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MHD & Therapeutics

MHD & Therapeutics · 2019. 7. 10. · 100 700 500 700 400 800 600 100 900 900 900 900 300 500 800 Non -Benzos

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Page 1: MHD & Therapeutics · 2019. 7. 10. · 100 700 500 700 400 800 600 100 900 900 900 900 300 500 800 Non -Benzos

MHD & Therapeutics

Page 2: MHD & Therapeutics · 2019. 7. 10. · 100 700 500 700 400 800 600 100 900 900 900 900 300 500 800 Non -Benzos

is proudto present

And Now Here Is The Host . . .

Insert Name Here

Page 3: MHD & Therapeutics · 2019. 7. 10. · 100 700 500 700 400 800 600 100 900 900 900 900 300 500 800 Non -Benzos

The categories for today’s Jeopardy on Sedative-Hypnotics will be:

Page 4: MHD & Therapeutics · 2019. 7. 10. · 100 700 500 700 400 800 600 100 900 900 900 900 300 500 800 Non -Benzos

GABA-A or -B

Page 5: MHD & Therapeutics · 2019. 7. 10. · 100 700 500 700 400 800 600 100 900 900 900 900 300 500 800 Non -Benzos

Isoforms

Page 6: MHD & Therapeutics · 2019. 7. 10. · 100 700 500 700 400 800 600 100 900 900 900 900 300 500 800 Non -Benzos

Benzos

Page 7: MHD & Therapeutics · 2019. 7. 10. · 100 700 500 700 400 800 600 100 900 900 900 900 300 500 800 Non -Benzos

Non-Benzos

Page 8: MHD & Therapeutics · 2019. 7. 10. · 100 700 500 700 400 800 600 100 900 900 900 900 300 500 800 Non -Benzos

Miscellaneous

Page 9: MHD & Therapeutics · 2019. 7. 10. · 100 700 500 700 400 800 600 100 900 900 900 900 300 500 800 Non -Benzos

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GABA-A or -B Benzos Miscellaneous

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Non-Benzos

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GABA

Page 10: MHD & Therapeutics · 2019. 7. 10. · 100 700 500 700 400 800 600 100 900 900 900 900 300 500 800 Non -Benzos

Row 1, Col 1

Mucimol is an agonist and bicuculline an antagonist of this receptor

What is GABA-A?

Page 11: MHD & Therapeutics · 2019. 7. 10. · 100 700 500 700 400 800 600 100 900 900 900 900 300 500 800 Non -Benzos

1,2

This receptor acts by causing a decrease in Ca++ conductance

What is GABA-B?

Page 12: MHD & Therapeutics · 2019. 7. 10. · 100 700 500 700 400 800 600 100 900 900 900 900 300 500 800 Non -Benzos

1,3

Baclofen (Lioresal) is a selective agonist of this receptor

What is GABA-B?

Page 13: MHD & Therapeutics · 2019. 7. 10. · 100 700 500 700 400 800 600 100 900 900 900 900 300 500 800 Non -Benzos

1,4

Benzodiazepines & other sedative hypnotics modulate this receptor

What is GABA-A?

Page 14: MHD & Therapeutics · 2019. 7. 10. · 100 700 500 700 400 800 600 100 900 900 900 900 300 500 800 Non -Benzos

1,5

This receptor acts by causing a hyperpolarization via an increase

in K+ conductance

What is GABA-B?

Page 15: MHD & Therapeutics · 2019. 7. 10. · 100 700 500 700 400 800 600 100 900 900 900 900 300 500 800 Non -Benzos

1,6

This is an metabotropic G-protein linked receptor

What is GABA-B?

Page 16: MHD & Therapeutics · 2019. 7. 10. · 100 700 500 700 400 800 600 100 900 900 900 900 300 500 800 Non -Benzos

1,7

Benzodiazepines & other sedative hypnotics do not modulate

this receptor

What is GABA-B?

Page 17: MHD & Therapeutics · 2019. 7. 10. · 100 700 500 700 400 800 600 100 900 900 900 900 300 500 800 Non -Benzos

1,8

This is an ionotropic receptor

What is GABA-A?

