Deja Ch 6 CV, Renal Flashcards
1
Q
Describe what happens during each of the following phases of the cardiac action potential for fast-response fibers: Phase 0
A
Sodium ion channels open (inward) which leads to membrane depolarization.
2
Q
Describe what happens during each of the following phases of the cardiac action potential for fast-response fibers: Phase I
A
Sodium ion channels are inactivated; potassium ion channels (outward) are activated; chloride ion channels (inward) are activated.
3
Q
Describe what happens during each of the following phases of the cardiac action potential for fast-response fibers: Phase II
A
Plateau phase; slow influx of calcium ion balanced by outward potassium ion current (delayed rectifier current IK)
4
Q
Describe what happens during each of the following phases of the cardiac action potential for fast-response fibers: Phase III
A
Repolarization phase; outward K+ current increases and inward calcium ion current decreases
5
Q
Describe what happens during each of the following phases of the cardiac action potential for fast-response fibers: Phase IV
A
Membrane returns to resting potential.
6
Q
On what phase(s) of the cardiac action potential do amiodarone and sotalol work?
A
Phase 0 and phase III
7
Q
On what phase(s) of the cardiac action potential do lidocaine, flecainide, and quinidine work?
A
Phase 0
8
Q
On what phase(s) of the cardiac action potential do β-blockers work?
A
Phase II and phase IV
9
Q
What is responsible for maintaining the electrochemical gradient at resting membrane potential?
A
Na+/K+-A TPase
10
Q
What ion current is responsible for the depolarization of sinoatrial (SA) and atrioventricular (AV) nodal fibers?
A
Calcium ion (inward)
11
Q
What ion current is responsible for the repolarization of SA and AV nodal fibers?
A
Potassium ion (outward)
12
Q
How does phase IV of the action potential in slow-response fibers (SA and AV nodes) differ from that of fast- response fibers?
A
Slow-response fibers display automaticity (ability to depolarize spontaneously); rising phase IV slope of the action potential = pacemaker potential
13
Q
What ion current is responsible for the “pacemaker current” (rising slope of phase IV) in slow-response fibers?
A
Sodium ion (inward); calcium ion (inward); potassium ion (outward)
14
Q
The pacemaker of the heart has the fastest uprising phase IV slope; where is this pacemaker in nondiseased patients?
A
SA node
15
Q
Where is the SA node located?
A
Right atrium
16
Q
How do the effective refractory period (ERP) and relative refractory period (RRP) differ from each other?
A
No stimulus, no matter the strength, can elicit a response with fibers in the ERP, whereas a strong enough stimulus will elicit a response with fibers in the RRP.
17
Q
What are the three states the voltage-gated Na+ channel exists in?
A
- Resting state 2. Open state 3. Inactivated state
18
Q
What state(s) of the voltage-gated Na+ channel is/are most susceptible to drugs?
A
Open state; inactivated state
19
Q
What two types of gates does the voltage-gated Na+ channel have?
A
- M (activating) 2. H (inactivating)
20
Q
Why is the rate of recovery from an action potential slower in ischemic tissue?
A
The cells are already partly depolarized at rest.
21
Q
What class of antiarrhythmic agents has membrane-stabilizing effects?
A
β-Blockers
22
Q
Antiarrhythmic agents are grouped into four classes according to what classification system?
A
Vaughn-Williams classification
23
Q
Give the general mechanism of action for each of the following antiarrhythmic drug classes: Class I
A
Na+ channel blockers
24
Q
Give the general mechanism of action for each of the following antiarrhythmic drug classes: Class II
A
β-Blockers
25
Give the general mechanism of action for each of the following antiarrhythmic drug classes: Class III
K+ channel blockers
26
Give the general mechanism of action for each of the following antiarrhythmic drug classes: Class IV
Ca++ channel blockers
27
Class I antiarrhythmics are further subdivided into what classes?
la; Ib; Ic
28
Give examples of antiarrhythmic drugs in class la:
Quinidine (antimalarial/antiprotozoal agent); procainamide; disopyramide
29
Give examples of antiarrhythmic drugs in class Ib:
Lidocaine; mexiletine; tocainide; phenytoin
30
Give examples of antiarrhythmic drugs in class Ic:
Encainide; flecainide; propafenone; moricizine
31
Give examples of antiarrhythmic drugs in class II:
Propranolol; esmolol; metoprolol
32
Give examples of antiarrhythmic drugs in class III:
Amiodarone; sotalol; ibutilide; dofetilide
33
Give examples of antiarrhythmic drugs in class IV:
Verapamil; diltiazem
34
Name three antiarrhythmic drugs that do not fit in the Vaughn-Williams classification system:
1. Digoxin 2. Adenosine 3. Magnesium
35
Magnesium is used to treat what specific type of arrhythmia?
Torsades de pointes (polymorphic ventricular tachycardia)
36
Adenosine is used to treat what types of arrhythmias?
Paroxysmal supraventricular tachycardia (PSVT), specifically narrow complex tachycardia or supraventricular tachycardia (SVT) with aberrancy; AV nodal arrhythmias (adenosine causes transient AV block). Note: synchronized cardioversion and not adenosine should be used on symptomatic patients or unstable tachycardia with pulses.
37
Where anatomically should the IV be placed to administer adenosine?
As close to the heart as possible, that is, the antecubital fossa since adenosine has an extremely short half- life. Adenosine rapid IV push should be followed immediately by a 5-10 cc (mL) flush of saline to facilitate its delivery to the heart.
38
What is the mechanism of action of adenosine?
Stimulates alpha1-receptors which causes a decrease in cyclic adenosine monophosphate (cAMP) (via Grcoupled second messenger system); increases K+ efflux leading to increased hyperpolarization; increases refractory period in AV node
39
What are the adverse effects of adenosine?
