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232 Cards in this Set
- Front
- Back
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pharmacokinetics
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what the body does to the drug
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absorption
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diffusion through mucosa into plasma
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bioavailability
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resulting plasma concentration
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distribution def.
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influence of blood/brain barrier, plasma protein binding, and fat (younger children need higher dosage due to lower volume of distribution)
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metabolism def.
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break down of patent drug to metabolites
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elimination def.
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clearance
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pharmacodynamics
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what the drug does to the body (desires vs. adverse effects)
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what leads to % bioavailability?
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drug absorption into systemic circulation
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PO route bioavailability
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requires liposolubility (tissue diffusion) and first pass hepatic metabolism by CP450 enzymes = 40-60% BA
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sublingual (topical) route bioavailability
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requires liposolubility and metablism of unknown amount swallowed = 80% BA
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IV, IM and SC routes bioavailability
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100% BA
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drug distribution (plasma to tissue)
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1) rate and amount dependent on degree of tissue prefusion (blood supply) and drug affintiy for that tissue; 2) sedative drugs with good lipid solubility are distrubuted in proportion to the degree of tissue perfusion (brain --> kidney/liver --> muscle --> fat/bone); 3) nature of capillary bed affects distribution (CNS capillaries have tight endothelial junctions for the "blood-brain barrier"); 4) plasma protein binding limits amount of free drug in the blood stream; 5) competition for the same protein binding sites increases amount of free drug availability (increases potential toxicity)
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metabolism
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1) generally done in gut mucosa and liver by cytochrome P450 enzymes; drugs influence enzyme systems differently, drug interactions may intensify or minimize drug action; 2) creates metabolites, some forms may also be active (codeine --> morphine)
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drugs that increase availability of codeine, hydrocodone and oxycodone
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cimetidine (tagamet), fluoxitine (prozac), paraxetine (paxil), other SSRIs
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drugs that decrease availability of codeine, hydrocodone and oxycodone
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rifampin
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drugs that increase availability of alprazolam (xanax), midazolam (versed), triazolam (halcion), alfentanil (alfenta) and lentanyl
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clarithromycin (biaxin), erythromycin, amiodarone, most protease inhibitors, grapefruit juice
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drugs that decrease availability of alprazolam (xanax), midazolam (versed), triazolam (halcion), alfentanil (alfenta) and lentanyl
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barbituates, carbamazepine (tegretol), phenytoin (dilantin), st. john's wart
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drug elimination
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1) drug half-life - time required to reduce plasma concentration by 50%; it takes 4 half-lives for complete elimination; 2) time concentration curve - IV drug does not require absorption or distribution like PO; once PO drug is distributed, it has the same elimination rate as IV drug; 3) half-life does not detemrine drug duration of action; drugs vary as to required threshold concentration to achieve effect
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drug action
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agonists and antagonists bind to like-receptors
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drug efficacy
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effectiveness
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drug potency
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amount required to create effect (not related to efficiacy or toxicity)
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drug safety
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therapuetic index - range between effective dose and toxic dose; not all adverse reactions are dose related (allergic vs. toxic reactions)
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therapeutic index
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LD(for 50% of pop) / ED (for 50% of pop); the higher the therapeutic index, the safer the drug
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drugs with wide therapeutic index
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1) penicillin, 2) acetaminophen, 3) ibuprofen, 4) antihistamines, 5) benzodiazepines
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drugs with narrow therapeutic index
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1) lidocaine, 2) epinephrine, 3) codeine, 4) demerol, 5) hydrocodone, 6) narcotics
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types of sedative drug side effects
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1) Type A: major adverse event, affecting VS (resp depression, bradycardia); 2) Type B: mild adverse event: hives, hiccups, diplopia, nausea, idiosyncratic; 3) Paradoxica: opposite of desired effect (euphoria vs. dysphoria) ; 4) potentiation: synergistic effect when combining drugs with similar actions (1+1 = 3)
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there is no magic bullet
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studies have found that there is no single drug or combination of agents superior in its efficacy for dental sedation
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procedural sedation (PS)
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acute application of agents to overcone situational anxiety/fear or induced pain/stimulation and to immobilize during treatment; requires higher doses, which may lead to toxicity
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lifestyle sedation
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chronic application of agents to manage everday living, requires lower doses and may lead to habit or tolerance
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where is the evidence to support best sedation practices?
