CNS Part I Flashcards
Describe the blood brain barrier (BBB)
- Highly selective
- Diffusion: non polar and lipophilic
- Carrier mediated
- Efflux systems: transport substances out of the brain
List the excitatory neurotransmitters
- Acetylcholine
- Glutamate
- Substance P
- Enkephalins
List the inhibitory neurotransmitters
- Norepinephrine
- Dopamine
- Serotonin
- GABA
Sites of drug action Slide 8
- re-uptake labeled 6 on image
Basics of sedative hypnotics
- 2 Main categories: Benzodiazepines. and Non-benzodiazepines
- Main uses: sleep (hypnosis), anxiety, seizures
- Pharmacokinetics: highly lipid soluble, metabolized via liver; adipose sequestering and active metabolics
Effects of sedative hypnotics Slide 11
Describe a GABA receptor
- Ion channel receptor
- Inhibitory neurotransmitter: GABA binds & allows more chloride ions to enter the cell this causes the cell to be hyper-polarized
- Sedative hypnotics either mimic GABA or enhance the binding of GABA
Slide 13 for benzodiazepines
Describe Benzodiazepines
- MOA: bind to the benzodiazepine receptor & facilitate opening of the GABA receptor
- SE: anterograde amnesia (memory loss), residual. effects (drowsiness, confusion, psychomotor slowing), tolerance & dependence
Define tolerance and dependence
- Tolerance: more drug is needed to have the same effect over time
- Dependence: withdrawal symptoms occur. when the drug is stopped; not the same as addiction
Slide 16
Describe benzodiazepines and older adults
- Increased body fat leading. to more adipose sequestering
- Increased susceptibility to side effects
- Decreased metabolism
Describe barbiturates
- MOA: binding site on the GABA receptor & increase the duration the GABA receptor is open; antagonize glutamate
- SE: narrow therapeutic index high abuse potential
Slide 19 and 20
Describe Z drugs
- MOA: selective agonist of GABA receptor
- SE: complex sleep behavior (black box), psychomotor slowing (increased in elderly), psychiatric & behavioral effects
Effects on rehabilitation
- Adverse drug reactions: sedation, musculoskeletal, and other somatic effects
- Decreased arousal or alertness
- Motor control dysfunction: weakness, increased response time, altered central processing, impaired function ability
Possible therapy solutions to the effects of CNS drugs on rehabilitation
- Explore options with physician regarding the risks & benefits. of the medication
- Schedule. therapy when drug levels. are the lowest in the system if excessive hangover or sedative effects are problematic
(True/False) Newer hypnotics do not produce excessive hangover effects. Also, for chronic anxiety conditions, antidepressants that are nonsedating like the selective serotonin reuptake inhibitors (SSRIs) may be more appropriate drugs
- True
Define depression
- Depressed mood or loss of interest or pleasure in daily activities for more than 2. weeks
NIH 2020 drug use and health survey for antidepressants
- 8.4% of all US adults
- Twice as prevalent in females as males
- Prevalence decreased with age
Pathophysiology of depression
- Complex interaction between genetic, environmental, and biochemical factors
- Disturbances in neurotransmitters: Serotonin, Norepinephrine, and Dopamine
Describe selective serotonin receptor inhibitor (SSRI)
- MOA: inhibit the re-uptake of serotonin into the presynaptic nerve; selective for serotonin synapses
- SE: nausea, diarrhea, jitteriness, anxiety, headache, sexual dysfunction, withdrawal effects if abruptly stopped, increase suicidal thoughts
Slide 28
Describe selective. serotonin. norepinephrine receptor inhibitor (SNRI)
- MOA: selectively inhibit the re-uptake of serotonin & norepinephrine into the presynaptic nerve, effects vary between the drugs in this class
- SE: nausea, diarrhea, increased HR/BP/CNS. activation (insomnia, agitation), sweating, sexual dysfunction, increase suicidal. thoughts
Slide 30
Serotonin Syndrome
- Anxiety, agitation/restlessness, and disorientation
- Ocular clonus, muscle rigidity, tremor, hyper-reflexia, muscle clonus, bilateral babinski reflex