Flushing; chest pain; dyspnea; hypotension
40
What 2 drugs can antagonize the effects of adenosine?
1. Theophylline 2. Caffeine
41
How is adenosine dosed?
6 mg initially by rapid IV push; if not effective within 1-2 minutes, give 12 mg repeat dose (follow each bolus of adenosine with normal saline flush). The 12 mg dose may be repeated once.
42
What is the most deadly ion that can be administered?
Potassium ion
43
What ECG changes are seen in hyperkalemia?
Flattened P waves; widened QRS complex; peaked T waves; sine waves; ventricular fibrillation
44
What ECG changes are seen in hypokalemia?
Flattened or inverted T waves; U waves; ST-segment depression
45
What do class la antiarrhythmics do to the Action potential duration?
Increase
46
What do class la antiarrhythmics do to the ERP
Increase
47
What do class la antiarrhythmics do to the Conduction velocity
Decrease
48
What do class la antiarrhythmics do to the Phase IV slope
Decrease
49
What do class Ib antiarrhythmics do to the Action potential duration
Decrease
50
What do class Ib antiarrhythmics do to the ERP
Little or no change
51
What do class Ib antiarrhythmics do to the Conduction velocity
Decrease (primarily in ischemic tissue)
52
What do class Ib antiarrhythmics do to the Phase IV slope
Decrease
53
What do class Ic antiarrhythmics do to the Action potential duration
Little or no change
54
What do class Ic antiarrhythmics do to the ERP
Little or no change
55
What do class Ic antiarrhythmics do to the Conduction velocity
Decrease
56
What do class Ic antiarrhythmics do to the Phase IV slope
Decrease
57
Drugs that affect the strength of heart muscle contraction are referred to as what types of agents?
Inotropes (either positive or negative)
58
Drugs that affect the heart rate are referred to as what types of agents?
Chronotropes (either positive or negative)
59
Drugs that affect AV conduction velocity are referred to as what types of agents?
Dromotropes (either positive or negative)
60
QT interval prolongation, and therefore torsades de pointes, is more likely to occur with what two classes of antiarrhythmics?
1. la 2. Ill
61
Which class la antiarrhythmic also blocks α-adrenergic and muscarinic receptors, thereby potentially leading to increased heart rate and AV conduction?
Quinidine
62
What are the adverse effects of quinidine?
Tachycardia; proarrhythmic; increased digoxin levels via protein-binding displacement; nausea; vomiting; diarrhea; cinchonism
63
What is cinchonism?
Syndrome that may include tinnitus; high-frequency hearing loss; deafness; vertigo; blurred vision; diplopia; photophobia; headache; confusion; delirium
64
What are the adverse effects of procainamide?
Drug-induced lupus (25%-30% of patients); proarrhythmic; depression; psychosis; hallucination; nausea; vomiting; diarrhea; agranulocytosis; thrombocytopenia; hypotension
65
What drugs can cause drug-induced lupus?
Procainamide; isoniazid (INH); chlorpromazine; penicillamine; sulfasalazine; hydralazine; methyldopa; quinidine; phenytoin; minocycline; valproic acid; carbamazepine; chlorpromazine
66
Which class la antiarrhythmic can cause peripheral vasoconstriction?
Disopyramide
67
What are the adverse effects of disopyramide?
Anticholinergic adverse effects, such as urinary retention; dry mouth; dry eyes; blurred vision; constipation; sedation
68
True or False? Lidocaine is useful in the treatment of ventricular arrhythmias?
TRUE
69
True or False? Lidocaine is useful in the treatment of atrial arrhythmias?
FALSE
70
True or False? Lidocaine is useful in the treatment of AV junctional arrhythmias?
FALSE
71
What are the adverse effects of lidocaine?
Proarrhythmic; sedation; agitation; confusion; paresthesias; seizures
72
What class Ib antiarrhythmic is structurally related to lidocaine?
Mexiletine
73
What class Ib antiarrhythmic can cause pulmonary fibrosis?
Tocainide
74
Propaf enone, even though a class Ic antiarrhythmic, exhibits what other type of antiarrhythmic activity?
β-Adrenergic receptor blockade
75
What famous trial showed that encainide and flecainide increased sudden cardiac death in postmyocardial infarction (MI) patients with arrhythmias?
Cardiac Arrhythmia Suppression Trial (CAST)
76
Sotalol, even though a class III antiarrhythmic, exhibits what other type of antiarrhythmic activity?
β-Adrenergic receptor blockade
77
Even though this agent is labeled as a Vaughn-Williams class III antiarrhythmic, it displays class I, II, III, and IV antiarrhythmic activity.
Amiodarone
78
What is the half-life of amiodarone?
40 to 60 days
79
What are the adverse effects of amiodarone?
Pulmonary fibrosis; tremor; ataxia; dizziness; hyperthyroidism; hypothyroidism; hepatotoxicity; photosensitivity; blue skin discoloration; neuropathy; muscle weakness; proarrhythmic; corneal deposits; lipid abnormalities; hypotension; nausea; vomiting; congestive heart failure (CHF); optic neuritis; pneumonitis; abnormal taste; abnormal smell; syndrome of inappropriate secretion of antidiuretic hormone (SIADH)
80
How should patients on amiodarone therapy be monitored?
ECG; thyroid function tests (TFTs); pulmonary function tests (PFTs); liver function tests (LFTs); electrolytes; ophthalmology examinations
81
Verapamil should not be given in what types of arrhythmias?
Wolff-Parkinson-White (WPW) syndrome; ventricular tachycardia
82
What are the adverse effects of verapamil?
Drug interactions; constipation; hypotension; AV block; CHF; dizziness; flushing
83
Digoxin is used to control ventricular rate in what types of arrhythmias?