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problem: poorly standardized research design makes cross-study comparison almost impossible; 1) small number of subjects, 2) lack of randomized subject assignemnt and control group, 3) varying age groups and behaviors/past experiences, 4) varying or poorly categorized pre-op behavior, 5) lack of quantifiable criteria for judging success/failure, 6) lack of interexaminer reliability and blindedness, 7) confounding variables not controlled (use of nitrous, local, current medications), 8) variations in drugs, dosages and routes used, 9) variation in waiting time prior to onset of procedure, 10) degree of physical stimulation, extent of invasive procedure
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select agents with:
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1) high therapeutic index, 2) low potential to deliver sedation beyond desired level, 3) minimum potential to create respiratory depression and somnolence, 4) reversal agent
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picking a sedative agent depends on the child's:
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1) age/emtional maturity, 2) cognitive development, 3) temperment and attachment characteristics, 4) coping and communicative skills, 5) level of displayed behavior, 6) current medications, 7) health history, 8) physical (risk) assessment, 9) past experience
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picking a sedative agent depends on the operator's:
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1) skills and training, 2) experience and preference, 3) estimated length of procedure, 4) desired goal (depth) of sedation
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continuum of consciousness
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1) awake, 2) minimal sedation: N2O + single benzodiazepine or antihistamine, 3) moderate sedation: low dose combines hyponotics, opiates, 4) deep sedation: hig dose combinations, 5) general anesthesia
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barbiturates: sedation, analgesia, amnesia
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1) sedation: +++, 2) analgesia: none , 3) amnesia: none
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benzodiazepines: sedation, analgesia, amnesia
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1) sedation: +++, 2) analgesia: none , 3) amnesia: +++
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opioids: sedation, analgesia, amnesia
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1) sedation: ++, 2) analgesia: +++ , 3) amnesia: none
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ketamine: sedation, analgesia, amnesia
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1) sedation: +++, 2) analgesia: +++ , 3) amnesia: ++
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propofol: sedation, analgesia, amnesia
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1) sedation: +++, 2) analgesia: none, 3) amnesia: +
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chloral hydrate: sedation, analgesia, amnesia
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1) sedation: ++, 2) analgesia: none, 3) amnesia: none
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nitrous oxide: sedation, analgesia, amnesia
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1) sedation: ++, 2) analgesia:++ , 3) amnesia: +
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trends in postdoctoral education
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trends in sedation practice
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AAPD member attitudes of sedation
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routes of administration
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1) inhalational, 2) enteral: PO, rectal, 3) parenteral: IV, IM, SC, SM, SL, IN
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oral route disadvantages
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1) unpredictable: level can be anticipated, but never preducted (must accept 30% failure rate), 2) not titratable to desired effect, redosing not advised, 3) low bioavailability due to first pass hepatic metabolism and variation in intestinal absorption (GI pH, motility, contents), 4) poor taste and GI disturbance, 5) slow onset and recovery
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common oral agents
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1) diazepam (valium), 2) midazolam (versed), 3) hydroxyzine (atarax), 4) promethazine (phenergan), 5) chloral hydrate, 6) meperidine (demerol)
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common single agents (minimal sedation for anxiolysis)
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1) diazepam, 2) midazolam, 3) hydroxyzine
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common combine agents (moderate sedation)
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1) chloral hydrate and hydroxyzine, 2) demerol and phenergan, 3) chloral hydrate, demerol, hydroxyzine
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benzodiazepines used
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1) triazolam (halcion), 2) diazepam (valium), 3) midazolam (versed)
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antihistamines used
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1) hydroxyzine (atarax), 2) promethazine (phenergan), 3) diphenhydramine (benedryl)
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advantages of oral benzodiazepines
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1) wide therapeutic index (safety/efficacy not easily affected by dosage), 2) acceptable properties (anxiolytic, amnestic, anticonvulsant, muscle relaxant), 3) short to intermediate onset and duration of action, 4) minimal adverse reactions, 5) reversal agent available (flumazenil)
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orla benzodiazepine properties
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1) sequence of effects occurring with increasing serum levels (receptor site occupancy): anxiolysis, anterograde amnesia, sedation; 2) sedative effect occurs due to interaction with GABA receptors increasign their inhibitory action
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triazolam (halcion) administration
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1) dose: 0.125 mg (child) or 0.25 (adult) oral or sublingual: crush tablet and sprinkle under tongue, has 28% better bioavailability; 2) little or no improvement in child's behavior; 3) use with caution in pediatrics and geriatrics; 4) onset: 30-60 min, half life: 2 hours; 5) promoted as "sleep dentistry" by DOCS; 6) booster (incremental) doses can lead to overdose
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diazepam (valium) properties
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1) safe and effective in children, 2) inexpensive, 3) muscle relaxant (spactic cerebral palsy), 4) delayed onset (30-60 min), 5) prolonged recovery due to active metabolites: desmethyldiazepam, temezepam, oxazepam, 5) drug interactions (influcend by CP450 enzymes) with ertyhromycin and grapefruit juice will increase sedation
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diazepam (valium) dosage
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1) solution = 5mg/5mL, 2) dosage = 0.2-0.5 mg/kg, 3) 2-5 yo = 2-5 mg; 6-10 yo = 5-10 mg; 11-16 yo = 10-15 mg; 4) guide: 1 mg/year of age
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midazolam vs: diazepam
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1) onset of action: midazolam-20-30 min; diazepam-45-60 min, 2) duration of action: midazolam-30-40 min; diazepam-60 min; 3) several studies have indicated that midazolam was more effective
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midazolam properties
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in comparison to diazepam: 1) water soluble (less iritating IM/IV), 2) higher lipid solubility (rapid onset), 3) greater potency = 2x diazepam, 4) faster recovery (half life = 2-3 hours), 5) stronger amnestic
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drugs that potentiate sedation (ingibits CP450 activity) with midazolam
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1) erythromycin, 2) clarithromycin, 3) grapefruit juice, 4) ketoconazole, 5) cimetidine (tagmet), 6) verapamil/diltazem
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drugs that inhibit sedation (induces CP450 activity) with midazolam
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1) carbamazepine (tegretol), 2) phenytoin (dilantin), 3) rifampin (rifadin)
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midazolam chemistry
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active midazolam has a pH >5 and is a closed ring; inactive midazolam has a pH =3.5 and is an open ring
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midazolam physiological complications
