MF2 - Cardiovascular Medicines

7/30/2019 MF2 - Cardiovascular Medicines

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Summary of CardiovascularMedicines

Submitted by: Anne Bernadette Barte


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Antihypertensive Drugs

Hypertension is defined as sustained, reproducible increase in blood pressure. Generally, diastolic values greater than 90 mm Hg and/osystolic values greater than 140 mm Hg warrant a diagnosis of hypertension. If untreated, hypertension leads to serious problems sucas stroke, renal failure, and problems in several other physiologic systems. Although the cause of hypertension is discernible in a smapercentage of patients, the majority of hypertensive individuals are classified as having essential hypertension, which means that thcause of their elevated blood pressure is unknown. Fortunately, several types of drugs are currently available to adequately controblood pressure in essential hypertension. Drugs such as diuretics, sympatholytics (alpha blockers, beta blockers, etc.), vasodilatorsangiotensin converting enzyme inhibitors, and calcium channel blockers have all been used in treating hypertension. These agents arusually prescribed according to a stepped-care protocol, where therapy is initiated with one drug, and subsequent agents are added arequired. Rehabilitation specialists should be aware of the potential side effects of these drugs. Physical therapists and occupationatherapists assume an important role in making patients aware of the sequelae of hypertension, and therapists should actively encouragpatients to comply with pharmacologic and nonpharmacologic methods of lowering blood pressure. Due to the prevalence hypertension, however, many patients receiving therapy for other problems will also be taking antihypertensive drugs, so knowledge othe pharmacology of these agents is essential.

Drug Therapy

Several major categories of drugs exist for the treatment of essential hypertension. These categories include diuretics, sympatholyt

drugs, vasodilators, angiotensin-converting enzyme inhibitors, and calcium channel blockers. The primary sites of action and effects oeach category are summarized in the table below.


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Diuretics

Diuretics - increase the formation and excretion of urine. These drugs are used as antihypertensive agents because of their ability increase the renal excretion of water and sodium, thus decreasing the volume of fluid within the vascular system. Hence, diuretics havbeen a mainstay in the treatment of hypertension for many years, and they remain one of the primary methods for treating this conditioin a large number of people.

Classifications of Diuretics

Thiazide Diuretics - These drugs act primarily on the early portion of the distal tubule of the nephron, where they inhibit sodiureabsorption, creating an osmotic force that also retains more water in the nephron. Since more sodium and water are passed througthe nephron, where they will ultimately be excreted from the body, a diuretic effect is produced. Thiazides are the most frequently usetype of diuretic for hypertension.

Loop Diuretics - These drugs act primarily on the ascending limb of the loop of Henle (hence the term loop diuretic). They exert thediuretic effect by inhibiting the reabsorption of sodium and chloride from the nephron, thereby preventing the reabsorption of the watethat follows these electrolytes.

Potassium-Sparing Diuretics - Several different drugs with diuretic properties are classified as potassium-sparing because they arable to prevent the secretion of potassium into the distal tubule. Normally, a sodium-potassium exchange occurs in the distal tubule

where sodium is reabsorbed and potassium is secreted. Although these agents do not produce a diuretic effect to the same extent athe loop and thiazide diuretics, potassiumsparing drugs have the advantage of reducing potassium loss and thus preventinhypokalemia.


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Sympatholytic DrugsDrugs that interfere with sympathetic discharge should be valuable as antihypertensive agents. These sympatholytic drugs can bclassified according to where and how they interrupt sympathetic activity. Sympatholytic drugs used to treat hypertension include betaadrenergic blockers, alpha-adrenergic blockers, presynaptic adrenergic neurotransmitter depletors, centrally acting drugs, anganglionic blockers .

Beta Blockers - exert their primary effect on the heart, where they decrease heart rate and force myocardial contraction. Ihypertensive patients, these drugs lower blood pressure by slowing down the heart and reducing cardiac output.

Alpha Blockers - Drugs that block the alpha-1adrenergic receptor on vascular smooth muscle will promote a decrease in vascularesistance. In a sense, alpha blockers act directly on the tissues that ultimately mediate the increased blood pressurethat is, thperipheral vasculature.

