Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
77 Cards in this Set
- Front
- Back
|
What are the 5 principal pharmacologic effects of benzodiazepines?
|
1. Sedation
2. Anxiolysis 3. Anticonvulsant actions 4. Spinal cord-mediated skeletal muscle relaxation 5. Anterograde amnesia |
|
|
What percent of the population use benzodiazepines as sleep aids?
|
4%
|
|
|
Benzodiazepines versus barbiturates: tolerance
|
Benzodiazepines have less tendency to produce tolerance than barbiturates
|
|
|
Benzodiazepines versus barbiturates: abuse
|
Benzodiazepines have less potential for abuse than barbiturates
|
|
|
Benzodiazepines versus barbiturates: margin of safety with overdose
|
Benzodiazepines have a greater margin of safety after overdose than barbiturates
|
|
|
Benzodiazepines versus barbiturates: drug interactions
|
Benzodiazepines have fewer and less serious drug interactions than barbiturates
|
|
|
What are the 3 main benzodiazepines?
|
1. Diazepam
2. Midazolam 3. Lorazepam |
|
|
What is the chemical structure of benzodiazepines?
|
A benzene ring and a 7 member diazepine ring
|
|
|
What do substitutions on the chemical structure of benzodiazepines affect?
|
Potency and biotransformation
|
|
|
What does the imidazole ring on midazolam contribute to?
|
Water solubility at a low pH
|
|
|
What occurs to midazolam at physiologic pH?
|
An intramolecular rearrangement, which changes the physiochemical properties, making it extremely lipid soluble
|
|
|
What is the mechanism of action of benzodiazepines?
|
Facilitation of gamma-aminobutyric acid (GABA)
|
|
|
What is GABA?
|
The principal inhibitory neurotransmitter in the central nervous system
|
|
|
What is GABA's effect at the receptor?
|
1. GABA binds to the receptor, enhancing the opening of chloride channels
2. Increased chloride conductance causes hyperpolarization of the postsynaptic cell membrane 3. Resistance to excitation |
|
|
Where is the highest density of GABA receptors located?
|
Cerebral cortex
|
|
|
Suggested effects of benzodiazepine receptor occupancy at 20%, 30-50%, and >60%
|
20% = anxiolysis
30-50% = sedation >60% = unconsciousness |
|
|
What was the original parenteral benzodiazepine?
|
Diazepam
|
|
|
Is diazepam water or lipid soluble and what does this entail?
|
Insoluble in water: dissolved in organic solvents for IV use
|
|
|
What is the most common organic solvent diazepam is dissolved in and what is this associated with?
|
Propylene glycol: associated with pain on injection and thrombophlebitis
|
|
|
What occurs with diazepam administration after PO administration? When are peak plasma levels?
|
Rapid absorption from GI tract: peak plasma levels in 60 minutes
|
|
|
After IV administration of diazepam, what accounts for termination of action?
|
Redistribution of drug (from CNS) to inactive tissue depots
|
|
|
Does diazepam have a low or high volume of distribution and what does this reflect?
|
Large volume of distribution: reflecting its high lipid solubility (1-1.5 L/kg)
|
|
|
Where does extensive uptake of diazepam occur?
|
Adipose tissue
|
|
|
Does diazepam cross the placenta?
|
Yes, rapidly crosses the placenta
|
|
|
Is diazepam protein-bound? How much?
|
Extensively protein-bound: >96%
|
|
|
What is diazepam primarily bound to in plasma?
|
Albumin
|
|
|
What disease states may increase the free fraction of diazepam?
|
Cirrhosis or renal failure
|
|
|
What kind of metabolism does diazepam undergo? Through what pathway?
|
Primary hepatic oxidation:
N-demethylation oxidative pathway |
|
|
What are the 2 principal metabolites of diazepam? Are they active or inactive?
|
Oxazepam
Desmethyldiazepam (both active) |
|
|
What is the elimination half-time of diazepam?
|
21-37 hours
|
|
|
What occurs to the elimination half-time of diazepam in the presence of cirrhosis? What does this reflect and result in?
|
Increased 5 times
Reflects increase in the volume of distribution secondary to decreased protein binding-- decreased hepatic clearance |
|
|
What is the elimination half-time of the active metabolite desmethyldiazepam?
|
48-96 hours
|
|
|
How long may drug clearance take for patients on chronic diazepam therapy?
|
May take a week or more to clear all metabolites after discontinuation of therapy
|
|
|
Where are diazepam metabolites cleared and how?
|
Cleared in the urine as conjugates of glucuronic acid
|
|
|
What drug delays clearance of diazepam and desmethyldiazepam? Why does this occur? What does this result in?
|
Cimetidine: inhibition of hepatic microsomal enzymes
Results in an increased elimination half-time (due to reduced clearance) |
|
|
What are 4 clinical uses of diazepam?
|
1. Preoperative anxiolysis
2. Treatment of delirium tremens 3. Treatment of local anesthetic induced seizures 4. Skeletal muscle relaxant in treatment of lumbar disc disease |
|
|
What is the maximum drug dose of lidocaine with epinephrine?
|
7 mg/kg
|
|
|
What is the maximum drug dose of lidocaine without epinephrine?
