Pharmacology of psychiatry Flashcards
What level of lithium classes as toxicity
> 1.2mmol/L
which anti-psychotics are most associated with weight gain
clozapine and olanzapine
what are the steps of the pharmacological approach to depression
- SSRI- eg. sertraline, fluoxetine
- taper down SSRI and add SNRI eg. venlataxine
- augmentation with anti-psychotic or another antidepressant
- Electroconvulsive therapy
Presentation of lithium toxicity
GI disturbances- D+V
polyuria/polydipsia (nephrogenic DI)
renal failure
sluggishness
ataxia
tremor
fits
ECG T wave flattening/ inversion
thyroid enlargement and hypothyroidism
What drugs can interfere with lithium
diuretics
ACEi
ARBs
NSAIDs
-> increase lithium levels
Liver enzyme inducers
CRAP GPs
Carbamazepine
Rifampicin
Alcohol
Phenytoin
Gisofulvin(antifungal)
Phenobarbitol
Sulphonyureas
Liver enzyme inhibitors
Isoniazid
Ketoconazole
fluconazole
erythromycin
chloramphenicol
metronidazole
Mood stabilisers
Lithium
sodium valporate- used in acute mania
Carbamazepine
What should be monitored with someone on lithium?
U&Es- renal function and calcium
TFTs- can cause hypothyroidism
every 6months
makesure to check baseline before starting lithium
pharmacological Mx of opioid OD
naloxone
Pharmacological Mx of paracetamol OD
- activated charcoal reduces absorption- must be given within 1 hr
- N-acetylecystine (if paracetamol levels over toxic dose (150mg/kg)
Mechanism of action of typical and atypical anti-psychotics
typical- inhibiit D2 receptors in the brain and therefore reduces neurotransmission
atypical- block 5-HT receptors and also D2 but weaker than typicals
side effects of antipsychotics
Extrapyramidal symptoms
- parkinsonism
- dystonia
- akathisia
-tardive dyskinesia
hyperprolactinaemia
- galactorrhoea
- amenorrhoea
- sexual dysfunction
Weight gain (esp clozapine and olanzepine)
agranulocytosis (clozapine)
hyponatraemia (olanzepine)
inc risk of DM (olanzepine)
dyslipidaemia
Alcohol withdrawal and addiction management pharmacology
Acute withdrawal
1. Pabrinex- if risk of wernickes encephalopathy
2. benzodiazepine or carbamazepine if needs some sedation
addiction management
1. Acamprostate - weak NMDA antagonist helps with cravings
2. disulfram: promotes abstinence - alcohol intake causes severe reaction due to inhibition of acetaldehyde dehydrogenase. Patients should be aware that even small amounts of alcohol (e.g. In perfumes, foods, mouthwashes) can produce severe symptoms
Opioid detoxification
- methadone (liquide)
- buprenorphine (sublingual)
- clonidine and lofexidine can help withdrawal symptoms
- Naloxone for rapid detox in OD
Alzheimers pharmacology
- Acetylcholinesterase inhibitors eg. donepezil, rivastigmine (milde-moderate alzheimers)
- Memantine (NMDA antagonist) severe alzhimers
Non alzheimers dementia pharmacology
- donepezil
- rivastigmine
NB: antipsychotics can worsen lewy body ddementa
Generalised anxiety disorder pharmacology steps
- SSRI- sertraline
- SNRI- venlataxine
- pregabilin
other
4. beta-blockers for treor sx (caution with asthma)
MOA of clozapine
blocks D1 and D4 receptors
side effects of clozapine
sedation
weight gain
agranulocytosis
reduced seizure threshold
GI disturbances
hypersalivation
Contraindications of clozapine and necessary tests before starting
and follow up monitoring
CI:
Hx of neutropenia, Hx of myocarditis, current liver disease
tests:
FBC
LFTs
ECG-
bloods weekly for 18weeks
then every 2 weeks for 1 year
monthly thereafter
SSRI contraindications
anyone with pre-existing QT prolongation
SSRI interactions
NSAIDS- give with PPI
warfarin/heparin
triptans
MAOI- risk of serotonin syndrome
what is serotonin syndrome
serious drug interaction causing build up of serotonin in the synapses
Sx:
adgitation and restlessness
dilated pupils
diarrhoea
raised BP
confusion, reduced GCS
insomnia
autonomic dysfunction- tachycardia
hyperreflexia, myoclonus, hypertonia
incidence <1%
Lithium monitoring
- baseline U&Es, LFTs and TFTs
- weekly lithium level monitoring until dose stabilised
- lithium blood levels checked every 3 months (12hrs post dose)
- TFTs and renal function every 6 months
When to treat depression with drugs
severe depression
If other options eg. computerised CBT, group CBT, 1-1 CBT, talking therapy, lifestyle changes haven’t worked
side effects of SSRIs + complications
headache
sleep disturbances/ vivid dreams
nausea, diarrhoea, constipation
sexual dysfunction
Complications:
hyponatraemia
GI bleeding
How long should someone be on SSRI for
continue for 6-12 months once pt feels well for first incidence of depression.
