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A little About Ourselves: Names: Rakesh Dewan, Lily Liang, Janet Truong, and Josh McPherson We are 2nd year pharmacy students from the University of British Columbia Purpose We will focus on the use of common medications used for different cardiovascular conditions We hope to provide you with information that will lead to a safe, effective, and positive medication experience Objectives Learn how different medications work Become aware of potential side effects and how to manage them Dispel common myths about heart medications Outline Statins ACE inhibitors ARBs Diuretics Beta-blockers Calcium channel blockers Blood thinners Nitrates Cholesterol Lowering Drugs HMG-CoA Reductase Inhibitors (AKA: “Statins”) Examples: Drug Simvastatin Atorvastatin Fluvastatin Pravastatin Lovastatin Rosuvastatin (brand) (Zocor) (Lipitor) (Lescol) (Pravachol) (Mevacor) (Crestor) Statins most effective and well tolerated LDL lowering agents 38-54% reduction of LDL used in addition to dietary and lifestyle modifications to lower LDL cholesterol lowering of LDL has been shown to reduce risk of heart attack and stroke equally effective at heart attack and stroke prevention How Statins Work HMG-CoA reductase is an enzyme that is responsible for an important step in the production of cholesterol in the liver. Statins block the action of HMG-CoA reductase leading to lowered LDL (bad cholesterol) HMG-CoA molecule Mevalonate HMG-CoA Reductase blocked by statins Cholesterol How Statins Work Primary action through lowering the liver production of LDL Side Effects Statins are generally well tolerated Upset stomach: can manage by taking Statin medication with food Headache: can manage by treatment with non- prescription pain medication (Tylenol or Advil) Unexplained muscle pain: Contact Doctor or Pharmacist Tips AVOID Grapefruit juice: grapefruit juice can increase the side effects of most statins liver function test total cholesterol: 20% diet + 80% produced in liver Skill Testing Question Statins work by: a) Blocking the actions of cholesterol b) Inhibiting HMG-CoA which is an enzyme found in the liver responsible for LDL production c) Inhibiting HMG-CoA which is an enzyme found in the kidney responsible for LDL production d) Inhibiting HMG-CoA which is an enzyme found in the liver responsible for HDL production Inhibitors of Angiotensin Angiotensin Converting Enzyme (ACE) Inhibitors Angiotensin Receptor Blockers (ARBs) General Used For: High Blood Pressure Heart Failure Stable Angina Post Myocardial Infarction...... BUT HOW DO THEY WORK, SIDE EFFECTS..?? Angiotension Converting Enzyme Inhibitors (ACEI) What are some of these medications? Captopril (CAPOTEN) Enalapril (VASOTEC) Ramipril (ALTACE) Lisinopril (PRINIVIL, ZESTRIL) Quinapril (ACCUPRIL) Trandolapril (MAVIK) Benazepril (LOTENSIN) 25 mg 20 mg 5 mg “The Prils...” 2.5 mg 10 mg ACEI: How Does It Work? To understand how ACE inhibitors and also how ARBs work, one must understand the AngiotensinRenin Pathway...... 20% of patients with hypertension have abnormally HIGH renin-angiotnesin activity ACE Inhibitors: A Closer Look Angiotensin Converting Enzyme (ACE) is a natural enzyme found in our body that works to increase blood pressure ACE Inhibitors work by preventing this enzyme from working, thereby, decreasing diastolic/ systolic blood pressure ACEI: But Are They Effective? in Post- MI patients: reduce afterload and preload prevent complications such as left ventricular remodeling (aka hypertrophy) and HF shown to improve overall survival, decrease development of severe heart failure, and reduce re-infarction and heart failure hospitalization rates • benefits begin within first few days of therapy ACE Inhibitors: Side Effects Dry Cough! -> SOLUTION? Sore Throat/ Fever? Others: metallic taste feeling, rash possibly, hypotension (low blood pressure) Ace Inhibitors: Tips Important that Doctor and Pharmacist are aware of all prescription, non-prescription, and natural health medications NSAIDs (Non-Steroidal Anti-Inflammatory Drugs) Others: Iron, Lithium, Diuretics, Allopurinol to name a few ACEI: What Do You Think? ACEIs are known to increase potassium levels in the blood, would a diuretic that is not potassium