE episode of depression for resolution of symptoms?
6-9 months
What are discontinuation symptoms?
Sleep disturbance Insomnia, nightmares, excessive dreaming
GI symptoms Nausea, vomiting, diarrhea
Affective symptoms Irritability, anxiety/agitation, low mood.
You get from SSRIs and SNRIs
What are the symptoms of serotonin syndrome?
Symptoms include high body temperature, agitation, increased reflexes, tremor, sweating, dilated pupils, and diarrhea.
Which drugs cause discontinuation symptoms?
Venlafaxine (SNRI) and Paroxitine (SSRI)
What does TCA’s work on?
Serotonin & Noradrenaline
What type of drug is duloxetine?
SNRI
Which class of anti-depressants can cause hyponatraemia?
SSRI
Which class of anti-depressants can cause GI disturbance?
SSRI, this may happen when medication is initiated and when the dose in increased.
Which class of anti-depressants can cause headaches?
All classes can cause headaches, especially TCAs, due to noradrenergic effect.
Which class of anti-depressants can cause hypotension, tachycardia & QTc prolongation?
SNRIs (work on Noradrenaline)
Which class of anti-depressants can cause a hypertensive crisis?
MAOIs, following tyrosine rich foods.
moclobemide, phenelzine, isocarboxazid and tranylcypromine
Which class of anti-depressants can cause discontinuation symptoms?
Venlafaxine & Paroxitine
Which class of anti-depressants can cause suicidality?
SSRIs, especially in young men <30. Window is often when they are started, with phase of high energy but low mood.
How long do we give anti-depressants to work?
2-4 weeks
Which drugs can you augment with, after dose escalation and switching drugs to tackle depression?
Add Lithium or Quetiapine, or Risperidone, or Aripiprazole
What combinations of anti-depressants can you use?
Use venlafaxine & mirtazapine or use Olanzapine & Fluoxetine.
Agomelatine is an anti-depressant, how does it work?
It is a melatonin receptor agonist and a selective serotonin-receptor antagonist; it does not affect the uptake of serotonin, noradrenaline or dopamine.
How does duloxetine work (SNRI)?
It inhibits the re-uptake of both serotonin and noradrenaline and is licensed to treat major depressive disorder.
What is flupentixol? (fluanxol)
It has anti-depressant properties when given by mouth in low doses.
How does Mirtazapine work?
It is a pre-synaptic alpha2-adrenoreceptor antagonist, increases central noradrenergic and serotonergic neurotransmission. It has few antimuscarinic effects but causes sedation during initial treatment.
How does reboxetine work?
It is a selective inhibitor of noradrenaline re-uptake, has been introduced for the treatment of depressive illness.
How does Venlafaxine work?
It is a serotonin and noradrenaline re-uptake inhibitor; it lacks the sedative and anti-muscarinic effects of the TCAs. Treatment with venlafaxine is associated with a higher rate of withdrawal effects compared with other anti-depressants.
What do anti-psychotics aim to work on but what can be the problem?
They work on the D2 receptor, however they are not specific or selective so it activates other receptors too which is why there are so many side effects.
What are D2 antagonism effects?
So too much dopamine in schizophrenics eg, so medication aims to block dopamine receptors.
What does D2 antagonists do to the mesolimbic pathway and what symptoms does this show?
Mesolimbic pathway (reward pathway) is associated with the positive symptoms of schizophrenia so D2 antagonists block this pathway. So schizophrenics have an overactive mesolimbic pathway to begin with). So they try and reduce the positive symptoms
What does the affect of anti-psychotics on the mesocortical pathway have on psychoisis and schizophrenia?
So it also blocks this pathway but this leads to a deterioration in cognition, affective symptoms, ie. increasing the negative symptoms.
What does the affect of anti-psychotics on the nigrostriatal pathway?
They also block this which causes EPSE, tardive dyskinesia and NMS
What does the affect of anti-psychotics on the tuberofundibular pathway?
It also blocks this pathway and this causes hyperprolactinaemia, sexual dysfunction and weight gain
What does blockade of the M1 receptors cause? (anti-psychotics do this also).
SE of constipation, blurred vision, dry mouth and drowsiness. (so blockage of parasympathetic pathway)
What does blockade of histaminergic receptors cause?
Sedation & weight gain
What does blockade of alpha adrenergic receptors cause? (blockage of sympathetic)
Tachycardia and changes in blood pressure
Is there a difference in efficacy between 1st and 2nd generation anti-psychotics?
No although except clozapine, but tolerability may vary.
How long should you assess a patient when started on new anti-psychotics?
Assess over 2-3 weeks then if theres no effect change the dose or medication or it there is some effect, continue the dose for 4 weeks.
When should you only consider clozapine?
After 2 anti-psychotics have been tried and unsuccessful
How long should anti-psychotic medication be continued for?
1-2 years
Which generation of anti-psychotic causes changes to seizure threshold?
Both generations
Which generation of anti-psychotic causes weight gain?
2nd generation
Which generation of anti-psychotic causes dyslipidaemia?
2nd generation
Which generation of anti-psychotic causes plasma glucose/diabetes?
2nd generation
Which generation of anti-psychotic causes QTc prolongation?
Both generations
Which generation of anti-psychotic causes Tardive dyskinesia?
1st generation
What is the pharmacological effect of clozapine and carbamazepine?
Can both cause agranulocytosis
What is the pharmacological effect of Risperidone >6mg/day?
EPSE
What is the pharmacological effect of anti-psychotic and metoclopramide?
EPSE, this is a dopamine antagonist (D2) too
What is the pharmacological effect of rapid dose changes of anti-psychotics?
Causes changes in blood pressure and seizure threshold issues.
What is the pharmacological effect of erythromicin and quetiapine?
Both affect QTc prolongation.
