Principles of Cardiovascular Pharmacology PDF

PHARMACOLOGY AND TOXICOLOGY PRINCIPLES OF CARDIOVASCULAR PHARMACOLOGY WO N G C H U N K E U N G 23 SEP 2024 1 WHAT IS CARDIOVASCULAR PHARMACOLOGY? Cardiovascular pharmacology focuses on the fundamental mechanisms of cardiovascular cells and how drugs...

PHARMACOLOGY AND TOXICOLOGY PRINCIPLES OF CARDIOVASCULAR PHARMACOLOGY WO N G C H U N K E U N G 23 SEP 2024 1 WHAT IS CARDIOVASCULAR PHARMACOLOGY? Cardiovascular pharmacology focuses on the fundamental mechanisms of cardiovascular cells and how drugs influence the heart and vascular system https://bibliotecadeinvestigaciones.wordpress.com/2011/04/18/sistema-circulatorio/ 2 CARDIOVASCULAR CELLS AND CARDIAC MUSCLE CELLS (CARDIOMYOCYTES) Cardiovascular cells – Cells of the cardiovascular system – Include cardiac muscle cells (cardiomyocytes), endothelial cells, vascular smooth muscle cells, lymphatic endothelial cells, etc – Plays the role in circulating, supporting and maintaining the cardiovascular activity Cardiac muscle cells (cardiomyocytes) – Striated, branched, contain many mitochondria, and under involuntary control 3 PRECAUTIONS FOR CARDIOVASCULAR MEDICATIONS Many different types and combinations of drugs exist for treating cardiovascular disease It is the responsible of the health care team to decide the best treatment plan for the patients It is important to understand the desired effects and possible side effects of the medications Never stop taking a medication without consulting the physician exmample :high blood pressure Never changing the dose or frequency of drugs without seeking advice from the health care professional. 4 PRINCIPLES OF CARDIOVASCULAR PHARMACOLOGY Types of heart medications Pharmacology of blood vessels Drugs for hyperlipidemia Anticoagulants and antiplatelet agents 5 COMMON HEART MEDICATIONS Common Heart Medications: Anti-Ischemic Drug Therapy Drug Therapy for Systemic Hypertension Pharmacotherapy for Acute and Chronic Heart Failure Pharmacotherapy for Cardiac Arrhythmias 6 MYOCARDIAL ISCHEMIA Reduced blood flow to heart Usually due to a partial or complete blockage of the heart's arteries (coronary arteries) Prevents heart muscle from receiving enough oxygen Reduces the ability of heart muscle to pump blood May cause abnormal heart rhythms Can lead to heart attack or myocardial infarction https://liveimmensely.wordpress.com/2011/08/27/myocardial-ischemia-due-to-coronary-artery-blockage/ 7 COMMON SYMPTOM OF MYOCARDIAL ISCHEMIA - ANGINA Not a disease itself Instead, it is a symptom of the other underlying condition Patient feel like pressure, squeezing or pain in the chest Angina occurs when part of the heart not receiving enough oxygen https://vivircomoadultomayor.blogspot.com/2016/08/que-es-la-angina-de-pecho.html 8 ANTI-ISCHEMIC DRUG THERAPY Anti-ischaemic drugs decrease myocardial oxygen consumption 76 Lowering heart rate, blood pressure, myocardial contractility or ventricular preload vessel dilated Increase myocardial oxygen supply (by coronary vasodilatation) https://wtcs.pressbooks.pub/pharmacology/chapter/6-3-common-cardiac-disorders/ 9 ANTI-ISCHEMIC DRUG THERAPY mostly for elderly Nitroglycerin – A vasodilatory drug (drugs that open the blood vessels) – Provide relief from anginal chest pain (chest pain due to reduced blood flow to heart muscles) – Acute relief of an attack of angina pectoris (or simply angina) https://thuocdantoc.vn/thuoc/glyceryl-trinitrate 10 INTRAVENOUS NITROGLYCERIN Available since early 1980s why dont use oral and tablet ? cuz when so painful u cant swallow Arterial dilation resulting hypotension occurs more quickly Dose necessary for relieving myocardial ischemia varies between patients Relief is usually achieved with 75 to 150 μg/min https://en.wikipedia.org/wiki/File:Vasoconstriction_and_Vasodilation.png 11 ANTI-ISCHEMIC DRUG THERAPY β-Adrenergic blockers – Reduce oxygen consumption – Decreasing heart rate – Decreasing the blood pressure – Decreasing myocardial contractility thus reduce myocardial oxygen demand – Increased collateral blood flow Redistribution of blood to ischemic areas β-Adrenergic blockers should be started early in ischemic