Pharmacology Summary

CHAPTER 42: INTRODUCTION TO THE CARDIOVASCULAR SYSTEM Cardiovascular System - responsible for delivering oxygen and nutrients to all of the cells of the body and for removing waste products for excretion - consists: 1. heart 2. pump3. interconnected series of tubes THE HEART - hollow, muscular organ divided into 4 chambers: atriums ( “porch” or entryway) and ventricles ( lower part) - is the pump that keeps blood flowing through 60,000 miles of tubes, constituting the cardiovascular system *auricle- attached to each atrium; collects blood that is pumped into the ventricles by arterial contraction ** a partition called a septum separates the right half of the heart from the left. The right receives deoxygenated blood from everywhere in the body through the veins ( vessels that carry blood toward the heart) and directs that blood into the lungs… *** arteries- where aorta delivers blood into the systemic circulation - vessels that carry blood away from the heart

mitral or bicuspid valve- valve on the left side of the heart; composed of two leaflets or cusps * systole - the contraction of ventricles

* absolute refractory period * The heart’s series of one- way valves keeps the blood flowing on the correct direction, as follows: 1. Deoxygenated blood: right atrium, though tricuspid valve to right ventricle, through pulmonary valve to the lungs 2. Oxygenated blood: through the pulmonary veins to ventricle, through aortic valve to the aorta CONDUCTION SYSTEM OF THE HEART - consist of: 1. SA node- located in top of the right atrium, acts as the pacemaker of the heart 2. AV nodes- slows the impulse, allowing for the delay needed for ventricular filling, and sends it from the atria into the ventricles by way of the bundle of His 3. Bundle of His- w/c enters the septum and divides into three bundle branches 4. Bundle branches- w/c conduct impulses through the ventricles 5. Purkinje fibers- w/c delivers the impulse the ventricular cells ***Sinoatrial (SA) node

CARDIAC CYCLE - … each period of the ventricles followed by a period of systole= cardiac cycle… * myocardium - fibers of cardiac muscle - form two intertwining networks called atrial and ventricular syncytia * Starling’s law of the heart -occurs when muscle fibers of the heart are stretched by the increase volume of blood that has returned spring back to normal size; is similar to stretching a rubber band… * Diastole - the period of cardiac muscle relaxation where the heart from the systemic and pulmonic veins, w/c flow into the right and left… * tricuspid- valve on the right side of the heart; composed of 3 leaflets or cusps

CONDUCTIVITY - where the specialized cells of the heart can conduct an impulse rapidly through the system so that the muscle cells of the heart are stimulated at approximately the same time…

AUTOMATICITY - where the cells can generate action potentials or electrical impulses without being excited to do so by external stimuli 5 phases: 1. Phase 0- points of stimulation; where: sodium gates open along the cell membrane, and sodium rushes into the cell, resulting in a positive state—an electrical potential called depolarization 2. Phase 1- when Na ions concentrations are equal inside and outside of the cell 3. Phase 2 (plateau stage)- cell membrane becomes less permeable to Na Ca slowly enters the cell K slowly leaves the cell 4. Phase 3- rapid repolarization  K rapidly moves out of the cell 5. Phase 4- cell comes to rest as the sodium- potassium pump returns the membrane spontaneous repolarization begins again

***** SA node is the dominant influences most of the time, keeping the resting heart rate at 70 to 80 beats per minute * Sarcomere- the basic unit of the cardiac muscle - made up of two contractile proteins: actin (thin filament) and myosin (thick filament) kept apart by the protein troponin * Degree of shortening- determined by the amount of Ca present—the more Ca is present, the more bridges will be formed… ARRYTHMIA OR DYSRYHTHMIA - a disruption in cardiac rate or rhythm - interfere with the work of the heart and can disrupt cardiac output, which affects every cell in the body - occurs when there is a shift in the pacemaker of the heart from the SA node to some other sit, called ectopic focus FIBRILLATION - very serious arrhythmias arise when the combination of ectopic foci and altered conduction set off an irregular, uncoordinated twitching of the atrial or ventricular muscle ELECTROCARDIOGRAPHY -is a process of recording the patterns of electrical impulses as they move through the heart - an important diagnostic tool in the care of the cardiac patients ELECTROCARDIOGRAPHY MACHINE - detects the patterns of electrical impulse generation and conduction though the heart and translates that information to a recorded pattern ELECTROCARDIOGRAM -a measure of electrical activity; provides no information about the mechanical activity of the heart The normal ECG pattern is made up of main waves: 1. P wave- formed as impulses originating in the SA node or pacemaker pass through the atrial tissue 2. P wave- precedes the contraction of the atria 3. Ta wave- appear around the QRS complex

Critical points of the ECG are as follows : 1. P-R interval: reflects the delay of conduction at the AV node 2. Q-T interval: reflects the critical timing of repolarization of the ventricles 3. S-T segment: reflects the important information about the repolarization of the ventricles

- also referred as arterial system - where the vessels can either constrict or dilate, increasing or decreasing resistance, based on the needs of the body

TYPES OF ARRHYTHMIAS 1. Sinus arrhythmias - has a slower- than- to normal heart rate (usually less than 60 beats/ min) w/ Normal- appearing ECG pattern 2. Supraventricular Arrhythmias - arrhythmias that originate above the ventricles but not in the SA node - feature an abnormally shaped P wave - includes the following: a. Premature atrial contractions (PAC’s)- reflect an ectopic focus in the atria that is generating an impulse out of the normal rhythm b. Paroxysmal atrial tachycardia (PAT)- runs of rapid heart originating in the atria c. Atrial flutter- characterized b sawtooth- shaped P waves reflecting a single ectopic focus that is generating a regular, fast atrial depolarization d. Atrial fibrillation- w/ irregular P waves representing many ectopic foci firing in an uncoordinated manner through the atria 3. Ventricular Arrhythmias - impulses that originate below the AV node originate from ectopic foci that do not use the normal conduction pathways

* capillary fluid shift - shifting of fluid in the capillaries - carefully regulated between hydrostatic (fluid pressure) forces in the arterial end of the capillary and oncotic pressure ( the pulling pressure of the large, vascular proteins)

ATRIOVENTRICULAR BLOCK - also called heart block - reflects a slowing or lack of conduction at the AV node -occur because of structural damage, hypoxia, or injury to the heart muscle - First degree of heart block= P-R interval beyond the normal 0.16 to 0.20 seconds

* end- artery circulation - a pattern of circulation

CARDIOVASCULAR SYSTEM CIRCULATION - follows two courses: 1. Heart lung or pulmonary circulation: the right side of the heart sends blood to the lungs, where carbon dioxide and some waste products are removed from the blood and oxygen is picked up by the red blood cells 2. Systemic circulation: the left side of the heart sends oxygenated blood out to all of the cells in the body * resistance system

* capillary system - where blood from tiny arterioles flows - connects the arterial and venous system

*Capacitance system - also referred as venous system - where the veins has the capacity to hold large quantities of fluid * sinuses of Valsalva - where the myocardium receives its blood through 2 main coronary arteries that branch off the base of the aorta *coronary arteries - these arteries encircle the heart in pattern resembling a crown *pulse pressure - the pressure that fills the coronary arteries - it is systolic minus diastolic blood pressure readings

The main forces hat determine the heart’s use of oxygen or oxygen consumption are as follows: 1. Heart rate: the more the heart has to pump, the more oxygen it will require to do that 2. Preload ( amount of blood that is brought back to the heart to be pumped around): the more blood that is returned to the heart, the harder it will have to work to pump the blood around. The volume of blood that is determinant of preload 3. Afterload ( resistance against which the heart has to beat): The higher the resistance in the system, the harder the heart will have to contract to force open the valves and pump the blood along. The blood pressure is measure of afterload SYTEMIC ARTERIAL PRESSURE * Hypotension

- occur if the blood pressure falls, either from the loss of blood flowing from high- pressure to low pressure areas - if severe, it can progress to shock and even death as cells are cut off from their oxygen supply * Hypertension - excessive high blood pressure - can damage the fragile lining of blood vessel - cause disruption of blood flow to the tissues - caused by neurostimulation of the blood vessels that cause them to constrict and to raise pressure * Vasomotor Tone - work to dilate the vessels if more blood flow is needed in an area *Cardiovascular center - the coordination of these impulses through the medulla RENIN – ANGIOTENSIN SYSTEM -determinant of Blood pressure - activated when the blood flow to the kidneys is decreased -…cells in the kidney release an enzyme called rennin - Angiotensin I travels to lungs  Angiotensin- converting enzyme (ACE)  reacts  Angiotensin II = Vasoconstriction (read: p. 635) CONGESTIVE HEART FAILURE - if the heart fails to do its job of effectively pumping through the system, blood backs up and system becomes congested - results: hydrostatic pressure on the venous end of the capillaries

CHAPTER 43: DRUGS AFFECTING BLOOD PRESSURE -

altering the body’s regulatory mechanisms alter the normal reflexes that control BP does not cure the disease but is aimed at maintaining the BP within normal limits to prevent the damage that hypertension can cause

Stepped-Care Approach to Treating Hypertension by the Seventh Joint National Committee on Prevention, Detection, Evaluation, and Treatment of Hypertension, from the National Institute of Health Step 1: Lifestyle Modifications o weight reduction o reduction of sodium intake o moderation of alcohol intake o smoking cessation o increased physical activity Step 2: Inadequate Response o continue lifestyle modifications o initial drug selection

1. 2.

Step o o o

diuretic or β-blocker ACE inhibitor, calcium channel blocker, α-blocker, α- and βblocker

3: Inadequate Response increase drug dose, or substitute another drug, or add a second drug from another class

Step 4: Inadequate Response o add a second or third agent or diuretic if not already prescribed Diuretics ↑ the excretion of sodium and water from the kidney first agents tried in mild hypertension ↑ urination and disturb electrolyte and acid-base balances Sympathetic Nervous System Blockers

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block the effects of the SNS useful in blocking many of the compensatory effects of the SNS

β-blockers

α- and βblockers α-adrenergic blockers

α1-blockers

α2-agonists

block vasoconstriction; ↓ HR; ↓ muscle cardiac contraction; ↑ blood flow to kidneys; used in monotherapy in Step 2 blocking of all receptors in SNS; patients complain of fatigue, loss of libido, inability to sleep, GI and GU disturbances inhibit postsynaptic α1adrenergic receptors, ↓ sympathetic tone in the vasculature and causing vasodilation; diagnose and manage episodes of pheochromocytoma block postsynaptic α1-receptor sites, ↓ vasculature and causing vasodilation; do not block presynaptic α2-receptor sites stimulate α2-receptors in the CNS and inhibit the CV centers, ↓BP; many adverse CNS, GI effects, cardiac dysrhythmias

Angiotensin-Converting Enzyme (ACE) Inhibitors -

block the conversion of angiotensin I to angiotension II in the lungs as monotherapy or combined with diuretics

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well absorbed, widely distributed metabolized in liver, excreted in urine and feces

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cross the placenta and associated with serious fetal abnormalities

Contraindications allergy impaired renal function pregnancy and lactation Caution CHF salt/volume depletion Adverse Effects effects of vasodilation and alterations in blood flow o reflex tachycardia, chest pain, angina, CHF, cardiac arrhythmias o GI irritation, ulcers, constipation, liver injury o renal insufficiency, renal failure, proteinuria o rash, alopecia, dermatitis, photosensitivity unrelenting cough associated with fetal pancytopenia and MI Drug-Drug Interactions

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allopurinol = risk of hypersensitivity reactions ↑

Food-Food Interactions food = absorption of oral ACE inhibitors ↓

Prototype: captopril (Capoten) for hypertension, congestive heart failure (CHF), diabetic neuropathy, left ventricular dysfunction after MI associated with fatal pancytopenia, cough, GI distress

Nursing Considerations encourage patient to implement lifestyle changes administer on empty stomach, 1 or 2 hours before meals monitor fluid volume

Therapeutic Actions and Indications ↓ BP and aldosterone release indicated for treatment of hypertension, alone or with other drugs

Angiotensin II Receptor Blockers (ARBs) selectively bind the angiotensin II receptors in blood vessels to prevent vasoconstriction prevents the release of aldosterone in the adrenal cortex