What drug is used to treat moderate to severe mania?
Lithium
What else is lithium used for?
It is used as prophylaxis for bipolar affective disorder.
What level of lithium is considered toxic?
> 1.5mmol/L
How often should you check eGFR when a patient is on lithium?
Every 6 months
What else should be monitored when someone is on lithium?
TFT, calcium, eGRF (as saif before 6/12), lithium, weight +
What defines bipolar affective disorder?
Bipolar depression to mania and an area in between.
What are the side effects of lithium?
Nausea, fine tremor and GI disturbance, polyuria and polydipsia
Which diuretics should you choose which don’t interact with lithium?
Use loop diuretics instead of potassium diuretics.
What affect do ACE inhibitors have when used with lithium?
They increase the level of lithium in the blood
What happens with thiazides and used with lithium?
They increase the level of lithium
Which pain relief should you not use with lithium?
Don’t use NSAIDs PRN
How does sodium valproate work?
It blocks voltage dependent sodium channels and this leads to increased levels of GABA, (it inhibits GABA break down and also inhibits re-uptake of GABA by inhibiting GABA degradative enzymes.
Which drug is more affective in bipolar, lithium or sodium valproate?-according to the lecture
Lithium
Who is sodium valproate not suitable in?
Women of child baring age- it is a major human tertogen
How many times a day do you take sodium valproate?
OD
What are the plasma levels of sodium valproate possible?
50-100mg/L
What is the interaction with sodium valproate and CYP?
Valproate inhibits CYP2C9, glucuronyl transferase, and epoxide hydrolase and is highly protein bound and hence may interact with drugs that are substrates for any of these enzymes or are highly protein bound themselves. It may also potentiate the CNS depressant effects of alcohol. HIGH BINDING PROTEIN. Also there is a slow discontinuation of sodium valproate
Name the ADR with sodium valproate concerning GI?
Causes gastric irritation
Name the ADR with sodium valproate concerning the mind?
Causes confusion
Name the ADR with sodium valproate concerning hair?
Hair loss with curly regrowth
Name the ADR with sodium valproate concerning the hand?
Dose related tremor
Name the ADR with sodium valproate concerning the blood?
Can cause thrombocytopenia
When do you use carbamazepine and what does it treat
You try it in bipolar affective disorder if they are unresponsive to lithium. It is also used to treat trigeminal neuraliga.
What do NICE recommend concerning carbamazepine?
They do not recommend it for treatment of lithium but they do recommend it for third line prophylactic treatment for mania.
How does carbamazepine work?
It is an hepatic enzyme inducer (interaction alert).
What plasma levels of carbamazepine are possible?
4-12mg/L
What are the risks associated with carbamazepine?
Hyponatraemia and agranulocytosis.
Which drugs are NOT compatible with carbamazepine?
Clozapine, paroxitine (also causes hyponatreamia), Chlortalidone
Which drugs can you use with carbamazepine?
Valproate, lorazepam, and lithium
What anxiolytics can you use for anxiety disorders? (GAD, PTSD, OCD, BDD, social phobia)?
Benzos (rapid relief, only for short term), SSRIs/SNRIs low dose should respond in 6-12/52, pregabilin (licensed for GAD)
What should you monitor when someones on SSRIs/SNRIs?
Monitor for akathisia, increase anxiety and suicidal ideation. Do NOT stop abruptly.
When are hypnotics used?
To induce sleep and used in the treatment of sever insomnia
What drugs are included as hypnotics?
barbiturates, benzodiazepines (short T1/2), zolpidem, zopiclone, chloral hydrate, chlormethiazole or the antihistamines promethazine, and diphenhydramine.
Use PRN and limit length of treatmentW
Which benzos have a short half life (ie less than 10 hours)?
Loprazolam
Lormetazepam Temazepam
Which benzos have a long half life (ie more than 15 hours)?
Nitrazepam Flurazepam Diazepam Alprazolam Clobazam Chlordiazepoxide
What should you not use hyponotics for?
Mild insomnia, excessive alcohol use, daytime catnapping, drinking monsters and severe hepatic impairment.
Can you use hypnotics in over 65?
yes
Which anti-depressant is used post MI?
Sertraline is the preferred antidepressant following a myocardial infarction as there is more evidence for its safe use in this situation than other antidepressants
What are the side effects of clozapine?
weight gain excessive salivation agranulocytosis neutropenia myocarditis arrhythmias
Why is cardiovascular disease prominent in schizophrenia?
Linked to antipsychotic medication and high smoking rates
What are the side effects of zuclopenthixol decanoate 200mg depot injection?
Parkinsonism symptoms, first generation anti-psychotic.
What are EPSE’s?
Parkinsonism
acute dystonia (e.g. torticollis, oculogyric crisis)
akathisia (severe restlessness)
tardive dyskinesia (late onset of choreoathetoid movements, abnormal, involuntary, may occur in 40% of patients, may be irreversible, most common is chewing and pouting of jaw).
After feeling well on a SSRI, how long should you stay on it for?
6 months
How do TCAs work?
They inhibit the reuptake of noradrenaline from the synaptic cleft.
Concerning CSF levels, what is often found here in a depressed person?
Levels of 5-HIAA (a serotonin metabolite) decreased in depression sufferers.
Which pathway goes from the VTA to the nucleus accumbens?
Mesolimbic pathway
Which pathway goes from the VTA to the (ventomedial) pre-frontal cortex?
mesocortical
Which pathway goes to the hypothalamus?
Tuborohypohyseal pathway
Which pathway goes from the substantia nigra to the striatum?
Nigrostriatal pathway
Prolatin symptoms- drug counselling…..
Amenorrhea, Galactorrhea, Gynaecomastia, Impotence, weight gain, osteoporosis
Rx change drug