patients Patients with high risk of perioperative cardiac morbidity – Should be started with β-blocker therapy before surgery and continued on this therapy for a suitable period 12 DRUG THERAPY FOR SYSTEMIC HYPERTENSION Beta blockers Calcium channel blocker Diuretics Angiotensin-converting enzyme (ACE) inhibitors Angiotensin receptor blockers (ARBs) 13 INTRAVENOUS BETA-ADRENERGIC BLOCKERS Propranolol Decreasing the heart rate and facilitating the heart to pump blood around the body Works differently if applying it for anxiety – In situation of anxious, the brain makes the chemical messengers of adrenaline and noradrenaline. It results in a fasting heart rate, sweating or shaking – Propranolol reduces anxiety by blocking the effects of these chemical messengers Propranolol prevents migraines – Headache usually on one side of the head with a pulsing sensation – May act by relaxing the blood vessels involved, or reducing the activity in visual cortex (brain cortical region that receives, processes and integrates the visual information from the retinas) where migraines are believed to start Propranolol is generally safe to take for a long time, under the advice of the doctor. A continuous infusion of 1 to 3 mg/hr can prevent hypertension 14 INTRAVENOUS BETA-ADRENERGIC BLOCKERS Metoprolol First clinically used cardioselective β-blocker Affinity for β1-receptors is nearly 30 times higher than its affinity for β2-receptors Difference between β1-receptors and β2- receptors β1-Adrenergic receptors predominate in the heart and in the cerebral cortex β2-adrenergic receptors predominate in the lung and cerebellum https://www.wikidoc.org/index.php/Metoprolol_tartrate_(injection) In many cases, β1- and β2-adrenergic receptors coexist in the same tissue 15 INTRAVENOUS BETA-ADRENERGIC BLOCKERS Esmolol Chemical structure similar to metoprolol and propranolol – There is a methylester group in the para position of the phenyl ring – Susceptible to rapid hydrolysis by red blood cell esterases – Hydrolysis leads to an acid metabolite and methanol having clinically insignificant levels Cardioselective, and block primarily the β1- receptors Hypotension is a common side effect https://www.sciencedirect.com/topics/chemistry/esmolol 16 CALCIUM CHANNEL BLOCKERS Medicines used to lower blood pressure Besides, it reduces the myocardial oxygen demands by depression of contractility The mechanism is stopping the calcium from entering the cells of the heart and arteries every muscle cells contract must have calcium Through blocking calcium, it allows blood vessels to relax and open Calcium channel blockers is effective in managing most angina https://www.wikidoc.org/index.php/Calcium_channel_blocker 17 COMMON CALCIUM CHANNEL BLOCKERS Nimodipine Lipid soluble Penetrates the blood-brain barrier Suitable for vascular spasm after intracerebral bleeding Vascular spasm Narrowing of the arteries Persistent contraction of the blood vessels This vasoconstriction reduce blood flow https://s3.amazonaws.com/static.wd7.us/f/fd/Nimodipine_label_01.jpg 18 COMMON CALCIUM CHANNEL BLOCKERS Nifedipine Relaxes blood vessels Increases the supply of blood and oxygen to the heart Available for oral administration – Liquid-filled oral capsules (30 mg) and oral solution (6 mg/mL and 30 mg/10 mL strength) – If the capsule cannot be swallowed Puncture of the capsule followed by sublingual administration May achieve an onset of effects in 2 to 3 minutes – Degenerates with presence of light 19 COMMON CALCIUM CHANNEL BLOCKERS Nicardipine Control angina (chest pain) Treat high blood pressure by by relaxing the blood vessels Longer half-life than nifedipine Potent relaxant of vascular smooth muscle Vascular selectivity for coronary and cerebrovascular beds Half-life of drug Time taken for amount of a drug's active substance in the body to reduce by half Vary from a few hours to a few days, or sometimes weeks 20 COMMON CALCIUM CHANNEL BLOCKERS Verapamil Calcium-channel blocker Relaxing the blood vessels - Heart does not have to pump as hard Treat high blood pressure and control angina (chest pain) Using alone or with other medications - Prevent and treat irregular