Pharm Quiz 1 Flashcards
What neurotransmitter and receptor sites does benzodiazepines stimulate and what is the mode of action?
GABA, upon activation GABA receptors conduct chloride through the channels in the cell membrane which leads to neuraa hyper polarization—> inhibitory neurotransmitter affects
What are the 5 reasons we give benzodiazepines?
Sedation Anxiolysis Anticonvulsant Skeletal Muscle Relaxation Anterograde amnesia
Multiple drugs interact with GABA receptors through multiple mechanisms, this can lead to what?
Cross tolerance
What is the reversal agent for benzodiazepines?
Flumazenil
Where are the only muscles that contain GABA receptors?
skeletal muscle
How do benzodiazepine compare to barbiturates?
- anything a barb can do a benzo can do better
- less tolerance
- less taxiphalxis
- less abuse potential
- greater margin of safety
- fewer drug reactions
- NO induction of microsomal enzymes
- less addiction potential compared to barbiturates
Benzodiazepines have no retrograde amnesia, true or false?
true—-> it has anterograde amnesia
retrograde = loss of stored information anterograde = forgetting things that happen from the time you receive the benzo
Describe the skeletal muscle relaxation characteristics of benzodiazepines
- No effects at the neuromuscular junction
- the effects are of central origin inadequate for surgey
What are the two most desirous effects preoperatively and intraoperatively for benzodiazepines?
anxiolysis and hypnosis
Are the anticonvulsant effects of benzodiazepines potent enough to stop a grand mal seizure?
yup
Chemically what is the structure of all benzodiazepines?
drugs with a benzene ring fused to a diazepine ring, all clinically useful benzodiazepines contain a 5-aryl substituent and a 1,4 - diazapine ring
What are the most common side affects of benzodiazepines?
- Fatigue and drowsiness are the most common
- sedation usually disappears in 2 weeks
- decreased coordination
- no significant BP or HR effects due to no GABA receptors in the heart or the vascular
- minimal ventilation effects unless lung disease present
- decreased cognitive function
- transient anterograde amnesia
- suppression of adrenal cortisol levels
Dependence may require ___ months of ___ use.
6 months of continuous use(6 months of continuous use of barbs you would probably be dead)
What symptoms may be seen in benzodiazepine withdrawals?
irritability, insomnia, tremulousness
What are the two metabolic pathways of benzodiazepines?
- Glucuronidation
2. Hepatic microsomal enzyme
Glucuronidation is the exclusive metabolic pathway for what 3 benzodiazepines?
- lorazepam
- oxazepam
- temazepam
Are there any ACTIVE benzodiazepine metabolites involved in Glucuronidation?
no
What if any effects by aging on Glucuronidation.
little effect by aging
Are there any ACTIVE benzodiazepine metabolites involved with Hepatic microsomal enzyme metabolism
yes
Describe the process of Hepatic microsomal enzyme metabolism
Oxidative process sensitive to aging, liver disease and anesthetic agent exposure
Can pregnant women receive benzodiazepines?
NO! They are class D and X drugs-potential for harm to unborn demonstrated
exposure to benzodiazepines during pregnancy has resulted in a slight risk of cleft palate in new borns
Midazolam is ___ soluble and it has a ___ ring
Water, imidazole
How much more potent is Midazolam(versed) over Diazepam(valium).
How much affinity does Midazolam have over Diazepam?
2-3X more potent and it has twice the affinity of Diazepam
What is the pKa of Midazolam?
6.1
What happens to the solublility of Midazolam as it reaches physiologic pH?
Midazolam at its pKa is water soluble, when it is injected into the body and reaches physiologic pH is becomes lipid soluble.
What happens to the Imidazole rings in response to pH and solubility?
- ph < than 4.1 Imidazole rings opens and Midazolam is water soluble
- when Midazolam reaches physiologic ph, the Imidazole rings close and it becomes lipid soluble
What impact of being water soluble have on the preparation of Midazolam?
Water soluble preparation means no propylene glycol solution like diazepam and less pain after IV injection
What % of Midazolam is absorbed from first pass clearance when given orally?
50%—>rapid GI absorption
Midazolam has a short duration of action from single dose due to what?
redistribution
By what speed does Midazolam cross the BBB?
Rapid passage across the BBB
By what speed does Midazolam have effect-site equilibration time?
slow effect-site equilibration time
What should you do knowing the effect-site equilibration time of Midazolam?
Space IV doses to allow peak clinical effects
Does intranasal have any first pass effects?
no
Based upon Midazolam’s extensive plasma protein binding, what effect would it have on someone with hypoalbuminemia?
a does would have an exaggerated affect
How does the sedation 1/2 life of Midazolam compare to diazepam and lorazepam
Its shorter
Is Midazolam the only benzo used for infusions?
yes
What is the elimination 1/2 time of Midazolam?
1-4 hours, but may be doubled in the elderly
How does the volume of distribution of Midaz compare to that of diazepam?
The Vd of midazolam = that of diazepam(valium) due to similar lipid solubility and high protein binding
How does being elder or obese affect the Vd of Versed?
Greater Vd due to increased peripheral tissue distribution aids in prolonging duration of action