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1) ataxia, loss of head control "floppy doll" (potential injury and airway problem), 2) hiccups, 3) diplopia (double vision), 4) respiratory depression (stridor, apnea, hypercarbia, more common with IM/IV routes), 5) paradoxical response (2%) - "negativism" - dysphoria (whining irritable), agitation (combativeness, anger, hostility, rage), higher incidence in ADHD; 6) nightmares/hallucinations
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midazolam paradoxical response
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1) dysphoria and agitation well documented, 2) uncontrolled screaming and thrashing not responsive to console attempts, 3) onset is about 45 minutes after administration and may last for several hours, 4) reversed by flumazenil
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midazolam operational approach
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1) unique properties of midazolam permits a change in operational phiolosophy: shorter appointments, quadrant restorative dentistry, faster turn around time, improved safety with reversal agent, efficient emergency dental service; 2) place child on to passive restraint, but do not wrap the child until behavior dictates
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midazolam oral dosage
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0.5-0.75 mg/kg, max dose = 20 mg; 4-7x parenteral dose
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midazolam oral route onset, duration, recovery, BA
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1) onset - 20-30 min (tmax = 1 hr); 2) duration of action - 30-45 min; 3) recovery 60-90 min (t1/2 = 2-3 hrs); 4) low bioavailability (36%); cytochrome P450 enzymes in GI mucosa cells and liver; the < BA, the > variability in clearance and blood levels (depth of sedation, predictable outcome)
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midazolam oral syrup
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2 mg/mL in 118 mL bottle
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midazolam injection form for oral route
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1) use the highest concetration (5 mg/mL) to minimize volume to be swallowed; 2) mask the bitter taste with flavoring agents; 3) national shortage so reserved for IN for now
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midazolam combinations with analgesics
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1) acetaminophen elixir, 15 mg/kg; 2) ibuprofen suspension, 10 mg/kg; 3) meperidine syrup, 1 mg/kg
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hydroxyzine properties
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1) antihistamine (decreases edema, inflammation), 2) bronchodilator, 3) anticholinergic (drying), 4) antiemetic, 5) sedative, 6) potentiates CNS depressants
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hydroxyzine dosage
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2 - 3.7 mg/kg (single agent with nitrous)
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hydroxyzine half life, onset, duration
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1) half life = 3-20 hrs, 2) onset - 30-40 min, 3) duration - 2-4 hrs
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hydroxyzine suspension types
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1) hydroxyzine pamoate (vistaril) - 25mg/5mL; 2) hydroxyzine hcl (atarax) - 10 mg/5mL (vanilla flavored)
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hydroxyzine capsules
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hydroxyzine pamoate - 50 mg or 25 mg; dissolve capsule into flavoring agent
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oral midazolam + hydroxyzine dosages
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1) 0.3 mg/kg midazolam + 3.7 mg/kg hydroxyzine OR 2) 0.5 mg/kg midazolam + 2.0 mg/kg hydroxyzine
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OTC diphenhydramine dosage
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1-2 mg/kg
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OTC diphenhydramine types
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1) benadryl tablets (25, 50 mg), syrup 12.5 mg/5mL and elixir 25 mg/5mL; 2) diphen tablets 25 mg
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benzodiazepine antagonist and its dosage
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flumazenil (romazicon) 1) 0.01 mg/kg initial dosage, up to max dose of 0.2 mg; 2) follow-up dosage 0.005 mg/kg up to max dose of 0.1 mg up to 4 additional times 3) max total dose is 0.05 mg/kg or 1 mg, whichever is lower
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flumazenil concentration
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0.1mg/mL in 5 and 10 mL vials; short shelf life and cost @ $12/mL dose
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flumazenil administration
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1) IV, onset of action 1-2 min, half life 1-1.5 hrs, 2) SM - maxillary tuberosity site away from LA site, onset of action within 5 minutes
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flumazenil example with 20 kg (6 yo) child
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1) initial dose = 0.01 mg/kg x 20 kg = 0.2 mg; 2) volume given = 0.2 mg / 0.1 mg/mL = 2 mL in 3mL syringe given SM or SL; 3) wait 3-5 minutes for desired effect; 4) follow-up dose 0.005 mg/kg x 20 kg = 0.1 mg / 0.1 mg/mL = 1 mL SM or SL
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flumazenil recovery
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1) airway support and oxygen supplementation, 2) half life = 20-30 min (1/4 that of midazolam), 3) observe patient for 2 hours, place on pulse oximeter, observe for signs of resedation, hypoventilation, anxiety
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oral administration techniques and syringe etiquette
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1) child is slightly reclined, 2) use slowly, 3) inject by side of tongue or alongside your finger, 4) complications: aspiration, laryngospasm, conjunctivitis, 5) pinch nostrils closed?
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nasal route advantages
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1) Cmax is equivalent between IV and IN reoutes, 2) rapid onset = 10 min, 3) does not require compliance, 4) beneficial with emergency extractions, 5) higher bioavailability, 6) avoids unpalatbale taste, 7) relaxed adherence to dietary precautions
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nasal route mechanism of absorption
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1) drugs sprayed on to nasal mucosa are absorbed rapidly through the cribiform plate into the CNS by 3 routes: olfactor neurons, surrounding capillary beds, CSF, 2) nasal mucosa is only location in the body that provides a direct link to the CNS
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nasal route use of atomizer
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1) small tip: fits into tiny naris, 2) bendable tip: better control, 3) semipermeable soft plug cathced fluid run back, seals and cushions the nose, 4) spray = 30 micrometer particel size, spray in short bursts, 1/2 dose in each naris, 0.1 mL dead space in system, 5) luer lock connection directly to 1 mL tuberculin syringe
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midazolam IN dosage
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0.2-0.35 mg/kg, max dose = 10 mg
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exceptions to a fized dosage regimen
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1) younger pts require higher dosage due to lower volume of distribution (0.35 vs 0.2 mg/kg IN and 0.65 vs. 0.5 mg/kg PO), 2) obese pts require lower dosage (if weight > weight for age norm, then give dose based on age, not weight, 3) observe maximum recommended dose limits (midazolam = 20 mg PO, 10 mg, IN)
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chloral hydrate pharamacokinetics
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1) rapid metabolism to trichloroethanol, 2) half life - 4-14 hrs, 3) converted in the liver to trichloroacetic acid, a cardiotoxic metabolite, 4) chemical structure resembles halothane- myocardium may be sensitized to adrenergic amines
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chloral hydrate advantages
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1) hypnotic - produces sleep, 2) long history of use/safety, 3) wide therapeutic range, 4) best used in children 2-5 years of age
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chloral hydrate disadvantages
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1) produces paradoxical reactions (agitation, disinhibition, dysphoria), 2) bitter taste, 3) mucosal/gastric irritation creates vomitting, 4) delayed onset and prolonged recovery, 5) somnolence and hypotonicity of glossal muscles may produce airway obstruction, 6) arousal frequency related to intensity of stimulation, 7) no reversal agent available
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chloral hydrate + hydroxyzine
