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82 Cards in this Set

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  • Back
What is the amino acid precursor for serotonin (5-HT)?
Tryptophan
Enzymes Tryptophan hydroxylase and 5-HTP decarboxylase are involved in the production of which neurotransmitter
Serotonin
What is the amino acid precursor for Norepinephrine (NE)?
Tyrosine
What is the rate limiting step in the synthesis of NE?
Tyrosine hydroxylase (first step in synthesis)
What is the rate limiting step in the synthesis of 5-HT?
Tryptophan hydroxylase (first step in synthesis)
What enzyme mediates the uptake of NE and 5-HT into vesicles?
VMAT
What enzyme mediates the degradation of NE and 5-HT?
MAO
(T/F) Only one of the 5-HT receptors are G-protein coupled?
False! All but one are G-protein coupled
Four serotonin receptors that are important for clinical depression:
-5HT1A
-5HT1D
-5HT2A
-5HT2C
What is 5HT1A? Where is it located?
This is a serotonin receptor.

It is located on sertonergic cell bodies in the raphe nuclei, and on postsynaptic neurons in the hippocampus
What is 5HT1D? What does it do?
This is a serotonin receptor.

It mediates the autoinhibitory mechanisms of 5HT neurotransmission at axon terminals
Name 4 NE receptor types.

Bonus: Which one is critical for autoinhibitory actions or NE neurotransmission?
Four types = Alpha1, Alpha2, Beta1, and Beta2.

Alpha 2 is critical for autoinhibitory actions
Which antihypertensive drug led to the discovery that 5-HT and NE are implicated in depression?
Reserpine. The drug inhibited the transport of these transmitters (plus dopamine) into synaptic vesicles.
Depression is not simply a deficiency of neurotransmitters, but is instead related to ____________?
Deficiency in receptor sensitivity
How do monoamine oxidase inhibitors work?
They stop the enzymatic destruction (deamination) of neurotransmitter.

Therefore, more is available.
What is a long term result of MAO blockade?
Neurotransmitter receptors can be down-regulated through desensitization.
Which type of antidepressants block the reuptake pump for neurotransmitters?
Tricyclic antidepressants
Blocking which subtype of MAO leads to antidepressant effects?
MAO-A
Review: Which drug is a selective MAO-B inhibitor that is also used in Parkinson's?
Selegiline
Phenelzine is a drug in which class?
MAO inhibitors (MAO-A?)
Which drug class can lead to a hypertensive crisis when foods containing tyramine are consumed?
MAO-A inhibitors
What are common (non-dietary) side effects you see with MAO inhibitors?
Weight gain, orthostatic hypotension, lightheadedness, and sedation, sexual dysfunction

The orthostatic hypotension and lightheadedness are an effect of alpha-adrenergic blockade.
What are the symptoms of a hypertensive crisis (besides hypertension)
headache, nausea, sweating, pallor, vomiting, and hyperpyrexia.
Five drugs that interact with MAO inhibitors:
-Stimulants
-Sympathomimetics (including OTCs)
-Other antidepressants
-L-Dopa
-Opioids (especially meperidine)
Do tri-cyclic antidepressants affect dopamine uptake?
No!
Name four representative TCA medications that we should know:

Which ones have the most side effects? Which ones have the lowest?
-Imipramine
-Amitriptyline
-Desipramine
-Notriptyline

Amitriptyline has the most side effects, while desipramine & nortriptyline have the fewest.
What is the most dangerous side effect of TCA's?
Cardiovascular problems

