Prescription drugs and medicines for diseases relating to the structure and function of the heart and blood vessels. The variety and scope of cardiovascular drugs have increased tremendously in the past few decades, and new drugs are being approved annually.
Thrombolytic therapy is an important clinical intervention for the patient experiencing acute myocardial infarction. The thrombus, which is composed of aggregated platelets bound together with fibrin strands, occludes the coronary artery, depriving the myocardium of oxygen previously supplied by that artery. The administration of a thrombolytic agent results in the lysis of the acute thrombus thus recanalizing, or opening, the obstructed coronary artery and restoring blood flow to the affected tissue.
The patient with recent onset of chest pain (less than 12 hrs duration) and persistent ST elevation (greater than 0.1mV in two or more contiguous leads) are considered candidates for thrombolytic therapy. Patient who present with bundle branch blocks that may obscure ST-segment analysis and a history suggestive of an acute MI are also considered candidates of therapy.
Most clinical protocols strive for administration of thrombolytics within 6 hrs window of time from the onset of symptoms.
Previously thrombolytics were not administered to patients over the age of 75, but current research shown that even elderly patients can benefit from thrombolytic therapy.
Exclusion criteria are usually based on the increased risk of bleeding. Patients who have stable clots that might be disrupted by thrombolytic therapy (those secondary to recent surgery, trauma or a cerebrovascular accidents).
Thrombolytic therapy selection criteria
- No more than 12 hrs from onset of chest pain; less if possible
- ST-segment elevation on ECG or new-onset left bundle branch block
- Ischemic chest pain of 30 minutes duration
- Chest pain unresponsive to sublingual nitroglycerin or nifedipine
- No conditions that might cause a predisposition to haemorrhage
SK is a thrombolytic agent derived from B-hemolytic streptococci, which when combined with plasminogen catalyzes the conversion of plasminigen to plasmin the enzyme responsible for clot dissolution in the body. SK can be administered either intravenously or intracoronary approach, which necessitates cardiac catheterisation.
The three major problems associated with the use of SK
- Its systemic lytic effects coupled with a long half life
- Potential antigenic effects if readministered, and hypotension.
- Bleeding is the most common complication.
- SK is a bacterial protein, it can produce a variety of allergic reactions. Anaphylaxis when administered to a patient who either has received SK therapy previously or has had a recent streptococcal infection.
Possible allergic manifestations related to streptokinase therapy
Delayed antibody formation: Symptoms may develop several days after infusion
Diphenhydramine (Benadryl) or steroids are often prescribed before SK administration to blunt this unwanted effect. Hypotension is sometimes associated with the rapid administration of SK. Usually responds to volume replacement but occasionally requires vasopressor support.
Tissue plasminogen activator (t-PA)
t-PA or alteplase is a naturally occurring enzyme (thus nonantigenic) that is a clot-specific and has a very short half –life( 3 to 4 mins). It converts plasminogen to plasmin after binding to fibrin-containing clot. This specifically results in an increased concentration and activity of plasmin at the site of the clot where it is needed. SK and t-PA has similar incidences of bleeding after administration. Approved specifically for IV admin. Accelerated dose t-PA is now considered the most effective in establishing early patency of the occluded vessel.
It is also known as anisoylated plasminogen –streptokinase activator complex (APSAC-Eminase). It was approved by FDA in 1990 for use in the treatment of acute MI. Often referred to as a second –generation streptokinase. It is inactive on admin, APSAC can be given rapidly as a bolus injection. The half-life of APSAC is markedly increased (90min), so concomitant heparin therapy, if employed, should begin at least 6 hrs after administrative to decrease the risk of bleeding associated with prolonged fibrinolytic activity.
- Potential for allergic reactions and hypotension.
- Efficiency similar to streptokinase in terms of clot lysis but is much more expensive.