Presynaptic Adrenergic Inhibitors - Drugs that inhibit the release of norepinephrine from the presynaptic terminals of peripheraadrenergic. In either case, depletion of norepinephrine from the presynaptic terminal decreases sympathetic-mediated excitation of thheart and peripheral vasculature, resulting in decreased blood pressure.

Centrally Acting Agents - Centrally acting sympatholytics are characterized as agonists and offers a rather unique approach thypertension because these drugs limit sympathetic activity at the source (brainstem vasomotor center) rather than at the peripher(cardiovascular neuroeffector junction).

Ganglionic Blockers - Drugs that block synaptic transmission at autonomic ganglia will dramatically and effectively reduce bloopressure by decreasing systemic sympathetic activity. These agents are essentially nicotinic cholinergic antagonists, which bloctransmission at the junction between presynaptic and postsynaptic neurons in sympathetic and parasympathetic pathways.


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VasodilatorsDrugs that directly vasodilate the peripheral vasculature will produce an antihypertensive effect by decreasing peripheral vascularesistance. Vasodilators are believed to inhibit smooth-muscle contraction by increasing the intracellular production of seconmessengers such as cyclic guanosine monophosphate, thus leading to vasodilation.

Inhibition of the Renin-Angiotensin SystemThe renin-angiotensin system involves several endogenous components that help regulate vascular tone in various organs and tissueRenin is an enzyme produced primarily in the kidneys. When blood pressure falls, renin is released from the kidneys into the systemcirculation. Angiotensinogen is a peptide that is produced by the liver and circulates continually in the bloodstream.

Calcium Channel BlockersDrugs that selectively block calcium entry into vascular smooth-muscle cells were originally developed to treat certain forms of anginpectoris and cardiac arrhythmias. Calcium appears to play a role in activating the contractile element in smooth muscle much in thsame way that calcium initiates actin-myosin interaction in skeletal muscle cells. Drugs that block calcium entry into vascular smootmuscle will inhibit the contractile process, leading to vasodilation and decreased vascular resistance.


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Angina Pectoris

Angina pectoris is pain that occurs in the chest region during ischemic heart disease. Attacks of angina pectoris begin suddenly and aroften described as a sensation of intense compression and tightness in the retrosternal region, with pain sometimes radiating to the jaor left arm. In many patients, episodes of angina pectoris are precipitated by physical exertion. Some forms of angina, however, maoccur spontaneously even when the patient is at rest or asleep.

Pain in the chest region, or angina pectoris, is a common symptom of ischemic heart disease. Anginal pain usually occurs because of aimbalance between myocardial oxygen supply and myocardial oxygen demand. Organic nitrates, beta blockers, and calcium channelblockers are the primary drugs used to treat angina pectoris. Organic nitrates and beta blockers primarily exert their effects bydecreasing myocardial oxygen demand, whereas calcium channel blockers primarily increase myocardial oxygen supply. Several formsof angina pectoris can be identified, and specific types of antianginal drugs are used alone or in combination with each other to treat orprevent various forms of angina.

Rehabilitation specialists must be aware of any patients who have angina pectoris and the possibility of patients having an anginalattack during a therapy session. Therapists should also be cognizant of what drugs are being taken to control the patients angina, aswell as any side effects that may influence certain rehabilitation procedures.


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Drugs Used to Treat Angina Pectoris

Three drug groups are typically used to treat the symptoms of angina pectoris: organic nitrates, beta blockers, and calcium channelblockers. These drugs exert various effects that help restore or maintain the balance between myocardial oxygen supply and myocardiaoxygen demand.

Organic NitratesOrganic nitrates consist of drugs such as nitroglycerin, isosorbide dinitrate, and isosorbide. The ability of these agents to dilate vasculasmooth muscle is well established. Nitrates are actually drug precursors (prodrugs) that become activated when they are converted tonitric oxide within vascular smooth muscle.Nitrates can also dilate the coronary arteries to some extent; these drugs are documented tohave an increase in coronary artery flow.

