OTOTOXICITYAND TINNITUSA PERSONAL EXPERIENCE

IAN MACKENZIE MD MSc FRCSSENIOR LECTURER

LIVERPOOL SCHOOL OF TROPICAL MEDICINE

UNIVERSITY OF LIVERPOOLDIRECTOR OF WHO PREVENTION OF DEAFNESS PROGRAMME IN THE UKTINNITUS HELP GROUP JUNE 2008

OTOTOXICITY CAN BE BROADLY DEFINED AS TENDENCY OF CERTAIN SUBSTANCES EITHER SYSTEMIC OR

TOPICAL TO CAUSE FUNCTIONAL IMPAIRMENT AND CELLULAR DAMAGE TO THE TISSUES OF THE INNER EAR

ESPECIALLY TO THE END ORGANS OF THE CENTRAL NERVOUS SYSTEM OF

HEARING AND BALANCE.I WILL HOPE TO DESCRIBE MY OWN

EXPERIENCE OF TINNITUS AND HOW THIS MAY GIVE SOME IDEAS ABOUT THE

FUTURE.

OTOTOXICITY:• Is not common in England but more

common in low income countries;

• Generates much interest;

• Controversy for those physicians who treat life threatening conditions on forgetting side effects of drugs in an effort to save lives.

OUTCOMES of drug overdose :

• To lose all or some hearing limits ability to communicate and can be worse with accompanying tinnitus Before travelling to africa I take chloroquine for malaria prophylaxis within 12 hours I have raging tinnitus but it stops 24hours after stopping drug WHY I always ask not an overdose

• To lose ones balance literally – robs ability to perform some physical activity – leads to loss of independence.

ACTION ON COCHLEAABILITY OF OTOTOXIC SUBSTANCES TO AFFECT

SPECIFIC TISSUES OF THE COCHLEA IS DEPENDENT ON ENTRY OF THE SUBSTANCE INTO

THE COCHLEAR COMPARTMENT.THAT TISSUES

ABILITY TO INTERACT WITH THE PHYSIOLOGY OF THE INNER EAR.

OTOTOXICITY SUBSTANCES ENTER COCHLEA USUALLY THROUGH VASCULAR SYSTEM.

THE CSF VIA EITHER THE COCHLEAR AQUEDUCT OF THE INTERNAL AUDITORY MEATUS OR VIA THE

MIDDLE EAR ACROSS THE ROUND WINDOW

MOST COMMON ANATOMICAL CHANGES OF THE COCHLEA IDENTIFIED

WITH OTOTOXIC SUBSTANCES ARE IN THE

OUTER HAIR CELLS WHICH ARE PHYSICALLY DAMAGED

VESTIBULAR LOSS AFFECTS BALANCE NERVE OF HEARING AND BALANCE ARE

ONE CALLED VESTIBULO COCHLEAR NERVE

LIKE TINNITUS THERE ALL THE TIME

UNILATERAL OFTEN LIES PERMANENTLY STILL

BILATERAL COMPLAIN OF OSCILLOPSIA EYES JUMPING UP AND DOWN

JUST CANNOT GET UP

SYSTEMIC TOXICITY

SALICYLATES: USED BY HIPPOCRATES COMMENTED ON AUDITORY PROBLEMS

MULLER 1977 – IDENTIFIED THE EFFECTS OF HIGH DOSE TOXICITY

WITH ASPIRINSERUM SALICYLATE AND PERILYMPH LEVELS HAVE BEEN

MEASURED

SERUM LEVELS IN BLOOD PEAK ½ HOUR AFTER TAKING

PERILYMPH LEVELS IN COCHLEA PEAK 2 HOURS AFTER INGESTION

ASPIRIN

COMMONEST CAUSE OF TINNITUS

VERY EASY TO TAKE OTOTOXIC DOSE

CHEAP AND EFFECTIVE

EVIDENCE OF CELL DAMAGE OF STRIAL VASCULARIS PART OF COCHLEA

MAY BE RELATED TO BLOOD FLOW

ASPIRIN the cheap painkiller

QUININE

COMMONLY USED DRUG IN DEVELOPING COUNTRIES FOR CONTROL OF MALARIA USED IN THIS COUNTRYAND IRELAND FOR PERSISTANT CRAMP OFTEN REVERSIBLETINNITUS AND VERTIGO COMMONTHIS CAN BE TREATEDNIMODIPINECALCIUM CHANNEL BLOCKER