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1) chloral hydrate - dosage[35-50 mg/kg], dose range [500-1500 mg], concentration [100 mg/mL], 2) hydroxyzine - dosage [1-2 mg/kg], dose range [25-50 mg], concentration [5 mg/mL]
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opioid (narcotic) agents
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1) meperidine (demerol), 2) fentanyl, 3) morphine, 4) codeine, 5) alphaprodine (nisentil)
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opioid properties
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1) analgesic, 2) sedative, 3) antispasmodic, 4) effects can be reversed with nalaxone (narcan)
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nalaxone
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1) give 0.1 mg/kg every 2-3 minutes up to 2 mg total, 2) 0.4 mg/mL in 10 mL vial, 3) for a 15 kg child - 1.5 mg (4 mL) SM in 10 mL syringe
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meperdine disadvantages
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1) gastric upset and emesis, 2) reduce MRD for LA as narcotics reduce plasma binding of LA (decrease seizure threshold), 3) produces respiratory depression and orthostatic hypotension, 4) releases histamines from mast cells (precuation with asthmatics without med consult)
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oral meperidine dosage
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1) 1-2 mg/kg, 2) max dose of 50 mg, 3) syrup = 50 mg/5 mL (bitter after taste), 4) often combines with promethazine
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promethazine (phenergan) properties
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1) antihistamine, 2) anticholinergic, 3) sedative (minimal when used alone), 4) bronchodilator, 5) lowers seizure threshold, 6) creates extrapyramidal responses (jerky limb movements)
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promethazine doage and types
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1) 1-2 mg/kg, 2) note to be given to a child <2 years of age, 3) vanilla flavor oral formulas: elixir (5mg/5mL), syrup plain (6.25 mg/5mL), syrup fortis (25 mg/5 mL)
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oral opioid combinations
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1) use has decreased in recent years, 2) has analgesic, anti-anxiety and sedation actions, 3) used for long apts on moderate to severely apprehensive pts when moderate to deep sedation is desired, 4) variable effects when taken orally, 5) may cause respiratory depression, hypotension, unconsciousness, increased risk of lidocaine toxicity, and nausea and vomiting, 6) effects begin in 45-60 minutes with duration of action 2-3 hours
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common oral opioid combinations
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1) meperidine 2 mg/kg + promethazine 1mg/kg, 2) meperidine 1-2 mg/kg + midazolam 0.5-0.75 mg/kg, 3) meperidine 2 mg/kg + chloral hydrate 30 mg/kg + hydroxyzine 2 mg/kg
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oral opioid combinations effect of respiration
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1) minute volume = RR + tidal volume, 2) meperidine - decreases RR, 3) chloral hydrate - decreases tidal volume 4) combination increases potential for respiratory depression
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meperidine + midazolam combination oral regimen
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1 mg/kg meperidine + 0.5 mg/kg midazolam (reduced by half the more potent agent)
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submucosal route
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infiltration in mucobuccal fold at maxillary tuberosity (high vascularity results in rapid absorption)
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meperidine given SM
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1) creates erythematous wheals, urticaria and pruritis (itching) at injection site (due to histamine release from mast cells), 2) often combines with promethazine (injection form = mepergan (1:1 ratio meperidine and promethazine))
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intraoperative submucosal midazolam augmentation technique
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1) augmentation of 50 mg/kg chloral hydrate PO with 0.2 mg/kg midazolam SM, 2) found to improve behavior, 3) given at beginning of procedure (45 min after CH), 3) given away from LA site, 4) can augment ineffective sedation, avoids oral titration, avoids early commitment to potential polypharmacy
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IM route advantages
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1) faster and more dependable absorption than oral route, 2) does not require patient compliance
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IM route sites and armentarium
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1) muscle sites: vastus lateralis (preferred site) - largest muscle group in children, can tolerate large injected volume (1-2 mL), absence of important nerves/blood vessels; ventrogluteal; dorsogluteal; deltoid; 2) armamentarium: 22-25 ga, 5/8-1 in needle
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ketamine properties
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1) used primarily for general anesthetic, but in a subanesthetic dose, produces a state resembling sedation, 2) recommended sedation dose = 1-2 mg/kg IM, 3) onset = 5-10 minutes, 4) duration of action = 10-25 min, 5) recovery time = 2 hours, 6) produces dissociative anesthesia (catalepsy, skeletal muscle rigidity, rotatory nystagmus, non-responsive, inability to communicate, 7) potent analgesic (low dose enhances effects of opioids)
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ketamine disadvantages
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1) hypersalivation (airway obstruction, laryngospasm), 2) nightmares in older children and adults, 3) hallucinations/delusions, 4) psychic reactions (agitated delerium, unpleasant recovery), 5) no reversal agent, 6) classified as "dissociative" anesthetic (interpreted as deep sedation/general anesthesia
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overcoming ketamine side effects
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1) decrease salivation with anticholinergic: atropine, scopalamine, glycophyrrolate [0.005-0.008 mg/kg IM], 2) decrease hallucinations with a benzodiazepine, midazolam [0.1-0.15 mg/kg IM], 3) emergence reactions: psychological prep
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ketamine physiological responses
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1) increased heart rate, cardiac output and blood pressure, 2) bronchodilator, 3) airway patency is maintained as muscle tone is increased, 4) protective reflexes are preserved, but there is some diminishment in their effectiveness
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ketamine contraindications
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1) high blood pressure, 2) high intracranial and intraoccular pressue, 3) severe psychotic disorders, 4) epilepsy, 5) history of CVA, 6) arteriosclerotic heart disease
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oral ketamine protocol
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1) dosage = 3-6 mg/kg PO with 0.03 mg/kg atropine, 2) combined with midazolam [0.5 mg/kg] to reduce psychedelic reactions, 3) add flavoring agent to mask bitter taste, dose-related vomiting = 6-33%, 4) onset = 20-30 min, 5) duration of action = 60 min, 6) poor BA
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IV propofol (diprivan)
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1) hypnotic, not analgesic like opioids, 2) used for induction of maintenance of general anesthesia, 3) short acting (minutes), IV infusion agent, 4) referred to as "milk of amnesia
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dexmedetomidine (precedex)
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1) IV route for procedural sedation, 2) dose: 2 mcg/kg/hr infusion after intitial bolus, 3) bradycardia and sinus arythmias, 4) motionless state produced (ideal for MRIs)
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pharmacokinetics
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what the body does to the drug
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absorption
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diffusion through mucosa into plasma
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bioavailability
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resulting plasma concentration
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distribution def.
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influence of blood/brain barrier, plasma protein binding, and fat (younger children need higher dosage due to lower volume of distribution)
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metabolism def.
