Pharm S2B3 - Cns - Anxiolytics

Front 1

Defintion: Drug that decreases anxiety without sedation

Back 1

Anxiolytic

Front 2

Definition: Decrease in motor activity, coordination, & mental acuity

Back 2

Sedation

Front 3

Definition: Increased tendency to sleep, but easily awakened

Back 3

Hypnosis

Front 4

Definition: Sleep induction, not easily awakened

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Anesthesia

Front 5

The general principle of current CNS depressants is that they generally do what?

Back 5

enhance inhibitory neurotransmission

Front 6

What is the difference between Complete depressants & Incomplete depressants?

Back 6

Complete depressants produce Anesthesia

Incomplete depressants do not produce Anesthesia

Front 7

What is the mechanism of action of the Barbiturates?

Back 7

1. Bind to the Barbiturate binding site on the GABA-A receptor
2. increase Chloride ion channel flux by increasing channel open time = Duration
3. Decrease neuron firing

Front 8

List some Complete CNS depressants Anxiolytics

Back 8

1. Barbiturates
2. Ethanol
3. Chloral Hydrate
4. Paraldehyde
**produce Anesthesia

Front 9

List some Incomplete CNS depressant Anxiolytics

Back 9

1. Benzodiazepines

2. Non-benzodiazepine BZ/omega receptor agonists
-Zolpidem
-Zaleplon
-Eszopiclone

Front 10

List some Non-depressant Anxiolytics/Hypnotics

Back 10

1. Buspirone

2. SSRI's

3. Melatonin agonist = Ramelteon

4. Antihistamines = Diphenhydramine

5. Beta-blockers = Propranolol

Front 11

What is the common ending for Barbiturates?

Back 11

"-barbital" + Thiopental

Front 12

What effects do Barbiturates have on the CNS?

Back 12

1. Complete CNS depressants
-Sedation, Hypnosis, Anesthesia, Coma, Death

2. Paradoxical excitement & euphoria

Front 13

What effects do Barbiturates have on the CNS?

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NO EFFECT UP TO ANESTHETIC DOSES

At Anesthetic doses:
1. decreases Respiration
2. decreases Blood Pressure due to Medullary depression

Front 14

What effects do Barbiturates have on the Liver?

Back 14

Chronic use increases Microsomal enzyme activity
-pharmacokinetic tolerance & can decrease plasma levels of other drugs

Front 15

Barbiturates can increase the synthesis of a certain product & are therefore contraindicated in this disease

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Porphyria

**increase the synthesis of Porphyrin
**Barbiturate causes increased Heme metabolism; Heme usually has negative feedback on ALA synthase (which produes Porphyrin)

Front 16

What are the clinical uses of Barbiturates?

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1. Hypnotics
-have been largely replaced by Benzodiazepines & Non-Benzodiazepine BZ/Omega receptor agonists

2. Anticonvulsants
3. Anesthetics

Front 17

Long-acting Barbiturate that is used for its Sedative & Anticonvulsant properties

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Phenobarbital

Front 18

2 Intermediate-acting Barbiturate that are used for their Hypnotic effects

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Pentobarbital

Secobarbital

"Sleep Producing" Barbs

Front 19

Ultra-short acting Barbiturate that is used for Anesthesia

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Thiopental

Front 20

Acute Barbiturate Toxicity:
1. Causes?

2. Signs/Symptoms?

3. Treatment?

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1. Overdose or interaction with other CNS depressants

2. Decrease in respiration & Blood Pressure; loss of consciousness

3. Maintain Respiration & BP; removal of drug

Front 21

What are the Chronic Toxicities associated with Barbiturates?

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1. ADDICTION = more common than opiate addiction

2. Tolerance develops over time

3. Withdrawal includes anxiety, tremor, nausea, vomiting, seizures, weight loss, psychiatric rxns

**treatment includes measured reduction over time (2-3 wks)

Front 22

Barbiturate Pharmacokinetics:
1. What does it diffuse across?
2. What does distribution depend on?
3. What accounts for differences in duration of action?
4. What can cause drug interactions?
5. Where metabolized?
6. Where excreted?

Back 22

1. All membranes
2. Lipophilicity of body part
3. Redistribution
4. Highly binds to Plasma proteins
5. Liver
6. Urine

Front 23

-Complete CNS depressant that is used as a Hypnotic with its active product being Trichloroethanol

-Irritating to G.I.