|
5 mg/kg
|
|
|
What is the maximum drug dose of bupivicane (cardiotoxic) with epinephrine?
|
3 mcg/kg
|
|
|
What is the maximum drug dose of bupivicane (cardiotoxic) without epinephrine?
|
2 mcg/kg
|
|
|
What is the most popular benzodiazepine for preoperative anxiolysis or conscious sedation?
|
Midazolam
|
|
|
How potent is midazolam compared to diazepam?
|
2-3 times more potent than diazepam
|
|
|
What pH is the parenteral solution of midazolam buffered to?
|
pH = 3.5
|
|
|
What is the chemical structure of midazolam characterized by?
|
A pH dependent ring opening phenomenon
|
|
|
What pH values does midazolam's imidazole ring remain open at? What does this maintain?
|
pH values < 4
Maintains the water solubility of the drug |
|
|
At what pH value does midazolam's imidazole ring close and what does this do to the drug?
|
pH values > 4
Converts midazolam into an extremely lipid soluble drug |
|
|
Because of midazolam's water solubility at pH < 4, what does this necessitate, and what does this cause?
|
A dissolving agent
Little to no venoirritation or thrombophlebitis |
|
|
What occurs to midazolam after PO administration?
|
Rapid absorption from the GI tract
Substantial first pass hepatic elimination-- 50% of dose reaches systemic circulation |
|
|
Is midazolam protein-bound?
|
Extensively bound to plasma proteins (>96%)
|
|
|
What is midazolam's volume of distribution and elimination half-time? Compared to diazepam?
|
Large volume of distribution
Relatively short elimination half-time: greater hepatic clearance than diazepam Elimination half-time: 1-4 hours |
|
|
What kind of metabolism does midazolam undergo?
|
Extensive hydroxylation by hepatic microsomal enzymes (cytochrome P450)
|
|
|
How are midazolam's (weakly active) metabolites excreted?
|
In the urine as glucuronic conjugates
|
|
|
Do H2 receptor antagonists interfere with the metabolism of midazolam?
|
No
|
|
|
What 2 drugs decrease cytochrome P450 enzyme activity that may decrease hepatic clearance of midazolam?
|
Erythromycin
Calcium channel blockers |
|
|
What are the 5 clinical uses of midazolam?
|
1. Preoperative anxiolysis
2. Sedation of pediatric patients 3. Adjunct for MAC cases 4. Induction of GA 5. Continuous infusion for facilitation of mechanical ventilation |
|
|
What is the pediatric dose of midazolam?
|
0.5 mg/kg PO
30 minutes prior to induction |
|
|
What is the potency of lorazepam compared to diazepam and midazolam?
|
More potent amnestic agent than diazepam or midazolam
|
|
|
What kind of metabolism does lorazepam undergo?
|
Hepatic oxidation
|
|
|
Does lorazepam have active or inactive metabolites and how are they excreted?
|
Inactive metabolites
Excreted in urine as glucuronide conjugates |
|
|
What is the oral dose for lorazepam for preoperative anxiolysis?
|
50 mcg/kg
|
|
|
How long does lorazepam provide anterograde amnesia?
|
Up to 6 hours
|
|
|
What are some other benzodiazepines used to treat insomnia, anxiety, or seizure disorders?
|
Oxazepam
Clonazepam Flurazepam Temazepam Triazolam Quazepam Alprazolam |
|
|
How do benzodiazepines affect:
-Cerebral vessels/CBF -CMRO2 |
Cerebral vasoconstriction- reduction in CBF (by 34%)
Reduction in CMRO2 |
|
|
What happens to the CBF to CMRO2 ratio with benzodiazepines?
|
Remains normal
|
|
|
What is the affect of benzodiazepines and seizure activity?
|
Potent anticonvulsants: increase seizure threshold to local anesthetics
|
|
|
What is the affect of benzodiazepines and EEG activity?
|
Do not produce burst suppression or an isoelectric EEG
|
|
|
What do benzodiazepines do to MAC for inhaled anesthetics?
|
Reduce MAC
|
|
|
What is the affect of benzodiazepines on respiration?
|
Dose-related central respiratory depression
|
|
|
Do benzodiazepines cause apnea?
|
Possible, but not common
Obstruction more likely |
|
|
What do benzodiazepines have a synergistic effect with?
|
Opioids
|
|
|
What affect do benzodiazepines have on hemodynamics?
|
Little to no effect
|
|
|
What affect do benzodiazepines have on blood pressure?
|
May cause slight reduction in BP
|
|
|
Are homeostatic reflex mechanisms affected by benzodiazepines?
|
Homeostatic reflex mechanisms are maintained
|
|
|
What is flumazenil?
|
Specific and exclusive benzodiazepine antagonist
Competitive antagonist: prevents or reverses all benzodiazepine agonist effects |
|
|
What is the dosing for flumazenil?
|
Initial: 0.2 mg IV
Additional 0.1 mg IV until desired effect reached |
|
|
What is the duration of action of flumazenil?
|
30-60 minutes
|
|
|
Flumazenil induced benzodiazepine antagonism is NOT associated with what?
|
Acute anxiety
Hypertension Tachycardia |
