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47 Cards in this Set
- Front
- Back
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Name the five principle pharmacological effects of benzodiazepines |
Sedation Anxiolysis Anticonvulsant actions Spinal cord mediated muscle relaxation Anterograde amnesia |
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Name 4 benefits of benziodiazepines compared to barbiturates |
Less tendency to produce tolerance Less potential for abuse Greater margin for safety after overdose Fewer/less serious drug interactions |
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Name the two chemical structural components of all benzodiazepines |
Benzene Ring 7 membered diazepine ring |
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Describe the mechanism of action of benzodiazepines |
Facillitate GABA (principal inhibitory NT in CNS) |
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Describe the action of GABA |
GABA binds receptor Enhanced opening of Cl- channel Increased chloride conductance Hyperpolarization of postsynaptic cell membrane Resistance to excitation |
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Highest density of GABA receptors in the __________
Also distributed through: |
cerebral cortex
hypothalamus, cerebellum, midbrain, hippocampus, medulla, and spinal cord |
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Describe the effects of benzodiazepines at different concentrations:
20% 30-50% >60% |
20 = anxiolysis 30-50 = sedation >60 = unconsciousness |
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Diazepam is _______ in water
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insoluble |
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Diazepam undergoes _______ absorption from the GI tract following oral administration and reaches peak plasma levels in ______ minutes |
rapid absorption from GI tract peak plasma levels in 60 minutes |
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After IV bolus of diazepam, termination of action is due to: |
redistribution to inactive tissue deposits |
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Diazepam has a ______ volume of distribution this is due to: |
large lipid solubility |
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The Vd of diazepam is __________ L/kg |
1-1.5 L/kg |
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Does diazepam cross the placenta? |
Yes |
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What percent of diazepam is protein bound? |
96% |
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Diazepam is primarily bound to _______ |
albumin |
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How do cirrhosis or renal failure affect protiein binding of diazepam? |
cirrhosis causes low levels of albumin renal failure causes uremic compounds to compete for binding sites on albumin
Both increase the free fraction of the drug |
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If a protein binding of diazepam changes from 96% to 92%, what happens to the free fraction of the drug? |
It doubles |
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Describe the metabolism of diazepam |
Primary hepatic oxidation via the N-demethylation oxidative pathway
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Name the two principle metabolites of diazepam: |
oxazepam desmethyldiazepam |
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What is the elimination half time of diazepam? |
21-37 hours |
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Name an active metabolite of diazepam |
Desmethyldiazepam |
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What is the elimination half time of desmethyldiazepam? |
48-96 hours |
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Describe the effect of cirrhosis on the elimination half time of diazepam. |
Decreased protein binding (increased Vd)
Decreased hepatic clearance
Elimination half time increased by five times |
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What factors affect volume of distribution |
Protein binding (inversely proportional) Ionization (Inversely proportional to % ionized) Solubility (directly proportional to lipid solubility) |
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How are diazepam metabolites cleared from the body? |
cleared in the urine as conjugates of glucuronic acid |
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Diazepam and desmethyldiazepam are metabolized by ______ enzymes. Why is this important |
microsomal enzymes
drugs like cimetidine are inhibitors of microsomal enzymes, which increases the elimination half-time. |
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Name four clinical uses for diazepam: |
Preoperative anxiolysis Treatment of delirium tremens Treatment of local anesthetic induced sz Skeletal muscle relaxant (lumbar disc disease) |
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How many times stronger is midazolam compared to diazepam? |
2-3 times more potent |
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Why is midazolam buffered to a pH of 3.5? |
Because the imidazole ring remains open at pH < 4. This makes midazolam water soluble prior to injection. |
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What happens to the imidazole ring on midazolam upon injection? |
Ring closes, and drug becomes highly lipid soluble. |
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What are two benefits of a water soluble drug? |
Obviates need for a dissolving agent Low incidence of venoirration or thrombophlebitis |
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How much of midazolam is protein-bound? |
>96% |
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What is the elimination half time of midazolam |
1-4 hours |
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Midazolam has a large volume of distribution, but a short elimination half time. Why is this? |
Because of the degree of hepatic clearance (greater than diazepam) |
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How much PO midazolam reaches systemic circulation? Why? |
Only 50 percent due to first pass hepatic extraction. |
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Describe metabolism of midazolam. |
Hepatic microsomal enzymes (cytochrome p450) weakly active metabolites exreted as glucuronide conjogates. |
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Does cimetidine affect metabolism of midazolam? |
No |
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Do any medications affect metabolism of midazolam? |
Erythromycin Calcium channel blockers (suppress p450 - inhibit metabolism)
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Clinical uses for midazolam |
preoperative anxyolysis sedation of pediatric patients adjunct for MAC cases |
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PO midazolam dose for pediatric patients pre-op |
0.5 mg/kg PO |
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Describe the potency of lorazepam compared to midazolam |
More potent amnestic than diazepam or midazolam. Produces anterograde amnesia up to 6 hours. |
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Desribe metabolism of lorazepam |
Hepatic oxidation Inactive metabolites Excreted as gluconurides |
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CNS effects of benzodiazepines (3) |
Anticonvulsant Dot suppress EEG Reduce MAC for inhaled anesthetic |
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Respiratory effects of benzodiazepines |
dose related central respiratory depression airway obstruction more common than apnea synergistic effects with opioids |
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Cardiovascular effects of benzodiazepines |
Little to no hemodynamic effects Slight reduction in ABP Homeostatic reflex mechanisms maintained |
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Flumazenil Dose and duration of action |
0.2 mg IV, the 0.1 mg Duration 30-60 min |
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Is flumazenil associated benzodiazepine antagonism associated with anxiety, hypertension, or tachycardia? |
NO |
