Psychopharmacology

What are the primary goals of sedative-hypnotic and anti-anxiety drugs?

-relax pt, promote normal sleep

-decrease anxiety

What are the primary agents of sedative hypnotic and anti anxiety drugs?

benzodiazepines & non-benzodiazepines

What are the effects of benzodiazepines?

-increases inhibitory effects of GABA

-bine to specific receptor in brain to provide therapeutic effects: sedation, hypnosis, decreased anxiety

What are the effects of barbituates when used as sedative hypnotic?

-increase inhibitory effects of GABA

-higher doses may directly reduce effects of glutamate and depress neuronal excitability

What do non-benzodiazepine sedative hypnotics preferably bind to?

GABAa receptors

T or F: Non-benzodiazepines bind to the same place as benzodiazepines in the brain

False; will both go on GABA receptors, but not at the same location

How does alcohol work as a sedative hypnotic?

may act on protein receptors and activate GABAa receptors increasing inhibition in CNS

What is the pharmacokinetics of sedative hypnotic drugs?

-highly lipid soluble and absorbed easily from GI tract

-systemic distribution with ability to reach CNS

-termination by hepatic enzymes or storage in non-CNS tissues

What is the purpose of newer anti-anxiety drugs?

stimulates serotonin receptors in the CNS; may decrease anxiety with less sedation, less physical dependence, and addiction

T or F: Antidepressants can have a anxiolytic effect as well

True

T or F: Antihistamines, antiseizure, antipsychotics, and beta-blockers can all be used as alternative anti-anxiety drugs

True

What are adverse effects of sedative hypnotic drugs?

-residual hangover-type effects (groggy, not alert)

-anterograde amnesia

-complex behaviors (sleep walking/driving)

What are adverse effects of sedative hypnotic & anti-anxiety drugs?

-rebound effect (insomnia, increase anxiety)

-falls

-tolerance and dependence

-benodiazepines have possible link to AD

What are rehab considerations regarding sedative hypnotic & anti-anxiety drugs?

-drugs tx the sx, not the cause of insomnia/anxiety

-consider trade off benefits vs. sedation

-trend towards use of non-benzo drugs

What defines depression?

loss of the ability to enjoy life; characterized by feelings of sadness and despair

What is the one common goal of all drugs used to tx depression?

increase or prolong the effect of one or more of the amine NTs

What are the types of antidepressant drugs?

SSRIS, SSNRIs, Tricyclics, MAO Inhibitors

What do SSRIs do to the body?

block re-uptake of serotonin the presynaptic terminals to allow serotonin to remain in the synaptic cleft and continue to exert effects longer

What do SSNRIs do to the body?

decrease serotonin and NE re-uptake, but NOT dopamine

What are SSNRIs beneficial in treating?

chronic pain associated with OA, peripheral neuropathy, and fibromyalgia

T or F: SSNRIs are different from SSRIs because in addition to serotonin, they block the re-uptake or norepinephrine and dopamine

False; only blocks serotonin and NE

T or F: Tricyclics are a type of non-selective anti-depressant

True

What do tricyclics do to the body?

affects synapses using all 3 primary amine NTs -- serotonin, NE, dopamine

Which anti-depressant affects all 3 primary amine neurotransmitters?

tricyclics

What does monoamine oxidase(MAO) do?

enzyme that elicits effects amine synapses by removing released NTs by enzymatic destruction

What do MAO inhibitors do?

inhibit the enzyme that removes NTs from the synapse, thus causing more NTs to remain in synaptic cleft to exert effect

T or F: MAO Inhibitors are more of a last resort drug, not necessarily a first choice drug

True

In general, antidepressants prolong the effects of neurotransmitters in one of two ways, which are....?

1. inhibiting reuptake of one or more NTs

2. decreasing NT breakdown

T or F: MAO inhibitors increase the concentration of norepinephrine, serotonin, and dopamine

True

When MAO inhibitors are used, what percentage of the NT actually does get broken down by the MAO enzyme still?

20-40%

What are the latest theories as to why increased amine NT decreases depression?

increases brain-derived neurotrophic factors (BDNF) which stimulates growth (neurogenesis) in the hippocampus

What are adverse effects of tricyclics?

-anticholinergic effects (dry mouth, confusion, urinary retention, constipation, tachycardia)

-CV effects (arrhythmias, OH)

-seizures

-risk of fatal OD

What are adverse effects of MAO inhibitors?

-CNS excitation

-increased BP

What are adverse effects of SSRIs/SSNRIs?

-usually pretty tolerated

-increase risk of seizures

-GI problems

In regards to antidepressants and their adverse effects, which category(ies) of drugs is important to monitor the CV system?

tricyclics and MAO

What is serotonin syndrome? When does it occur? What happens? What are sx? What is tx?

-occurs with use of antidepressant drug

-when the CNS serotonin receptors are overstimulated

-sx = increased HR & BP, confusion, hallucinations, agitation, sweating, shivering, dytonias, dyskinesia, muscle pain, GI problems

-tx: usually reversible if addressed immediately, but could be fatal if not tx

What are the sx associated with serotonin syndrome?

-increased BP & HR

-confusion

-hallucinations

-agitations

-sweating

-shivering

-dystonias

-dyskinesias

-muscle pain

-GI problems

Antidepressnts might be prescribed for off-label use for what conditions?

-fibromyalgia

-neuropathic pain

-headache

-LBP

-Raynaud's phenomenon

-other chronic pain syndrome

What is the only antidepressant drug approved by the FDA for treating pain?