Specific AgentsNitroglycerin (Nitro-Bid, Nitrostat, Nitro-Dur, many others) - In addition to being used as a powerful explosive,nitroglycerin is perhaps the most well known antianginal drug. The explosive nature of this agent is rendered inactiveby diluting it with lactose, alcohol, or propylene glycol. Nitroglycerin is administered for both the prevention andtreatment of anginal attacks and is available in oral, buccal, sublingual, and transdermal forms

Isosorbide Dinitrate - Like nitroglycerin, isosorbide dinitrate is used for the treatment of acute episodes of angina aswell as for the prevention of anginal attacks. The antianginal and hemodynamic effects last longer with isosorbidedinitrate, however, so this drug is often classified as a long-acting nitrate.For acute attacks, isosorbide dinitrate isadministered sublingually, buccally, or by chewable tablets. For prevention of angina, oral tablets are usually given.

Isosorbide Mononitrate - This drug is another long-acting nitrate that is similar in structure and function to isosorbid

dinitrate. It is typically given orally for prevention of anginal attacks.

Amyl Nitrite - This drug is supplied in small ampules that can be broken open to inhale during acute anginal attacks.Absorption of the drug through the nasal membranes causes peripheral vasodilation and decreased cardiac preloadand afterload. Clinical use of inhaled amyl nitrite is very limited, however, and this type of antianginal treatment hasgenerally been replaced by safer and more convenient methods of nitrate administration (e.g., nitroglycerin patches).


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Beta-Adrenergic BlockersBy antagonizing beta-1 receptors on the myocardium, beta blockers tend to decrease the heart rate and force of myocardial contractionthus producing an obvious decrease in the work that the heart must perform and a decrease in myocardial oxygen demand. Betablockers help maintain an appropriate balance between myocardial oxygen supply and demand by preventing an increase in myocardiaoxygen demand. Consequently, beta blockers are given to certain patients with angina to limit the oxygen demands of the heart. This

prophylactic administration prevents the onset of an anginal attack.


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Calcium Channel BlockersThese drugs block the entry of calcium into vascular smooth muscle. In vascular smooth muscle, calcium ions facilitate contraction byinitiating actin-myosin interaction. Calcium channel blockers decrease the entry of calcium into vascular smooth-muscle cells, thuscausing relaxation and vasodilation. Consequently, a primary role of calcium channel blockers in angina pectoris is to directly increasecoronary blood flow, thus increasing myocardial oxygen supply.

Specific AgentsBepridil (Vascor). Bepridil is a nonselective calcium channel blocker that inhibits calcium influx into vascular smoothmuscle and cardiac striated muscle.D ecreases heart rate (negative chronotropic effect) and cardiac contractility(negative inotropic effect) through an inhibitory effect on the myocardium.

Diltiazem (Cardizem, Dilacor) - Like the other calcium channel blockers, diltiazem is able to vasodilate the coronaryarteries and the peripheral vasculature. Diltiazem also produces some depression of electrical conduction in thesinoatrial and atrioventricular nodes, an effect that may cause slight bradycardia. This bradycardia can be worsenedby beta blockers or in patients with myocardial conduction problems, and diltiazem should probably be avoided inthese individuals

Nifedipine (Adalat, Procardia) and Other Dihydropyridines - Nifedipine and similar drugs are members of thedihydropyridine class of calcium channel blockers. This class is distinguished by drugs with an -ipine suffix, includingfelodipine (Plendil), isradipine (DynaCirc), and nicardipine (Cardene). These drugs are relatively selective forvascular smooth muscle as compared to cardiac striated muscle, and they vasodilate the coronary arteries andperipheral vasculature without exerting any direct effects on cardiac excitability or contractility.

Verapamil (Calan, Isoptin) - Verapamil has been used to treat angina because of its ability to vasodilate the coronarvessels. Verapamil, however, seems to be moderately effective compared to the other antianginal drugs, andverapamil also depresses myocardial excitability and decreases heart rate. Because of its negative effects oncardiac excitation, verapamil is probably more useful in controlling certain cardiac arrhythmias.


