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Pharmacology > Deja Ch 6 CV, Renal > Flashcards

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.

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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.

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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)

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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

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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.

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6
Q

On what phase(s) of the cardiac action potential do amiodarone and sotalol work?

A

Phase 0 and phase III

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7
Q

On what phase(s) of the cardiac action potential do lidocaine, flecainide, and quinidine work?

A

Phase 0

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8
Q

On what phase(s) of the cardiac action potential do β-blockers work?

A

Phase II and phase IV

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9
Q

What is responsible for maintaining the electrochemical gradient at resting membrane potential?

A

Na+/K+-A TPase

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10
Q

What ion current is responsible for the depolarization of sinoatrial (SA) and atrioventricular (AV) nodal fibers?

A

Calcium ion (inward)

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11
Q

What ion current is responsible for the repolarization of SA and AV nodal fibers?

A

Potassium ion (outward)

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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

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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)

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14
Q

The pacemaker of the heart has the fastest uprising phase IV slope; where is this pacemaker in nondiseased patients?

A

SA node

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15
Q

Where is the SA node located?

A

Right atrium

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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.

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17
Q

What are the three states the voltage-gated Na+ channel exists in?

A
  1. Resting state 2. Open state 3. Inactivated state
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18
Q

What state(s) of the voltage-gated Na+ channel is/are most susceptible to drugs?

A

Open state; inactivated state

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19
Q

What two types of gates does the voltage-gated Na+ channel have?

A
  1. M (activating) 2. H (inactivating)
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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.

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21
Q

What class of antiarrhythmic agents has membrane-stabilizing effects?

A

β-Blockers

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22
Q

Antiarrhythmic agents are grouped into four classes according to what classification system?

A

Vaughn-Williams classification

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23
Q

Give the general mechanism of action for each of the following antiarrhythmic drug classes: Class I

A

Na+ channel blockers

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24
Q

Give the general mechanism of action for each of the following antiarrhythmic drug classes: Class II

A

β-Blockers

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25
Q

Give the general mechanism of action for each of the following antiarrhythmic drug classes: Class III

A

K+ channel blockers

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26
Q

Give the general mechanism of action for each of the following antiarrhythmic drug classes: Class IV

A

Ca++ channel blockers

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27
Q

Class I antiarrhythmics are further subdivided into what classes?

A

la; Ib; Ic

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28
Q

Give examples of antiarrhythmic drugs in class la:

A

Quinidine (antimalarial/antiprotozoal agent); procainamide; disopyramide

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29
Q

Give examples of antiarrhythmic drugs in class Ib:

A

Lidocaine; mexiletine; tocainide; phenytoin

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30
Q

Give examples of antiarrhythmic drugs in class Ic:

A

Encainide; flecainide; propafenone; moricizine

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31
Q

Give examples of antiarrhythmic drugs in class II:

A

Propranolol; esmolol; metoprolol

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32
Q

Give examples of antiarrhythmic drugs in class III:

A

Amiodarone; sotalol; ibutilide; dofetilide

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33
Q

Give examples of antiarrhythmic drugs in class IV:

A

Verapamil; diltiazem

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34
Q

Name three antiarrhythmic drugs that do not fit in the Vaughn-Williams classification system:

A
  1. Digoxin 2. Adenosine 3. Magnesium
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35
Q

Magnesium is used to treat what specific type of arrhythmia?

A

Torsades de pointes (polymorphic ventricular tachycardia)

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36
Q

Adenosine is used to treat what types of arrhythmias?

A

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.

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37
Q

Where anatomically should the IV be placed to administer adenosine?

A

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.

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38
Q

What is the mechanism of action of adenosine?

A

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

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39
Q

What are the adverse effects of adenosine?

A

Flushing; chest pain; dyspnea; hypotension

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40
Q

What 2 drugs can antagonize the effects of adenosine?

A
  1. Theophylline 2. Caffeine
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41
Q

How is adenosine dosed?

A

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.

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42
Q

What is the most deadly ion that can be administered?

A

Potassium ion

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43
Q

What ECG changes are seen in hyperkalemia?

A

Flattened P waves; widened QRS complex; peaked T waves; sine waves; ventricular fibrillation

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44
Q

What ECG changes are seen in hypokalemia?

A

Flattened or inverted T waves; U waves; ST-segment depression

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45
Q

What do class la antiarrhythmics do to the Action potential duration?

A

Increase

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46
Q

What do class la antiarrhythmics do to the ERP

A

Increase

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47
Q

What do class la antiarrhythmics do to the Conduction velocity

A

Decrease

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48
Q

What do class la antiarrhythmics do to the Phase IV slope

A

Decrease

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49
Q

What do class Ib antiarrhythmics do to the Action potential duration

A

Decrease

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50
Q

What do class Ib antiarrhythmics do to the ERP

A

Little or no change

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51
Q

What do class Ib antiarrhythmics do to the Conduction velocity

A

Decrease (primarily in ischemic tissue)

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52
Q

What do class Ib antiarrhythmics do to the Phase IV slope

A

Decrease

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53
Q

What do class Ic antiarrhythmics do to the Action potential duration

A

Little or no change

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54
Q

What do class Ic antiarrhythmics do to the ERP

A

Little or no change

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55
Q

What do class Ic antiarrhythmics do to the Conduction velocity

A

Decrease

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56
Q

What do class Ic antiarrhythmics do to the Phase IV slope

A

Decrease

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57
Q

Drugs that affect the strength of heart muscle contraction are referred to as what types of agents?