Pharmacokinetics

Prototype: losartan (Cozaar) used alone or as part of combination therapy treatment of diabetic neuropathy with an elevated serum creatinine an d proteinuria Therapeutic Actions and Indications selectively bind with angiotensin II receptor sites in vascular smooth muscle and in the adrenal gland to block vasoconstriction and aldosterone release treatment of hypertension and for CHF in patients who are intolerant to ACE inhibitors Pharmacokinetics well absorbed, metabolized in liver excreted in urine and feces crosses the placenta, associated with serious fetal abnormalities and death Contraindications allergy pregnancy and lactation Cautions hepatic or renal dysfunction hypovolemia Adverse Effects headache, dizziness, syncope, weakness hypotension, GI complaints symptoms of upper respiratory tract infections and cough

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rash, dry skin, alopecia

Drug-Drug Interactions phenobarbital = risk of ↓ serum levels and loss of effectiveness ↑ Nursing Considerations encourage patient to implement lifestyle changes administer without regard to meals; give with food

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suggest use of barrier contraceptives monitor fluid volume

Calcium Channel Blockers prevent the movement of calcium into the cardiac and smooth muscle cells when the cells are stimulated leading to loss of smooth muscle tone, vasodilation, ↓ peripheral resistance ↓ BP

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very effective for treatment of angina

Prototype: diltiazem (Cardizem, Tiamate) sustained-release preparation treatment of hypertension Therapeutic Actions and Indications inhibit the movement of calcium ions across the membranes of myocardial and arterial muscle cells Pharmacokinetics well absorbed, metabolized in liver, excreted in urine cross the placenta, enters breast milk Contraindicaitons allergy heart block or sick sinus syndrome renal or hepatic dysfunction pregnancy or lactation Adverse Effects CNS effects

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GI effects CV effects skin flushing, rash

Drug-Drun Interactions cyclosporine = ↑ serum levels and toxicity of cyclosporine Vasodilators produce relaxation of the vascular smooth muscle, ↓ peripheral resistance and reducing BP do not block reflex tachycardia reserved for use in severe hypertension and hypertensive emergencies Prototype: nitroprusside (Nitropress) used intravenously

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treatment of hypertensive crisis and maintain controlled hypertension during surgery toxic levels cause cyanide toxicity

Therapeutic Actions and Indications act directly on vascular smooth muscle to cause muscle relaxation, leading to vasodialtion and drop in BP Pharmacokinetics rapidly absorbed and widely distributed metabolized in the liver and excreted in urine cross the placenta and enter breast milk Contraindications allergy pregnancy and lactation cerebral insufficiency Cautions peripheral vascular disease, CAD, CHF, tachycardia Adverse Effects related to changes in BP cyanide toxicity may occur with nitroprusside o dyspnea o imperceptible o headache pulse o absent reflexes o vomiting o dilated pupils o dizziness o pink color o ataxia o distant heart o loss of sounds consciousne o shallow breathing ss Nursing Considerations monitor BP and fluid volume Other Hypertensive Agents only drug: mecamylamine (Inversine) ganglionic blocker that occupies cholinergic receptor sites of autonomic neurons, blocking the effects of acetylcholine at both sympathetic and parasympathetic ganglia can cause o severe hypotension, CHF

o o

o

CNS symptoms of dizziness, syncope, weakness, vision changes parasympathetic blocking symptoms of dry mouth, glossitis, nausea, vomiting, constipation, urinary retention impotence

hypertension, bradycardia dizziness, vision changes, vertigo, headache problems with urination

calcium flow into the myocardial cells and causing increased contraction, positive inotropic effect

Drug-Drug Interactions risk of ↑ effects and toxicity of cardiac glycosides, beta-blockers, alphaadrenergic agents, corticosteroids if taken with midodrine

4. CARDIOTONIC DRUGS - drugs that affect the intracellular calcium levels in the heart muscle, leading to increased contractility - increase in contraction strength leads to increased cardiac output, which causes increased renal blood flow decreases rennin release -increases urine output -decreased blood flow - relieve CHF - has two types:

o o o

ANTIHYPOTENSIVE AGENTS -

severe hypotension leads to shock

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sympathomimetic drug: first choice drug for treating shock

Sympathetic Adrenergic Agonists effects of a sympathetic stress response: o ↑ BP o ↑ blood volume o ↑ strength of cardiac muscle contraction only drug: midodrine (ProAmatine) treat orthostatic hypotension Therapeutic Actions and Indications activates alpha-receptors in arteries and veins to ↑ in vascular tone and BP indicated for the symptomatic treatment of orthostatic hypotension Pharmacokinetics rapidly absorbed in GI tract metabolized in liver and excreted in urine Contraindications

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supine hypertension, CAD, pheochromocytoma acute renal disease urinary retention

Cautions pregnancy and lactation visual problems renal or hepatic impairment Adverse Effects related to stimulation of alpha-receptors o piloerection, chills, rash

Nursing Considerations monitor BP do not administer to bedridden patients monitor HR regularly

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monitor patients with visual problems encourage patients to void before taking drug

CHAPTER 44: CARDIOTONIC AGENTS Congestive heart failure (CHF) -condition where the heart fails to effectively pump blood around the body - called “dropsy’ or compensation TREATMENTS OF CHF: 1. VASODILATORS - used to treat CHF because they can decrease the workload of the overworked cardiac muscle

A. CARDIC GYCOSIDES - used for hundred of years - derived form foxglove or digitalis plant Drugs: 1. Digoxin (Lanoxin, Lanoxicaps) -treatment of acute congestive heart failure, atrial arrhythmias

2. DIURETICS - use to decrease blood volume, which decreases venous return and blood pressure - end result: decrease in afterload and preload and a decrease in the heart’s workload

* THERAPEUTIC ACTIONS 1.increase intracellular calcium and allow more calcium to enter myocardial cells during depolarization, causing following effects: a. Increased force of myocardial contraction b. Increased cardiac output and renal perfusion c. Slowed heart rate d. decreased conduction velocity through the artrioventricular node

3. BETA- ADRENERGIC AGONISTS - stimulate the beta receptors in the sympathetic nervous system, increasing

**PHARMACOKINETICS 1. absorbed widely 2. excreted unchanged in urine

3. caution w/ presence of renal impairements 4. not given during pregnancy 5. enters breast milk *** CONTRAINDICATION 1. presence of allergy 2. tachycardia or fibrillation 3. heart block or sick sinus syndrome 4. idiopathic hypertrophic subaortic stenosis (IHSS) 5. acute MI 6. renal insufficiency 7. electrolyte abnormalities ****CAUTION 1. pregnant or lactating women 2. **pediatric and geriatric patients *****ADVERSE EFFECTS 1. headache, weakness, drowsiness and vision changes 2. GI upset and anorexia 3. risk of arrhythmia development *****DRUG-DRUG INTERACTION 1. taken with veramil, aminodarone, quinidine, quinine, erythromycin, tetracycline or cyclosporine = increased therapeutic effects NURSING CONSIDERATION DIAGNOSIS 1. Risk for deficient fluid volume related to diuresis 2. Ineffective Tissue perfusion related in cardiac output 3. Impaired Gas exchanged related to changes in Cadiac Output 4. Deficient Knowledge regarding drug therapy

IMPLEMENTATION 1. Consult with the prescriber about the end for a loading dose when beginning therapy 2. Monitor apical pulse for 1 full minute before administration of drugs 3. Monitor pulse for any change in quality or rhythm 4. check for dosage and preparation carefully 5. Check pediatric dosage with extreme extra care 6. follow dilution instructions 7.administer IV doses very slowly at least 5 minutes 8. Avoid IM administration 9. Arrange the patient to be weighed 10. Avoid administering oral drug with food or antacids 11. Monitor patient digoxin level ( 0.5 to 3 ng/mL) B. PHOSPHODIESTERASE INHIBITORS - belong to a second class of drugs that act as cardiotonic (intropic) agents Drugs: 1. Inamripone (Inocor) - treatment of adults with congestive heart failure not responsive to digoxin, diuretics or vasodilators 2. Milrinone (Pimacor) - shorterm management of CHF in adults receiving digoxin and diuretics *THERAPEUTIC ACTIONS 1. block the enzyme phosphodiesterase 2. leads to an increase in myocardial cell cyclic adenosine monophosphate (cAMP) 3. increases calcium levels in the cells

4. increased cellular calcium causes contraction and prolongs effects of sympathetic stimulation 5. indicated for shortterm CHF that has not responded to digoxin or diuretics **PHARMACOKINETICS 1. widely distributed after injection 2. metabolized in the liver 3. excreted in the urine ***CONTRAINDICATIONS 1. has allergy 2. w/ severe aortic or pulmonic valvular disease 3. fluid volume deficit ****CAUTIONS 1. Elderly 2. pregnant or lactating women ***** ADVERSE EFFECTS 1. ventricular arrhythmias, hypotension and chest pain 2. GI effects: nausea, vomiting, anorexia, abdominal pain 3. Thrombocytopenia 4. hypersensitivity reactions: vasculitis, pericarditis, pleurititis, and ascites *******DRUG-DRUG INTERACTION 1. avoid Fluosemide ( Diuretics) NURSING CONSIDERATIONS DIAGNOSIS 1. decreased cardiac output arrhythmias or hypotension

related

to

2. risk for injury related to CNS or Cardiovascular effects 3. Innefective tissue perfusion related to hypotension or arrythmias 4. Deficient knowledge regarding drug therapy

ANTIARRHYTHMIC DRUGS -

IMPLEMENTATION 1. Protect drug form light 2. monitor input and output 3. monitor platelet count 4. monitor injection sites

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affect the action potential of the cardiac cells, altering their automaticity, conductivity, or both proarrhythmic: can also produce new arrhythmias used in emergency situations when the hemodynamics arising from the patient’s arrhythmia are severe and fatal may block reflex arrhythmias and help keep the CV system in balance, or they may precipitate new, deadly arrhythmias

Class I Antiarrhythmics CHAPTER 45 ANTIARRHYTHMIC AGENTS CORONARY ARTERY DISEASE (CAD) -

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

progressive growth of atheromatous plaques, or atheromas in the coronary arteries → plaques begin as fatty streaks in the endothelium → they injure the endothelial lining → development of foam cells (by inflammatory process) → platelets, fibrin, other fats, and remnants collect on the injured vessel lining → cause atheroma to grow → blood vessel narrows and limits blood flow injury to the vessel also causes scarring and thickening of cell wall the softer, more lipid atheromas appear to be more likely to rupture than stable, harder cores

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block the sodium channels in the cell membrane during an action potential local anesthetics or membranestabilizing agents preferable in situations such as tachycardia

Class IA Drugs depress Phase 0 of the action potential and prolong the duration of the action potential o disopyramide (Norpace)

o o o

moricizine (Ethmozine) procainamide (Pronestyl) quinidine (Quinaglute)

Class IB Drugs depress Phase 0 somewhat and actually shorten the duration of the action potential o lidocaine (Xylocaine)

o

mexiletine (Mexitil)

Class IC Drugs markedly depress Phase 0, with a resultant extreme slowing of conduction

o o

flecainide (Tambocor) propafenone (Rythmol)

Therapeutic Actions and Indications binding to Na channels, depressing Phase 0 of action potential, changing the duration of action potential have a local anesthetic effect treatment of potentially life-threatening ventricular arrhythmias Pharmacokinetics widely distributed after injection of after rapid absorption through the GI tract undergo hepatic metabolism excreted in urine cross the placenta and enter breast milk Contraindicaitons allergy bradycardia or heart block CHF, hypotension, shock electrolyte disturbances Cautions renal or hepatic dysfunction pregnancy Adverse Effects associated with their membranestabilizing effects and effects on action potentials o CNS effects o GI effects o CV effects respiratory depression and respiratory arrest rash, hypersensitivity reactions, loss of hair, bone marrow depression Drug-Drug Interactions - digoxin, beta-blockers = ↑ risk for arrhythmias digoxin = ↑ digoxin levels and digoxin toxicity

