Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Pharmacology Exam 5 > Sedative Hypnotics & Alcohol > Flashcards

Sedative Hypnotics & Alcohol Flashcards

1
Q

Sedative

A

reduces anxiety (anxiolytic) and irritation, produces a calming effect

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Hypnotic

A

produces drowsiness, aids sleep onset or maintenance

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Sedative Hypnotics Uses

A
  • Anxiety Disorder
  • Anesthesia
  • Seizure Disorders
  • Treating Withdrawal-Benzodiazepines (first line)
  • Sleep Disorder- Hypnotic
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Sedative-hypnotics are drugs that produce…

A

…sedation at lower doses AND hypnosis at higher doses

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

ALCOHOL USE DISORDER (AUD)

A
  • impaired ability to stop or control alcohol use despite adverse social, occupational, or health consequences
  • Severity (mild, moderate or severe) is determined by number of clinical criteria (DSM-5) met during a 12-month period
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Alcohol tolerance

A

with chronic use, same alcohol amount produces less effect

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Alcohol dependence

A

chronic use produces physiological changes that can result in alcohol withdrawal (potentially fatal condition) on stopping alcohol use

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

At low doses alcohol produces anxiolysis, disinhibition and relaxation via:

A
  • Agonist activity at GABAA receptors
  • Agonist activity at inhibitory glycine receptors
  • Antagonist at excitatory NMDA (glutamate) receptors
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Glutamate

A

major excitatory neurotransmitter in brain, and the most abundant (80% of all neurons); increases likelihood of action potentials firing

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

GABA

A

major inhibitory neurotransmitter (20% of all neurons); both produce fast, powerful effects on other neurons

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

ALCOHOL CNS DEPRESSANT EFFECTS

A
  • Balance between excitatory and inhibitory neurotransmission is often synchronized and rhythmic, oscillating on small (msec) and large-scale (day/night)
  • Rhythmic electrical activity is involved in regulating sleep/wake, consciousness / unconsciousness, seizures, etc.
  • Alcohol CNS depressant effects range through relaxation, anti-convulsant effects, sleep, unconsciousness, coma and death
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

EUPHORIA AND REWARDING EFFECTS

A
  • Result from activation of the brain’s major reward circuit, the mesolimbic dopamine pathway
  • When neurons in the ventral tegmental area (VTA) detect a rewarding stimulus, they release dopamine onto the nucleus accumbens (NAc) → reward sensation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Affects of Alcohol on Rewarding Effects

A
  • Alcohol increases firing of dopamine VTA neurons

* VTA releases dopamine onto NAc, signaling reward

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

NAc (Nucleus accumbens)

A

selectively activated during the perception (or imagining) of pleasant, (positive emotion) situations

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

CHRONIC CNS EFFECTS (DEPENDENCE)

A

• CNS responds to chronic ethanol with compensatory changes to counteract acute ethanol effects (attempt to normalize CNS activity level)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

When you build tolerance to alcohol you will…

A

(1) more alcohol needed to produce same effect

2) abrupt removal of alcohol results in CNS hyperexcitation (withdrawal symptoms

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Drugs for managing alcohol withdrawal

A

Thiamine and Benzodiazepines

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Drugs for preventing alcohol dependence relapse

A

Naltrexone, Acamprosate, Disulfiram, Topiramate, Gabapentin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Benzodiazepines

A
  • treating agitation and minimizing symptom progression (moderate to severe withdrawal)
  • gradually re-equilibrate GABAergic neurotransmission levels) - dose must be tapered off gradually
  • Chlordiazepoxide, diazepam, and lorazepam
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

NALTREXONE

A
  • USE: First-line for treating moderate to severe AUD and preventing relapse - Available PO or long-acting injectable
  • MOA: Long-acting mu opioid receptor antagonist, blocks reward signaling
  • Also used to treat opioid addiction → screen for concurrent opioid use to avoid triggering opioid withdrawal
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

ACAMPROSATE

A
  • USE: PREVENTING RELAPSE; alternative to naltrexone, patient with liver disease - administered 3x daily
  • MOA: Weak NMDA glutamate receptor antagonist (and possibly weak GABAA agonist) - slow normalization of compensatory neurochemical changes
  • Primarily renally-excreted
  • Contraindicated in renal dysfunction
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

DISULFIRAM

A
  • USE: PREVENTING RELAPSE; use is limited to certain motivated patients; efficacy is weaker
  • MOA: acetaldehyde causes unpleasant effects (e.g., sweating, headache, nausea, vomiting) when alcohol is consumed by irreversibly inhibiting ALDH enzyme → causes acetaldehyde to accumulate
  • Requires 48 hours of total abstinence before use
  • Appropriate counseling and patient consent is always necessary
  • AE: hepatotoxicity and psychosis
23
Q