A

Inotropes (either positive or negative)

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58
Q

Drugs that affect the heart rate are referred to as what types of agents?

A

Chronotropes (either positive or negative)

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59
Q

Drugs that affect AV conduction velocity are referred to as what types of agents?

A

Dromotropes (either positive or negative)

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60
Q

QT interval prolongation, and therefore torsades de pointes, is more likely to occur with what two classes of antiarrhythmics?

A
  1. la 2. Ill
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61
Q

Which class la antiarrhythmic also blocks α-adrenergic and muscarinic receptors, thereby potentially leading to increased heart rate and AV conduction?

A

Quinidine

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62
Q

What are the adverse effects of quinidine?

A

Tachycardia; proarrhythmic; increased digoxin levels via protein-binding displacement; nausea; vomiting; diarrhea; cinchonism

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63
Q

What is cinchonism?

A

Syndrome that may include tinnitus; high-frequency hearing loss; deafness; vertigo; blurred vision; diplopia; photophobia; headache; confusion; delirium

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64
Q

What are the adverse effects of procainamide?

A

Drug-induced lupus (25%-30% of patients); proarrhythmic; depression; psychosis; hallucination; nausea; vomiting; diarrhea; agranulocytosis; thrombocytopenia; hypotension

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65
Q

What drugs can cause drug-induced lupus?

A

Procainamide; isoniazid (INH); chlorpromazine; penicillamine; sulfasalazine; hydralazine; methyldopa; quinidine; phenytoin; minocycline; valproic acid; carbamazepine; chlorpromazine

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66
Q

Which class la antiarrhythmic can cause peripheral vasoconstriction?

A

Disopyramide

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67
Q

What are the adverse effects of disopyramide?

A

Anticholinergic adverse effects, such as urinary retention; dry mouth; dry eyes; blurred vision; constipation; sedation

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68
Q

True or False? Lidocaine is useful in the treatment of ventricular arrhythmias?

A

TRUE

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69
Q

True or False? Lidocaine is useful in the treatment of atrial arrhythmias?

A

FALSE

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70
Q

True or False? Lidocaine is useful in the treatment of AV junctional arrhythmias?

A

FALSE

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71
Q

What are the adverse effects of lidocaine?

A

Proarrhythmic; sedation; agitation; confusion; paresthesias; seizures

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72
Q

What class Ib antiarrhythmic is structurally related to lidocaine?

A

Mexiletine

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73
Q

What class Ib antiarrhythmic can cause pulmonary fibrosis?

A

Tocainide

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74
Q

Propaf enone, even though a class Ic antiarrhythmic, exhibits what other type of antiarrhythmic activity?

A

β-Adrenergic receptor blockade

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75
Q

What famous trial showed that encainide and flecainide increased sudden cardiac death in postmyocardial infarction (MI) patients with arrhythmias?

A

Cardiac Arrhythmia Suppression Trial (CAST)

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76
Q

Sotalol, even though a class III antiarrhythmic, exhibits what other type of antiarrhythmic activity?

A

β-Adrenergic receptor blockade

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77
Q

Even though this agent is labeled as a Vaughn-Williams class III antiarrhythmic, it displays class I, II, III, and IV antiarrhythmic activity.

A

Amiodarone

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78
Q

What is the half-life of amiodarone?

A

40 to 60 days

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79
Q

What are the adverse effects of amiodarone?

A

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)

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80
Q

How should patients on amiodarone therapy be monitored?

A

ECG; thyroid function tests (TFTs); pulmonary function tests (PFTs); liver function tests (LFTs); electrolytes; ophthalmology examinations

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81
Q

Verapamil should not be given in what types of arrhythmias?

A

Wolff-Parkinson-White (WPW) syndrome; ventricular tachycardia

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82
Q

What are the adverse effects of verapamil?

A

Drug interactions; constipation; hypotension; AV block; CHF; dizziness; flushing

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83
Q

Digoxin is used to control ventricular rate in what types of arrhythmias?

A

Atrial fibrillation; atrial flutter

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84
Q

Digoxin-induced arrhythmias are treated by what drugs?

A

Lidocaine; phenytoin

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85
Q

Digoxin does what to AV conduction velocity

A

Decreases (negative dromotrope)

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86
Q

Digoxin does what to Strength of heart muscle contraction

A

Increases (positive inotrope)

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87
Q

Digoxin does what to Heart rate

A

Decreases (negative chronotrope)

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88
Q

What does QTc stand for?

A

Corrected QT interval

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89
Q

How is QTc calculated?

A

(QT)/(square root of R to R interval)

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90
Q

Why must the QT interval be corrected?

A

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.

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91
Q

What is the normal value for QTc?

A

Less than 440 milliseconds

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92
Q

What does a long QT interval put a patient at risk for?

A

Torsades de pointes, a ventricular arrhythmia that can degenerate into ventricular fibrillation

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93
Q

What is the cardiac output equation?

A

Cardiac output (CO) = heart rate (HR) × stroke volume (SV)

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94
Q

What is normal CO?

A

5 L/min

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95
Q

What is the most common cause of right-sided heart failure?

A

Left-sided heart failure

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96
Q

Name three compensatory physiologic responses seen in congestive heart failure (CHF):

A
  1. Fluid retention 2. Increased sympathetic drive 3. Hypertrophy of cardiac muscle
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97
Q

Define preload:

A

The pressure stretching the ventricular walls at the onset of ventricular contraction; related to left ventricular end-diastolic volume/pressure

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98
Q

Define afterload:

A

The load or force developed by the ventricle during systole

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99
Q

What drugs are used to decrease preload?

