Review - CVS/Renal Agents Flashcards Preview

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Flashcards in Review - CVS/Renal Agents Deck (307):
0

Fast response fibers - phase 0?

Na ion channels open (inward) which leads to membrane depolarization.

1

Fast response fibers - phase I?

Na channels are inactivated.
K channels (outward) are activated.
Cl channels (inward) are activated.

2

Fast response fibers - phase II?

Plateau phase.
Slow influx of Ca balanced by OUTWARD K current (delayed rectifier current Ik).

3

Fast response fibers - phase III?

Repolarization phase.
Outward K current increases.
Inward Ca current decreases.

4

Fast response fibers - phase IV?

Membrane returns to resting potential.

5

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

Phase 0 and III.

6

On what phase of the cardiac AP do lidocaine + flecainide + quinidine work?

Phase 0

7

Beta blockers - what phase(s) of cardiac AP?

II and IV

8

Responsible for maintaining electrochemical gradient?

Na/K ATPase.

9

Ion current responsible for depolarization of SA and AV nodal fibers?

Ca (inward)

10

Ion current responsible for REpolarization of SA and AV nodal fibers?

K (outward)

11

Phase IV of AP in SLOW-response fibers (SA/AV node) - difference from phase IV in fast?

Slow --> Automaticity - ability to depolarize spontaneously.
Rising phase IV slope of the action potential = pacemaker potential.

12

Ion current responsible for the "pacemaker" current - rising slope of phase IV?

Na (inward)
Ca (inward)
K (outward)

13

Pacemaker of the heart has fastest uprising phase IV slope - where is this pacemaker in healthy individuals?

SA node

14

Effective refractory period vs Relative refractory period - difference?

No stimulus, no matter the strength, can elicit a response with fibers in the ERP - a strong one can elicit stimulus in the RRR.

15

Three states of voltage-gated Na channel?

1. Resting
2. Open
3. Inactivated

16

Two types of GATES of voltage-gated Na channel?

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

17

Why is the rate of recovery from an AP slower in ischemic tissue?

Cells are already partly depolarized at rest.

18

Antiarrhythmics with membrane-stabilizing effects?

Beta blockers

19

Antiarrhythmic are grouped into 4 classes according to what classification system?

Vaughn-Williams classification.

20

Class I antiarrhythmics - mechanism?

Na blockers

21

Class II antiarrhythmics - mechanism?

Beta blockers

22

Class III antiarrhythmics - mechanism?

K blockers

23

Class IV antiarrhythmics - mechanism?

Ca blockers

24

Class I - further subdivisions?

Ia
Ib
Ic

25

Class Ia antiarrhtyhmics?

1. Quinidine (antimalarial/antiprotozoal agent)
2. Procainamide
3. Disopyramide

26

Class Ib antiarrhythmics?

1. Lidocaine
2. Mexiletine
3. Tocainide
4. Phenytoin

27

Class Ic antiarrhythmics?

1. Encainide
2. Flecainide
3. Propafenone
4. Moricizine

28

Class II antiarrhythmics?

1. Propranolol
2. Esmolol
3. Metoprolol

29

Class III antiarrhythmics?

1. Amiodarone
2. Sotalol
3. Ibutilide
4. Dofetilide

30

Class IV antiarrhythmics?

1. Verapamil
2. Diltiazem

31

3 antiarrhythmics that do NOT fit in the Vaughn-Williams classification system?

1. Digoxin
2. Adenosine
3. Mg

32

Mg is used to treat what specific type of arrhythmia?

Torsades de pointes - polymorphic ventricular tachycardia.

33

Adenosine - what types of arrhythmia?

1. Paroxysmal supraventricular tachycardia (PSVT)
2. Specifically narrow complex tachycardia or supraventricular tachycardia (SVT) with aberrancy.
3. AV nodal arrhythmias - adenosine causes transient V block.

34

Symptomatic patients or unstable tachycardia with pulses - adenosine or cardioversion?

Cardioversion

35

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 extremely short half-life.

36

Adenosine rapid IV push - followed by?

5-10cc flush of saline to facilitate its delivery to the heart.

37

Mechanism of action of adenosine?

Stimulates A receptors --> decr. in cAMP (via Gi).
+ incr. K efflux leading to increased hyperpolarization
+ incr. refractory period in AV node.