heartbeats Intravenous verapamil – Peaking at around15 minutes – Lasting up to 6 hours During long-term oral administration – Accumulation of the drug occurs with prolonged half-life 21 COMMON CALCIUM CHANNEL BLOCKERS Diltiazem Direct action on cardiac tissue May be used in association with other antihypertensive drugs or as monotherapy Common starting doses: 120–240 mg/day Can be increased up to 540 mg/day based on individual needs After oral dosing, the bioavailability of diltiazem is greater than that of verapamil 22 TWO MAIN TYPES OF CALCIUM CHANNEL BLOCKERS Dihydropyridines Nondihydropyridines Nimodipine Diltiazem Nicardipine Verapamil Nifedipine Dihydropyridines target blood vessels and cause them to relax Non-dihydropyridines. There are two calcium channel blockers approved in the U.S. that aren’t dihydropyridines. They target heart muscle as well as blood vessels, effective at treating heart rhythm problems 23 POSSIBLE SIDE EFFECTS OF CALCIUM CHANNEL BLOCKERS Dihydropyridines: Headaches. Swelling in your limbs Feeling lightheaded or dizzy Feeling flushed Non-dihydropyridines Slow heartbeat (bradycardia) Reducing the heart’s blood pumping ability Increase in symptoms of gastroesophageal https://www.youtube.com/watch?v=zAGJNpxIgN4 reflux disease (GERD) or heartburn Constipation 24 DIURETICS Medicines helping to move extra fluid and salt out of your body Help patient with frequent urination Used to treat high blood pressure Also used to treat fluid retention due to heart failure Relieve symptoms of oedema (swelling) in legs, lungs or abdomen Commonly take diuretics once or twice a day 25 MOST COMMONLY PRESCRIBED DIURETICS Thiazides are the most commonly prescribed diuretics Not only decrease fluids, thiazides also cause the blood vessels to relax Avoid diuretics if you: Have severe dehydration Have anuria (lack of urine production) Have an electrolyte abnormality Have a known hypersensitivity https://www.pharmacy180.com/article/sar-of- thiazide-diruretics-2268/ 26 POSSIBLE SIDE EFFECTS OF DIURETICS Diuretics are normally safe. Side effects may include: More frequent urination Too little sodium in the blood. Too little potassium in the blood Gout Headaches Dizziness Muscle cramps Dehydration https://commons.wikimedia.org/wiki/Thiazide_diuretics Erectile dysfunction for male 27 ANGIOTENSIN-CONVERTING ENZYME (ACE) INHIBITORS Medicines that help relax the veins and arteries Lower the blood pressure Prevent an enzyme in the body from making angiotensin II – Angiotensin II is the substance that https://healthjade.com/ace-inhibitors/#google_vignette narrows blood vessels – Angiotensin II cause high blood pressure 28 COMMON ANGIOTENSIN-CONVERTING ENZYME (ACE) INHIBITORS Enalapril Fosinopril Imidapril https://1.bp.blogspot.com/- M3vtl5kQRqs/TmCs1pPEVHI/AAAAAAAANcY/_aTfZcqteUs/w1200- h630-p-k-no-nu/enalapril%2BODT.jpg Lisinopril 29 POSSIBLE SIDE EFFECTS OF ANGIOTENSIN- CONVERTING ENZYME (ACE) INHIBITORS Headaches Loss of taste Extreme dizziness and tiredness if blood pressure going too low Too much potassium in the blood Dry cough Rarely, short-term worsening of kidney function 30 DIFFERENCE BETWEEN A BETA BLOCKER AND AN ACE INHIBITOR Both used for conditions of high blood pressure and heart failure ACE inhibitors mainly lower blood pressure by relaxing blood vessels Beta blockers mainly lower the heart rate, they can also relax blood vessels in the body 31 ANGIOTENSIN RECEPTOR BLOCKERS (ARBS) Also known as angiotensin II receptor antagonists Used to treat high blood pressure and heart failure Also used in chronic kidney disease and prescribed following a heart attack 32 WHY ARB IS BETTER THAN ACE INHIBITOR? Angiotensin II receptor blockers (ARBs) and angiotensin-converting enzyme (ACE) inhibitors are both good choice groups of medications for treating high blood pressure They have similar benefits and both work well in the human body ARBs seem to cause less side effects than ACE inhibitors The major advantage associated with ARBs: – Higher treatment compliance and – Lower rate of withdrawal due to adverse events (compared to ACE inhibitors) 33 WHAT IS THE MOST POPULAR ARB MEDICATION? Losartan (Cozaar) is the