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Cardiac Arrhythmias

An arrhythmia can be broadly defined as any significant deviation from normal cardiac rhythm. Various problems in the origination andconduction of electrical activity in the heart can lead to distinct types of arrhythmias. If untreated, disturbances in normal cardiac rhythmresult in impaired cardiac pumping ability, and certain arrhythmias are associated with cerebrovascular accidents, cardiac failure, andother sequelae that can be fatal. Fortunately, a variety of drugs are available to help establish and maintain normal cardiac rhythm.

Drugs affecting acetylcholine-mediated responses are classified as cholinergic stimulants and anticholinergic drugs. Cholinergicstimulants increase cholinergic activity by binding to the acetylcholine receptor and activating the receptor (direct-acting stimulants) or binhibiting the acetylcholinesterase enzyme, thus allowing more acetylcholine to remain active at the cholinergic synapse (indirect-actingstimulants). Anticholinergic drugs inhibit cholinergic activity by acting as competitive antagonists; that is, they bind to the cholinergicreceptor but do not activate it. Cholinergic stimulants and anticholinergic drugs affect many tissues in the body and are used to treat avariety of clinical problems. Cholinergic stimulants are often administered to increase gastrointestinal and urinary bladder tone, to treatconditions such as glaucoma, myasthenia gravis, and Alzheimer disease, and to reverse the neuromuscular blockade produced bycurarelike drugs. Anticholinergic drugs are used principally to decrease gastrointestinal motility and secretions, and to decrease thesymptoms of Parkinson disease, but they may also be used to treat problems in several other physiologic systems. Because of theability of cholinergic stimulants and anticholinergic drugs to affect different tissues, these drugs may be associated with a number of sideffects. Considering the diverse clinical applications of cholinergic stimulants and anticholinergics, physical therapists and occupationaltherapists may frequently encounter patients taking these drugs. Rehabilitation specialists should be aware of the rationale for drugadministration as well as possible side effects of cholinergic stimulants and anticholinergic agents.

Classification of Antiarrhythmic DrugsDrugs used to treat cardiac arrhythmias are traditionally placed in one of four distinct classes according to their mechanism of action.The classification system has been criticized somewhat because it has several limitations, including the fact that certain drugs may havcharacteristics from more than one class, and that certain drugs with antiarrhythmic properties (e.g., digitalis) do not fit into this system.

Class I: Sodium Channel BlockersClass I antiarrhythmic drugs are essentially sodium channel blockers. These drugs bind to membrane sodium channels in variousexcitable tissues, including myocardial cells. In cardiac tissues, class I drugs normalize the rate of sodium entry into cardiac tissues andthereby help control cardiac excitation and conduction.

Class IA. Drugs in this group are similar in that they produce a moderate slowing of phase 0 depolarization and a moderate

slowing of action potential propagation throughout the myocardium. Class IA agents include quinidine, procainamide, anddisopyramide; these drugs are used to treat a variety of arrhythmias originating in the ventricles or atria.

Class IB. These drugs display a minimal ability to slow phase 0 depolarization, and produce a minimal slowing of cardiacconduction. In contrast to IA drugs, class IB drugs usually shorten cardiac repolarization; that is, the effective refractory periodis decreased. Class IB drugs include lidocaine, mexiletine, and moricizine. These drugs are primarily used to treat ventriculararrhythmias such as ventricular tachycardia and premature ventricular contractions (PVCs).

Class IC. These drugs produce both a marked decrease in the rate of phase 0 depolarization and a marked slowing of cardiacconduction. They have little effect on repolarization. Class IC drugs include flecainide and propafenone, and appear to be bestsuited to treat ventricular arrhythmias such as ventricular tachycardia and PVCs.

