Module 3 - Drugs Affecting the Cardiovascular & Renal Systems Flashcards
1
Q
What blood pressure range is considered prehypertensive?
A
A systolic BP of 120 to 139 mmHg or a diastolic BP of 80 to 89 mmHg is considered prehypertensive and requires health-promoting lifestyle modifications
2
Q
What is the BP goal for patient’s age 90+ who do not have diabetes of chronic kidney disease?
A
BPs <150/90 mm Hg
3
Q
What is the BP goal for patient’s 18-59 yrs old, including African Americans, patient’s w/ diabetes, and CKD?
A
BP goal is <140/90 mm Hg.
4
Q
What are the 1st line drugs for hypertension?
A
thiazide-type diuretics, calcium channel blockers, ACEIs and ARBs.
5
Q
What is the initial therapy for hypertension in patients of African descent w/o CKD?
A
CCB & thiazide diuretics
6
Q
What is the initial therapy for hypertension in patients w/ CKD?
A
ACEIs or ARBs
7
Q
Is it recommended to use an ACEI and an ARB for HTN?
A
No the JNC panel does not recommend it
8
Q
What are the recommendations for patient’s whose BP is not controlled with a beta-blocker?
A
- A thiazide-type diuretic (chlorthalidone is preferred), a calcium channel blocker, ACE inhibitor, or an ARB (angiotensin II receptor blockers) as initial therapy for HTN in non-black patients.
- A thiazide-type diuretic or a CCB is preferred for initial treatment of black patients.
9
Q
What are the side effects of beta-blockers?
A
- Difficult breathing or a night cough (symptoms of CHF)
- Bradycardia
- Dizziness
- Lightheadedness
- Confusion
- Fatigue
- CNS effects (depression, sleep disturbances, nightmares)
- Male sexual dysfunction
- Worsen symptoms of peripheral vascular diseases
- Decreased cardiac output may lead to reduction in exercise tolerance
- Nonselective agents may cause bronchoconstriction
- May prevent and mask catecholamine-mediated glucose mobilization (hence exacerbate hypoglycemia)
- Patients, especially those with coronary disease, should be told not to discontinue their beta-blocker therapy abruptly (worsening of angina, cardiac arrest, and acute myocardial infarctions have been reported).
10
Q
What are the common adverse effects of ACE inhibitors?
A
- The most common SE: DIzziness, headache, hypotension, fatigue, diarrhea, and cough.
- The most prominent AE: are cough, angioedema, 1st dose hypotension, and hyperkalemia.
11
Q
Should ACE inhibitors be used during pregnancy?
A
- Using ACE inhibitors during the 2nd and 3rd trimesters of pregnancy can injure the developing fetus. Specific effects include hypotension, hyperkalemia, skull hypoplasia, pulmonary hypoplasia, anuria, renal failure (reversible and irreversible), and death.
- Pregnancy Risk D
- Women who become pregnant while using ACE inhibitors should discontinue treatment as soon as possible.
12
Q
What is the MOA of thiazide diuretics?
A
- Decreases reabsorption of NaCl in the kidneys (although less so than Loop diuretics), which leads to an initial decrease in intravascular volume, a decrease in cardiac output, & ultimately a decrease in BP
- These drugs are proven to decrease mortality in patients w/ HTN; a reasonable choice for initial tx of HTN in many patients.
13
Q
What are the indications for using hydrochlorothiazide?
A
- Hypertension - Thiazide-type diuretics are appropriate for most patients with mild to moderate hypertension and normal renal and cardiac function. The thiazides are “first step” agents. They are mild acting agents but are additive to most other antihypertensives, many of which tend to cause sodium and water retention
- Treatment of edema - Thiazides are useful for treating mild edematous states associated with disease or drug therapy
14
Q
What are the s/x of using hydrochlorothiazide?
A
- Hyponatremia - Hyponatremia was 4 times more likely to occur in elderly subjects compared with younger patients
- Hypokalemia - Most patients taking long-term thiazide therapy develop some degree of potassium loss. Patients may be told to increase intake of potassium-rich foods (bananas, orange juice, Lite Salt), or take potassium supplements (MicroK, K-tabs, Adolph’s salt substitute), or potassium-sparing diuretics (spironolactone)
- Hyperuricemia. Thiazides may reduce uric acid excretion and simultaneously reduce blood volume, which concentrates uric acid in the blood. This may predispose a hyperuricemic patient to gout.
- Hyperglycemia - Hyperglycemia is of concern for type 2 diabetic or prediabetic patients. It is believed the hypokalemia produced by thiazides may decrease release of insulin. Blood glucose levels should be evaluated regularly and frequently, especially during early treatment.
