Pharm: Sedatives

Front 1

MOA of sedatives as far as receptor? Result? Why are newer agents more selective?

Back 1

allosterically bind (different location) to GABAa receptors -> stimulates opening of Cl channel -> hyperpolarizes cell. Newer agents are more selective to what subtype of the unit they bind to (alpha1 -not adrenergic)

Front 2

How are BZ generally absorbed? 2) Onset? 3) How is Clorazepate absorbed?

Back 2

rapidly and completely absorbed. 2) related to the degree of lipid solubility (high amount of variance). 3) is a prodrug. First decarboxylated in gastric juice to active metabolite -> N-desmethyldiazepam

Front 3

List 4 drugs with fast onset:

Back 3

1) Fluorazepam. 2) Diazepam. 3) Triazolam. 4) Chlorazepate

Front 4

List 3 drugs with slow onset:

Back 4

1) Lorazepam. 2) Oxazepam. 3) Chlordizepoxide.

Front 5

The duration of fast onset BZ is due to what AFTER A SINGLE DOSE? 2) What about slow onzet BZ?

Back 5

High lipid solubitily allows rapid distribution from brain to peripheral tissues. 2) Duration of less lipid soluble BZ is due to transformation from active to inactive metabolites.

Front 6

List 5 drugs with long duration:

Back 6

1) Flurazepam. 2) Diazepam. 3) Chlorazepate. 4) Chlordiazepoxide. 5) Prazepam

Front 7

List 4 drugs with short-intermediate duration:

Back 7

1) Lorazepam. 2) Oxazepam. 3) Triazolam. 4) Alprazolam

Front 8

Biotransformation occurs in what 3 steps:

Back 8

1) N-dealkylation. 2) hydroxylation. 3) conjugation

Front 9

What metabolite do many BZ become? 2) How? 3) active?

Back 9

N-desmethyldizepam. 2) N-dealkylation. 3) active with long halflife

Front 10

BZ with what halflife are more active to cause residual or cumulative effects?

Back 10

long halflife

Front 11

Termination of less lipid soluble BZ are prmarily due to what?

Back 11

ring hydroxylation and glucuronidation to inactive metabolites

Front 12

In general what kind of anxieties do BZ treat? List 4 specific kinds with appropriate other drug Tx.

Back 12

Urgent, short term -> else use SSRI for long term. 1) Situational anxiety, propranolol. 2) Generalized anxiety -> SSRI! Or TCA, propranolol. 3) Panic disorder -> SSRI! Or TCA, MOA. 4) Social Anxiety Disorder

Front 13

What 2 conditions do you NOT treat with BZ? What do you use?

Back 13

OCD and PTSD. Use SSRI

Front 14

2 BZ to initiate sleep? 2 non-BZ?

Back 14

Triazolam and Lorazepam. 2) Zaleplon and Zolpidem.

Front 15

2 BZ to sustain sleep?

Back 15

Flurazepam and temazepam

Front 16

2 BZ to Tx status epilepticus or drug/toxin induced seizures?

Back 16

Diazepam and Lorazepam

Front 17

Pre-anesthetic medication or surgical procedures

Back 17

Midazolam iv.

Front 18

BZ for muscle relaxation for spasms or cerebral palsy? What two places does this exert an effect?

Back 18

Diazepam. 2) Central sedative action or dec motor neuron firing in the spinal cord

Front 19

2 BZ for withdrawal/physical depended on alcohol and other acute BZs? Why these 2?

Back 19

Diazepam and Chlorodiazepoxide. Long-acting with less severe withdrawal.

Front 20

2 BZ for acute mania -> the initial management of agitation

Back 20

Diazepam and Lorazepam

Front 21

3 adverse effects of BZ

Back 21

1) CNS depression: sedation, ataxia, confusion. 2) Anterograde amnesia -> esp. Lorazepam or midazolam. 3) Respiratory depression

Front 22

BZ tolerance develops to certain effects but not to one. Which?

Back 22

Tolerance does not develop to anxiolytic activity. Tolerance does develop to sedative, muscle relaxant, and anticonvulsant effects.

Front 23

Withdrawal Sx are much more pronounced with what kind of BZ? 2) How do you manage this?