Recombinant Plasminogen activator (r-PA)
r-PA or reteplase is a variant of natural human enzyme t-PA. , less fibrin selective and has a longer half-life than t-PA, making it suitable for bolus administration rather than as a continuous infusion…is given as a double bolus and then followed with heparin infusion. Unlike t-PA, reteplase dose not require weight-based dosing. Reteplase is as effective as t-PA in the treatment of acute MI and is easier to administer.
Tenecteplase (TNKase) is the newest of the thrombolytic agents. It is a genetically engineered variant of alteplase with slower plasma clearance and better fibrin specificity. …effective as alteplase, with similar rates of bleeding complications. It requires only a single bolus injection which may help facilitate more rapid treatment both in and out of hospital.
Evidence of reperfusion
Recognition of non-invasive markers of reperfusion is essential of documenting the patient’s response to thrombolytic therapy and those are:
- Cessation of chest pain
- Reperfusion disarrythmia primarily ventricular
- Rerun of elevated ST segment to baseline
- Early and marked peaking of creatinine kinase
Pain and reperfusion disrhythmias
Ischemic chest pain ceases abruptly as blood flow is restored and causes appearance of various reperfusion dysrhythmias. The reason of occurrence for these remains unclear but is thought to be the result of restored flow to ischemic tissue. Reperfusion dysrhythmias are self limiting or non-sustained and aggressive antidysrhythmic therapy is not required. Monitoring of patients ECG is required.
There is rapid resolution of the previously elevated ST segments. For this reason a monitoring lead should be chosen that clearly demonstrates ST elevation before initiation of therapy.
The serum concentration of creatine kinase (formerly known as creatine phosphokinase) rises rapidly and markedly after reperfusion of the ischemic myocardium. This phenomenon is termed as washout because it is thought to result from rapid readmission of creatine kinase – an enzyme released by damaged myocardial cells-into the circulation after restoration of blood flow to previous unperfused areas of the heart.
Residual coronary stenosis
Residual coronary stenosis resulting from the atherosclerotic process remains, even after successful thrombolysis. Therefore thrombolytic therapy is recognised as an emergency procedure to restore patency until more definitive therapy can be initiated to effectively reduce the degree of stenosis. (interventional catheter procedure) (coronary artery bypass surgery)
- Checklists are used to facilitate rapid identification of patients who are candidates for thrombolytics.
- Nurse prepares the patient for thrombolytic therapy by starting intravenous lines and obtaining baseline laboratory values and vital signs.
- Post thrombolytic therapy
- Ineffective cardiopulmonary tissue perfusion related to acute myocardnal ischemia
- Acute pain related to transmission and perception of cutaneous, visceral, muscular or ischemic impulses
- Anxiety related to threat of biologic, psychologic and/or social integrity
- Deficient fluid volume related to absolute loss
- Deficient knowledge: discharge regimen related to lack of previous exposure to information
Common complication related to thrombolysis is bleeding, not only as results of thrombolyic therapy but also because the patient routinely receives anti-coagulation therapy for several days to minimise the possibility of re-thrombosis. Therefore nurse must monitor clinical manifestation of bleeding such as
- Bleeding or hematoma at puncture sites
- Hematuria, hemaremesis, hemoptysis, melena, epistaxis
- Bruising or petechiae (pinpoint haemorrhages)
- Flank ecchymoses with complaints of low back pain (suggestive of retroperitoneal bleeding)
- Gingival bleeding
- Change in neurologic status (intracranial bleeding)
- Deterioration in vital signs, decreased hamatocrit values (internal bleeding)
Antidysrhytmic drugs compromise a diverse category of pharmacologic agents used to terminate or prevent an array of abnormal cardiac rhythms. The classification scheme is:
Class I drugs
Class I agents are sodium channel blockers that decrease the influx of sodium ions through fast channels during phase 0 depolarisation. This prolongs the absolute (effective) refractory period, thus decreasing the risk of premature impulses from ectopic foci. ..Depress automatically by slowing the rate of spontaneous depolarisation of pacemaker cells during the resting phase (phase 4).
Class I drugs can be further subdivided into three groups according to their potency as sodium channel inhibitor and their effect on phase 3 repolarisation.