Atrial fibrillation; atrial flutter
84
Digoxin-induced arrhythmias are treated by what drugs?
Lidocaine; phenytoin
85
Digoxin does what to AV conduction velocity
Decreases (negative dromotrope)
86
Digoxin does what to Strength of heart muscle contraction
Increases (positive inotrope)
87
Digoxin does what to Heart rate
Decreases (negative chronotrope)
88
What does QTc stand for?
Corrected QT interval
89
How is QTc calculated?
(QT)/(square root of R to R interval)
90
Why must the QT interval be corrected?
The QT interval is dependent on heart rate, so higher heart rates will display shorter QT intervals on ECG. It is corrected to remove the variable of the heart rate.
91
What is the normal value for QTc?
Less than 440 milliseconds
92
What does a long QT interval put a patient at risk for?
Torsades de pointes, a ventricular arrhythmia that can degenerate into ventricular fibrillation
93
What is the cardiac output equation?
Cardiac output (CO) = heart rate (HR) × stroke volume (SV)
94
What is normal CO?
5 L/min
95
What is the most common cause of right-sided heart failure?
Left-sided heart failure
96
Name three compensatory physiologic responses seen in congestive heart failure (CHF):
1. Fluid retention 2. Increased sympathetic drive 3. Hypertrophy of cardiac muscle
97
Define preload:
The pressure stretching the ventricular walls at the onset of ventricular contraction; related to left ventricular end-diastolic volume/pressure
98
Define afterload:
The load or force developed by the ventricle during systole
99
What drugs are used to decrease preload?
Diuretics; vasodilators; angiotensin-converting enzyme inhibitors (ACEIs); angiotensin II receptor blockers (ARBs); nitrates
100
What drugs are used to decrease afterload?
Vasodilators; ACEIs; ARBs; hydralazine
101
What drugs are used to increase contractility?
Digoxin; phosphodiesterase inhibitors (amrinone and milrinone); β-adrenoceptor agonists
102
What is the mechanism of action of digoxin?
Inhibition of the Na+/K+-ATPase pump which leads to positive inotropic action (via increased intracellular sodium ions that exchanges with extracellular calcium ions; resulting increase in intracellular calcium ions leads to increased force of contraction)
103
What are the two digitalis glycosides?
1. Digoxin 2. Digitoxin
104
What are the adverse effects of digoxin?
Arrhythmias; nausea; vomiting; anorexia; headache; confusion; blurred vision; visual disturbances, such as yellow halos around light sources
105
What electrolyte disturbances predispose to digoxin toxicity?
Hypokalemia; hypomagnesemia; hypercalcemia
106
Digoxin can cause what types of arrhythmias?
Supraventricular tachycardias; AV nodal tachycardias; AV block; ventricular tachycardias; ventricular fibrillation; complete heart block
107
Can digoxin be used in WPW syndrome?
No. Since digoxin slows conduction through the AV node, the accessory pathway present in WPW is left unopposed, leading to supraventricular tachycardias and atrial arrhythmias.
108
How is digoxin toxicity treated?
Correction of electrolyte disturbances; antiarrhythmics; anti-digoxin Fab antibody (Digibind)
109
What drugs can increase digoxin concentrations?
Quinidine; amiodarone; erythromycin; verapamil
110
What drugs can decrease digoxin concentrations?
Loop diuretics; thiazide diuretics; corticosteroids
111
Does digoxin therapy in CHF lead to prolonged survival?
No. It is of symptomatic benefit only, improving quality, but not necessarily duration of life.
112
What classes of medications have been shown to increase survival in CHF patients?
ACEs/ARBs; β-blockers
113
How does dobutamine work in CHF?
β-Adrenergic agonist (sympathomimetic that binds to (β1-adrenoceptors) that increases force of contraction
and vasodilation via increased cAMP
114
How do amrinone and milrinone work in CHF?
Inhibits phosphodiesterase (PDE) thereby increasing cAMP levels; increased cAMP leads to increased intracellular calcium; increased intracellular calcium leads to increased force of contraction; increased cAMP also leads to increased vasodilation
115
What are the side effects of the PDEIs?
Milrinone may actually decrease survival in CHF; amrinone may cause thrombocytopenia.
116
How do diuretics work in CHF?
Decrease in intravascular volume thereby decrease in preload; reduce pulmonary and peripheral edema often seen in CHF patients
117
How can increased sympathetic activity in CHF be counteracted?
β-Blockers
118
What two β-blockers have specific indications for the treatment of CHF?
1. Metoprolol 2. Carvedilol (mixed α-/β-blocker)
119
What is the mechanism of action of nesiritide?
Recombinant B-type natriuretic peptide that binds to guanylate cyclase receptors on vascular smooth muscle and endothelial cells, thereby increasing cyclic guanosine monophosphate (cGMP) levels; increased cGMP leads to increased relaxation of vascular smooth muscle
120
How do ACEIs work in CHF?
Inhibition of angiotensin-II (AT-II) production thereby decreasing total peripheral resistance (TPR) and thus afterload; prevents left ventricular remodeling
121
Define angina pectoris:
Chest pain resulting from a myocardial oxygen demand that is not met by adequate oxygen supply; seen in patient with myocardial ischemia
122
What type of angina is caused by spontaneous coronary vasospasm?
Prinzmetal (variant) angina
123
What type of angina is caused by atherosclerosis of coronary vessels and is precipitated by exertion?
Classic angina
124
What type of angina can be acute in onset and is caused by platelet aggregation?
Unstable angina
125
What two mechanistic strategies are used in the treatment of angina?
1. Increase oxygen supply to the myocardium 2. Decrease myocardial oxygen demand
126
What types of drugs can increase oxygen supply?
Nitrates; calcium channel blockers (CCBs)
127
What types of drugs can decrease oxygen demand?
