Anxiolytics, Sedatives and Hypnotics

Question 1

Why is it harder to overdose on benzos than barbituates?

Answer 1

Barbituates have increasing effects with increasing dose

Benzos max out with increasing dosage (safer)

Question 2

At minimal concentrations what effect do benzos and barbs have?

Answer 2

Anti-anxiety

Question 3

What happens with severe toxicity in sedative-hypnotics?

Answer 3

respiratory and cardiovascular depression

Question 4

What ion does GABA-A pump?

Answer 4

Cl-

Question 5

What are more selective, benzo, barbituates or newer hyponotics?

Answer 5

Newer hyponotics are the most seletive, then benzos and barbituates bind to multiple isoforms and sites (AMPA receptors)

Question 6

What role does a1 subunit binding have?

Answer 6

Sedation
Amnesia
Ataxia

Question 7

What role does a1 and a3 subunit binding have?

Answer 7

Anxiolytic

Muscle relaxing

Question 8

What role does a5 subunit binding have?

Answer 8

Memory impairment?

Question 9

Does cross tolerance in sedative-hypnotics occur?

Answer 9

Yes

Question 10

How do you alleviate withdrawal symptoms of short-acting sedative-hypnotics?

Answer 10

Longer acting sedative hypnotics

Question 11

What happens if you stop a sedative-hypnotic suddenly?

Answer 11

Death

Question 12

What happens causes withdrawal symptoms of sed-hypn?

Answer 12

The long term effects have caused downregulation of GABA-A and upregulation of GluTR receptors

Question 13

How quick is the absorption and distribution of barbituates and why?

Answer 13

Its rapid because they are lipophilic

Question 14

What sed-hypn do you use for headaches?

Answer 14

Butalbital

Question 15

What did they use for truth interviews?

Answer 15

Amobarbital

Question 16

What exam findings might you get from barbituate toxicity?

Answer 16

Small to midpoint pupils

Diminished reflexes

Question 17

What are severe toxic effects of barbituates?

Answer 17

coma
hypothermia
resp failure
decreased myocardial contractility

Question 18

What is the major contraindication of barbituates?

Answer 18

patients with porphyria

Question 19

What are some reasons for the decline in barbituate use?

Answer 19

Ease of suicide/low margin of safety
No antidote
Addiction/physiological dependence
Cardiovascular/autonomic effects

Question 20

Where in the brainstem can you find the cardiovascular and respiratory centers that hypnotics depress?

Answer 20

Medulla

Question 21

What effect do benzos have on gabaergic neurons?

Answer 21

allosteric agonists increase freq of opening events

Question 22

What effect do barbituates have on gabaergic neurons?

Answer 22

Increase the duration of opening events in GABA
Gabamimetic - directly activate chloride channels
ALSO!!! Depress actions of glutamate

Question 23

What three benzodiazepines can be given to liver failure patients? Why?

Answer 23

Lorazepam
Temazepam
Oxazepam
(No active metabolites)

Question 24

What are short acting benzos usually used for?

Answer 24

Anesthesia

Question 25

What are long acting benzos usually used for?

Answer 25

Anxiety, keeping a patient asleep

Question 26

What benzo can be used for anesthesia? Why?

Answer 26

Midazolam | Fast onset

Question 27

What are intermediate duration benzos used for compared with long duration?

Answer 27

Intermediate - falling asleep | Long - staying asleep

Question 28

Advantages of benzodiazepines?

Answer 28

Rel high therapeutic index Rapid onset of action Antidote (flumazenil) Minimal CV and autonomic effects

Question 29

What patients will have adverse reactions to benzos?

Answer 29

Cardio or pulm patients can more easily resp depression

Question 30

What are newer hypnotics used for?

Answer 30

Sleep aids

Question 31

What are the 3 Zs?

Answer 31

Zolpidem Zalepon Eszopiclone

Question 32

What effects do benzos and barbs have on sleep?

Answer 32

Increase stage 2 sleep | Decrease REM and stage 4

Question 33

What does zolipdem do to sleep patterns?

Answer 33

decreases REM

Question 34

Zalepon has what effect on sleep patterns?

Answer 34

decreases latency of sleep but little effect on total sleep time

Question 35

Eszopiclone effects

Answer 35

increases total sleep time | Increases stage 2 NREM

Question 36

When is tolerance induced to newer hypnotics?

Answer 36

>1-2 wks

Question 37

What are adverse effects of zolpidem?

Answer 37

Parasomnias

Question 38

What drugs does flumazenil block and how?

Answer 38

Benzos and newer hypnotics acts as a competitive antagonist at GABA-A

Question 39

What limits its use?

Answer 39

Adverse effects - seizures, cardiac arrythmias

Question 40

Why is ramelteon useful?