Page 18: MHD & Therapeutics · 2019. 7. 10. · 100 700 500 700 400 800 600 100 900 900 900 900 300 500 800 Non -Benzos

1,9

This receptor acts by causing an increase in the opening of Cl

channels

What is GABA-A?

Page 19: MHD & Therapeutics · 2019. 7. 10. · 100 700 500 700 400 800 600 100 900 900 900 900 300 500 800 Non -Benzos

2,1

α β γ ρ

There are 6 different isoforms of this type of subunit

What is α?

Page 20: MHD & Therapeutics · 2019. 7. 10. · 100 700 500 700 400 800 600 100 900 900 900 900 300 500 800 Non -Benzos

2,2

The GABA-A is composed of this many subunits

What is 5?(heteropentameric)

Page 21: MHD & Therapeutics · 2019. 7. 10. · 100 700 500 700 400 800 600 100 900 900 900 900 300 500 800 Non -Benzos

2,3

Because the benzodiazepine receptor is an allosteric

modulatory site, in addition to the benzodiazepine, this needs to be present to alter the function

of the GABA A receptor

What is GABA?

Page 22: MHD & Therapeutics · 2019. 7. 10. · 100 700 500 700 400 800 600 100 900 900 900 900 300 500 800 Non -Benzos

2,4

Previously referred to as the benzodiazepine receptor, this

binding pocket is located at the interface of these subunits

What is α -γ ?

Page 23: MHD & Therapeutics · 2019. 7. 10. · 100 700 500 700 400 800 600 100 900 900 900 900 300 500 800 Non -Benzos

2,5

Regarding the benzodiazepine receptor, α1, α2, α3, α5 isoforms all bind benzodiazepines, but only this

isoform binds imidazopyridines & pyrrolopyrazine

What is α1?

Page 24: MHD & Therapeutics · 2019. 7. 10. · 100 700 500 700 400 800 600 100 900 900 900 900 300 500 800 Non -Benzos

2,6

α1 α2 α3 α4 α5 α6=====================================GABA receptors with these 2 αisoforms are diazepam insensitive

What is α4 & α6?

Page 25: MHD & Therapeutics · 2019. 7. 10. · 100 700 500 700 400 800 600 100 900 900 900 900 300 500 800 Non -Benzos

2,7

The region at the interface between these two subunits provides 2 sites

for both GABA agonists and antagonists

What is α- β ?

Page 26: MHD & Therapeutics · 2019. 7. 10. · 100 700 500 700 400 800 600 100 900 900 900 900 300 500 800 Non -Benzos

2,8

While there are many possible combinations, the most common

GABA-A receptor subtype is a generic composition of

these subunits

What is 2α, 2β, 1γ ?

Page 27: MHD & Therapeutics · 2019. 7. 10. · 100 700 500 700 400 800 600 100 900 900 900 900 300 500 800 Non -Benzos

2,9

While the α-γ interface provides a binding pocket for 1 benzodiazepine, the α-β interface

provides this many site(s) for GABA agnonists & antagonists

What is two sites?

Page 28: MHD & Therapeutics · 2019. 7. 10. · 100 700 500 700 400 800 600 100 900 900 900 900 300 500 800 Non -Benzos

3,1

Benzos that have a short t1/2, do not go through Phase I metabolism & are known by the mnemonic LOT are

this, this, & this

What is lorazepam, oxazepam, & temazepam?(Ativan, Serax, & Restoril )

Page 29: MHD & Therapeutics · 2019. 7. 10. · 100 700 500 700 400 800 600 100 900 900 900 900 300 500 800 Non -Benzos

3,2

Alprazolam (Xanax)Chlordiazepoxide (Librium)

Chlorazepate (Tranxene)Diazepam (Valium)

========================All have desmethyldiazepam as a bioactive intermediate except this

What is alprazolam (xanax)?

Page 30: MHD & Therapeutics · 2019. 7. 10. · 100 700 500 700 400 800 600 100 900 900 900 900 300 500 800 Non -Benzos

3,3

Alprazolam (Xanax)Clonazepam (Klonopin)

Lorazepam (Ativan)Midazolam (Versed)

=================================Of all the benzos, the one primarily used IV

in anesthesia that has a very short t1/2 & a very fast onset of action is this

What is Midazolam (Versed)?

