REVIEW OF ORAL DRUGS USED IN STROKE PREVENTION

BEFORE I TALK ABOUT THE DRUGS USED IN THE TREATMENT OF STROKE, I WOULD LIKE FIRST TO REVIEW THE PHYSIOLOGY OF HOW STROKES HAPPEN.

THE PROPER MEDICAL TERM FOR STROKE IS CEREBROVASCULAR ACCIDENT. THE TERM INDICATES THAT THE DISORDER ORIGINATES FROM THE BLOOD VESSELS OF THE BRAIN.

WHAT HAPPENS IN STROKE IS AN INTERRUPTION OF THE NORMAL BLOOD FLOW TO THE BRAIN. THE INTERRUPTION CAN LAST FROM SECONDS TO MINUTES OR MAY BE PERMANENT.

THE RESULTING SYMPTOMS WILL VARY FROM PATIENT TO PATIENT DEPENDING ON THE REGION OF THE BRAIN AFFECTED AND HOW WIDESPREAD THE DAMAGE IS.

THERE ARE THREE WAYS BLOOD SUPPLY TO THE BRAIN CAN BE DISRUPTED.

IN THE FIRST SCENARIO A CLOT, CALLED A THROMBUS CAN BE FORMED- THIS HAPPENS RARELY IN HEALTHY INDIVIDUALS. IT HAPPENS IN A CONDITION CALLED ATHEROSCLEROSIS.

IN ATHEROSCLEROSIS A THICK, ROUGH DEPOSIT FORM ON THE WALL OF A BLOOD VESSEL AND GRADUALLY NARROWS THE PASSAGEWAY SO BLOOD FLOW SLOWS. THE ROUGHENED DEPOSITS JUT INTO THE BLOOD STREAM AND BLOOD CLOTS FORM AROUND THEM, BLOCKING THE BLOOD VESSEL COMPLETELY. THIS IS CALLED THROMBOTIC STROKE.

IN THE SECOND SCENARIO: THE CLOT CAN BREAK LOOSE AND BLOCK A BLOOD VESSEL IN A DIFFERENT AREA FROM WHERE IT ORIGINATED. THIS IS CALLED AN EMBOLIC STROKE. ANOTHER WAY AN EMBOLIC STROKE CAN HAPPEN IS WHEN A BLOOD CLOT ORIGINATING FROM ANOTHER PART OF THE BODY, THE HEART FOR EXAMPLE, GETS LODGED IN A BRAIN ARTERY AND BLOCKS IT.

THE THIRD SCENARIO: A BLOOD VESSEL BURSTS. IN THIS CASE THE CELLS NOURISHED BY THAT SUPPLY ARE DEPRIVED OF OXYGEN AND FOOD. ALSO, THE ACCUMULATED BLOOD CLOTS DISPLACING BRAIN TISSUE AND INTERFERING WITH NORMAL FUNCTION OF OTHER WISE HEALTHY TISSUE. THIS IS CALLED HEMORRHAGIC STROKE.

SPEECH MAY BE AFFECTED, SIGHT, MOVEMENT, BLADDER CONTROL, EMOTIONS, ETC. DEPENDING ON THE REGION OF THE BRAIN AFFECTED AND HOW WIDESPREAD THE DAMAGE IS.

THROMBOTIC AND EMBOLIC TYPE STROKES OCCUR MORE FREQUENTLY THAN HEMORRHAGIC STROKES.

THE BODY IS A MIRACULOUS ORGANISM, IT TRIES TO REPAIR ITSELF. SMALL NEIGHBORING ARTERIES GET LARGER AND TRY TAKE OVER PART OF THE DAMAGED ARTERIES' WORK, IN THIS WAY AFFECTED NERVE CELLS MAY RECOVER PARTIALLY AND SOMETIMES EVEN FULLY.

ALSO THERE ARE MECHANISMS IN THE BODY TO DISSOLVE THE CLOTS.