Class II: Beta BlockersDrugs that block beta-1 receptors on the myocardium are one of the mainstays in arrhythmia treatment. Beta blockers are effectivebecause they decrease the excitatory effects of the sympathetic nervous system and related catecholamines (norepinephrine andepinephrine) on the heart. This effect typically decreases cardiac automaticity and prolongs the effective refractory period, thus slowingheart rate. Beta blockers also slow down conduction through the myocardium, and are especially useful in controlling function of theatrioventricular node. Hence, these drugs are most effective in treating atrial tachycardias such as atrial fibrillation. Some ventriculararrhythmias may also respond to treatment with beta blockers.

Class III: Drugs That Prolong RepolarizationClass III agents delay repolarization of cardiac cells, which prolongs the effective refractory period of the cardiac action potential. Thisdelay lengthens the time interval before a subsequent action potential can be initiated, thus slowing and stabilizing the heart rate. Theeffects of class III drugs are complex, but their ability to lengthen the cardiac action potential is most likely mediated by inhibition of


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potassium efflux during repolarization. That is, these drugs limit the ability of potassium to leave the cell during phase 2 and 3 of theaction potential, which prolongs repolarization and prevents the cell from firing another action potential too rapidly. Class III drugs areused to treat ventricular arrhythmias such as ventricular tachycardia and ventricular fibrillation, and supraventricular arrhythmias such apostoperative atrial fibrillation. Interest in using these drugs and developing new class III agents has increased recently because theyaffect both atrial and ventricular problems and are relatively safe compared to other agents such as the class I drugs.

Class IV: Calcium Channel BlockersClass IV drugs have a selective ability to block calcium entry into myocardial and vascular smooth-muscle cells. These drugs inhibitcalcium influx by binding to specific channels in the cell membrane. As discussed previously, calcium entry plays an important role in th

generation of the cardiac action potential, especially during phase 2. By inhibiting calcium influx into myocardial cells, calcium channelblockers can alter the excitability and conduction of cardiac tissues. Calcium channel blockers decrease the rate of discharge of the SAnode and inhibit conduction velocity through the AV node.5 These drugs are most successful in treating arrhythmias caused by atrialdysfunction, such as supraventricular tachycardia and atrial fibrillation.


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Cardiac glycoside

Cardiac Glycosides have two prominent effects:Increased Contractility of the HeartThe longer calcium stays in a cell, the harder and longer the contraction will be. Cardiac glycosides decrease the hearts ability to pumpcalcium out of the cardiac cell so we get increased contractility of the heart. This is known as an increased inotropic effect. Thisleads to an increase in cardiac output (greater contractility and duration) in a failing heart.Decreased AV Node ConductionThe AV node is the gate. When you decrease AV node conduction, the gate stays closed longer and the amount of electrical activitygoing from the atrium to the ventricle decreases. This is known as adecreased chronotropic effect. This helps prevent atrial fibrilla-tion from becoming ventricular fibrillation.

Therapeutic MonitoringThe lower end dose works on increasing contractility.The higher end dose works on decreasing AV node conduction.But the therapeutic index is verynarrow so we dont have a lot of play with this.We must hold the dose if the apical pulse is


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Pharmacokinetics of Cardiac GlycosidesSteady-state: If we give a person a drug orally, it goes through the intestinal tract, blood levels kick in, and when the kidneys kick in, wstart eliminating the drug. We need to know the half-life of a drug because thats what the dose is based on. Before the drug blood levdrops too much due to the half-life, we give another dose. The average blood level will increase every time we redose. After the 5th hallife, we reachsteady-state and this is the range we want to stay in permanently.

Digoxin, the most common glycoside, has a half-life of 24 hours for those with normal kidney functions. It will take 5 days to reach asteady state concentration if we give them digoxin. In an emergency, this is unacceptable, so the other option we have is to give a loading dose.

Loading Dose: A loading dose is typically given by IV instead of orally. So we give a dose that hopefully gets them up to the steadystate faster. We calculate the dose based on their body weight, fat, etc but if we are wrong with that calculation, they could be toxic. Swe give them half the loading dose, then 6 hours later we give a quarter of the loading dose and then 6 hours later we give another loading dose. So in 12 hours we can get the person to the steady state.