Page 31: MHD & Therapeutics · 2019. 7. 10. · 100 700 500 700 400 800 600 100 900 900 900 900 300 500 800 Non -Benzos

3,4

For victims of date rape who were given Flunitrazepam (Rohypnol®), this common benzo side effect hinders

efforts to bring the criminal to justice

What is amnesia?

Page 32: MHD & Therapeutics · 2019. 7. 10. · 100 700 500 700 400 800 600 100 900 900 900 900 300 500 800 Non -Benzos

3,5

The majority (80%) of benzo abuse is part of polydrug abuse by patients,

most commonly with this drug

What is opioids?

Page 33: MHD & Therapeutics · 2019. 7. 10. · 100 700 500 700 400 800 600 100 900 900 900 900 300 500 800 Non -Benzos

3,6

Duration/half-life Time to action onset Time length drug taken Potency Dose

===============================Risk of developing tolerance increases as

this(these) factor(s) decrease

What is duration/half-life & time to action onset?

Page 34: MHD & Therapeutics · 2019. 7. 10. · 100 700 500 700 400 800 600 100 900 900 900 900 300 500 800 Non -Benzos

3,7

Benzos with long t1/2 or bioactive metabolites should not be prescribed for daily use in elderly patients or patients with compromised liver function due to the risk of this

What is drug accumulation?

Page 35: MHD & Therapeutics · 2019. 7. 10. · 100 700 500 700 400 800 600 100 900 900 900 900 300 500 800 Non -Benzos

3,8

If discontinuing benzos on a patient at high risk of withdrawal, treatment strategies include switching to a longer t1/2 benzo

(with lower potency and less rapid onset of action) and

gradually doing this

What is taper down the drug dose?

Page 36: MHD & Therapeutics · 2019. 7. 10. · 100 700 500 700 400 800 600 100 900 900 900 900 300 500 800 Non -Benzos

3,9

While tolerance may develop to the sedating effects of benzodiazepines,

tolerance has not been observed to this effect

What is anxiolytic (or muscle relaxant) effects?

Page 37: MHD & Therapeutics · 2019. 7. 10. · 100 700 500 700 400 800 600 100 900 900 900 900 300 500 800 Non -Benzos

4,1

GABA is not needed for the GABA-A’s Chloride channel to open in the presence of higher doses of drugs from this class

What is barbiturates?

Page 38: MHD & Therapeutics · 2019. 7. 10. · 100 700 500 700 400 800 600 100 900 900 900 900 300 500 800 Non -Benzos

4,2

Melatonin 1 & 2 receptors are bound, but benzodiazepine receptors are not, by this

unique sedative hypnotic drug

What is ramelteon (rozerum)?

Page 39: MHD & Therapeutics · 2019. 7. 10. · 100 700 500 700 400 800 600 100 900 900 900 900 300 500 800 Non -Benzos

4,3

A particularly short t1/2 results in minimal morning after sedation for

this selective non-benzodiazpine from the imidazopyradine class

What is zaleplon (Sonata)?

Page 40: MHD & Therapeutics · 2019. 7. 10. · 100 700 500 700 400 800 600 100 900 900 900 900 300 500 800 Non -Benzos

4,4

Being able to prescribe for longer term use in the treatment of insomnia is an

advantage for this pyrrolopyrazine drug

What is eszopiclone (lunesta)?

Page 41: MHD & Therapeutics · 2019. 7. 10. · 100 700 500 700 400 800 600 100 900 900 900 900 300 500 800 Non -Benzos

4,5

Pyrrolopyrazine BarbituratesImidazopyridine Benzodiazepine

====================================Due to a low therapeutic index, risk of abuse,

dependence & withdrawal, & stimulation of P450 activity and hepatic microsomal oxidases, the most dangerous sedative

hypnotic is this

What are Barbiturates?

Page 42: MHD & Therapeutics · 2019. 7. 10. · 100 700 500 700 400 800 600 100 900 900 900 900 300 500 800 Non -Benzos

4,6

Complex sleep related activities like sleep driving and sleep eating may be a side effect with these 3 medications

What is zolpidem (Ambien), zaleplon (Sonata) & eszopiclone (Lunesta)?

