Intra tympanic medications allow for focused application of drugs at high levels directly to the inner ear through the round window membrane. Steroids such as methylprednisolone are commonly used intra tympanically to treat sudden sensorineural hearing loss and autoimmune inner ear disease due to their anti-inflammatory and vascular effects in the cochlea. Aminoglycoside antibiotics can also be delivered directly to the inner ear using the Silverstein micro wick technique to preferentially treat inner ear infections. Potential complications include persistent perforation of the eardrum and hearing loss.

1. Intra Tympanic Medications Dr. T. Balasubramanian M.S. D.L.O.

2. Why ? Focused application High drug levels where it is needed most Use of smaller quantity of the drug

3. Round window anatomy Round window is about 70 µ thick Consists of 3 layers Acts as a semi permeable membrane Blood labyrinthine barrier

4. What drugs can be used ? Gentamycin Lignocaine Steroids Inner ear cells could be potential targets for gene therapy Calpain inhibitors (leupeptin)

5. Lignocaine as I.T. infusion Silences the hyper functional neuronal pathways which causes tinnitus Causes intense vertigo and nausea Effect does not last long hence abandoned

6. Indications for intra tympanic steroids Idiopathic sudden s/n loss Idiopathic rapidly progressive s/n loss Otologic manifestations of systemic auto immune disease

7. SSNHL New onset unilateral hearing loss developing within 72 hours Patient feels a sudden pop with development of tinnitus Hearing drops precipitously Hearing fluctuations are common Medical emergency

8. Causes of SSNHL Traumatic Immunologic Toxic Circulatory Neurologic Metabolic Viral

9. Pharmacology of steroids Genomic actions Non genomic immediate actions

10. Action of steroids in the ear Anti inflammatory action Increases cochlear vascularity Reduces degeneration of stria vascularis due to its anti oxidant effects

11. What steroid to use ? ? Methyl prednisolone ? Hydrocortisone ? Dexamethosone

12. Why Methyl prednisolone ? Methyl prednisolone reached high concentration in the inner ear fluids This high concentration is retained for a longer period of time. The anti inflammatory potential of Methyl prednisolone was the best

13. Mode of administration Through a middle ear catheter Through a grommet Continuous infusion pump

14. Factors affecting the transfer of drug through round window Size of the particle Charge Presence of facilitating substances Thickness of the round window membrane Presence of inflammation in the round window membrane

15. Facilitators Histamine Prostaglandins Leukotrienes E.coli endotoxin Staphylococcal exotoxin Ethacrinic acid

16. Aminoglycosides Gets preferentially concentrated in the endolymph Damages type I cells preferentially in the ampullar area Delivered using Silverstein micro wick technique through a grommet

17. Silverstein Micro wick technique Made of polyvinyl acetate Passed through a ventilation tube The wick is 1mm in diameter and 9 mm long Drugs can be self administered Wick must be replaced once a month lest it is difficult to remove and becomes adherent to round window

19. Complications of IT medications Persistent perforation Mastoiditis Deafness

20. Role of reactive oxygen species Reactive oxygen species causes extensive damage to stria vascularis They are extremely toxic to cellular and sub cellular structures It is generated by noise trauma and also by aging Aminoglycosides cause trauma to cochlea by releasing R.O.S.

21. R.O.S. blockers Gluthathione D. Methionine Resveratrol Oxygen

22. Role of gene therapy Improves neuronal survival Prevents oxidative stress Regenerates auditory and vestibular hair cells

23. Gene therapy Direct delivery of genes Cochlea is suited because it is isolated from the remaining body by the blood labyrinth barrier Perilymph permits virus to reach the cochlea hence genes can be transmitted using a virus or non virus vectors