pharma;antid Flashcards by Honor Moffat

indication

establish a diagnosis and identify target symptoms that will be used to monitor therapy response

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management

adjust dosage for optimum benefit, safety and compliance

use adjunctive and combination therapies if needed however always strive for simplest regime

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antidepressant indications

unipolar + bipolar depression
organic mood disorders
schizoaffective disorder
anxiety disorders incl OCD, panic, social phobia, PTSD

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antidepressant classifications

tricyclics (TCA)
monoamine oxidase inhibitors (MAOIs)
selective serotonin reuptake inhibitors (SSRIs)
serotonin/noradrenaline reuptake inhibitors (SNRIs)
novel antidepressants

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how do antidepressents work

we don’t actually know

neurotransmitters noradrenaline and serotonin are involved and antidepressants increase these levels in different ways

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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

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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

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tertiary TCAs examples

imipramine
amitriptyline
doxepin
clomipramine

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secondary TCAs

are often metabolites of tertiary amines

primarily block noradrenaline

side effects as same as tertiary TCAs but genereallu

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antihistaminic

weight gain

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anticholinergic

dry mouth

blurred vision

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secondary TCAs examples

desipramine

notrtriptyline

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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

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MAOIs side effects

orthostatic hypotension 
weight gain 
dry mouth 
sedation 
sexual dysfunction 
sleep disturbance

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MAOIs: cheese reaction

hypertensive crisis can develop when MAOIs are taken with tyramine-rich foods or sympathomimetics
*cheese reaction

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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