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Anes. Pharm I Test 2

benzodiazepines, flumazenil, naloxone, doxapram

What are the 5 pharmacologic effects of benzodiazepines? sedation, anxioslysis, anticonvulsant actions, skeletal muscle relaxation, antegrade amnesia
What is the mechanism of action of benzodiazepines? Benzo receptors are part of GABA receptor, which, when activated cause increased binding of GABA to its receptor, opening Cl- channels = hyper polarization = inhibition of excitation of neuron
Benzodiazepines also have an attraction to ________ receptors in the brainstem and spinal cord glycine
What is GABA? a major inhibitory neurotransmitter in the CNS
What is glycine? the major inhibitory neurotransmitter in the brainstem and spinal cord
Sedative and anticonvulsant effects are explained by what mechanism of action of benzodiazepines? enhancement of GABA inhibitory effect
Muscle relaxation effect is explained by what mechanism of action of benzodiazepines? glycine-like inhibition in the spinal cord motor neurons
Anxiolytic effect is explained by what mechanism of action of benzodiazepines? inhibition of afferent conduction to anxiety centers at the brainstem level
GABA receptors have separate binding sites for what 3 things? benzodiazepines, barbiturates, and ETOH
If the GABA receptor is activated at more than one site, the inhibition of the CNS to excitation is __________ synergistic
Midazolam (Versed) is water soluble at what pH? 3.5
Midazolam is lipid soluble at a pH > 4. What chemical structure of midazolam accounts for this? imidazole ring
Does Midazolam cause pain on IV or IM injection? Why or why not? No; because it does not have to be dissolved in a carrier agent since it is water soluble at 3.5 pH; carrier agents are what cause the sting upon administration
What 2 things is midazolam IV compatible with? opioids and LR
What routes can midazolam be given in? PO, IM, IV, sublingual, intranasal (very rapid onset)
What are 4 uses of midazolam for the CRNA? premedication, sedation, induction of anesthesia, maintenance of anesthesia
What are the effects of midazolam on the CV system? decrease in BP r/t SVR decrease, increase in HR, no change in CO; the hemodynamic effect is exaggerated in hypovolemic patients
What are the effects of midazolam on the respiratory system? dose-dependent decrease in ventilation (COPD patient show exaggerated effect), apnea possible with big doses
What are the effects of midazolam on the CNS? decreases CMRO2 and cerebral blood flow
Can midazolam cause an EEG to become isoelectric? No
Excitement occurs in less than 1% of patients who receive midazolam. What do you treat this with? Flumazenil
What is the onset of midazolam? 0.9 - 5.6 minutes (be sure to allow equilibration before redosing)
What is the elimination 1/2 time of midazolam? 1 - 4 hours; may be doubled in the elderly
How is midazolam metabolized? in the liver via C-P450 metabolism (patients with endured enzymes may require frequent re-dosing or higher doses)
What is the dosage of midazolam used for pediatric premedication? 0.3 - 0.5 mg/kg PO (allow 30 minutes for effect)
What is the dosage of midazolam used for sedation? 1 - 2.5 mg IV
What is the dosage of midazolam used for induction? 0.1 - 0.2 mg/kg IV (though will probably never do this)
Is diazepam (valium) water soluble? What are the implications of this? No; must be dissolved in carrier agent which causes pain on injection
Rapidly absorbed orally with peak concentrations in _____ 1 hour
True or false: IM or IV are the best routes to give diazepam False! will probably never give IV and should never be given IM r/t unreliable absorption
What are the CV effects of diazepam? minimal decreases in BP, CO, SVR; synergistic decreases in these three with fentanyl admin; decreases are exaggerated with hyopvolemic patients
What are the respiratory effects of diazepam? depresses response to CO2 (minimal depressant effects until 0.2 mg/kg), decrease in TV
What are the CNS effects of diazepam? decreased CMRO2, cerebral blood flow, and ICP; relaxant effect on skeletal muscle tone; decreased MAC up to 30%; anxiolysis, amnestic; anticonvulsant prophylaxis
Rank the amnestic effect of the 3 benzodiazepines we have studied from greatest to least lorazepam > midazolam > diazepam
What are the 2 active metabolites of diazepam? desmethyldiazepam and oxazepam
Because desmethyldiazepam (a metabolite of diazepam) is only slightly less potent than diazepam, drowsiness returns ________ after admission 6 - 8 hours; causes prolonged effect of diazepam
What is the elimination 1/2 life of diazepam? 21 - 37 hours; increases with age; increases with cirrhosis of liver; prolonged by cimetidine (Tagamet)
What is the dosage of diazepam in adults and when does it reach its peak effect? 10 - 15 mg PO; peak effect 55 minutes after admin
Is Lorazepam (Ativan) soluble in water? No; must be dissolved in carrier agent (polyethylene glycol or propylene glycol)
