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CMP – 5-6 Mood Disorders PART B
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Possible Test Questions
- TCAs – cardiovascular and anticholinergic SEs are the big problem, commonly discontinued for these reasons
- Fluvoxamine – CYP450 lots of Drug interactions
- Wellbutrin (buproprion) and Mirtazapine (Remeron) – are the two anti-depressants that DO NOT have sexual
Side effects. Mirtazapine good for elderly folks – helps them sleep, gain weight.
- Always test thyroid before you prescribe Lithium.
- Lamictal and Tegretol  Steven Johnson Syndrome.
- Depakote  neural tube defects.
- Xanax (alprazolam) = shortest half life of all benzodiazepines = most addictive and worst withdrawal
His Random Pearls
- Document reasons for using benzos long term
- Choice of benzo depends on its half life and the route of administration
- May have breakthrough anxiety on once or twice dosing no matter what textbooks say
- Effexor XR and SSRIs are effective alternatives to the benzos, they just take longer to act
- Buspar, if it works at all, works only for chronic anxiety
- SSRIs are the Drug of Choice for panic
- Agoraphobics should be encouraged to get out and explore the world
- Patients with anxiety should minimize caffeine
- GAD can respond to relaxation techniques
- OCD responds to behavior therapy and high doses of SSRIs = may need combo meds
- PTSD – combo of meds.
This lecture was a total clusterf$*k so…you might just want to stop here...just in case though, here is the whole
thing…
Common Neurotransmitter Receptors found in Psych. Drugs and their effects
- SERT – Serotonin Transporter – Serotoin Reuptake Inhibitors (SRI’s or SSRI’s) – i.e. some drugs,
particularly the SSRIs, blockade (antagonize) the SERT  leading to ↓ reuptake of serotonin back into the presynaptic neurons and ↑ serotonin present in the synapse  down regulation of serotonin receptors  >
proportion of serotonin in synapse : serotonin receptors  > binding  make you happy (in theory).
- NET – Norepinephrine Transporter - Norepinephrine Reuptake inhibitors (NRI’s or SNRI’s) - Does the
same thing as SERT except with norepinephrine. SNRI’s = serotonin-norepinephrine reuptake inhibitors – and
can be generally though of as the new anti-depressants that tend to have > stimulating effects as well.
- H1 – Histamine 1 – H1 antagonism (blockade) is a common effect of many drugs, including antihistamines,
TCA’s and others. Common effects of H1 blockade include sedation and weight gain.
- Alpha 1 Adrenergic Receptors – think catecholamines i.e. norepinephrine and epinephrine. Typically in
psych drugs Alpha 1 receptors can be antagonized  leading to the negative side effect of orthostatic
hypotension.
- M1 – Muscarinic cholinergic receptors – blockade of these receptors leads to many common side effects
fitting into the classic anti-cholinergic caterogory - such as dry mouth, constipation, blurred vision.
- 5-HT receptors = The Serotonin Receptors  modulate the release of many other neurotransmitters. There
are several different classes of 5-HT receptors with varying effects depending on whether they are being
agonized or antagonized. Generally speaking (BUT not all the time)…most of the psych drugs are geared to act
as antagonists  exerting their effect by blockade of pre-synaptic autorecptors  extinguishing the negative
feedback loop to the pre-synaptic neuron which would normally down regulate release of serotonin. Many
psychedelic and recreational drugs act as 5HT partial agonists.
o 5HT1A – Agonism  improved cognition, anxiolytic, antidepressant effects (Buspirone and Viibryd)
o 5HT2A – Antagonism  anxiolytic, antidepressant, sleep restoring, ↓ sexual dysfunction
o 5HT2C – Antagonism  anxiolytic, antidepressant, weight gain
o 5HT3 – Antagonism  ↓ GI problems, ↓ nausea
- Dopamine Receptors – the biggest activity of psychotropics on Dopamine receptors has to do with Dopamine
receptor antagonism of anti-psychotic medications…another lecture.
- This list is not at all complete.
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Tri-cyclic Antidepressants – TCA’s
- These are old school antidepressants, the majority of which are not as commonly used anymore d/t the fact
that they are pretty “dirty” i.e. they have lots of activity at lots of different neurotransmitter receptors  lots
off side effects – Cardiovascular and Anticholinergic SE’s TEST QUESTION *$*$*$.