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cimetidine = ↑ serum levels and toxicity oral anticoagulants = ↑ risk for bleeding

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absorbed from GI tract, hepatic metabolism, excreted in urine used only when the benefit to the mother outweighs the risk to the fetus

Drug-Food Interactions foods that alkalize urine (citrus juices, vegetables, antacids, milk products) = ↑ quinidine levels and toxicity grapefruit juice = ↑ serum levels and toxic effects

Contraindications - sinus bradycardia (rate less than 45 beats/min) and AV block cardiogenic shock, CHF, asthma, respiratory depression pregnancy and lactation

Nursing Considerations monitor cardiac rhythm maintain life support equipment on standby give parenteral forms only if the oral form is not feasible - titrate the dose to the smallest amount needed

Cautions diabetes and thyroid dysfunction renal and hepatic dysfunction

Class II Antiarrhythmics -

beta-adrenergic blockers that block beta receptors, causing a depression of Phase 4 of the action potential slow the recovery of cells, leading to slowing of conduction and ↓ automaticity

Prototype: propanolol (Inderal) used as an antihypertensive, antianginal, antimigraine headache drug and as an antiarrhythmic to treat supraventricular tachycardias caused by digoxin or catecholamines Therapeutic Actions and Indications competitively block beta-receptor sites in the heart and kidneys - stabilize excitable cardiac tissue and ↓ BP indicated for the treatment of supraventricular tachycardias or PVCs Pharmacokinetics

Adverse Effects related to the effects of blocking beta receptors in the SNS o CNS effects o CV effects o respiratory effects o GI effects

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loss of libido, ↓ exercise tolerance, alterations in blood glucose levels

Drug-Drug Interactions verapamil = ↑ risk of adverse effects insulin = ↑ hypoglycemia Nursing Considerations (same as Class I Antiarrhythmics) Class III Antiarrhythmics

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block K channels, prolonging Phase 3 of the action potential, which prolongs repolarization and slows the rate and conduction of the heart

Prototype: sotalol (Betapace, Betapace AF) indicated for the treatment of documented life-threatening arrhythmias and maintenance of normal sinus rhythm proarrhythmic

Therapeutic Actions and Indications block K channels and slow the outward movement of K during Phase 3 of the action potential indicated for o life-threatening ventricular arrhythmias o conversion of recent-onset atrial fibrillation or atrial flutter to normal sinus rhythm o maintenance of sinus rhythm after conversion of atrial arrhythmias Pharmacokinetics well absorbed and widely distributed metabolized in the liver excreted in the urine used only when the benefit to the mother outweighs the risk to the fetus Cautions shock, hypotension, respiratory depression, prolonged QTc interval renal or hepatic disease Adverse Effects related to the changes they cause in action potentials o nausea, vomiting, GI distress o weakness and dizziness o hypotension, CHF, arrhythmias fever toxicity, ocular abnormalities, serious cardiac arrhythmias Drug-Drug Interactions digoxin or quinidne = serious toxic effects Class IV Antiarrhythmias -

block Ca channels in the cell membrane, leading to depression of depolarization and a prolongation of Phases 1 and 2 of repolarization, slowing automaticity and conduction

Prototype: diltiazem (Cardizem) administered IV

-

treat paroxysmal tachycardia

supraventricular

Therapeutic Actions and Indications block the movement of Ca ions across the cell membrane, depressing the generation of action potentials, delaying Phases 1 and 2 or repolarization, and slowing conduction through the AV node. treatment of supraventricular tachycardia and to control the ventricular response to rapid atrial rates Pharmacokinetics well absorbed metabolized in liver and excreted in the urine used only when the benefit to the mother outweighs the risk to the fetus Contrindications allergy sick sinus syndrome or heart block lactation CHF or hypotension Caution idiopathic hypertrophic subaortic stenosis (IHSS) impaired renal or liver function

Adverse Effects related to their vasodilation of blood cells throughout the body o CNS effects o GI effects hypotension, CHF, shock, arrhythmias, edema Drug-Drug Interactions - beta-blockers = ↑ risk of cardiac depression digoxin = additive AV slowing dogixin, carbamazepine, prazosin, quinidine = ↑ serum levels and toxicity

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-

atracurium, gallamine, metocurine, pancuronium, rocuronium, tubocurarine, vecuronium = ↑ respiratory depression calcium products or rifampin = ↓ effects given IV within 48 hours if IV betaadrenergic drugs = risk of severe cardiac effects diltiazem + cyclosporine = ↑ serum levels and toxicity

Nursing Considerations (same as Class I Antiarrhythmics) Other Drugs Used to Treat Arrhythmias adenosine (Adenocard) convert supraventricular tachycardia to sinus rhythm drug of choice for terminating supraventricular tachycardia o very short duration of action (15 sec), picked up by circulating RBCs, and cleared through the lvier o associated with very few adverse effects digoxin (Lanoxin, Lanoxicaps) slows Ca from leaving cell, prolonging the action potential and slowing conduction and HR treatment for atrial arrhythmias - positively inotropic, leading to ↑ cardiac output Nursing Considerations (same as Class I Antiarrhythmics)

3. w/ head trauma or cerebral hemorrhage 4. during pregnancy and lactation CHAPTER 46: ANTIANGINAL AGENTS ANTIANGINAL DRUGS - are used to help restore the supply- and- demand ratio in oxygen delivery to the myocardium when rest is not enough - these drugs can work to improve blood delivery to the heart muscle in 2 ways: 1. by dilating blood vessels ( e.i. increasing the supply of oxygen) 2. by decreasing the work of the heart (i.e. decreasing the demand of oxygen)

Caution 1. patients with hepatic or renal disease 2. w/ hypotension, hypovolemia, and conditions that limit cardiac output Adverse Effects 1. CNS effects: headache, dizziness, weakness 2. GI effects: nausea, vomiting, incontinence 3. cardiovascular problems: hypotension, reflex tachycardia, syncope, angina 4. skin related effects: flushing, pallor, increased perspiration 5. dermatitis and local hypersensitivity reactions

I. Nitrates - are drugs that act directly on smooth muscle to cause relaxation and to depress muscle tone - decreases: preload, afterload, myocardial contractility , oxygen demand

Dug- drug interaction • ergot derivatives= risk of hypertension and decreased anti- anginal effects • heparin = decreased effects

Prototype: Nitrogylcerin (Nitro-Bid, Nitrostat) - treatment of acute angina attack; prevention of anginal attacks

Nursing Considerations: 1. Give SQ preparations in the tongue or in buccal pouch, and encourage the patient not to swallow 2. ask the patient if the tablet “ fizzles” or burns 3. Give sustained- release forms with water and caution the patient not patient not to chew or crush them 4. Rotate the sites of topical forms 5. Make sure that transligual spray is used to under the tongue and not inhaled 6. Break an amyl nitrate capsule and wave it under the nose of the angina patient 7. Taper the dosage gradually

Therapeutic Actions and Indications - direct relaxation of smooth muscle with a resultant decrease in venous return and decrease in arterial pressure, effects that reduce cardiac workload and decrease myocardial oxygen consumption Pharmacokinetics 1. rapidly absorbed 2. metabolized in liver 3. excreted in urine 4. cross placenta 5. enter breast milk Contraindications: 1. presence of allergy 2. w/ severe anemia

II. Beta- Blockers - used to block the stimulatory effects of the sympathetic nervous system - block beta- adrenergic receptors and vasoconstriction - prevent the increase in heart rate and increased intensity of myocardial contractility that occur with sympathetic stimulation such as exertion or stress

- decrease the cardiac workload

Prototype: metoprolol (Toprol, Toprol XL) - treatment of stable angina pectoris and hypertension; prevention of reinfarction in MI patients, and treatment of stable, symptomatic CHF Therapeutic Actions and Indications 1. completely block- adrenergic receptors in the heart and juxtaglomerular apparatus, decreasing the influence of the sympathetic nervous system on these tissues and thereby decreasing the excitability of the heart, decreasing cardiac output, decreasing cardiac oxygen compensation and lowering blood pressure Pharmacokinetics 1. absorbed from the GI tract and undergo hepatic metabolic 2. found to increase bioavailability of propranolol, but this effect has not been found with other betaadrenergic blocking agents 3. excreted in the urine 4. has teratogenic effects Contraindications: 1. w/ bradycardia, heart block, cardiogenic shock, asthma, or COPD 2. pregnancy and lactation Caution: 1. with diabetes, peripheral vascular disease or thyrotoxicosis Adverse Effects 1. CNS effects: dizziness, fatigue, emotional depression and sleep disturbances 2. GI problems: gastric pain, nausea, vomiting , colitis and diarrhea 3. Cardiovascular effects: congestive heart failure, reduced cardiac output, and arrhythmias

4. Respiratory symptoms: bronchospasm, dyspnea, and cough Drug- Drug interaction 1. beta blockers= paradoxical hypertension 2. w/ clonidine= withdrawal NURSING CONSIDERATIONS ( same with beta blockers : Chapter 31) III. CALCIUM CHANNEL BLOCKERS -prevent the movement of calcium into the cardiac and smooth muscle cells when the cells are stimulated, interfering with their ability to contract Prototype: diltiazem ( Cardizem, Cardizem SR) - treament of prinzmetal’s angina, effortassociated angina, chronic stable angina; used to treat essential hypertension, paroxysmal supraventricular tachycardia Therapeutic Actions and Indications • inhibit the movement of calcium ions across the membranes of myocardial and arterial muscle cells, altering the action potential and blocking muscle cell contraction Pharmacokinetics 1. well absorbed 2. metabolized in the live 3. excreted in urine 4. cross placenta and enter milk 5. fetal toxicity reported Contraindications 1. presence of allergy 2. with heart block or sick sinus syndrome 3. with renal or hepatic dysfunction 4. during pregnancy and lactation Adverse Effects 1. CNS effects: dizziness, light- headedness, headache, fatigue

2. GI effects: nausea and hepatic injury 3. Cardiovascular effects: hypotension, bradycardia, peripheral edema, and heart block 4. Skin effects: flushing and rash Drug-Drug interactions 1. toxicity of cyclosporines if taken w/ diltiazem 2. increased risk of heart block and digoxin toxicity if combined with verapamil NURSING CONSIDERATIONS 1.monitor patient’s blood pressure, cardiac rhythm, cardiac output while the drug is titrated or dosage is being changed 2. Monitor blood pressure very carefully if the patient is also taking nitrates 3. Periodically monitor blood pressure and cardiac rhythm while the patient is using these drugs

→ → CHAPTER 47 LIPID-LOWERING AGENTS CORONARY ARTERY DISEASE (CAD) -

-



progressive growth of atheromatous plaques, or atheromas in the coronary arteries → plaques begin as fatty streaks in the endothelium → they injure the endothelial lining → development of foam cells (by inflammatory process) → platelets, fibrin, other fats, and remnants collect on the injured vessel lining → cause atheroma to grow → blood vessel narrows and limits blood flow injury to the vessel also causes scarring and thickening of cell wall the softer, more lipid atheromas appear to be more likely to rupture than stable, harder cores

ANTIHYPERLIPIDEMIC AGENTS -

often used in combination should be part of an overall health care regimen that includes exercise, dietary restrictions, and lifestyle changes to ↓ risk of CAD

Bile Acid Sequestrants Prototype: cholestyramine (Questran) powder mixed with liquids and taken up to 6 times a day Therapeutic Actions → bind with bile acids in the intestine to form a complex that is excreted in the feces

liver must use cholesterol to make more bile acids ↓ serum levels of cholesterol and LDLs

Indications reduce serum cholesterol in patients with primary hypercholesterolemia as an adjunct to diet and exercise cholestyramine: treat pruritus associated with partial biliary obstruction Pharmacokinetics - form an insoluble complex excreted in feces not absorbed systematically Contraindications allergy complete biliary obstruction abnormal intestinal function pregnancy or lactation Adverse Effects direct GI irritation ↑ bleeding times - vitamin A and D deficiencies muscle aches and pains

