Lecture 4: Antidepressants Flashcards
What is the MONOAMINE HYPOTHESIS?
Enhancement of monoamine neurotransmission.
what does RESERPINE do?
a. What happens to peeps who are treated with this drug?
Depletes neurons of NR and 5-HT
a. Develop depression
Why do we think it takes 2-3 weeks for Antidepressant effect to work?
we think it’s due to NEURONAL PLASTICITY.
What is the NEUROTROPHIC HYPOTHESIS
Loss of Neurotrophic agents may contribute to depression. We think it’s due to BDNF. This can lead to NEURONAL LOSS in the HIPPOCAMPUS
What is the NEUROENDOCRINE HYPOTHESIS?
Depression due to DYSREGULATION of the HPA Axis. Peeps w/depression may have increased Glucocorticoid release in response to stress.
What is the LONG-TERM treatment w/Antidepressants?
They Down Regulate Auto-receptors. Increases Firing rate of Amine Neurons
TCAs
- What do they inhibit?
- Tertiary Amines do what?
a. Major side effect?
b. What 2 are there? (AI) - Secondary Amines do what?
a. Side effects? (2)
b. What 2 are there? (ND)
- Uptake of NE and 5-HT
- Inhibit 5HT and NE Re-UPTAKE
a. They’re very sedating
b. Amitriptyline and Imipramine - More effect on NE Re-Uptake
a. Less sedating, FEWER CARDIOVASCULAR EFFECTS
b. Nortriptyline and Desipramine
TCAs
- What other 3 Receptors do they BLOCK?
- Abuse potential?
- What do they do for depressed patients?
- A-ADRENERGIC, HISTAMINE, and MUSCARINIC RECEPTORS
- Low. Don’t produce euphoria
- Improve mood, increase appetite, and improve sleep patterns
TCAs: Pharmacokinetics
- How do you take them?
- Length of Half Life?
- What metabolizes them?
- oral
- Long
- Liver: DRUG INTERACTIONS COMMON
TCAs: Pharmacological Effects
- CNS
a. drowsiness and sedation occurs form blockade of what receptors?
b. Which drugs are more sedating?
c. Analgesia results from ACTIVATION of what? What does this do?
d. Impairment of memory and cognition due to effects of what?
- a. of HISTAMINE RECEPTORS
b. Tertiary Amines
c. of Descending Noradrenergic Pathways in spinal cord; Increases Endorphin Release and Decreases Substance P release
d. Anticholinergic Effects
TCAs: Pharmacological Effects
- Peripheral
a. What can develop in the Heart?
- a. Cardiac Arrhythmias. (TORSADES DE POINTES)
TCAs: Uses
- Depression or PANIC DISORDER
a. Why are they not used often for this?
b. What gets used in its place?
c. What TCA is considered the STANDARD of EFFICACY in DEPRESSION? - Chronic Pain
a. Best at what doses? - Fibromyalgia
a. TCAs treat this. What do we think causes it? - ENURESIS: What drug is used?
- a. Due to Toxicity and Side Effects
b. SSRIs more commonly used
c. Imipramine - a. Much lower than those for treating depression. (10% of that used for Depression)
- a. it’s muscle pain. Thought to be caused by Poor Sleep. Dose is much lower than those needed for Antidepressant
- Imipramine is commonly used for this purpose
TCAs: Side Effects
- What results in blurred vision, tachycardia, constipation, dry mouth, palpitations?
a. Effects are more common with which compounds? - CARDIOVASCULAR EFFECTS due to what?
- What is VERY COMMON?
- What do we see in patients w/history of seizures and in children?
- What happens to ADH?
- What happens to sexual use?
- Can they be used in pregnancy?
- CHOLINERGIC BLOCKADE
a. Tertiary Compounds - Alpha 1 block. (AVOID TCAs in patients w/Myocardial Infarction)
- WEIGHT GAIN
- DECREASE IN SEIZURE THRESHOLD
- INAPPROPRIATE ADH SECRETION
- SEXUAL DYSFUNCTION is very common
- YES
TCAs: OVERDOSE
- What can happen?
- Treatment?
They’re very dangerous when Overdosed. Depressed pt’s can be suicidal….so do small amts at first, no refill.
- Cardiac monitoring, supportive care; Gastric Lavage and Charcoal; Magnesium and Isoproteronal and cardia pacing for Torsades de pointes.
Lidocaine, propranolol, and phenytoin to manage arrhythmias and/or prevent seizures
Sodium bicarbonate and potassium chloride to restore acid base balance
TCAs: Drug Interactions
- What can Cause SEROTONIN SYNDROME?
a. What is it?
b. When should you stop TCAs? - Combination of what can cause TCAs to reach Toxic Levels?
- MAOIs and TCAs together
a. Severe CNS toxicity: Hyperpyrexia, Convulsions, Coma
b. 2-3 wks before administration of a MAOI - FLUOXETINE and other SSRIs