- Oliguria - High doses of thiazides, particularly in elderly subjects or patients with impaired renal function, can reduce GFR and renal blood flow. The drug is contraindicated in oliguria. Monitor urine output and BUN levels. If urine output falls, notify the physician.
- Thiazides should not be given to pregnant or breast-feeding women. The drug is potentially dangerous in pregnancy.
15
Q
What type of drug is furosemide (Lasix) and what is its MOA?
A
- Many effects are similar to the thiazides but the maximum diuretic effect far exceeds that of other diuretics, hence the term “high ceiling.” They are more efficacious than thiazides as diuretics but less efficacious as antihypertensive agents.
- Loop diuretics inhibit a transporter of sodium, potassium, and chloride primarily in the thick ascending limb of the loop of Henle and also cause excretion of magnesium and calcium.
16
Q
What is Furosemide (Lasix) used for?
A
- Management of chronic edema - particularly that accompanying acute pulmonary edema and congestive heart failure. They are especially important in the treatment of acute pulmonary edema.
- Primary hypertension - the loop diuretics are less efficacious than thiazides in control of blood pressure, particularly in edema-free patients. In general, loop diuretics should be reserved for hypertensive patients with chronic renal insufficiency.
17
Q
What are the s/x of using Furosemide (Lasix)?
A
- The most common adverse effects are anorexia, nausea, vomiting, headache, and vertigo. Take with food or milk
- High-ceiling diuretics may quickly cause volume depletion, hyponatremia, hypochloremia, dehydration, hypotension, and shock
- Hearing Loss
- Not safe for use in pregnant women
18
Q
What type of drug is Spironolactone (Aldactone) and what is its MOA?
A
- Potassium-sparing diuretic
- It competitively blocks the effect of aldosterone on kidney tubules. (Aldosterone stimulates the Na+/K+ pump in the distal tubule to cause reabsorption of sodium in exchange for excretion of potassium).
19
Q
What are the indications for Spironolactone (Aldactone)?
A
- Treat hypertension or for relieving edema, but they are by far more commonly prescribed in combination with thiazide diuretics and used primarily to prevent thiazide-induced hypokalemia
- They may be used in the treatment of hypokalemia or mineralocorticoid excess.
- Spironolactone is also indicated for the treatment of hyperaldosteronism (either primary or secondary to CHF, cirrhosis, or nephrotic syndrome). It may also correct magnesium deficiencies.
20
Q
What are the s/x of using Spironolactone (Aldactone)?
A
- (When used alone potassium-sparing diuretics are unlikely to cause significant water or salt loss.
- Hyperkalemia - Excessive potassium retention is an important side effect but this usually occurs only when these agents are used with potassium supplements, potassium-rich foods, or other drugs which cause hyperkalemia (e.g., ACE inhibitors) or in elderly patients with poor renal function. Hyperkalemia is a contraindication for use of these drugs.
- Spironolactone interferes with synthesis of testosterone and may increase the formation of estradiol from testosterone, thus leading to endocrine abnormalities such as impotence, gynecomastia, and decreased libido in 50% of males and menstrual abnormalities in females.
- Spironolactone also interferes with the renal excretion of digoxin and increases slightly the risk of digoxin toxicity.
- These drugs may cause GI upset; take with food. They may cause dizziness, headache or visual disturbances. Rashes, vomiting, diarrhea, paresthesias has been reported in neonates. Use with caution in patients with impaired renal function.
21
Q
What are the s/x of direct-acting vasodilators (i.e. hydralazine) & Why they are considered 3rd line drugs for HTN?
A
- Side effects: headache, anorexia, nausea, vomiting, diarrhea, hypotension, palpitations, tachycardia, edema, angina pectoris
- They are 3rd line drugs for HTN because they can cause reflex tachycardia, and salt and water retention. They can also produce an effect like Systemic Lupus Erythematosus and should be stopped if this occurs.
22
Q
What type of drug is Prazosin and what is its MOA?
A
- Alpha 1 Blocker
- These agents selectively block postsynaptic α1-adrenergic receptors, dilating both resistance (arterioles) and capacitance (veins) vessels (alpha 1B receptors). They also block α1A receptors in the prostate gland.
23
Q
What are the s/x of Prazosin?
A
- These agents can cause marked hypotension (especially postural hypotension with decreased venous return) and syncope with the first few doses or with a rapid increase in dosage.
- This effect is minimized by limiting the initial dose to the smallest possible and giving it at bedtime.
24
Q
What are the indications for using Alpha 1 blockers?
