Sedatives/Hypnotics/Anxiolytics

Question 1

TEST: stress circuit:

Answer 1

in the HPA (hypothalamic pituitary adrenal axis), cortisol feeds back into the brain to suppress CRH release, and this neg feedback is thought to be important in normal regulation of stress, and it’s thought that the disruption of this neg feedback causes the problems

Question 2

TEST: manipulating different areas or specific areas of the circuit can literally turn on or off fear and anxiety responseswhile there are certainly disruptions in the HPA axis that cause problems, there are key brain circuits that are disregulated in addition to the ones that regulate the HPA axis that are probably responsible for alot of the behavioral phenotypes that we see and we know because of cortical mapping

Answer 2

manipulating different areas or specific areas of the circuit can literally turn on or off fear and anxiety responses

Question 3

while _____ are first line of anxiety drugs, ____ are still important

Answer 3

SSRI, benzodiazapines

Question 4

TEST: one issue with the pharmacotherapy of anxiety drugs is:

Answer 4

while you need a drug that has an anxiolytic effect (control or prevent anxiety), they also have sideffects which are not desirable: SEDATIVE, HYPNOTIC (put you to sleep), ANESTHETIC (insensibility) effects benzo have bad side effects (not necessarily anesthetics in high dose like some)

Question 5

Stress activates the Hypothalamic Pituitary Adrenal (HPA) axis which, in concert with other physiological responses:

Answer 5

coordinates our normal behavioral response to our environment.

Question 6

Stress-induced CRF release also:

Answer 6

activates extrahypothalamic brain circuits that contribute to anxiety-like behaviors

Question 7

test: theres a wide range of benzos that are still on the market, they all do EXACTLY the same thing (same moa), yet some are marketed for alcoholism, some sleep, some etc. This is all dependent on their:

Answer 7

half life; all has to do with elimination (widely varied)
halcion (triazolam) have a half life of 1-2 hours while quazepam has a half life of 40-120 hours, you prescribe them both for insomnia, but possibly different depending on what type of insomnia, i.e. triazolam if you have trouble falling asleep, quazepam if you have trouble staying asleep
for generalized anxiety and youre taking it daily, you want a drug with a lengthy half life:
take home:
TYPE OF BENZO IS CHOSEN BASED ON THE HALFLIFE

Question 8

TEST: In addition to anti-anxiety, benzos are:

Answer 8

anticonvulsants and used for seizures (not chronically, but if someone presents in ed) and ALCOHOL WITHDRAWL TO AVOID SEIZURES

Question 9

TEST: another use for benzos:

Answer 9

muscle relaxation: benzos are VERY effective at relieving acute muscle spasm in shoulder muscles

Question 10

TEST: while people take benzos to fall asleep, they don’t do much for quality of sleep, so why take it?

Answer 10

they decrease the latency or time it takes to fall asleep. They actually decrease ALL components of sleep EXCEPT STAGE 2!
NOTE: development of a tolerance to benzos develops but not to angiolitic effects, they actually get stronger, not sure why

Question 11

TEST: Benzo toxicity:

Answer 11

an overdose will only put you to sleep, BUT all suicides and overdoses occur WHEN COMBINED WITH ALCOHOL OR OTHER MEDICATION; bzd and alcohol cause death by RESPIRATORY FAILURE
also note, benzos work as soon as they enter your body where as ssri take weeks

Question 12

TEST: the deadly cocktail refers to_______; there has been a 400% increase in _____ and in about 30% of the cases,

Answer 12

opiods and bzd; opioid and bzd deaths, most all of these alcohol is present, but bzd, opioids and alcohol, the BZP enhance the high, but also enhance the sedative and respiratory depressant effects of these drugs- caution whenever prescribing two different hypnotic sedative drugs together

Question 13

TEST: BZD MOA:

Answer 13

Really good allosteric modulators of GABAa receptors; GABAa receptors modulate fast inhibition throughout the brain, and BZD BOOST that inhibitory function; NOT DIRECT AGONIST OF GABAa receptor! This is why we call them allosteric; They don’t activate the receptor directly, but they BOOST the effects of GABAa when BZD is present (enhances Cl current resulting in hyperpolarization, resulting in a net decrease of neuronal activity); No antipsychotic activity; We believe BZD reduces anxiety by selectively inhibiting neuronal circuits in the limbic system and relaxes muscles by increasing presynaptic inhibition in the spinal cord.

Question 14

TEST: Zolpidem (Ambien) and Eszopiclone (Lunesta) are:

Answer 14

they are non-bzd GABAergic drugs, and while they ARE STRUCTURALLY UNRELATED to bzd, they do bind to the same bzd site (as opposed to the GABA site), and they also enhance GABAergic inhibition. They have very minimal anxiolytic activity, but are good at binding to alpha1 subunits: so they’re better at sleep induction

Question 15

TEST: not high yield: barbiturates have largely been replaced by benzodiazepines bc:

Answer 15

they actually do bind to GABA receptors and cause activation of GABAa receptors, and thus they can cause respiratory failure and death with overdose, they are occasionally used to keep people in a coma like state in hospitals; low theraputic index

Question 16

TEST: buspirone:

Answer 16

lead the transition from bzd to ssri, really good anxiolytic, but not anticonvulsant, hypnotic or muscle relaxer. Originally 5-HT partial agonist, and apparently d3 agaonist. Takes a few weeks to start taking effect (same as SSRI) but not going to work for immediate anxiety attack so you have to prescribe benzo first then taper off and transition, pretty short half life and pretty benign side effects