A

Diuretics; vasodilators; angiotensin-converting enzyme inhibitors (ACEIs); angiotensin II receptor blockers (ARBs); nitrates

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100
Q

What drugs are used to decrease afterload?

A

Vasodilators; ACEIs; ARBs; hydralazine

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101
Q

What drugs are used to increase contractility?

A

Digoxin; phosphodiesterase inhibitors (amrinone and milrinone); β-adrenoceptor agonists

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102
Q

What is the mechanism of action of digoxin?

A

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)

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103
Q

What are the two digitalis glycosides?

A
  1. Digoxin 2. Digitoxin
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104
Q

What are the adverse effects of digoxin?

A

Arrhythmias; nausea; vomiting; anorexia; headache; confusion; blurred vision; visual disturbances, such as yellow halos around light sources

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105
Q

What electrolyte disturbances predispose to digoxin toxicity?

A

Hypokalemia; hypomagnesemia; hypercalcemia

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106
Q

Digoxin can cause what types of arrhythmias?

A

Supraventricular tachycardias; AV nodal tachycardias; AV block; ventricular tachycardias; ventricular fibrillation; complete heart block

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107
Q

Can digoxin be used in WPW syndrome?

A

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.

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108
Q

How is digoxin toxicity treated?

A

Correction of electrolyte disturbances; antiarrhythmics; anti-digoxin Fab antibody (Digibind)

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109
Q

What drugs can increase digoxin concentrations?

A

Quinidine; amiodarone; erythromycin; verapamil

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110
Q

What drugs can decrease digoxin concentrations?

A

Loop diuretics; thiazide diuretics; corticosteroids

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111
Q

Does digoxin therapy in CHF lead to prolonged survival?

A

No. It is of symptomatic benefit only, improving quality, but not necessarily duration of life.

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112
Q

What classes of medications have been shown to increase survival in CHF patients?

A

ACEs/ARBs; β-blockers

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113
Q

How does dobutamine work in CHF?

A

β-Adrenergic agonist (sympathomimetic that binds to (β1-adrenoceptors) that increases force of contraction
and vasodilation via increased cAMP

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114
Q

How do amrinone and milrinone work in CHF?

A

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

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115
Q

What are the side effects of the PDEIs?

A

Milrinone may actually decrease survival in CHF; amrinone may cause thrombocytopenia.

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116
Q

How do diuretics work in CHF?

A

Decrease in intravascular volume thereby decrease in preload; reduce pulmonary and peripheral edema often seen in CHF patients

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117
Q

How can increased sympathetic activity in CHF be counteracted?

A

β-Blockers

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118
Q

What two β-blockers have specific indications for the treatment of CHF?

A
  1. Metoprolol 2. Carvedilol (mixed α-/β-blocker)
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119
Q

What is the mechanism of action of nesiritide?

A

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

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120
Q

How do ACEIs work in CHF?

A

Inhibition of angiotensin-II (AT-II) production thereby decreasing total peripheral resistance (TPR) and thus afterload; prevents left ventricular remodeling

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121
Q

Define angina pectoris:

A

Chest pain resulting from a myocardial oxygen demand that is not met by adequate oxygen supply; seen in patient with myocardial ischemia

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122
Q

What type of angina is caused by spontaneous coronary vasospasm?

A

Prinzmetal (variant) angina

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123
Q

What type of angina is caused by atherosclerosis of coronary vessels and is precipitated by exertion?

A

Classic angina

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124
Q

What type of angina can be acute in onset and is caused by platelet aggregation?

A

Unstable angina

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125
Q

What two mechanistic strategies are used in the treatment of angina?

A
  1. Increase oxygen supply to the myocardium 2. Decrease myocardial oxygen demand
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126
Q

What types of drugs can increase oxygen supply?

A

Nitrates; calcium channel blockers (CCBs)

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127
Q

What types of drugs can decrease oxygen demand?

A

Nitrates; CCBs; β-blockers

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128
Q

What is the drug of choice for immediate relief of anginal symptoms?

A

Sublingual nitroglycerin (NTG)

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129
Q

What is the mechanism of action of nitrates?

A

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

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130
Q

How does cGMP lead to relaxation of vascular smooth muscle?

A

Causes dephosphorylation of myosin light chains

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131
Q

How do nitrates increase oxygen supply?

A

Dilation of coronary vessels which leads to increased blood supply

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132
Q

How do nitrates decrease oxygen demand?

A

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

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133
Q

What are the adverse effects of nitrates?

A

Headache; hypotension; reflex tachycardia; facial flushing; metnemoglobinemia

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134
Q

Why must patients have at least a 10- to 12-hour “nitrate-free” interval every day?

A

Tolerance (tachyphylaxis) develops to nitrates if given on a continuous (around-the-clock) basis

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135
Q

Nitrates are contraindicated in patients taking any of what three medications?

A
  1. Sildenafil 2. Vardenafil 3. Tadalafil
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136
Q

Methemoglobin formation, specifically by amyl nitrite, can be used to treat what type of poisoning?

A

Cyanide

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137
Q

What are the common formulations of nitrates?

A

NTG; isosorbide mononitrate; isosorbide dinitrate

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138
Q

What is the time to peak effect of sublingual NTG?

A

2 minutes

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139
Q

What is the dosing frequency of sublingual NTG during an anginal episode?

A

Every 5 minutes for a maximum of three doses

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140
Q

How do β-blockers work in the treatment of angina?