Nitrates; CCBs; β-blockers
128
What is the drug of choice for immediate relief of anginal symptoms?
Sublingual nitroglycerin (NTG)
129
What is the mechanism of action of nitrates?
Nitrates form nitrites; nitrites form nitric oxide (NO); NO activates guanylyl cyclase to increase cGMP; increased cGMP leads to increased relaxation of vascular smooth muscle
130
How does cGMP lead to relaxation of vascular smooth muscle?
Causes dephosphorylation of myosin light chains
131
How do nitrates increase oxygen supply?
Dilation of coronary vessels which leads to increased blood supply
132
How do nitrates decrease oxygen demand?
Dilation of large veins which leads to preload reduction; decreased preload reduces the amount of work done by the heart; decreased amount of work results in decreased myocardial oxygen requirement
133
What are the adverse effects of nitrates?
Headache; hypotension; reflex tachycardia; facial flushing; metnemoglobinemia
134
Why must patients have at least a 10- to 12-hour "nitrate-free" interval every day?
Tolerance (tachyphylaxis) develops to nitrates if given on a continuous (around-the-clock) basis
135
Nitrates are contraindicated in patients taking any of what three medications?
1. Sildenafil 2. Vardenafil 3. Tadalafil
136
Methemoglobin formation, specifically by amyl nitrite, can be used to treat what type of poisoning?
Cyanide
137
What are the common formulations of nitrates?
NTG; isosorbide mononitrate; isosorbide dinitrate
138
What is the time to peak effect of sublingual NTG?
2 minutes
139
What is the dosing frequency of sublingual NTG during an anginal episode?
Every 5 minutes for a maximum of three doses
140
How do β-blockers work in the treatment of angina?
Inhibition of α1-adrenoceptors which leads to decreased CO, HR, and force of contraction, thereby reducing the workload of the heart and oxygen demand
141
Do α-blockers increase oxygen supply?
No
142
For each of the following CCBs, state whether their primary effects are on the myocardium or peripheral vasculature: Verapamil
Myocardium (greater negative inotropic effects)
143
For each of the following CCBs, state whether their primary effects are on the myocardium or peripheral vasculature: Dihydropyridines (DHP; nifedipine, amlodipine, felodipine, isradipine, nicardipine)
Peripheral vasculature (more potent vasodilators)
144
For each of the following CCBs, state whether their primary effects are on the myocardium or peripheral vasculature: Diltiazem
Myocardium
145
How do CCBs work in the treatment of angina?
Block vascular L-type calcium channels which leads to decreased heart contractility and increased vasodilation
146
According to JNC 7 guidelines, please define the following: Normal blood pressure
Less than 120/80 mm Hg
147
According to JNC 7 guidelines, please define the following: Prehypertension
120 to 139/80 to 89 mm Hg
148
According to JNC 7 guidelines, please define the following: Stage I hypertension
140 to 159/90 to 99 mm Hg
149
According to JNC 7 guidelines, please define the following: Stage II hypertension
≥ 160/100 mm Hg
150
What is the goal blood pressure (BP) in patients without diabetes niellitus (DM) or chronic kidney disease?
Less than 140/90 mm Hg
151
What is the goal BP in patients with DM or chronic kidney disease?
Less than 130/80 mm Hg
152
Define essential hypertension (HTN):
HTN of unknown etiology, that is, primary hypertension
153
True or False? The majority of HTN cases are essential.
TRUE
154
What is the BP equation?
Blood pressure (BP) = cardiac output (CO) x total peripheral resistance (TPR)
155
What is responsible for moment-to-moment changes in BP?
Baroreceptor reflexes (autonomic nervous system)
156
Where are the baroreceptors that are sensitive to the moment-to-moment changes in BP located?
Aortic arch; carotid sinuses
157
What organ is responsible for the long- term control of BP?
Kidney
158
The kidney responds to reduced BP by releasing what peptidase?
Renin
159
Renin is responsible for what enzymatic reaction?
Conversion of angiotensinogen to angiotensin-I (AT-I)
160
What enzyme is responsible for converting AT-I to AT-II?
Angiotensin-converting enzyme (ACE)
161
Where is ACE found?
In the lungs
162
What function does AT-II have with regard to BP regulation?
Vasoconstriction (increases TPR thereby increases BP); stimulation of aldosterone release
163
Where is aldosterone synthesized?
Zona glomerulosa of the adrenal cortex
164
What function does aldosterone have with regard to BP regulation?
Increases reabsorption of sodium ion in exchange for potassium ion; water osmotically follows sodium ion, therefore, aldosterone leads to salt and water retention thereby increasing BP
165
What is the name of the most common thiazide diuretic used in the treatment of HTN?
Hydrochlorothiazide (HCTZ)
166
What are the immediate/acute effects of thiazide diuretics?
Increased sodium, chloride, and water excretion which leads to decreased blood volume
167
What are the chronic effects of thiazide diuretics?
Decreased TPR
168
What is the site of action of thiazide diuretics?
Distal convoluted tubule of nephron
169
What transporter (in the distal convoluted tubule) is inhibited by thiazide diuretics?
Na+/Cl co-transporter
170
Give examples of thiazide diuretics:
HCTZ; chlorothiazide; chlorthalidone
171
Thiazide diuretics may be ineffective in patients with creatinine clearances of less than what?
50 mL/min
172
With regard to blood concentrations, state whether each of the following electrolytes will be increased or decreased in patients on thiazide diuretic therapy: Calcium
Increased
173
With regard to blood concentrations, state whether each of the following electrolytes will be increased or decreased in patients on thiazide diuretic therapy: Magnesium
Decreased
174
With regard to blood concentrations, state whether each of the following electrolytes will be increased or decreased in patients on thiazide diuretic therapy: Potassium
Decreased
175
With regard to blood concentrations, state whether each of the following electrolytes will be increased or decreased in patients on thiazide diuretic therapy: Sodium
Decreased
176
With regard to increased renal calcium reabsorption, what are thiazide diuretics sometimes used for?
