Anxiolytics, Sedatives and Hypnotics Flashcards
Why is it harder to overdose on benzos than barbituates?
Barbituates have increasing effects with increasing dose
Benzos max out with increasing dosage (safer)
At minimal concentrations what effect do benzos and barbs have?
Anti-anxiety
What happens with severe toxicity in sedative-hypnotics?
respiratory and cardiovascular depression
What ion does GABA-A pump?
Cl-
What are more selective, benzo, barbituates or newer hyponotics?
Newer hyponotics are the most seletive, then benzos and barbituates bind to multiple isoforms and sites (AMPA receptors)
What role does a1 subunit binding have?
Sedation
Amnesia
Ataxia
What role does a1 and a3 subunit binding have?
Anxiolytic
Muscle relaxing
What role does a5 subunit binding have?
Memory impairment?
Does cross tolerance in sedative-hypnotics occur?
Yes
How do you alleviate withdrawal symptoms of short-acting sedative-hypnotics?
Longer acting sedative hypnotics
What happens if you stop a sedative-hypnotic suddenly?
Death
What happens causes withdrawal symptoms of sed-hypn?
The long term effects have caused downregulation of GABA-A and upregulation of GluTR receptors
How quick is the absorption and distribution of barbituates and why?
Its rapid because they are lipophilic
What sed-hypn do you use for headaches?
Butalbital
What did they use for truth interviews?
Amobarbital
What exam findings might you get from barbituate toxicity?
Small to midpoint pupils
Diminished reflexes
What are severe toxic effects of barbituates?
coma
hypothermia
resp failure
decreased myocardial contractility
What is the major contraindication of barbituates?
patients with porphyria
What are some reasons for the decline in barbituate use?
Ease of suicide/low margin of safety
No antidote
Addiction/physiological dependence
Cardiovascular/autonomic effects
Where in the brainstem can you find the cardiovascular and respiratory centers that hypnotics depress?
Medulla
What effect do benzos have on gabaergic neurons?
allosteric agonists increase freq of opening events
What effect do barbituates have on gabaergic neurons?
Increase the duration of opening events in GABA
Gabamimetic - directly activate chloride channels
ALSO!!! Depress actions of glutamate
What three benzodiazepines can be given to liver failure patients? Why?
Lorazepam
Temazepam
Oxazepam
(No active metabolites)
What are short acting benzos usually used for?
Anesthesia
What are long acting benzos usually used for?
Anxiety, keeping a patient asleep
What benzo can be used for anesthesia? Why?
Midazolam
Fast onset
What are intermediate duration benzos used for compared with long duration?
Intermediate - falling asleep
Long - staying asleep
Advantages of benzodiazepines?
Rel high therapeutic index
Rapid onset of action
Antidote (flumazenil)
Minimal CV and autonomic effects
What patients will have adverse reactions to benzos?
Cardio or pulm patients can more easily resp depression
What are newer hypnotics used for?
Sleep aids
What are the 3 Zs?
Zolpidem
Zalepon
Eszopiclone
What effects do benzos and barbs have on sleep?
Increase stage 2 sleep
Decrease REM and stage 4
What does zolipdem do to sleep patterns?
decreases REM
Zalepon has what effect on sleep patterns?
decreases latency of sleep but little effect on total sleep time
Eszopiclone effects
increases total sleep time
Increases stage 2 NREM
When is tolerance induced to newer hypnotics?
> 1-2 wks
What are adverse effects of zolpidem?
Parasomnias
What drugs does flumazenil block and how?
Benzos and newer hypnotics acts as a competitive antagonist at GABA-A
What limits its use?
Adverse effects - seizures, cardiac arrythmias
Why is ramelteon useful?
Helps falling asleep without effecting sleep architecture
What does ramelteon do?
Turn you into a woman!!!
Reduces testosterone and increase prolactin
How and where does buspirone act?
Partial agonist at 5HT1A recepetors
What is buspirone used for?
GAD
Buspirone disadvantage
More than a week to have an effect
Buspirone advantage
Low abuse liability
When is dexmedetomidine used most?
Intubation
What receptor and how does dexmedetomidine act?
Alpha2 adrenergic receptor agonist
How does dexmedetomidine induce sedation?
Lowers sympathetic activity
Advantages of dexmedetomidine
NO respiratory depression
Disadvantages dexmedetomidine
$$$$
contrindicated in CV patients (heart block or severe ventricular dysfunction)
What are concerns for sed-hynos with pregnant patients?
All cross placental barrier
Can get withdrawal symptoms in newborns
What drug has the same effect as a common alcohol related genetic deficiency?
Disulfiram is used in alcohol-use disorders because it causes the build up of acetaldehyde. Asians commonly lack the acetaldehyde dehydrogenase gene
What antagonist effects does alcohol have in the CNS?
It blocks glutamates ability to open the NMDA channel
Acute effects of ethanol
Heart: Depression of contractility
Smooth muscle: Vasodilator, uterine relaxation
GI: Nausea, vomiting
Why might an alcoholic suffer from malnutrition symptoms?
1) Chronic pancreatitis
2) Injury to small intestine - malabsorption of vitamins
3) Dietary deficiency
4) Gastritis
What is the progression of an alcoholic liver?
Fatty liver -> alcoholic hepatitis -> cirrhosis
Why is heart failure possible in alcohols?
Dilated L cardiomyopathy
Withdrawal symptoms of alcohol and why?
Delirium tremens, hyperexcitability, seizures
Upregulation of NMDA receptors and Ca2+ channels underlie seizures
Does alcohol have neurotoxic effects?
Dementia
Generalized symmetric peripheral neuropathy
Cerebellar - ataxia
Optic nerve degeneration
Can alcohol lead to cancer?
Acetaldehyde can damage DNA -> mouth, larynx, pharynx, esophageal, liver cancer (anything the alcohol touches)
Why might an alcoholic present as an anemic?
Inhibits proliferation of cellular elements in bone marrow
Impairs hematopoiesis
Why might an alcoholic come in with pneumonia?
Immune system is impaired in lungs
NOTE: It is enhanced or even redirected to pancreas and liver
How much alcohol can get into the placenta and why is this dangerous?
Teratogenic.
Alcohol can reach levels equal to that of the mother in the fetus and cannot be metabolized because of the lack of alcohol dehydrogenase.
Why should an alcoholic avoid tylenol?
Alcohol has inductive effects which would convert acetaminophen to to reactive hepatotoxic metabolites
Why should someone taking a sleep aid or anti-anxiety avoid alcohol?
Alcohol inhibits metabolism of other drugs which creates additive CNS depression
What three key vitamins and nutrients are important to give an acute alcoholic intoxication?
Thiamine
Glucose
Long acting benzodiazepine
When is alcohol withdrawal a medical emergency?
Delirium tremens
Who do you give naltrexone to?
a reformed alcoholic without liver issues or opioid history who has severe craving
What can you use to treat alcohol dependence?
Naltrexone
Acamprosate
Disulfiram
What patients cannot handle acamprosate?
Renal failure/disease
What type of learning behavior does disulfiram exhibit?
Punishment - causes extreme discomfort for those who drink because of acetaldehyde build up
Who should not be given disulfiram?
Patients with poor compliance
How do you treat someone with metabolic acidosis and visual disturbances?
Methanol poisoning
Support respiration - sudden cessation = death
Fomepizole (alcohol dehydrogenase inhibitor) or alcohol (competitively inhibits)
Bicarb - counteract metabolic acidosis
Hemodialysis
Patient presents with oxolate crystals in urine, anion gap acidosis, and osmolar gap but NO visual symptoms. What do you give?
Fomepizole and hemodialysis