A

Inhibition of α1-adrenoceptors which leads to decreased CO, HR, and force of contraction, thereby reducing the workload of the heart and oxygen demand

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141
Q

Do α-blockers increase oxygen supply?

A

No

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142
Q

For each of the following CCBs, state whether their primary effects are on the myocardium or peripheral vasculature: Verapamil

A

Myocardium (greater negative inotropic effects)

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143
Q

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)

A

Peripheral vasculature (more potent vasodilators)

144
Q

For each of the following CCBs, state whether their primary effects are on the myocardium or peripheral vasculature: Diltiazem

A

Myocardium

145
Q

How do CCBs work in the treatment of angina?

A

Block vascular L-type calcium channels which leads to decreased heart contractility and increased vasodilation

146
Q

According to JNC 7 guidelines, please define the following: Normal blood pressure

A

Less than 120/80 mm Hg

147
Q

According to JNC 7 guidelines, please define the following: Prehypertension

A

120 to 139/80 to 89 mm Hg

148
Q

According to JNC 7 guidelines, please define the following: Stage I hypertension

A

140 to 159/90 to 99 mm Hg

149
Q

According to JNC 7 guidelines, please define the following: Stage II hypertension

A

≥ 160/100 mm Hg

150
Q

What is the goal blood pressure (BP) in patients without diabetes niellitus (DM) or chronic kidney disease?

A

Less than 140/90 mm Hg

151
Q

What is the goal BP in patients with DM or chronic kidney disease?

A

Less than 130/80 mm Hg

152
Q

Define essential hypertension (HTN):

A

HTN of unknown etiology, that is, primary hypertension

153
Q

True or False? The majority of HTN cases are essential.

A

TRUE

154
Q

What is the BP equation?

A

Blood pressure (BP) = cardiac output (CO) x total peripheral resistance (TPR)

155
Q

What is responsible for moment-to-moment changes in BP?

A

Baroreceptor reflexes (autonomic nervous system)

156
Q

Where are the baroreceptors that are sensitive to the moment-to-moment changes in BP located?

A

Aortic arch; carotid sinuses

157
Q

What organ is responsible for the long- term control of BP?

A

Kidney

158
Q

The kidney responds to reduced BP by releasing what peptidase?

A

Renin

159
Q

Renin is responsible for what enzymatic reaction?

A

Conversion of angiotensinogen to angiotensin-I (AT-I)

160
Q

What enzyme is responsible for converting AT-I to AT-II?

A

Angiotensin-converting enzyme (ACE)

161
Q

Where is ACE found?

A

In the lungs

162
Q

What function does AT-II have with regard to BP regulation?

A

Vasoconstriction (increases TPR thereby increases BP); stimulation of aldosterone release

163
Q

Where is aldosterone synthesized?

A

Zona glomerulosa of the adrenal cortex

164
Q

What function does aldosterone have with regard to BP regulation?

A

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
Q

What is the name of the most common thiazide diuretic used in the treatment of HTN?

A

Hydrochlorothiazide (HCTZ)

166
Q

What are the immediate/acute effects of thiazide diuretics?

A

Increased sodium, chloride, and water excretion which leads to decreased blood volume

167
Q

What are the chronic effects of thiazide diuretics?

A

Decreased TPR

168
Q

What is the site of action of thiazide diuretics?

A

Distal convoluted tubule of nephron

169
Q

What transporter (in the distal convoluted tubule) is inhibited by thiazide diuretics?

A

Na+/Cl co-transporter

170
Q

Give examples of thiazide diuretics:

A

HCTZ; chlorothiazide; chlorthalidone

171
Q

Thiazide diuretics may be ineffective in patients with creatinine clearances of less than what?

A

50 mL/min

172
Q

With regard to blood concentrations, state whether each of the following electrolytes will be increased or decreased in patients on thiazide diuretic therapy: Calcium

A

Increased

173
Q

With regard to blood concentrations, state whether each of the following electrolytes will be increased or decreased in patients on thiazide diuretic therapy: Magnesium

A

Decreased

174
Q

With regard to blood concentrations, state whether each of the following electrolytes will be increased or decreased in patients on thiazide diuretic therapy: Potassium

A

Decreased

175
Q

With regard to blood concentrations, state whether each of the following electrolytes will be increased or decreased in patients on thiazide diuretic therapy: Sodium

A

Decreased

176
Q

With regard to increased renal calcium reabsorption, what are thiazide diuretics sometimes used for?

A

Treatment of calcium stones in the urine

177
Q

What are the adverse effects of HCTZ?

A

Hypercalcemia; hypokalemia; hypomagnesemia; hyperglycemia; hyperuricemia; pancreatitis; metabolic alkalosis; Stevens-Johnson syndrome; hyperlipidemia

178
Q

Patients allergic to what class of antimicrobials may also be sensitive to thiazide diuretics?

A

Sulfonamides

179
Q

What is the site of action of loop diuretics?

A

Loop of Henle (thick ascending limb)

180
Q

Give examples of loop diuretics:

A

Furosemide; bumetanide; ethacrynic acid; torsemide

181
Q

Which loop diuretic can be given safely to patients with allergy to sulfonamide antimicrobials?

A

Ethacrynic acid

182
Q

What transporter (in the thick ascending loop of Henle) is inhibited by loop diuretics?

A

Na+/K-2Cl~ transporter

183
Q

True or False? Loop diuretics increase calcium excretion.

A

TRUE

184
Q

What are the adverse effects of loop diuretics?