38

Adenosine - side effects?

1. Flushing
2. Chest pain
3. Dyspnea
4. Hypotension

39

2 drugs that antagonize adenosine?

1. Caffeine
2. Theophylline

40

How is adenosine dosed?

1. 6mg initially by rapid IV push.
2. If NOT effective within 1-2min, give 12mg repeat dose.
3. Follow each bolus of adenosine with normal saline flush.
4. 12mg dose may be repeated once.

41

Most deadly ion that can be administered?

K

42

HYPERkalemia - ECG?

1. Flattened P waves
2. Widened QRS
3. Peaked T waves
4. Sine waves
5. V-fib

43

HYPOkalemia - ECG?

1. Flattened or inverted T wave
2. U waves
3. ST-segment depression

44

Ia antiarrhythmics - effect on AP duration?

UP

45

Ia antiarrhythmics - effect on ERP?

UP

46

Ia antiarrhythmics - effect on conduction velocity?

DOWN

47

Ia antiarrhythmics - effect on phase IV slope?

DOWN

48

Ib antiarrhythmics - effect on AP duration?

DOWN

49

Ib antiarrhythmics - effect on ERP?

Little or no change.

50

Ib antiarrhythmics - effect on conduction velocity?

Decrease (primarily in ischemic tissue).

51

Ib antiarrhythmics - phase IV slope?

DOWN

52

Ic antiarrhythmics - AP?

Little or no change

53

Ic antiarrhythmics - ERP?

Little or no change

54

Ic antiarrhythmics - conduction velocity?

DOWN

55

Ic antiarrhythmics - Phase IV slope?

Down

56

Dromotropes?

Drugs that affect AV conduction velocity.

57

QT interval prolongation, and therefore torsades, is more likely to occur with what 2 classes of antiarrhythmics?

Ia and III

58

Class Ia antiarrhythmic that also blocks α receptors + muscarinic receptors --> potentially leading to incr. HR and AV conduction?

Quinidine

59

Side effects of quinidine?

1. Tachycardia
2. Proarrhythmic
3. Incr. digoxin levels via protein-binding displacement
4. Nausea
5. Vomiting
6. Diarrhea
7. Cinchonism

60

Cinchonism?

Syndrome that may include:
1. Tinnitus
2. High-frequency hearing loss
3. Deafness
4. Vertigo
5. Blurred vision
6. Diplopia
7. Photophobia
8. Headache
9. Confusion
10. Delirium

61

Procainamide - side effects?

1. Drug-induced lupus (25-30% of patients)
2. Proarrhythmic
3. Depression
4. Psychosis
5. Hallucination
6. Nausea
7. Vomiting
8. Diarrhea
9. Agranulocytosis
10. Thrombocytopenia
11. Hypotension

62

Drug-induced lupus - drugs?

1. Procainamide
2. Isoniazid
3. Chlorpromazine
4. Penicillamine
5. Sulfasalazine
6. Hydralazine
7. Methyldopa
8. Quinidine
9. Phenytoin
10. Minocycline
11. Valproic acid
12. Carbamazepine

63

Ia antiarrhythmic - peripheral vasoconstriction?

Disopyramide

64

Disopyramide - side effects?

Anticholinergic side effects:
1. Urinary retention
2. Dry mouth
3. Dry eyes
4. Blurred vision
5. Constipation
6. Sedation

65

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

True.

66

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

False

67

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

False

68

Lidocaine - side effects?

1. Proarrhythmic
2. Sedation
3. Agitation
4. Confusion
5. Paresthesia
6. Seizures

69

Ib antiarrhythmic structurally related to lidocaine?

Mexiletine

70

Ib antiarrhythmic - pulmonary fibrosis?

Tocainide

71

Propafenone - Ic antiarrhythmic - other type of antiarrhythmic activity?

β-adrenergic blockade.

72

Encaine + flecainide increase what IMPORTANT risk?

Increase sudden cardiac death in post-MI patients with arrhythmias!!!
Cardiac Arrhythmia Suppression Trial (CAST).

73

Sotalol - Class III - other antiarrhythmic activity?

Beta-blockade

74

Antiarrhythmic with class I, II, III, IV activity?

Amiodarone

75

Amiodarone half-life?

