Sweatman - Vertigo, Hearing Loss, N/V Flashcards
1
Q
What anti-histamines/anti-cholinergics are used to tx vertigo/N/V?
A
- Meclizine hydrochloride
- Diphenhydramine
- Scopolamine
- Promethazine HCl
2
Q
What benzo, CCS, and D2 antags are used to treat vertigo/N/V?
A
- BENZO: Diazepam
- CCS: Dexamethasone, Methylprednisolone
- D2 ANTAGS: Prochlorperazine, Chlorpromazine
3
Q
What 5-HT3 antags, NK1 antags, and cannabinoid receptor agonists are used to tx vertigo/N/V?
A
- 5-HT3 ANTAGS: Dolasteron, Granisetron, Ondansetron, Palonosteron
- NK1 ANTAGS: Aprepitant, Fosaprepitant
- CANNABINOID AGONISTS: Dronabinol, THC
4
Q
Name 3 principle drugs that produce irreversible ototoxicity.
A
- Aminoglycosides
- Cisplatin
- Loop diuretics (depending on circumstance of the individual pt)
5
Q
What is vertigo? Can drugs cause it? How?
A
- Multisensory sensorimotor syndrome w/perceptual, postural, ocular motor, and autonomic manifestations induced by:
1. Unusual, unadapted (motion) stimulation of intact sensory systems (motion sickness; height vertigo), or
2. Pathological (lesional) dysfunction - Some 377 drugs/drug combos report vertigo as AE
1. May be result of factors outside vestibular apparatus, like changes in BP leading to feeling of faintness
2. Those with most prominent effects usually do so by impacting structure/func of vestibular apparatus (e.g., hair cells of inner ear)
6
Q
What are the 8 ototoxic/vestibulotoxic drugs? Which ones have a dose-dependent effect? Which are reversible?
A
- Aminoglycoside and Cisplatin effects are IRREVERSIBLE
- For loop diuretics, adverse consequence may be reversible, depending on circumstances of individual patient
7
Q
How do aminoglycosides cause ototoxicity?
A
- Drug entry into outer hair cell leads to cell death by caspace-dependent or caspase-independent mechs
- STEPS: AG entry into outer hair cell via mechano-electrical transducer channels
1. Formation of AG-iron complex can react w/e- donors like AA to form ROS, like superoxide, hydroxyl radical, and hydrogen peroxide
2. ROS can activate JNK, which can translocate to nucleus to activate genes in cell death pathway
3. Genes can translocate to mito, causing release of cyt c, which can trigger apoptosis via caspases
8
Q
How does Cisplatin cause ototoxicity?
A
- Entry into outer hair cells results in cell death due to primarily caspase-dependent mechanism
- STEPS: CP entry into outer hair cell via mechano-transducer channels
1. Can be aquated to form monohydrate complex (MHC) in cells, which is more highly reactive
2. CP and/or MHC can activate NOX-3, resulting in ROS production -> ROS may activate JNK
3. JNK can translocate to cell nucleus to activate genes involved in cell death pathway
4. Genes translocate to mito, causing release of cyt c, which can trigger apoptosis via caspase-dependent mechanisms
9
Q
How do the loop diuretics cause otoxicity?
A
- Loops can cause either temporary or permanent loss of hearing by INH Na/K/2Cl co-transporter -> usually only temporary, but influenced by comorbid conditions
- Animal studies: act on similar ion transport process in the stria vascularis (responsible for production and maintenance of endolymph), producing edema and temporary LOF (upset fluid balance), resulting in DEC in endocochlear potential
- Effect dose-rate dependent -> conc gradient is critical factor in penetration of drugs into this part of body
- This can result in secondary effects on sound-evoked measures of hearing
10
Q
How do you manage short-term tx of vertigo?
A
- YELLOW X: H1 and M1 receptor antagonists
1. Meclizine hydrochloride
2. Diphenhydramine
3. Scopolamine transdermal patch
4. Promethazine hydrochloride - Diazepam (red x): useful for psychosomatic (anxiety-induced) vertigo, e.g., nausea arising from higher brain centers mediating fear, emotion, anticipation, etc.
11
Q
What are the salient similarities b/t the muscarinic and histaminergic antagonists (table)?
A
- Vary in duration of action: transdermal patch app of Scopolamine has longest (don’t touch, then touch eye)
- All undergo hepatic metabolism
- Diphenhydramine/Promethazine are CYP2D6 INH, so potential for drug-drug interactions
1. BBW for severe tissue injury w/Promethazine injection (also, don’t use in under 2-y/o) - All capable of producing dizziness/drowsiness, and additive effects possible w/o/sedatives, anti-muscs
- According to Beers criteria, all considered potentially inappropriate in geriatric pts
12
Q
What should be in your DDx for N/V? Which causes should we focus on for the purposes of this lecture?
A
- Agents in GI tract: alcohol, NSAID’s, oral AB’s
- Drugs in circulation reaching chemo-trigger zone, where presence is sensed by specialized cells in direct contact w/passing blood: anti-tumor chemo, alcohol, CCB’s, opioids
- Vestibular disorders via motion sickness/migraine: labyrinthitis, Meniere’s disease
- Psychogenic factors via higher brain centers: anticipatory vomiting
13
Q
How is vomiting coordinated? Describe the pathways and chemicals involved.
A
- Coordinated by central emesis center in lateral reticular formation of mid-brainstem, adjacent to (CTZ) chemoreceptor trigger zone in area postrema (AP) at bottom of 4th ventricle, and solitary tract nucleus (STN)
1. Lack of BBB allows CTZ to monitor blood and CSF constantly for toxic substances and to relay info to emesis center to trigger N/V - Info also relayed from gut, mainly from Vagus (via STN), but also from splanchnic afferents via spinal cord
- 2 other important inputs from cerebral cortex (esp. in anticipatory N/V) and vestibular apparatus (motion sickness)
- Center then sends out efferents to nuclei responsible for resp, salivary, and vasomotor activity + striated smooth mm involved
- NOTE: CTZ has high concentration of receptors for 5-HT3 (serotonin), D2 (dopamine), and opioids; STN rich in receptors for enkephalin, histamine, Ach, 5-HT3
14
Q
What is the role of vomiting? Steps?
A
- Act of emesis/sensation of nausea generally viewed as protective reflexes that serve to rid stomach and sm intestine of toxic substances, preventing further ingestion
- It is a complex process that consists of:
1. Pre-ejection: gastric relaxation, retroperistalsis
2. Retching: rhythmic axn of resp mm preceding vomiting, consisting of abdominal and intercostal mm and diaphragm against closed glottis
3. Ejection: intense contraction of abdominal mm and relaxation of upper esophageal sphincter
15
Q
What are some features that accompany vomiting? What if it is protracted?
A
- Accompanied by multiple autonomic phenomena, incl. salivation, shivering, and vasomotor changes
- During protracted episodes, marked behavioral changes, incl. lethargy, depression, and withdrawal may occur