Treatment of calcium stones in the urine
177
What are the adverse effects of HCTZ?
Hypercalcemia; hypokalemia; hypomagnesemia; hyperglycemia; hyperuricemia; pancreatitis; metabolic alkalosis; Stevens-Johnson syndrome; hyperlipidemia
178
Patients allergic to what class of antimicrobials may also be sensitive to thiazide diuretics?
Sulfonamides
179
What is the site of action of loop diuretics?
Loop of Henle (thick ascending limb)
180
Give examples of loop diuretics:
Furosemide; bumetanide; ethacrynic acid; torsemide
181
Which loop diuretic can be given safely to patients with allergy to sulfonamide antimicrobials?
Ethacrynic acid
182
What transporter (in the thick ascending loop of Henle) is inhibited by loop diuretics?
Na+/K-2Cl~ transporter
183
True or False? Loop diuretics increase calcium excretion.
TRUE
184
What are the adverse effects of loop diuretics?
Hypersensitivity; hypocalcemia; hypokalemia; hypomagnesemia; metabolic alkalosis; hyperuricemia; ototoxicity
185
Which loop diuretic is the most ototoxic?
Ethacrynic acid
186
Which renal tubular segment is responsible for the majority of sodium reabsorption?
Proximal convoluted tubule (>60%)
187
What is the mechanism of action of mannitol?
Acts as an osmotic diuretic, thereby drawing water via increased osmolality, into the proximal convoluted tubule, loop of Henle (thin descending limb), and the collecting ducts
188
What is mannitol used for?
Decreases intraocular and intracranial pressure; prevents anuria in hemolysis and rhabdomyolysis
189
Give two examples of carbonic anhydrase inhibitors (CAIs):
1. Acetazolamide 2. Dorzolamide
190
What is the mechanism of action of carbonic anhydrase inhibitors (CAIs)?
Increased excretion of sodium and bicarbonate
191
What metabolic disturbance may be caused by carbonic anhydrase inhibitors (CAIs)?
Metabolic acidosis
192
What are carbonic anhydrase inhibitors (CAIs) used for?
Altitude sickness (decreases cerebral and pulmonary edema); glaucoma (decreases aqueous humor formation thereby decreasing intraocular pressure); metabolic alkalosis; to enhance renal excretion of acidic drugs
193
Name three potassium-sparing diuretics:
1. Spironolactone 2. Triamterene 3. Amiloride
194
What is the mechanism of action of spironolactone?
Aldosterone receptor antagonist
195
Where in the kidney is the aldosterone receptor found?
Basolateral membrane of the principal cell in the collecting duct
196
Where in the kidney does triamterene and amiloride work?
Sodium ion channel on the luminal side of the principal cell in the collecting duct
197
What are the adverse effects of spironolactone?
Hyperkalemia; metabolic acidosis; gynecomastia
198
Triamterene is often used in combination with what other diuretic?
HCTZ
199
Spironolactone is used to treat what conditions?
HTN; CHF; ascites
200
Amiloride is used to treat what conditions?
HTN; CHF; lithium-induced diabetes insipidus
201
With regard to BP = CO × TPR, how do β-blockers lower BP?
Decrease CO
202
What is the prototype β-blocker?
Propranolol
203
Is propranolol cardioselective?
No
204
Because of their cardioselectivity, what two β-blockers have gained the most widespread use?
1. Metoprolol 2. Atenolol
205
Patients with what specific disease states should not receive nonselective β-antagonists?
Asthma (increased risk of bronchospasm); diabetes; peripheral vascular disease
206
What action do β-blockers have on the kidneys?
They decrease renin release by preventing stimulation of renin release by catecholamines and also likely by direct depression of the renin-angiotensin-aldosterone system.
207
What are the adverse effects of β-blockers?
Hypotension; lipid abnormalities; rebound HTN with abrupt withdrawal; fatigue; insomnia; sexual dysfunction; hallucinations; depression; hyperglycemia
208
Which β-blocker has the shortest half-life?
Esmolol (9 min), therefore esmolol is usually administered as a continuous drip.
209
With regard to BP = CO × TPR, how do ACE inhibitors decrease BP?
Decrease TPR
210
In addition to conversion of AT-I to AT-II, what other reaction does ACE catalyze?
The breakdown of bradykinin. ACE is also known as kininase.
211
What action does bradykinin have on vascular smooth muscle?
Vasodilation
212
Increased bradykinin levels may lead to what adverse reaction experienced by patients who take ACE inhibitors?
Dry cough
213
How do ACE inhibitors decrease sodium and water retention?
Decreased levels of AT-II leads to decreased levels of aldosterone and therefore reduced sodium and water retention.
214
What are the adverse effects of ACE inhibitors?
Hypotension; dry cough; hyperkalemia; angioedema; fever; altered taste
215
Give examples of ACE inhibitors:
Benazepril; captopril; enalapril; fosinopril; lisinopril; quinapril; ramipril
216
Give two contraindications for ACE inhibitor therapy:
1. Pregnancy (teratogenic) 2. Bilateral renal artery stenosis
217
What is the mechanism of action of losartan?
AT-II receptor blocker
218
Give examples of ARBs:
Candesartan; eprosartan; irbesartan; losartan; olmesartan; telmisartan; valsartan
219
Which specific receptor type do ARBs antagonize?
AT-II type 1 receptor
220
Do ARBs cause dry cough?
No (ARBs do not inhibit the breakdown of bradykinin)
221
Is there a pregnancy contraindication for ARBs?