- Hyperthermia, dilated pupils, dry mucus membranes, tachycardia, sweating, diarrhoea, vomiting
- Potentially life threatening
Describe tricyclic antidepressants. (TCA)
- MOA: inhibit the re-uptake of serotonin & norepinephrine into the presynaptic nerve; effect many other receptors resulting in more side effects & toxicity
- SE: dry mouth, blurred vision, constipation, sedation, confusion, delirium (elderly), orthostatic hypotension, cardiac toxicity
Slide 33
Describe monoamine oxidase inhibitor (MAOI)
- MOA: breaks down NTs (MAOa and MAOb); MOAI prevent the breakdown of NTs resulting in an increase in NTs in the nerve ending
- SE: orthostatic hypotension, restlessness, agitation, insomnia, confusion, delirium, constipation, hypertensive crisis (food interaction)
MAOIs interaction with tyramine and tyramine foods
- Tyramine stimulates release of endogenous catecholamines
- MAO metabolizes catecholamines
- Foods: red wines, fermented cheese, pickled foods
Slide 36
Basics of antipsychotics
- Psychosis is a severe form of mental illness that encompasses several disorders
- Inability to distinguish b/w. reality & what is not (delusions, hallucinations, disorganized thoughts)
- Historically tranquilizers were used as primary treatment
Neurotransmitter Hypothesis of Schizophrenia
- Dopamine hypothesis: ↑ DA (dopamine activity) limbic system (positive symptoms) and ↓ DA mesocortical system (negative and cognitive symptoms)
- Serotonin hypothesis: ↑ 5HT2A (serotonin) cortex and limbic systems (hallucinations)
- Glutamate hypothesis
Mechanism of antipsychotics
- Dopamine antagonist: Block postsynaptic dopamine receptors; Newer agents also block serotonin receptors
- First generation high affinity for D2
- Second generation inhibit serotonin receptors and have weak affinity for D2
Extrapyramidal effects of antipsychotics
- Akathisia: feeling of restlessness
- Dystonia: happens more is face/neck
- Psuedoparkinsonism: Tremor and Bradykinesia
- Tardive dyskinesia: Irreversible, Involuntary movements of mouth, tongue, and jaw, Dystonia of neck and truck,
Choreoathetosis - Dopamine activity decreased in nigrostriatal pathway
- Acetylcholine activity increased in nigrostriatal pathway
Slide 45 and 46
Intramuscular antipsychotics short. versus long acting
- Short: acute psychosis; onset is minutes & last a few hours
- Long: improve adherence leading to decreased hospitalizations & relapses; traditional side effects in addition to injection related side effects
Slide 48
Describe older adults and antipsychotics
- Agitation or aggression treatment: black box warning associated with death & treatment of dementia psychosis
- Increased side effects: anticholinergic, sedation, hypotension
When might you notice increased participation with therapy in a patient started on an SSRI for depression?
- SSRI’s take a while to show effect and may not immediately participate in therapy when started on an SSRI
Effects of antidepressants on rehabilitation
- Depression & side effects of antidepressants can impact participation of clients
- Improvement in symptoms can take several weeks to months
- Watch for increased thought of suicide (
Sedative hypnotics effects on rehabilitation
- Adverse effects: sedation, confusion, and weakness
- Possible solutions: discussion with provider about risk/benefit, scheduling of sessions, and nonpharmacologic sleep interventions
Antidepressant effects on rehabilitation
- Depression and side effects of antidepressants can impact participation of clients
- Improvement in symptoms can take several weeks to months
- Watch for increased thought of suicide (most common at the start)
- These medications can also be used to improve pain
- May help to improve outcomes of therapy
- Be mindful of dangerous side effects or possible overdose situation
Antipsychotic effects on rehabilitation
- Side effects: Cognitive and psychomotor slowing, sedation, orthostatic hypotension, movement related, and metabolic
- Possible solutions: Extra monitoring, use of pictures, timing of therapy, physical activity programs, and fall prevention