Topiramiate

A
  • USE: PREVENTING RELAPSE; Anticonvulsant drug (also used for migraine)
  • MOA: increasing GABAA activity and reducing glutamate signaling
  • Preferred for patients who have a seizure disorder that can be treated with topiramate, and who have failed initial treatment with naltrexone or acamprosate
24
Q

Gabapentin

A
  • USE: PREVENTING RELAPSE; Anticonvulsant drug (also used for neuropathic pain),
  • MOA: interferes with voltage-dependent calcium channel activity in the brain
  • Good efficacy in patients who failed other options
  • Disadvantage: addictive potential
25
Q

LIST OF BARBITURATES DRUGS (-tal)

A
  • Thiopental (ultra short-acting)
  • Secobarbital (short-acting)
  • Amobarbital (intermediate)
  • Phenobarbital (long-acting)
26
Q

LIST OF BENZODIAZEPINES DRUGS (-lam, -pam, -poxide)

A

• Midazolam (short-acting)

  • Alprazolam (intermediate)
  • Clonazepam (intermediate)
  • Lorazepam (intermediate)
  • Diazepam (long-acting)
  • Chlordiazepoxide (long-acting)
27
Q

BENZODIAZEPINE ANTAGONIST DRUG

A

Flumazenil

28
Q

Other Sedative Hypnotics Drug

A

Ethanol

29
Q

BARBITURATES USES

A
  • Seizure disorders (phenobarbital has some use in partial epilepsy)
  • Anesthesia induction (thiopental has rapid onset / offset of effect)
  • Medically-induced coma (pentobarbital or thiopental)
  • Lethal injection, assisted suicide (secobarbital, pentobarbital)
  • Most are rarely used today, due to danger in overdose, dependence risk → replaced by newer, safer agents
  • A few are currently used as antiepileptics or anesthetics
30
Q

BARBITURATES MOA

A

• MOA:

  • bind the GABAA receptor at multiple sites (can bind to α or β subunits), distinct from GABA and other drug binding sites
  • positive allosteric modulators of GABAA , increasing the duration of Cl- ion channel opening when GABA binds
  • antagonist at glutamate AMPA receptors
  • primary GABAA receptor agonist (at high concentrations, opens channel on own)
31
Q

BARBITURATES DRUG INTERACTIONS

A
  • CNS depression - dose-dependent barbiturate effect; interaction with other CNS depressants can produce lethal effects
  • Enzyme induction - chronic barbiturate use markedly increases CYP enzyme levels → drug interactions
32
Q

BARBITURATES ADVERSE EFFECTS & RISKS

A
  • Risk of abuse - disinhibition, sleep promotion and euphoric effects make these very abuse-liable (DEA schedule II-IV)
  • Dependence risk - tolerance development (similar to alcohol dependence, neuronal adaptations result in withdrawal symptoms if drug is stopped)
  • Overdose risk - dose-dependent CNS, cardiovascular and respiratory depression
33
Q

BENZODIAZEPINES USES

A
  • Status epilepticus: diazepam or lorazepam are first-line - IV diazepam has nearly instant onset of effect
  • Pre-surgery sedation: midazolam (Versed)
  • Short-term treatment of anxiety: alprazolam (Xanax) or beta blockers; SSRIs antidepressants are used for long-term treatment
  • Management of alcohol withdrawal: chlordiazepoxide (Librium) is first-line (long duration provides smooth tapering of GABAA activation)
34
Q

BENZODIAZEPINES MECHANISM OF ACTION

A
  • positive allosteric modulators of GABAA , but they increase the frequency of channel opening (opens at lower GABA concentration)
  • Bind GABAA receptor at a single site (only at interface between an α and γ subunit)
35
Q

BENZODIAZEPINE ADVERSE EFFECTS & RISKS

A
  • CNS depression - Like barbiturates, benzos can potentiate CNS depressant effects of other drugs - Agents with active metabolites require caution, particularly in elderly
  • Risk of abuse - disinhibition, sleep promotion and euphoric effects
  • Dependence risk - moderate dependence risk (potential for withdrawal symptoms) is the main reason that benzodiazepines are usually recommended only for short-term use
  • Overdose risk - much less dangerous than barbiturates, due to:
  1. Shallower dose-response curve (does not progress to coma / death)
  2. Availability of an antidote: flumazenil
36
Q