A
- Treatment of hypertension (prazosin & terazosin & doxazosin)
- Symptoms associated with BPH (terazosin & doxazosin)
25
Which Alpha 1 blockers are useful in the TX of HTN & BPH?
doxazosin & terazosin
26
What type of drug is Tamsulosin (Flomax) and what is it used for?
It is a specific prostatic α1A antagonist for treatment of signs & symptoms of BPH
27
What is the mechanism of action of ACE Inhibitors?
The ACE inhibitors are orally effective agents that competitively but incompletely inhibit angiotensin I converting enzyme, decreasing the availability of angiotensin II and, secondary to decreased angiotensin II, preventing the release of aldosterone. Decreasing the availability of angiotensin II results in the decreased release of aldosterone. Aldosterone not only causes sodium & water retention in the kidneys it also promotes cardiac remodeling and fibrosis.
28
What are some common side effects of Tamsulosin (Flomax)?
Common side effects include a headache, dizziness, orthostatic hypotension, rhinitis, and abnormal ejaculation.
29
What are the most prominet adverse effects of ACE inhibitors?
Cough, angioedema, 1st-dose hypotension, and **hyperkalemia**
30
What increases the risk of hyperkalemia in pts taking ACE inhibitors?
The ACE inhibitors may increase serum potassium levels but excessive potassium retention occurs only in patients with
* **impaired renal function**
* patients receiving **supplemental potassium**
* Pts on potassium-sparing diuretics.
31
What is the ACE Inhibitors prototype?
Captopril [Capoten] is the prototype. It is given TID 1 hour before meals. It may cause a decrease in the ability of the patient to taste (dysgeusia). Some reports attribute this to a specific moiety in captopril but “taste alteration” is listed as a side effect with other ACE inhibitors.
32
What type of drug is nitroprusside sodium (Nipride) and what is it's MOA?
* **Type:** It is a vasodilator used for HTN urgencies
* **MOA:** Nitroprusside is a potent intravenous agent that causes relaxation of vascular smooth muscle of peripheral arteries and veins.
33
What is the indication for using nitroprusside sodium (Nipride)?
It is indicated for immediate reduction of blood pressure of patents in hypertensive crises and for production of controlled hypotension to reduce bleeding during surgery.
34
What are the s/x of Nitroprusside sodium (Nipride)?
excessive hypotension, cyanide poisoning (rare), thiocynate toxicity, may cause retention of sodium and water (use Lasix).
35
What type of drug is Hydralazine and what is its MOA?
* **Type:** Vasodilator
* **MOA:** Produce a peripheral vasodilating effect through direct relaxation of vascular smooth muscle (with little effect on venous capacitance vessels). The exact mechanism is not clear.
36
What is the indication for using hydralazine?
indicated for the treatment of primary hypertension **(usually considered a 3rd step drug because of reflex tachycardia & salt & water retention.)** It is also indicated to produce afterload reduction in patients with CHF.
37
What are the s/x of hydralazine?
headache, anorexia, nausea, vomiting, diarrhea, hypotension, palpitations, tachycardia, edema, and angina pectoris. Patients should be informed about the symptoms of hypotension (lightheadedness, dizziness) and told to sit or lie down if these occur.
38
What are the endings of common ACE inhibitors & ARBs?
ACE inhibitors = -pril
ARBs = -sartan
39
What type of drug is Losartan (Cozzar) and what is its MOA?
* **Type:** Angiotensin II receptor blocker
* **MOA:** iIt s a selective angiotensin II receptor type 1 blocker. It prevents angiotensin-induced vasoconstriction & release of aldosterone as well as other known effects of angiotensin
## Footnote
**This is the prototype drug for this class**
40
What are the indications for using Losartan (Cozzar)?
It is approved for treatment of hypertension, heart failure, and diabetic nephropathy and to reduce the risk for stroke in patients with hypertension and left ventricular hypertrophy
41
What are the s/x of using Losartan (Cozzar)?
asthenia/fatigue, edema/swelling, abdominal pain, nausea, headache, & pharyngitis. **Unlike ACE inhibitors, losartan does not cause** **cough** **or angio edema**
42
What type of drug is Verapamil and what is its MOA?
* **Type:** Calcium Channel Blocker
* **MOA:** It produces a blockade of calcium channels resulting in a decreased rate of SA depolarization is largely dependent blockers relax arterial smooth muscle but have little effect on most venous beds (hence, theoretically, do not affect cardiac preload significantly).
43
What are the indications for using verapamil?
1. **SVT -** it is effective in terminating paroxysmal supraventricular tachycardia by delaying conduction of the cardiac impulse through the AV node.
