Treatment of inner ear diseases

Dr Muhammad Raza

Treatment of inner ear diseases

Treatment of inner ear diseases

Treatment of inner ear diseases

Treatment of inner ear diseases

Treatment of inner ear diseases

Objectives

• Enumerate drugs that can be used to treat ear infections (Otitis E, O media).

• Enumerate different classes of drugs with examples that are used to treat vertigo.

• Describe their MOA in the treatment of vertigo.• Mention the drugs used to treat Miener’s disease.• Mention their MOA, indications and side effects.• List the drugs that induce ototoxicity (inner ear disorders)• Explain major MOA of these drugs in the induction of

ototoxicity

Antibiotics for Ear Infections• Many antibiotics are approved by the Food and Drug

Administration (FDA) to fight otitis media. Most antibiotics for ear infections fall under four families: Penicillins

Amoxicillin, Side effects may include mild diarrhea and rashes. Mild-to-moderate infections caused by highly susceptible organisms:

ADULTS: 500 mg PO q12h or 250 mg PO q8h; Severe infections or infections caused by less susceptible organisms: 875 mg PO q12h or 500 mg PO q8h

<40 kg: 80-90 mg/kg/d PO divided q8-12h for 10 d

Augmentin®- amoxicllin + clavulanate

– Adult: 875 mg PO q12h or 500 mg PO q8h for 10 d– Pediatric: <40 kg: 40-45 mg/kg/d PO divided q8h for 10 d

Sulfonamides: Cotrimoxazole (sulfamethoxazole + trimetoprim) TMP and SMZ are synthetic folate antagonists that are effective antimicrobials as

individual agents. TMP is usually bactericidal and acts by inhibiting sequential enzymes of the folic acid–synthesis pathway. SMZ is a structural analog of PABA and competitively inhibits formation of dihydrofolic acid from PABA. and interference with bacterial nucleic acid and protein formation.

Adult: 160 mg (TMP component)/800 mg (SMZ component) PO q12h; Pediatric: ≥ 2 months: 7.5-8 mg (based on TMP component)/kg/d PO divided bid

Antibiotics for Ear Infections Cephalosporins

Cefaclor: 2nd -generation PO cephalosporin indicated for infections caused by susceptible gram-positive cocci and gram-negative rods. used primarily to treat OM, sinusitis, and URIs caused by H influenzae that are resistant to ampicillin or amoxicillin.

Adult: IR: 250-500 mg PO q8h; not to exceed 4 g/d; SR: 375-500 mg PO q12h for 7-10 d; Pediatric: >1 month: 20-40 mg/kg/d PO q8h; may be divided bid to treat OM or pharyngitis;

not to exceed 2 g/d

Cefprozil: PO, semisynthetic, 2nd -generation cephalosporin. Binds to one or more PBPs, which, in turn, inhibit cell wall synthesis and result in bactericidal activity. Possible second-line therapy for AOM or initial therapy for OME. Therapeutic uses include OM, soft tissue infections, and respiratory tract infections

Adult: 250-500 mg PO q12h for 10 d; Pediatric: >6 months: 15 mg/kg PO q12h for 10 d; not to exceed 1 g/d

Cefuroxime: 2nd -generation cephalosporin maintains the gram-positive activity of first-generation cephalosporins and adds activity against Proteus mirabilis, H influenzae, E coli, K pneumoniae, and M catarrhalis. Common clinical uses include OM, and surgical prophylaxis.

Adult: OM: 250-500 mg PO bid; PEDS: 250 mg PO bid pc in children able to swallow tabs.

Antibiotics for Ear Infections Cephalosporins ----Contd

Cefixime: 3rd - generation cephalosporin available in an PO formulation. As with ceftriaxone, has enhanced antibacterial activity and increased stability against many beta-lactamases. By binding to one or more PBPs, it arrests bacterial cell wall synthesis and inhibits bacterial growth. When treating OM, susp is preferred due to higher serum concentrations achieved with this dosage form compared with tabs.

Adult and >50 kg: 400 mg/d PO qd or divided bid

Ceftriaxone: 3rd -generation cephalosporin with broad-spectrum gram-negative activity; lower efficacy against gram-positive organisms; higher efficacy against resistant organisms. Arrests bacterial growth by binding to one or more PBPs.

Adult: Not recommended; Pediatric: 50 mg/kg IM once; not to exceed 1 g/dose

Cefpodoxime: PO prodrug, Spectrum is similar to 3rd -generation cephalosporins.

