Pharm

Question 1

Depression hypothesis

Answer 1

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

Question 2

Choosing antidep

Answer 2

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)

Question 3

SSRIs

Answer 3

Fluoxetine
Paroxetine
Sertraline
(Es)Citalopram

for “typical” depression

side FX: decreased libido, serotonin syndrome (esp if no washout; rare)

Question 4

Serotonin syndrome

Answer 4

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

Question 5

Atypical antidepressants

Answer 5

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

Question 6

TCAs: how to use side FX profiles to treat concurrent conditions

Answer 6

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

Question 7

MAOIs

Answer 7

Mainly target norepinephrine (blocking its destruction)

Can cause hypertensive crisis especially when consumed with tyramine

Question 8

Mood disorders: 1st-line Tx

Answer 8

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

Question 9

Valproate

Answer 9

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)

Question 10

2nd line agents for mood

Answer 10

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

Question 11

Benzos

Answer 11

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

Question 12

Tx of anxiety

Answer 12

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)

Question 13

Will knock out someone with severe agitation

Answer 13

“B52” - lorazepam, haloperidol, Benadryl

Question 14

Antipsychotics: indications

Answer 14

For SCZ and other psychotic D/Os

Question 15

+ and - Sx caused by which receptors?

Answer 15

+ 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

Question 16

Typical antipsychotics

Answer 16

Primarily target dopamine, i.e. D-2C antagonists - not specific (block all dopamine) - highly incisive, high side FX - used to treat positive Sx

Question 17

Typical antipsychotics in order of highest to lowest potency

Answer 17

Haloperidol - fluphenazine - thioridazine - chlorpromazine

Question 18

If instead you block dopamine in tubuloinfundibular neurons, you lead to release of ___

Answer 18

prolactin - leads to gynecomastia, galactorrhea, amenorrhea

Question 19

If instead you block dopamine in nigrostriatal tract, you get ____

Answer 19

EPS

Question 20

NMS clin pres & Tx

Answer 20

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

Question 21

2 other side FX of typical antipsych

Answer 21

sedation, anticholinergic

Question 22

Atypical antipsychotics

Answer 22

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.

Question 23

5 atypicals

Answer 23

risperidone, quetiapine, olanzapine, aripiprazole, ziprasadone

Question 24

3 main side FX of atypicals

Answer 24

diabetes, weight gain, prolonged QT (olanzapine rather bad for diabetes and weight gain)

Question 25

Clozapine

Answer 25

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

Question 26

EPS - Tx of each

Answer 26

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

Question 27

How to pick antipsychotic?

Answer 27

1. If patient is perfect patient (know they have disease, want to be fixed, good insight) -use atypical PO (safest, easiest, most compliant)
2. 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.
3. 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.
4. Aggressive pt / psychotic / in ED: B52 them
5. Elderly: be on atypicals since they suffer so much from anticholinergic side FX
6. Everything else has failed: clozapine
7. Fever, tachycardia, altered mental status, lead-pipe rigidity: get CK level and give dantrolene