A

Hypersensitivity; hypocalcemia; hypokalemia; hypomagnesemia; metabolic alkalosis; hyperuricemia; ototoxicity

185
Q

Which loop diuretic is the most ototoxic?

A

Ethacrynic acid

186
Q

Which renal tubular segment is responsible for the majority of sodium reabsorption?

A

Proximal convoluted tubule (>60%)

187
Q

What is the mechanism of action of mannitol?

A

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
Q

What is mannitol used for?

A

Decreases intraocular and intracranial pressure; prevents anuria in hemolysis and rhabdomyolysis

189
Q

Give two examples of carbonic anhydrase inhibitors (CAIs):

A
  1. Acetazolamide 2. Dorzolamide
190
Q

What is the mechanism of action of carbonic anhydrase inhibitors (CAIs)?

A

Increased excretion of sodium and bicarbonate

191
Q

What metabolic disturbance may be caused by carbonic anhydrase inhibitors (CAIs)?

A

Metabolic acidosis

192
Q

What are carbonic anhydrase inhibitors (CAIs) used for?

A

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
Q

Name three potassium-sparing diuretics:

A
  1. Spironolactone 2. Triamterene 3. Amiloride
194
Q

What is the mechanism of action of spironolactone?

A

Aldosterone receptor antagonist

195
Q

Where in the kidney is the aldosterone receptor found?

A

Basolateral membrane of the principal cell in the collecting duct

196
Q

Where in the kidney does triamterene and amiloride work?

A

Sodium ion channel on the luminal side of the principal cell in the collecting duct

197
Q

What are the adverse effects of spironolactone?

A

Hyperkalemia; metabolic acidosis; gynecomastia

198
Q

Triamterene is often used in combination with what other diuretic?

A

HCTZ

199
Q

Spironolactone is used to treat what conditions?

A

HTN; CHF; ascites

200
Q

Amiloride is used to treat what conditions?

A

HTN; CHF; lithium-induced diabetes insipidus

201
Q

With regard to BP = CO × TPR, how do β-blockers lower BP?

A

Decrease CO

202
Q

What is the prototype β-blocker?

A

Propranolol

203
Q

Is propranolol cardioselective?

A

No

204
Q

Because of their cardioselectivity, what two β-blockers have gained the most widespread use?

A
  1. Metoprolol 2. Atenolol
205
Q

Patients with what specific disease states should not receive nonselective β-antagonists?

A

Asthma (increased risk of bronchospasm); diabetes; peripheral vascular disease

206
Q

What action do β-blockers have on the kidneys?

A

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
Q

What are the adverse effects of β-blockers?

A

Hypotension; lipid abnormalities; rebound HTN with abrupt withdrawal; fatigue; insomnia; sexual dysfunction; hallucinations; depression; hyperglycemia

208
Q

Which β-blocker has the shortest half-life?

A

Esmolol (9 min), therefore esmolol is usually administered as a continuous drip.

209
Q

With regard to BP = CO × TPR, how do ACE inhibitors decrease BP?

A

Decrease TPR

210
Q

In addition to conversion of AT-I to AT-II, what other reaction does ACE catalyze?

A

The breakdown of bradykinin. ACE is also known as kininase.

211
Q

What action does bradykinin have on vascular smooth muscle?

A

Vasodilation

212
Q

Increased bradykinin levels may lead to what adverse reaction experienced by patients who take ACE inhibitors?

A

Dry cough

213
Q

How do ACE inhibitors decrease sodium and water retention?

A

Decreased levels of AT-II leads to decreased levels of aldosterone and therefore reduced sodium and water retention.

214
Q

What are the adverse effects of ACE inhibitors?

A

Hypotension; dry cough; hyperkalemia; angioedema; fever; altered taste

215
Q

Give examples of ACE inhibitors:

A

Benazepril; captopril; enalapril; fosinopril; lisinopril; quinapril; ramipril

216
Q

Give two contraindications for ACE inhibitor therapy:

A
  1. Pregnancy (teratogenic) 2. Bilateral renal artery stenosis
217
Q

What is the mechanism of action of losartan?

A

AT-II receptor blocker

218
Q

Give examples of ARBs:

A

Candesartan; eprosartan; irbesartan; losartan; olmesartan; telmisartan; valsartan

219
Q

Which specific receptor type do ARBs antagonize?

A

AT-II type 1 receptor

220
Q

Do ARBs cause dry cough?

A

No (ARBs do not inhibit the breakdown of bradykinin)

221
Q

Is there a pregnancy contraindication for ARBs?

A

Yes, they are pregnancy category C for the first trimester and category D for the second and third trimester.

222
Q

How do CCBs work in the treatment of HTN?

A

Block vascular L-type calcium channels which leads to decreased heart contractility and increased vasodilation of coronary and peripheral vasculature

223
Q

What are the adverse effects of the DHP CCBs?

A

Peripheral edema; hypotension; reflex tachycardia; headache; flushing; gingival hyperplasia

224
Q

What are the adverse effects of verapamil?

A

Drug-drug interactions; constipation; AV block; headache

225
Q

What action do CCBs have on the kidney?

A

Natriuretic activity

226
Q

Which CCB is used in subarachnoid hemorrhages to prevent vasospasm?

A

Nimodipine

227
Q

Give an example of a T-type CCB used in the treatment of absence seizures:

A

Ethosuximide

228
Q

Name three α1-adrenergic antagonists used in the treatment of HTN:

A
  1. Doxazosin 2. Prazosin 3. Terazosin
229
Q

How do α1-adrenergic antagonists decrease BP?