most commonly used ARB Other options includes irbesartan, olmesartan, telmisartan, candesartan and valsartan https://blog.kakaocdn.net/dn/c65T6a/btszlHrBR6p/F mhKduIFqJEpbY5uterJ5K/img.webp 34 WHAT IS THE MOST COMMON SIDE EFFECT OF ARBS? The main side effect of ARBs is dizziness Which ARB is safe for kidneys? –Based on the results clinical trials, losartan and irbesartan may be indicated for treating diabetic nephropathy and are the ARBs of choice in these patients 35 PHARMACOTHERAPY FOR ACUTE AND CHRONIC HEART FAILURE https://en.wikipedia.org/wiki/Heart_failure 36 WHAT IS CHRONIC AND ACUTE HEART FAILURE? Chronic Heart Failure A condition that the heart has trouble pumping blood through the body The condition may develop over a long period of time Symptoms include shortness of breath, swelling of the ankles, feet and abdomen, problems exercising and fatigue Acute heart failure A sudden, life-threatening condition that the heart can no longer do its job 37 DRUG OF CHOICE FOR CHRONIC HEART FAILURE? Angiotensin-converting enzyme (ACE) inhibitors Relaxing and opening up the blood vessels Favour for the heart to pump blood around the body Examples of ACE inhibitors include: Enalapril Fosinopril Imidapril Lisinopril 38 DRUG OF CHOICE FOR ACUTE HEART FAILURE? Diuretics remain the standard therapy Intravenous method of administration of a loop diuretic Potentially poor absorption of the oral form in the presence of bowel edema Examples of diuretic include: Furosemide Bumetanide Torsemide 39 WHAT ARE LOOP DIURETICS AND HOW DO THEY WORK? Loop diuretics are the most potent diuretics Reduce Extracellular Fluid (ECF), cardiac output, and blood pressure The mechanism of action for loop diuretics: – Inhibiting the apical sodium/potassium/chloride transporter in the thick ascending limb of the loop of Henle – Reduces sodium, potassium and chloride absorption – Increased urine production helps reduce fluid retention and edema in the body – Reduce intravascular volume, leading to a decrease in central venous pressure, right and left heart filling pressures 40  PHARMACOTHERAPY FOR CARDIAC ARRHYTHMIAS Digitalis may be used for treating congestive heart failure (CHF) and heart rhythm problems (atrial arrhythmias). 41 DIGITALIS PREPARATIONS Used for treating heart rhythm problems and Congestive heart failure Increase blood flow throughout the body Leads to better blood circulation Reduce swelling in your hands and ankles Most commonly used digitalis preparations are digoxin and digitoxin https://medsgo.ph/prescription-medicines/cardio/lanoxin-digoxin-50mcg-ml-elixir-60ml/ 42 HOW DOES DIGITALIS WORK? Strengthen the force of the heartbeat – Increasing the calcium amount in the heart’s cells Digitalis medicines binds to sodium and potassium receptors of heart muscle – Stops the calcium from leaving the heart muscle cells – Calcium builds up in the cells – Calcium stimulates the heartbeat – Causes a stronger heartbeat Digitalis medicines also control arrhythmias (irregular heart rhythms) – Slow down the signals starting in the sinoatrial (SA) node – Reduces the number of signals that travel through the atrioventricular (AV node) – Fewer signals lead to fewer arrhythmias 43 INTERACTION OF DIGITALIS WITH OTHER MEDICINE Other medicines can interact with digitalis They can increase or decrease the effect of digitalis Categories of medicines that may increase or decrease the effects of digitalis includes: – Calcium channel blockers – Other heart medicines – Ulcer or stomach medicines – Antacids – Certain antibiotics – Certain antifungal medicines – Certain cholesterol-lowering medicines – Certain anti-anxiety medicines – Certain cancer medicines 44 SIDE EFFECTS OF DIGITALIS Side effects may include: Nausea Vomiting Diarrhea Eye sensitivity to light Blurry eyesight, double vision Irregular heartbeat Unusual tiredness or weakness A skin rash 45 BEST TREATMENT FOR CARDIAC ARRHYTHMIA? Antiarrhythmic drugs that convert the arrhythmia to sinus rhythm (normal rhythm) thus can prevent an arrhythmia Medicines that control your heart rate Anticoagulant or antiplatelet therapy drugs, such as warfarin or aspirin, that reduce the risk of blood