40-60days

76

Amiodarone side effects?

1. Pulmonary fibrosis
2. Tremor
3. Ataxia
4. Dizziness
5. HYPER + HYPOthyroidism
6. Hepatotoxicity
7. Photosensitivity
8. Blue skin discoloration (!)
9. Neuropathy
10. Muscle weakness
11. Proarrhythmic
12. Corneal deposits
13. Lipid abnormalities
14. Hypotension
15. Nausea/vomiting
16. CHF
17. Optic neuritis
18. Pneumonitis
19. Abnormal taste
20. Abnormal smell
21. SIADH

77

Amiodarone - patient monitoring?

1. ECG
2. Thyroid function tests
3. Pulmonary function tests
4. Liver function tests
5. Electrolytes
6. Ophthalmology examination

78

Verapamil - DO NOT give in what arrhythmias?

1. Wolff-Parkinson-White (WPW) syndrome
2. Ventricular tachycardia

79

Verapamil side effects?

1. Drug interactions
2. Constipation
3. Hypotension
4. AV block
5. CHF
6. Dizziness
7. Flushing

80

Digoxin - what arrhythmias?

1. A-fib
2. A-flutter

81

Digoxin-INDUCED arrhythmias - what give?

1. Lidocaine
2. Phenytoin

82

How is QTc calculated?

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

83

Why must QT be corrected?

QT depends on HR, so higher HR will display shorter QT on ECG.
It is corrected to remove the variable of HR.

84

Normal value for QTc?

Less than 440msec.

85

Long QT - risk for?

Torsades - Ventricular arrhythmia that can degenerate into v-fib.

86

Normal CO?

5L/min

87

3 compensatory physiologic responses in CHF?

1. Fluid retention
2. Incr. sympathetic drive
3. Hypertrophy of cardiac muscle

88

Define preload:

The pressure stretching the ventricular walls at the onset of ventricular contraction - related to LVEDV/P.

89

Define afterload:

The load or force developed by the ventricle during systole.

90

Drugs to DECREASE PRELOAD?

1. Diuretics
2. Vasodilators
3. ACEIs
4. ARBs
5. Nitrates

91

Drugs to DECREASE AFTERLOAD?

1. Vasodilators
2. ACEIs
3. ARBs
4. Hydralazine

92

Drugs to increase CONTRACTILITY?

1. Digoxin
2. Phosphodiesterase inhibitors - amrinone, milrinone
3. Beta agonists

93

Digoxin side effects?

1. Arrhythmias
2. Nausea/vomiting
3. Anorexia
4. Headache
5. Confusion
6. Blurred vision
7. Visual disturbances, such as YELLOW HALOS around light sources.

94

Electrolyte abnormalities that predispose to digoxin toxicity?

1. Hypokalemia
2. Hypomagnesemia
3. Hypercalcemia

95

Digoxin-induced arrhythmias?

1. Supraventricular tachycardias
2. AV nodal tachycardias
3. AV block
4. V-tach
5. V-fib
6. Complete heart block

96

Digoxin - use in WPW syndrome?

No - Since digoxin slows conduction through the AV node, the accessory pathway present in WPW is left UNOPPOSED --> SVT and A-arrhythmias.

97

Digoxin toxicity - treat?

1. Correction of electrolyte disturbances
2. Antiarrhythmics
3. Anti-digoxin Fab antibody (Digibind)

98

Drugs that INCREASE digoxin concentrations?

1. Quinidine
2. Amiodarone
3. Erythromycin
4. Verapamil

99

Drugs that DECREASE digoxin concentration?

1. Loop diuretics
2. Thiazide diuretics
3. Corticosteroids

100

Does digoxin therapy in CHF lead to prolonged survival?

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

101

Classes of medications that have been shown to increases survival in CHF patients?

ACEIs/ARBs
Beta-blockers

102

How does dobutamine work in CHF?

Beta-1 agonist:
1. Incr. CONTRACTILITY
2. Incr. vasodilation
via UP cAMP.

103

Amrinone + milrinone mechanism?

Inhibits phosphodiesterase --> UP cAMP --> UP intracell. Ca --> UP contractility + VASODILATION.

104

PDEIs side effects?