Adult: 200 mg PO bid; Pediatric: 10 mg/kg/d PO divided bid; not to exceed 400 mg/d

Antibiotics for Ear InfectionsErythromycins. Macrolides

Erythromycin: Binds to 50S subunit of the 70S ribosome, blocking RNA-mediated bacterial protein synthesis.

Adults: 250 mg (erythromycin stearate/base) or 400 mg (ethylsuccinate) q6h PO 1 h ac, or 500 mg q12h;

Children and infants: 20-50 mg/kg/d PO divided q6h

Clarithromycin: PO macrolide antibiotic similar to erythromycin and azithromycin. Binds to 50S subunit of the 70S ribosome, thereby blocking RNA-mediated bacterial protein synthesis. Can be bacteriostatic or bactericidal in action, depending on concentration and the particular organism and its inoculum.

Adult: IR: 500 mg PO q12h for 7-14 d; Pediatric: >6 months: 7.5 mg/kg PO q12h for 10 d; not to exceed 1 g/d

Azithromycin: macrolide subgroup of azalides. Similar in structure to erythromycin. Inhibits protein synthesis in bacterial cells by binding to the 50S subunit of bacterial ribosomes.

Adult: 1 g PO as single dose: Pediatric: ≥ 6 months: Day 1: 10 mg/kg PO as single dose; not to exceed 500

mg/d; Days 2-5: 5 mg/kg/d PO; not to exceed 250 mg/d

Treatment of chronic suppurative OMDrugs Use/route/Dose/DurationCiprofloxacin(Pregnancy C)

Ototopical fluoroquinolone ē hydrocortisone. Has a broad spectrum of activity. Fluoroquinolones do not cause vestibular or cochlear toxicity recognized with aminoglycosides; 5-10 gtt instilled in affected ear bid; Children: >1 year: as in adults

Tobramycin(Pregnancy C)

Ototopical aminoglycoside ± corticosteroid is widely used today. Risk of vestibular or cochlear toxicity with prolonged use or use on the noninflamed middle ear exists; consider this when choosing to treat chronic suppurative otitis media with this class of medication; 5-10 gtt instilled in affected ear bid; Children: as in adults

Piperacillin(Pregnancy B)

Inhibits biosynthesis of cell wall mucopeptides and stage of active multiplication. Has antipseudomonal activity. 2-3 g IV/IM q6-12h; not to exceed 2 g with IM injection; Serious infections: 3-4 g IV/IM q4-6h; not to exceed 24 g/d; Children: 200-300 mg/kg/d IV divided q4-6h; not to exceed 24 g/d

Ceftazidime(Pregnancy B)

Effective IV antibiotic for systemic treatment of CSOM. Penetrates the middle ear mucosa effectively and does not cause vestibular or cochlear toxicity; 1-2 g IV q8-12h; Children: 30-50 mg/kg/dose IV q8h; not to exceed 6 g/d

VertigoVertigo is a subjective sensation of motion while motionless

• Vertigo is a subjective sensation of movement, usually rotatory but sometimes linear. It is often accompanied by pallor, sweating and vomiting. The objective sign of vertigo is nystagmus.

• Bodily balance is maintained by the input to the brain from the inner ear, the eyes and the proprioceptive organs, especially of the neck; dysfunction of any of these systems may lead to imbalance.

• The diagnosis of the cause of vertigo or imbalance depends mostly on history, much on examination and little on investigation. The particular questions to be asked relate to three areas.

1. Timing: episodic, persistent.2. Aural symptoms: deafness, fluctuating or progressive; tinnitus;

earache; discharge.3. Neurological symptoms: loss of consciousness; weakness; numbness;

dysarthria; diplopia; fitting

Treatment of VertigoThe goals of pharmacotherapy are to relieve vertigo, reduce morbidity, and prevent complications

Antihistamine: These drugs prevent the histamine response in sensory nerve endings and blood vessels and are effective in treating vertigo.

• Meclizine: – ↘es excitability of inner-ear labyrinth and blocks conduction in inner-ear

vestibular-cerebellar pathways. Effects are associated with therapeutic effects in relief of nausea and vomiting. Most effective if used prn for 2-3 d with episodes of true vertigo.

– Adult:25 mg PO q4-6h; Pediatric: >12 years: Administer as in adults• Dimenhydrinate (Dramamine)

– Diminishes vestibular stimulation and depresses labyrinthine function by means of central anticholinergic activity.