clots forming 46  HYPERLIPIDEMIA Abnormally high levels of fats (lipids) in the blood Including cholesterol and triglycerides May inherit it or develop it from lifestyle factors Including too little physical activity and diet factors Commonly link this disease to atherosclerosis (hardening of the arteries) and other serious conditions like stroke, heart attack and peripheral artery disease 47  MAIN CAUSES OF HYPERLIPIDEMIA Various hyperlipidemia causes include: Smoking Alcohol drinking Foods with a lot of saturated fats or trans fats Being overweight Being stressed Inheriting genes that make the cholesterol levels unhealthy 48  MEDICATIONS FOR HYPERLIPIDEMIA If lifestyle changes not enough to treat the hyperlipidemia, the doctors may prescribe medications Statins are the first line medication for hyperlipidemia, including – atorvastatin (Lipitor) – fluvastatin (Lescol XL) https://thuocdantoc.vn/wp-content/uploads/2019/04/thuoc-lipitor-40mg.png – lovastatin (Altoprev) – pitavastatin (Livalo) – pravastatin (Pravachol) – rosuvastatin (Crestor) – simvastatin (Zocor) 49 SIDE EFFECTS OF STATINS The most common statin side effects include: Diarrhea Constipation Belly cramping or pain Bloating or gas Dizziness Nausea or vomiting Headache Muscle aches 50  COAGULATIONS DISORDERS Conditions that affect the blood's clotting activities Hemophilia,Von Willebrand disease, clotting factor deficiencies, hypercoagulable states and deep venous thrombosis are common coagulations disorders Hemophilia and Von Willebrand disease are among the best known 51 MAIN CAUSES OF HEMOPHILIA AND VON WILLEBRAND DISEASE Both are bleeding disorders that the blood does not clot properly Due to not enough blood-clotting proteins (clotting factors) The main differences between the two: –Hemophilia primarily affects males, whereas Von Willebrand disease affects both females and males. –Von Willebrand disease tends to be milder than hemophilia. 52 MANAGEMENT OF VON WILLEBRAND'S DISEASE Most common of management is using desmopressin (also known as DDAVP®) Act by increasing the levels of Von Willebrand Factor and Factor VIII in the blood through releasing them from storage https://s3.amazonaws.com/static.wd7.us/0/0f/Desmopressin_oral_drug_lable01.png Given as an injection under the skin or into a vein or tablet 53 SIDE EFFECTS OF DESMOPRESSIN Lowers the amount of sodium in the blood Confusion Nausea Vomiting Muscle cramps or spasms Unusual tiredness or weakness 54  MANAGEMENT OF HEMOPHILIA Replacing the clotting factor through a tube in a vein Replacement therapy may be given to treat a bleeding episode in progress Or it can be given on a regular schedule to help prevent bleeding episodes Medicine is used to prevent bleeding chromosome related Gene therapy 55  SIDE EFFECTS ASSOCIATED WITH CLOTTING FACTOR REPLACEMENT Potential for the development of inhibitors Which are antibodies binding to and neutralizing the replacement clotting factors Inhibitors may reduce the effectiveness of treatment and Increase the risk of bleeding 56 THROMBOPHILIA Blood forming clots too easily Increases your risk of – Deep vein thrombosis (DVT) Blood clot in a vein, commonly in the leg – Pulmonary embolism https://cdn.xcode.life/wp-content/uploads/2023/07/Hereditary-Thrombophilia_01-1.png Blocked blood vessel in the lungs 57  MANAGEMENT OF THROMBOPHILIA Blood thinning medication, called anticoagulation, such as heparin and warfarin Medication that can break up the clot Work by allowing blood to flow around a trapped clot https://thuocdantoc.vn/wp-content/uploads/2019/08/Warfarin- Preventing clot from travelling to the 1.jpg lungs 58 SLIDE EFFECTS OF BLOOD THINNING MEDICATION Gastrointestinal issues Ulcers in the stomach or intestines Hemorrhagic stroke Increase the risk of a hemorrhagic stroke When a blood vessel in the brain ruptures 59 TUTORIAL What is a myocardial infarction or heart attack? https://www.youtube.com/watch?v=jYHN7wi5_FA Mechanism of action for Calcium Channel Antagonists https://www.youtube.com/watch?v=pjbEHeNPeYQ Study finds new treatment for high cholesterol https://www.youtube.com/watch?v=CMOdsymhwK0 60 PRINCIPLES OF CARDIOVASCULAR PHARMACOLOGY 61