They affect sodium channels causing potentially lethal conducting delays.
TCAs actually have 5 actions. Name them:
1. Blocking reuptake of serotonin
2. blocking reuptake of NE
3. Blocking alpha 1 adrenergic receptors
4. Blocking histamine receptors
5. Blocking muscarinic receptors
Sedation, weight gain, impaired coordination, orthostatic hypotension falls, and cognitive impairment are side effects caused by which action of TCAs?
Histaminic action
Dry mouth, constipation, urinary hesitancy, aggravated glaucoma, tachycardia, and impotence are caused by which action of TCAs?
Muscarinic blockade
Orthostatic hypotension, dizziness, reflex tachycardia, ejaculation difficulties, cognitive impairment, and tachycari are side effects of which action of TCAs?
Alpha-adrenergic blockade
Anxiety, jitteriness, anorexia, nausea, diarrhea, insomnia, sedation, weight gain, and sexual side effects (desire/arousal/orgasm) are side effects caused by which action of TCAs?
Serotonin reuptake blockade
Anxiety, tremor, and tachycardia are side effects caused by which action of TCA's?
Norepinephrine reuptake blockade
In addition to depression, what 4 other disorders do SSRIs treat?
OCD
Panic disorder
PTSD
Social phobias
SSRI's inhibit serotonin reuptake which increases serotonin levels. This leads to which two effects?
Increased 5-HT receptor activation
Enhanced postsynaptic response
Name four representative drugs of SSRIs that we should know:
Fluoxetin
Sertraline
Paroxetine
Citalopram
Besides blocking serotonin reuptake, what other neurotransmitter receptors are affected by SSRI's (there's a whole bunch)
NE reuptake inhibition
Dopamine reuptake inhibition
Serotonin 2C agonist actions
Muscarininc antagonist actions
Sigma interactions
Inhibition of nitric oxide synthetase
CYP450 / 2DC / 3A4 / 1A2
What happens to the somatodendritic area of the serotonin neuron as a result of SSRI administration?
The autoreceptors become desensitized
What happens as a result of down-regulation of dendritic autoreceptors?
the neuron releases more 5HT at the axon terminal

This takes time (2 weeks)
What (possibly) explains the reduction in side effects seen as SSRI tolerance develops?
Desensitization of postsynaptic serotonin receptors
What are the hallmarks of serotonin syndrome?

What can cause serotonin syndrome
Mental and autonomic disturbances
(confusion, insomnia, diaphoresis, hyperpyrexia, tachycardia, hypertension, rigidity, tremor)
Caused by 5HT overactivity. Often when SSRIs are administered with another serotonergic drug.
Describe the withdrawal syndrome seen with discontinuing SSRIs?

Who is affected most?
Which drug is less likely to cause withdrawal?
Flu-like symptoms, restlessness, confusion, irritability, sleep disruption.

More commonly seen in neonate

Longer lasting drugs (like fluoxetine) are less likely to cause withdrawal symptoms
What do you have to worry about when prescribing Venlafaxine?
Increase in diastolic blood pressure
Name two mixed NE-5HT reuptake inhibitors (SNRIs)
Venlafaxine & Duloxetine
Which antidepressant is an alpha-2adrenergic antagonist that enhances noradrenergic neurotransmission. This drug also increases neurotransmission of serotonin via 5HT2A blockade.
Mirtazapine
Which drug has an unclear mechanism that involves augmenting NE release, dopamine reuptake inhibition, and comes with an increased risk of seizures. The drug is also used to reduce craving associated with smoking?
Bupropion
Which antidepressant is a 5HT2a antagonist, is associated with priapism (penis stays erect), and is extremely sedating. It is also used in low doses to treat insomnia.
Trazodone
Which antidepressant, which is now off the market, is associated with hepatic compromise?
Nefazodone
What is the take home message regarding antidepressant use and suicide?
Antidepressant use has been linked to suicide (especially in children); however, the risk of taking a person off antidepressants can be even worse than keeping them on the drugs
(T/F) Overdosing by ingesting as little as a 7 to 10 day supply of MAOIs, TCAs, and SSRIs can be fatal.
False! An overdose of 7-10 days worth of meds can be fatal for MAOIs and TCAs, but you would need much more to die from an SSRI overdose (25 days worth of pills)
(T/F) TCAs are more effective, overall, in treating depression compared to SSRIs
False! They both have the same efficacy overall
Which drug class has the slight advantage in treating severe depression?
TCAs (slight edge over SSRIs)
What is the standard of care in treating psychotic depression?
Combining antidepressants with an antipsychotic
In which population of patients should you implement a start low, go slow principle when using drugs to treat depression?
The elderly
What considerations should you make when treating depression in someone who has a co-morbid medical illness?
-Drug clearance
-Side effect vulnerabilities (cardiac problems / seizures)
- Risk of untreated depression
- iatrogenic depression
Which side effect of drug therapy is linked to increased risk in suicidal patients?
Akathisia (unpleasant inner restlessness)
The metabolism of most anti-depressants involves which class of metabolic enzymes?
P450 isoenzymes
What is the take home message of using antidepressants in pregnancy?
The drugs often cross into the placenta and breast milk. There is some evidence that they cause an increase in spontaneous abortions
However, the risk of untreated depression in terms of smoking, alcohol use, attachment, and maternal functioning may be worse.
What is the single most effective treatment for depression and acute mania?
Electroconvulsive therapy (ECT)
(T/F) What you seen in the movies about electroconvulsive therapy causing amnesia and long term memory loss is common and neurological damage can be seen on autopsies.

