Vertigo, Hearing Loss & N/V-Drugs Flashcards
name 3 major classes of drugs that have ototoxicity
aminoglycosides
cisplatin
loop diuretics
name the drug class: causes ototoxicity that is usually not reversible; possible improvement w/ N-acetylcysteine; dose dependent
aminoglycosides
which class of drugs produces irreversible ototoxicity?
cytostatic drugs (cisplatin)
is the ototoxicity with loop diuretics reversible?
can be irreversible
are most of the drugs that cause ototoxicity reversible or irreversible?
reversible
which drug class enters into outer hair cell –> cell death by either caspase-dependent or caspase independent mechanisms?
aminoglycoside
which drug enters outer hair cells and results in cell death, which appears to be primarily caspase-dependent?
cisplatin
how do the loop diuretics cause ototoxicity?
interfering with the production and maintenance of endolymph in the stria vascularis
- upset the fluid balance & this results in edema & loss of function
- the effect is dose-rate dependent (the concentration gradient is an important factor in the penetration of drugs into this area of the body)
meclizine, diphenhydramine, & promethazine all work to treat vertigo via which two types of receptors?
H1 & M1 receptors
which drug is useful for nausea arising from higher brain centers mediating fear, emotion, anticipation?
diazepam
which drug used to treat vertigo has the longest duration of action?
scopolamine
diphenhydramine & promethazine are inhibitors of what CYP enzyme?
CYP2D6
what are the general adverse effects of the drugs that treat vertigo?
drowsiness, dizziness
scopolamine is an antagonist at what receptor?
M1
diphenhydramine, meclizine, & promethazine all block which 2 receptors in the treatment of vertigo?
H1 & M1
which drug used to treat vertigo has a BBW for use by injection?
promethazine
which drug used to treat vertigo has an adverse effect of fatal respiratory depression in <2 y/o?
promethazine
all 4 drugs to treat vertigo (diphenhydramine, meclizine, promethazine, & scopolamine) are all inappropriate in what pt population?
geriatric
the vomiting process appears to be coordinated by what center in the lateral retcular formation of the mid-brainstem adjacent to both the CTZ in the area postrema at the bottom of the 4th ventricle & the solitary tract nucleus?
central emesis center
the lack of a BBB allows the CTZ to monitor blood & CSF constantly for toxins & to relay info to what center to trigger nausea and vomiting?
emesis center
other than the CTZ, what are four other inputs to the emesis center?
- vagus nerve (via solitary tract nucleus)
- splanchnic afferents via the spinal cord
- cerebral cortex
- vestibular apparatus
the CTZ has high concentrations of what 3 receptors?
serotonin (5-HT3), Dopamine (D2), Opioids
the solitary tract nucleus has what 4 types of receptors?
Enkephalin
histamine
ACh
5-HT3
what is the efferent component for the emesis center?
sends efferents to nuclei responsible for respiratory, salivary, vasomotor activity, and striated & smooth muscle involved in act of vomiting
what is the only 5HT-3 antagonists that has to be adjusted in hepatic disease?
ondansetron
all the 5HT-3 antagonists have what cardiac adverse effect?
QT-prolongation
ECG monitoring is recommended in pts taking which two 5HT-3 antagonists?
dolasetron or Ondansetron
what are the most common adverse effects of the 5-HT3 antagonists?
headache
constipation
diarrhea
the serotonin antagonists are used for CINV & PONV prophylaxis, often with what other drug class?
corticosteroid
which two D2 receptor antagonists are considered general purpose anti-nausea & anti-emetic drugs?
prochlorperazine
Chlorpromazine
Prochlorperazine & Chlorpromazine are D2 receptor antagonists and have what two other functions?
- antihistaminic
- anticholinergic
(used in other forms of Nausea, such as motion sickness)
chronic use of D2 receptor antagonists can have what adverse effect?
bone marrow suppression / blood dyscrasias
co-administration of D2 receptor antagonists with what other drug class may cause increased CNS adverse effects?
antipsychotics
phenothiazines (prochlorperazine, chlorpromazine) are associated with what cardiac adverse effect?
risk of QT prolongation w/ Torsades de pointes
what is the MOA for aprepitant?
substance P/NK-1 receptor antagonist
- central action (solitary tract) essential
- peripheral effects (vagal terminals in GI tract) also contribute
Aprepitant is metabolized by what CYP enzyme?
CYP3A4
what is the name of the pro-drug substance P / NK-1 receptor antagonist that is activated by extra-hepatic metabolism?
fosaprepitant
MOA dronabinol
G-protein coupled decreased neuronal activity in the medullary vomiting center & solitary tract nucleus
- oppose 5-HT3 mediated stim of vagal afferents
- appetite stim. via CB receptors in lateral hypothalamus (lower doses than for antiemetic action)
emesis is most likely from what 6 anti-neoplastic drugs?
cisplatin mechlorethamine streptozotocin cyclophosphamide carmustine dacarbazine
what is the treatment of choice for prophylaxis against acute emesis?
serotonin receptor antagonist + corticosteroid & possibly NK-1 antagonist
how do corticosteroids help reduce emesis caused by antineoplastic drugs?
corticosteroids act on steroid receptors in solitary tract nucleus (reduced release o serotonin has been proposed)
