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;
192 Cards in this Set
- Front
- Back
|
2 oxy barbs?
|
secobarbital
pentobarbital |
|
|
methylated barb?
|
methohexital (brevital)
|
|
|
methohexital metabolism?
|
demethylation and oxidation at carbon-5 and ring hydrolysis occurs
|
|
|
barbs synthesized how?
|
by condensation of urea and malonic acid to form barbituric acid ring
|
|
|
thiopental is first metabolized to? then?
|
desulfuration to pentobarbital (hangover effect), then oxidation of carbon-5 radicals (ring hydrolysis also occurs)
|
|
|
no brevital with hx of?
|
seizures
|
|
|
what change gives the barbs a sedative hypnotic effect?
|
by replacing both hydrogen atoms at position 5 with alkyl or aryl group
|
|
|
what alterations give barbs increased potency?
|
longer side chain lengths
|
|
|
what # carbon for thio or oxy barbs?
|
replacementg of carbon 2 with sulfer or oxygen
|
|
|
what structural changes give barbs increased lipid solubility
|
sulfurization
|
|
|
methohexital is produced by?
|
methylation of phenobarbital at carbon-1
|
|
|
what changes give barbs a more rapid onset and shorer duration? (but also increased excitatory side effects)
|
methylation (methohexital)
|
|
|
barbs are weak ______?
|
acids
|
|
|
NMDA non-competitive antagonist?
|
ketamine
|
|
|
Structural similarities to phencyclidine?
|
ketamine
|
|
|
Ketamine lipid solubility?
|
more lipid soluble than thiopental (5 to 10 times)
|
|
|
Structure has imidazole,gives H2O solubility?
|
etomidate
|
|
|
Structure is alkylated phenol, insoluble in H2O?
|
propofol
|
|
|
Fentanyl and alfentanil increase concentrationon what agent?
|
propofol
|
|
|
which agent inhibits cortisol and aldosterol synthesis?
|
etomidate
|
|
|
barbiturate with incidence of hiccups and coughing?
|
methohexital
|
|
|
_______ compounds cause release of histamine from mast cells.
|
Thiol
|
|
|
Hyperanalgesic, increase reaction to painful stimuli at subanesthetic doses?
|
barbiturates
|
|
|
most lipophilic barbiturate?
which means that it distributes the _________? |
secobarbital
fastest |
|
|
least lipophilic barbiturate?
which means that it distributes the _________? |
phenobarbital
slowest |
|
|
barbiturates whose onset parallels the rate of absorption and duration parallels elimination.
|
Oxybarbiturates (secobarb, phenobarb)
|
|
|
barbiturates whose onset and duration are more closely related to the pattern of distribution.
|
Thiobarbiturates (thiopental)
|
|
|
barbiturates with 100% P450 Metabolism? (4)
|
Amobarbital
Butabarbital Pentobarbital Secobarbital |
|
|
the more lipophilic a drug the higher/lower the rate of renal reaborption?
|
more lipophilic = more reabsorbed
|
|
|
only barbiturate that has any significant excretion without being unchanged?
|
Phenobarbital
|
|
|
barbiturates compared to benzodiazepines? [2]
|
more addicitve (intoxicated side effects)
smaller TI |
|
|
ph of lipophilic midalolam form?
|
physiologic ph
|
|
|
benzodiazepines effect on adesosine receptor?
|
Agonist activity=increases effect because inhibits uptake of adenosine.
|
|
|
percent protien bound?
propofol |
98
|
|
|
percent protien bound?
etomidate |
75
|
|
|
percent protien bound?
ketamine |
12
|
|
|
percent protien bound?
thiopental |
80-85
|
|
|
percent protien bound?
methohexital |
85
|
|
|
percent protien bound?
midazolam |
94
|
|
|
percent protien bound?
diazepam |
98
|
|
|
percent protien bound?
lorazepam |
98
|
|
|
elimination t 1/2
thiopental |
10-12 hr
|
|
|
elimination t 1/2
methohexital |
2-4 hr
|
|
|
elimination t 1/2
etomidate |
2-5 hr
|
|
|
elimination t 1/2
propofol |
1-5 hr
|
|
|
elimination t 1/2
ketamine |
2-3 hr
|
|
|
elimination t 1/2
midazolam |
2-4 hr
|
|
|
elimination t 1/2
diazepam |
20-50 hr
|
|
|
elimination t 1/2
lorazepam |
10-20 hr
|
|
|
highest clearance-non barb
|
propofol
|
|
|
lowest clearance non barb
|
ketamine
|
|
|
highest clearance barb
|
methohexital
|
|
|
highest clearance benzo
|
midazolam
|
|
|
lowest clearance benzo
|
diazepam
|
|
|
highest HR increase barb
|
methohexital
|
|
|
most decrease in SVR barb
|
thiopental
|
|
|
highest HR incrase non barb
|
ketamine
|
|
|
most BP decrease of all IV agents?