Therapeutic Actions → block the formation of cellular cholesterol → ↓ serum cholesterol and LDLs, slight ↑ or no change in HDLs Indications adjuncts with diet and exercise for the treatment of ↑ cholesterol and LDL levels slow the progression of CAD prevent first MI Pharmacokinetics absorbed from GI tract - first-pass metabolism in liver excreted through feces and urine pregnancy category X Contraindications allergy active liver disease or history of alcoholic liver disease pregnancy or lactation Caution impaired endocrine function

Drug-Drug Interactions ↓ or delay the absorption of thiazide diuretics, digoxin, warfarin, thyroid hormones, corticostreriods:

Adverse Effects GI system CNS effects - ↑ concentration of liver enzymes rhabdomyolysis with acute renal failure

Nursing Considerations do not administer powdered agents in dry form (mix with juices, soups, etc.) - ensure tablets are not cut, chewed, or crushed give drug before meals administer oral medicatiosn 1 hour before or 5 to 6 hours after the bile acid sequestrant arrange for bowel program

Drug-Drug Interactions erythromycin, cyclosporine, gemfibrozil, niacin, antifungal drugs = ↑ risk for rhabdomyolysis digoxin, warfarin = ↑ serum levels and resultant toxicity oral contraceptives = ↑ estrogen levels grapefruit juice = ↑ serum levels and risk of toxicity

HMG-CoA REDUCTASE INHIBITORS (“statins”)

Nursing Considerations administer drug at bedtime monitor serum cholesterol and LDL levels, including liver function, before and during therapy

Prototype: atorvastatin (Lipitor) associated with severe liver complications

-

arrange for ophthalmic medications ensure patient has attempted a cholesterollowering diet and exercise program for at least 3 to 6 months before therapy encourage patient to make lifestyle changes

Cholesterol Absorption Inhibitors Prototype: ezetimibe (Zetia) Therapeutic Actions → works in the brush border of the small intestine to ↓ absorption of dietary cholesterol → drop in serum cholesterol levels Indications lower cholesterol level treatment for homozygous familial hypercholesterolemia - reduce elevated sitosterol and campesterol levels Pharmacokinetics absorbed well metabolized in the liver and small intestine excretion is through feces an urine Contraindications allergy pregnancy, lactation, severe liver disease (if in combination with statin) Cautions pregnancy or lactation elderly patients or with liver disease Adverse Effects mild abdominal pain and diarrhea headache, dizziness, fatigue, upper respiratory tract infection (URI), back pain, muscle aches and pains Drug-Drug Interations - cholestyramine, fenofibrate, gemfibrozil, antacids = ↑ risk of elevated serum levels of ezetimibe cyclosporine = ↑ risk of toxicity

-

fibrate = ↑ risk of cholethiasis ezetimibe = ↑ warfarin levels

Nursing Considerations - monitor serum cholesterol, triglyceride, LDL levels, liver function test before and during therapy ensure patient has attempted a cholesterollowering diet and exercise program for several months before therapy encourage patient to make lifestyle changes Other Drugs Used to Affect Lipid Levels fibrates → stimulate the breakdown of lipoproteins from the tissues and their removal from the plasma → ↓ in lipoprotein and triglyceride synthesis and secretion -

absorbed from GI tract metabolized in liver excreted in urine

vitamin B3 → inhibits release of free fatty acids from adipose tissue → ↑ rate of triglyceride removal from plasma → ↓LDL and triglyceride level, ↑ HDL levels → also ↓ levels of apoproteins needed to form chylomicrons -

associated with intense cutaneous flushing, nausea, abdominal pain, development of gout given at bedtime administer 4 to 6 hours after the bile acid sequestrant

Combination Therapy if the patient shows no response to strict dietary modifications, exercise, and lifestyle changes, and the use of lipid-lowering agent, combination of therapy may be initiated to achieve desirable serum LDL and cholesterol levels

ANTICOAGULANTS - are drugs that interfere with the normal coagulation process - affect the process at any step to slow or prevent clot formation I. ANTIPLATELET DRUGS - alter the formation of the platelet plug, or - decrease the formation of the platelet plug by decreasing the responsiveness of the platelet to stimuli that would cause them to stick and aggregate a vessel wall - effectively to treat cardiovascular diseases that are prone to produce occluded vessels; for the maintenance of venous and arterial grafts; to prevent cerobrovascular occlusion, and adjuncts to thrombolytic therapy in the treatment of MI and prevention of infarction

CHAPTER 48 – Drugs Affecting Blood Coagulation CARDIOVASCULAR SYSTEM is a closed system

•

Consistently, the system must maintain an intricate balance between the tendency to clot or form a solid state, called coagulation, and the need to “unclot” or reverse coagulation to keep the vessel open and the blood flowing…

• Blood coagulation - is a complex process that involves vasoconstriction, platelet clumping or aggregation, and a cascade of clotting factors produced by the liver that eventually react to break down fibrinogen ( a protein also produced in the liver) into soluble fibrin threads . • Vasoconstriction - can seal off any break and allow the area to heal • Platelet aggregation - causes platelets in the circulating blood to stick or adhere to the site of injury platelets release ADP (adenosine triphosphate- precursor of prostaglandin) and other chemicals that attract other platelets, causing them to gather or aggregate and to stick as well thromboxane A2 cause local vasoconstriction = platelet aggregation and adhesion •

Hageman Factor

Prototype: Aspirin ( generic) - reduction of the risk if recurrent TIAs or strokes in males with history of TIA due to fibrin or platelet emboli; reduction of death or nonfatal MI patients with history of infarction or stable angina; MI prophylaxis, also used as anti-inflammatory, analgesics, and anti-pyretic Therapeutic Actions: • inhibit platelet adhesion and aggregation by blocking receptor sites on the platelet membrane, preventing platelet- platelet interaction of the interaction of platelets w/ other clotting chemicals

Drug- Drug interactions • risk of excessive bleeding increases if any of these drug is combined with another drug that affects blood clotting Nursing considerations 1. provide small and frequent meals 2. provide comfort measures and analgesia for headache 3. suggest safety measures, including the use of electric razor and avoidance of contact sports 4. provide increase precautions against bleeding 5. Mark the chart of any patient teaching receiving this drug 6. Provide thorough patient teaching, including the name of the drug, prescribed, measures to avoid adverse effects, warning signs of problems, the need for periodic monitoring and evaluation II. ANTICOAGULANTS Interfere with coagulation process by interfering with the clotting cascade and thrombin formation Therapeutic Actions and Indications Anticoagulants interfere with the normal cascade of events involved in the clotting process. Warfarin causes a decrease in the production of vit. K—dependent clotting factors in the liver. Heparin, argatroban and bivalirudin block while Antithrombin formationof thrombinfrom prothrombin. These drugs are used to treat thromboembolic disorders such as atrial fibrillation, MI, pulmonary embolus, and evolving dtroke and to prevent the formation of thrombi.

Pharmacokinetics • well absorbed • highly bound to plasma proteins • metabolized in the liver • excreted in urine • increased bleeding

Prototype: Heparin (generic) half-life 30-180 minutes, metabolize in the cells and excreted in the urine SQ onset 20-6- minutes, peak 2-4 hours, duration 8-12 hours IV – immediate onset, peak minute, duration 2-6 hours Warfarin – effects last 4-5 days, onset of action in 3 days

Contraindications 1. presence of allergy 2. during pregnancy and lactation

Contraindicated to known allergy to the drugs. They should not be use with conditions that can increase bleeding tendencies; hemorrhagic disorders, recent trauma, spinal puncture, GI ulcers, recent surgery, intraunterine device placement, tuberculosis, presence of indwelling catheter, and threatened abortion.Contratindicated to pregnancy, lactation, renal or hepatic disease

Caution 1. Presence of Known bleeding disorder 2. recent surgery 3. closed head surgeries Adverse Effects 1. Bleeding ( increased bruising and bleeding while bruising the teeth) 2. Headache, dizziness, and weakness 3. Nausea and GI distress may occur 4. Skin rash

Contraindications

Cautions In patients with CHF, thyrotoxicocic, saenility, or psychosis, diarrhea, fever Adverse effects

The most common adverse effect is bleeding (bleeding in gums with tooth brushing to severe intrernal hemorrhage), clotting shoud be monitored. Nausea, GI upset, diarrhea, and hepatic dysfunctiondue to toxicity. Warfarin can cause alopecia,dermatitis, bone marrow depression and prolonged and painful erections. Drug to drug Interaction Heparin + (oral anticoagulants, salicylates, penicillins, cephalosporins) =Increase bleeding Heparin + nitroglycerin = Decrease coagulation Nursing Considerations -screen for allergy -evaluate for therapeutic effects of warfarin --prothrombin time (PT) 1.5 to 2.5 times control value or ratio of PT to INR (International Normalized Ratio) of 2 to 3 -Evaluate for herapeutic effects of heparin—whole blood clotting time (WBCT) 2.5 to 3 times control or activated partial thromboplastin time (APTT) 1.5 to 3 times the control value - evaluate for signs of blood loss -maintain antidotes on standby (protamine sulfate for heparin, vit, K for warfarin) -monitor the patient when a drug is added or withdrawn from the drug regimen of a patient receiving warfarin -make sure patient receives regular follow up and monitoring -provide health teaching, name of drug and its effects Low Molecular-Weight Heparins These drugs inhibit thrombus and clot formation by blocking factors Xa and IIa. Because of size and nature of their molecules, theses drugs do not greatly affect thrombin, clotting or PT; they cause fewer adverse effects. They block angiogenesis, process that allows cancer cells to develop new blood vessels. Prototype: Strptokinase (streptase, kabikinase) Therapeutic actions and indications Thrombolytic agents work to activate the natural clotting system, conversion of plasminogen to plasmin, which in turn breaks down fibrin threads in a clot to dissolve a formed clot. They are indicated for the treatment of MI, to treat pulmonary emboli and ischemic stroke and to open clotted IV catheter. Pharmacokenetics Must me injected and cleared from the body after liver metabolism, crosses the placenta and have adverse fetal effects, should not be used during pregnancies unless benefits to the

mother out ways the potential risks to the fetus. Cautions should be used during lactation.

Replace normal clotting factors and are processed as such by the body.

Contraindications and cautions Contraindicated to allergy of these drugs, should not be used with conditions that could worsen the dissolution of clots, recent surgery, active internal bleeding, cerebrovascular accident within the last two months, aneurysm, recent serious GI bleeding, liver disease.

Contraindications and cautions Contraindicated in the presence of known allergy to mouse proteins. Factor IX is contraindicated in the presence of liver disease with signs of Intravascular coagulation or fibrinolysis. Coagulation factor VII is contraindicated with known allergies to mouse, hamster or bovine products. Not recommended during lactation and pregnancy.

Adverse effects Adverse effects The most common adverse effect is bleeding, cardiac arrhythmias and hypotensions Drug to drug interaction Risk of hemorrhage increases if thrombolytic agents are used with anticoagulant or antiplatelet drug. Nursing consideration -Discontinue heparin if given before administration of thrombolytic agent, unless ordered for coronary artery infusion. -evaluate for signs of blood loss (bleeding gums, bruises, dark colored stools and urine, petechiae) -institute treatment within 6 hours after the onset of symptoms of acute MI -arrange to type and cross match blood. -monitor cardiac rhythm -increase precautions against bleeding during invasive procedures. Drugs used to control bleeding On the other end of the spectrum of coagulation problems are various bleeding disorders: hemophilia, a genetic lack of clotting factor that leaves the patient vulnerable to excessive bleeding with injury.

The most common is risks with the use of blood products, e.g. hepatitis, aids. Headache, flushing, chills, fever and lethargy. Nausea, vomiting and itching, stinging and burning at injection site Nursing consideration -administer by IV only -monitor clinical response and clotting factor levels regularly. -monitor for sign of thrombosis -decrease the rate of infusion if headache, chills, fever or tingling occurs. -arrange to type and cross match blood. Systemic hemostatic agents A used to stop bleeding. Some situation result in fibrinolytic state with excessive plasminogen activity and risk of bleeding from clot dissolution. Prototype: Aminocaproic acid (amicar) Pharmacokinetics Parameters are different for each drug

Liver disease, clotting factors and proteins needed for clotting are not produce. Bone marrow disorders, insufficient platelets are formed. Antihemophilic agents Drugs used to treat hemophilia are replacement factors for the specific clotting factors that are genetically missing. Prototype: Antihemophilic factor (bioclate, others) Therapeutic actions and indications Replace clotting factors that are either genetically missing or low in a particular type of hemophilia. Used to prevent blood loss from injury or surgery and treat bleeding episode.

