Depression/Insomnia Med Chem Flashcards
1
Q
Depression
A
- Multitude of symptoms, lack of objective measures of illness/recovery
- Characterizations: sadness, helplessness, inferiority, despair, worthlessness, crying, guilt, suicidal tendencies, and episodic frequency
- Monoamine reuptake inhibitors, MAOI, and electroshock therapies all elevate monoamines at the synapse and exert antidepressant effects
2
Q
TCA
A
-2 6-member rings and a center 7-member ring
-MoA: inhibits reuptake of neurotrasmitters including NE, DA, and 5HT
-Also possess antagonist effects to some degree for muscarinic and H1 receptors
-Symptoms often not alleviated for 2-4 weeks
SE: dry mouth, blurred vision, decreased GI motility and secretion
Know Imipramine structure
3
Q
SSRI
A
- No 7-membered central ring
- MoA: blocks reuptake of 5HT in CNS (selective)
- Lack some of the SE that TCAs have but the same effectiveness
- Fewer and weaker SE
- Toxic dose is extremely high
- *Know Fluoxetine structure**
4
Q
Hyponotics
A
- Produce drowsiness and help the onset and maintenance of the state of sleep
- Supposed to help resemble natural sleep in EEG characteristics from which the recipient may be easily aroused
5
Q
Hypnotic Activity Spectrum
A
- No line of demarcation between hypnotics and sedatives, often the difference is based in dose
- Sedation, hypnosis, and general anesthesia are usually regarded as merely increasing depths of CNS depression
- Additionally used as anti-epileptics, muscle relaxants, anxiolytics, and adjuncts to general anesthesia due to CNS depression effects
6
Q
Major Sedative-Hyponotic Drug Classes
A
- Barbiturates
- Benzodiazepines
- Zolpidem
7
Q
Barbiturates
A
- Barbital was first drug as a sedative-hypnotic, followed by phenobarbital
- Dominated until benzodiazepines were introduced
8
Q
Barbiturates Structure and Activity
A
- Derivatives of barbituric acid
- MUST be a weak acid and possess a lipid-water partition coefficient within certain limits
- pKa preferably between 7-8
9
Q
Modifications at C-5 - Barbs
A
- Increases lipid solubility until total carbon count is between 6-10
- Then further increasing carbon atoms decreases hypnotic activity despite increased lipid solubility
10
Q
Barb Metabolism
A
- Grouped by duration of action
- Long-acting: anticonvulsants and sedatives
- Short-intermediate: hypnotics
- Ultra-short: IV anesthetics
11
Q
Barbital Metabolism
A
- Undergoes very little metabolism, excreted mostly unchanged in urine
- Detected in urine for as long as 8-12 days
- Duration of action is determined by rate of metabolism
12
Q
Aliphatic Oxidation
A
- Aliphatic substituents at C-5 undergo w-1 hydroxylation if it has 4-5 carbons
- Faster for compounds with longer chains
- Branching hinders the oxidation
13
Q
Aromatic Oxidation
A
- Phenobarbital form of metabolism
- Hydroxylation at the para position on the phenyl ring
- Slow compared to aliphatic oxidation
- Half life ~ 100 hours for phenobarbital
14
Q
Benzodiazepine Spectrum of Activity
A
- Wide spectrum of therapeutic utility
- Used also as muscle relaxants, anesthesia induction agents, anxiolytics, anticonvulsants, and sedative-hypnotics
15
Q
Benzos as Sedative-Hypnotics
A
- No benzo can be exclusively a hypnotic agent
- Many are promoted as specifically sleep inducers
- This promotion based in to PK properties: speed of onset and duration of action
- Quick onsets and half-life tends to be around ~10 hours for most
- *Know Flurazepam structure**