|
propofol (decrease SVR)
|
|
|
most respiratory depressant?
|
propofol
|
|
|
what does etomidate decrease?
|
RR
|
|
|
HR -propofol?
|
no change or decreased
|
|
|
CBF with midazolam?
|
increase or decrease
|
|
|
how do NSAIDs work in general?
|
they inhibit formation of
algogenic substances |
|
|
how do opiods work in general?
|
they inhibit neurotransmission of pain signals
|
|
|
Phenanthrenes?
|
OPIODS
|
|
|
Benzylisoquinolines?
|
Benzodiazepines
|
|
|
the 3 STRONG PO opiods?
|
Methadone (Dolophine)
Hydromorphone (Dilaudid) Oxycodone (OxyContin) strongest |
|
|
methadone uses...
metab/solubility? strength? |
analgesia and addiction
not used for anesthesia slow metabolism, high lipid solubility, t1/2 24-36 hours STRONG |
|
|
Hydromorphone strength?
dangers? structure? |
STRONG 8x MS
death with ETOH (facilitates absortption) Hydrogenated ketone |
|
|
Oxycodone (OxyContin) atregnth?
Why so desired? |
STRONGEST
Oxycontin is SR high bioavialibility via a number of routes |
|
|
What are the 4 moderate PO opiods?
|
Codeine
Hydrocodone(Vicodin, Lorcet, Lortab,etc.) Propoxyphene (Darvon, Darvocet) Oxymorphone |
|
|
Codeine strength?
dangers? pro-drug of? |
moderate
histamine release morphine-demethylation |
|
|
Hydrocodone strength?
special considerations? |
moderate
NO MAOs |
|
|
Propoxyphene strength?
special considerations? |
moderate
can be used for withdrawal low TI and efficacy can be used and a local anesthetic extensive 1st pass/toxic metabolites does not use an opiod receptor |
|
|
Oxymorphone strength?
special considerations? |
moderate
OH grp added to hydromorphone the 'blues' |
|
|
Tramadol strength?
special considerations? |
weak-10 time weaker than morphine
not related in structure to other opiods can interact with coumadin/SSRI's(potentiate) can cause sz'z |
|
|
Loperamide strength?
special considerations? |
weak
for diarrhea |
|
|
diphenoxlate? (Lomotil) strength?
special considerations? |
weak
for diarrhea with atropine |
|
|
dextromethorphan strength?
special considerations? |
weak
antitussive |
|
|
How do the opioid agonist-antagonists work?
|
Lack complete agonist effect at mu receptors so less respiratory depression and lower chance fro drug dependence than the complete opioid agonists. Also less constipation
|
|
|
side effects of opiod agonist/antagonist?
|
Side effects are anxiety, nightmares, psychotomimetic effects such as hallucinations because of kappa agonist activity. If patient is on a full agonist, can cause withdrawal.
|
|
|
4 opioid agonist-antagonists?
|
Pentazocine (Talwin)
Nalbuphin (Nubaine) Butorphanol (Butorfanol) Buprenorphrine (Buprenex) |
|
|
Pentazocine (Talwin)?
special considerations? |
opiod agonist/antagonist
Kappa and sigma receptor agonist Supplement to anesthesia Paraenteral use can cause severe condiopulmonary reactions |
|
|
Butorphanol (Butorfanol)
special considerations? |
opiod agonist/antagonist
Kappa receptor agonist Partial agonist/antagonist at mu receptor Paraenteral Supplement to anesthesia Relief of pain during labor |
|
|
Nalbuphine (Nubain)
special considerations? |
opiod agonist/antagonist
Kappa receptor agonist Partial agonist/antagonist at mu receptor Paraenteral Supplement to anesthesia |
|
|
Nalorphine (not used)special considerations?
|
opiod agonist/antagonist
has analgesic properties, antagonist activity is that it displaces opioid agonists – precipitates withdrawal high incidence of dysphoria impending death which is probably sigma agonism) |
|
|
Buprenorphine(Buprenex)
special considerations? |
opiod agonist/antagonist
Partial mu agonist Slow dissociation so longer activng IM, IV, oral sublingual Approved for treatment of opioid dependence Formulated with Naloxone to lower abuse |
|
|
2 opioid antagonists
|
naloxone
naltrexone (cepulan) |
|
|
naloxone considerations?
|
IV for rapid termination of opioid respiratory depression (poor oral bioavailability
Short half-life May need repeated dosing |
|
|
naltrexone considerations?