Therapeutic actions and indications Stop the natural plasminogen clot – dissolving mechanism by blocking its activation or by directly inhibiting plasmin. These drugs are used to prevent or treat excess bleeding in hyperfibrinolytic states, including repeat CABG surgery. Contraindications and cautions Contraindicated to allergy to these drugs and with acute DIC. Caution should be used in the following conditions: cardiac disease, renal and hepatic dysfunction, pregnancy and lactation Adverse effects The most common is excessive clotting. CNS effects include hallucinations, drowsiness, dizziness, headache and psychotic states. GI effects including nausea, cramps, and diarrhea.

Pharmacokenetics Drug to drug interaction

-

Increase risk of bleeding if combined with heparin Nursing considerations -monitor clinical response and clotting factor levels -monitor for signs of thrombosis -orient patients and offer support and safety measure if hallucinations or psychoses occur.

-

-

Topical hemostatic agents Used to injuries that involve damage to the small vessels in the area that clotting does not occur and blood is slowly and continually lost Absorbable gelatin (gellfoam) and microfibrilar collagen (avitene), are apllied directly to the injured area until the bleeding stops Thrombin (thrombinar, thrombostat) derived from bovine sources and mixed with the blood

CHAPTER 49: DRUGS USED TO TREAT ANEMIAS BLOOD -

essential for cell survival contains oxygen and nutrients and removes waste products that could be toxic to the tissues o contains clotting factors that help maintain the vascular system and keep it sealed o contains important components of the immune system that protect the body from infection

o

Blood Components composed of liquid and formed elements: plasma, leukocytes, erythrocytes, platelets Types of Anemia 1.

2.

Deficiency Anemia occurs when the diet cannot supply enough of a nutrient, or enough of a nutrient cannot be absorbed Megaloblastic Anemia

occurs when the bone marrow contains a large number of megaloblasts, or large, immature RBCs because these RBCs are so large, they become crowded in the bone marrow and fewer RBCs are produced patients usually have a lack of vitamin B12 or folic acid

Iron Deficiency Anemias a negative iron balance occurs in situations in which blood is being lost (such as heavy menstrual flow, internal bleeding) -

only enough iron is absorbed to replace the amount of iron lost each day only about 1 mg of iron is lost every day

Megaloblastic Anemias - there is no sufficient folic acid or vitamin B12 to adequately create the stromal structure needed in a healthy RBC

Folic Acid Deficiency folic acid is essential for cell division in all types of tissue deficiencies in folic acid are first noticed in rapidly growing cells may occur in: o certain malabsorption states (such as sprue or celiac diseases) o malnutrition that accompanies alcoholism o repeated pregnancies o extended treatment with certain antiepileptic medications treated by the administration of folic acid or folate Vitamin B12 Deficiency - vitamin B12 is used in minute amounts by the body and is stored for use it is necessary for the health of the RBCs and for the formation and maintenance of the myelin sheath in the CNS

-

vitamin B12 deficiency may occur in: strict vegetarians o inability of the GI tract to absorb the needed amounts of vitamin B12 treated with vitamin B12 replacement therapy o

-

Pernicious Anemia - occurs when the gastric mucosa cannot produce intrinsic factor and vitamin B12 cannot be absorbed person may complain of fatigue, lethargy, and CNS effects because of damage to the myelin sheath - treated with injections of vitamin B12 to replace the amount ERYTHROPOIETINS -

for patients who are no longer able to produce erythropoietin in the kidneys

Prototype: epoetin alfa (Epogen, Procrit) Therapeutic Actions acts like the natural glycoprotein erythropoietin to stimulate the production of RBCs in the bone marrow Indications treatment of anemia with renal failure to ↓ the need for blood transfusion in patients undergoing surgery treatment of anemias related to treatment for AIDS - treatment of anemia associated with cancer chemotherapy (Procrit only) Pharmacokinetics metabolized through the process - half life of 4 to 13 hours

normal

Contraindications presence of uncontrolled hypertension allergy lactation

kinetic

Adverse Effects result of cellular response to glycoprotein: CNS effects nausea, vomiting, diarrhea related to ↑ in RBC numbers: CV symptoms Nursing Considerations confirm chronic, renal failure before drug administration give epoetin alfa 3 times a week, IV or SQ do not mix with any other drug solution monitor access lines for clotting arrange for hematocrit reading before drug administration evaluate iron stores before and during therapy maintain seizure precautions on standy IRON PREPARATIONS -

iron deficiency anemia is common in certain groups: o menstruating women o pregnant and nursing women o rapidly growing adolescents o persons with GI bleeding and slow bleeding

Prototype: ferrous sulfate (Feosol) Therapeutic Actions elevate the serum iron concentration Indications treatment of iron deficiency anemias adjunctive therapy in patients receiving epoetin alfa Pharmacokinetics absorbed from small intestine transported in the blood used during pregnancy and lactation Contraindications allergy hemochromatosis (excessive iron) hemolytic anemias

-

normal iron balance peptic ulcer, colitis, regional enteritis

Adverse Effects direct GI irritation - with increasing serum levels, iron can be CNS toxic, causing coma and death parenteral iron: severe anaphylactic reactions, local irritation, staining of the tissues, phlebitis Drug-Drug Interactions antacids, tetracyclines, cimetidine = ↓ iron absorption ciproflaxin, norfloxacin, ofloxacin = ↓ antiinfective response chloramphenicol = ↑ iron levels levodopa = ↓ effects of levodopa Drug-Food Interactions antacids, eggs, milk, coffee, tea = iron is not absorbed

o

lack of intrinsic factor in the stomach

Prototype: hydroxocobalamin (Hydro-Crysti 12) given IM everyday for 5 to 10 days, then once a month for life used in states of ↑ demand or dietary deficiency Therapeutic Actions - folic acid and vitamin B12 : for cell growth and division, and production of strong stroma in RBCs - Vitamin B12: maintenance of the myelin sheath in nerve tissue Indications replacement therapy for dietary deficiencies replacement in high-demand states (such as pregnancy and lactation) treat megaloblastic anemia folic acid: rescue drug for cells exposed to some toxic chemotherapeutic agents

Nursing Considerations - confirm deficiency anemia before drug administration administer with meals have patients drink solutions through a straw caution patient that stool may be dark or green administer IM only through Z-track technique arrange for hematocrit and hemoglobin measurements before and during therapy

Pharmacokinetics well absorbed after injection metabolized mainly in liver excreted in urine highly protein bound considered essential during pregnancy and lactation

FOLIC ACID DERIVATIVES AND VITAMIN B12 Folate deficiencies usually occur o secondary to ↑ demands o absorption problems in the small intestine o secondary to the malnutrition of alcoholism

Cautions pregnant or lactating who have anemias nasal cyanocobalamin presence of nasal erosion or ulcers

Prototype: folic acid (Folvite) parenteral drugs are preferred for patients with potential absorption problems Vitamin B12 deficiencies usually occur o with poor diet or increased demand

Contraindication allergy

Adverse Effects pain and discomfort at injection sites nasal irritation with the use of nasal sprays Nursing Considerations confirm the nature of megaloblastic anemia give both types of drugs in pernicious anemia

-

parenteral Vitamin B12 must be given IM each day for 5 to 10 days, then once a month for life arrange for nutritional consultation monitor for hypersensitivity reactions arrange for hematocrit and hemoglobin measurements before and during therapy

Chapter 50 - Introduction to the Kidneys and the Urinary Tract Renal system: • Urinary tract • Ureters • Urinary bladder • Urethra

• 4 major functions of the renal system: • Maintain the value and composition of the body fluids w/in normal range • Regulating vitamin D activation • Regulating blood pressure • Regulating red blood cell production • >the kidneys are two small organs that receive about 25% of the cardiac output Nephron • the functional unit of the kidneys • is composed of the Bowman’s capsule, proximal convoluted tubule, loop of Henle, distal convoluted tubule, and collecting duct • Renal Processes a.) Filtration - straining fluid into the nephron >approximately 125 mL of fluid is filtered each minute, or 180L/day >99% of the filtered fluid is returned to the bloodstream >approx. 1% of the filtrate, less than 2 L of fluid is excreted each day in the form of urine b.) Secretion – actively removing components from the capillary

system and depositing them into the tubule c.) Absorption – removing from the tubule to return them to the capillary system and circulation >about 99% of the water filtered at the glomerulus is reabsorbed >the filtrate components include the vitamins, glucose, electrolytes, sodium bicarbonate, and sodium chloride >precision of the reabsorption process allows the body to maintain the correct extracellular fluid volume and composition Maintenance of Volume and composition of Body Fluids Sodium Regulation Sodium  Is one the body’s major cations(positively charged ions)  Reabsorbed via transport system that functions under the influence if the catalyst carbonic anhydrase, à carbonic acid à sodium bicarbonate 2 hormones that influence sodium levels in the filtrate:  Aldosterone-a hormone produced the adrenal gland - is released into the circulation in response to the high potassium levels,

sympathetic stimulation, or angiotensin III - stimulates Na-K exchange pump in the cells of the distal tubule, w/c reabsorbs Na in exchange for K, as a result Na is reabsorbed into the system and K lost in the filtrate  Natriuretic Hormone- probably produced by the hypothalamus - causes decrease in Na reabsorption from the distal tubules w/ a resultant dilute urine or increase volume - is released in response to the fluid overload or hemodilution Countercurrent Mechanism  in the medullary nephrons allow for the concentration or dilution of urine under the influence of ADH secreted by the hypothalamus Potassium Regulation Potassium  is another cation that ios vital to proper functioning of the nervous system, muscles, and cell membranes  65% is filtrated at the glumerulus is reabsorbed at the Bowman’s capsule and proximal convoluted tubule  25%-30% is r5eabsorbed at the loop of Henle

Chloride Regulation Chloride  Is an important negatively charged ion that helps to maintain electrical neutrality with the movement of cations across the cell membrane  Primarily absorbed in the loop of Henle, where it promotes the movement of sodium out of the cell *the kidneys play a role Sodium Regulation Calcium  Is important in muscle function, blood clotting, bone formation, contraction of cell membranes and muscle movement.  Filtered at the glomerulus and mostly reabsorbed in the proximal convoluted tubule and ascending Loop of Henle.  Fine tuning reabsorption occurs in the distal convoluted tubule.

Urinary Tract Urinary Bladder- is the muscular pouch that stretches and holds

the urine until it is excreted from the body. Uterus- have smooth endothelial lining and circular muscular linings. • The female urethra is very short and leads to an area populated by normal flora including e.coli. • The male urethra is much longer and passes through the prostate gland. Prostate Gland- a small gland that produces an acidic fluid that is important in maintaining the sperm and lubricating the tract.

-

drugs that increase the amount of urine the greater significance of diuretics is their ability to increase sodium excretion.

THIAZIDE AND THIAZIDE- LIKE DIURETICS

-

Therapeutic actions and indications: -

-

-

prevent the cell’s lining the renal tubule from reabsorbing an excessive proportion of the sodium ions in the glomerular filtrate. as a result, sodium and other ions are lost in the urine instead of being return to the blood, where they would cause increase intravascular volume and therefore increase hydrostatic pressure, which could result in leaking of fluids at the capillary level. Indicated for the treatment of edema associated with congestive heart failure, acute pulmonary edema, liver disease, and renal disease, and for the treatment of hypertension. Also use to decrease fluid pressure in the eye (intraocular pressure), which is useful in treating glaucoma. Diuretics that decrease potassium levels may also be indicated in the treatment of conditions that cause hyperkalemia.