1. Milrinone --> may decr. survival in CHF.
2. Amrinone --> may cause thrombocytopenia.

105

How do diuretics work in CHF?

Decr. in intravascular volume - thereby DECREASE in preload.
Reduce pulmonary and peripheral edema - often seen in CHF patients.

106

2 beta blockers with specific indications for treatment of CHF?

1. Metoprolol
2. Carvedilol (mixed alpha-/beta-blocker)

107

Nesiritide - mechanism?

Recombinant BNP --> UP cGMP in vascular smooth muscle + endothelial cells.

108

ACEIs effect on CHF?

Inhibition of AT-II production --> Decr. TPR --> Decr. AFTERLOAD.
+ Prevents LV remodeling.

109

2 strategies in treatment of angina?

1. Incr. O2 supply
2. Decr. O2 demand

110

Drugs that increase O2 supply?

1. Nitrates
2. CCBs

111

Drugs that decrease O2 demand?

1. Nitrates
2. CCBs
3. Beta-blockers

112

Drugs of choice for immediate relief of anginal symptoms?

Sublingual nitroglycerin (NGT).

113

Mechanism of action of nitrates?

Nitrates form NITRITES --> Nitrites form NO --> NO incr. cGMP --> Incr. cGMP leads to incr. relaxation of vascular smooth muscle.

114

How does cGMP leads to relaxation of vascular smooth muscle?

Causes DEPHOSPHORYLATION of myosin light chains.

115

How do nitrates incr. O2 supply?

Dilation of coronary vessels --> incr. blood supply.

116

How do nitrates DECREASE O2 demand?

1. Dilation of large veins --> PRELOAD reduction.
2. Decr. preload --> reduced work of heart.
3. Decr. work of heart --> decr. O2 demand.

117

Nitrates side effects?

1. Headache
2. Hypotension
3. Reflex tachycardia
4. Facial flushing
5. Methemoglobinemia

118

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.

119

Nitrates contraindicated in patients taking any of which 3 drugs?

1. Sildenafil
2. Vardenafil
3. Tadalafil

120

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

Cyanide

121

Common formulations of nitrates?

1. NTG
2. Isosorbide
3. Mononitrate
4. Isosorbide dinitrate

122

Time for peak effect of sublingual NTG?

2min.

123

Dosing frequency of sublingual NTG during an anginal episode?

Every 5 minutes for a maximum of 3 doses.

124

How do beta-blockers work in angina?

Block of beta-1 --> Decr. CO, HR, Contractility --> reducing workload of the heart + O2 demand.

125

Do beta-blockers increase O2 supply?

NO

126

Verapamil - effect on the myocardium or peripheral vasculature?

Myocardium - greater negative inotropic effects.

127

Dihydropyridines - effect on myocardium or peripheral vasculature?

Peripheral vasculature - more potent vasodilators.

128

Diltiazem - effect on myocardium or peripheral vasculature?

Myocardium

129

Dihydropyridines are?

1. Nifedipine
2. Amlodipine
3. Felodipine
4. Isradipine
5. Nicardipine

130

CCBs in the treatment of angina?

Block vascular L-type calcium channels which leads to decreased heart contractility + incr. vasodilation.

131

Goal BP in patients without DM or chronic kidney disease?

<140/90

132

Goal BP in patients with DM or chronic kidney disease?

<130/80

133

Kidney responds to reduced BP by releasing what peptidase?

Renin

134

Renin is responsible for what enzymatic reaction?

Angiotensinogen --> AT-I.

135

Where is ACE found?

Lungs

136

Immediate/acute effects of thiazide diuretics?

1. Incr. Na
2. Incr. Cl
3. Incr. H2O exertion
--> Decr. blood volume.

137

Chronic effects of thiazide diuretics?

Decr. TPR.

138

Thiazides - site of action?

Disstal convoluted tubule of nephron.

139

Thiazides - inhibit what transporter?

Na/Cl transporter

140

Examples of thiazides?

1. HCTZ
2. Chlorothiazide
3. Chlorthalidone

141

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

50mL/min.

142

Thiazides - Serum Ca?

Increased

143

Thiazides - Serum Mg?

Decreased

144

Thiazides - Serum K?

Decreased

145

Thiazides - Serum Na?

Decreased

146

Thiazides for Ca stones in the urine?