Yes, they are pregnancy category C for the first trimester and category D for the second and third trimester.
222
How do CCBs work in the treatment of HTN?
Block vascular L-type calcium channels which leads to decreased heart contractility and increased vasodilation of coronary and peripheral vasculature
223
What are the adverse effects of the DHP CCBs?
Peripheral edema; hypotension; reflex tachycardia; headache; flushing; gingival hyperplasia
224
What are the adverse effects of verapamil?
Drug-drug interactions; constipation; AV block; headache
225
What action do CCBs have on the kidney?
Natriuretic activity
226
Which CCB is used in subarachnoid hemorrhages to prevent vasospasm?
Nimodipine
227
Give an example of a T-type CCB used in the treatment of absence seizures:
Ethosuximide
228
Name three α1-adrenergic antagonists used in the treatment of HTN:
1. Doxazosin 2. Prazosin 3. Terazosin
229
How do α1-adrenergic antagonists decrease BP?
Antagonize α1-receptors in vascular smooth muscle, thereby causing vasodilation and reduced TPR
230
What are the two main adverse effects of α1-antagonists?
1. First dose syncope 2. Reflex tachycardia
231
What class of drugs can be used to block the reflex tachycardia caused by α1-antagonists?
β-Blockers
232
α1-Adrenergic antagonists are most commonly used for what condition other than hypertension?
Benign prostatic hyperplasia (BPH)
233
How does clonidine work as an antihypertensive?
Central α2-adrenergic agonist (decreases sympathetic outflow from the CNS, producing a decrease in TPR,
HR, and BP)
234
Why are diuretics often given to patients on clonidine therapy?
Clonidine causes sodium and water retention.
235
Other than HTN, what is clonidine used for?
Nicotine withdrawal; heroin withdrawal; alcohol dependence; migraine prophylaxis; severe pain; clozapine- induced sialorrhea
236
What are the adverse effects of clonidine?
Bradycardia; sedation; dry mouth; rebound HTN with abrupt withdrawal (must taper down dose when discontinuing therapy); edema
237
Can clonidine be used in patients with renal dysfunction?
Yes, because renal blood flow and glomerular filtration rate are not compromised with clonidine therapy.
238
α-Methyldopa is converted to what active metabolite?
Methylnorepinephrine
239
What is the mechanism of action of α-methyldopa?
Central α2-adrenergic agonist
240
Can α-methyldopa be used in patients with renal dysfunction?
Yes
241
Is α-methyldopa contraindicated in pregnancy?
No, it is one of the antihypertensive drugs of choice in pregnant women.
242
What are the adverse effects of α-methyldopa?
Sedation; hemolytic anemia; drug-induced lupus; edema; bradycardia; dry mouth
243
What arterial vasodilator decreases TPR, often requires a β-blocker to counteract the subsequent reflex tachycardia, and may cause drug-induced lupus?
Hydralazine
244
What class of drugs are used to counteract the fluid retention caused by hydralazine?
Diuretics
245
What are the adverse effects of hydralazine?
Reflex tachycardia; fluid retention; drug-induced lupus; headache; flushing
246
What enzyme is responsible for the metabolism of hydralazine?
N-acetyltransferase
247
What is the mechanism of action of minoxidil?
Opens potassium channels which leads to membrane hyperpolarization and subsequent arterial vasodilation
248
Minoxidil is a prodrug that is activated by what mechanism?
Sulfation
249
What is a common side effect of minoxidil?
Hypertrichosis (used in the treatment of alopecia)
250
What drug is a direct acting vasodilator, used in hypertensive emergencies, and can also be used to prevent hypoglycemia in patients with insulinoma?
Diazoxide
251
How does diazoxide work to prevent hypoglycemia in patients with insulinoma?
It decreases insulin release.
252
What drug is used during hypertensive emergencies, acts via increasing cGMP through NO mechanisms, and forms thiocyanate and cyanide metabolites?
Sodium nitroprusside
253
What class of antihypertensives may help prevent left ventricular remodeling seen in patients with CHF?
ACE inhibitors
254
What class of antihypertensives may improve patients' lipid profiles?
α1-Adrenergic antagonists
255
What two classes of antihypertensives may protect renal function in patients with DM?
ACE inhibitors and ARBs by decreasing microalbuminuria
256
What is the mechanism of action of the "statin" class of antihyperlipidemics?
Inhibition of hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase (rate-limiting step of cholesterol biosynthesis), thereby inhibiting the intracellular supply of cholesterol; increases number of cell surface low- density lipoproteins (LDL) receptors which further reduces plasma cholesterol levels via increased metabolism
257
How do statins affect the lipid profile?
Mainly reduces LDL; moderate reduction of triglycerides (TGs); moderate elevation of high-density lipoproteins (HDL)
258
Give examples of medications in the statin drug class:
Atorvastatin; rosuvastatin; simvastatin; pravastatin; lovastatin; fluvastatin
259
What are the adverse effects of statin drugs?
Increased liver function tests (LFTs); dose-dependent rhabdomyolysis, myalgia, and myopathy; diarrhea; drug-induced lupus; drug-drug interactions; contraindicated in pregnancy (category X)
260
What laboratory tests should be used to monitor for statin toxicity?
LFTs; creatine phosphokinase (CPK)
261
What is the most potent antihyperlipidemic agent to elevate high-density lipoprotein (HDL)?
Niacin
262
Niacin is also known as what?
Vitamin B3; nicotinic acid
263
What is the mechanism of action of niacin?
High-dose niacin inhibits very low-density lipoprotein (VLDL) and apoprotein synthesis in hepatocytes; increases tissue plasminogen activator (tPA); decreases fibrinogen
264
How does niacin affect the lipid profile?