-

*Thiazide- like drugs Chlorthalidone (Hygroton) Indapamide (Lozol) Metolazole (Mykrox) Quinethazone (Hydromox) Therapeutic actions and indications: -

Contraindications and cautions: -

presence of allergy to any of the drugs given fluid and electrolyte imbalances severe renal disease caution should be used with systemic lupus erythematosus (SLE) glucose tolerance abnormalities or diabetes mellitus gout liver disease pregnancy and lactation

Adverse effects: -

the most common adverse effects seen with diuretics include GI upset, fluid and electrolyte imbalances, hypotension, and electrolyte disturbances.

Drug- drug interactions:

-

CHAPTER 51: Diuretic Agents Diuretic Agents

-

antiarrhythmics (digoxin), drugs that depend on a particular electrolyte balance for their therapeutic effects. Quinidine, drugs that depend on urine alkalinity for proper excretion. Antihypertensive ad antidiabetic agents, depend on normal reflexes to balance their effects.

Thiazide diuretics belong to a chemical class of drugs called sulfonamides. Thiazide- like diuretics has a slightly different chemical structure but work in the same way that thiazide diuretics do. Their action is to block the chloride pump. Usually indicated for the treatment of edema associated with CHF or with liver or renal disease. Also used as monotherapy or as adjuncts for the treatment of hypertension.

Pharmacokinetics: -

onset of action: 1-3 hours metabolize in the liver and excreted in the urine well absorbed in the GI tract

Contraindications and cautions: -

drugs that altered the actions of diuretics: -

Hydrochlorothiazide (hydroDIURIL), the most frequently used of the thiazide diuretics, often used in combination with other drugs for the treatment of hypertension. Chlorothiazide (Diuril), the oldest of this class, and considered the prototype. Bendroflumethiazide (Naturetin) Hydroflumethiazide (Diucardin) Methyclothiazide (Aquatensen) Trichlormethiazide (Diurese)

contraindicated with allergy to thiazides or sulfonamides, fluid or electrolyte imbalances and renal and liver disease. Additional cautions include: gout, SLE, diabetes, hyperparathyroidism, bipolar disorder, and pregnancy and lactation.

Adverse effects: -

Hypokalemia (weakness, muscle cramps, and arrhythmias) Decrease calcium excretion, which leads to increase calcium level. Decrease uric acid excretion (gout, high level of uric acid)

-

Urine will slightly alkalinized

-

Drug- drug interactions: -

decrease absorption of this drugs if combined with cholestyramine or colestipol, if combination is used, it should be taken separated by at least 2 hours. Risk of digoxin toxicity increases due to potential changes in potassium levels; serum potassium level should be monitored if this combination is used. Decrease effectiveness of antidiabetic agents may occur related to the changes in glucose metabolism; dosage adjustment of those agents may be needed. Risk of lithium toxicity may increase if these drugs are combined. Serum lithium levels should be monitored and appropriate dosage adjustment made as needed.

-

They should not be used during pregnancy, unless the benefit to the mother far outweigh the potential risk, it enters in the breastmilk. Safety for use in children younger than 18 years of age, has not been establish. If one of this drug is used for a child, carefully monitor child’s fluid and electrolyte balance is needed.

Contraindication and cautions: -

LOOP DIURETICS -work in the loop in henle

allergy to loop diuretics, electrolyte depletion, anuria, severe renal failure, hepatic coma, pregnancy and lactation. Caution on patient with SLE, gout, and/or diabetes mellitus.

Adverse effect: -

Furosemide (Lasix), most common less powerful than new loop diuretics. Bumetanide (Bumex) Torsemide (Demadex) Ethacrynic acid (Edecrine)

-

hyperkalemia is a very common adverse effect. Alkalosis (a drop in serum pH to an alkaline state.) Hypotension, dizziness, ototoxicity, deafness. This may occur in conduction of fragile nerve in CNS.

Therapeutic action and indications: Drug- drug interactions: -

-

referred to as high-ceiling diuretics because they cause greater degree of diuresis. Block the chloride pump in the ascending loop of henle, where normally 30% of all filtered sodium is reabsorbed. These drugs work even in the presence of acid- base disturbances, renal failure, electrolyte imbalances, or nitrogen retention. A drug of choice when rapid and extensive diuresis is needed. In case of severe edema, it is important to remember that these drugs can have an effect only on the blood the nefron. In pulmonary edema, this fluid then circulates back to the lungs pulls fluid out of the interstitial spaces by its oncotic pull, and delivers fluid to the kidneys where the water is pulled out completing the cycle. Commonly indicted for treatment of acute CHF, pulmonary edema, edema associated with CHF or with renal or liver disease and hypertension.

Pharmacokinetics: -

metabolized and excreted through urine.

-

risk for ototoxicity increase with amino glycosides or cysplapin. Anticoagulation effect may increase with anticoagulant. Decrease loss of sodium and decrease antihypertensive effect with indomethacin, ibuprofen, salicylates, or another NSAIDs.

- Use as a drug adjuncts to other diuretics when a more intense diuresis is needed - Acetalozamide is used to treat mountain sickness Pharmacokinetics -rapidly absorbed widely distributed excreted in the urine - another method of feeding the infant should be used if one of this drugs is needed during lactation. Contraindicaions and Cautions -Allergy to drugs or antibacterial sulfunamides or thyazide or chronic noncongestive angle closure glaucoma -cautios use is recommended in patients who are breastfeeding, who have fluid imbalances, renal or hepatic disease, adrenocortical insufficiency, respiratory acidosis or COPD Adverse Effects metabolic acidosis hypokalemia paresthesias (tingling), confusion and drowsiness Drug to Drug Interaction - there maybe an increase excretion of salicylates and lithium if they are combined with this drugs Potassium- Sparring Diuretics These drugs are used for patients wha are at risk for hypokalemia associated with diuretic use. Retain potassium instead of wasting it. Amiloride (Midamore) Spironolactone (Aldactone) Triamterene (Dyrenium) Therapeutic Actions and Indication -

CARBONIC ANHYDRASE INHIBITOR -

relatively mild diuretics. Used to treat glaucoma

Acetazolamide (Diamox) Methazolamide (Meptazane) Therapeutic Actions and Indication - the enzyme carbonic anhydrase is a catalyst for the formation of sodium bicarbonate. -This diuretics lacks the effects of carbonic anhydrase that slows down the movement of hydrogen ions, as a result more sodium and bicarbonate are lost in the urine

-

These drugs are often used as adjuncts with thiazide or loop diuretics. Spironolactone is the drug of choice for treating hyperaldosteronism, a condition seen in cirrhosis of the liver and nephronic syndrome.

Pharmacokinetics These drugs are well absorbed, protein bound and widely distributed. These drugs cross the placenta and enter breast milk. Contraindicaions and Cautions Allergy to the drug Hyperkalemia Renal disease Anuria Patients who are taking Amiloride or triamterene

Adverse Effects Hyperkalemia OSMOTIC DIURETICS Pull water into the renal tubule without sodium loss. Drug of choice for Increase cranial pressure or acute renal failure.

Urinary Tract Anti-Infectives

to destroy bacteria, either through a direct antibiotic effect or through acidification of the urine.

DRUGS:

PHARMACOKINETICS:

2 types: antibiotics & anti infectives works to acidify the urine

Because these drugs are from several different chemical classes, the pharmacokinetic data are different for each drug. CONTRAINDICATIONS:

Antibiotics Glycerin (osmoglyn) Mannidol (Osmitrol) Urea (ureaphil) Therapeutic Actions and Indication It acts to pull large amounts of fluid into the urine by the osmotic pull of the large sugar molecule. These drugs are often used in acute situation . Prevent oliguric phase of renal failure, and to promote of toxic substances through the kidneys. Pharmacokinetics These drugs are freely filtered at the renal glomerulus, poorly reabsorbed by the renal tubules and not secreted by the tubule, and resistant to metabolism. Contraindications and Cautions Renal disease and anuria from sever renal disease, pulmonary congestion, intracranial bleeding, dehydration and CHF. Adverse Effects Sudden drop of fluid levels Cardiac decompensation and even shock

•

Cinoxacin(Cinobac)interferes with the DNA replication in gram negative bacteria • Norfloxacin (Noroxin)- a newer and more broad spectrum drug, is effective against even more gram negative strains than cinoxacin • Fosfomycin (Monurol)- has the convenience of only one dose. It is not recommended for patients younger than 18 years of age • Nalidixic (NegGram)is an older drug that is not effective against as many strains of gram-negative bacteria as the other antibiotics used for UTIs • Nitrofurantion (Furadantin)- is another older drug with a very short half-life (20-60 minutes) Anti-infective works to acidify urine • •

Chapter 52- Drugs affecting the Urinary Tract and the Bladder

Methenamine (Hiprex)- undergoes metabolism in the liver and is excreted in the urine Methylene blue (Urolene Blue)is widely distributed, metabolized in the tissues, and excreted in urine, bile, and feces

ACTION: The urinary anti-infectives act specifically within the urinary tract

These drugs are contraindicated in the presence of any of these drugs. They should be used with caution in the presence of renal dysfunction, which could interfere with the excretion and action of these drugs, and with pregnancy and lactation because of the potential for adverse effects on the fetus or neonate. ADVERSE EFFECTS: • •

•

nausea, vomiting, diarrhea, anorexia, bladder irritation, and dysuria infrequent symptoms include pruritus, urticaria, headache, dizziness, nervousness, and confusion GI irritation caused by the agent, which is alleviated if drug is taken with food

DRUG-DRUG INTERACTIONS: Drug interactions that can occur are very specific to the drug being used. Urinary Tract Antispasmodics DRUGS: •

Flavoxate (Urispas)smooth muscle specifically in the

prevent spasm urinary

•

•

•

tract, but it is associated with CNS effects (blurred vision, dizziness, confusion) that make it less desirable to use in certain patients Oxybutynin (Ditropan)is a potent urinary antispasmodic, but it has numerous anticholinergic effects, making it undesirable in certain conditions or situations that might be aggravated by decreased sweating, urinary retention, tachycardia, and changes in the GI activity. Tolterodine (Detrol,Detrol LA)is a newer agent that blocks muscarinic receptors, preventing bladder contraction and spasm Trospium (Sanctura)is the newest drug approved to block urinary tract spasms. It also specifically blocks muscarinic receptors and reduces the muscle tone of the bladder. It is specifically indicated for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and urinary frequency.

ACTION: Inflammation in the urinary tract, such as cystitis, prostatics, urethritis, and euthrocystitis/urethrotrigonitis, causes smooth muscle spasms along the urinary tract. Irritation of the urinary tract leading to muscle spasm also occurs in patient with neurologic bladder.

in urine. Caution should be used in the presence of hepatic or renal impairment because of the potential of alterations in metabolism or excretion of the drugs.

urinary tract mucosa. It is used to relieve symptoms related to urinary tract irritation from infection, trauma, or surgery. PHARMACOKINETICS:

CONTRAINDICATIONS: These drugs are contraindicated in the presence of any allergy to these drugs; with pyloric or duodenal obstruction or recent surgery because anticholinergic effects can cause serious complications.

Phenazopyridine is rapidly absorbed and has a very rapid onset of action. It is widely distributed, crossing the placenta and entering breast milk. It is metabolized in the liver and excreted in the urine. CONTRAINDICATIONS:

ADVERSE EFFECTS: •

•

adverse effects of urinary antispasmodics are related to blocking of the parasympathetic system nausea and vommitng, dry mouth, nervousness, tachycardia, and vision changes

DRUG-DRUG INTERACTIONS: Decreased effectiveness of phenothiazines and haloperidol has been associated with the combination of these drugs with oxybutynin. If any such combinations must be used, the patient should be monitored closely and appropriate dosage adjustments made. Urinary Tract Analgesic DRUGS: •

PHARMACOKINETICS:

Phenazopyridine (Azo-Standard, Baridium, and others) is a dye that is used to relieve pain. ACTION:

These drugs are rapidly absorbed, widely distributed, metabolized in the liver, and excreted

When phenazopyridine is excreted in urine, it exerts a direct, topical analgesic effect on the

This drug is contraindicated in the presence of any allergy to the drug and serious renal dysfunction, which would interfere with the excretion and effectiveness of the drug. ADVERSE EFFECTS: • •

GI upset, headache, rash, reddish-orange coloring of urine Hepatic toxicity, this drug should not be used for longer than 2 days because the toxic effects may be increased.