Class IA drugs
quinidine, procainamide and disopyramide block not only the fast sodium channel but also phase 3 repolarization and thereby prolong the action potential duration. Clinically this may result in measurable increases in the QRS duration and QT interval. They depress myocardinal contractility, with dispyramide having the most potent negative ionotropic effect.
Class IB drugs
They have only moderate effect on sodium channels and accelerate phase 3 repolarisation to shorten the action potential duration. Eg lidocain, mexiletine, and tocainide belong in this group.
Class IC drugs
These agents are most potent sodium channel blockers with little effect on repolarisation. They increase both PR & QRS interval. Eg encainide, flecainide, and propaferone. But use of these agents in clinical practise has been decreased.
CLASS II drugs
They cause spontaneous depolarisation during resting phase (phase 4) is depressed and atrio-ventricular conduction is slowed. This is subdivided into cardio-selective (beta 1 only) and non-cardio selective beta blockers (beta 1 and beta 2). Potential adverse effects are bronchospasm by non-cardioselective beta-blockers in patients with COPD. They are also negative ionotropes and must be used cautiously in patients with LVF. Esmolol, metoprolol and propranololare available in IV form. Esmolol offers significant advantage to critically ill patients because of its short half life (9 min). Used in treatment of SVT, AF and atrial flutter.
CLASS III drugs
They include amiodarone, bretylium, ibutilide and sotalol. They slow the rate of phase 3 repolarisation increasing effective refractory period and the action potential duration. IV amiodarone was originally approved for the treatment of serious ventricular dysrhythmias that refractory to other medications. Because of its effectiveness, it is now been used with increasing frequency for atrial and ventricular dysrhythmias.
CLASS IV drugs
These are calcium channel blockers that inhibit influx of calcium through slow calcium channels during the plateau phase 2. This effect occurs primarily in tissues in which slow calcium channels predominate primarily in sinus and AV node and the atrial tissues. Verapamil was the first drug under this category. This depresses sinus and AV node conduction and is effective in terminating SVT cased by AV nodal re-entry pathway. Diltiazem is also available in IV form as effective as Verapamil. In treating supra-ventricular dysrhttmias with few hypotensive side effects.
Both these agents must be avoided in treatment of atrial fibrillation for patients with WPW syndrome.
It is a newer drug under this category. It occurs endogenously in the body as building block of ATP. Given IV bolus, it slows conduction through AV node causing transient AV block. It is clinically use to convert SVT to facilitates differential diagnosis for rapid dysrhythmias.
Because of it’s short half life, drug is administrative IV as rapid bolus followed by a saline flush.
The blous is delivered as centrally as possible so that drug reaches the heart before it metabolise. Side effects are transient because drug is rapids taken up by cells and is cleared from body within 10 secs.
It act as antidysrhythmic agents. It may reduce both ventricular and supraventricular dysrhythmias. It’s a treatment of choice in patients with torsades de pointes. For Acute treatment, 1-2 gm of Mg is admin over 1-2 mins. In patients with confirmed hypo-magnecemia, this bolus is followed with 24 hrs infusion.
Critically ill patients with compromised cardiac function often require the use of medications to enhance myocardial contractility (positive inotropes). Clinically available inotropes include cardiac glycosides, sympathomimetics and phophodiasterase inhibitors.
It include digitalis and its derivatives. Although these drugs have been used for centuries, their slow onset of action and risk of toxicity make them more appropriate for the management of chronic heart failure. Because of digoxine also causes slowing of the sinus rate and decrease in AV conduction. It may be admi IV in the acute care setting control supravetricular dysrhytmias.
It stimulate adrenergic receptors, thereby stimulating effect of sympathetic nerve stimulation. Included in this category are natuarally occurring catchlamines (epinephrine, dopamine, and norepinephrine), as well as synthetic catecholamines (dobutamine and isoproterenol).