sparing: a) Increase the potassium further in the blood b) Decrease the potassium in the blood to balance it with the ACEI c) Do nothing Angiotension Receptor Blockers (ARBs) What are some of these medications? Candesartan(ATACAND) Eprosartan (TEVETEN) Irbesartan (AVAPRO) Losartan (COZAAR) Olmesartan (BENICAR) Telisartan (MICARDIS) Valsartan (DIOVAN) Do you see a pattern in the naming? ARB: How Does It Work? Recall the renin-angiotensin pathway...... ARBs Inhibitors: A Closer Look Again, the main action is to relax the arteries in order to allow for more blood flow.... Uses are similar to ACEI, recall....hypertension, post-MI, heart failure, stable angina....often useful if ACEI intolerable Benefits? similar to ACEI; first-line in non-blacks and for patients with diabetes or ischemic heart disease ARBs: Side Effects Digestive Nausea, vomiting, diarrhea Body: headache, dizziness What about cough?? Others: metallic taste, hypotension, rash Side effects are usually mild and transient ARBs: Tips Important that Doctor and Pharmacist are aware of all prescription, non-prescription, and natural health medications Diuretics: may occasionally experience an excessive reduction of blood pressure after initiation of therapy; can be minimized by discontinuing the diuretic prior to initiation of treatment and/or lowering the initial dose of ARB Potassium Supplements/ Drugs that Increase Potassium (ie. Potassium sparing diuretics)..... ARBs: What do You think? Which of the following is FALSE? a) ARB stands for Angiotensin Receptor Blocker b) ARBs can cause coughing, just like ACEIs c) ARBs are useful for the management of hypertension What else? What else can I do? Manage a health weight Regular exercise: 23 ½ hours?? Healthy eating Medication compliance Find Heart Disease Resource Groups! Diuretics 3 classes – “water pill” I. Thiazides II. Loop Diuretics III. Potassium Sparing Diuretics How do diuretics lower blood pressure? Removal of sodium (salt) and water from the body I. Thiazide Diuretics Common Examples: Hydrochlorothiazide Indapamide Chlorothiazide Metoazone How do Thiazides work? A: They act on the DCT and inhibit Na+ and Cl- transporters USES: High blood pressure I. Thiazide Diuretics Where do Thiazides work? What percentage of sodium reabsorption happen in the DCT? II. Loop Diuretics Common Examples: Furosemide (Lasix) How do Loop Diuretics work? A: Similar to Thiazides except they act on the ascending loop of Henle USES: High blood pressure, and edema associated with heart failure II. Loop Diuretics Where do Loop Diuretics work? What percentage of sodium reabsorption happens in the ascending loop of Henle? III. Potassium Sparring Diuretics Common Examples: Amiloride Triamterene Spironolactone How do Potassium Sparring Agents work? A: Prevent the loss of potassium and interferes with the sodium-potassium exchange sites in the CT USES: High blood pressure, combination with other diuretic drugs to prevent hypokalemia Diuretics Common Side Effects: Upset stomach/Abdominal pain Frequent Urination Dryness of mouth Thirst Dizziness Photosensitivity* Low potassium levels* Diuretics Helpful Tips: Take with food Take medication early in the day, or at a flexible time to suit you Drink lots of water Rise slowly from a seat or lying position Apply sunscreen* Potassium rich foods* II. Beta-Blockers Common Examples: Propanolol Pindolol Labetaolol Metoprolol Bisoprolol Atenolol How do Beta-Blockers work? A: reducing heart rate and blood pressure USES: High blood pressure, angina, and heart failure II. Beta-Blockers Common Side Effects: Drowsiness Fatigue Dizziness and lightheadedness Dryness of the mouth, eyes and skin Cold hands and feet II. Beta-Blockers Helpful Tips: Rise slowly from a seat or lying position Drink lots of water Prepare ahead of time Exercise Calcium Channel Blockers Drug Amlodipine Nifedipine Felodipine Diltiazam Verapamil (Brand) _ (Norvasc) (Adalat) (Plendil) (Cardizem) (Isoptin) Calcium Channel Blockers Used alone or in combination with other medications for the treatment of: - hypertension -angina -irregular heart beats -migraines -Reynaud's syndrome -Brain aneurysm complications How Calcium Channel Blockers Work When a muscle fibre is stimulated, calcium channels open