DRUG-DRUG INTERACTIONS: The risk of toxic effects of this drug increases if it is combined with anti-bacterial agents used for treating UTIs. If this combination is used, the phenazopyridine should not be used for longer than 2 days.

The respiratory system’s function is to supply the blood with oxygen in order for the blood to deliver oxygen to all parts of the body. The respiratory system does this through breathing, thus allowing gas exchange to occur. The normal functioning of the respiratory system depends on an intricate balance of the nervous system, cardiovascular, and musculoskeletal systems. It is composed of two parts namely the upper respiratory tract and the lower respiratory tract. THE UPPER RESPIRATORY TRACT The upper respiratory tract or conducting airways is composed of the nose, mouth, pharynx, larynx, trachea, and the upper bronchial tree. In here, air usually moves into the body through nose and into nasal cavity. The structures of the upper respiratory tract are moist with mucus (which are produced by the goblet cells in the epithelial lining of the nasal cavity) and are lined with cilia (microscopic hair-like projections of the cell membrane). The cilia constantly move and direct mucus and any trapped substances down toward the throat. Pairs of sinuses (air-filled spaces, communicating with the nasal cavity, within the bones of the skull and face) open into the nasal cavity. From the sinus, the mucus drains into the throat and is swallowed into the gastrointestinal tract, where stomach acid destroys foreign materials.

Chapter 53 – Introduction to the Respiratory System

Air moves from the nasal cavity into the pharynx and larynx. The larynx contains the vocal chords and the epiglottis (which closes during swallowing). From the larynx, air proceeds to the trachea, the main conducting airway to the lungs. The trachea divides into two main bronchi, which further divide into smaller and smaller branches. These bronchial tubes are composed of three layers: cartilage, muscle, and epithelial cells. All of these tubes contain mucus-producing goblet cells and cilia. The cilia in these tubes moves the mucus up to the trachea and into the throat, where again it is swallowed. The walls of the trachea and conducting bronchi are highly sensitive to

irritation. When receptors in the walls are stimulated, a central nervous system reflex is initiated and a cough reflex results, which causes air to be pushed through the bronchial tree to clean out any foreign irritant. This reflex, along with the sneeze reflex, forces foreign materials directly out of the system. Around the airways, many macrophage scavengers freely move about the epithelium and destroy invaders. Mast cells are present in abundance and release histamine, serotonin, and adenosine triphosphate (ATP), and other chemicals to ensure rapid and intense inflammatory reaction to any cell injury. The end result of these various defense mechanisms is that the lower respiratory tract is virtually sterile-an important protection against respiratory infection that could interfere with essential gas exchange. THE LOWER RESPIRATORY TRACT The lower respiratory tract is composed of the smallest bronchioles and alveoli which both are the functional units of the lungs. Within the lungs are network of bronchi, alveoli, and blood vessels. The lung tissue receives its blood supply from the bronchial artery, which branches directly off the aorta. The alveoli receives unoxygenated blood from the right ventricle via the pulmonary artery. This delivery of blood to the alveoli is referred to as perfusion. Gas exchange or ventilation occurs in the alveoli where carbon dioxide is lost from the blood and oxygen is to the blood. The alveolar sac holds the gas, allowing needed oxygen to diffuse across the respiratory membrane into the capillary while carbon dioxide, which is more abundant in the capillary blood, diffuses across the membrane and enters the alveolar sac to be expired. The respiratory membrane is made up of the capillary endothelium, the capillary basement membrane, the interstitial space, and the surfactant layer. The sac is able to stay open because of the surface tension of the cells is decreased by the lipoprotein surfactant which is produced by the type II cells in the alveoli.

Absence of collapse.

surfactant

leads

to

alveolar

The oxygenated blood is returned to the left atrium via the pulmonary veins; from there it is pumped throughout the body to deliver oxygen to the cells and to pick up waste products. RESPIRATION The central nervous system controls the respiration or the act of breathing. The respiratory center in the medulla stimulates the inspiratory muscle to contract, it also receives input from chemoreceptors and increase the rate of depth and/or rate of respirations to maintain homeostasis. The vagus nerve, a predominantly parasympathetic nerve, plays a key role in stimulating diaphragm constriction and inspiration. Vagal stimulation also leads to bronchoconstriction or tightening. The sympathetic system also innervates the respiratory sytem by increasing rate and depth of respiration and dilation of the bronchi. RESPIRATORY PATHOLOGY UPPER RESPIRATORY TRACT CONDITION •

The Common Cold

Common cold is caused by a number of different viruses that invade the upper respiratory tract, initiating the release of histamine and prostaglandins and causing an inflammatory response. As a result, mucous membranes become engorged with blood, the tissues swell, and the goblet cells increase the production of mucus. These effects cause the person to complain sinus pain, nasal congestion, runny nose, sneezing, watery eyes, scratchy throat, and headache. In susceptible, this swelling can block the outlet of Eustachian tube, which may lead to an ear infection (otitis media). •

Seasonal Rhinitis

Seasonal rhinitis or commonly called as hay fever occurs when the upper airways respond to specific antigen with vigorous inflammatory response, resulting in nasal congestion, sneezing, stuffiness, and watery eyes. •

Sinusitis

Sinusitis occurs when the epithelial lining of the sinus cavities becomes inflamed. The resultant swelling often causes severe pain. The danger of sinus infection is that, if left untreated, microorganisms can move up the sinus passages and into brain tissue. Pharyngitis and Laryngitis Pharyngitis and Laryngitis are infections frequently caused by common bacteria or viruses. These conditions are frequently seen with influenza. LOWER RESPIRATORY TRACT CONDITIONS •

Atelectasis

Atelectasis, the collapse of onceexpanded lung tissue, can occur as a result of outside pressure against the alveoli or pleural effusion. Atelectasis most commonly occurs as a result of airway blockage, which prevents air from entering the alveoli, keeping the lung expanded. This condition occurs when a mucus plug, edema of the bronchioles, or a collection of pus or secretions occludes the airway and prevents movement of air. Patients may present rales, dyspnea, fever, cough, hypoxia, and changes in chest wall movement. •

Pneumonia

Pneumonia is an inflammation of the lungs caused either by bacterial or viral invasion of the tissue or by inspiration of foreign substances into the lower respiratory tract. The respiratory tract leads to a localized swelling, engorgement, and exudation of protective sera. The respiratory membrane is affected, resulting in decreased gas exchange. Patients complain of difficulty breathing and fatigue, and they present

with fever and noisy poor oxygenation. •

breath

sounds,

and

Bronchitis

Acute bronchitis occurs when bacteria, viruses, or foreign materials infect inner layer of the bronchi. The person with bronchitis may have a narrowed airway during the inflammation; this condition can be very serious in a person with obstructed or narrowed airflow. Chronic the bronchi that does not clear. • Bronchiectasis Bronchiectasis is a chronic disease that involves the bronchi and bronchioles. It is characterized by dilation of the bronchial tree and inflammation of the bronchial passages. With chronic inflammation, the bronchial epithelial cell membranes, combined with the dilation of the bronchial tree, leads to chronic infections in the now unprotected lower areas of the lung tissue. Patients with this condition often have an underlying medical condition that makes them more susceptible to infections. Patients present with the signs and symptoms of acute infection, including fever, malaise, myalgia, arthalgia, and a purulent, productive cough. Obstructive Pulmonary Diseases •

Asthma

It is characterized by reversible bronchospasm, inflammation and hyperactive airways. The hyperactivity is triggered by allergens or nonallergic inhaled irritants or by factors such as exercise and emotions. The triggers cause an immediate release of histamine, which result in bronchospasm in about 10 minutes. The later response (3 to 5 hours) is cystokine-mediated inflammation, mucus production, and edema contributing to obstruction. The extreme case of asthma is the status asthmaticus which can be lifethreatening because bronchospasm does not respond to usual treatment and occludes air flow into the lungs.

•

Chronic Obstruction Disease (COPD)

Pulmonary

COPD is a permanent, chronic obstruction of airways, often related to cigarette smoking. It is caused by two related disorders, emohysema and chronic bronchitis. Emphysema is characterized by loss of elastic tissue of the lungs, destruction of the alveolar walls, and a resultant hyperinflation and tendency to collapse with expiration. Chronic bronchitis is a permanent inflammation of the airways with mucus secretion, edema, and poor inflammatory defenses. Persons with COPD are characterized by both disorders. •

Cystic Fibrosis

Cystic fibrosis is a hereditary disease that results in the accumulation of copious amounts of very thick secretions in the lungs. Eventually, the secretions obstruct the airways, leading to destruction of the lung tissue. Treatment is aimed at keeping the secretions fluid and moving and maintaining airway patency as much as possible. •

Respiratory Distress Syndrome (RDS)

Respiratory distress syndrome is frequently seen in premature babies whose lungs are not yet fully developed and their surfactant levels are still very low. Surfactant is necessary for lowering the surface tension in the alveoli so that they can stay open to allow the flow of gases. Treatment is aimed at instilling surfactant to prevent atelectasis and to allow the lungs to expand. Adult respiratory distress syndrome (ARDS) is characterized by progressive loss of lung compliance and increasing hypoxia. This syndrome occurs as a result of severe insult to the body.

Chapter 54- Drugs Acting on the Upper Respiratory Tract

These drugs work to keep the airways open and gas to move freely.  Antitussives- blocks the cough reflex  Decongestants- decrease the blood flow to the upper respiratory tract and decrease the overproduction of secretions  Antihistamines- block the release or action of histamine, a chemical released during inflammation that increases secretions and narrows airways.  Expectorants- increase productive cough to clear the airways.  Mucolytics- increase or liquefy respiratory secretions to aid the clearing of the airways. Antitussives Drugs that suppress the cough reflex. Act directly on the medullary cough center of the brain to depress the cough reflex. Acts as a local anesthetic on the respiratory passages, lungs, and pleurae, blocking the effectiveness of the stretch receptors that stimulate a cough reflex. Contraindicated for patients w/ postoperative and those who have undergone abdominal or thoracic surgery. Caution should be used in patients who are hypertensive or have a history of addiction to narcotics T ½ of 2-4 hrs; metabolized in liver and excreted in urine Side effects include: dizziness, respiratory depression and dry mouth Drugs in this class: benzonatate(Tessalon); codeine(generic); P dextromethorpan(Benylin); hydrocodone(Hydocan) Implemetation: teach the pt. the proper administration of the drug to ensure therapeutic effect

caution pts. not to use the drug longer than 5 days to facilitate detection of the underlying medical conditions that may require treatment. provide safety measures if dizziness occurs to prevent patient injury offer support and encouragement to help the patient cope with the disease and the drug regimen Decongestants Drugs that cause local vasoconstriction Decrease the blood flow to the irritated and dilated capillaries of the mucous membranes lining the nasal passages and sinus cavities. • Topical Nasal Congestants are sympathomimetics cause vasoconstriction, leading to decreased edema and inflammation of the nasal membranes caution in patients with lesions or erosions in the mucous membranes. T ½ of 0.4-0.7 hr; absorbed systematically, metabolized in the liver and excreted in the urine. Side effects include: disorientation, confusion, light headedness, nausea, vomiting, fever, dyspnea, rebound congestion Drugs in this class: P ephedrine(Kondon’s Nasal); oxymetazoline(Afrin, Allerest); phenylephrine(Coricidin); trahydrozoline(Tyzine); xylometazoline(Otrivin) • Oral Decongestants -decrease nasal congestion related to common colds,sinusitis,and allergic rhinitis. -relieve pain and congestion of otitis media - shrink the nasal mucous membrane by stimulating the alpha-adrenergic receptors in the nasal mucus membrane,promoting drainage of the sinuses and improving air flow. -Pseudoephedrine peak levels- 20 to 45 minutes. -ask the patient to void before taking the drug. -contraindicated to patient with glaucoma,hypertension,diabetes,thyroid disease,coronary disease and prostate problems.