|
Oral and transdermal
High oral bioavailability Can be used long term Also for alcohol dependence |
|
|
duration of action depends on? [3}
|
lipophilicity
volume of destribution metabolism clearance |
|
|
what 2 agents have some degree of extra-hepatic metabolism?
|
etomidate
propofol |
|
|
what 2 agents can cause enzyme induction?
what does this cause? |
ketamine
barbiturates increased metabolism |
|
|
how does a large Vd affect elimination?
|
it prolongs it
|
|
|
if drug-drug interactions occur in the liver, what is the effect?
|
usually slows metabolism of the drug you are giving or slows the metabolism of other drugs. There is competition for the enzymes. This can produce prolonged drug effects of the main drug of interest usually
|
|
|
a steep slope on the dose-response curve indicates what?
|
high potency
|
|
|
all barbiturates have a _______ TI.
|
low
|
|
|
With barbiturates, the R3 position has N and can be substituted. T/F
|
True
|
|
|
a low TI has what type of curve?
|
steep curve
|
|
|
isomerism is at postion #?
|
1 for brevital plus #5 for all of the others.
|
|
|
With Barb's, N can be substituted at position #?
|
3
|
|
|
Glutamate receptors are inhibitory or excitatory?
|
excitatory
|
|
|
How do we inhibit the glutamate receptor?
|
steric hindrance....we keep the Na+ from coming in
|
|
|
Do we want agonism or antagosism of the glutamate receptor?
|
antagonism
|
|
|
What does serotonin do?
|
promotes sleepiness
|
|
|
Do we want antagonism or agonism of the adenosine receptor?
|
we wnat agonism-we inhibit the uptake of adenosine
|
|
|
What does caffiene do?
|
it is an adenosine pathway antagonist
|
|
|
How do barbiturate act on the nicotinic cholinergic (ionotropic) receptor?
|
the lodge in the pore (steric hindrance) to keep the Na+ out.
|
|
|
What receptors do the barbiturates antagonize?
|
Ach
Nicotinic muscarinic |
|
|
barbs with 100% p450 metabolism
|
amobarbital
butabarbital secobarbital |
|
|
barbs with 75% p450 metabolism
|
phenobarbita
pentobarbital |
|
|
barbiturate induction of microsomal enzymes (liver) leads to high clearance of what other drugs?
|
TCAs
ICS coumadin estrogen/progesterone digoxin |
|
|
what interaction with MAO's?
|
inhibit p450
|
|
|
benzo?
7 figured ring? diaza? |
benzine ring
-epine 2 nitrogens |
|
|
triazo groups are more?
|
more potent, less metabolized
|
|
|
Adenosine receptors contribute to?
do we want antag/agonism? |
sleepiness
agonize |
|
|
benzo's work on what GABA subunit?
|
gamma
|
|
|
lowest Vd benzo?
|
lorazepam
|
|
|
why do we use propylen glycol as a solvent?
|
slight h20 solubility secondary to OH groups
brings drug into solution |
|
|
onset depends on distribution to__________ which is dependent on ____________.
|
brain
lipophilic character |
|
|
benzo drug-drug interactions that slow metabolism (Cyp3A)
|
cimetidine
e-mycin,antifungals Ca+ channel blockers fentanil grapefruit juice |
|
|
benzo with only phase 2?
|
lorazepam
|
|
|
benzo that undergoes phase once twice?
|
diazepam
|
|
|
benzo with no phase 2?
|
midazolam
|
|
|
benzo with active metabolite?
|
diazepam
|
|
|
benzo where elimination does paralled duration?
|
diazepam d/t active metabolites
|
|
|
elimination/duration is ussally _______ with drugs with INactive metabolites?
|
paired/parrallel
|
|
|
benzo same site antagonist?
|
flumazenil
|
|
|
benzo different site antagonist?
|
physostigmine/aminophyline
|
|
|
benzo antagonist that is a CNS stimulant?
|
physostigmine/aminophyline
|
|
|
benzo metabolized solely by conjugation?
|
lorazepam
|
|
|
Ketamine Pka?
therefore? |
7.5
50/50 ionized at phys pH. |
|
|
never mix ketamine with a ?
|
base
|
|
|
Ketamine suppresses neutrophi production of inflammatory mediators which does what?
|
improves blood flow
inhibits cytokines |
|
|
ketamine is formulated at a pH of 3-5, why?
|
acidic to form a water soluble salt/conjugate acid form.
|
|
|
ketamine is a NMDA?
|
non-competitive antagosist
poss opiod (kappa) |
|
|
ketamine hepatic Cl, ER?
|
high, high
|
|
|
ketamine metabolite activity?
|
some active, some not
|
|
|
ketamine metabolism?
|
dealkylation
|
|
|
ketamine S/A's
|
sympathetic stim
nystagmus hypertonus increased AW secretions |
|
|
no ketamine with?