Yes - Incr. Ca reabsorption.

147

Side effects of HCTZ?

1. Hypercalcemia
2. Hypokalemia
3. HypoMg
4. HYPERGLYCEMIA
5. HYPERURICEMIA
6. Pancreatitis
7. Metabolic ALKALOSIS
8. Stevens-Johnson
9. Hyperlipidemia

148

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

Sulfonamides.

149

Loops?

1. Furosemide
2. Bumetanide
3. Ethacrynic
4. Torsemide

150

Which loop can be given safely to patients with allergy to sulfonamides?

Ethacrynic

151

Loops increase Ca exertion?

Yes.

152

Side effects of loops?

1. Hypersensitivity
2. Hypocalcemia
3. Hypokalemia
4. HypoMg
5. Met alkalosis
6. HYPERURICEMIA
7. OTOTOXICITY

153

Loop that is MOST OTOTOXIC?

Ethacrynic

154

Mannitol - mechanism of action?

Osmotic diuretic - thereby drawing water via increased osmolality into the PCT, LOH (thin descending) + collecting ducts.

155

Mannitol - used for?

1. Decr. in INTRAOCULAR + INTRACRANIAL pressure.
2. Prevents ANURIA in hemolysis + rhabdomyolysis.

156

Carbonic anhydrase (CA) inhibitors?

1. Acetazolamide
2. Dorzolamide

157

CA inhibitors - mechanism?

Incr. EXCRETION of Na + HCO3.

158

CA inhibitors - metabolic disturbance?

Met ACIDOSIS.

159

CA inhibitors used for?

1. Altitude sickness (decr. cerebreal and pulmonary edema).
2. Glaucoma - decr. aqueous humor formation thereby decreasing intraocular pressure.
3. Metabolic alkalosis
4. Enhance RENAL EXCRETION of acidic drugs.

160

3 K-sparing diuretics?

1. Spironolactone
2. Triamterene
3. Amiloride

161

Spironolactone - mechanism?

Aldosterone receptor blocker.

162

Where in the kidney is the aldosterone receptor found?

Basolateral membrane of the principal cell in the collecting duct.

163

Where in the kidney does triamterene and amiloride work?

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

164

Spironolactone - side effects?

1. Hyperkalemia
2. Metabolic acidosis
3. Gynecomastia

165

Triamterene often used with?

HCTZ

166

Spironolactone - used for?

1. HTN
2. CHF
3. Ascites

167

Amiloride is used to treat what conditions?

1. HTN
2. CHF
3. Li-induced diabetes insipidus

168

2 Cardioselective beta blockers that are widely used?

1. Metoprolol
2. Atenolol

169

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

1. Asthma (incr. risk of bronchospasm).
2. Diabetes
3. Peripheral vascular disease

170

Beta blockers action on the kidney?

DECREASE RENIN RELEASE --> Prevent renin stimulation by catecholamines + likely DIRECT depression of the RAA system.

171

Beta blockers side effects?

1. Hypotension
2. Lipid abnormalities
3. Rebound HTN with abrupt withdrawal
4. Fatigue
5. Insomnia
6. Sexual dysfunction
7. Hallucinations
8. Depression
9. Hyperglycemia

172

Beta blocker with shortest half-life?

Esmolol (9min) - usually administered as a continuous drip.

173

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.

174

Action of bradykinin on vascular smooth muscle?

Vasodilation

175

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

Dry cough!

176

ACEIs - side effects?

1. Hypotension
2. Dry cough
3. Hyperkalemia
4. Angioedema
5. Fever
6. Altered taste

177

ACEIs - 2 contraindications?

1. Pregnancy (teratogenic)
2. Bilateral renal artery stenosis

178

Specific receptor type that ARBs antagonize?

AT-II type 1 receptor.

179

Do ARBs cause dry cough?

No - ARBs do not inhibit the breakdown of bradykinin.

180

Is there a pregnancy contraindication for ARBs?

Yes - pregnancy category C for the 1st semester and pregnancy category D for the 2nd and 3rd.

181

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.

182

DHP CCBs side effects?

1. Peripheral edema
2. Hypotension
3. Reflex tachycardia
4. Headache
5. Flushing
6. Gingival hyperplasia

183

Verapamil - side effects?

