Pharmacology Flashcards
what is the monoamine hypothesis
depression results from a functional deficit of monoamine transmitters in particular serotonin (5HT) and noradrenaline
what does serotonin influence
mood sleep feeding behaviour sensory perception
what is the post-synaptic serotonin receptor
5-HT
what is the post-synaptic noradrenaline receptor
a1
b
serotonin is synthesised in the presynaptic neurone from what
tryptophan
noradrenaline is synthesised in the presynaptic neurone from what
tyrosine
when serotonin and noradrenaline are reuptaken into the presynaptic neurone what breaks them down
Monoamine oxidase
give an example of a reversible MAOI
moclobemide
give an example of an irreversible MAOI
phenelzine
what is a major side effect of MAOIs
cheese reaction
what is a cheese reaction
hypertensive crisis caused by a build up of tyramine
how does a hypertensive/cheese reaction occur
MAOIs block MAO-A in the gut and liver which breaks down dietary tyramine. The build up of tyramine causes NA release which makes BP skyrocket
or by interaction with other drugs that potentiate amine transmission e.g. other antidepressants (SSRI, TCA), pseudoephedrine
what foods should be avoided when taking MAOI
foods that have been aged or fermented
red wine
cheese
soy
what other issues arise with MAOI
potentiate the effects of other drugs
what are some side effects of MAOI
insomnia, postural hypotension, peripheral oedema, dizziness
what drugs can MAOIs potentiate the action of
TCAs, barbiturates, morphine, ethanol, pseudoephedrine
how do TCAs work
block the reuptake of noradrenaline and serotonin into presynaptic terminals by blocking their transporters
what additional actions do TCAs have and what does this lead to
also block dopamine, histamine and muscarinic Ach receptors leading to lots of side effects
give 6 examples of tricyclics
imipramine amitriptyline clomipramine doxepin dosulepin lofepramine
what are some side effects of tricyclics
cardiovascular
anticholinergic
weight gain and sedation
TCAs are ____ in overdose
cardiotoxic in overdose
what are the anticholinergic side effects of TCAs
blurred vision dry mouth constipation urinary retention sexual dysfunction
what are some cardiovascular effects of TCAs
postural hypotension
tachycardia
arrhythmias - QT prolongation
give 5 examples of SSRIs
fluoxetine sertraline citalopram escitalopram paroxetine
how do SSRIs work
selectively block the reuptake of serotonin (5HT) from the synaptic cleft
what are some things to be careful of when using SSRIs in the elderly
hyponatraemia and falls
what are some things to be careful of when using SSRIs in young people
transient increase in suicidality in first few weeks
what are some side effects of SSRIs
increased anxiety, sweating vivid dreams, insomnia head ache sexual dysfunction GI upset
what kind of GI symptoms do you get with SSRIs
nausea
abdominal pain
constipation
increased risk of GI bleed
when does the nausea with SSRIs usually settle
2 weeks
SSRIs are ____ in overdose
safe
what should be done when stopping an SSRI and why
taper dose as assoc. with withdrawal
some SSRIs can alter drug levels - how?
inhibit CP450 enzyme
how do SNRIs work
block the reuptake of noradrenaline and 5HT into the pre-synaptic terminals
give 2 examples of SNRIs
venlafaxine
duloxetine
what is another time when duloxetine is used
stress incontinence
what are the side effects of SNRIs
GI upset similar to SSRIs
cardiovascular
what cardiovascular side effects do you get with SNRIs
hypertension
palpitations
dizziness
why are SNRIs preferred to TCAs
lack major receptor blocking properties of TCAs so more limited range of SEs
how does mirtazapine work
blocks a2, 5HT2 and 5HT3 presynaptic receptors
- noradrenaline, serotonin and histamine
why is mirtazapine beneficial when given with an SSRI
blocks serotonergic side effects
what are some side effects of mirtazapine
sedation and weight gain
how does bupropion work
dopamine uptake inhibitor
how does trazadone work
potent serotonin and noradrenaline receptor antagonist
what is the main side effect of trazadone
sedation
when should patients be reviewed after starting antidepressant
2 weeks
how long should treatment be continued before switching drug
should have treatment for 4 weeks (6 in elderly)
following remission how long should an antidepressant be continued
6 months
how long should patients be treated for GAD
12 months
Patients with a history of recurrent depression should receive maintenance treatment for _____
at least 2 years
what should be considered in all patients who develop drowsiness, confusion, or convulsions while taking an antidepressant
hyponatraemia
what is 1st line in the treatment of depression
SSRI
if the SSRI doesn’t work what should you consider
dose increase
swap drug
combine drug
or augment
what drug could you combine the SSRI with
mirtazapine
what can be used to augment the SSRI
antipsychotic or lithium
what could be considered in severe refractory depression
ECT
what are absolute contraindications to ECT
recent MI (3 months)
recent CVA
intracranial mass lesion
phaeochromocytoma
what are relative contraindications to ECT
angina CHF severe pulmonary disease severe osteoporosis pregnancy
if a patient with capacity is detained under the MHA and is refusing ECT can you give it anyway
no
what are some side effects of ECT
headache memory problems muscle aches confusion nausea
when is lithium used
LT treatment of bipolar to stabilise mood and prevent recurrence of both depression and mania
lithium is normally given as
lithium carbonate
how does lithium work
blocks phosphatidylinositol pathway
inhibits glycogen synthase kinase 3B
when are lithium levels checked
12 hours post dose
levels checked weekly until stable then 3 monthly
over what level is lithium toxic
> 1.5 mmol/L
what are some side effects of lithium