Importance of Bioavailability of DigoxinYou dont have to memorize the numbers, but understand the concept.Intravenous = 100%Intramuscular = 80%Tablet = 70%Sometimes youll see an ordersuch:

Digoxin 0.25mg p.o. daily. If unable to swallow, give dose IVP.Whats wrong with this order? Were dealing with a drug with a very narrow therapeutic index and if we do it through IV push, theyregoing to get 100% of the drug instead of 70%. The physician has not specified the IVdosage! It would need to be reduced by atleast 30%.Toxicities

A-V Block (1st degree = delayed PR interval, 3rd degree = nothing getting through the AV node)Sinus bradycardia (apical pulse


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Thrombolysis

Thrombolytic agents: mechanism of action, indications, contraindications and side effectsThrombolytic agents are used to lyse already formed blood clots in clinical settings where ischemia may be fatal ( acute mycardialinfarction, pulmonary embolism, ischemic stroke, and arterial thrombosis). Very precise indications rule the use of these drugs, whichare not free from serious side effects ( bleeding).

The image below shows how serine protease thrombin (also called activated factor II) converts fibrinogen tofibrin.Fibrin polymerizes and constitutes a mesh that acts as hemostatic clot (in conjunction with platelets) over a wounded site.

This plasmin meshwork can be cleaved by plasmin, which derives from an inactive precursor: plasminogen.Plasminogen can be activated by the tissue plasminogen activator (t-PA), which is released by endothelial cells.

As can be seen in the image, streptokinase acts by activating plasminogen conversion into plasmin, which promotes clot lysis.Since streptokinase is a protein obtained from Streptococci cultures, it is capable of eliciting antigenic responses in humans.The following animation integrates the concepts previously explained, showing how endothelial cells release t-PA.
http://media.pharmacologycorner.com/wp-content/uploads/2009/05/plasminogen-plasmin1.jpghttp://media.pharmacologycorner.com/wp-content/uploads/2009/05/fibrinmesh1.pnghttp://media.pharmacologycorner.com/wp-content/uploads/2009/05/plasminogen-plasmin1.jpghttp://media.pharmacologycorner.com/wp-content/uploads/2009/05/fibrinmesh1.png


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Agent Abbreviation Source

Streptokinase (Streptase) SK Streptococcal culture

Urokinase UK Renal cell culture

Alteplase or Tissue plasminogenactivator(trade names Retavase,Rapilysin)

t-PA Recombinant technology

Anistreplase or Acylated plasminogen:streptokinase activator)

APSAC Streptococcal

Prourokinase or Single-chain urokinaseplasminogen activator

SCU-PA Renal cell culture

Pharmacological propertiesStreptokinase is a protein produced by Beta-hemolytic streptococci as a component of that organism tissue destroying machinery.There are two drawbacks for streptokinase therapy:Previous administration of the drug is a contraindication, because of the risk of anaphylaxis.The thrombolytic actions are relatively nonspecific and can result in systemic fibrinolysis.Since t-PA is produced by endothelial cells, it is nonantigenic and causes a more selective thrombolysis than streptokinase. Alteplase,the recombinant t-PA, is produced by recombinant DNA technology. It is effective in recanalizing occluded coronary arteries, limitingcardiac dysfunction and reducing mortality following an ST elevation myocardial infarction. At pharmacologic doses it can trigger asystemic lytic state and cause unwanted bleeding.

A genetically engineered variant of t-PA. Tecneplase has a longerhalf life than t-PA which allows it to be administered as a singleweight-based bolus.It has an increased half life than t-PA and increased specificity for fibrin. Its efficacy and adverse effect profile are similar to those ofstreptokinase and t-PA.Therapeutic considerations
http://pharmacologycorner.com/definition-of-half-life-of-drugs/http://pharmacologycorner.com/definition-of-half-life-of-drugs/


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Agent Indication

Streptokinase ST elevation myocardial infarction.Arterial thrombosis.Deep vein thrombosis.Pulmonary embolism.Intra-arterial or intravenous catheter occlusion.

t-PA Acute myocardial infarction.Acute cerebrovascular thrombosis.