- NT receptor activity of TCAs
o SRI = serotonin re-uptake inhibition (desirable)
o Alpha 1 blockade (side effects)
o Histamine 1 blockade (side effects..mostly)
o NRI = norepi re-uptake inhibition (desirable)
o M1 blockade (side effects…mostly)
SSRIs – Selective Serotonin Reuptake Inhibitors
- The drugs that basically changed everything about how depression is treated. Everyone is on them now.
- Receptor Activity
o Varies depending on the particular drug, but all characterized by significant Serotonin Reuptake
inhibition.
o Receptor Activity items to note:
 Fluoxetine – the first – activating – primarily d/t to additional NRI activity
 Sertraline – cleaner than fluoxetine, at high doses  Dopamine Reuptake Inhibition
 Paroxetine – anticholinergic SEs d/t M1 blockade activity
 Fluvoxamine – lots of Drug interactions
 Citalopram and Escitalopram are related – escitalopram = best-tolerated SSRI
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Third Generation and Special Antidepressants
- 5HT2 Antagonists
o Nefazadone (not really used at all!! Hepatitis association) and Trazadone – used primarily as a
medication to be taken at night to promote sleep…also has some antidepressant qualities…but very
sedating d/t 5HT2 antagonism.
- SNRIs - Venlafaxine and Duloxetine – greatly increased NRI activity.
- Bupoprion - In a class of it’s own – NRI and DRI activity. NO sexual side effects! TEST QUESTION *$*$*$
- Mirtazapine - In a class of it’s own – Alpha 2 antagonism, H1 antagonism and lots of 5HT activity. NO sexual
side effects.
o An alpha-adrenergic receptor blocker with specific action on serotonin 1-3 receptors.
o Causes sedation and weight gain that makes it a perfect medication for SKINNY, NERVOUS,
INSOMNIACS with Depression.
o FEWER sexual side effects. TEST QUESTION *$*$*$
 In combo with SSSRI or SNRI can increase risk of serotonin syndrome.
Medications to Augment Anti-depressants
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Mood Stabilizers – He didn’t really give us much information on these…here is what he did
- Lithium (Lithobid and others)
o Tremor, nausea, hypothyroidism
o Toxic dose close to therapeutic dose
o Excreted in Urine – anything that effects the kidneys effects your lithium level –
- Valproic Acid (Depakote)
o Gastritis
o Liver abnormalities
- Lamotrogine (Lamictal)
o Steven Johnson rash in 3/1000
o Drug of Choice in Bipolar Type II and rapid cycling
Atypical Antipsychotics – D2 and 5HT2A antagonism 
- Dopamine antagonism  ↓ hallucination and delusions
- 5HT2A Antagonism  see above
- The Drugs
o Risperidone (Risperdal)
o Olanzapine (Zyprexa)
o Paliperidone (Invega)
o Aripiprazole (Abilify) – one of the two that do not seem to be as bad re: weight gain and diabetes
o Ziprasidone (Geodon) – one of the two that do not seem to be as bad re: weight gain and diabetes
o Quetiapine (Seroquel) – he described this on as the safest d/t it’s attaching and re-attaching quickly
on D2  less of a D2 efect and more of a serotonin effect.
o Clozapine (Clozaril) –
- Treatment of Acute Agitation in Manic Patients
o Haldol IM (oldschool typical antipsychotic – stronger D2 blockade)
 2.5-10mg
 Adverse events
 Akathisia – 9%
 EPS – 11.5%
 Dystonia – 8%
 Hypertonia – 10%
 QT prolongation
 Calming dose dopes people up
o Geodon IM
 10-20mg
 Adverse events
 Same as Haldol, but far less common
 Calms without obtunding
 Similar QT prolongation.
CMP – 5-6 Mood Disorders PART B
Anxiety Disorder Drugs and Tx.
Buspirone (Buspar)
- Selectively binds to 5HT1A receptors – partial serotonin agonist
- No sedation or addiction potential
- 15 mg TID
- Side effects = dizziness 9%, nausea 3%, HA 3%
- No better than placebo
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Dependence and Addiction
- Therapeutic Dependence = medication mitigates clinical manifestations
- Psychological Dependence = craving for the pleasurable experiences the drug arouses and/or compulsion to
take a drug to avoid discomfort.
- Physical Dependence = physiologic symptoms occur when the drug is withdrawn
o Shorter the half life, the more intense the withdrawal. TEST QUESTION *$*$*$
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