Chemical precursor of norepinephrine, which in addition to both alpha and beta receptor stimulation, can activate dopaminergic receptors in the renal and mesenteric blood vessels. The action of these drug are entirely dose-related. Low dosages of 1-2 mg/kg/min, dopamine stimulates dopaminergic receptor causing renal and mesenteric vasodilatation. The resultant decrease in renal perfusion increases urinary output. Moderate dosages results in stimulation of beta 1 receptors to increase myocardial contractility and improve cardiac output.
Dosages greater than 10mg/kg/min, dopamine predominantly stimulate alpha receptors resulting in vasoconstriction that often negates both the beta-adrenergic and dopaminergic effects.
This is a synthetic catecholamine predominantly with beta 1 effects. It also produces some beta 2 stimulation, resulting in mild vasodilatation. Dobutamine is useful in the treatment of heart failure especially in hypotensive patients who can not tolerate vasodilator therapy. The usual dosage range is 2.5 to 20mg/kg/min, titrated based on hemodynamic parameters.
Epinephrine (adrenaline) is produced by the adrenal gland as apart of the body’s response to stress.. This agent has the ability to stimulate both alpha and beta receptors depending on the dose administered. At doses of 1 to 2 mg/min, epinephrine binds with beta-receptors to increase heart rate, cardiac conduction, contractility and vasodilatation, thereby increasing cardiac output. As the dosage is increased, alpha-receptors are stimulated, resulting in increase vascular resistance and blood pressure. At these doses, epinephrine’s impact on cardiac output depends on the heart’s ability to pump against the increased after load. Epinephrine accelerates the sinus rate and may precipitates ventricular dysrhythmias in the ischemic heart. Other side effects include restlessness, angina and headache.
Norepinephrine (Levophed) is similar to epinephrine in its ability to stimulate beta and alpha receptors, but it lacks the beta 2 effects.. At low infusion rates, beta 1 receptors are activated to produce increased contractility and thus augment cardiac output. At higer doses the inotropic effects are limited by marked vasoconstriction mediated by alpha receptors. Clinically, norepinephrine us ised most often as a vasopressor to elevate blood pressure in shock states.
Pure beta-receptor stimulate with no alpha effects. It produces dramatic increase in heart rate conduction and contractility via beta-1 stimulation and vasodilation via beta-2 stimulation. It produced vasodilation of pulmonary arteries and bronchodilation. It greatly increases automaticity of cardiac cells and frequently precipiitates dysrhythmias such as PVC, and even VT’s. Its use is temporary treatment for symptomatic bradycardia until pace maker is available.
These drugs inhibit enzyme phosphodiesteratse resulting in increase levels of cyclic AMP and intra-cellular Ca eg Amrinone (inocor) and Milrinone (Primacor). It causes inotropic effect and reduces after load by vasodilation. Filling pressure tends to decrease whereas heart rate and BP remains fairly constant. Amrinone may cause thrombocytopenia so platelet count needs to be observed and patient need to monitor for haemorrhagic complications. Milrinone is associated with low rate of thrombocytopenia but it induce ventricular dysrhythmias such as PVCs and VT.
Vasodilators improve cardiac performance by various degrees of arterial and venous dilations or both.
Direct smooth muscle relaxants
This group consists of Sodium nitroprusside, Nitroglycerin and Hydralazine
It is rapidly acting venous and arterial dilator. It is commonly use in hypertensive emergencies and perioperative period for reducing the blood pressure. It is also effective for afterload reduction in case of heart failure. Side effects are hypotension, thiocynate toxicity and reflex tachycardia. It is administered continuous IV infusion. Dosage is titrated to maintain desired BP and SVR.
IV NTG causes both arterial and venous vasodilation but its venous effect is more pronounced. It Is commonly used for acute heart failure as it reduces cardiac filling pressure, relives pulmonary congestion and decreases cardiac workload and oxygen consumption. It also dilates coronary arteries, thus helpful in treatment of unstable angina and acute MI. Initial dosage is 10mg / min and infusion is titrated to achieve desired effect / reduction and elimination of chest pain, reduction in pulmonary artery occlusion pressure or blood pressure. It is also administered prophylactically to prevent vasospasm after PTCA and thrombolytic therapy. Common side effects are hypotension, flushing and headache.
