Pharm Flashcards
Depression hypothesis
Monoamine hypothesis - essentially not enough neurotransmitter in brain - mainly serotonin (primary candidate) and norepinephrine - best results 2-4 wks after starting antidep, therefore increased NT leads to plasticity ultimately leading to increased mood
Choosing antidep
Trial and error - makes pt feel better and they can tolerate side FX - 6-6-3-max rule (trial >6 wks, tx >6 months, >3 wks washout; achieve max dose; > is greater than or equal to)
SSRIs
Fluoxetine
Paroxetine
Sertraline
(Es)Citalopram
for “typical” depression
side FX: decreased libido, serotonin syndrome (esp if no washout; rare)
Serotonin syndrome
Caused by accumulation of too much serotonin in brain - causes tremor (myoclonus), generates heat/fever, tachycardia, altered mental status
Tx: Stop tremor (pararlyze if necessary) & supportive care & Withdraw serotoninergic drug
Atypical antidepressants
Buproprion (wellbutrin) - also for stopping smoking - but make sure they’re not bullimic or they might have seizure; usually gain weight
Trazodone (side effect of sedation) - pretty bad antidep but good for sedation (& safe for this); may cause priapism (med emerg)
Mirtazapine (SNRI) - assoc with weight gain
Venlafaxine (SNRI) - diastolic hypertension
TCAs: how to use side FX profiles to treat concurrent conditions
Amitryptiline can be used to also Tx enuresis and/or neuropathic pain
Nortryptiline can also be used to Tx neuropathic pain
Desipramine has significant anticholinergic side FX
All TCAs can cause Convulsion (seizure), Cardiac (prolonged QT - need baseline ECG), Coma
MAOIs
Mainly target norepinephrine (blocking its destruction)
Can cause hypertensive crisis especially when consumed with tyramine
Mood disorders: 1st-line Tx
Li - first-line (USE IT if no contraindications); it is a teratogen, is nephrotoxic, causes nephrogenic DI, has narrow therapeutic index (measure levels) - choose lithium if the question does not give you a good reason NOT to be on it; otherwise choose valproate
Valproate
Valproate is 1st line if you can’t use Li - assoc with spina bifida, so give mom folate; can cause pancreatitis, low platelets, agranulocytosis (follow with CBC)
2nd line agents for mood
Carbamazepine - can also treat trigeminal neuralgia; assoc with cleft palate, AV block
Lamotrigene - assoc with blurry vision
Both assoc with rash that can lead to Stevens Johnson syndrome
Benzos
Tx for panic attacks, good for ABORTING (not preventing) anxiety, good for Tx EtOH withdrawal (long-acting); addictive, also have withdrawal syndrome identical to alcohol withdrawal
Lorazepam (Ativan) - short-acting
Diazepam (Valium) - medium
Clonazepam - long
Tx of anxiety
What type of anxiety is it? How bad is it right now?
SSRI - Tx of choice for chronic anxiety (OCD, PTSD, GAD) - be careful for serotonin syndrome, decreased libido
In specific circumstances, use beta-blocker: public speaking (specific anxiety) - potential for bradycardia (but usually given in too low doses)
Will knock out someone with severe agitation
“B52” - lorazepam, haloperidol, Benadryl
Antipsychotics: indications
For SCZ and other psychotic D/Os
+ and - Sx caused by which receptors?
+ Sx caused by mesolimbic dopamine receptor (D-2C) activation - block these to Tx +Sx
- Sx controlled by serotonin receptor (5-HT1) activation - block these to Tx -Sx
Typical antipsychotics
Primarily target dopamine, i.e. D-2C antagonists - not specific (block all dopamine) - highly incisive, high side FX - used to treat positive Sx
Typical antipsychotics in order of highest to lowest potency
Haloperidol - fluphenazine - thioridazine - chlorpromazine
If instead you block dopamine in tubuloinfundibular neurons, you lead to release of ___
prolactin - leads to gynecomastia, galactorrhea, amenorrhea
If instead you block dopamine in nigrostriatal tract, you get ____
EPS
NMS clin pres & Tx
fever, lead-pipe rigidity, altered mental status - check CK level (will be elevated) - give dantrolene (to uncouple electron transport chain and uncouple fever production) - never restart the same antipsychotic
2 other side FX of typical antipsych
sedation, anticholinergic
Atypical antipsychotics
Increased specificity for D2C, 5HT1 - decreased potency, decreased side FX
Treat both + and - Sx (target D2C, 5HT1)
Can still get EPS, increased prolactin but much more rare
FIRST LINE, but more expensive; NO DEPOT FORM; just PO.
5 atypicals
risperidone, quetiapine, olanzapine, aripiprazole, ziprasadone
3 main side FX of atypicals
diabetes, weight gain, prolonged QT (olanzapine rather bad for diabetes and weight gain)
Clozapine
in a class by itself - “prototypical atypicals” - exquisitely specific for D2C and 5HT1 - the BEST drug at controlling both + and - Sx
Dont use it as 1st line because it causes agranulocytosis (unintended consequence) - causes it so often and so fatal - so in order to put someone on clozapine, have to have tried everything else, and need weekly CBCs for a month and monthly CBCs for a year - put them on a drug that might kill them when there are no other options left
EPS - Tx of each
akathesia - restlessness - Tx: reduce dose
acute dystonia - involuntary spastic contractions (torticolis, handwringing) - eg. oculogyric crisis (eyes get locked looking up or down; not medical emerg) - Tx: anticholinergics (with oculogyric crisis, can also continue the antipsych)
parkinsonism (aka dyskinesia) - park disease = too little dopamine in nigrostriatal tract - if you treat someone with parkinsonism with dopamine agonists, you can induce psychosis, so if you have a nonspecific dopamine antagonist, rather than blocking the mesolimbic tract, you may also block the nigrostriatal tract, causing parkinsonism - Tx: anticholinergics (Tx like parkinsons disease = amantadine)
tardive dyskinesia - irrev sensitization of the system, resulting in facial tics (patient can suppress tics but will speak with funny twitches) - blocked the go signal for mvt and body has responded by upreg dopamine receptors - so treating this with dopamine blockade just makes it worse - Tx: stop the drug
How to pick antipsychotic?
- If patient is perfect patient (know they have disease, want to be fixed, good insight) -use atypical PO (safest, easiest, most compliant)
- Noncompliant? (poor insight, won’t take med). Can use sublingual, but pt will stop taking pills when they get a chance. So can use typical depot.
- Hospitalized pt off meds: start with atypical PO at lowest dose avail, and increase dose qday until (a) psychosis is resolved, or (b) at max dose. If failed at max dose, switch to another atypical at lowest dose. If burn through all options, try typical or clozapine.
- Aggressive pt / psychotic / in ED: B52 them
- Elderly: be on atypicals since they suffer so much from anticholinergic side FX
- Everything else has failed: clozapine
- Fever, tachycardia, altered mental status, lead-pipe rigidity: get CK level and give dantrolene