2. **Angina pectoris -** Verapamil (PO or IV), diltiazem (PO) or nifedipine and amlodipine (PO) are equally effective
3. **Primary HTN -** All are equally effective in lowering blood pressure but a significant advantage over conventional antihypertensive drugs is debated. **This drug may decrease HR and CO**
44
What type of drug is Nifedipine (Procardia) and what is its MOA?
* **Type:** Vasodilator
* **MOA:** Blocks calcium channels (CC) in vascular smooth muscle promoting vasodilation. Nifedipine has little effect on the SA or AV node therefore acts primarily as a vasodilator. As a result it is not used to treat dysrhythmias, does not cause cardiac suppression and is less likely to exacerbate preexisting cardiac disorders. Prompt release formulations lead to rapid increase in drug concentration and short duration
45
What are the s/x of using Nifedipine (Procardia)?
* Flushing, dizziness, HA, peripheral edema, gingival hyperplasia, many also have a risk of chronic eczema in older adults, **reflex tachycardia (it increases cardiac oxygen demand and cause increased pain in angina patients)**.
* To decrease reflex tachycardia nifedipine can be combined with a beta blocker (i.e. metoprolol). Rarely causes constipation
* **Administration with grapefruit juice has caused excessive hypotension.**
46
What type of drug is propranolol and what is its MOA?
* It is a nonselective beta blocker that lacks ISA (it blocks beta 1 and beta 2 receptors equally
* **It decreases HR and cardiac output**, especially during exercise or in the presence of increased sympathetic activity. Concomitant block of b2 receptors **results in increased peripheral vascular resistance including coronary vascular** **resistance,** **but decreased heart rate & myocardial contractility predominate**, thus propranolol may relieve myocardial ischemia even though drug-induced increases in coronary vascular resistance decrease coronary blood flow. Slowing of heart failure-induced tachycardia improves cardiac output.
47
What is the prototype drug for non-selective betablockers?
Propanolol
48
What are the indications for propranolol?
* Hypertension
* Angina pectoris
* supraventricular arrhythmias - prolongs effective refractory period & slows AV conduction
* ventricular arrhythmias; PVCs;
* digitalis-induced tachyarrhythmias
* resistant tachyarrhythmias; sinus tachycardia; myocardial infarction;
* pheochromocytoma; hypertrophic aortic stenosis; essential tremors;
* migraine headache prophylaxis (80 mg/d in divided doses or 80 mg LA qd
49
What is the prototype drug for selective betablockers?
Metoprolol
50
What are the two beta-blockers that also block alpha receptors?
* However, **labetalol** decreases blood pressure more promptly than other beta-blockers, is equally effective in black and white patients, and does not affect serum lipids. They are indicated for the treatment of hypertension and CHF.
* **Carvedilol** is less likely to interfere with glycemic control in patients with type 2 diabetes and hypertension than is metoprolol. (Carvedilol is # 49 in top 50 prescribed drugs in 2013)
51
What are some s/x of using spironolactone in males?
Spironolactone interferes with synthesis of testosterone and may increase formation of estradiol from testosterone, thus leading to endocrine abnormalities such as impotence, gynecomastia, and decreased libido in 50% of males
52
What type of drug is atorvastatin (Lipitor) and what is its MOA?
* **Type:** Anti-hyperlipidemic
* **MOA:** Atorvastatin is a selective, competitive inhibitor of HMG-CoA reductase, the ratelimiting enzyme that converts 3-hydroxy-3-methylglutaryl-coenzyme A to mevalonate, a precursor of sterols, including cholesterol
53
What labs do you want to follow prior to starting and during Statin medication treatment?
Labels have been revised to remove the need for routine periodic monitoring of liver enzymes (ALT & AST) in patients taking statins. The labels now recommend that liver enzyme tests should be performed before starting statin therapy and as clinically indicated thereafter. FDA has concluded that serious liver injury with statins is rare and unpredictable in individual patients, and that routine periodic monitoring of liver enzymes does not appear to be effective in detecting or preventing serious liver injury.
54
What type of drug is Niacin and what is its MOA?
* Inhibits lipoprotein synthesis
* Niacin is a water-soluble “B” vitamin that is thought to inhibit the production of VLDL, the immediate precursor of LDL. Low doses (1.5-2 g/d) lower triglycerides and increase HDL; higher doses are required for substantial reductions of LDL cholesterol.
55
What are the s/x of using Niacin?
* Flushing (with warmth & pruritus), headache, GI distress (nausea; diarrhea), blurred vision, **glucose intolerance**, hyperuricemia, and orthostatic hypotension
* **Niacin causes insulin resistance. Diabetes is a relative (not absolute) contraindication to the use of niacin**
56
What type of drug is Ezetimibe (Zetia) and what is its MOA?