Back 23

long term use of short acting BZ (what are the 4….). 2) To manage taper withdrawal over weeks and substitute longer acting BZ

Front 24

BZ interact with what other drugs to do what? 2) What effects metabolism of BZ?

Back 24

1) alcohol and drugs with CNS depressant activity (antihistamines, TCA, antihypertensive) -> respiratory depression (potentially fatal). 2) Cimetidine and grapefruit juice inhibit CYP3A4

Front 25

Diazepam (3) uses:

Back 25

1) muscle relaxant. 2) seizures. 3) physical dependence.

Front 26

Diazepam: 1) solubility. 2) absorption rate. 3) onset. 4) duration.

Back 26

1) high lipid solubility. 2) high absorption rate. 3) fast onset. 4) long duration

Front 27

Chlordiazepoxide use?

Back 27

withdrawal

Front 28

Chlordiazepoxide: 1) absorption rate. 2) onset. 3) duration

Back 28

1) low absorption rate 2) slow onset 3) long duration

Front 29

Lorazepam: 1) absorption rate. 2) onset. 3) duration.

Back 29

1) low absorption rate. 2) slow onset. 3) short-intermediate duration

Front 30

Oxazepam: 1) absorption rate. 2) onset. 3) duration.

Back 30

1) low absorption rate. 2) slow onset. 3) short-intermediate duration

Front 31

Flurazepam, temazepam, and triazolam use?

Back 31

Flurazepam and temazepam to sustain sleep. Triazolam to initate.

Front 32

Flurazepam: lipid solubility. 2) absorption rate. 3) onset. 4) duration

Back 32

1) high lipid solubility. 2) high absorption rate. 3) fast onset. 4) long duration

Front 33

Temazepam termination?

Back 33

directly conjugated to inactive metabolites

Front 34

Triazolam absorption rate. 2) duration. Onset?

Back 34

1) high absorption rate. 2) short duration. 3) fast onset

Front 35

Chlorazepate: 1) absorption rate. 2) duration 3) onset

Back 35

1) high absorption rate. 2) long duration. 3) fast onset

Front 36

Ramelton: 1) Agonist at what receptors? 2) located where? 3) Implication? 4) Usef for? 5) Effects?

Back 36

1) Agonist at melatonin MT1 and MT2 receptors. 2) suprachiasmatic nuclie. 3) No effet on GABA-R. 4) Pts having trouble falling asleep. 5) dizziness, lethargy, endocrine changes

Front 37

Busprione use? 2) what makes it attractive compared to BZ? Receptor?

Back 37

Generalized anxiety. 2) Anxiolytic w/o the other effects of BZ. 3) partial agonist at 5HT1a

Front 38

Zolpidem, Zaleplon, Eszopiclone use? 2) onset and duration. 3) receptor?

Back 38

1) short term Tx of insomnia. 2) Rapid onset, short duration. 3) acts on BZ receptors assoc. with GABA type 1 (BZ1/omega1)

Front 39

Zolpidem, Zaleplon, Eszopiclone: effect? Adverse effects? 3 drug interactions?

Back 39

Sedation w/o anticonvulsant/anxiolytic activity. Amenisa, daytime sedation, rebound insomina. 1) actions blocked by flumazenil. 2) ethanol inc respiratory depression. 3) Rifampin dec halflife of zolpidem

Front 40

Flumazenil is a what? 2) What 2 uses? 3) duration? 4) withdrawal?

Back 40

BZ-R antagonist. 2) Tx respiratory depression of BZ/alcohol and speed recovery from BZ in anesthetic procedures. 3) shorter duration than most BZ. 4) can precipitate withdrawal with seizures

Front 41

Barbiturates include what drug w/o barbital in the name?

Back 41

Thiopental

Front 42

Thiopental and phenobarbital duration? 2) reason? 3) What is rate and use for pentobarbital?

Back 42

1) Thiopental short duration from rate of redistribution and used to induce anesthesia. 2) phenobarbital has a long duration from rate of metaboism (and urine pH) and used for anticonvulsant. 3) pentobarbital is rarely used as anesthesia

Front 43

Barbiturate effect at low doses? 2) high doses?

Back 43

1) allosterically prolongs GABA induced Cl channels -> enhanced GABA inhibitory activity (prolong=duration). 2) at higher doses, has direct actions on GABA receptor to open Cl channels independently of GABA!!! (GABA-mimetic)