A

Antagonize α1-receptors in vascular smooth muscle, thereby causing vasodilation and reduced TPR

230
Q

What are the two main adverse effects of α1-antagonists?

A
  1. First dose syncope 2. Reflex tachycardia
231
Q

What class of drugs can be used to block the reflex tachycardia caused by α1-antagonists?

A

β-Blockers

232
Q

α1-Adrenergic antagonists are most commonly used for what condition other than hypertension?

A

Benign prostatic hyperplasia (BPH)

233
Q

How does clonidine work as an antihypertensive?

A

Central α2-adrenergic agonist (decreases sympathetic outflow from the CNS, producing a decrease in TPR,
HR, and BP)

234
Q

Why are diuretics often given to patients on clonidine therapy?

A

Clonidine causes sodium and water retention.

235
Q

Other than HTN, what is clonidine used for?

A

Nicotine withdrawal; heroin withdrawal; alcohol dependence; migraine prophylaxis; severe pain; clozapine- induced sialorrhea

236
Q

What are the adverse effects of clonidine?

A

Bradycardia; sedation; dry mouth; rebound HTN with abrupt withdrawal (must taper down dose when discontinuing therapy); edema

237
Q

Can clonidine be used in patients with renal dysfunction?

A

Yes, because renal blood flow and glomerular filtration rate are not compromised with clonidine therapy.

238
Q

α-Methyldopa is converted to what active metabolite?

A

Methylnorepinephrine

239
Q

What is the mechanism of action of α-methyldopa?

A

Central α2-adrenergic agonist

240
Q

Can α-methyldopa be used in patients with renal dysfunction?

A

Yes

241
Q

Is α-methyldopa contraindicated in pregnancy?

A

No, it is one of the antihypertensive drugs of choice in pregnant women.

242
Q

What are the adverse effects of α-methyldopa?

A

Sedation; hemolytic anemia; drug-induced lupus; edema; bradycardia; dry mouth

243
Q

What arterial vasodilator decreases TPR, often requires a β-blocker to counteract the subsequent reflex tachycardia, and may cause drug-induced lupus?

A

Hydralazine

244
Q

What class of drugs are used to counteract the fluid retention caused by hydralazine?

A

Diuretics

245
Q

What are the adverse effects of hydralazine?

A

Reflex tachycardia; fluid retention; drug-induced lupus; headache; flushing

246
Q

What enzyme is responsible for the metabolism of hydralazine?

A

N-acetyltransferase

247
Q

What is the mechanism of action of minoxidil?

A

Opens potassium channels which leads to membrane hyperpolarization and subsequent arterial vasodilation

248
Q

Minoxidil is a prodrug that is activated by what mechanism?

A

Sulfation

249
Q

What is a common side effect of minoxidil?

A

Hypertrichosis (used in the treatment of alopecia)

250
Q

What drug is a direct acting vasodilator, used in hypertensive emergencies, and can also be used to prevent hypoglycemia in patients with insulinoma?

A

Diazoxide

251
Q

How does diazoxide work to prevent hypoglycemia in patients with insulinoma?

A

It decreases insulin release.

252
Q

What drug is used during hypertensive emergencies, acts via increasing cGMP through NO mechanisms, and forms thiocyanate and cyanide metabolites?

A

Sodium nitroprusside

253
Q

What class of antihypertensives may help prevent left ventricular remodeling seen in patients with CHF?

A

ACE inhibitors

254
Q

What class of antihypertensives may improve patients’ lipid profiles?

A

α1-Adrenergic antagonists

255
Q

What two classes of antihypertensives may protect renal function in patients with DM?

A

ACE inhibitors and ARBs by decreasing microalbuminuria

256
Q

What is the mechanism of action of the “statin” class of antihyperlipidemics?

A

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
Q

How do statins affect the lipid profile?

A

Mainly reduces LDL; moderate reduction of triglycerides (TGs); moderate elevation of high-density lipoproteins (HDL)

258
Q

Give examples of medications in the statin drug class:

A

Atorvastatin; rosuvastatin; simvastatin; pravastatin; lovastatin; fluvastatin

259
Q

What are the adverse effects of statin drugs?

A

Increased liver function tests (LFTs); dose-dependent rhabdomyolysis, myalgia, and myopathy; diarrhea; drug-induced lupus; drug-drug interactions; contraindicated in pregnancy (category X)

260
Q

What laboratory tests should be used to monitor for statin toxicity?

A

LFTs; creatine phosphokinase (CPK)

261
Q

What is the most potent antihyperlipidemic agent to elevate high-density lipoprotein (HDL)?

A

Niacin

262
Q

Niacin is also known as what?

A

Vitamin B3; nicotinic acid

263
Q

What is the mechanism of action of niacin?

A

High-dose niacin inhibits very low-density lipoprotein (VLDL) and apoprotein synthesis in hepatocytes; increases tissue plasminogen activator (tPA); decreases fibrinogen

264
Q

How does niacin affect the lipid profile?

A

Elevation of HDL; reduction of LDL; reduction of VLDL; reduction of TGs

265
Q

What are the adverse effects of niacin?

A

Facial flushing; hyperuricemia; hyperglycemia; hepatotoxicity; pruritus; nausea; abdominal pain

266
Q

How is facial flushing counteracted in patients on niacin therapy?

A

Pretreatment with aspirin to counteract the prostaglandin release

267
Q

What new antihyperlipidemic agent works by inhibiting absorption of cholesterol at the brush border in the small intestine?

A

Ezetimibe

268
Q

What are the adverse effects of ezetimibe?