metallic taste in mouth polydipsia, polyuria tremor hypothyroidism LT reduced renal function / nephrogenic DI weight gain
what does lithium toxicity look like
D+V, course tremor, ataxia, myoclonus, drowsiness, coma
convulsions, confusion, seizures, restlessness, electrolyte disturbance, renal failure, arrhythmia (QTP) , death
what drug should lithium not be given with and why
NSAID –> renal impairment
what is the treatment of lithium toxicity
stop lithium
gastric lavage or dialysis depending on severity
is lithium safe in pregnancy
not in first trimester - teratogenic
name 3 anticonvulsants sometimes used in LT treatment of bipolar
valproic acid
lamotrigine
carbamazepine
what can valproate cause if given during pregnancy
neural tube defects
how does valproate work
inhibits enzymes that block GABA
what are some side effects of valproate and carbamazepine
drowsiness
ataxia
cardiovascular effects
induces liver enzymes
what is there a very small risk of when taking lamotrigine
stevens johnson syndrome
what is the first line treatment in acute bipolar mania
antipsychotic
olanzapine, quetiapine, risperidone
what is the first line treatment in acute bipolar depression
antipsychotic + antidepressant
quetiapine, olanzapine) (fluoxetine
how do antipsychotics work
dopamine D2 receptor antagonists blocking dopaminergic transmission in the mesolimbic pathways
are typical or atypical antipsychotics associated with EPSEs
typical
give 2 examples of typical antipsychotics
haloperidol
chlorpromazine
what EPSEs can typical antipsychotics cause
parkinsonism
Acute dystonia
Akathasia
Tardive Dyskinesia
what is parkinsonism
bradykinesia + resting tremor + rigidity
what is acute dystonia
sustained muscle contraction usually in eyes, jaw, neck
occurs within a few hours of starting treatment
what is an important feature of acute dystonia
oculogyric crisis
what is an oculogyric crisis
restlessness, agitation and involuntary upward deviation of the eyes
what is akathasia
severe restlessness, constant need to wander
what is tardive dyskinesia
occurs with LT use, late onset of choreoathetoid movements (abnormal, involuntary)
- chewing, facial grimaces, blinking, lip smacking, pouting of jaw
when antipsychotics are used in the elderly there is an increased risk of what
stroke
thromboembolism
what is the main advantage of atypical antipsychotics
no EPSEs
what drug can be used to manage EPSEs with typical antipsychotics
procyclidine, prochlorperazine
what are some side effects of antipsychotics in general
anticholinergic sedation, weight gain, increased appetite raised prolactin neuroleptic malignant syndrome prolonged QT interval
prolonged QT interval occurs particularly with what antipsychotics
haloperidol
atypicals more than typicals can do what
reduce seizure threshold
raised prolactin can lead to what
galactorrhoea impaired glucose tolerance sexual dysfunction amenorrhoea infertility
why do you get raised prolactin from antipsychotics
dopamine negatively feeds back on prolactin release so its blockade results in raised prolactin
what is neuroleptic malignant syndrome
seen with all antipsychotics but particularly typicals
- hyperthermia
- muscle rigidity and bradykinesia
- altered mental state
- autonomic dysfunction
what autonomic dysfunction is seen with neuroleptic malignant syndrome
tachycardia, tachypnoea, dilated pupils, sweating
what antipsychotics should be 1st line in schizophrenia
atypical
what are the side effects of atypical antipsychotics
weight gain, drowsiness, increased appetitie T2DM, metabolic syndrome hyperprolactinaemia increased risk seizures sexual dysfunction
name 6 atypical antipsychotics
clozapine olanzapine quetiapine risperidone amisulpride aripiprazole
true/false
EPSEs can be seen at higher doses of some atypical antipsychotics
true
what 2 atypical antipsychotics have the most significant weight gain
clozapine
olanzapine (risk of dyslipidaemia and obesity)
which atypical antipsychotic is particularly good for raised prolactin
aripiprazole
with clozapine there is a risk of what
agranulocytosis
when should you do a FBC for someone on clozapine
weekly for 1st 6 months fortnightly for next 6 months every 4 weeks thereafter 1 month after stopping sore throat
what should be taken before starting clozapine
ECG and FBC
why is an ECG needed before starting clozapine
risk of myocarditis
how can you treat hypersalivation caused by clozapine
hyocine hydrobromide
when should clozapine be used
schizophrenia that is not controlled despite use of 2 antipsychotics
what should someone that smokes on clozapine be told
smoking reduces levels so suddenly stopping smoking can make levels dramatically increase
what are the 3 parts to CBT
NATs
dysfunctional assumptions
core belief/schema
what is the usual course of ECT
twice a week for 3 to 6 weeks (6 to 12 sessions in total)
metabolic syndrome occurs more with atypicals/typicals
atypicals - 5HT2C receptors
antagonism of what causes sedation
H1 receptors (histamine)
histamine blockade also leads to what
increased appetite
____ blockade can reduce nausea and vomiting
histamine
a-adrenergic blockade can cause what
hypotension and interruption of baroreflex response –> dizziness, lightheadedness, fainting when going from sitting to standing
what antipsychotic would you recommend to a woman on LT lithium who wants to have a child
olanzapine - doesnt pass across placenta or into breast milk
what causes serotonin syndrome
Consumption of excessive amounts or multiple drugs that increase amount of serotonin
what are the s/s of serotonin syndrome
Cognitive: headache, anxiety, agitiation, hallucination, confusions, coma.
Autonomic: shivering, sweating, hyperthermia, tachycardia, dilated pupils, nausea and diarrhoea.
Somatic: myoclonus (twitching), tremor, rigidity, hyper reflexia