BENZODIAZEPINE ADVERSE EFFECTS & RISKS

A
  • CNS depression - Like barbiturates, benzos can potentiate CNS depressant effects of other drugs - Agents with active metabolites require caution, particularly in elderly
  • Risk of abuse - disinhibition, sleep promotion and euphoric effects
  • Dependence risk - moderate dependence risk (potential for withdrawal symptoms) is the main reason that benzodiazepines are usually recommended only for short-term use
  • Overdose risk - much less dangerous than barbiturates, due to:
  1. Shallower dose-response curve (does not progress to coma / death)
  2. Availability of an antidote: flumazenil
37
Q

Flumazenil

A
  • an imidazobenzodiazepine, is the only GABAA receptor antagonist
  • flumazenil occupies the benzodiazepine binding site without producing any effect (competitive GABAAR antagonist)
  • Reverses CNS depressant effects produced by overdoses of benzodiazepines and Z-drugs
  • Flumazenil is short-acting; additional doses must be administered until the agonist is cleared from the body
38
Q

Sleep Disorders

A

conditions that cause persistent interference with sleep amount (too much / too little) and/or quality, causing distress and impairment

39
Q

LIST OF Z-DRUGS

A
  • Eszopiclone
  • Zaleplon
  • Zolpidem
40
Q

LIST OF MELATONIN AGONISTS

A
  • Ramelteon

* Tasimelteon

41
Q

LIST OF OREXIN AGONIST

A

• Suvorexant

42
Q

Z-DRUGS MOA

A
  • Z-drugs bind to the same site on the GABAA receptor as benzodiazepines, and also increase Cl ion conductance
  • z-drugs bind selectively between α1 and γ subunits only (much more selective than benzodiazepines, which bind between any α and γ subunit)
43
Q

Z-DRUGS EFFECTS AND USES

A
  • USE: insomnia only
  • EFFECTS:
  • Shortened time to sleep onset (by about 20 min)
  • Small increase in sleep time / quality

• PK & DOSING:

  • Rapid onset of action (take ~30m before bed)
  • Effect duration intended to be <8hr (so you can wake up!)
44
Q

Z - DRUGS ADVERSE EFFECTS & RISKS

A

Common effects: dizziness, memory loss, disinhibition, GI upset, hallucinations

Parasomnias (less common)

Abuse: abuse risk

Dependence: after ~2 weeks of use, taper dose to avoid withdrawal symptoms

45
Q

MELATONIN RECEPTOR AGONISTS MOA

A

Ramelteon and tasimelteon are agonists at melatonin MT1 and MT2 receptors (reset circadian rhythms)

46
Q

MELATONIN RECEPTOR AGONISTS USES

A
  • Insomnia with sleep onset difficulty

* Non-24-hour sleep-wake disorder

47
Q

MELATONIN RECEPTOR AGONISTS EFFICACY, SIDE EFFECTS, AND ADVANTAGES

A

Efficacy: Modest improvement in time to sleep onset vs. placebo

Side Effects: Generally mild - headaches, vivid dreams

Advantages: No CNS depressant effects, negligible tolerance / dependence / abuse risk → not a scheduled substance

48
Q

OREXIN RECEPTOR ANTAGONISTS MOA

A

Suvorexant is a dual antagonist at orexin OX1R / OX2R receptors (reduces activity of wake-promoting neurons in hypothalamus)

49
Q

OREXIN RECEPTOR ANTAGONISTS USES

A

Insomnia due to difficulty with sleep onset or sleep maintenance

50
Q

OREXIN RECEPTOR ANTAGONISTS EFFICACY AND SIDE EFFECTS

A

Efficacy: reduces sleep latency (~20 min), increases duration (~20 min)

Side Effects: somnolence, headache

Warnings: complex sleep behaviors, increased suicide risk

Tolerance / dependence / abuse risk is present (schedule IV agents)

51
Q

LIST OF SEDATIVES/ANXIOLYTICS

A

Buspirone

52
Q

LIST OF SEDATIVE OF OTHER DRUGS FOR MANAGING ANXIETY

A
  • Antidepressants

* Beta Blockers

53
Q

Buspirone

A

MOA: serotonin 5HT1A receptor agonist (actual mechanism of anxiolysis unknown)

USES: long-term anxiety disorders

Effects: Anxiolytic effects only

Dosing / PK:
• Slow onset of action (like antidepressants, takes 3-4 weeks for full effect to develop) • Metabolized by CYP3A4

Advantages:
• No CNS depressant effects
• Negligible tolerance / dependence / abuse risk
• Apparently safe in pregnancy

Side Effects: tachycardia, paresthesia, nausea

Pharmacology Exam 5 (3 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions