Sunday, March 27, 2011

Drugs used in otology and their formulations

Introduction: Various drugs and formulations are used in otological practice. Some of them may be of questionable value from the therapeutic stand point, still it is worthwhile knowing about these formulations. Topical otological preparations are so unique they need to be studied in detail.

Advantages of topical drug use in otology:
  1. The drug can be administered right where it is needed
  2. First pass metabolism doesnt come into play
  3. Drug is delivered in a targetted manner, in adequate doses. Toxicity is not common
  4. Chronic inflammatory diseases of middle ear cavity causes a certain amount of fibrosis preventing adequate concentrations of systemically administered drug reaching it.

Ear drops are solutions / suspensions of medicines in solvents like water, glycerol, diluted alcohol, or propylene glycol. These solutions can be instilled into the ear. For these ear drops to be effective sufficient contact time should be provided.

Indications for use of topical ear drops:

  1. Bacterial / fungal infections of external auditory canal
  2. Chronic suppurative otitis media with a large drum perforation
  3. To liquefy accumulated wax in the external auditory canal
  4. Myringitis granulosa

If drops are to reach the middle ear in adequate concentration the ear drum perforation should be fairly large. The method of administration of ear drops to reach the middle ear cavity is known as the displacement method. In this method the external ear is made dependent by turning the head to the opposite side, with the chin touching the shoulder. The external auditory canal is filled with ear drops. Pressure is applied to the external ear by alternate pressing of the tragus. This maneuver displaces the air from the middle ear cavity which is duly filled up by the ear drops.

Difference between solution and solvent ear drops:

Solution usually consists of a drug which is dissolved in a solvent where as suspension consists of an insoluble drug distributed in a liquid medium. Some of the ear drops can be used as eye drops also. To facilitate such multi usage certain adjuvant drugs are added to the drops in addition to the active drug. Commonly used adjuvants in such drops which can be used as eye and ear drops include:

  1. 0.01% Benzalkonium chloride – This acts as an antifungal agent
  2. Sodium metabisulphite – This agent acts as a buffer maintaining the pH of the solution. This strict maintenance of pH prevents easy degradation of the active drug molecule present in the drops. It also minimizes the irritation caused due to application of the drops. It also retards the oxidation of the active drug there by prolonging the effect of the active drug.
  3. Disodium edetate – This is another adjuvant commonly used. It also acts as an excellent buffering agent. This adjuvant drug increases the bactericidal and antifungal activity of Benzalkonium chloride.
  4. Steroids – Beclamethazone is the commonly used steroid adjuvant drug in the ear drops for its antiinflammatory effect.

Some of the local drug preparations to be used in the external auditory canal may be in the form of creams / ointments. These ointments usually contain antibiotics and antiinflammatory agents in a suitable base like liquid paraffin, wool fat, yellow soft paraffin. Ointments usually have paraffin base. Ointaments are very useful in managing dry scaly skin conditions of external auditory canal. Ointment preparations with Lanolin as the base (wool fat) should be marked clearly on the tube because some patients may develop hypersensitivity reaction to this component of the medicine.

Acetic acid ear drops – Acetic acid in concentration of 2% is an excellent antibacterial and antifungal agent. Acetic acid ear drops can be used to treat mild otitis externa. This is commonly used in paediatric age group.

Aluminium acetate ear drops: This is an astringent drug which can be administered as ear drops or by dipping a cotton wick in the drug and inserting the same into the external auditory canal. Astringent belongs to a group of medicine that causes shrinkage of tissue on local application. Shrinkage of tissue is caused due to the hydroscopic effect of the drug. Hence it can be used to reduce oedema involving the external auditory canal. If this drug needs to be used for its astringent effect then it should be administered using a cotton wick. This drug is known to cause deposition of aluminium acetate crystals in the external auditory canal. Hence periodic cleansing of the ear is a must when this drug is used. This drug can be safely used even in pregnant mothers. In fact this is safest drug that can be administered during pergnancy.

Boric acid ear drops: Formerly this drug was used for their bacteriostatic and antifungal efects. It can be used in varying concentrations. Maxium concentration that can be safely used is 5%. This drug gets absorbed via the inflammed skin leading on to systemic toxicity due to the drug.

Antibiotic & steroid ear drops:
Betnesol / prednisolone sodium phosphate can be administered along with antibiotics like gentamycin / neomycin / quinolenes. When used in combination with these antibiotics they faciliate better effects due to their antiinflammatory effects.

Clotrimazole ear drops:
Clotrimazole is a broad spectrum antifungal agent. This drug inhibits ergosterol synthesis by the fungal cell wall. This destroys the fungus. Fungal infections involving the external auditory canal can also be caused due to inappropriate use of steroid ear drops. Administration of clotrimazole can cause burning sensation in the external auditory canal. Patient should be advised to tolerate it.

Ceruminolytic ear drops:
These are the most commonly used ear drops. Drugs belonging to this group include oil / aqueous preparations. These drugs are known to soften the wax facilitating its removal by aural syringing. 0.9% sodium choloride solution can be used as ceruminolytic agent. 5% sodabicarb solution can also be used as ceruminolytic agent.
Olive oil / coconut oil / liquid paraffin can also be used as ceruminolytic agents.
Organic solvents like chlorbutanol / paradichlorobenzene can also be used as solvents, but may cause irritation to meatal skin.

Indications for administration for systemic antibiotics:

  1. Acute otitis media
  2. Furunculosis of external auditory canal
  3. Perichondritis of pinna
  4. Acute mastoiditis
  5. Malignant otitis externa

Drugs administered systemically include:

  1. Amoxycillin
  2. Flucloxacillin
  3. Ciprofloxacillin
  4. Penicillins

Drugs used in the management of vertigo:

Betahistine can be used in the management vertigo associated with meniere's disease. This drug reduces the endolymph pressure by improving microvascular circulation in the striavascularis of the cochlea. It also reduces the vertigenous sensation by inhibiting the firing rate of vestibular nuclei. Betahistine is known to reduce vertigo / tinnitus but does little to improve hearing. It is usually prescribed in doses of 16 mg thrice a day.
This drug should be used with caution in patients with bronchial asthma / peptic ulcer.

Dopamine antagonists: Prochlorperazine belongs to this group. Goes by the popular name Stemetil. It is a dopamine antagonist acting by blocking the chemoreceptor trigger zone. It is less sedating with fewer antimuscarinic effects.

Antihistamines: Drugs belonging to this group acts on H1 receptor at the level of chemoreceptor trigger zone thereby blocking the vomiting centre. Examples of drugs belonging to this group are cinnarizine and cyclizine. Cinnarizine can be used as prophylaxis for migraine in doses of 30 mg three times a day. Cyclizine is useful only during acute attacks and is given in doses of 50 mg thrice a day.

Diuretics in the management of meniere's disease: Thiazides and acetazolamide can be used in the management of acute symptoms of Meniere's disease. The cause decompression of the endolymphatic sac due to their diuretic effects.

Steroids in the treatment of sudden sensorineural hearing loss: Steroids have been used in the management of sudden sensorineural hearing loss with varying degress of success. Dosage regimen is as follows:
60 mg on day I
50 mg on day II
40 mg for following three days
30 mg for subsequent three days

Use of antiviral drugs in otology:

Acyclovir is the classic example of drug belonging to this group. It can be administered in patients with Herpes Zoster oticus. It acts by inhibiting nucleic acid synthesis. It is administered orally in doses of 800 mg five times a day for 5 days. If administered within 72 hours after development of rash it reduces post herpetic neuralgia.

Use of sodium fluroide in otosclerosis:
sodium fluroide is used tto slow down the development of sensorineural hearing loss in a patient with otospongiosis. It acts due to its enzyme inhibiting activity there by preventing osteoclastic bone resorption. Usually it is administered in doses of 40 mg per day for a period of 3-6 weeks. This drug is really useful in patients with cochlear otosclerosis. It has propensity to cause gastric irritation and renal damage.

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