1. Drug-drug interactions
2. Constipation
3. AV block
4. Headache

184

CCB action on the kidney?

Natriuretic activity

185

CCB that is used in subarachnoid hemorrhages to prevent vasospasm?

Nimodipine

186

T-type CCB used in absence seizures?

Ethosuximide

187

Name 3 alpha-1 blockers used for HTN?

1. Doxazosin
2. Prazosin
3. Terazosin

188

2 main side effects of alpha-1 blockers?

1. 1st dose syncope
2. Reflex tachycardia

189

What class of drugs can be used to block the reflex tachycardia caused by alpha-1 blockers?

Beta blockers

190

Alpha-1 blockers are most commonly used for what condition other than hypotension?

BPH

191

Clonidine mechanism as antihypertensive?

Central alpha-2 agonist --> Decr. sympathetic outflow from the CNS, producing a decrease in TPR, HR, and BP.

192

Why are diuretics often given to patients on clonidine therapy?

Clonidine causes Na/H2O retention.

193

Other than HTN, what is clonidine used for?

1. Nicotine withdrawal
2. Heroin withdrawal
3. Alcohol dependance
4. Migraine prophylaxis
5. Severe pain
6. Clozapine-induced sialorrhea

194

Clonidine side effects?

1. Bradycardia
2. Sedation
3. Dry mouth
4. Rebound HTN with ABRUPT withdrawal (must taper down dose when discontinuing therapy)
5. Edema

195

Can clonidine be used in patients with renal dysfunction?

Yes, because renal blood flow and GFR are not compromised with clonidine therapy.

196

Alpha-methyldopa is converted to what active metabolite?

Methyl-norepinephrine

197

Mechanism of action of alpha-methyldopa?

Central alpha-2 agonist.

198

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

Yes

199

Is alpha-methyldopa contraindicated in pregnancy?

NO - It is one of the antihypertensive drugs of choice in pregnant women.

200

Side effects of alpha-methyldopa?

1. Sedation
2. Hemolytic anemia
3. Drug-induced lupus
4. Edema
5. Bradycardia
6. Dry mouth

201

Name the drug:
1. Decreases TPR
2. Ofter requires beta-blocker to counteract subsequent tachycardia.
3. May cause drug-induced lupus

Hydralazine

202

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

Diuretics

203

Side effects of hydralazine?

1. Reflex tachycardia
2. Fluid retention
3. Drug-induced lupus
4. Headache
5. Flushing

204

Enzyme responsible for the metabolism of hydralazine?

N-acetyltransferase

205

Minoxidil - mechanism?

Opens K channels which leads to membrane hyperpolarization and subsequent arterial vasodilation.

206

Minoxidil is a prodrug that is activated by what mechanism?

Sulfation

207

Common side effect of minoxidil?

Hypertrichosis - used in treatment of alopecia.

208

Name the drug:
1. Direct acting vasodilator, used in hypertensive emergencies
2. Can be used to prevent hypoglycemia in patients with insulinoma

Diazoxide

209

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

It decreases insulin release.

210

Name the drug:
1. Used in hypertensive emergenies.
2. Acts via incr. cGMP through NO mechanisms
3. Forms thiocyanate and cyanide metabolites

Sodium nitroprusside

211

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

ACEIs

212

What class of antihypertensives may improve patient's lipid profiles?

Alpha-1 blockers.

213

What 2 classes of antihypertensives may protect renal function in patients with DM?

ACEIs and ARBs --> DECREASE MICROALBUMINURIA.

214

Statins - how do they affect the lipid profile?

1. Mainly reduces LDL
2. Moderate reduction of TGs
3. Moderate elevation of HDLs

215

Statins - side effects?

1. Incr. LFTs
2. Dose-dependent rhabdomyolysis
3. Myalgia
4. Myopathy
5. Diarrhea
6. Lupus
7. Drug-drug interaction
8. Contra in pregnancy - Category X

216

Lab tests for monitoring statin toxicity?

LFT
CPK

217

Most potent antihyperlipidemic agent to elevate HDL?

Niacin

218

Another name for niacin?

B3, nicotinic acid.

219

Niacin - mech of action?

1. High-dose niacin INHIBITS VLDL and apoprotein synthesis in liver.
2. Incr. t-PA
3. Decr. fibrinogen

220

How does niacin affect the lipid profile?