– Adult:50 mg PO/IM q4-6h or 100-mg supp q8h– Pediatric: 6-12 years: 25-50 mg PO q6-8h; not to exceed 150 mg/d; >12

years: Administer as in adults

Treatment of VertigoThe goals of pharmacotherapy are to relieve vertigo, reduce morbidity, and prevent complications

Benzodiazepine: By binding to specific receptor sites, these agents appear to potentiate effects of GABA and facilitate inhibitory GABA neurotransmission and other inhibitory transmitters. These effects may prevent vertigo and emesis.

• Diazepam (Valium)– Effective in treating vertigo. Depresses all levels of CNS, including limbic

and reticular formation, possibly by increasing activity of GABA, major inhibitory neurotransmitter. Effective for acute episodes. Discontinue as quickly as possible to maximize cerebellar vestibular compensation process.

– Adult: 5-10 mg PO/IV/IM q4-6h– Pediatric: >6 months: 0.05-0.3 mg/kg/dose IV/IM over 2-3 min, repeat in

2-4 h prn0.12-0.8 mg/kg/d PO divided q6-8h; not to exceed 10 mg/dose

Treatment of Vertigo• Phenothiazine

– These drugs are effective in treating emesis, possibly because of their effects in the dopaminergic mesolimbic system.

– Promethazine (Phenergan)– Antidopaminergic effective in treatment of emesis. Blocks

postsynaptic mesolimbic dopaminergic receptors in brain and reduces stimuli to brainstem reticular system. • Adult: 25 or 50 mg PO/IM/PR q4-6h• Pediatric: >2 years: 0.25-1 mg/kg PO/IV/IM/PR 4-6 times/d prn

– Prochlorperazine (Compazine)– Antidopaminergic drug that blocks postsynaptic mesolimbic

dopamine receptors. Has anticholinergic effect and can depress reticular activating system (possibly responsible for relieving nausea and vomiting).• Adult: 5-10 mg PO/IM q6h or 25-mg supp PR q12h• Pediatric: 2.5 mg PO/PR q8h or 5 mg PO/PR q12h prn; not to exceed 15

mg/d

Treatment of Vertigo

• Monoaminergic– These agents may be used to treat vertigo, possibly

by modulating the sympathetic system– Ephedrine• Stimulates release of epinephrine stores, producing alpha-

and beta-adrenergic receptors.• Adult: 5-10 mg PO/IM q6h or 25-mg supp PR q12h• Pediatric: 2-5 years: 3 mg PO q6-8h; and >5 years: 6.25 mg

PO q6-8h

Treatment of Vertigo

• Anticholinergic agent• These agents are thought to work centrally by suppressing conduction in

the vestibular-cerebellar pathways.

– Glycopyrrolate (Robinul)• Blocks action of acetylcholine at parasympathetic sites. Robinul safer and

has fewer adverse effects. Well tolerated in elderly patients and does not have potential for extrapyramidal syndrome.

• Adult: 1-2 mg PO bid/tid• Pediatric: >12 years: 40-100 mcg/kg/dose PO tid/qid

– Scopolamine• Blocks action of acetylcholine at parasympathetic sites in smooth muscle,

secretory glands, and CNS. Antagonizes histamine and serotonin action. Transdermal may be most effective agent for motion sickness. Use in treatment of vestibular neuronitis limited by slow onset of action. Severe adverse effects preclude use in elderly.

• Adult: 0.6 mg PO q4-6h or 0.5 mg TD q3d• Pediatric: 6 mcg/kg/dose IV/IM/SC; not to exceed 0.3 mg/dose; or 0.2

mg/m2 repeated q6-8h

Menière’s Disease • is a disorder of the inner ear resulting in the

clinical triad of vertigo, tinnitus and hearing loss.• The underlying mechanism is believed to be

distortion of the membranous labyrinth due to overaccumulation of endolymph.

• TREATMENT– The diagnosis of Ménière's disease is based on history

and clinical findings. Relief of the clinical findings is baseline for its management.• Control of vertiginous sensation using the medications

discussed before• IV hydration and antiemetics for nausea and vomiting

Drugs used to treat Menière’s Disease • All the drugs used to control vertigo are used to

manage vertigo symptoms in Menière’s Disease• Antihistamine (Meclizine, Dimenhydrinate)• Benzodiazepine (Diazepam)• Phenothiazine (Promethazine, Prochlorperazine)• Monoaminergic (Ephedrine)

• Anticholinergic agent (Glycopyrrolate, Scopolamine)• Corticosteroids• Antiemetics