SO, THE SMALLER THE AREA AFFECTED THE BETTER ARE THE ODDS FOR FULLER RECOVERY

NO MEDICATION CAN CURE A STROKE ONCE IT HAS OCCURRED.

THE GOOD NEWS IS THAT WHAT WE CAN DO IS SPEEDUP AND ENHANCE THE BODY'S OWN REPAIR MECHANISM.

INITIALLY WHEN A STROKE PATIENT IS BROUGHT INTO THE HOSPITAL THE ATTENDING PHYSICIAN WOULD ORDER A SERIES OF TESTS TO DETERMINE THE TYPE OF STROKE HE IS TREATING.

THERAPY INVOLVES STABILIZING VITAL SIGNS WHICH ENTAILS:

• MAINTAINING THE AIRWAYS SO THE PATIENT BREATHS EASILY

• BLOOD PRESSURE CONTROL

• DETECTING AND CORRECTING IRREGULAR HEAT RHYTHM

• BLADDER CARE IF NEEDED

• PROPER POSITIONING AND TURNING IN BED TO PREVENT BEDSORES

• PHYSIOTHERAPY AND SPEECH THERAPY AS NEEDED.

• AND DRUG THERAPY

  ANY ONE OR COMBINATION OF THESE MODES OF THERAPY MAY BE USED

  I WILL NOW TALK ABOUT DRUG THERAPY IN MORE DETAIL

  AS I SAID EARLIER THERE IS NO CURE FOR STROKE.

  THE GOAL OF DRUG THERAPY IS TO PREVENT THE RECURRENCE OF STROKE, AND TO TREAT THE SYMPTOMS RESULTING FROM THE STROKE. THE RESULTING SYMPTOMS MAY BE DEPRESSION, PAIN, LOSS OF BLADDER CONTROL AND SO ON.

  I DON'T WANT TO TALK ABOUT TREATING THE RESULTING SYMPTOMS BECAUSE THE TREATMENT WOULD NECESSARILY BE VERY INDIVIDUAL, VARYING FROM PATIENT TO PATIENT. WHAT I WOULD LIKE TO TALK ABOUT IS THE DRUGS WE HAVE AVAILABLE TO US TO PREVENT THE RECURRENCE OF STROKE.

  WE KNOW THAT THE MAJORITY OF STROKES ARE CAUSED BY CLOTS, EMBOLIC OR THROMBOTIC. PATIENTS WHO HAVE HAD THOSE TYPES OF STROKES ARE THEREFORE TREATED WITH ANTI-COAGULANTS, COMMONLY REFERRED TO AS BLOOD THINNERS.

  THE DRUGS USED ARE:

  1. ASPIRIN

  2. WARFARIN

  3. TICLOPIDINE

  4. DIPYRIDAMOLE

  5. SULFINPYRAZONE

  I AM SURE YOU ARE ALL FAMILIAR WITH ASPIRIN.

  ASPIRIN HAS BEEN WITH US FOR ABOUT A HUNDRED YEARS. WE USE IT RELIEVE PAIN, TO LOWER BODY TEMPERATURE WHEN WE ARE SICK AND TO TREAT MINOR ACHES AND PAINS.

  IN THE TREATMENT OF STROKE ASPIRIN INHIBITS THE ACTIONS OF BLOOD PLATELETS.

  THE PRIMARY FUNCTIONS OF THESE PLATELETS IS TO ASSIST IN THE NORMAL BLOOD CLOTTING PROCESS TO PREVENT EXCESSIVE BRUISING AND BLEEDING IN THE EVENT OF MINOR INJURY. UNDER NORMAL CONDITIONS THE PLATELETS SEAL SMALL LEAKS IN SMALLER BLOOD VESSELS AND BY DOING SO THEY PRESERVE THE INTEGRITY OF THE VESSELS.

  ASPIRIN INHIBITS THE ACTIONS OF THE PLATELETS BY PREVENTING THE PRODUCTION OF A CHEMICAL CALLED THROMBOXANE. THIS THROMBOXANE IS RESPONSIBLE FOR THE PLATELETS STICKING TO EACH OTHER AND FORMING THE "SEED" OF THE CLOT.