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break down of patent drug to metabolites
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elimination def.
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clearance
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pharmacodynamics
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what the drug does to the body (desires vs. adverse effects)
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what leads to % bioavailability?
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drug absorption into systemic circulation
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PO route bioavailability
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requires liposolubility (tissue diffusion) and first pass hepatic metabolism by CP450 enzymes = 40-60% BA
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sublingual (topical) route bioavailability
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requires liposolubility and metablism of unknown amount swallowed = 80% BA
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IV, IM and SC routes bioavailability
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100% BA
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drug distribution (plasma to tissue)
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1) rate and amount dependent on degree of tissue prefusion (blood supply) and drug affintiy for that tissue; 2) sedative drugs with good lipid solubility are distrubuted in proportion to the degree of tissue perfusion (brain --> kidney/liver --> muscle --> fat/bone); 3) nature of capillary bed affects distribution (CNS capillaries have tight endothelial junctions for the "blood-brain barrier"); 4) plasma protein binding limits amount of free drug in the blood stream; 5) competition for the same protein binding sites increases amount of free drug availability (increases potential toxicity)
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metabolism
|
1) generally done in gut mucosa and liver by cytochrome P450 enzymes; drugs influence enzyme systems differently, drug interactions may intensify or minimize drug action; 2) creates metabolites, some forms may also be active (codeine --> morphine)
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drugs that increase availability of codeine, hydrocodone and oxycodone
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cimetidine (tagamet), fluoxitine (prozac), paraxetine (paxil), other SSRIs
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drugs that decrease availability of codeine, hydrocodone and oxycodone
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rifampin
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drugs that increase availability of alprazolam (xanax), midazolam (versed), triazolam (halcion), alfentanil (alfenta) and lentanyl
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clarithromycin (biaxin), erythromycin, amiodarone, most protease inhibitors, grapefruit juice
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drugs that decrease availability of alprazolam (xanax), midazolam (versed), triazolam (halcion), alfentanil (alfenta) and lentanyl
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barbituates, carbamazepine (tegretol), phenytoin (dilantin), st. john's wart
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drug elimination
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1) drug half-life - time required to reduce plasma concentration by 50%; it takes 4 half-lives for complete elimination; 2) time concentration curve - IV drug does not require absorption or distribution like PO; once PO drug is distributed, it has the same elimination rate as IV drug; 3) half-life does not detemrine drug duration of action; drugs vary as to required threshold concentration to achieve effect
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drug action
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agonists and antagonists bind to like-receptors
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drug efficacy
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effectiveness
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drug potency
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amount required to create effect (not related to efficiacy or toxicity)
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drug safety
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therapuetic index - range between effective dose and toxic dose; not all adverse reactions are dose related (allergic vs. toxic reactions)
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therapeutic index
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LD(for 50% of pop) / ED (for 50% of pop); the higher the therapeutic index, the safer the drug
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drugs with wide therapeutic index
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1) penicillin, 2) acetaminophen, 3) ibuprofen, 4) antihistamines, 5) benzodiazepines
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drugs with narrow therapeutic index
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1) lidocaine, 2) epinephrine, 3) codeine, 4) demerol, 5) hydrocodone, 6) narcotics
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types of sedative drug side effects
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1) Type A: major adverse event, affecting VS (resp depression, bradycardia); 2) Type B: mild adverse event: hives, hiccups, diplopia, nausea, idiosyncratic; 3) Paradoxica: opposite of desired effect (euphoria vs. dysphoria) ; 4) potentiation: synergistic effect when combining drugs with similar actions (1+1 = 3)
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there is no magic bullet
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studies have found that there is no single drug or combination of agents superior in its efficacy for dental sedation
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procedural sedation (PS)
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acute application of agents to overcone situational anxiety/fear or induced pain/stimulation and to immobilize during treatment; requires higher doses, which may lead to toxicity
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lifestyle sedation
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chronic application of agents to manage everday living, requires lower doses and may lead to habit or tolerance
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where is the evidence to support best sedation practices?
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problem: poorly standardized research design makes cross-study comparison almost impossible; 1) small number of subjects, 2) lack of randomized subject assignemnt and control group, 3) varying age groups and behaviors/past experiences, 4) varying or poorly categorized pre-op behavior, 5) lack of quantifiable criteria for judging success/failure, 6) lack of interexaminer reliability and blindedness, 7) confounding variables not controlled (use of nitrous, local, current medications), 8) variations in drugs, dosages and routes used, 9) variation in waiting time prior to onset of procedure, 10) degree of physical stimulation, extent of invasive procedure
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select agents with:
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1) high therapeutic index, 2) low potential to deliver sedation beyond desired level, 3) minimum potential to create respiratory depression and somnolence, 4) reversal agent
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picking a sedative agent depends on the child's:
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1) age/emtional maturity, 2) cognitive development, 3) temperment and attachment characteristics, 4) coping and communicative skills, 5) level of displayed behavior, 6) current medications, 7) health history, 8) physical (risk) assessment, 9) past experience
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picking a sedative agent depends on the operator's:
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1) skills and training, 2) experience and preference, 3) estimated length of procedure, 4) desired goal (depth) of sedation
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continuum of consciousness
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1) awake, 2) minimal sedation: N2O + single benzodiazepine or antihistamine, 3) moderate sedation: low dose combines hyponotics, opiates, 4) deep sedation: hig dose combinations, 5) general anesthesia
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barbiturates: sedation, analgesia, amnesia
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1) sedation: +++, 2) analgesia: none , 3) amnesia: none
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benzodiazepines: sedation, analgesia, amnesia
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1) sedation: +++, 2) analgesia: none , 3) amnesia: +++
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opioids: sedation, analgesia, amnesia
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1) sedation: ++, 2) analgesia: +++ , 3) amnesia: none
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ketamine: sedation, analgesia, amnesia
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1) sedation: +++, 2) analgesia: +++ , 3) amnesia: ++
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propofol: sedation, analgesia, amnesia
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1) sedation: +++, 2) analgesia: none, 3) amnesia: +
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chloral hydrate: sedation, analgesia, amnesia
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1) sedation: ++, 2) analgesia: none, 3) amnesia: none
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nitrous oxide: sedation, analgesia, amnesia
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1) sedation: ++, 2) analgesia:++ , 3) amnesia: +
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trends in postdoctoral education
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.