Duloxetine (Cymbalta)

What are important rehab considerations with antidepressants?

-time lag before beneficial effects are realized (2-3 weeks sometimes)

-chance of increased depression during initial beginning of tx

-need to recognigze/acknowledge mood changes

What encompasses bipolar syndrome?

-"manic-depressive" disorder

-associated with mood swings from one extreme to the other

-manic episodes include euphoria, hyperactivity, talkativeness

What is the classic treatment of bipolar syndrome?

lithium

What may be some proposed mechanisms of lithium's action in the body?

-stabilize neurons?

-might be neuroprotective?

Is lithium metabolized? why or why not? How does it get excreted?

NOT metabolized!

it is an element that gets eliminated INTACT by the kidneys

What is a risk for taking lithium?

lithium toxicity

What are sx of moderate to severe lithium toxicity?

CNS = ataxia, nystagmus, confusion, tremor, dysarthria, etc...

GI = vomit & diarrhea

CV = syncope, bradycardia, AV block, arrythmias

renal = insufficiency, permanent damage of kidneys, decreased filtration

What is important when considering serum levels of lithium in the body?

there is a small therapeutic window as the therapeutic upper level of acute manic episodes is right at where toxicity might begin

At what serum level of lithium toxicity does the pt require toxicity tx?

>2.0mEq/L

What type of drugs, other than lithium, can treat bipolar syndrome?

-antiseizure drugs

-antipsychotics

What are rehab considerations regarding bipolar disorder?

-be alert for behavior changes that could indicate toxic level

What is psychosis and what is the cause? What NTs are involved?

psychosis is a severe form of mental illness caused by increased dopamine activity in specific CNS pathways

NTs: 5HT (serotonin), glutamate, ACh

What is the main action of antipsychotics?

block CNS dopamine receptors, especially D2 receptors in the mesolimbic pathway

What are the two categories of antipsychotics?

typical(traditional) and atypical(newer)

What are common characteristics of traditional antipsychotics?

-tend to bind to several types of CNS dopamine receptors, including those that influence motor function of the BG

-less predictable

-pt to pt variability

-side effects & potential for long term implications

What are common characteristics of atypical antipsychotics?

-weak blockers of D2 receptors

-strong blockers of specific serotonin receptors (5HT receptors)

-might be better at treating psychosis and have less serious side effects

-less incidence of relapse due to improved tolerance and pt compliance

T or F: Atypical antipsychotics have less side effects than traditional

True

T or F: Traditional antipsychotics are more predictable than atypical antipsychotics

False; vise versa

What are adverse effects of traditional antipsychotics?

-OH

-sedation

-anticholinergic effects (dry mouth, constipation, etc)

What are adverse effects of atypical antipsychotics?

-wt gain

-disturbed lipid/glucose metabolism

What is a primary concern with taking all antipsychotics?

extrapyrimidal (motor) side effects

-tardive dyskinesia

-pseudoparkinsonism

-akathisia

-other dystonias & dyskinesias

What are extrapyramidal side effects?

-tardive dyskinesia

-pseudoparkinsonism

-akathisia

-other dystonias & dyskinesias

What is tardive dyskinesia? What is the prevelence and cause? What are risk factors? Tx?

abnormal involuntary movements

prevalence = 25% of pts on long term traditional antipsychotics

cause = denervation, super-sensitivity

risk factors: age, genetic predisposition, affective mood disorder, DM. hx of alc abuse >6mo

tx: early recognition & change in dose/type drug

What does NMS mean?

Neuroleptic malignant syndrome

When does NMS happen? What are sx? What is risk? Tx?

-can occur with all antipsychotics

-sx: catatonia, rigidity, tremors, fever

-risk: dose is high, pt agitated, pt mental function impairment

tx: critical need to detect early and d/c drug

What are possible non-motor effects of antipsychotic drugs?

-wt gain

-increased plasma lipids

-DM

What are rehabilitation considerations on those taking antipsychotic meds?

-consider benefit vs. sedation

-be alert for OH

-recognize extrapyramidal side effects

What is the goal of drug therapy in dementia?

-improve cognitive and intellectual function

-improve/modify behavior

T or F: There is decreased ACh activity in the brain with dementia

True

What is the purpose of cholinergic stimulates?

increase ACh activity either directly or indirectly

What are the effects in the body of indirect cholinergic stimulants?

-drug inhibits cholinerterase, therefore ACh breakdown is inhibited and its activity/effects are prolonged

What is the efficacy seen in pts taking cholinergic stimulants?

help pts retain more cognitive/intellectual function in early stages of AD

What is the role of Memantine(Namenda) in dementia drug therapy?

-blocks NMDA-glutamate receptors in the brain

-normalizes glutamate influence

-provides another strategy to slow AD progression, sustain memory & intellect

Aducanumab (Aduhelm) is a new dementia drug that targets what?

targets the fundamental pathophys for dementia -- amyloid plaques & neurofibrillary tangles -- which ultimately affects the pt's ability to remember and think

was approved by FDA under accelerated approval

What are adverse effects of Aducanumab (Aduhelm), a new dementia drug?

-temporary swelling of brain which may/not cause sx

-hypersensitivity angioedema & urticaria (hives)

-headache

-falls

-diarrhea

-confusion/delirium/altered mental status/disorientation

What are drugs used to improve or modify behavior in dementia pts?

antidepressnts, antianxiety, antipsychotics

T or F: Government has regulations to curb the use of antipsychotics when treating AD

True

What are rehab implications for AD?

need to consider how a pt's behavior impacts the POC