Elevation of HDL; reduction of LDL; reduction of VLDL; reduction of TGs
265
What are the adverse effects of niacin?
Facial flushing; hyperuricemia; hyperglycemia; hepatotoxicity; pruritus; nausea; abdominal pain
266
How is facial flushing counteracted in patients on niacin therapy?
Pretreatment with aspirin to counteract the prostaglandin release
267
What new antihyperlipidemic agent works by inhibiting absorption of cholesterol at the brush border in the small intestine?
Ezetimibe
268
What are the adverse effects of ezetimibe?
Diarrhea; abdominal pain; headache; arthralgias
269
Which antihyperlipidemic drug class decreases VLDL, LDL, TGs and increases HDL by activating lipoprotein lipase?
Fibrates
270
Give examples of medications in the fibrate drug class:
Gemfibrozil; clofibrate; fenofibrate
271
What is the major effect that fibrates have on the lipid profile?
Reduction of TGs
272
What are the adverse effects of gemfibrozil?
Cholelithiasis; nausea; diarrhea; abdominal pain; myositis; hypokalemia; increased levels of warfarin and sulfonylureas via protein-binding displacement
273
What is the mechanism of action of bile acid sequestrants?
Anion exchange resins that bind bile acids/salts in the small intestine, thereby preventing their reabsorption; decreased bile acids results in increased plasma cholesterol uptake by hepatocytes to replenish bile acid levels, thereby decreasing plasma LDL levels
274
Give examples of bile acid sequestrants:
Cholestyramine; colestipol; colesevelam
275
What are the adverse effects of bile acid sequestrants?
Constipation; bloating; flatulence; nausea; impaired absorption of fat-soluble vitamins; impaired absorption of warfarin; digoxin; acetyl salicylic acid (ASA); tetracycline (TCN); thiazide diuretics
276
What over-the-counter medication, naturally found in certain fish, can decrease TG levels and be useful in the prevention of coronary heart disease (CHD)?
Omega-3 fatty acids
277
Where is prostacyclin made?
Vascular endothelial cells
278
Where is thromboxane A2 made?
Platelets
279
Increased prostacyclin leads to an increase of what second messenger?
cAMP
280
cAMP does what to platelets?
Inhibits platelet activation and release of platelet aggregating factors
281
How does ASA work as a platelet aggregation inhibitor?
Irreversible inhibition, via acetylation, of cyclooxygenase (COX) thereby reducing thromboxane A2 levels
282
What two drugs inhibit platelet aggregation and platelet-fibrinogen interaction by blocking adenosine diphosphate (ADP) receptors?
1. Clopidogrel 2. Ticlopidine
283
What are the major adverse effects of ticlopidine?
Neutropenia; agranulocytosis; thrombotic thrombocytopenic purpura (TTP)
284
How should patients on ticlopidine therapy be monitored?
Complete blood count (CBC) with differential every 2 weeks for the first 3 months of therapy and as needed thereafter
285
How does dipyridamole work as a platelet aggregation inhibitor?
Inhibits phosphodiesterase (PDE) thereby increasing cAMP levels; cAMP potentiates prostacyclin and inhibits thromboxane A2 synthesis
286
Dipyridamole is usually given in combination with what drug?
Aspirin
287
What are the two main systems that feed into the common pathway of the clotting cascade?
1. Intrinsic system 2. Extrinsic system
288
Activation of clotting factor VII to VIIa marks the beginning of which clotting system?
Extrinsic system
289
Activation of clotting factor XII to XIIa marks the beginning of which clotting system?
Intrinsic system
290
Activation of which clotting factor marks the beginning of the common pathway?
Activation of factor X to factor Xa
291
What is another name for factor II? What is another name for factor IIa?
Prothrombin
292
What factor is also known as "Christmas factor"?
Thrombin
293
What factor is deficient in hemophilia A?
Factor IX
294
What factor is deficient in hemophilia B?
Factor VIII Factor IX
295
How does heparin work as an anticoagulant?
Complexes with antithrombin-III to increase inactivation of clotting factors IIa, IXa, Xa, XIa, XIIa, and XHIa
296
Which system of the clotting cascade is mainly affected by heparin?
Intrinsic system
297
Which laboratory test is used to monitor heparin therapy?
Partial thromboplastin time (PTT); therapeutic PTT levels are 1.5 to 2.5 times that of normal
298
How is heparin administered?
Intravenously (IV), subcutaneously (SQ)
299
Why is intramuscular administration of heparin contraindicated?
Hematoma formation
300
What are the therapeutic indications of heparin?
Prevention and treatment (by preventing expansion of the clot) of deep vein thrombosis (DVT) and pulmonary embolism (PE); used for anticoagulation during MI
301
What is the onset of action of heparin?
IV = immediate onset of action; SQ = 20 to 30 minutes
302
Does heparin cross the placental barrier?
No, therefore it is safe in pregnancy.
303
What are the adverse effects of heparin?
Bleeding; hypersensitivity; osteoporosis; heparin-induced thrombocytopenia (HIT)
304
Heparin undergoes what type of metabolism?
Hepatic; reticuloendothelial system
305
What drug is used to counteract heparin overdose?
Protamine sulfate
306
Roughly, how many units of heparin are neutralized by 1 mg of protamine sulfate?
100 units
307
What is the onset of action of protamine sulfate?
5 minutes
308
What paradoxical adverse effect can protamine cause at high doses?
Anticoagulation leading to hemorrhage
309
What is the mechanism of action of enoxaparin?
Low-molecular-weight heparin (LMWH) that has a higher ratio of antifactor Xa to antifactor Ha activity versus unfractionated heparin (UFH)
310
What is the half-life of LMWH?
Two to four times that of UFH
311
Does PTT need to be monitored in patients on LMWH therapy?