HEAVY METALS

MERCURY

LEAD

IN ASIA – CINNABAR A NATURALLY OCCURRING MERCURIC SULPHIDE USED WITH CHINESE HERBAL MEDICATION FOR 200 YR USED AS A SEDATIVE IN CHILDREN CAN BE CATASTROPHIC

LOOP DIURETICS – EG FRUSEMIDE

ALTER HAIR CELL ENERGY METABOLISM MAY BE TRANSIENT LOSS DEPENDENT ON RATE OF INFUSION

FLUCTUATING HEARING

CHEMOTHERAPY FOR CANCER

MOST OF THESE DRUGS CAUSE DEAFNESS AND TINNITUS

MOST COMMONLY USED

CISPLATINUM

USUALLY GIVEN – INTRAVENOUSLY

YOUNG MEN VULNERABLE 90% SUFFER DEAFNESS OR TINNITUS

CISPLATINUM

- CANCER OF CERVIX

- LUNG CANCER

- OVARIAN CANCER

ACCOMPANYING TINNITUS

DIFFICULT TO CARRY OUT

PURE TONE AUDIOMETRY

CHEMOTHERAPY FOR INFECTIONS

AMINOGLYCOSIDES (PSEUDOMONUS CLOSTRIDIA)

END IN MYCIN

GENTAMYCIN

STREPTOMYCIN

VANCOMYCIN

AVOID ELEVATED TROUGH CONCENTRATION

ALSO AFFECT KIDNEYS

MYCINS RANGE OF DRUGS

COMMONLY PRESCRIBED FOR SEVERE INFECTIONS

OFTEN NOT REVERSIBLE

BLOOD LEVELS IF NOT DONE IN HOSPITAL NEGLIGENT BECAUSE OF SUBSEQUENT DEAFNESS

MYCINS

ROUND WINDOW PRINCIPAL WEAKNESS IN TOPICAL APPLICATIONS

DEGREE OF OTOTOXICITY APPEARS TO BE DIRECTLY RELATED TO THE DURATION AND DOSE OF THE PREPARATION

IS THIS USEFUL KNOWLEDGE?

YES

IF SOMEONE IS TAKING OTOTOXIC MEDICATION, HEARING MAY DETERIORATE QUICKLY

OFTEN DIFFICULT TO TEST BECAUSE OF TINNITUS

THE FUTURE

KNOWN FOR 40 YEARS STREPTOMYCIN AND QUININE CAUSE DEAFNESS AND TINNITUS MAINLY FROM WORK DONE AFTER WW 2 1940-1945

MOST POPULAR DRUGS IN SUB SAHARAN AFRICA FOR TREATMENT OF MALARIA AND T.B.

HOW CAN WHAT WE KNOW HELP THE FUTURE RESEARCH INTO TINNITUS

THE COCHLEAR IS VERY SENSITIVE

WE KNOW SOMETHING TO DO WITH HAIR CELL DAMAGE

WE ARE LOOKING AT THE COCHLEA WITH NEW IMAGING TECHNIQUES USING DYES WHAT CHANGES IN BRAIN WHEN TINNITUS PRESENT

AS FAR AS HAIR CELLS GO CERTAINLY GROWN IN THE EARS OF HAMSTERS NOW TRYING TO GROW IN HUMANS SOLDIERS WITH NOISE DAMAGE

THE FUTURE• THERE IS HOPE SOLDIERS ARE GUINEA PIGS IN AMERICA• NEW TECHNIQUES FOR UNDERSTANDING TINNITUS• NEW TECHNIQUES FOR GROWING PARTS OF THE

COCHLEAR• IF DAMAGED PARTS CAN BE REPAIRED• WHY NOT STOP TINNITUS• NOISE DAMAGED HEARING PILL WITHIN 10 YEARS

• THANKS FOR LISTENING A PREDICTION I HOPE IS LIKELY