Page 43: MHD & Therapeutics · 2019. 7. 10. · 100 700 500 700 400 800 600 100 900 900 900 900 300 500 800 Non -Benzos

4,7

Pyrrolopyrazine BarbituratesImidazopyridine Benzodiazepine

====================================The order, from the highest risk of becoming

habit forming to the lowest risk, is this

What is Barbiturates to Benzos to Imidazopyridine to Pyrrolopyrazine?

Page 44: MHD & Therapeutics · 2019. 7. 10. · 100 700 500 700 400 800 600 100 900 900 900 900 300 500 800 Non -Benzos

4,8

Pyrrolopyrazine BarbituratesImidazopyridine Benzodiazepine

=================================A competitive antagonist may be used to treat patients who have overdosed on this

(these) med(s)

What is Benzos, Pyrrolopyrazine, & Imidazopyradine?

Page 45: MHD & Therapeutics · 2019. 7. 10. · 100 700 500 700 400 800 600 100 900 900 900 900 300 500 800 Non -Benzos

4,9

Pyrrolopyrazine BarbituratesImidazopyridine Benzodiazepine

=================================The competitive antagonist that may be used

to treat patients who have overdosed on at least 1 of these meds is this

What is flumazenil (Romazicon)?

Page 46: MHD & Therapeutics · 2019. 7. 10. · 100 700 500 700 400 800 600 100 900 900 900 900 300 500 800 Non -Benzos

5,1

Lorazepam (Ativan) 1 mgClonazepam (Klonopin) 0.25Alprazolam (Xanax) 0.5 mg

Diazepam (Valium) 5 mg==========================While equivalent doses, the most

potent drug is this

What is Clonazepam (Klonopin)?

Page 47: MHD & Therapeutics · 2019. 7. 10. · 100 700 500 700 400 800 600 100 900 900 900 900 300 500 800 Non -Benzos

5,2

While diazepam (valium) does not have a short half life, it is highly

lipophilic which increases the risk for this

What is misuse/abuse, tolerance & dependence?

Page 48: MHD & Therapeutics · 2019. 7. 10. · 100 700 500 700 400 800 600 100 900 900 900 900 300 500 800 Non -Benzos

5,3

If an alcohol intoxicated patient is given flumazenil

(Romazicon), this will happen

What is nothing?

Page 49: MHD & Therapeutics · 2019. 7. 10. · 100 700 500 700 400 800 600 100 900 900 900 900 300 500 800 Non -Benzos

5,4

3 4 5 6=============================

Lack of effects from a high dose of diazepam (valium) is due to GABA

receptors with this α isoform

What is 4 & 6?

Page 50: MHD & Therapeutics · 2019. 7. 10. · 100 700 500 700 400 800 600 100 900 900 900 900 300 500 800 Non -Benzos

5,5

Chlordiazepoxide (Librium)Diazepam (Valium)

============================The parent compound that has a longer

half life than its common metabolite of desmethyldiazepam is this

What is neither?

Page 51: MHD & Therapeutics · 2019. 7. 10. · 100 700 500 700 400 800 600 100 900 900 900 900 300 500 800 Non -Benzos

5,6

If a patient who has overdosed on zolpidem (Ambien) is given

flumazenil (Romazicon), this will happen

What is flumazenil blocks zolpidem’s effects ?

Page 52: MHD & Therapeutics · 2019. 7. 10. · 100 700 500 700 400 800 600 100 900 900 900 900 300 500 800 Non -Benzos

5,7

Benzos, Barbiturates Barbiturates, Benzos

In the presence of GABA, the duration the chloride channel is open is by this, whereas the frequency of the Cl

channel opening is by that

What is Barbiturates, Benzos?Barbiturates-duration

Benzos-freqeuncy

Page 53: MHD & Therapeutics · 2019. 7. 10. · 100 700 500 700 400 800 600 100 900 900 900 900 300 500 800 Non -Benzos

5,8

Benzodiazepines—at least in theory—could be used to treat

this sleep related side effect of both zolpidem (Ambien)

& zaleplon (Sonata)

What is sleep walking?

Page 54: MHD & Therapeutics · 2019. 7. 10. · 100 700 500 700 400 800 600 100 900 900 900 900 300 500 800 Non -Benzos

5,9

While different studies do not agree, use of benzodiazepines during pregnancy

may increase the risk of this teratogenic outcome

What is cleft lip/cleft palate?