* **Type:** Inhibitor of cholesterol absorption
* **MOA: It i**s absorbed and extensively conjugated to a pharmacologically active glucuronide and is excreted both in the bile and kidneys. The majority of the drug is secreted via the biliary system where it binds to the intestinal cell wall and **inhibits the enzyme system that is important in the absorption of cholesterol. **
57
What are the indications for using Ezetimibe (Zetia)?
* It inhibits the cholesterol transport system located within intestinal cell walls. It does not impair the reabsorption of bile acids or other drugs.
* It is indicated (2nd line drug) for the treatment of hypercholesterolemia alone or in combination with HMG-CoA reductase inhibitors (statin drugs)
58
What happens when ezetimibe and statins are combined for the treatment of hypercholesterolemia?
the combination of ezetimibe and the statins significantly lowered LDL-cholesterol to a greater extent than the statin alone (but did not improve morbidity).
59
What type of drug is nitroglycerin and what is its MOA?
* **Type:** Nitrate
* **MOA:** Nitrates are thought to release nitric oxide, which stimulates guanylate cyclase within the smooth muscle cell producing relaxation by dephosphorylation (by cGMP) of the myosin light chain. All smooth muscle, including the bronchi, GI & GU tract, are affected but the brief effect limits usefulness in these areas.
* The predominate action of the nitrates in angina is the reduction of myocardial oxygen demand mainly by venodilation (reduced preload).
* Nitroglycerin is readily absorbed from the sublingual mucosa. It is also absorbed through the skin, which provides a gradual release of the drug that reaches target organs before hepatic inactivation. **Given orally, the nitrates have a large first pass effec**t
* **Nitroglycerin has a short half-life (1-4 min) and is quickly metabolized in the liver**
60
What are the s/x of using nitroglycerin?
Nausea & vomiting, headache (may be severe and persistent but tolerance often develops), tachycardia, and hypotension (exacerbated by alcohol and other vasodilators [e.g., nifedipine, sildenafil]).
61
What are the recommendations when using nitroglycerin for chest pain?
* Traditionally, failure to respond to three tablets given 5 min apart suggests a myocardial infarction and requires hospitalization.
* Note: **The American College of Cardiology suggests take one dose sublingually for chest discomfort. I**f pain is unimproved in 5 minutes, call 911. Transport via EMS usually generates better assistance than self transportation.
62
Why are beta-blockers used for the treatment of angina?
* Beta blockers are considered by some to be a drug of choice in unstable angina except in asthmatic patients (use verapamil or amlodipine) but should not be used in vasospastic angina.
* **By blocking beta1 receptors in the heart the beta-blockers reduce heart rate and contractility of the myocardium, thus reducing the** **work load** **of the heart and myocardial oxygen demand (improving symptoms).**
63
What type of drug is sildenafil (Viagra) and what is its MOA?
* **Type:** Vasodilator for erectile dysfunction
* **MOA:** selective inhibitors of the specific enzyme phosphodiesterase type 5 [PDE5] that is responsible for degradation of cyclic guanosine monophosphate (cGMP) in the corpus cavernosum. When sexual stimulation causes local release of nitric oxide, **it activates cyclic guanosine monophosphate (cGMP), which causes vascular smooth muscle relaxation and inflow of blood in the corpus cavernosum (an erection is produced)**
64
What are the s/x of using Viagra, Cialis, or Levitra?
* Headache, flushing, and back pain
* **They are contraindicated in patients concurrently using organic nitrates and alpha-1 antagonists including tamsulosin (potentiates hypotensive effects).**
65
What are the indications for Sildenafil (Viagra)?
* It can be used to treat erectile dysfunction
* Sildenafil inhibits hypoxic pulmonary vasoconstriction and is useful in various forms of pulmonary artery hypertension
66
What are some drugs that diminish the effectiveness of furosemide (Lasix)?
Loop diuretics produce some of their effect by inducing the synthesis of renal prostaglandins in the normal kidney. loop diuretic will be diminished if a cyclooxygenase inhibitor [e.g. NSAID] is administered concurrently although this effect is minimal in normal subjects.
67
What is the first choice drug for management of patients with heart failure?
**ACE inhibitor alone may be all that is needed for AHA class I HF.** If symptoms of overload occur, a diuretic should be added (NYHA class II). Some practitioners consider addition of beta blockers as first-line therapy. The AHCPR guidelines state that digoxin should be used in patients with severe HF and should be added to the medical regimen of patients with mild or moderate failure who remain symptomatic after optimal management with ACEI and diuretics.
68
What type of drug is Digoxin and what is its MOA?
