Antidepressants and Anxiolytics Med Chem Flashcards
What is the most common mood disorder in adults?
Major depressive disorder
Criteria required for diagnosis of major depressive disorder
One or more depressive episodes without a history of manic, mixed or hypomanic episodes
Monoamine hypothesis
Deficiency or imbalances in the monoamine neurotransmitters (serotonin, norepinephrine, dopamine) causes depression
Based on the monoamine hypothesis, increasing which two neurotransmitters could alleviate depression?
Serotonin and norepinephrine
Drugs that selectively increase which neurotransmitter decrease depression?
Serotonin
Hypercholinergic hypothesis of depression
Hyperactivity of cholinergic system and excessive nicotinic receptor activity can lead to depression
Examples of antidepressants with nicotinic acetylcholine receptor inhibitory activity
Bupropion
Nicotinic transdermal patch
Which amino acid is a precursor for serotonin?
Tryptophan
Which enzyme is responsible for serotonin synthesis?
Tryptophan hydroxylase
Which amino acid is a precursor for norepinephrine?
Tyrosine
Which enzyme is responsible for norepinephrine synthesis?
Tyrosine hydroxylase
True or false: For all monoamines, the first synthetic step is rate limiting
True
Serotonin is transported into the vesicles via what?
Vesicular monoamine transporter (VMAT)
Reserpine binds irreversibly to what to inhibit packaging of DA, NE, EPI, and 5-HT into vesicles?
VMAT
What two compounds degrade serotonin?
Monoamine oxidase (MAO) and catechol-O-methyl-transferase (COMT)
MAO inhibitor MOA
Increase serotonin and norepinephrine available in the cytoplasm by blocking the deamination of monoamines via MAO
MAOi contrindications
Concomitant use of: sympathomimetic drugs, other MAOIs, L-DOPA, L-tryptophan, phenylalanine, bupropion, excessive coffee, chocolate intake, high tyramine containing foods, heart failure, general anesthesia, local anesthesia with vasoconstrictors, liver disease
What is the result of MAOi use with high levels of tyramine?
Hypertension
Between tertiary and secondary amines, which exhibit more selectivity?
Secondary amines selectively inhibit norepinephrine reuptake (still have some serotonin reuptake activity)
Examples of tertiary amine TCAs
Clomipramine
Imipramine
Doxepin
Amitriptyline
Fluoxetine 20mg target plasma level
200 ng/mL
SSRI contraindication
Concomitant use of MAOi
Concomitant use of SSRIs and MAOis can lead to what?
Serotonin syndrome
SSRI monotherapy in bipolar patients can lead to what?
Mania
SSRI examples
Fluoxetine
Paroxetine
Sertraline
Fluvoxamine
Citalopram
Escitalopram
SNRI contraindication
Concomitant use of MAOi
SNRI examples
Venlafaxine
Desvenlafaxine
Duloxetine
Milnacipran
Levomilnacipran
Bupropion (NDRI) contraindications
Concomitant use of MAOi
Seizure disorders
Eating disorders
Patients undergoing abrupt discontinuation of alcohol or sedatives
Common adverse effects of agents with mixed serotonergic effects
Nausea, vomiting, diarrhea, constipation, dizziness
Examples of mood stabilizers
Carbamazepine
Valproic acid
Lithium carbonate
Lithium MOA
Therapeutic plasma levels of lithium deplete inositol pool available for resynthesis, reducing neuronal activity in the brain
The R-enantiomer of ketamine has a (higher/lower) affinity for NMDA receptors than the S-enantiomer
Lower
Esketamine contraindications
Ketamine hypersensitivity, aneurysmal vascular disease, intracerebral hemorrhage
Ketamine MOA
NMDA receptor antagonist; increases synaptic glutamate activity
Generalized anxiety disorder
Persistent and excessive anxiety and worry
Panic disorder
Recurrent unexpected panic attacks and is persistently concerned or worried about having more panic attacks or changes their behavior in maladaptive ways because of panic attacks
Social anxiety disorder
Fearful or anxious about or avoidant of social interactions and situations
Substance/medication-induced anxiety disorder
Substance intoxication or withdrawal or to a medication treatment
(Ionotropic/Metabotropic) GABA receptors bind GABA and open intrinsic Cl- channels
Ionotropic (GABAa)
Which drug class is most effective and most commonly prescribed drugs for rapid relief of anxiety symptoms?
Benzodiazepines
Benzodiazepine MOA
Positive allosteric modulators that enhance GABAa receptor channels in the presence of GABA
Benzodiazepine antagonist
Flumazenil (Romazicon)
What pharmacokinetic property of benzodiazepines explains their rapid and complete absorption?
Highly lipophilic
Classify and explain reaction between benzodiazepines and alcohol
Pharmacodynamic. Additive CNS depressive effects
Classify and explain reaction between benzodiazepines and CYP450 inhibitors (ketoconazole, ritonavir, etc.)
Pharmacokinetic. Increase concentration of benzodiazepines
Which class of agents are considered first line in managing generalized anxiety disorder?
Antidepressants
What is the place of therapy of buspirone in managing generalized anxiety disorder?
Second line agent