No
312
What synthetic pentasaccharide causes an antithrombin-III-mediated selective inhibition of factor Xa?
Fondaparinux
313
Which system of the clotting cascade is mainly affected by warfarin?
Extrinsic system
314
Which laboratory tests are used to monitor warfarin therapy?
Prothrombin time (PT); international normalized ratio (INR) → therapeutic INR levels are between 2 and 3
315
How does warfarin work as an anticoagulant?
Inhibits synthesis of vitamin-K-dependent clotting factors II, VII, IX, and X via inhibition of vitamin K epoxide reductase; also inhibits synthesis of protein C and protein S
316
What is the onset of action of warfarin?
36 to 72 hours (anticoagulant action)
317
How long after initiation of warfarin therapy is the full therapeutic effect seen?
5 to 7 days (antithrombotic action)
318
Acute alcohol intoxication does what to warfarin metabolism?
Inhibits warfarin metabolism, thereby increasing warfarin blood levels
319
Chronic alcohol use does what to warfarin metabolism?
Induces warfarin metabolism, thereby decreasing warfarin blood levels
320
What happens to the INR of warfarin patients who begin thyroid replacement medication?
INR increases; thyroid hormone increases the metabolism of clotting factors, thereby potentiating the effects of warfarin
321
What happens to the INR of warfarin patients who begin antimicrobial therapy with sulfonamides?
INR increases; sulfonamides inhibit CYP-450 2C9, thereby increasing warfarin levels
322
Does warfarin cross the placental barrier?
Yes (contraindicated in pregnancy); warfarin is teratogenic
323
What are the adverse effects of warfarin?
Bleeding; drug-drug interactions; skin necrosis (seen within the first few days of warfarin therapy and is secondary to decreased protein C levels); "purple toes syndrome" (caused by cholesterol microembolization)
324
What can be used to counteract the effects of warfarin?
Vitamin K (slow onset); fresh frozen plasma (rapid onset)
325
How is warfarin metabolized?
Hepatic cytochrome β-450 enzymes
326
The synthesis of what two factors is inhibited first when warfarin therapy is initiated?
1. Factor VII 2. Protein C (therefore patients may initially be hypercoagulable when warfarin is first initiated)
327
Why are factor VII and protein C inhibited first when warfarin therapy is initiated?
These proteins have the shortest half-lives when compared to the half-lives of factors II, IX, X, and protein S
328
What is the mechanism of action of abciximab, eptifibatide, and tirofiban?
Blockade of the glycoprotein IIb/IIIa receptor on platelets, thereby inhibiting platelet aggregation
329
What is the physiologic ligand for the glycoprotein Ilb/IIIa receptor?
Fibrinogen
330
What is the mechanism of action of thrombolytic agents?
Conversion of plasminogen to plasmin; plasmin cleaves fibrin, thereby leading to lysis of thrombi
331
What is the main adverse effect of thrombolytic agents?
Hemorrhage
332
Thrombolytic agents are contraindicated in what settings?
Active internal bleeding; history of cerebrovascular accident (CVA); recent intracranial or intraspinal surgery; intracranial neoplasm; AV malformation; severe uncontrolled HTN (systolic blood pressure [SBP] >185 mm Hg or diastolic blood pressure [DBP] >110 mm Hg); evidence of intracranial hemorrhage; suspected aortic dissection; seizure at the onset of stroke; current use of anticoagulants or an INR >1.7; lumbar puncture within 1 week
333
What are the therapeutic indications of thrombolytic therapy?
Acute MI; acute PE; acute ischemic stroke
334
What is the "therapeutic time window" for administering thrombolytic agents to patients with acute ischemic stroke?
Within the first 3 hours of the onset of symptoms
335
Give examples of thrombolytic agents:
Alteplase; anistreplase; streptokinase; urokinase
336
What two drugs can counteract thrombolytic agent therapy?
1. Aminocaproic acid 2. Tranexamic acid (both agents inhibit plasminogen activation)
337
With regard to thrombolytic agents, what does "clot-specific" mean?
The drug specifically activates plasminogen that is bound to fibrin in a thrombus with a low affinity for free, circulating plasminogen
338
Which thrombolytic agent is "clot-specific"?
Alteplase
339
Alteplase is also known as what?
tPA (tissue plasminogen activator)
340
What is the half-life of tPA?
5 minutes
341
Where does tPA come from?
Recombinant DNA technology
342
What type of enzymatic activity does tPA possess?
Serine protease activity
343
Where does streptokinase come from?
Group C β-hemolytic streptococci
344
How does streptokinase work as a thrombolytic agent?
Forms a 1:1 complex with plasminogen; complexed plasminogen then converts free plasminogen into plasmin (active form)
345
Does streptokinase have any enzymatic activity?
No
346
Is streptokinase "clot-specific"?
No
347
What other proteins does the streptokinase-plasminogen complex degrade?
Fibrinogen; factor V; factor VII
348
What laboratory value is monitored with streptokinase therapy?
Thromboplastin time
349
Why is streptokinase antigenic?
It is recognized as a foreign protein (antigen).
350
What adverse reactions are specific to streptokinase?
Anaphylaxis; rash; fever
351
What is the half-life of anistreplase?
90 minutes
352
How does anistreplase work as a thrombolytic?
Anisoyl group blocks the active site of plasminogen; as complex binds to fibrin, anisoyl group is removed and the complex becomes activated.
353
Does urokinase have enzymatic activity?
Yes
354
Originally, where did urokinase come from?
Human urine
355
Where does urokinase come from now?
Fetal renal cells (human)
356
Is urokinase antigenic?
No, since it is not a foreign protein.
357
Will streptokinase, at normal doses, work in patients with a recent history of streptococcal infection?
No, because antibodies made against recent streptococcal antigens will bind to and inactivate streptokinase.