-Adverse effects: rebound congestion,anxiety,tenseness tremors,hypertension,arrythmias,sweating,and pallor. -encourage patient not to use this drug for more than 1 week. • Topical Nasal Steroid Decongestants treatment for allergic rhinitis,been found to be effective in patient that doesn’t respond with other decongestants. Has an anti-inflammatory action that produce direct local effect. Onset of action may not be immediate, and may require up to a week to cause any changes. If no effects after 3 weeks , discontinue the drug. Relieve inflammation after removal of nasal polyps. Contraindicated with Candida Albicans infection,caution to those with TB,chickenpox,and measles. Drugs in this class: P flunisolide, Beclomethasone (Beclovent), Budesonide (Rhinocort) ,Dexamethasone (Decaderm),Fluticasone (AeroBid),Triamcinolone ( Kenacort) Antihistamines -blocks the effect of histamine 1 receptor sites, bringing relief to the patient to patients suffering from itchy eyes,swelling,congestion,and drippy nose. -treatment for seasonal and perennial allergic rhinitis,uncomplicated urticaria,angioedema -also has anticholinergic effects and antipruritic effect. -most effective if used before the onset of symptoms. -Onset of action 1-3 hours. -caution to those with arrythmias and prolonged Q-T intervals.

-Adverse effects: drying of the respiratory and GI mucous membranes,GI upset , nausea,dysuria,urinary hesitancy,and skin eruption and itching associated with dryness. -increase effect if taken with MAOI, ketoconazole,and erythromycin. -administer drug in an empty stomach -have patient void before each dose -Avoid alcohol Drugs in this class: P Diphenhydramine (Benadryl) T ½ of 2.5-7 hours 1st generation: Azelastine (Astelin),Brompheniramine, Buclizine ( Bucladin S),Cetirizine(Reactine),Chlorpheniramine (Allerchlor),Clemastine (Tavist),Cyclizine (Marezine),Cyproheptadine(Periactin),Dexclorphe niramine(Dexchlor),Dimenhydrinate (Dimentabs),Hydroxyzine (Vistaril),Meclizine (Bonine),Phenindamine (Nolohist),Promethazine(Phenergan). 2nd generation : Desloratadine (Clarinex),Fexofenadine (Allegra),Loratadine ( Claritin). Expectorants -liquefy lower respiratory tract secretions,reducing viscosity of these secretions, and making it easier for patient to cough them out. -reduces adhesiveness and surface tension of secretions,movement of less viscous secretions -more productive cough, decreased frequency of coughing. -P Guaifenesin (symptomatic reliefof respiratory condition characterized by dry, nonproductive, cough, and in the presence of mucus in respiratory cough) -adverse effects: Nausea,vomiting,headache,dizziness,rash. -Not to use this drug for more than 1 week. -Advise the use of small,frequent meals.

Mucolytics -aid in high –risk respiratory patient in coughing up thick secretions,tenacious secretions. -for COPD, cystic fibrosis,pneumonia,tuberculosis,atelectasis,diagnos tic bronchoscopy, Postoperative patients with tracheostomy. -administer through instillations or nebulization. -caution with acute brochospasm,peptic ulcer,and esophageal varices. -splits links in mucoproteins contained in secretions,decreasing viscosity. Drugs in this class : P Acetylcysteine (Mucomyst) T ½ 6.25 hr ,Dornase alfa (Pulmozyme)

Chapter 55 - Drugs Used To Treat Obstructive Pulmonary Disease Bronchodilators/ Antiasthmaticsdilating airways Xanthines -main treatment for bronchospasm and asthma. -has direct effect on the smooth muscles of respiratory tract,both in the bronchi and in the blood vessels. - stimulate 2 prostaglandins resulting in smoothe muscle relaxation, which then increase the vital capacity. - inhibit the SRSA. - Unlabeled use: stimulation in respiration Cheyne Stokes respiration. - Peak levels within 2 hours. - Caution with patient with GI problems,coronary disease,respiratory dysfunction,renal or hepatic lung disease,alcoholism,hyperthyroidism. - Increases with nicotine. Drugs in the class: P Theophylline ( Siobid ,Theo Dur) T ½ of 3-15 hr (nonsmoker),4-5 hr (smoker), Aminophylline(Truphylline), Caffeine, Dyphylline (Dilor). -administer drug with food or milk. Sympathomimetics -mimic the effects of the sympathetic nervous system.

-dilates the bronchi and increased the rate and depth of respiration. -beta2 selective adrenergic agonists. -Adverse effects: increase BP,HR,vasoconstriction,decreased renal and GI bloodflow. -rapidly absorb after injection. Half life of < 1 hour. -Caution on those with cardiac disease,vascular disease,diabetes,hyperthyroidism, pregnancy and lactation - avoid combination with bronchodilators,general anesthetics cyclopropane,and halogenated hydrocarbon. - administer with small frequent meals. Drugs in this class: P Epinephrine (Sus – Phrine, EpiPen), Albuterol(Proventil), Bitolterol (Tornalate), Ephedrine,Formoterol (Foradil), Isoetharine(Bronkosol), Isoproterenol (Isuprel), Levalbuterol (Xopenex), Metaproterenol (Alupent). Anticholinergic Bronchodilators -not as effective as sympathomimetics but can provide some relief to those patient who could not respond to other drugs. -has an effect in the vagus nerve,which block or antagonize the action of the

neurotransmitter acetylcholine at vagalmediated receptor sites, leading to relaxation of smooth muscles by bronchodilation. Drugs in this class: P Ipratropium with an onset of action of 15 minutes when inhaled.Peak of 1-2 hours,Thiotropium has rapid onset and longer duration with half life of 5 to 6 days. -Encourage client to void before each dose. -Provide small frequent meals and sugarless lozenges. -Caution patient not to use inhalator for more than 12 inhalations in 24 hours. Inhaled Steroids -very effective for treatment of bronchospasm. -decrease inflammatory response in the airway,thus increasing air flow and facilitate respiration. -Has 2 effects:  Decreased swelling associated with inflammation and promotion in the beta – adrenergic receptor activity.  Inhibit bronchoconstriction. -used for prevention and treatment of asthma,treat chronic steroid-dependent bronchial asthma. -should be taken 2-3 weeks to achieve effects. -Adverse effects: sore throat,coughing,dry mouth,and pharyngeal and laryngeal fungal infection.

-have patient use decongestant drops before using inhaled steroid. -Have patient rinse his mouth after inhaler. Drugs in this class include:P Flunisolide (AeroBid) T ½ of 1-2 hours., beclomethasone (beclovent),Budesonide (Pulmicort),Fluticasone (Flovent),Triamcinolone (Azmacort). Leukotriene Receptor Anatagonist -selectively,and competitively blocks the receptor for production of leukotrienes D4 ,E4 components of SRSA. -blocks many signs and symptoms of asthma,such as neutrophil,eosinophil migration,neutrophil,and monocyte aggregation,leukocyte adhesion,increased capillary permeability,and smooth muscle contraction. -prophylaxis for bronchial asthma and in patients younger than 12 years of age.Not indicated for treatment of acute asthma attack. -metabolized via cytochrome P450 and excreted in feces. -Abverse effects: headache,dizziness,myalgia,nausea,diarrhe a,elevated liver enzymes,vomiting,fever,pain. -Increased toxicity if taken with propanolol,theophylline,and warfarin Drugs in this class : P Zafirlukast (Accolate),Montelukast(Singulair),Zileuto n (Zyflo). -administer drug in an empty stomach.

-Caution patient not to stop meds in symptom –free periods. Lung Surfactant -naturally occurring substance lipoproteins containing lipids, and apoproteins that reduce the surface tension within the alveoli for gas exchange. -used to replace the surfactant that is missing in lungs of neonates with RDS. -begin to act immediately on instillation into the trachea. -No contraindications -Adverse effects: patent ductus arteriosus in infants,hypotension,intraventricular hemorrhage,pneumothorax,pulmonary air leak,hyperbilirubinemia,and sepsis. Drugs in this class: P Beractant (Survanta),Calfactant(Infasurf),Colfosceril (Exosurf, Neonatal ), Poractant (Curosurf). -suction the infant immediately before administration,but do not suction for 2 hours after administration. Mast Cell Stabilizers -prevent release of inflammatory and bronchoconstricting substances when mast cells are stimulated to release these substances because irritation. Drugs in this class: P Cromolyn T ½ of 80 min(inhibit release of histamine and SRSA,and is inhaled in a capsule but may not reach its peak effect for 1 week).Nedocromil (inhibit mediators of

inflammatory cells including eosinophils,neutrophils,macrphages,and mast cells. -treatment of mild-moderate bronchial asthma of >12 years old patients. -Cromolyn not recommended for children younger than 2 years old,and nedocromil not recommended for children younger than 12. -Adverse effects: headache,dizziness,nausea,sore throat,dysuria,cough and nasal congestion. -Administer oral drug 30 minutes before meals and at bedtime. -Instruct patient not to wear contact lenses if using Cromolyn eye drops. -Dizziness and fatigue common problem in takinh Nedocromil.

CHAPTER 56 – INTRODUCTION TO THE GASTROINTESTINAL SYSTEM The gastrointestinal (GI) system is the only system in the body that is open to the external environment. The GI system is composed of one continuous tube that begins at the mouth; progresses through the esophagus, stomach and small and large intestines; and ends at the anus. The pancreas, liver and gallbladder are accessory organs that support the functions of the GI system. Composition of the Gastrointestinal Tract The GI tube is composed of four layers: • The Mucosa – provides the inner lining of the GI tract • The Muscularis Mucosa – is made up of muscles. It helps the tube open and squeezing the tube to aid digestion and motility. It also helps propel the gastrointestinal contents down the tract. • The Nerve Plexus – these gives the GI tract local control of movement, secretions, and digestion. • The Adventitia – outer layer of the GI tract, serves as a supportive layer and helps the tube maintain its shape and stay in position.

Gastrointestinal Activities The system has four major activities: • Secretion • Absorption • Digestion • Motility Secretion – secretes various compounds to aid the movement of the food bolus through the GI tube, to protect the inner layer of the GI tract from injury and to facilitate the digestion and absorption of nutrients. - Saliva – contains water and digestive enzymes and facilitate swallowing by making bolus slippery - Histamine 2 receptors – gastrin and parasympathetic system stimulates it, causing the cells to release hydrochloric acid into the lumen of the stomach. - Bile – contains detergent like substance that breaks apart fat molecules so that they can be processed and absorbed. - Gallstones – develop when the concentrated bile crystallizes.

Digestion – process of breaking food into usable, absorbable nutrients. Absorption – active process of removing water, nutrients and other elements from the GI tract and delivering them to the bloodstream for use for the body. Motility – GI tract depends on this to keep things moving through the system. - Peristalsis – basic movement in the esophagus. It is a constant wave of contraction that moves from the top to the bottom of the esophagus. - Swallowing – response to a food bolus in the back of the throat stimulates the peristaltic movement that directs the food bolus into the stomach. - Segmentation – involves contraction of one segment of small intestine while the next segment then relaxes, and the relaxed segment contracts.

Local Gastrointestinal Reflexes • Gastroenteric reflex: stimulatiuon of the stomach by stretching, the presence of food, or cephalic stimulation causes an increase in activity in the small intestine. It is thought that this prepares the small intestine for the coming chyme. • Gastrocolic reflex: stimulation of the stomach also causes increased activity in the colon, again preparing to empty any contents to provide space for the new chime. • Duodenal-colic reflex: the presence of food or stretch in the duodenum stimulates colon activity and mass movement, again to empty the colon for the new chime. Other local GI reflexes: • Ileogastric reflex • Intestinal-intestinal reflex • Peritoneointestinal reflex • Renointestinal reflex • Vesicointestinal reflex • Somatointestinal reflex Central Reflexes Two centrally mediated reflexes Swallowing reflex and Vomiting reflex –

are very important to the functioning of the GI tract.  Swallowing – is a centrally mediated reflex that is important in delivering food to the GI tract for processing. It is controlled by the medulla and involves a complex series of timed reflexes.  Vomiting – is controlled by the chemoreceptor trigger zone (CTZ) in the medulla or by the emetic zone in immature or injured brains. The CTZ is stimulated by several different processes and initiates a complex series of responses that first prepare the system for vomiting and then cause a strong backward peristalsis to rid the stomach of its contents.