-Rapid onset, short duration of action

-Acute & chronic toxicity are same as barbiturates

Back 23

Chloral Hydrate

Front 24

-Complete CNS depressant used as an Anxiolytic

-Irritating to the G.I.

-Rapid onset & short duration of action

-Acute & chronic toxicity are the same as Barbiturates

Back 24

Paraldehyde

Front 25

What the is mechanism of action of the Benzodiazepines?

Back 25

1. Bind to the Benzodiazepine binding sites (BZ/omega) on the GABA-A receptor
2. increases affinity of GABA-A receptors for GABA
3. increase the FREQUENCY of Cl- channel opening

Front 26

Give a possible reason as to why Benzodiazepines are probably Incomplete CNS Depressants

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they act at a smaller subset of GABA-A receptors than the Barbiturates
-there are atleast 3 BZ binding site subtypes: BZ1-BZ3

Front 27

What are the CNS effects of the Benzodiazepines?

Back 27

1. INCOMPLETE depressant
2. Skeletal muscle relaxant = Anti-spastic (via Central effect)
3. Anticonvulsant (status epilepticus)
4. Hypnotic
5. Paradoxical excitement & euphoria

Front 28

What Benzodiazepine effects does tolerance develop to? (3)

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1. Sedative

2. Hypnotic

3. Anticonvulsant

Front 29

Which one has more risk of Respiratory depression, Coma, & decreased Blood Pressure...Barbiturates or Benzodiazepines?

Back 29

Barbiturates

Front 30

What is the common ending for most Benzodiazepines?

Back 30

"-azepam"

Front 31

What are the 4 clinical uses of Benzodiazepines?

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1. Anxiolytics

2. Sedative/Hypnotics = night terrors, sleepwalking

3. Muscle relaxants / Antispastic

4. Pre-anesthetic / Anesthetic

Front 32

Short acting (t1/2 = 2-4 hrs) that is the most rapidly inactivated Benzodiazepine
-Produces Anesthesia I.V.
-Primarily used as Anesthetic/Pre-anesthetic in surgical settings

Back 32

Mid-azolam

Front 33

Short acting (T1/2 = 2-4 hrs) Benzodiazepine used as a Hypnotic = short-term treatment of insomnia w/out producing morning drowsiness

Back 33

Tri-azolam

Front 34

Moderate acting (T1/2 = 10-14 hrs) that is an Anxiolytic/Hypnotic often used for Panic Attacks
-has rapid Oral absorption/onset

Back 34

Alpr-azolam

Front 35

Moderate acting (t1/2 = 10-14 hrs) Benzodiazepine that is Anxiolytic, Pre-anesthetic. Generally used in Alcohol Detox & Pre-surgery anxiety

Back 35

Chlordiazepoxide

Front 36

Moderate acting (t1/2 = 10-14 hrs) Benzodiazepine that is Anxiolytic/Hypnotic, Pre-anesthetic
-generally used for Status Epilepticus

Back 36

Lorazepam

Front 37

Long acting Benzodiazepine (t1/2 = 24 hrs) used as an Anti-convulsant

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Clonazepam

Front 38

Very long acting Benzodiazepine (t1/2 = 43 hrs) that has active metabolites

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Diazepam

Front 39

What are the clinical uses of Diazepam?

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1. Anxiolytic
2. Anticonvulsants
3. Muscle relaxant
4. Antispastic
5. Pre-anesthetic

Front 40

Very long acting Benzodiazepine that has a half-life of 74 hours & has active metabolites

Back 40

Flurazepam

Front 41

Benzodiazepine that is fast-acting & causes amnesia = used as a "date rape" drug

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Flunitrazepam

Front 42

What would you treat an overdose of Benzodiazepines with?

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Flumazenil = competitive antagonist at GABA receptor

**short t1/2 requires repeated doses

Front 43

What are the side effects & toxicities of the Benzodiazepines?

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1. Sedation & ataxia (loss of muscle coordination)

2. Amnesia

3. Idiosyncratic responses: nightmares, irritability, anxiety, seizures

4. Abuse liability

5. Withdrawal, especially with shorter-acting compounds

Front 44

Most Benzodiazepines are administered orally, but which ones can be administered via IV & IM?

Back 44

1. Chlordiazepoxide

2. Diazepam

3. Lorazepam

4. Midazolam

Front 45

Which Benzodiazepine can be given rectally?