* **Type:** Digitalis glycoside
* **MOA:** The main pharmacodynamic property of digitalis is its ability to increase the force of myocardial contractions (positive inotropic effect). **In CHF this results in** **increased** **cardiac output with** **decrease** **in heart size, blood volume, and venous pressure; and diuresis resulting in relief of edema.**
69
What are the indications of digoxin?
* **Congestive heart failure**, - 2nd step drug. (Benefits of digoxin are limited to symptom reduction; it does not prolong survival.) Because benefits of digoxin therapy are limited to symptomatic relief, and because the risk of toxicity is substantial, digoxin is now considered a 2nd –line drug for treating HF.
* **Used to slow** the ventricular response rate in patients with **SVT, Afib, & Aflutter (Adenosine is preferred for treatment of paroxysmal atrial and AV nodal tachycardia).**
70
Why might digoxin be reduced in an elderly patient?
Hypokalemia and toxicity results from pts with decreased renal function. This is due to renal excretion of digoxin. Elderly are known for decreased renal function resulting in higher sensitivity. **Accordingly, dosage must be reduced if kidney function declines.** About 23% of of digoxin in plasma is bound to proteins, mostly albumin, with decreased albumin in elderly, this results in higher amounts of free drug digoxin.
71
What are the signs and symptoms of Digoxin toxicity?
The most common early manifestations of digoxin toxicity are:
* Anorexia, nausea, and vomiting (but are also associated with CHF).
* Diarrhea and GI discomfort may occur (direct effect of digitalis on GI smooth muscle as well as CNS actions).
* **Headache****, fatigue, visual disturbances (blurred vision; green or yellow halos around lights) and drowsiness may occur early.**
* Dysrhythmias (coupled beats [bigeminy; trigeminy] and increased automaticity) and delayed conduction through the AV node (heart block) also occur.
* **Ventricular fibrillation is the most common cause of death from digitalis toxicity.**
72
Why does the heart rate slow w/ digoxin in a person w/ CHF?
Autonomic effects of cardiac glycosides include increased parasympathetic system activity due to sensitization of arterial baroreceptors (carotid sinus; via action on ion transport in nerve terminals) and activation of vagal nuclei & nodose ganglion in the CNS. **Enhanced parasympathetic (PNS), activity produced by therapeutic concentrations of digitalis, results in decreased activity of the SA node and prolongation of the effective refractory period and thus the time for conduction of cardiac impulses through the AV node**. Manifestation of these effects is a slowed heart (especially in atrial fibrillation).
73
What drugs increase the risk of arrhythmias with digoxin without a change in blood levels of digoxin?
By lowering serum potassium, thiazides (and other potassium-losing diuretics) increase the incidence of digoxin-induced cardiac arrhythmias without altering the digoxin blood level.
74
What type of drug is heparin and what is its MOA?
* **Type:** Anticoagulant
* **MOA:** The heparin molecule that binds to antithrombin and enhances its ability to accelerate the formation or hasten the activity of antithrombin III --\> It prevents the conversion of fibrinogen to fibrin (which is used to form clots)
## Footnote
**It is considered one of the 1st line drugs for treatment of deep vein thrombosis or pulmonary embolism**
75
What is the onset of action for heparin?
* The onset of anticoagulant effect is almost instantaneous following IV injection and occurs 20-30 minutes after subcutaneous injection.
* **Durations are prolonged in liver and kidney dysfunction**. Heparin is metabolized by the liver to inactive metabolites that are eliminated by the kidneys.
76
What labs are important to monitor with heparin?
Heparin effect is monitored by the **activated partial thromboplastin time (aPTT).** It does affect prothrombin time but not bleeding time. The goal of therapy is an aPTT value of 1.5 to 2 times (some say 2-2.5) the normal value of 30-40 sec. For anti-Xa activity the range of 0.3-0.7 units/mL should be obtained.
77
What is the antidote for heparin?
* **The specific antidote to heparin is protamine sulfate.**
* Protamine sulfate is a strongly basic low-molecular weight protein that ionically forms a stable salt with heparin, neutralizing the anticoagulant effect of both heparin and protamine.
* Its half-life is shorter than heparin and may have to be given repeatedly (given slowly IV over 10 min). 1 mg neutralizes about 100 U of heparin
78
What type of drug is Warfarin (Coumadin) and what is its MOA?
* **Type:** Oral Anticoagulant
* **MOA:** The anticoagulant effect is due to interference with hepatic synthesis of vitamin K-dependent clotting factors (factors II, VII, IX, and X). Warfarin inhibits a subunit of vitamin K epoxide reductase, preventing regeneration of vitamin K epoxide, an essential cofactor in the synthesis of clotting factors
79
What is the onset of action of Warfarin (Coumadin)?
