Lec. 5: Antidepressants Flashcards
What are the two main categories of 1st generation drugs for depression?
- Tricyclic
2. MAO Inhibitors
What are the four main categories for the 2nd and 3rd generation drugs used to treat depression?
- Tetracyclics and Unicyclics
- 5-HT(2) antagonists
- SSRI
- SNRI
What is the hypothesis of the pathophysiology of depression?
The monoamine hypothesis
What is the monoamine hypothesis?
Depletion of monoamines in CNS causes symptoms of depression.
What are the main monoamines in the monamine hypothesis?
NE and serotonin
What is the main action of most antidepressant drugs?
Increase neurotransmission of amines (5-HT and NE)
Antidepressant drugs are categorized based on their effect on the re-uptake of ? or ?.
- Ne
2. 5-HT
Name two antidepressants that have little effect on re-uptake of either 5-HT or NE.
- Bupropion
2. Mirtazapine
Name the drug that inhibits NE re-uptake with great potency (about 500-fold more than 5-HT reuptake).
Maprotiline
T or F. Drugs that inhibit 5-HT reuptake with greater potency will have greater than 100-fold more than the inhibition on NE reuptake.
False. 50-fold
T or F. There are also drugs that inhibit reuptake of NE and 5-HT with similar potencies.
True
Tricyclic antidepressants are ? generation antidepressants. List five examples.
1st generation
- Imipramine
- Desipramine
- Amitriptyline
- Protriptyline
- Doxepine
List seven mechanisms of action of tricyclic antidepressants.
- Blockade of NE uptake
- Blockade of serotonin reuptake
- Blockade of muscarinic/cholinergic receptors
- Blockade of alpha-1 NE receptors
- Blockade of alpha-2 NE receptors
- Blockade of histamine H1 receptors
- Blockade of cardiac Na channels and Na pump
List the five most common areas effected by TCAs.
- Sympathomimetic
- Cardiovascular
- Endocrine/metabolic
- Anticholinergic
- Neurological
What are three sympathomimetic side effects of TCAs?
- Hypotension
- Compensatory tachycardia
- Tremors
What are three cardiovascular side effects of TCAs?
- Orthostatic hypotension
- ECG abnormalities
- Arrhythmias
What is a endocrine side effect of TCAs?
Weight gain
What are five anticholinergic side effects of TCAs?
- Dry mouth
- Blurred vision
- Constipation
- Urinary hesitancy
- Loss of libido and ED
What are three neurological side effects of TCAs?
- Paresthesias
- Seizures
- Hallucinations
Sedative effects of TCAs are enhanced by ?. Some examples include (name three).
CNS depressants
- BZDs
- Barbiturates
- Alcohol
Inhibitors of ? enzyme will increase the concentration of TCAs.
Cytochrome P-450
Name an example of an induce of cytochrome P-450.
Carbamazepine
Name two examples of monoamine oxidase inhibitors.
- Phenelzine
2. Tranylcypromine
T or F. Both Phenelzine and Tranylcypromine irreversibly inhibit MAO-A and MAO-B enzymes.
True
Combination of antidepressants and ? may cause malignant serotonin syndrome?
MAOI
MAO-A is located in the ? and preferentially oxidizes ?.
- Gut
2. 5-HT
MAO-B is located in ? and preferentially oxidizes ?.
- Platelets
2. Dopamine
Would you consider MAOI a first line drug for depression?
No. Phenelzine and Tranylcypromine should not be used as first line drugs for depression due to serious adverse effects.
What does SSRI stand for?
Selective Serotonin Reuptake Inhibitor
Name five examples of SSRI drugs.
- Fluoxetine
- Sertraline
- Paroxetine
- Citalopram
- Escitalopram
What serotonin receptor is mainly responsible for adverse effects?
5-HT(2) and 5-HT(3)
What serotonin receptor is primarily involved in antidepressants and anxiolytic activity?
5-HT(1)
What is the main mechanism of action of SSRIs?
They block the reuptake of 5-HT and enhance postsynaptic activity at all serotonin receptors.
T or F. A side effect of SSRI antidepressant drugs is suicidal ideation.
True
Serotonin syndrome is associated with what antidepressant drug?
SSRIs (selective serotonin reuptake inhibitors)
Name three second generation antidepressants that are categorized as 5-HT(2) antagonists.
- Trazodone
- Nefazodone
- Bupropion
Name the three second generation antidepressants that are categorized as TETRAcyclic and UNIcyclic.
- Amoxapine
- Maprotiline
- Mirtazepine
T or F. The major anti-depressant drugs are equally effective in relieving depression but vary in producing undesirable side effects.
True
What is the main difference between tricyclic antidepressants and 2nd/3red generation antidepressants?
The degree of sedation and their anti-muscarininc effects.
What is the main line drug used to treat bipolar disorder?
Lithium salts
Describe the two mechanisms of action for Lithium salts in treating bipolar disorder.
- Li+ inhibits inositol monophophatase, which inhibits intracellular signaling.
- Li+ inhibits glycogen synthase kinase-3b and cell-cell interaction.
T or F. Lithium has a wide therapeutic index.
False. The therapeutic range of Li+ is between 1.0-1.2 mEq/liter
What is considered a lethal toxicity dose when taking Li+?
Anything greater than 5 mEq/liter
How does an decrease in Na+ excretion, thiazide diuretics, ACE inhibitors, and NSAIDs all relate to Li+ toxicity?
They all lead to an increase in Li+ retention and potential toxicity
What two substances promote Li+ excretion?
- Caffeine
2. Alcohol
Bipolar disorder is alternating episodes of ? and ?.
- Depression
2. Mania
What does SNRI (drugs used to treat depression) stand for?
Serotonin Norepinephrin reuptake inhibitor
Name the two drugs used to treat depression that are serotonin NE reuptake inhibitors.
- Venlafaxine
2. Desvenlafaxine