continue for 2 years if recurrent depression
MOA of MAOs
inc availability of 5-HT +NA in synapses
What is the tyramine interaction
when eat foods that are high in tyramine when on MAOs can lead to hypotensive crisis
food egs. Cheese, yoghurt, chocolate
what are the RFs for Serotonin Syndrome
anti depressants
combination
lithium
ECT
opiates
antiemetics
Complications of Serotonin Syndrome
DIC
rhabdomyolisis
renal failure
metabolic acidosis
seizures
SE and complications of lithium use
SEs:
GI upset
fine tremor
metallic taste in mouth
sedation
Polyuria/polydipsia -> neprogenic DI
T wave flattening
hair changes
Complications:
teratogen (ebsteins anomaly), CKD (nephrogenic DI), arrhythmia, hyperparathyroidism/hypercalcaemia, hypothyroidism
Lithium therapeutic window range
0.4-1mmol/L
narrow so careful monitoring
TCAs MOA and some examples
5-HT and NA reuptake inhibition.
Older ‘dirty’ drug
eg. Amitriptyline, nortiptyline, clomipramine, lofepramine
starting on lithium
FBC, calcium, TFTs, ECG (if RFs or known cardiac disease)
consulting
- stay hydrated
-careful in hot countries
Olanzapine uses and SEs
anti-psychotic used in
acute mania
off license
rapid effect
sodium valporate SEs
terato genic -> spina bifida
PCOS
GI upset
tremor
sedation
wt gain
loss of hair
thrombocytopenia
anticonvulsant and mood stabiliser used in acute mania
Lamotrigine complications
Stevens johnson syndrome- warn about rash and stop, slow titration
Mania management
1st epidode/ acute mania:
- antipsychotic eg. olanzapine
- if no response could add lithium or valporate
long term (bipolar)- lithium, valporate or carbamazapine
Consulting someone strated on SSRIs
- will need to continue medication for at least 6 months after improvement of Sx then gradually titre down
- small evidence of an increased suicide risk- SN and regular reviews
SEs and issues with TCAs
SE:
antimuscarinic and anticholinergic: dry mouth, bluured vision, constipation, urinary retention
Cardiotoxis- prolonged QT, ST elevation, AV block
antihistaminergic: sedation, postural hypotension
discontinuation syndrome
lethal in overdose
just as effective as SSRIs!
Example of a newer version of MAO
moclobemide
NaSSA MOA side effects and example
blocks presynaptic alpha-2
adrenergic receptors. Autoreceptor
hence less feedback and more NA
release
SE:
Weight gain, increased appetite, drowsiness
eg. Mirtazapine
(useful drug to give to someone who needs to put on weight eg in anorexia nervosa)
What is discontinuation syndrome
symptoms experienced when stopping antidepressents especially SSRIs.
not the same as withdrawal
Sx:
trouble sleeping
flu like Sx
anxiety
‘electrick shocks’
GI disturbances
dizziness
headaches
management of serotonin syndrome
stop causative medications
A-E approach: manage airways, fluids, renal support, temp control
cyproheptadine- anti-histamine and serotonin antagonist
management of serotonin syndrome
stop causative medications
A-E approach: manage airways, fluids, renal support, temp control
cyproheptadine- anti-histamine and serotonin antagonist
Carbemazepine uses and SEs
mood stabiliser and anticonvulasant
Not really recommended by nice
strong CYP450 inducer
N+V
blurred vision
agranulocytosis
Management of acute mania
- stop any antidepressants, recreational drugs, steroids that may induce mania
- Monitor fluids
- if not on any medication give an antipsychotic and short course of benzo
-olanzepine, quitiepine - if already on medication check compliance, adjust dose, consider adding antipsychotic
- ECT if unresponsive to medication
managament of bipolar depression
dont use SSRI alone- may precipitate mania. augment with antipsychotic
eg. orlanzepine with fluoxetine OR lamotrigine
what are the 4 systems affected in the brain by anti-psychotics according to the dopamine theory- and what aspects of schizophrenia do they target
Mesolimbic pathway –> +ve symptoms
Mesocortical pathway –> -v3 symptoms
Nigrostriatal –> EPSEs
tuberoinfundibular –> prolactin
what are some uses of antipsychotics in medicine
psychosis
mood stabilisation in BPAD
antidepressant augmentation
Tourettes
give some examples of typical antipsychotics
Haloperidol, zuclopenthixol, chlorpromazine
give some examples of atypical antipsychotics
Clozipine, olanzipine, risperidone, aripriprazole
what are the pros and cons of clozapine?