The anticoagulant effect of warfarin is delayed for 8-12 hours, reflecting the onset of inhibition of synthesis of clotting factors and the elimination half-times of previously formed clotting factors which are not altered by the oral anticoagulant. Peak effects of warfarin do not occur for 36-72 hours. Because the effect of warfarin is delayed, patients who need anticoagulant therapy are usually started on both heparin and warfarin and the heparin continued until full effect of warfarin is attained (usually at least 5 days). Because heparin affects the PT, blood is drawn for a PT after heparin has lost its effect (trough level).
80
What labs are important to monitor for Warfarin (Coumadin)?
* The prothrombin time (PT) varies from hospital to hospital depending on the reagent used but is usually **15 to 20 seconds.**
* INR which is the prothrombin time ratio raised to a power of the WHO International Sensitivity Index assigned to thromboplastin. **The desired INR value is 2.0 to 3.0 for most indications,** with the exception of high-risk mechanical prosthetic valves in which the target INR value is 2.5 to 3.5.
81
What is the antidote for Warfarin (Coumadin)?
* The antidote for warfarin is vitamin K1 (phytonadione; Aqua Mephyton), however the onset of action is slow (several hours with 12-24 h for maximum effect) and vitamin K, in doses \>0.5 mg. IV or 3 mg.
* Administration of vitamin K for anticoagulant reversal may cause transient warfarin resistance for up to 3 weeks.
82
What is the desired HgB range for patients with anemia who also have chronic renal failure?
In patients with anemia of CRF, Erythropoietin can increase the risk of serious CV events and death if hemoglobin levels are driven too high. The goal is to reach a target hemoglobin range of 10-11 g/dL. If hemoglobin rises above 11gm/dL (for pt on dialysis) or 10gm/dL (pt not on dialysis), epoetin should be temporarily withheld.
83
What type of drug is Dabigatran and what is its moa?
* **Type:** Oral Anticoagulants
* **Moa:** It is an oral direct thrombin inhibitor (binds with and inhibits thrombin) and has been approved for prevention of thromboembolic stroke in patients with non-valvular atrial fibrillation
84
What is the antidote for danigatran?
darucizumab [Praxbind] is approved for urgent reversal of the anticoagulant effect of dabigatran, a direct thrombin inhibitor,
85
How does Dabigatran differ from warfarin?
* Compared with warfarin the oldest oral anticoagulant; dabigatran has a rapid onset (hours), no need to monitor anticoagulation, few drug-food interaction; lower risk of major bleeding and a fixed dose since responses are predictable. Dabigatran has limited clinical experience.
* Warfarin on the other hand, has decades of clinical experience, delayed onset (days), blood test required (PT (INR)), no fixed dose, significant risk of hemorrhage, and many food-drug interactions. Antidote is available for overdose
86
What type of drug is Clopidogrel (Plavix) and what is its moa?
* **Type:** Oral Anti-platelet drug
* **MOA:** It inhibits binding of ADP to platelet receptors and inhibits platelet aggregations irreversibly modifying the P2Y12 platelet receptor. It increases bleeding times and reduces blood viscosity
**Clopidogrel is listed by some as an** **alternate** **to aspirin as 1st line therapy for prevention of ischemic stroke; others list it as a 2nd line drug because of its cost**
87
What is the Most common adverse effect of using thrombolytic drugs?
Bleeding, the most serious risk being intracranial hemorrhage
88
What is the drug of choice for SVT?
* **Adenosine** inhibits particularly SA node and AV node conduction. A bolus dose directly inhibits AV node conduction and may cause a very brief AV block (it does not have negative inotropic effects). **Its major use is in the acute treatment of supraventricular arrhythmias that involve reentry.**
* It is considered a drug of choice for paroxysmal supraventricular tachycardias because of its high efficacy (95%) and very short duration (half-life \< 10 sec.). ACLS 2000 recommendations state that adenosine is the drug of choice for termination of narrow complex PSVT
89
What type of drug is quinidine and what is it moa?
**Type:** Antiarrhythmic; sodium channel blocker
**MOA:** Quinidine blocks sodium channels, slows conduction in the AV node, and reduces automaticity in the ventricles. It directly depresses excitability of most cardiac tissue and slows impulse conduction (by increasing the refractory period). It decreases sodium conductance, resulting in slowing of conduction velocity, and decreases membrane responsiveness.
90
What are the indications for using quinidine?