  POSSIBLE ADVERSE EFFECTS ARE:

  STOMACH IRRITATION (NAUSEA, VOMITING)

  BLEEDING AND ULCERATION

  IN HIGH DOSE IT CAN CAUSE HEARING LOSS OR RINGING IN THE EARS (DOSES USED IN STROKE ARE MUCH TOO LOW TO CAUSE THIS)

  SKIN RASH

  ALLERGIC REACTIONS (BREATHING DIFFICULTIES, SWELLING)

  STOMACH IRRITATION CAN BE AVOIDED IF YOU TAKE ASPIRIN WITH FOOD OR MILK. ALSO THERE ARE COATED ASPIRINS (ENTROPHEN OR GENERICS) WHICH MAY BE LESS IRRITATING TO THE STOMACH, AND THERE ARE BUFFERED ASPIRINS.

  YOU SHOULD REPORT TO YOUR DOCTOR IMMEDIATELY IF YOU HAVE

  BLOOD IN THE URINE

  SEVERE OR PERSISTENT DIARRHEA

  DIFFICULTY IN SWALLOWING

  DIZZINESS, LIGHTHEADEDNESS, OR FEELING OF FAINT (SEVERE)

  HALLUCINATIONS

  INCREASED THIRST

  SEVERE OR PERSISTENT NAUSEA OR VOMITING

  TROUBLE BREATHING

  CHEST TIGHTNESS

  WHEEZING

  SWELLING OF EYELIDS , LIPS, FACE

  UNEXPLAINED FEVER

  VISION PROBLEMS

  AS YOU SEE, ASPIRIN ALTHOUGH IS A READILY AVAILABLE DRUG THAT DOES NOT REQUIRE A DOCTOR'S PRESCRIPTION, CAN POTENTIALLY CAUSE SERIOUS HARM IF NOT USED APPROPRIATELY. IT MUST BE TREATED WITH THE SAME RESPECT YOU WOULD ANY PRESCRIPTION DRUG.

  A FEW YEARS AGO A NEW DRUG BECAME AVAILABLE ON THE CANADIAN MARKET-

  TICLOPIDINE- TRADE NAME TICLID.

  THIS DRUG, LIKE ASPIRIN PREVENTS THE PLATELETS FROM STICKING TO EACH OTHER AND TO THE WALLS OF BLOOD VESSELS AND THUS REDUCING THE TENDENCY FOR CLOT FORMATION IN NARROWED BLOOD VESSELS.

  TICLID IS USUALLY TAKEN TWICE A DAY.

  IT IS RECOMMENDED TO BE TAKEN WITH FOOD TO LESSEN THE STOMACH IRRITATION.

  TICLID CAN SOMETIMES INTERFERE WITH THE NORMAL PRODUCTION OF WHITE BLOOD CELLS WHICH THE BODY NEEDS TO FIGHT INFECTION. IF THIS IS GOING TO HAPPEN IT WILL USUALLY HAPPEN WITHIN THE FIRST THREE MONTHS OF THERAPY. THE CONDITION IS REVERSIBLE, THEREFORE CAREFUL BLOOD MONITORING BY YOUR DOCTOR IS VERY IMPORTANT IN THE EARLY PHASE OF THERAPY- EVERY TWO WEEKS FOR THE FIRST THREE MONTHS.

  REPORT TO YOUR DOCTOR IMMEDIATELY IF YOU HAVE:

• BLEEDING OR BRUISING THAT IS GREATER THAN USUAL

• ANY SIGN OF INFECTION (FEVER, CHILLS, OR SORE THROAT)

• ANY SERIOUS LONG LASTING DIARRHEA

• SKIN RASH

• P>STOMACH DISCOMFORT

• COLOR CHANGES (ESPECIALLY YELLOWING) IN YOUR SKIN, URINE, BOWEL MOVEMENT, OR WHITES OF YOUR EYES.