What routes of administration can lorazepam be given in? PO, IM, IV
Due to Lorazepam's slow onset and prolonged duration of action, it's use is limited. Is it useful in outpatients for anesthetic purposes? What patient population is it useful in? Not good for outpatients r/t long effects; good for heart surgery patients because of long effects
How long can antegrade amnesia last with administration of lorazepam? up to 6 hours
Does lorazepam have active or inactive metabolites? inactive
Why does lorazepam have a longer clinical effect than diazepam? lorazepam is more slowly released from GABA receptors
What is the dose of lorazepam? 50 mcg/kg (up to 4 mg)
What is the peak concentration of lorazepam? 2 - 4 hours
What is the elimination 1/2 life of lorazepam? 10 - 20 hours
What is the mechanism of action of flumazenil? competes with benzodiazepines for the benzodiazepine receptor sites on GABA receptors
Reversal of benzodiazepine effects with flumazenil is buffered by the _____________ weak agonist effects
In contrast to nalaxone, what will you NOT see with flumazenil administration? acute anxiety, stress response, HTN, tachycardia
What could you see with administration of flumazenil in those patients who are on seizure treatment? withdrawal seizures
What is the initial dose of flumazenil? 0.2 mg IV (8 - 15 mcg/kg)
What is the onset of flumazenil? 2 minutes
What is the additional dose(s) of flumazenil? 0.1 mg IV (up to total of 1 mg)
What is the duration of flumazenil? 30 - 60 minutes
If the goal is to decrease the sedative effect of a benzodiazepine, what would the dose of flumazenil be? 0.3 - 0.6 mg
If the goal is to abolish the benzodiazepine effect altogether, what would the dose of flumazenil be? 0.5 - 1 mg
What is the mechanism of action of naloxone? the attraction of naloxone for the receptor displaces the opioid from the receptor. the antagonist then binds with the receptor and inactivates it.
What receptors does naloxone respond to the most? mu receptors more than kappa and delta
What are the clinical indications for the use of naloxone? opioid overdose, post op ventilatory depression due to maternal opioids, adverse effects of spinal and epidural opioids
What is the dose of naloxone? 0.5 - 1 mcg/kg q 3 - 5 minutes
What is the onset and duration of naloxone? onset: 1 - 3 minutes; duration: 30 - 45 minutes
Where is naloxone metabolized primarily? the liver
What are the positive effects of the administration of naloxone? if titrated properly, ventilatory depression caused by opioids can be reversed without weakening analgesic effect; return of airway reflexes
What are the negative effects of the administration of naloxone? acute pulmonary edema, sympathetic stimulation - pain, tachycardia, ventricular irritability, HTN, N/V
Can naloxone cross the placenta? Yes; it can cause withdrawal symptoms in neonate if opioid-abusing mother
If a patient is dependent on opioids and appears normal on them and a CRNA administers too large of a dose of opioids and needs to reverse the adverse effects, what will happen with naloxone administration? it may precipitate abstinence syndrome
What 6 patient populations should you be careful with and possibly avoid naloxone administration? critically ill, CAD, preexisting lung disease, CHF, cardiac surgery, opioid dependence
What is doxapram? a CNS stimulant
What is the mechanism of action of doxapram? stimulates hypoxic drive via the activation of the chemoreceptors in the carotid bodies
Does doxapram primarily produce an increase in respiratory rate or tidal volume? tidal volume, produces small increase in respiratory rate
What are 2 indication for the use of doxapram? COPD patients who breath based on hypoxic drive but need supplemental O2; ventilatory depression and CNS depression due to drugs
What is the dose of doxapram? 0.5 - 1 mg/kg (max 4 mg/kg)
What is the onset and duration of doxapram? onset: 1 minute; duration: 5 - 10 minutes
Where is the primary site of metabolism of doxapram? the liver
What are the CNS effects of doxapram? stimulates hypoxic drive r/t activation of chemoreceptors in carotid; confusion, dizziness, seizures, increased sympathetic outflow, vomiting, increased body temperature
What are the respiratory effects of doxapram? increases minute volume by increasing Vt and slightly increasing RR, increases O2 consumption, wheezing, tachypnea
What are the CV effects of doxapram? increased sympathetic stimulation, HTN, tachycardia, cardiac dysrhythmias
What are 7 patient populations in which you should be careful with and possibly avoid administration of naloxone? seizure disorder, cerebrovascular disease, acute head injury, coronary artery disease, HTN, asthma, patients who have been given halothane
1 mg/kg of doxapram makes the body think that its PaO2 is what? 38 mmHg
Created by: Mary Beth



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