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Diazepam

Front 46

List the 2 BZ1 agonists that are not actually Benzodiazepines

Back 46

1. Zolpidem

2. Zaleplon

**used as Hypnotics for Insomnia in those who have trouble falling asleep
"Help you get your ZZZ's"

Front 47

Non-selective BZ receptor agonist that is not actually a Benzodiazepine

Back 47

Eszopiclone

Front 48

What is the clinical use of Eszopiclone? What are its general properties?

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Hypnotic = for insomnia
-minimal muscle relaxant or anticonvulsant activity
-less amnestic than Benzodiazepines = less memory loss
-Tolerance develops to Hypnotic effects

"EaSy Z's"

Front 49

Anxiolytic that is not a CNS depressant but is a partial agonist at the 5-HT(1A) site

Back 49

Buspirone

**"1 pirate on a bus (Buspirone) takes Exit 1A to get off the stressful highway (Anxiolytic)"

Front 50

What is the onset of action of Buspirone? What does it cause at high doses?

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Onset of action = 1-2 weeks = not useful for initial panic attacks

High doses = Dysphoric = unpleasant or uncomfortable mood = less addiction/abuse

Front 51

Anxiolytics that increase the synaptic availability of 5-HT (Serotonin)? What are they used for?

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SSRI's & other Antidepressants

Generalized anxiety & as prophylaxis for Panic disorder

Front 52

Melatonin agonist indicated for Insomnia with prolonged sleep onset (takes a long time to fall asleep)
-MT1 & MT2 melatonin receptor agonist

Back 52

Ramelteon

Front 53

Common OTC sedative that is a Histamine-1 (H1) blocker

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Antihistamines = Diphenhydramine

Front 54

Why would Beta-blockers such as Propranolol be used for Anxiety?

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Blocks peripheral symptoms of anxiety such as Heart Rate & Tremor

Front 55

Is Ethanol a Complete or Incomplete CNS depressant?

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Complete

Front 56

What is Ethanol's mechanism in being a Complete CNS depressant?

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-affects a variety of receptors & ion channels but no specific receptor interactions have been identified

-Affects membrane fluidity at high doses

Front 57

What CNS effects does Ethanol possess?

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1. impairs vision & muscular coordination
2. lengthens reaction time
3. decreases anxiety, removes inhibitions -> Euphoria

Front 58

What GI effects does Ethanol possess?

Back 58

1. increases salivation & gastric secretion
2. decreases intestinal motility
3. directly irritating to mucosa -> nausea & vomiting

Front 59

What Respiratory effect does Ethanol possess?

Back 59

little effect at low to moderate doses

Respiratory decrease at Anesthetic doses

Front 60

What Cardiovascular effects does Ethanol possess?

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1. Vasodilation -> sensation of warmth

2. Anesthetic doses -> decrease in Blood Pressure

Front 61

What Hepatic/Renal effects does Ethanol possess?

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1. Cirrhosis

2. increases Microsomal enzyme activity

3. increase in Urine Flow & Volume due to increase in fluid intake & inhibition of ADH

Front 62

List the metabolic pathway of Ethanol

Back 62

-

Front 63

What are the contraindications of Ethanol?

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1. Hepatic disease
2. Renal disease
3. Ulcers
4. Epilepsy
5. Other CNS depressants = additive or syergistic CNS depression
6. Pregnancy

Front 64

What are the Acute Toxicity symptoms of Ethanol?

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1. Coma
2. Hypothermia
3. Decreased Respiration
4. Vomiting

Front 65

What are the symptoms of Chronic Toxicity of Ethanol?

Back 65

1. Withdrawal = restlessness, tremor, fear, hallucinations, convulsions
-potentially life-threatening

2. Cirrhosis of the Liver

Front 66

What is the treatment for Withdrawal symptoms of Ethanol?

Back 66

Slowly reduce dose over time

Benzodiazepines for acute symptoms

Front 67

What is the mechanism of action of Disulfarim? What are the side effects?

Back 67

Inhibits Acetaldehyde Dehydrogenase = Aldehyde increases
-increase in HR
-dizziness
-vomiting
-unconsciousness
-can be fatal

Front 68

What should you warn patients about when using Disulfarim?

Back 68

usage of Alcohol-containing consumer products such as mouthwash, cough syrups, etc.