(Please don't miss this one!)
False. Amnesia is very rare
Bright light therapy is particularly useful in which type of mood disorder?
Seasonal affective disorder (SAD)
Although evidence is mixed about St. John's wart, the current thinking is that its actions are similar to which class of antidepressants?
MAO inhibitors
St. John's Wart interferes with which classes of drugs?
Immunosuppressants, oral contraceptives, oral anticoagulants, and HIV protease inhibitors

It may reduce bioavailability of digoxin.
This drug blocks the phosphatidylinositol signaling cascade by inhibiting inositol phosphatase
Lithium
Which is the only bipolar medication known to decrease the risk of suicide in someone with bipolar disorder?
Lithium
Lithium is eliminated through which organ system?
Renal!
What are the dietary considerations when using lithium?
As sodium intake increases less lithium can be absorbed resulting in increased lithium excretion.
Conversely, decreased sodium intake results in increased lithium absorption
Hyperthyroidism is a major concern in the long term use of which drug
Lithium
(T/F) The majority of patients will experience at least one side effect when taking Lithium.
True
What is the therapeutic index of lithium? What does imply?
Lithium has a narrow therapeutic index

This implies that it doesn't take much of an overdose to kill someone (about 7 days worth of lithium)
Signs and symptoms of early lithium overdose:
Marked, coarsened tremor, nausea, vomiting, diarrhea,
vertigo, blurred vision, frank delirium, increased deep tendon reflexes.
Four drugs that cause an elevation in lithium levels:
ACE inhibitors, NSAIDs, Diuretics, some antibiotics
Five drugs that can a decrease in lithium levels:
Caffeine
Carbonic anhydrase inhibitor diuretics
Laxatives
Osmotic diuretics
Theophylline
What is the consensus when it comes to using lithium during pregnancy:
Lithium is well known to cause problems (Ebstein's anomaly among other complications)
However; it's not as bad as we once thought it was and lithium is probably safer than other bi-polar medications
How does Valproic acid work?
It increases brain concentrations of GABA in CNS
Also, it may inhibit enzymes that catabolize GABA or block reuptake of GABA
Valproic acid is approved for which phase of bipolar, and which type of bipolar disorder?
It is approved for MANIC phase, and rapid cycling bipolar disorder
What is the main teratogenic defect seen in valproic acid?
Neural tube defects
What is the rule of thumb when prescribing valproic acid to women of child-bearing age?
Don't do it!
What is an attractive alternate to carbamazepine?
oxcarbazepine
Which other drug, besides valproic acid can cause teratogenic problems?
Carbamezepine
What is Stevens-Johnson syndrome? Which bipolar medication has been associated with it?
A dangerous rash, the syndrome is associated with lamotrigine
Does the evidence support using anticonvulsants like topiramate or gabapentin to treat bipolar disorders?
Nope