A

Diarrhea; abdominal pain; headache; arthralgias

269
Q

Which antihyperlipidemic drug class decreases VLDL, LDL, TGs and increases HDL by activating lipoprotein lipase?

A

Fibrates

270
Q

Give examples of medications in the fibrate drug class:

A

Gemfibrozil; clofibrate; fenofibrate

271
Q

What is the major effect that fibrates have on the lipid profile?

A

Reduction of TGs

272
Q

What are the adverse effects of gemfibrozil?

A

Cholelithiasis; nausea; diarrhea; abdominal pain; myositis; hypokalemia; increased levels of warfarin and sulfonylureas via protein-binding displacement

273
Q

What is the mechanism of action of bile acid sequestrants?

A

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
Q

Give examples of bile acid sequestrants:

A

Cholestyramine; colestipol; colesevelam

275
Q

What are the adverse effects of bile acid sequestrants?

A

Constipation; bloating; flatulence; nausea; impaired absorption of fat-soluble vitamins; impaired absorption of warfarin; digoxin; acetyl salicylic acid (ASA); tetracycline (TCN); thiazide diuretics

276
Q

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)?

A

Omega-3 fatty acids

277
Q

Where is prostacyclin made?

A

Vascular endothelial cells

278
Q

Where is thromboxane A2 made?

A

Platelets

279
Q

Increased prostacyclin leads to an increase of what second messenger?

A

cAMP

280
Q

cAMP does what to platelets?

A

Inhibits platelet activation and release of platelet aggregating factors

281
Q

How does ASA work as a platelet aggregation inhibitor?

A

Irreversible inhibition, via acetylation, of cyclooxygenase (COX) thereby reducing thromboxane A2 levels

282
Q

What two drugs inhibit platelet aggregation and platelet-fibrinogen interaction by blocking adenosine diphosphate (ADP) receptors?

A
  1. Clopidogrel 2. Ticlopidine
283
Q

What are the major adverse effects of ticlopidine?

A

Neutropenia; agranulocytosis; thrombotic thrombocytopenic purpura (TTP)

284
Q

How should patients on ticlopidine therapy be monitored?

A

Complete blood count (CBC) with differential every 2 weeks for the first 3 months of therapy and as needed thereafter

285
Q

How does dipyridamole work as a platelet aggregation inhibitor?

A

Inhibits phosphodiesterase (PDE) thereby increasing cAMP levels; cAMP potentiates prostacyclin and inhibits thromboxane A2 synthesis

286
Q

Dipyridamole is usually given in combination with what drug?

A

Aspirin

287
Q

What are the two main systems that feed into the common pathway of the clotting cascade?

A
  1. Intrinsic system 2. Extrinsic system
288
Q

Activation of clotting factor VII to VIIa marks the beginning of which clotting system?

A

Extrinsic system

289
Q

Activation of clotting factor XII to XIIa marks the beginning of which clotting system?

A

Intrinsic system

290
Q

Activation of which clotting factor marks the beginning of the common pathway?

A

Activation of factor X to factor Xa

291
Q

What is another name for factor II? What is another name for factor IIa?

A

Prothrombin

292
Q

What factor is also known as “Christmas factor”?

A

Thrombin

293
Q

What factor is deficient in hemophilia A?

A

Factor IX

294
Q

What factor is deficient in hemophilia B?

A

Factor VIII Factor IX

295
Q

How does heparin work as an anticoagulant?

A

Complexes with antithrombin-III to increase inactivation of clotting factors IIa, IXa, Xa, XIa, XIIa, and XHIa

296
Q

Which system of the clotting cascade is mainly affected by heparin?

A

Intrinsic system

297
Q

Which laboratory test is used to monitor heparin therapy?

A

Partial thromboplastin time (PTT); therapeutic PTT levels are 1.5 to 2.5 times that of normal

298
Q

How is heparin administered?

A

Intravenously (IV), subcutaneously (SQ)

299
Q

Why is intramuscular administration of heparin contraindicated?

A

Hematoma formation

300
Q

What are the therapeutic indications of heparin?

A

Prevention and treatment (by preventing expansion of the clot) of deep vein thrombosis (DVT) and pulmonary embolism (PE); used for anticoagulation during MI

301
Q

What is the onset of action of heparin?

A

IV = immediate onset of action; SQ = 20 to 30 minutes

302
Q

Does heparin cross the placental barrier?

A

No, therefore it is safe in pregnancy.

303
Q

What are the adverse effects of heparin?

A

Bleeding; hypersensitivity; osteoporosis; heparin-induced thrombocytopenia (HIT)

304
Q

Heparin undergoes what type of metabolism?

A

Hepatic; reticuloendothelial system

305
Q

What drug is used to counteract heparin overdose?

A

Protamine sulfate

306
Q

Roughly, how many units of heparin are neutralized by 1 mg of protamine sulfate?

A

100 units

307
Q

What is the onset of action of protamine sulfate?

A

5 minutes

308
Q

What paradoxical adverse effect can protamine cause at high doses?

A

Anticoagulation leading to hemorrhage

309
Q

What is the mechanism of action of enoxaparin?

A

Low-molecular-weight heparin (LMWH) that has a higher ratio of antifactor Xa to antifactor Ha activity versus unfractionated heparin (UFH)

310
Q

What is the half-life of LMWH?

A

Two to four times that of UFH

311
Q

Does PTT need to be monitored in patients on LMWH therapy?

A

No

312
Q

What synthetic pentasaccharide causes an antithrombin-III-mediated selective inhibition of factor Xa?