1. Elevation of HDL
2. Reduction of LDL
3. Reduction of VLDL
4. Reduction of TGs

221

Niacin - side effects?

1. Facial flushing
2. Hyperuricemia
3. Hyperglycemia
4. Hepatotoxicity
5. Pruritus
6. Nausea
7. Abdominal pain

222

How is facial flushing counteracted in patients on niacin therapy?

Pretreatment with aspirin to counteract PG release.

223

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

Ezetimibe

224

Side effects of ezetimibe?

1. Diarrhea
2. Abdominal pain
3. Headache
4. Arthralgias

225

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

Fibrates.

226

Mention some fibrates?

1. Gemfibrozil
2. Clofibrate
3. Fenofibrate

227

Major effect that fibrates have on the lipid profile?

Reduction of TGs.

228

Side effects of gemfibrozil?

1. Cholelithiasis
2. Nausea
3. Diarrhea
4. Abdominal pain
5. Myositis
6. Hypokalemia
7. Incr. levels of warfarin + sulfonylureas via protein-binding displacement.

229

Mechanism of action of bile acid sequestrants?

Anion exchange resins that bind bile acids/salts in the small intestine, thereby preventing their reabsorption; decr. bile acids results in incr. plasma cholesterol uptake by hepatocytes to replenish bile acid levels, thereby decreasing plasma LDL levels.

230

Give examples of bile acid sequestrants?

1. Cholestyramine
2. Colestipol
3. Colesevelam

231

Side effects of bile acid sequestrants?

1. Constipation
2. Bloating
3. Flatulence
4. Nausea
5. Impaired absorption of fat-soluble vitamins
6. Impaired absorption of warfarin
7. Digoxin
8. ASA
9. Tetracycline
10. Thiazides

232

What OTC 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.

233

Where is PGI2 made?

Vascular endothelial cells

234

Where is TXA2 made?

Platelets

235

Incr. PGI2 leads to an increase of what 2nd messenger?

cAMP

236

cAMP does what to platelets?

Inhibits platelet activation and release of platelet aggregating factors.

237

How does ASA work as a platelet aggregation inhibitor?

Irreversible inhibition, via ACETYLATION of COX --> reducing TXA2 levels.

238

What 2 drugs inhibit platelet aggregation + platelet fibrinogen interaction by blocking ADP receptors?

1. Clopidogrel
2. Ticlopidine

239

Ticlopidine - side effects?

1. Neutropenia
2. Agranulocytosis
3. TTP

240

How should patients on ticlopidine therapy be monitored?

CBC with differential every 2 weeks for the first 3 months of therapy and as needed thereafter.

241

Dipyridamole - mechanism as a platelet aggregation inhibitor?

Inhibits phosphodiesterase (PDE) thereby incr. cAMP levels --> cAMP potentiates PGI2 + Inhibits TXA2 synthesis.

242

Dipyridamole - usually given with?

Aspirin

243

Another name for factor II?

Prothrombin

244

Another name for factor IIa?

Thrombin

245

How does heparin work as an anticoagulant?

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

246

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

Intrinsic pathway.

247

Which lab test is used to monitor heparin therapy?

PTT, therapeutic PTT levels are 1.5 to 2.5 times that of normal.

248

How is heparin administered?

IV or SQ

249

Why is intramuscular administration of heparin contraindicated?

Hematoma formation

250

Trerapeutic indications of heparin?

1. Prevention and treatment (by preventing expansion of the clot) of DVT and pulmonary embolism (PE).
2. Used for anticoagulation during MI.

251

Onset of action of heparin?

IV = Immediate onset
SQ = 20-30min

252

Does heparin cross the placental barrier?

No, therefore it is safe in pregnancy.

253

What are the adverse effects of heparin?

1. Bleeding
2. Hypersensitivity
3. Osteoporosis
4. Heparin-induced thrombocytopenia (HIT)

254

Heparin undergoes what type of metabolism?

1. Hepatic
2. Reticuloendothelial system

255

What drug is used to counteract heparin OD?

Protamine sulfate.

256

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

100 units.

257

Onset of action of protamine sulfate?

5min

258

What paradoxical side effect can protamine cause at high doses?