It is a potent arterial vasodilator, given as continuous IV infusion. Dosage is 5-10 mg/ every 4-8 hrs. Major side effect is reflex tachycardia and is dismissed by concomitant administration of beta-blockers.
Calcium channel blocker
It is used primarily as arterial vasodilators. These drugs reduce the influx of calcium in the arterial resistance vessels. Both coronary and peripheral arteries are affected. They are used in the critical care setting to treat hypertension. Nifedipine is available in an oral form only but often is prescribed sublingually during hypertensive emergencies.
Verapamil (Calan, Isoptin) and diltiasem dilate coronary arteries but have little effect on the peripheral vasculature. They are used in the treatment of angina, especially that which has a vasospastic component, and as antidysrhytmics in the treatment of supraventricular tachycardias.
Angiotensin-converting enzyme (ACE) inhibitors produce vasodilation by blocking the conversion of angiotensine I to angiotensin II. Because of angiotensin is a potent vasoconstrictor, limiting its production decreases peripheral vascular resistance. In contrast to the direct vasodilators and nifedipine, ACE inhibitors do not cause reflex tachycardia or induce sodium and water retention. However these drugs may cause a profound fall in blood pressure, especially in patients who are volume depleted. Blood pressure must be monitored carefully, especially during initiation of therapy. Captopril (capoten) and enalapril (Vasotec) are used in patients with heart failure to decrease SVR (afterload) and pulmonary artery in an oral form only but has relatively rapid onset of action (approx 1 hr). Enalapril is available in an IV form and may be used to decrease afterload in more emergent situations.
Alpha adrenergic blockers
Peripheral adrenergic blockers block alpha receptors in arteries and veins, resulting in vasodilatation. Orthostatic hypotention is a common side effect and may result in sycope. Long-term therapy also may be complicated by fluid and water retention.
Labetalol (Normodyne), a combined alpha and beta blocker, is used in the treatment of hypertensive emergencies. Because the blockade of beta 1 receptors permits the decrease of blood pressure without the risk of reflexive tachycardia ad increased cardiac output, this drug also is useful in the treatment of acute aortic dissection.
Phentolamine (regitine) is a peripheral alpha-blocker that causes decreased afterload via arterial vasodilatation. It is given as a continuous infusion at the rate of 1-2 mg/min and is titrated to achieve the required reduction in blood pressure and SVR. Phentolamine is the drug of choice in the treatment of pheochromocytoma. This drug also is used to treat the extravasation of dopamine. If this occurs, 5-10 mg is diluted in 10ml normal saline and administered intradermally into the infiltrated area.
Fenoldopam (Corlopam) is the first of few class of vasodilators called selective specific dopamine DA-1-receptor agonists. The drug is a potent vasodilator that affects both peripheral and renal arteries. Fenoldopam is an effective alternative to nitroprusside in the treatment of hypertensive emergencies and does not have the risk of thiocynate toxicity. It is administered IV at 0.03 – 1.6 ug/kg/min, titrated to blood pressure effect. The drug can be used safely in patients with renal dysfunction or those at high risk for renal insufficiency. At lower doses, fenoldpam has effects similar to renal dose dopamine.
Vasopressors are sympathomimetic agents that mediate peripheral vasoconstriction through stimulation of alpha receptors. This results in increased systemic vascular resistance and thus elevates blood pressure. Some of these drugs (epinephrine and norepinephrine) also have the ability to stimulate beta receptors. Vasopressors are not widely used in the treatment of critically ill cardiac patients, because the dramatic increase in afterload is taxing to maintain organ perfusion in shock states. For example, phenylephrine (neo-synephrine) or norepinephrine (Levophed) may be administered as a continuous IV infusion to maintain organ perfusion by increasing peripheral vascular resistance in the warm phase of septic shock.