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trends in sedation practice
|
.
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AAPD member attitudes of sedation
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.
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routes of administration
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1) inhalational, 2) enteral: PO, rectal, 3) parenteral: IV, IM, SC, SM, SL, IN
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oral route disadvantages
|
1) unpredictable: level can be anticipated, but never preducted (must accept 30% failure rate), 2) not titratable to desired effect, redosing not advised, 3) low bioavailability due to first pass hepatic metabolism and variation in intestinal absorption (GI pH, motility, contents), 4) poor taste and GI disturbance, 5) slow onset and recovery
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common oral agents
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1) diazepam (valium), 2) midazolam (versed), 3) hydroxyzine (atarax), 4) promethazine (phenergan), 5) chloral hydrate, 6) meperidine (demerol)
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common single agents (minimal sedation for anxiolysis)
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1) diazepam, 2) midazolam, 3) hydroxyzine
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common combine agents (moderate sedation)
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1) chloral hydrate and hydroxyzine, 2) demerol and phenergan, 3) chloral hydrate, demerol, hydroxyzine
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benzodiazepines used
|
1) triazolam (halcion), 2) diazepam (valium), 3) midazolam (versed)
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antihistamines used
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1) hydroxyzine (atarax), 2) promethazine (phenergan), 3) diphenhydramine (benedryl)
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advantages of oral benzodiazepines
|
1) wide therapeutic index (safety/efficacy not easily affected by dosage), 2) acceptable properties (anxiolytic, amnestic, anticonvulsant, muscle relaxant), 3) short to intermediate onset and duration of action, 4) minimal adverse reactions, 5) reversal agent available (flumazenil)
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orla benzodiazepine properties
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1) sequence of effects occurring with increasing serum levels (receptor site occupancy): anxiolysis, anterograde amnesia, sedation; 2) sedative effect occurs due to interaction with GABA receptors increasign their inhibitory action
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triazolam (halcion) administration
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1) dose: 0.125 mg (child) or 0.25 (adult) oral or sublingual: crush tablet and sprinkle under tongue, has 28% better bioavailability; 2) little or no improvement in child's behavior; 3) use with caution in pediatrics and geriatrics; 4) onset: 30-60 min, half life: 2 hours; 5) promoted as "sleep dentistry" by DOCS; 6) booster (incremental) doses can lead to overdose
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diazepam (valium) properties
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1) safe and effective in children, 2) inexpensive, 3) muscle relaxant (spactic cerebral palsy), 4) delayed onset (30-60 min), 5) prolonged recovery due to active metabolites: desmethyldiazepam, temezepam, oxazepam, 5) drug interactions (influcend by CP450 enzymes) with ertyhromycin and grapefruit juice will increase sedation
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diazepam (valium) dosage
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1) solution = 5mg/5mL, 2) dosage = 0.2-0.5 mg/kg, 3) 2-5 yo = 2-5 mg; 6-10 yo = 5-10 mg; 11-16 yo = 10-15 mg; 4) guide: 1 mg/year of age
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midazolam vs: diazepam
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1) onset of action: midazolam-20-30 min; diazepam-45-60 min, 2) duration of action: midazolam-30-40 min; diazepam-60 min; 3) several studies have indicated that midazolam was more effective
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midazolam properties
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in comparison to diazepam: 1) water soluble (less iritating IM/IV), 2) higher lipid solubility (rapid onset), 3) greater potency = 2x diazepam, 4) faster recovery (half life = 2-3 hours), 5) stronger amnestic
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drugs that potentiate sedation (ingibits CP450 activity) with midazolam
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1) erythromycin, 2) clarithromycin, 3) grapefruit juice, 4) ketoconazole, 5) cimetidine (tagmet), 6) verapamil/diltazem
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drugs that inhibit sedation (induces CP450 activity) with midazolam
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1) carbamazepine (tegretol), 2) phenytoin (dilantin), 3) rifampin (rifadin)
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midazolam chemistry
|
active midazolam has a pH >5 and is a closed ring; inactive midazolam has a pH =3.5 and is an open ring
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midazolam physiological complications
|
1) ataxia, loss of head control "floppy doll" (potential injury and airway problem), 2) hiccups, 3) diplopia (double vision), 4) respiratory depression (stridor, apnea, hypercarbia, more common with IM/IV routes), 5) paradoxical response (2%) - "negativism" - dysphoria (whining irritable), agitation (combativeness, anger, hostility, rage), higher incidence in ADHD; 6) nightmares/hallucinations
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midazolam paradoxical response
|
1) dysphoria and agitation well documented, 2) uncontrolled screaming and thrashing not responsive to console attempts, 3) onset is about 45 minutes after administration and may last for several hours, 4) reversed by flumazenil
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midazolam operational approach
|