Anticoagulation leading to hemorrhage.

259

What is the mechanism of action of enoxaparin?

LMWH that has higher ratio of antifactor Xa to antifactor IIa activity vs unfractionated heparin (UFH).

260

Half-life of LMWH?

2-4 times that of UFH.

261

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

No.

262

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

Fondaparinaux

263

Which pathway is mainly affected by warfarin?

Extrinsic

264

Which lab tests are used to monitor warfarin?

PT - INR --> Therapeutic levels are between 2 and 3.

265

Warfarin - mechanism?

1. Inhbitis synthesis of vit-K-dependent clotting factors II, VII, IX, X via inhibition of vitK epoxide reductase.
2. Also inhibits synthesis of protein C and protein S.

266

Warfarin onset of action?

36-72hrs (anticoagulant action)

267

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

5-7 days (antithrombotic action).

268

Acute alcohol intoxication does what to warfarin metabolism?

Inhibits warfarin metabolism - thereby increasing warfarin blood levels.

269

Chronic alcohol use does what to warfarin metabolism?

Induces warfarin metabolism, thereby decreasing warfarin blood levels.

270

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.

271

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

INR increases.
Sulfonamides inhibit CYP-450 2C9 --> Incr. warfarin levels.

272

Does warfarin cross the placenta?

YES - Contra in pregnancy - teratogenic.

273

Warfarin side effects?

1. Bleeding
2. Drug-drug interactions
3. Skin necrosis (seen within the first few days of warfarin therapy and is secondary to decr. protein C levels).
4. "Purple toes syndrome" --> by cholesterol microemboli!!!

274

What can be used to counteract the effects of warfarin?

Vit K --> SLOW onset.
Fresh frozen plasma --> Rapid onset.

275

The synthesis of which 2 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.

276

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 II, IX, X, S.

277

Mechanism of action of abciximab, eptifibatide, tirofiban?

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

278

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

Fibrinogen

279

What is the mechanism of action thrombolytic agents?

Conversion of plasminogen to plasmin --> cleaves fibrin, thereby leading to lysis of thrombi.

280

What is the main side effect of thrombolytic agents?

Hemorrhage

281

Thrombolytic agents - contra in what settings?

1. Active internal bleeding
2. History of cerebrovascular accident
3. Recent intracranial or intraspinal surgery
4. Intracranial neoplasm
5. AV malformation
6. Severe uncontrolled HTN (SBP>185, or DBP>110).
7. Evidencce of intracranial hemorrhage
8. Suspected aortic dissection
9. Seizure at the onset of stroke
10. Current use of anticoagulants or an INR >1.7
11. Lumbar puncture within 1 week

282

Therapeutic indications of thrombolytic therapy?

1. Acute MI
2. Acute PE
3. Acute ischemic stroke

283

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.

284

Give examples of thrombolytic agents?

1. Alteplase
2. Anistreplase
3. Streptokinase
4. Urokinase

285

What 2 drugs can counteracct thrombolytic agent therapy?

1. Aminocaproic
2. Tranexamic acid
--> BOTH inhibit plasminogen activation.

286

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

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

287

Which trombolytic agent is "clot-specific"?

Alteplase

288

Alteplase is also known as?

tPA

289

tPA half-life?

5min

290

Where does tPA come from?

Recombinant DNA tech.

291

What type of enzymatic activity does tPA possess?

Serine protease activity.

292

Where does streptokinase come from?

Group C β-hemolytic streptococci.

293

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).

294

Does streptokinase have any enzymatic activity?

No

295

Is streptokinase "clot-specific"?

NO

296

What proteins does the streptokinase-plasminogen complex degrade?

1. Fibrinogen
2. V
3. VII

297

What lab value is monitored with streptokinase therapy?

Thromboplastin time.

298

Why is streptokinase antigenic?

It is recognized as a foreign protein (antigen).

299

What side effects are specific to streptokinase?

1. Anaphylaxis
2. Rash
3. Fever

300

Half-life of anistreplase?

90min

301

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.

302

Does urokinase have enzymatic activity?

Yes

303

Originally, where did urokinase come from?

Human urine

304

Where does urokinase come from now?

Fetal renal cells (human).

305

Is urokinase antigenic?

No, since it is not a foreign protein.

306

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

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

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