Pulmonary embolism.Central venous catheter occlusion

Tenecteplase (TNK) and reteplase Acute myocardial infarction

Adverse effects common to all agents of the class:- Major bleeding.- Cardiac arrhythmias.- Cholesterol embolus syndrome.- Anaphylactoid reaction.- Cerebrovascular accident.- Intracraneal hemorrhage.

Steptokinase adverse effects:- Non-cardiogenic pulmonary edema.- Hypotension.- Fever and shivering.- History of cerebrovascular hemorrhage at any time.- Nonhemorrhagic stroke or other cerebrovascular event within the past year.- Marked hypertension ( reliably determined systolic arterial pressure >180 mmHg and/or a diastolic pressure >110 mmHg) at any timeduring presentation.- Suspicion of aortic dissection.- Active internal bleeding (excluding menses).- Relative contraindications to thrombolytic therapy

- Current use of anticoagulats (INR 2).- A recent (


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Antilipemic drugs

Antilipemic drugs are used to lower abnormally high blood levels of lipids, such as cholesterol, triglycerides, and phospholipids. The risk

of developing CAD increases when serum lipid levels are elevated. Drugs are used in combination with lifestyle changes (such as

proper diet, weight loss, and exercise) and treatment of an underlying disorder causing the lipid abnormality to help lower lipid levels.

The classes of antilipemic drugs include:

bile-sequestering drugs fibric acid derivatives 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors nicotinic acid cholesterol absorption inhibitors.Bile-sequestering drugs

The bile-sequestering drugs are cholestyramine, colestipol, and colesevelam. These drugs are resins that remove excess bile acids

from the fat deposits under the skin.

Pharmacokinetics

Bile-sequestering drugs arent absorbed from the GI tract. Instead, they remain in the intestine, where they combine with bile acids for

about 5 hours. Eventually, theyre excreted in stool.

Pharmacodynamics

The bile-sequestering drugs lower blood levels of low-density lipoproteins (LDLs). These drugs combine with bile acids in the intestines

to form an insoluble compound thats then excreted in stool. The decreasing level of bile acid in the gallbladder triggers the liver to

synthesize more bile acids from their precursor, cholesterol. Getting out of storage

As cholesterol leaves the bloodstream and other storage areas to replace the lost bile acids, blood cholesterol levels decrease. Becaus

the small intestine needs bile acids to emulsify lipids and form chylomicrons, absorption of all lipids and lipid-soluble drugs decreases

until the bile acids are replaced.

Pharmacotherapeutics

Bile-sequestering drugs are the drugs of choice for treating type IIa hyperlipoproteinemia (familial hypercholesterolemia) when the

patient cant lower his LDL levels through diet alone. Patients whose blood cholesterol levels place them at a severe risk of CAD will

most likely require one of these drugs in addition to dietary changes.

Drug interactions

Bile-sequestering drugs produce the following drug interactions:

They may bind with acidic drugs in the GI tract, decreasing their absorption and effectiveness. Acidic drugs likely to be affectedinclude barbiturates, phenytoin, penicillins, cephalosporins, thyroid hormones, thyroid derivatives, and digoxin.

Bile-sequestering drugs may decrease absorption of propranolol, tetracycline, furosemide, penicillin G, hydrochlorothiazide andgemfibrozil.

Bile-sequestering drugs may reduce absorption of lipid-soluble vitamins, such as vitamins A, D, E, and K. Poor absorption of vitaminK can affect prothrombin times significantly, increasing the risk of bleeding.

Warning!

Adverse reactions to bile-sequestering drugs

Short-term adverse reactions to these drugs are relatively mild. More severe reactions can result from long-term use. Adverse GI effect

with long-term therapy include severe fecal impaction, vomiting, diarrhea, and hemorrhoid irritation.

Rarely, peptic ulcers and bleeding, gallstones, and inflammation of the gallbladder may occur.

MF2 - Cardiovascular Medicines

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