1) unique properties of midazolam permits a change in operational phiolosophy: shorter appointments, quadrant restorative dentistry, faster turn around time, improved safety with reversal agent, efficient emergency dental service; 2) place child on to passive restraint, but do not wrap the child until behavior dictates
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midazolam oral dosage
|
0.5-0.75 mg/kg, max dose = 20 mg; 4-7x parenteral dose
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midazolam oral route onset, duration, recovery, BA
|
1) onset - 20-30 min (tmax = 1 hr); 2) duration of action - 30-45 min; 3) recovery 60-90 min (t1/2 = 2-3 hrs); 4) low bioavailability (36%); cytochrome P450 enzymes in GI mucosa cells and liver; the < BA, the > variability in clearance and blood levels (depth of sedation, predictable outcome)
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midazolam oral syrup
|
2 mg/mL in 118 mL bottle
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midazolam injection form for oral route
|
1) use the highest concetration (5 mg/mL) to minimize volume to be swallowed; 2) mask the bitter taste with flavoring agents; 3) national shortage so reserved for IN for now
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midazolam combinations with analgesics
|
1) acetaminophen elixir, 15 mg/kg; 2) ibuprofen suspension, 10 mg/kg; 3) meperidine syrup, 1 mg/kg
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hydroxyzine properties
|
1) antihistamine (decreases edema, inflammation), 2) bronchodilator, 3) anticholinergic (drying), 4) antiemetic, 5) sedative, 6) potentiates CNS depressants
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hydroxyzine dosage
|
2 - 3.7 mg/kg (single agent with nitrous)
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hydroxyzine half life, onset, duration
|
1) half life = 3-20 hrs, 2) onset - 30-40 min, 3) duration - 2-4 hrs
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hydroxyzine suspension types
|
1) hydroxyzine pamoate (vistaril) - 25mg/5mL; 2) hydroxyzine hcl (atarax) - 10 mg/5mL (vanilla flavored)
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hydroxyzine capsules
|
hydroxyzine pamoate - 50 mg or 25 mg; dissolve capsule into flavoring agent
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oral midazolam + hydroxyzine dosages
|
1) 0.3 mg/kg midazolam + 3.7 mg/kg hydroxyzine OR 2) 0.5 mg/kg midazolam + 2.0 mg/kg hydroxyzine
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OTC diphenhydramine dosage
|
1-2 mg/kg
|
|
|
OTC diphenhydramine types
|
1) benadryl tablets (25, 50 mg), syrup 12.5 mg/5mL and elixir 25 mg/5mL; 2) diphen tablets 25 mg
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benzodiazepine antagonist and its dosage
|
flumazenil (romazicon) 1) 0.01 mg/kg initial dosage, up to max dose of 0.2 mg; 2) follow-up dosage 0.005 mg/kg up to max dose of 0.1 mg up to 4 additional times 3) max total dose is 0.05 mg/kg or 1 mg, whichever is lower
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|
|
flumazenil concentration
|
0.1mg/mL in 5 and 10 mL vials; short shelf life and cost @ $12/mL dose
|
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|
flumazenil administration
|
1) IV, onset of action 1-2 min, half life 1-1.5 hrs, 2) SM - maxillary tuberosity site away from LA site, onset of action within 5 minutes
|
|
|
flumazenil example with 20 kg (6 yo) child
|
1) initial dose = 0.01 mg/kg x 20 kg = 0.2 mg; 2) volume given = 0.2 mg / 0.1 mg/mL = 2 mL in 3mL syringe given SM or SL; 3) wait 3-5 minutes for desired effect; 4) follow-up dose 0.005 mg/kg x 20 kg = 0.1 mg / 0.1 mg/mL = 1 mL SM or SL
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|
flumazenil recovery
|
1) airway support and oxygen supplementation, 2) half life = 20-30 min (1/4 that of midazolam), 3) observe patient for 2 hours, place on pulse oximeter, observe for signs of resedation, hypoventilation, anxiety
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|
oral administration techniques and syringe etiquette
|
1) child is slightly reclined, 2) use slowly, 3) inject by side of tongue or alongside your finger, 4) complications: aspiration, laryngospasm, conjunctivitis, 5) pinch nostrils closed?
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|
|
nasal route advantages
|
1) Cmax is equivalent between IV and IN reoutes, 2) rapid onset = 10 min, 3) does not require compliance, 4) beneficial with emergency extractions, 5) higher bioavailability, 6) avoids unpalatbale taste, 7) relaxed adherence to dietary precautions
|
|
|
nasal route mechanism of absorption
|
1) drugs sprayed on to nasal mucosa are absorbed rapidly through the cribiform plate into the CNS by 3 routes: olfactor neurons, surrounding capillary beds, CSF, 2) nasal mucosa is only location in the body that provides a direct link to the CNS
|
|
|
nasal route use of atomizer
|
1) small tip: fits into tiny naris, 2) bendable tip: better control, 3) semipermeable soft plug cathced fluid run back, seals and cushions the nose, 4) spray = 30 micrometer particel size, spray in short bursts, 1/2 dose in each naris, 0.1 mL dead space in system, 5) luer lock connection directly to 1 mL tuberculin syringe
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|
midazolam IN dosage
|
0.2-0.35 mg/kg, max dose = 10 mg
|
|
|
exceptions to a fized dosage regimen
|
1) younger pts require higher dosage due to lower volume of distribution (0.35 vs 0.2 mg/kg IN and 0.65 vs. 0.5 mg/kg PO), 2) obese pts require lower dosage (if weight > weight for age norm, then give dose based on age, not weight, 3) observe maximum recommended dose limits (midazolam = 20 mg PO, 10 mg, IN)
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|
|
chloral hydrate pharamacokinetics
|
1) rapid metabolism to trichloroethanol, 2) half life - 4-14 hrs, 3) converted in the liver to trichloroacetic acid, a cardiotoxic metabolite, 4) chemical structure resembles halothane- myocardium may be sensitized to adrenergic amines
|
|
|
chloral hydrate advantages
|
1) hypnotic - produces sleep, 2) long history of use/safety, 3) wide therapeutic range, 4) best used in children 2-5 years of age
|
|
|
chloral hydrate disadvantages
|