  TICLID IS USUALLY PRESCRIBED TO PEOPLE WHO DO NOT TOLERATE ASPIRIN WELL, OR IN WHOM ASPIRIN HAS NOT BEEN EFFECTIVE.

  ANOTHER WAY WE CAN REDUCE CLOT FORMATION IS BY BLOCKING THE ACTION OF VITAMIN K. THIS VITAMIN PROMOTES THE PRODUCTION OF PROTHROMBIN, WHICH IS A FACTOR IN THE CLOTTING MECHANISM.

  THE DRUG USED TO BLOCK VITAMIN K IS WARFARIN. (ONE OF THE TRADE NAME S IS COUMADIN)

  IT IS USED TO PREVENT CLOTS IN THE ARMS, LEGS, LUNGS, OR HEART IN SUSCEPTIBLE PATIENTS. BY USING WARFARIN WE CAN PREVENT EMBOLIC TYPE STROKES.

  SIDE EFFECTS INCLUDE:

  Gastrointestinal: Anorexia, nausea, vomiting, diarrhea (occasional)

  Hematologic: Hemorrhage (common), incidence varies with risk factors and degree of prothrombin time prolongation.

  Hepatic: Cholestasis (rare)

  Other: Urticaria, alopecia, elevated transaminases (uncommon), necrosis of skin, breast, genitalia, abdomen etc.

  PATIENT INSTRUCTIONS:

  1. TAKE THIS MEDICATION IN THE EXACT DOSAGE PRESCRIBED BY YOUR PHYSICIAN. IT MUST BE TAKEN REGULARLY TO BE FULLY EFFECTIVE. ALWAYS KEEP AN ADEQUATE SUPPLY ON HAND.

  2. TAKE THE MEDICATION AT THE SAME TIME EACH DAY. SHOULD YOU FORGET TO TAKE A DOSE, TAKE IT AS SOON AS YOU REMEMBER AND THEN GO BACK TO THE REGULAR SCHEDULE.. HOWEVER, IF YOU MISS A DOSE AND DO NOT REMEMBER UNTIL THE NEXT DAY, OMIT THE MISSED DOSE COMPLETELY AND TAKE ONLY THE NEXT DOSE AT ITS REGULARLY SCHEDULED TIME. DO NOT TAKE A DOUBLE DOSE TO MAKE UP FOR THE MISSED ONE.

  3. MANY DRUGS, INCLUDING ASPIRIN (ACETYLSALICYLIC ACID) AND A LARGE NUMBER OF NON PRESCRIPTION MEDICATIONS, MAY CHANGE THE WAY THIS DRUG WORKS. BEFORE USING PAIN RELIEVERS, COLD REMEDIES, SLEEP AIDS, OR ANY OTHER DRUG-STORE ITEM, CONSULT YOUR PHYSICIAN OR PHARMACIST.

  4. WHILE ON THIS MEDICATION, AVOID ACTIVITIES WHICH MAY CAUSE YOU TO BE INJURED. ALSO USE A SOFT TOOTH BRUSH AND FLOSS GENTLY SO AS TO PREVENT THE OCCURRENCE OF BLEEDING FROM GUMS. USE AN ELECTRIC RAZOR TO AVOID NICKS OR SCRAPES.

  5. YOUR PHYSICIAN MAY WISH TO PERFORM PERIODIC EXAMINATIONS AND TESTS TO ASSESS THE EFFECTIVENESS OF YOUR THERAPY. MAINTAIN CLOSE CONTACT WITH YOUR PHYSICIAN.

  FOODS RICH IN VITAMIN K MAY REDUCE THE EFFECTIVENESS OF WARFARIN, THEREFORE ONE SHOULD AVOID LARGE AMOUNTS OF THESE FOODS. THEY INCLUDE: ASPARAGUS, BACON, BEEF LIVER, CABBAGE, CAULIFLOWER, FISH, GREEN LEAFY VEGETABLES. MODERATE AMOUNTS ARE OK.