A

Fondaparinux

313
Q

Which system of the clotting cascade is mainly affected by warfarin?

A

Extrinsic system

314
Q

Which laboratory tests are used to monitor warfarin therapy?

A

Prothrombin time (PT); international normalized ratio (INR) → therapeutic INR levels are between 2 and 3

315
Q

How does warfarin work as an anticoagulant?

A

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
Q

What is the onset of action of warfarin?

A

36 to 72 hours (anticoagulant action)

317
Q

How long after initiation of warfarin therapy is the full therapeutic effect seen?

A

5 to 7 days (antithrombotic action)

318
Q

Acute alcohol intoxication does what to warfarin metabolism?

A

Inhibits warfarin metabolism, thereby increasing warfarin blood levels

319
Q

Chronic alcohol use does what to warfarin metabolism?

A

Induces warfarin metabolism, thereby decreasing warfarin blood levels

320
Q

What happens to the INR of warfarin patients who begin thyroid replacement medication?

A

INR increases; thyroid hormone increases the metabolism of clotting factors, thereby potentiating the effects of warfarin

321
Q

What happens to the INR of warfarin patients who begin antimicrobial therapy with sulfonamides?

A

INR increases; sulfonamides inhibit CYP-450 2C9, thereby increasing warfarin levels

322
Q

Does warfarin cross the placental barrier?

A

Yes (contraindicated in pregnancy); warfarin is teratogenic

323
Q

What are the adverse effects of warfarin?

A

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
Q

What can be used to counteract the effects of warfarin?

A

Vitamin K (slow onset); fresh frozen plasma (rapid onset)

325
Q

How is warfarin metabolized?

A

Hepatic cytochrome β-450 enzymes

326
Q

The synthesis of what two factors is inhibited first when warfarin therapy is initiated?

A
  1. Factor VII 2. Protein C (therefore patients may initially be hypercoagulable when warfarin is first initiated)
327
Q

Why are factor VII and protein C inhibited first when warfarin therapy is initiated?

A

These proteins have the shortest half-lives when compared to the half-lives of factors II, IX, X, and protein S

328
Q

What is the mechanism of action of abciximab, eptifibatide, and tirofiban?

A

Blockade of the glycoprotein IIb/IIIa receptor on platelets, thereby inhibiting platelet aggregation

329
Q

What is the physiologic ligand for the glycoprotein Ilb/IIIa receptor?

A

Fibrinogen

330
Q

What is the mechanism of action of thrombolytic agents?

A

Conversion of plasminogen to plasmin; plasmin cleaves fibrin, thereby leading to lysis of thrombi

331
Q

What is the main adverse effect of thrombolytic agents?

A

Hemorrhage

332
Q

Thrombolytic agents are contraindicated in what settings?

A

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
Q

What are the therapeutic indications of thrombolytic therapy?

A

Acute MI; acute PE; acute ischemic stroke

334
Q

What is the “therapeutic time window” for administering thrombolytic agents to patients with acute ischemic stroke?

A

Within the first 3 hours of the onset of symptoms

335
Q

Give examples of thrombolytic agents:

A

Alteplase; anistreplase; streptokinase; urokinase

336
Q

What two drugs can counteract thrombolytic agent therapy?

A
  1. Aminocaproic acid 2. Tranexamic acid (both agents inhibit plasminogen activation)
337
Q

With regard to thrombolytic agents, what does “clot-specific” mean?

A

The drug specifically activates plasminogen that is bound to fibrin in a thrombus with a low affinity for free, circulating plasminogen

338
Q

Which thrombolytic agent is “clot-specific”?

A

Alteplase

339
Q

Alteplase is also known as what?

A

tPA (tissue plasminogen activator)

340
Q

What is the half-life of tPA?

A

5 minutes

341
Q

Where does tPA come from?

A

Recombinant DNA technology

342
Q

What type of enzymatic activity does tPA possess?

A

Serine protease activity

343
Q

Where does streptokinase come from?

A

Group C β-hemolytic streptococci

344
Q

How does streptokinase work as a thrombolytic agent?

A

Forms a 1:1 complex with plasminogen; complexed plasminogen then converts free plasminogen into plasmin (active form)

345
Q

Does streptokinase have any enzymatic activity?

A

No

346
Q

Is streptokinase “clot-specific”?

A

No

347
Q

What other proteins does the streptokinase-plasminogen complex degrade?

A

Fibrinogen; factor V; factor VII

348
Q

What laboratory value is monitored with streptokinase therapy?

A

Thromboplastin time

349
Q

Why is streptokinase antigenic?

A

It is recognized as a foreign protein (antigen).

350
Q

What adverse reactions are specific to streptokinase?

A

Anaphylaxis; rash; fever

351
Q

What is the half-life of anistreplase?

A

90 minutes

352
Q

How does anistreplase work as a thrombolytic?

A

Anisoyl group blocks the active site of plasminogen; as complex binds to fibrin, anisoyl group is removed and the complex becomes activated.

353
Q

Does urokinase have enzymatic activity?

A

Yes

354
Q

Originally, where did urokinase come from?

A

Human urine

355
Q

Where does urokinase come from now?

A

Fetal renal cells (human)

356
Q

Is urokinase antigenic?

A

No, since it is not a foreign protein.

357
Q

Will streptokinase, at normal doses, work in patients with a recent history of streptococcal infection?

A

No, because antibodies made against recent streptococcal antigens will bind to and inactivate streptokinase.

Pharmacology (25 decks)

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