Quinidine is a broad-spectrum antiarrhythmic used to treat acute & chronic atrial, supraventricular, and ventricular dysrhythmias and to suppress PVCs. When quinidine, procainamide or disopyramide are given to a patient with atrial flutter, the ventricular rate may increase as the atrial rate slows. An AV-nodal blocking agent such as digoxin, verapamil, or a beta-blocker is usually given first. **Katzung states quinidine is seldom used because of cardiac and extracardiac adverse effects.**
91
What type of drug is Amiodarone and what is its MOA?
* **Type:** Potassium Channel blocker
* **MOA:** They prolong the duration of action potential of atrial & ventricular muscle without altering resting membrane potential, increasing the refractory period hence causing QT prolongation. They depress SA and AV node function.
92
What are the major physiological side effects of using Amiodarone?
* The most common side effects of amiodarone IV are **hypotension (15-20%) and bradycardia (5%).**
* With oral administration, adverse effects occur in about 75% of patients and may result in corneal deposits and impaired vision, pulmonary fibrosis, constipation, and discoloration of the skin.
* **Because it contains 38% iodine, it may cause hypothyroidism (more common) or hyperthyroidism.**
* The package brochure has a major warning about its use only in life-threatening arrhythmias because of potentially fatal toxicities, **the most important of which is pulmonary hypersensitivity pneumonitis, fatal about 10% of the time.**
93
When is it indicated to use ferrous sulfate orally for the treatment of anemia?
The only clinical indication for iron therapy is treatment or prevention of iron deficiency anemia.
94
Which populations tend to get iron deficiency anemia and what are the s/x of this disease?
* Iron deficiency anemia is seen most commonly in infants, especially premature, children during rapid growth periods, and pregnant and lactating women.
* **The most common cause is blood loss. Women lose about 30 mg of iron with each menstrual period.**
* **Iron deficiency leads to pallor, fatigue, dizziness, and exertional dyspnea.**
* Ingestion of iron is of value only when the iron stores are depleted.
* When iron is administered to a person with hypochromic anemia, the hematocrit and hemoglobin levels begin to increase in 3 days but maximum response does not occur for 2-4 weeks.
95
What are the s/x of ferrous sulfate?
* Local effects of orally administered iron reflect its action as an irritant and astringent, causing nausea vomiting, constipation, or diarrhea, and abdominal distress.
* **Side effects are related to the dose of elemental iron.**
* **The stools may be dark** because of fecal elimination of iron. (Black stool caused by iron must be differentiated from black tarry stools that are a result of gastric bleeding).
* **Iron is best absorbed if taken on an empty stomach**, however gastric upset may be diminished by giving iron immediately after a meal or by switching to an iron preparation that contains less elemental iron. (Amount of elemental iron in a 325 mg tablet: ferrous fumarate 106 mg; ferrous sulfate 65 mg; ferrous gluconate 36 mg.)
96
What are some toxicities that can occur when ingesting too much iron?
* Acute toxicity occurs mainly in children who ingest iron tablets (as few as 10 tablets may be fatal). Urgent treatment of iron toxicity in children is necessary (whole bowel irrigation; deferoxamine).
* •ngestion of large amounts of oral iron causes necrotizing gastroenteritis, vomiting, abdominal pain, bloody diarrhea, shock, lethargy, and dyspnea. This may be followed by severe metabolic acidosis, coma, and death
97
What drugs interact with the absorption of iron?
* Antacids interfere with the absorption of iron.
* Iron may interfere with the absorption of tetracyclines and fluoroquinolones. High doses of zinc decrease the bioavailability of ferrous sulfate 56% (Nutrition 2007;23:292). Give iron separate from other drugs.
98
What drugs can be used to treat iron overload/toxicity?
* Deferasirox (Exjade) is an oral chelating agent for treatment of chronic iron overload due to blood transfusions. Doses of 20-30 mg/kg/d produced reductions in liver iron concentrations similar to those with deferoxamine.
* The tablets (125, 250 & 500 mg) are dissolved in a glass of water, orange juice, or apple juice and taken 30 minutes before eating. Common adverse effects were mainly GI in nature. The drug costs about $4600 for 30 days treatment.
* Deferiprone [Ferriprox tabs 500 mg) is an oral chelating agent used in the treatment of transfusion iron overload. Given 25 mg/kg tid, it is monitored by serum ferritin concentration and has a black box warning of causing agranulocytosis.
99
What are the recommendations for folic acid intake during pregnancy?
Pregnant women require increased folic acid intake (deficiency results in fetal neural tube defects, which occurs between day 21 and 28 after conception). The US Preventive Services Task Force recommends all women planning or capable of pregnancy take a daily supplement of 0.4 to 0.8 mg each day in addition to the folate they get from food (US Preventive Services Task Force.