  ASPIRIN, TICLOPIDINE, AND WARFARIN ARE THE MOSS COMMONLY USED DRUGS FOR THE PREVENTION OF STROKE RECURRENCE.

  THE OTHER TWO DRUGS, DIPYRIDAMOLE AND SULFINPYRAZONE ARE NOT USED AS MUCH ANYMORE BECAUSE THE OTHERS HAVE BEEN SHOWN TO BE MORE EFFECTIVE.

  SULFINPYRAZONE

  SULFINPYRAZONE (TRADE NAME ANTURAN) WAS ORIGINALLY MARKETED FOR A CONDITION CALLED GOUT. IT HAS ALSO BEEN SHOWN TO HAVE SOME ANTIPLATELET ACTIVITY BUT IT IS NOT AS EFFECTIVE AS ASPIRIN.

  SIDE EFFECTS INCLUDE:

  Central nervous system: Dizziness, vertigo, tinnitus

  Dermatologic: Rash

  Gastrointestinal: abdominal pain, nausea, reactivation or aggravation of peptic ulcers

  Hematologic: Rarely anemia, leukopenia, agranulocytosis, thrombocytopenia.

  DIPYRIDAMOLE

  DIPYRIDAMOLE (TRADE NAME PERSANTINE) WAS INTRODUCED IN THE 70'S AS AN ANTIANGINA DRUG. MORE EFFECTIVE AGENTS ARE NOW AVAILABLE, BUT IT IS STIL USED AS AN ANTIPLATELET DRUG. IT IS OFTEN USED TOGETHER WITH ASPIRIN. THERE IS A COMBINATION PRODUCT AVAILABLE CALLED ASASANTINE. THE EFFECTIVENESS OF THIS DRUG HAS NOT BEEN DEFINITELY PROVEN.

  IT IS THOUGH THAT IT TAKES ABOUT ONE WEEK BEFORE THERE IS A SIGNIFICANT REDUCTION IN PLATELET ACTIVITY.

  THE DRUG SHOULD BE TAKEN WITH A FULL GLASS OF WATER ON AN EMPTY STOMACH. HOWEVER, IF YOU EXPERIENCE STOMACH IRRITATION IT MAY BE TAKEN WITH FOOD TO LESSEN THE IRRITATION.

  POSSIBLE SIDE EFFECTS:

  COMMON: NAUSEA/DIARRHEA

  RARE: HEADACHE, FLUSHING, DIZZINESS/FAINTNESS- REASON TO DISCUSS WITH YOUR DOCTOR

  RASH- IF THIS HAPPENS STOP THE DRUG AND CALL YOUR DOCTOR

  THERE ARE NO FOOD RESTRICTIONS WHEN TAKING DIPYRIDAMOLE.

  ANTACIDS MAY REDUCE ITS EFFECTIVENESS.

  AS WITH ALL ANTI-COAGULANTS BE ON THE LOOKOUT FOR UNUSUAL OR EASY BRUISING AND EXCESSIVE BLEEDING.

  NOW ABOUT HEMORRHAGIC STROKES

  UP UNTIL A FEW YEARS AGO THERE WAS NO DRUG TREATMENT FOR HEMORRHAGIC STROKES. THEN A DRUG CALLED NIMODIPINE (TRADE NAME NIMOTOP) WAS INTRODUCED. IT IS USED TO RELIEVE SYMPTOMS OF SUB ARACHNOID HEMORRHAGE- A HEMORRHAGE OF THE LINING OF THE OUTSIDE OF THE BRAIN.

  THE EXACT WAY IN WHICH IT BRINGS ABOUT RELIEF IS NOT FULLY UNDERSTOOD. IT IS THOUGH TO INCREASE CEREBRAL BLOOD FLOW, IMPROVE OXYGEN AND GLUCOSE UPTAKE AND UTILIZATION, DECREASE BLOOD VESSEL SPASMS, AND POSSIBLY REDUCE PLATELET FUNCTION.

