pharma;antid Flashcards
indication
establish a diagnosis and identify target symptoms that will be used to monitor therapy response
management
adjust dosage for optimum benefit, safety and compliance
use adjunctive and combination therapies if needed however always strive for simplest regime
antidepressant indications
unipolar + bipolar depression
organic mood disorders
schizoaffective disorder
anxiety disorders incl OCD, panic, social phobia, PTSD
antidepressant classifications
tricyclics (TCA)
monoamine oxidase inhibitors (MAOIs)
selective serotonin reuptake inhibitors (SSRIs)
serotonin/noradrenaline reuptake inhibitors (SNRIs)
novel antidepressants
how do antidepressents work
we don’t actually know
neurotransmitters noradrenaline and serotonin are involved and antidepressants increase these levels in different ways
TCAs
very effective but potentially unacceptable side effect profile i.e. antihisaminic, anticholinergic,
lethal in overdose
can cause QT lengthening even at therapeutic serum level
tertiary TCAs
have tertiary amine side chains
side chains are prone to cross react with other types of receptors which leads to more side effects
tertiary TCAs examples
imipramine
amitriptyline
doxepin
clomipramine
secondary TCAs
are often metabolites of tertiary amines
primarily block noradrenaline
side effects as same as tertiary TCAs but genereallu
antihistaminic
weight gain
anticholinergic
dry mouth
blurred vision
secondary TCAs examples
desipramine
notrtriptyline
MAIOs
bind irreversibly to monoamine oxidase thereby preventing inactivation of amines such as norepinephrine, dopamine and serotonin leading to increased synaptic levels
very effective for resistant depression
MAOIs side effects
orthostatic hypotension weight gain dry mouth sedation sexual dysfunction sleep disturbance
MAOIs: cheese reaction
hypertensive crisis can develop when MAOIs are taken with tyramine-rich foods or sympathomimetics
*cheese reaction
MAOIs: serotonin syndrome
can develop if take MAOI with meds than increase serotonin or have sympathomimetic actions
serotonin syndrome: abdo pain, diarrhoea, sweats, tachycardia, hrn, myoclonus, irritability, delirium
MAOIs: avoiding serotonin syndrome
need to wait 2 weeks before switching from an SSRI to an MAOI
exception is fluoxetine where need to wait 5wks because of long half life
SSRIs
block the presynaptic serotonin uptake, increasing level of serotonin
treat both anxiety and depressive symptoms
SSRIs side effects
GI upset sexual dysfunction anxiety restlessness nervousness insomnia fatigue sedation dizziness
SSRIs: discontinuation syndrome
can develop this with agitation, nausea, disequilibrium and dysphoria
activation syndrome
caused by increased serotonin. can be distressing for patient
nausea, inc anxiety, panic and agitation
typically lasts 2-10days - warn patients
discontinuation syndrome
agitation, nausea, disequilibrium and dysphoria
more common with shorter half life drugs so consider switching to fluoxetine
sertraline pros
very weak P450 interactions (only slight CYP2D6_
short half life with lower build-up of metabolities
less sedating when compared to paroxetine
sertraline cons
max absorption requires a full stomach
increased number of GI adverse drug reactions
fluoxetine (prozac) pros
long half-life so decreased incidence of discontinuation syndrome. good for patients with medication non-compliance issues
fluoxetine (prozac) cons
long half life and active metabolite may build up (not good for pt with hepatic illness)
initial activation may increase anxiety and insomnia
more likely to induce mania than some of other SRRIs
SNRIs
inhibit both serotonin and noradrenergic reuptake like the TCAs but without antihistamine and anticholinergic side effects
used for depression, anxiety and possibly neuropathic pain
SNRIs: venlafaxine pros
minimal drug interactions and almost no P450 activity
short half life and fast renal clearance
SNRIs: venlafaxine cons
can cause a 10-15mmHg dose dependent incr in BP
may cause sig nausea
can cause bad discontinuation syndrome
sexual side effects in >30%
duloxetine pros
some data to suggest efficacy for the physical symptoms of depression
duloxetine cons
cannot break capsule, as active ingredient not stable within stomach
in pooled analysis had higher drop out rate
novel antidepressants: mirtazapine pros
different mechanism of action
can be utilised as a hypnotic at lower doses secondary to antihistaminic effects
novel antidepressants: mirtazapine cons
inc serum cholesterol by 20% in 15% pts and triglycerides in 6%
assoc with weight gain
very sedating at lower doses
TCA overdose ECG signs
long QT
wide QRS
tachycardia
