What is tranquilization?
the patient is relaxed, unconcerned with his or her surorundings and is FULLY FUNCTIONAL
What does a sedative do?
decreases activity, moderates excitement and calms patient although PATIENT IS AWAKE
What does a hypnotic do?
produces drowsiness and facilitates the onset and maintenance of sleep, but patient may be EASILY AROUSED
How are hypnotics different from general anesthetics?
when a patient is under general anesthetics they can't be aroused
What are barbiturates classified?
their mechanism of action is all the same, so they're classified by their duration of action:
ultra-short acting
short-intermediate acting
long acting
What are the characteristics of ultra-short acting barbiturates?
(i.e. why are they so fast acting, how is function terminated)
their half life is only minutes because they're very lipid soluble
they reach the CNS very quickly
termination of action is thorugh redistribution to muscle and other sites
What are two examples of ultra-short acting barbiturates?
thiopental (pentothal)
methohexital (brevital)
How long is the half life for the short-intermediate acting barbiturates? What does it depend on?
half-life is hours
depends on rate of metabolism
What is an example of a short-intermediate acting barbiturate?
secobarbital (seconal)
What is the half life for the long acting barbiturates? How?
days
very slow metabolism - can be excreted wholly or partially unchanged
What is an example of a long acting barbiruate?
phenobarbital
What tissues do barbiturates cause depression in?
produces reversible depression of ALL excitable tissue (nervous, smooth muscle, cardiac muscle)
CNS most sensitive
What barbiturate is selectively anticonvulsant, while the remainder are relatively unselective in their depression of the CNS?
phenobarbital
What are barbiturates affect on pain?
pain is the one function which is not impaired until unconsciousness
in fact, at small doses you have hyperalgesia!
What effects of barbiturates will develop tolerance and which won't>
tolerance developes for: mood, sedation and hypnosis
Not to anticonvulsant and lethal effects
With repeated use of a barbiturate, there is a ____ in the drug's therapeutic index.
Why is this really important public health-wise?
decrease
this is important because barbiturate shave the highest rate of accidental OD among drug abusers because of it.
What is the mechanism of the barbiturates?
it facilitates GABA- mediated neuronal hyperpolarization by Cl- inflow
specifically, they increase the duration the Cl- channels are open
it potentiates GABA's inhibitory effect on CNS function
When will respiratory and CV depression occur with barbiturates?
ONLY at toxic doses
What is the effect of barbiturates on liver metabolism?
barbiturates are inducers of drug metabolism
repeated exposure causes an increase in the liber's drug metabolizing activity, meaning the barbiturate will be broken down faster with repeated use
How are barbiturates administered?
oral - as sedative or anticonvulsant
IV - as anesthetic induction agent
NOT given IM because the solution is alkaline and will cause tissue necrosis
In what populations is barbiturate metabolism slower?
geriatric and neonates
In terms of barbiturate elimination, what effect will increasing urinary pH have?
What does this mean for barb OD treatment
weak acids are reabosrbed at low pH
so...if you increase urinary pH (make more basic), you get more drug excretion
this means that an OD of phenobarbital can be treated by administering sodium bicarbonate intravenously to elevate urinary pH
Why is the sodium bicarb trick only really successful for phenobarbital and not the other barbiturates?
phenobarb isn't really metabolized much before it's excreted
the others are
What symptoms occur in a barbiturate hangover?
it's basically extended CNS depression
disrotions in mood, impaired judgmenet and fine motor skills as well as intellectual performance
these effect smay be noticeable as long as a day after usage
What is paradoxical excitement with barbiruates and who does it occur in?
the patient will appear intoxicated
seen most often in geriatric and weakened patients
What are the 3 main clinical uses of barbiturates?
anxiolytic/hypnotic
anticonvulsant
anesthesia inducer
What are the other clinical uses for barbiturates that are less common?
1. combined with other drugs to manage GI disorders or asthma
2. combined with other drugs for analgesia
3. decrease cerebral edema form surgery, injury or ischemia
4. treat hyperbilirubinemia and kernictus in neonates via induction of hepatic metabolism
5. anxiolytic-sedative-hypnotic with alcohol withdrawal
What are the steps of effect with benzodiazepines?
1. tranquilization
2. sedation
3. hypnosis
(actually, the true nesthetic depth is never reached, awareness of pain persists, but anterograde amnesia does occur, creating the illusion of previous anesthesia)
Why do only some benzodiazepines block seizures and produce muscle relaxation?
some are partial agonists vs. full agonists
some interact with specifi GABAa subunit receptor combinations and not others
What is the effect of benzodiazepines on sleep?
decrease sleep latency (faster onset)
diminish # of awakenins
overall effect is an increase in total sleep time
(greatest effect in patients with short baseline of sleep, not in those who normally sleep well)
What is the mechanism of action for the benzodiazepines?
they faciliate GABA-mediated neuronal hyperpolarizaiton by increasing the frequency of Cl- channel openings
Unlike the barbiturates, what is the effect of benzodiazepines on systems other than the CNS?
really very little effect on anything otuside the CNS
Why are the pharacokinetics of the benzos as a group so complex?
most benzos have active metabolites
the duration of behavioral effects does NOT coincide with plasma half life of the parent compound because they're metabolized at such different rates
What sort of amnesia can be caused with benzos taken with alcohol or high doses?
anterograde - memory after the drug has been taken
this is why Rohypnol is a "date rape" drug
Which are safer in general, barbs or benzos?
benzos - they have a high therapeutic index and death is rare unless other drugs like alcohol are present
Although Benzo toxicity is rare, what drug can be given as a benzo receptor antagonist?
flumazenil (romazicon)
What is the mechanism of action for the non-benzodiazepine benzodiazepine receptor agonists?
they bind only certain subtypes of the GABAa receptor at the benzo binding site
What are the advantages to the non-benzo benzo-receptor agonists?
they have rapid onset
short duration with no residual effects upong wakening
slow tolerance development
What are three examples of the non-benzo benzo-receptor agonists?
zolpidem (ambien)
zaleplon (sonata)
eszoplicone (lunesta)
What is the mechanism of Ramelteon (rozerem)?
It is an agonist at the maltonin MT1 and MT2 receptors in the brain's suprachiasmatic nucleus - the body's master clock
What does Ramelteon do for sleep?
It regulates 24-hour circadian rhythms, including sleep-wake cycles
thus, is normalizes sleep without any adverse effects or formation of dependence or abuse!
What is the difference between pharmacokinetic and pharmacodynamic tolerance? Which do you see with barbiturates?
pharmacokinetic = dispositional (induction of metabolism means repeated administration will lead to lower blood concentration and smaller effect)
pharmacodynamic = cellular adaptation (a functional change in the cell itself such that it becomes less responsive to the drug)
WIth the barbiturates, for the first 10 days or so you'll se pharmacokinetic tolerance, but then blood concentration levels start staying constant. However at that point you get pharmacodynamic tolerance, so you still get a gradually decreasing effectiveness