  THIS DRUG SHOULD BE TAKEN ON AN EMPTY STOMACH BUT IF STOMACH IRRITATION DEVELOPS, IT MAY BE TAKEN WITH FOOD TO LESSEN THE IRRITATION.

  FOR NIMODIPINE TO BE OPTIMALLY EFFECTIVE, TREATMENT MUST BEGIN WITHIN 96 HOURS OF THE HEMORRHAGING.

  POSSIBLE SIDE EFFECTS:

  THE MOST COMMON SIDE EFFECTS ARE DIARRHEA AND HEADACHE.

  LESS COMMON SIDE EFFECTS INCLUDE SWELLING OF ARMS AND LEGS, CHANGES IN BLOOD PRESSURE, ITCHING, RASH, FLUSHING, MUSCLE CRAMPS.

  IF YOU EXPERIENCE ANY OF THESE AND THEY ARE PERSISTENT OR PARTICULARLY ANNOYING, NOTIFY YOUR DOCTOR.

  WHAT WORKS FOR ONE KIND OF STROKE CAN POTENTIALLY BE DANGEROUS FOR ANOTHER.

  ANTICOAGULANTS CAN POTENTIALLY AGGRAVATE HEMORRHAGIC STROKE.

  IN ADDITION TO THE DRUGS DISCUSSED ABOVE SOME STROKE SURVIVORS MAY BE ON OTHER MEDICATIONS USED TO TREAT MEDICAL CONDITIONS WHICH WE KNOW PUT PEOPLE AT A HIGHER RISK OF HAVING A STROKE. THESE MAY BE MEDICATIONS TO TREAT HEART DISEASE, OR DIABETES. AS WITH ALL OTHER MEDICATIONS, IT IS IMPORTANT THAT YOU TAKE THEM EXACTLY AS DIRECTED BY YOUR PHYSICIAN. DO NOT SKIP DOSES, AND IF YOU EXPERIENCE ANY PERSISTENT UNDESIRABLE EFFECTS, REPORT THEM TO YOUR DOCTOR OR PHARMACIST. THERE ARE LIKELY TO BE ALTERNATIVE DRUGS THAT WILL BE AS EFFECTIVE IN TREATING YOUR CONDITION, BUT MAY NOT HAVE THE SAME ADVERSE EFFECTS ON YOU.

  SMOKING IS ANOTHER KNOWN RISK FACTOR THAT IS CONTROLLABLE- IF SMOKE DISCUSS WITH YOUR DOCTOR HOW WE/SHE CAN HELP YOU QUIT.

  WE KNOW THAT PEOPLE WHO HAVE HAD ONE STROKE ARE AT A HIGHER RISK OF HAVING A SECOND STROKE. RECOGNIZING THE EARLY SYMPTOMS OF STROKE AND GETTING THE PATIENT TO HOSPITAL EARLY FOR TREATMENT AND REHABILITATION WILL GREATLY IMPROVE THE CHANCES FOR BETTER RECOVERY.

  THE EARLY SYMPTOMS OF STROKE ARE:

• A SUDDEN WEAKNESS OF THE FACE, ARM, OR LEG ON ONE SIDE OR BOTH SIDES OF THE BODY, USUALLY LASTING ONLY A FEW MINUTES

• P>TEMPORARY DIFFICULTY OR LOSS OF SPEECH, OR TROUBLE UNDERSTANDING SPEECH

• SUDDEN, TEMPORARY DIMNESS OR LOSS OF VISION

• DOUBLE VISION WHICH LASTS A SHORT TIME

• UNEXPLAINED HEADACHES

• UNEXPLAINED MOOD SWINGS

• TEMPORARY UNSTEADINESS OR DIZZINESS

  THERE IS CONSTANT RESEARCH IN THE AREA OF STROKE PREVENTION.

  THE MOST RECENT RESULTS ARE THE TWO NEW DRUGS DISCUSSED HERE.

  THANKS TO THE ONGOING RESEARCH, THE DEATH RATE DUE TO STROKE HAS BEEN REDUCED BY 50% SINCE THE 1960'S.

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