pros:
-best drug for treating psychosis
-only antipsychotic that has evidence for treatng the negative Sx
Cons:
-dirty drug binding to 30+ receptors means it has lots of adverse effects and SEs
- high risk of rebound psychosis if stopped abruptly
SEs:
-sedation
-neutropenia/ leukopenia/agranulocytosis
- myocarditis, cardiomyopathy
-increased appetite and wt gain
-lowers seizure threshold
- prothrombotic
-severe constipation -> bowel perf
-low BP, dizziness
-double vision
-hypersalivation
NB: due to all these SEs, clozipine is only used in Rx resistant psychosis
What needs to be monitored before and during antipsychotic treatment
starting ECG and regular checks (QTc prologation)
regular FBCs (esp clozipine)
examples of some antipsychotics available as depots
zuclopenthixol
flupentixol
haloperidol
olanzepine
aripriprizole
paliperidone
how long does it take for the sedative and antipsychotic effects to kick in
sedative –> rapid, within mins-hrs
antipsychotic –> within 1-2weeks, peak benefit after 6 weeks
what do you use for rapid tranquilisation in a severely agitated psychiatric pt
IM olanzepine or haloperidol
(in medicine usually use short acting benzo eg. lorazepam for sedation in severely agitatied)
What do you need to be aware of/ cautious about when giving IM olanzepine?
- not to give IM olanz within 1hr of IM lorazepam due to risk of respiratory depression
- no more than 3 days of IM olanzepine due to risk of post injection syndrome
what are the Sx of hyperprolactinaemia in women
reduced libido
amenorrhoea
galactorrhea
osteoporosis (dop potentiates effects of oestrogen)
what are the Sx of hyperprolactinaemia in men
reduced libido
erectile dysfunction
gynaecomastia
galactorrhea
what antipsychotics do not affect prolactin
quetiapine
ziprasidone
use with aripriprazole
what are the normal QT intervals and when is it really concerning?
men <440ms
women <470ms
if over >500ms v.v dangerous!
what does the QT interval represent and what happens if it is prolonged
ventricular depolarisation and repolarisation
prolongation risks developing torsades de pointes –> polymorphic VT –> reduced CO –> shock –> death
what are the causes of prolonged QT interval
long QT syndrome
electrolytes: low k, low Mg, low Ca
drugs: antipsychotics (esp haloperidol), citalopram, venlafaxine, clarithromycin, fluconazole
which antipsychotics have no to low effect on QTc
no- aripriprazole, zuclopenthixole, lurasidone
low- clozapine, olanzepine, risperidone
neuroleptic malignant syndrome:
RFs, features, investigations, management
RFs:
high dose typicals, rapid dose change, male, younger age
features:
hyperthermia/fever, rigidity/tremor, hyperreflexia, clonus, low BP, tachycardia
Investigations:
Bloods:
leukocytosis, enzymes high CK, renal function tests (rhabdomyolysis), LFTs deranged
Managament
1. stop antipsychotic
2. admit to medical ward/ ITU
3. supportive with fluids, electrolytes and cool
4. benzos for rigidity
5.bromocriptine (dop agonist)
what are the features of EPSEs?
Parkinsonism:
-rigidity, tremor, bradykinesia, shuffle, pin rolling, hypomimia, reduced arm swing, stooped
acute dystonia:
- gurning, upward eye movements (oculogyric crisis), head and neck twisting (torticollis), compromised airway (laryngeal dystonia)
–> Mx with anticholinergics eg. procyclidine
akanthisia
- restlessness, trouble staying still, pacing, rocking back and forth
–> Mx: change meds, diphrenhydramine, propranolol
tardive dyskinesia (chronic antipsychotic use)
- lip smacking, tongue protrusion, chewing
What metabolic effects to antpsychotics have?
+Mx
more common in atypicals
wt gain, dyslipidaemia, insulin insensitivity (T2DM)
esp- clozipine, quetiapine, olanzeptine (those which affect the H1 receptor)
Mx:
monitor wt, BP, lipids, HbA1c
education on lifestyle
statins, diabetic meds, antihypertensives
MOA of SSRIs
Stops the channels from clearing serotonin from the gap between neurones which means there is a build up of serotonin and this is able to stimulate the nerves in your brain
How does lithium work (explaining to a pt)
Its not fully understood but it basically works to change the release of certain chemicals in your brain allowing you to have more control over your emotions
drugs CI in pregnancy
Lithium –> ebsteins anomaly
sodium valporate, carbamazepine –> NTD
SSRI (paroxetine highest risk of CHD in 1st trim or persistant pulmonary hypertension in 3rd trim)- encourage psychological approaches
drugs CI in breastfeeding (All for Obs)
BREAST
Benzodiazepines
Radioactive isotopes
Ergotamine/ caffeine
Amiodarone, amphetimines
Sex hormones, stimulant laxatives
Tetracyclines
side effects of SSRIs
the 5 S’s
Suicidal ideation
Sexual dysfunction
Sleep disturbances (vivid dreams)
Stomach (wt gain, N&V)
Serotonin syndrome