Answer 40

Helps falling asleep without effecting sleep architecture

Question 41

What does ramelteon do?

Answer 41

Turn you into a woman!!! | Reduces testosterone and increase prolactin

Question 42

How and where does buspirone act?

Answer 42

Partial agonist at 5HT1A recepetors

Question 43

What is buspirone used for?

Answer 43

GAD

Question 44

Buspirone disadvantage

Answer 44

More than a week to have an effect

Question 45

Buspirone advantage

Answer 45

Low abuse liability

Question 46

When is dexmedetomidine used most?

Answer 46

Intubation

Question 47

What receptor and how does dexmedetomidine act?

Answer 47

Alpha2 adrenergic receptor agonist

Question 48

How does dexmedetomidine induce sedation?

Answer 48

Lowers sympathetic activity

Question 49

Advantages of dexmedetomidine

Answer 49

NO respiratory depression

Question 50

Disadvantages dexmedetomidine

Answer 50

$$$$ | contrindicated in CV patients (heart block or severe ventricular dysfunction)

Question 51

What are concerns for sed-hynos with pregnant patients?

Answer 51

All cross placental barrier | Can get withdrawal symptoms in newborns

Question 52

What drug has the same effect as a common alcohol related genetic deficiency?

Answer 52

Disulfiram is used in alcohol-use disorders because it causes the build up of acetaldehyde. Asians commonly lack the acetaldehyde dehydrogenase gene

Question 53

What antagonist effects does alcohol have in the CNS?

Answer 53

It blocks glutamates ability to open the NMDA channel

Question 54

Acute effects of ethanol

Answer 54

Heart: Depression of contractility Smooth muscle: Vasodilator, uterine relaxation GI: Nausea, vomiting

Question 55

Why might an alcoholic suffer from malnutrition symptoms?

Answer 55

1) Chronic pancreatitis 2) Injury to small intestine - malabsorption of vitamins 3) Dietary deficiency 4) Gastritis

Question 56

What is the progression of an alcoholic liver?

Answer 56

Fatty liver -> alcoholic hepatitis -> cirrhosis

Question 57

Why is heart failure possible in alcohols?

Answer 57

Dilated L cardiomyopathy

Question 58

Withdrawal symptoms of alcohol and why?

Answer 58

Delirium tremens, hyperexcitability, seizures | Upregulation of NMDA receptors and Ca2+ channels underlie seizures

Question 59

Does alcohol have neurotoxic effects?

Answer 59

Dementia Generalized symmetric peripheral neuropathy Cerebellar - ataxia Optic nerve degeneration

Question 60

Can alcohol lead to cancer?

Answer 60

Acetaldehyde can damage DNA -> mouth, larynx, pharynx, esophageal, liver cancer (anything the alcohol touches)

Question 61

Why might an alcoholic present as an anemic?

Answer 61

Inhibits proliferation of cellular elements in bone marrow | Impairs hematopoiesis

Question 62

Why might an alcoholic come in with pneumonia?

Answer 62

Immune system is impaired in lungs | NOTE: It is enhanced or even redirected to pancreas and liver

Question 63

How much alcohol can get into the placenta and why is this dangerous?

Answer 63

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.

Question 64

Why should an alcoholic avoid tylenol?

Answer 64

Alcohol has inductive effects which would convert acetaminophen to to reactive hepatotoxic metabolites

Question 65

Why should someone taking a sleep aid or anti-anxiety avoid alcohol?

Answer 65

Alcohol inhibits metabolism of other drugs which creates additive CNS depression

Question 66

What three key vitamins and nutrients are important to give an acute alcoholic intoxication?

Answer 66

Thiamine Glucose Long acting benzodiazepine

Question 67

When is alcohol withdrawal a medical emergency?

Answer 67

Delirium tremens

Question 68

Who do you give naltrexone to?

Answer 68

a reformed alcoholic without liver issues or opioid history who has severe craving

Question 69

What can you use to treat alcohol dependence?

Answer 69

Naltrexone Acamprosate Disulfiram

Question 70

What patients cannot handle acamprosate?

Answer 70

Renal failure/disease

Question 71

What type of learning behavior does disulfiram exhibit?

Answer 71

Punishment - causes extreme discomfort for those who drink because of acetaldehyde build up

Question 72

Who should not be given disulfiram?

Answer 72

Patients with poor compliance

Question 73

How do you treat someone with metabolic acidosis and visual disturbances?

Answer 73

Methanol poisoning Support respiration - sudden cessation = death Fomepizole (alcohol dehydrogenase inhibitor) or alcohol (competitively inhibits) Bicarb - counteract metabolic acidosis Hemodialysis

Question 74

Patient presents with oxolate crystals in urine, anion gap acidosis, and osmolar gap but NO visual symptoms. What do you give?

Answer 74

Fomepizole and hemodialysis