Drugs used to treat Menière’s Disease Corticosteroids• These agents have anti-inflammatory properties and cause profound

and varied metabolic effects. – Prednisone– Useful in the treatment of inflammatory and allergic reactions. By reversing

increased capillary permeability and suppressing PMN activity, it may decrease inflammation.• Adult: A short course (3-5 d) of oral prednisone can be used; a starting dose of 40-

60 mg PO qd should be considered• Pediatric: A short course (3-5 d) can be used in children, with a starting dose of 5-10

mg PO

Antiemetics: These agents are used for treating emesis.– Metoclopramide: Dopamine antagonist that stimulates acetylcholine

release in the myenteric plexus. Acts centrally on chemoreceptor triggers in the floor of the fourth ventricle, which provides important antiemetic activity.• Adult: 5-10 mg PO or 5-20 mg IV/IM tid• Pediatric: 1-2 mg/kg IV/IM q2-4h

Drug induced Ototoxicity• A drug is considered ototoxic if it has the potential to cause toxic

reactions to structures of the inner ear, including the cochlea, vestibule, semicircular canals and otoliths, thus causing sensorineural hearing loss.

• Drug damage to the auditory and vestibular structures may cause hearing loss, tinnitus, disequilibrium or dizziness.

• Factors affecting ototoxicity include – dose, – duration of therapy, – concurrent renal failure, – infusion rate, – lifetime dose (prolonged use), – co-administration with other drugs having ototoxic potential, and – genetic susceptibility.

• Ototoxic drugs should not be used for otic topical application when the tympanic membrane is perforated because the drugs might diffuse into the inner ear.

Ototoxic drugs and site of action• Streptomycin tends to cause more damage to the vestibular

portion than to the auditory portion of the inner ear. – Severe loss of vestibular sensitivity may persist, sometimes

permanently. Loss of vestibular sensitivity causes difficulty walking, especially in the dark, and oscillopsia (a sensation of bouncing of the environment with each step). 1 g/day for > 1 wk which usually occurs after 7 to 10 days latency and slowly worsens if treatment is continued. Complete, permanent deafness may follow.

• Neomycin has the greatest cochleotoxic effect of all antibiotics. When large doses are given orally or by colonic irrigation for intestinal sterilization, enough may be absorbed to affect hearing

• Kanamycin and amikacin are close to neomycin in cochleotoxic potential and are both capable of causing profound, permanent hearing loss while sparing balance.

• Viomycin has both cochlear and vestibular toxicity.

Ototoxic drugs and site of action

• Gentamicin and tobramycin have vestibular and cochlear toxicity, causing impairment in balance and hearing. It may result from antibiotic binding to NMDA receptors in the cochlea and damaging neurons through excitotoxicity. The mechanism of aminoglycoside ototoxicity is mediated by disruption of mitochondrial protein synthesis and the formation of free oxygen radicals. The cellular basis for aminoglycoside hearing loss is a destruction of cochlear hair cells, specifically the outer hair cells. Co-administration of N-acetylcysteine may protect against aminoglycoside-induced ototoxicity.

• Vancomycin can cause hearing loss, especially in the presence of renal insufficiency.

• Cisplatin and carboplatinChemotherapeutics, (containing platinum ), can cause tinnitus and hearing lossthat can be profound and permanent, occurring immediately after the first dose, or can be delayed until several months after completion of treatment. Sensorineural hearing loss strikes bilaterally. Cisplatin and related agents are absorbed by the cochlear hair cells and result in ototoxicity through the production of reactive oxygen species.

Ototoxic drugs and site of action

• Ethacrynic acid and furosemide given IV have caused profound, permanent hearing loss in patients with renal failure who had been receiving aminoglycoside antibiotics. The ototoxic effects of loop diuretics seem to be associated with the stria vascularis, which is affected by changes in the ionic gradients between the perilymph and endolymph. These changes cause edema of the epithelium of the stria vascularis.

• Salicylates in high doses (> 12, 325-mg tablets of aspirin per day) cause temporary hearing loss and tinnitus. Salicylic acid quickly enters the cochlea, and perilymph levels parallel serum levels. Increasing levels produce tinnitus and, generally, a reversible flat sensorineural hearing loss. The mechanism is multifactorial but appears to cause metabolic rather than morphologic changes within the cochlea.

• NSAIDS such as Meloxicam have also be shown to be ototoxic. This can result in sensorineural hearing loss, dysequilibrium, or both.

• Quinine and its synthetic substitutes can also cause temporary hearing loss. Hearing loss is usually sensorineural and reversible. Discontinue- Improves symptoms.