1) produces paradoxical reactions (agitation, disinhibition, dysphoria), 2) bitter taste, 3) mucosal/gastric irritation creates vomitting, 4) delayed onset and prolonged recovery, 5) somnolence and hypotonicity of glossal muscles may produce airway obstruction, 6) arousal frequency related to intensity of stimulation, 7) no reversal agent available
|
|
|
chloral hydrate + hydroxyzine
|
1) chloral hydrate - dosage[35-50 mg/kg], dose range [500-1500 mg], concentration [100 mg/mL], 2) hydroxyzine - dosage [1-2 mg/kg], dose range [25-50 mg], concentration [5 mg/mL]
|
|
|
opioid (narcotic) agents
|
1) meperidine (demerol), 2) fentanyl, 3) morphine, 4) codeine, 5) alphaprodine (nisentil)
|
|
|
opioid properties
|
1) analgesic, 2) sedative, 3) antispasmodic, 4) effects can be reversed with nalaxone (narcan)
|
|
|
nalaxone
|
1) give 0.1 mg/kg every 2-3 minutes up to 2 mg total, 2) 0.4 mg/mL in 10 mL vial, 3) for a 15 kg child - 1.5 mg (4 mL) SM in 10 mL syringe
|
|
|
meperdine disadvantages
|
1) gastric upset and emesis, 2) reduce MRD for LA as narcotics reduce plasma binding of LA (decrease seizure threshold), 3) produces respiratory depression and orthostatic hypotension, 4) releases histamines from mast cells (precuation with asthmatics without med consult)
|
|
|
oral meperidine dosage
|
1) 1-2 mg/kg, 2) max dose of 50 mg, 3) syrup = 50 mg/5 mL (bitter after taste), 4) often combines with promethazine
|
|
|
promethazine (phenergan) properties
|
1) antihistamine, 2) anticholinergic, 3) sedative (minimal when used alone), 4) bronchodilator, 5) lowers seizure threshold, 6) creates extrapyramidal responses (jerky limb movements)
|
|
|
promethazine doage and types
|
1) 1-2 mg/kg, 2) note to be given to a child <2 years of age, 3) vanilla flavor oral formulas: elixir (5mg/5mL), syrup plain (6.25 mg/5mL), syrup fortis (25 mg/5 mL)
|
|
|
oral opioid combinations
|
1) use has decreased in recent years, 2) has analgesic, anti-anxiety and sedation actions, 3) used for long apts on moderate to severely apprehensive pts when moderate to deep sedation is desired, 4) variable effects when taken orally, 5) may cause respiratory depression, hypotension, unconsciousness, increased risk of lidocaine toxicity, and nausea and vomiting, 6) effects begin in 45-60 minutes with duration of action 2-3 hours
|
|
|
common oral opioid combinations
|
1) meperidine 2 mg/kg + promethazine 1mg/kg, 2) meperidine 1-2 mg/kg + midazolam 0.5-0.75 mg/kg, 3) meperidine 2 mg/kg + chloral hydrate 30 mg/kg + hydroxyzine 2 mg/kg
|
|
|
oral opioid combinations effect of respiration
|
1) minute volume = RR + tidal volume, 2) meperidine - decreases RR, 3) chloral hydrate - decreases tidal volume 4) combination increases potential for respiratory depression
|
|
|
meperidine + midazolam combination oral regimen
|
1 mg/kg meperidine + 0.5 mg/kg midazolam (reduced by half the more potent agent)
|
|
|
submucosal route
|
infiltration in mucobuccal fold at maxillary tuberosity (high vascularity results in rapid absorption)
|
|
|
meperidine given SM
|
1) creates erythematous wheals, urticaria and pruritis (itching) at injection site (due to histamine release from mast cells), 2) often combines with promethazine (injection form = mepergan (1:1 ratio meperidine and promethazine))
|
|
|
intraoperative submucosal midazolam augmentation technique
|
1) augmentation of 50 mg/kg chloral hydrate PO with 0.2 mg/kg midazolam SM, 2) found to improve behavior, 3) given at beginning of procedure (45 min after CH), 3) given away from LA site, 4) can augment ineffective sedation, avoids oral titration, avoids early commitment to potential polypharmacy
|
|
|
IM route advantages
|
1) faster and more dependable absorption than oral route, 2) does not require patient compliance
|
|
|
IM route sites and armentarium
|
1) muscle sites: vastus lateralis (preferred site) - largest muscle group in children, can tolerate large injected volume (1-2 mL), absence of important nerves/blood vessels; ventrogluteal; dorsogluteal; deltoid; 2) armamentarium: 22-25 ga, 5/8-1 in needle
|
|
|
ketamine properties
|
1) used primarily for general anesthetic, but in a subanesthetic dose, produces a state resembling sedation, 2) recommended sedation dose = 1-2 mg/kg IM, 3) onset = 5-10 minutes, 4) duration of action = 10-25 min, 5) recovery time = 2 hours, 6) produces dissociative anesthesia (catalepsy, skeletal muscle rigidity, rotatory nystagmus, non-responsive, inability to communicate, 7) potent analgesic (low dose enhances effects of opioids)
|
|
|
ketamine disadvantages
|
1) hypersalivation (airway obstruction, laryngospasm), 2) nightmares in older children and adults, 3) hallucinations/delusions, 4) psychic reactions (agitated delerium, unpleasant recovery), 5) no reversal agent, 6) classified as "dissociative" anesthetic (interpreted as deep sedation/general anesthesia
|
|
|
overcoming ketamine side effects
|
1) decrease salivation with anticholinergic: atropine, scopalamine, glycophyrrolate [0.005-0.008 mg/kg IM], 2) decrease hallucinations with a benzodiazepine, midazolam [0.1-0.15 mg/kg IM], 3) emergence reactions: psychological prep
|
|
|
ketamine physiological responses
|
1) increased heart rate, cardiac output and blood pressure, 2) bronchodilator, 3) airway patency is maintained as muscle tone is increased, 4) protective reflexes are preserved, but there is some diminishment in their effectiveness
|
|
|
ketamine contraindications
|
1) high blood pressure, 2) high intracranial and intraoccular pressue, 3) severe psychotic disorders, 4) epilepsy, 5) history of CVA, 6) arteriosclerotic heart disease
|
|
|
oral ketamine protocol
|
1) dosage = 3-6 mg/kg PO with 0.03 mg/kg atropine, 2) combined with midazolam [0.5 mg/kg] to reduce psychedelic reactions, 3) add flavoring agent to mask bitter taste, dose-related vomiting = 6-33%, 4) onset = 20-30 min, 5) duration of action = 60 min, 6) poor BA
|
|
|
IV propofol (diprivan)
|
1) hypnotic, not analgesic like opioids, 2) used for induction of maintenance of general anesthesia, 3) short acting (minutes), IV infusion agent, 4) referred to as "milk of amnesia
|
|
|
dexmedetomidine (precedex)
|
1) IV route for procedural sedation, 2) dose: 2 mcg/kg/hr infusion after intitial bolus, 3) bradycardia and sinus arythmias, 4) motionless state produced (ideal for MRIs)
|
