Sedative-Hypnotics/Anti-anxiety
What is the mechanism of action of Benzodiazepines?
Increase effects of GABA by binding to GABA receptors in the CNS, and inhibit neuronal activity by increasing the conductance of chloride ions into the neuron making it harder to raise the neuron to its firing threshold
What are the types of antidepressants?
-SSRIs: selective serotonin reuptake inhibitors
-SNRIs: serotonin-norepinephrine reuptake inhibitors
-Tricyclics
-MAO inhibitors: monoamine oxidase inhibitors
-Others: Nefazodone (Serzone) and Trazodone (Desyrel), Bupropion (Wellbutrin), and Mirtazapine (Remeron)
What is the classic treatment for bipolar syndrome? What does it do?
-lithium
-mood stabilizer, prevents manic episodes
What is the mechanism of action of anti-psychotics?
block CNS dopamine receptors, especially D2 receptors in mesolimbic pathways
What is the mechanism of action of indirect cholinergic stimulants?
-drug inhibits cholinesterase enzyme
-ACh breakdown is inhibited
-ACh activity/effects are prolonged
What are the adverse effects of sedative-hypnotics and anti-anxiety drugs?
-residual (hangover) effects; anterograde amnesia
-complex behaviors (sleepwalking/driving)
sed-hyp and anti-anxiety:
-rebound effect (insomnia, increased anxiety)
-falls
-tolerance and dependence
-BZDa: possible link to Alzheimer's Disease
What is the mechanism of action of antidepressants?
prolong effects of amine neurotransmitters by either:
-inhibiting reuptake of one or more amine neurotransmitters (SSRIs, SNRIs, Tricyclics, Others)
-decreasing neurotransmitter breakdown (MAO inhibitors)
How is lithium eliminated by the body? Why can this be a problem?
-intact by kidneys
-can accumulate rapidly, causing lithium toxicity
What are some adverse effects of antipsychotics?
-traditional agents: OH, sedation, and anticholinergic effects
-atypical (newer agents): weight gain, disturbed lipid/glucose metabolism
-primary concern all anti-psychotics: extrapyramidal (motor) side effects
What is the mechanism of action of Memantine (Namenda)?
-blocks NMDA-glutamate receptors in the brain (too much glutamate might promote damage causing Alzheimer's Disease)
-drug therapy normalizes glutamate influence
What are some non-drug strategies that might compliment and eventually replace these drugs?
-regular exercise
-decrease caffeine, ETOH intake
-establish "pre-bedtime" routine
-sleep environment
-dark, quiet room
-no TV, phone
-soothing sounds; white noise
Anxiety:
-regular exercise
-try to identify and reduce source of anxiety
-counseling, support groups
-use meditation, relaxation techniques (breathing, imagery, etc.)
What are the adverse effects of antidepressants?
-tricyclics: sedation, anticholinergic effects, CV (OH, arrhythmias), seizures, and increased risk of fatal OD
-MAO inhibitors: CNS excitation, increase BP (especially with other drugs/foods that catecholamine release)
-SSRIs, SNRIs: generally better tolerated, may increase seizures, some GI problems
What systems will lithium toxicity effect?
CNS, GI, CV, Renal
What are the extrapyramidal side effects? What causes them?
-tardive dyskinesia
-pseudo parkinsonism
-akathisia
-other dystonias, dyskinesia
Cause:
-disruption in dopamine activity in the limbic system
What is the mechanism of action of Aducanumab (Aduhelm)?
- antibody; binds to amyloid beta protein fragments; decreases their ability to accumulate into plaques in brain neurons
What are some sedation-hypnotics/anti-anxiety rehab concerns?
-treat "symptoms", do not treat the cause of insomnia, anxiety
-trade-off: benefits versus sedation, risk of falls, possible long-term effects on brain
-trend towards non-benzodiazepine sedative-hypnotics and anxiolytics
What is serotonin syndrome?
-possible with all antidepressants
-occurs when CNS serotonin receptors are overstimulated
-symptoms: increased HR/BP, confusion, hallucinations, agitation, sweating, shivering, dystonias, dyskinesia, muscle pain, GI problems
-usually reversible, can be fatal if left unchecked
What are the other bipolar treatments?
-Cariprazine (Vraylar): partial agonist D3/2 and 5-HT1A; antagonist 5-HT2A
-other drugs with anti-manic effects:
--anti-seizure drugs: carbamazepine, valproate, gabapentin, and lamotrigine
--anti-psychotics: aripiprazole, clozapine, and resperidone
What is tardive dyskinesia? What is the best treatment?
What:
-extensive movements around the face/jaw
-most feared because it is permanent
Treatment:
-early recognition
-change in type or dose of drug
-drugs that block vesicular transporters in pre-synaptic terminals which will prevent storage of monoamines (DA,NE,5HT) in pre-synaptic terminals and deplete neurotransmitters from these terminals
What drugs are used to improve or modify behavior? What changes has the government made to these drugs?
Drugs:
-antidepressants
-anti-anxiety agents
-anti-psychotics
Government:
-curb use of anti-psychotics
-more emphasis on using symptom-specific medications
What are the primary goals of sedative-hypnotics and anti-anxiety drugs?
-relax patient
-promote "normal" sleep
-decrease anxiety
What is the time lag of antidepressants before beneficial effects?
-often 1-2 weeks before taking effect
-may take 6-8 weeks for max effect
How can ketamine be used as an antidepressant?
-blocks NMDA receptors; decreases effects of excitatory amino acids (glutamate)
-ketamine and metabolites may also affect many other receptors (GABA, DA, 5-HT, opioid, ACh, and ion channels)
-sub-anesthetic doses may cause a decrease in depression in severe, resistant cases that have not responded to other treatments
What is Neuroleptic malignant syndrome? (symptoms, risk factors, prognosis)
-can occur with all anti-psychotics
-symptoms: catatonia, rigidity, tremors, fever
-increased risk if high dose, agitated patient, impaired mental function
-can be fatal; critical need to detect early, d/c drug
Why are anti-dementia drug effects lost?
-effectiveness is lost when neurons have degenerated beyond a certain point
-the drugs won't work if these neurons degenerate to the point where they are no longer producing this neurotransmitter (ACh)