and allow calcium to rush in Calcium activates a protein called calmodulin Calmodulin bound to calcium starts the pathway that leads to muscle contraction Calcium channel blockers block the calcium channels that are present on the muscle fibres of vasculature and the heart End result is less contraction of vasculature and heart muscles leading to dilated vasculature or decreased force of heart contraction How Calcium Channel Blockers Work block calcium influx decreased muscle contraction dilated blood vessels and softer heart contractions Side Effects Dizziness: changing positions slowly may help to avoid sudden dizziness Flushing: strategies to help cool down may include the use of fans, layering clothes, or applying cool water to over-heated areas Ankle Swelling: support socks or stockings and elevation of the legs may be helpful Tips Grapefruit juice may increase the levels of calcium channel blockers leading to increased risk of side effects Some herbal supplements may counteract the desired effects of calcium channel blockers Some herbal supplements may lead to additive decrease in blood pressure leading to increased side effects. Skill Testing Question While on a Calcium Channel Blocker: a) Grapefruit juice should be regularly consumed to ensure effective therapy b) Blood vessels are usually constricted due to calcium channel blocker c) Herbal supplements that are known to decrease blood pressure may lead to more side effects (dizzyness, flushing, etc.) d) A common side effect is joint and muscle pain Blood Thinners: Anti-Coagulants Delay the clotting time through inferring with a series of chemical reactions that result in blood clots in arteries and veins. Oral examples: Warfarin (Coumadin) Dabigatran (Pradax) Rivaroxaban (Xarelto) Warfarin How does it work? Inhibit the synthesis of vitamin K dependent clotting factors by blocking vitamin K reduction enzyme activity. Warfarin Side effects: Gas Fatigue, dizziness Decreased clotting time for wounds Easily bruised GI bleeds Tips of taking warfarin: Regular INR blood test Unexpected bleedings (e.g increased frequency of nose bleeds) Take on an empty stomach Same time daily Warfarin Special Dietary consideration: 1) Vitamin K: -high intake can reduce the effectiveness of warfarin -daily dietary needs are 80 mcg (recommended 90-120mcg) - mainly in dark leafy green vegetables. Examples: Cabbage, brussel sprouts, collard greens, kale, lentils, soybean oil, spinach, turnip greens, asparagus, cheese, beef liver, green tea. *Does that mean I have to cut off from green vegetables? -No Or considering eating more low Vitamin K greens: - Green beans, peas, celery, cucumber, pepper, zucchini. Warfarin 2) Alcohol: - >3 drinks daily can increase the effect of warfarin. 1 drink = 5 ounces of wine, 12 ounces of beer, 1 ½ ounces of liquor *Best to avoid all alcoholic beverages. 3) Vitamin E: -avoid high doses (1,000 IU increases the risk of bleeding, 800 IU may be safe, more studies needed). 4) Herbal Supplements: Examples: garlic, ginkgo biloba, St. John’s Wort, arnica, wheat grass, bilberry, ginger. *check with pharmacist 5) OTC: - Limit use of Advil, Motrin, Aleve, Aspirin. Game of Truth……….or False 1) Warfarin reduces already formed clots. False Dabigatran (Pradax) How does it work? Direct reversible inhibition of thrombin that mediates a coagulation cascade producing blood clotting. Dabigatran Side effects: nausea, diarrhea Upset stomach, stomach pains Heart burn, indigestion Easily bruised (mild) Interactions: herbal supplement and OTC similar to those of warfarin. antacids Tips: With or without food Swallow whole Outside stable for 30 days. Warfarin or Dabigatran? Advantages of Dabigatran: Less incidences of bleedings Less INR monitoring are needed Less dosage adjustment are needed. May have less drug interactions. Less food interaction, especially no restrictions on Vit K foods. Disadvantages of Dabigatran: Twice daily dosing rather than one daily dosing in Coumadin. Relative new drug, long term effects are no known More expensive, not covered by Pharmacare. Blood Thinner: Platelet Aggregation Inhibitor Inhibit platelets from clumping together to form blood clots in vessels. Oral examples: Acetylsalicylic acid (Aspirin, Anacin, Entrophen) Clopidogrel (Plavix) Dipyridamole (Parsantine) ASA (Aspirin) How does it work? Permanent blockage of COX-1, leading to inactivation of COX system and subsequent blood clotting. COX-1 derives TXA2, which induces platelet aggregation. ASA Does that mean I have no functional platelets while I am ASA? -New platelets are continuously produced -10-20% platelet replaced -ASA inhibition for 1 hour out of 24 hour cycle - low percentage of platelets are inactivated. ASA Side effects: Heart burn, upset stomach Nausea increased risk of GI bleeds Things to avoid/limit: 1) NSAIDs (Aleve, Advil, Motrin) Infrequent use take ASA 1st. 2) Alcohol 3) Curry powder, paprika and licorice (large amount) 3) Herbal supplements examples: Glucosamine, ginkgo biloba, ginseng *check with pharmacist. ASA Tips: 75mg -325mg daily used in practice. Don’t crush EC tablet Full glass of water (8 ounces) Avoid laying down for 10 minutes after use Should not be taken in event of a stroke. Cool facts: Can prevent vascular death by 15% and nonfatal vascular events by 30%. Clopidogrel (Plavix) How does it work? Permanent inhibition of adenosin diphosphate (ADP) binding to platelet receptors on platelet membrane that causes aggregation. Clopidogrel Side effects: Easily bruised Fatigue, dizziness and headache Diarrhea, constipation Increased risks of GI bleeding Skin related reactions (rashes, itchiness) *due to nature of reaction may resemble that of allergic reaction, consult your pharmacist or doctor before continuing or discontinuing. Interactions: 1) NSAIDs (Advil and Aleve) 2) Herbal Examples: blueberry, anise, garlic, ginger, ginkgo biloba, ginseng, green tea Check with pharmacist* Tips: Take with or without food. Anti-coagulants or antiplatelets Question: Aren’t they both anti-clotting agents, don’t they do the same thing? Should I take both? Different mechanisms in blood clotting formations. Ongoing debate on which is more effective in prevention of stroke or thrombus. Decision for taking combination therapy is highly dependent on the medical condition and should only be made in discussion with your doctor. Are there non-drugs measures I can do to prevent blood clots in blood vessels? Avoid squatting, sitting or crossing your legs for long periods of time. inactive for long time, walk around for few minutes every one to two hours. flex your ankles, curl your feet or toes more often through the trip. Exercise. Prevent dehydrations. Limit your salt intake. Nitroglycerin (Nitrates) Prevention vs. Treatment Nitrate (Nitroglycerin): How Does It Work? Vasodilator that works by relaxing the blood vessels, decreasing the need for the heart to work as hard and lessen its need of oxygen. Nitroglycerin: Treat or Prevent? Why do we have all these different dosage forms? Short-acting: treating attacks of angina and can prevent angina if taken few minutes before engaging in activities that can trigger angina (sublingual tablet or sprays) Long-acting: Prevention of angina attacks, not for emergency relieve. (Transdermal patches, ointment, and extended releases capsules. Nitrate (Nitroglycerin): How To Take? Pumpspray? Nitrate (Nitroglycerin): How To Take? Patch? Nitrate (Nitroglycerin): How To Take? . Ointment? Every 6 to 8 hours if necessary, and wiped off at bedtime to provide a nitrate- free interval; may require as much as 10 to 12.5 cm and/or application every 4 hours. Apply to nonhairy skin area may be used; some patients prefer the chest. Sublingual Tablets? Sudden Attack? Preventative Use? . Nitrate (Nitroglycerin): Side Effects & Interactions Side Effects: Headache is most common. Others: flushing, dizziness, weakness, palpitations Nausea, vomiting, diarrhea Side effects are usually mild and transient Interactions: Alcohol Phosphodiesterase 5 inhibitors: sildenafil (Viagra) Herbals: long list (ginger, ginseng, licorice)….check with pharmacist if unsure Nitrate (Nitroglycerin): Tips Avoid taking alcohol Store in tight sealing container Protect from light Use your dosage form correctly Can I crush/ chew my SL Tablets? Last T or F Nitroglycerin (short-acting) can be taken multiply times throughout the day without serious side effects. True THE END Thank you for listening! Any questions? Now we have a question for YOU...