|
theophylline
|
|
|
ketamine effects on librium?
|
increased duration
|
|
|
diazepam effect on ketamine?
|
increased CV stimulation and increased elim t1/2
|
|
|
No ketamine with what patient?
|
HTN, CAD, CHF, aneurysms
increased ICP glaucoma |
|
|
Etomidate acid/base? pKa?
|
weakly basic
4.2 |
|
|
Etomidate formulation?
|
pH 7. base in base
highly non-ionized |
|
|
etomidate GABA effect?
|
modulator only
GABA must be present |
|
|
Etomidate GABAa subunit receptor?
|
alpha, increases affinity for GABA ligand
|
|
|
Etomidate mech of action?
|
depresses RAS
|
|
|
rational for Etomidate myoclonus?
|
disinhibition of extrapyramidal motor activity
|
|
|
Etomidate ionization?
protien binding? |
highly non-ionized
75% bound |
|
|
Etomidate context sensitive 1/2 time versus thiopental?
|
etomidate has shorter 1/2 life
|
|
|
Etomidate S/A's
|
N/V
adrenocortical suppresion immune depression (decrese stress response) |
|
|
fentanil/alfentanil effects of etomidate?
|
increase plasma levels and decrease elim t1/2
|
|
|
opiod effects on etomidate?
|
decrese myoclonus
|
|
|
propofol structure?
|
alkylated phenol
|
|
|
propofol mech of action?
|
GABA modulator
decreases the rate of release of GABA |
|
|
propofol++'s
|
antiemetic
anticonvulsant antipruritic |
|
|
propofol Vd?
|
LARGE (lungs, too)
|
|
|
Propofol hepatic metab?
|
clearance exceeds hepatic blood flow.
has a weak metabolite |
|
|
propofol HR response
|
impairs baroreflexes
ussually no change in HR |
|
|
Vd effect on propofol dosing?
|
increased dosage needed with lower Vd (elderly, neonates)
increased dosage for women |
|
|
fentanil/alfentanil effect on propofol?
|
they increase serum concentration
|
|
|
Ketamine may result in decreased CO and MAP if.....
|
cathecholimine stores are exhausted
|
|
|
drugs that increase HR?
|
barbs
benzo's(possibly) meperidine ketamine droperidol |
|
|
drugs that decrease HR?
|
opiods except meperidine
|
|
|
drugs that decrease BP/MAP?
|
barbs
benzos(depends) opiods (a little) etomidate (a little) propofol the most |
|
|
inactivated barbs don't have ______?
|
carbon chains at the 5th position
|
|
|
What change in barb SAR leads to a more rapid onset and shorter duration?
|
sulfer-incrased lipophilicity
|
|
|
2 5-sustituents required for _______
|
GABA activity with barbs
|
|
|
barbs are acid/base?
|
acidic secondary to amide group
|
|
|
hypnotic activity is increased with what barb SAR change?
|
side chains at postion 5, especially if branched
|
|
|
barb acid+acid='s
|
non-ionized
lipophilic fast absrption |
|
|
if the patient becomes more acidotic, how does this affect the ionization with barbs?
|
more unionized=more drug available
|
|
|
muscarinic receptors are?
where? |
Ach g-coupled
only parasympathetic at the effector organ |
|
|
antimuscarinics? [2]
|
atropine
scoplamine |
|
|
barbiturates at pharmacologic concentrations allosterically increase binding of _________ to thier respective binding sites.
|
benzodiazepines
|
|
|
pain causing substances? [2]
|
interluekins
prostaglandins |
|
|
which Cox activity for analgesia?
|
cox-2 (we inhibit)
|
|
|
# rings-phenanthrine?
|
3-morphine
|
|
|
the 'coming out' ring on a phenanthrine?
|
piperdine ring
|
|
|
benzoisoquinolones?
|
fentanil
sufenanil remifentanil alfentanil |
|
|
methadone solubility, metabolism rate?
|
high lipid solubility
slow metabolism not as potent as MS not a phenanthrine |
|
|
oxycodone++'s
|
selective for Mu
high bioavailability |
|
|
CYP2D6 deficiency?
|
incrased codiene-toxicity
|
|
|
cannot be mixed with MAO's
|
hydrocodone
vicodin, lortab |
|
|
unique property of propoxyphene?
|
can be used as a local
does not use an opiod receptor |
|
|
PO med that does not ustilize an opiod receptor\?
|
propoxyphene
|
|
|
propoxyphene negatives
|
addicitive
low TI extensive 1st pass effect toxic byproducts |
|
|
Tramodol's unique mech of action?
|
descending pathway (serotonin)
inhibit the uptake of nor-epi |
|
|
stadol is?
|
butrophanol
|
|
|
buprenophine specifically approved for?
|
treatment of opiod dependence
|
