Cardio Exam 1 Part 2

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Bowen and Hassan Pharmacology
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1

What are the 5 critical points that should be considered when discussing the heart?

  • Heart contractions must be synchronized.
  • The valves of the heart must open completely (not stenotic).
  • The valves of the heart must not leak (not insufficient or regurgitant).
  • Myocardial muscle cells must provide enough force to move the blood.
  • The ventricles must be able to fill during diastole.
2

What are the 3 essential mechanisms in regards to the circulatory system?

  • There must be sufficient blood flow in the capillaries.
  • Diffusion between capillaries and interstitial fluid must be small.
  • Arterial blood must have the correct physiological parameters.
3

Blood flow within the lungs involving the O2 and CO2 gas exchange between the blood and the alveoli is known as what?

Pulmonary Circulation

4

Blood flow involving all the blood vessels in the body except for the lungs.

Systemic Circulation

5

Pulmonary circulation occurs at what pressure?

Low pressure

6

Does systemic circulation occur at low or high pressure?

high pressure

7

The pulmonary and systemic circuits are arranged how?

in-series (therefore, the two systems pump essentially the same amount of blood called the cardiac output which is approximately 5-6 L/min)

8

The phase of ventricular relaxation and filling is known as what?

Diastole

9

The phase of ventricular contraction is known as what?

Systole

10

The following bullet describes what?

  • The ventricular wall tension [force] at the end of diastole. In clinical terms, it is the stretch on the ventricular fibers just before contraction, often approximated by the end-diastolic volume (EDV) or end-diastolic pressure (EDP).

Preload

11

The following bullet describes what?

  • Property of heart muscle that accounts for changes in the strength of contraction, independent of the preload and afterload. Reflects chemical or hormonal influences (e.g., catecholamines) on the force of contraction

Contractility

12

The following bullet describes what?

  • The ventricular wall tension [force] during contraction; the force that must be overcome for the ventricles to eject its contents. Often approximated by the systolic ventricular (or arterial) pressure.

Afterload

13

The quantity of blood pumped per minute from each of the ventricles is defined as what?

Cardiac output (CO)

14

What correlates an increase in venous return and ventricular preload to an increase in stroke volume (SV)?

Frank-Starling Mechanism

15

What can be used clinically to define preload rather than calculating the wall stress?

  • LVEDP
  • LVEDV
16

What is the ratio of the stroke volume (SV) divided by the end diastolic volume (EDV), and it represents the fraction of the blood pumped out of the ventricle?

Ejection Fraction

17

What is chronotropy?

heart rate

18

What is dromotropy?

conduction velocity

19

What is inotropy?

contractility

20

What is lusitropy?

relaxation

21

The beta-1 receptor is coupled to which G-protein?

Gs

22

The alpha-1 receptor is coupled to which G-protein?

Gq

23

The M2 receptor is coupled to which G-protein?

Gi

24

The beta-2 receptor is coupled to which G-protein?

Gs

25

The alpha-2 receptor is coupled to which G-protein?

Gi

26

In the normal heart, the ejection fraction is greater than what percent?

>55%

27

Which neurotransmitter is released from sympathetic nerve terminals and binds to postfunctional adrenoceptors on the heart?

NE

28

What is the order of importance among adrenoceptors in the heart?

Beta-1 > Beta-2 > Alpha-1

29

The binding of NE to adrenoceptors of the heart results in what response?

Increase in:

  • inotropy
  • chronotropy
  • dromotropy
30

Pre-junctional Alpha-2 adrenoceptors serve as a feedback mechanism to do what?

inhibit NE release

31

Parasympathetic (vagal) nerves release which neurotransmitter?

ACh

32

ACh released from parasympathetic nerves bind to which receptors in the heart?

M2

33

The binding of ACh to M2 receptors in the heart results in what response(s)?

Decrease in:

  • inotropy
  • chronotropy
  • dromotropy
34

ACh also binds to prejunctional muscarinic receptors (M2) on sympathetic nerve terminals to do what?

Inhibit NE release

35

What term is used to describe not opening properly resulting in the heart having to work harder to pump blood through the valve?

Stenosis

36

At what stage in the circulation does the heart receive its blood supply?

At the very beginning of the blood coming out of the aorta

37

Does coronary artery circulation happen when the heart is resting or pumping?

resting

38

What is the difference between in-series and in-parallel?

In-series is one organ after the next (receiving blood) while in-parallel is multiple organs receiving blood simultaneously.

39

What is the exception to an in-series arrangement in systemic circulation?

blood flowing from the GI tract to the liver

40

A greater concentration of ANP would be found in patients that have what?

Heart failure

41

What degrades ANP in the body?

NEP

42

The more or less afterload you have the greater the SV?

less afterload

43

The more or less preload you have the greater the SV?

more preload

44

The more or less contractility you have the greater the SV?

more contractility

45

What is another name for the visceral pericardium?

epicardium

46

What is the role of the pericardium surrounding the heart?

Protects the heart/prevents heart from over-expanding

47

The fluid inside the pericardium does what?

cushioning the heart from friction

48

List the functional roles of the pericardium:

  • Extra layers of protection
  • Structural anchoring to neighboring structures
  • Viscous fluid reduces frictional forces
  • Constrains the amount of blood filling
49

Simple squamous epithelium lines the inner chambers of the heart as well as the valve and is indistinguishable from the lining of the blood vessels. What layer of the pericardium is this?

Endocardium

50

The serous membrane on the outside of the middle layer of the heart. This is synonymous with the visceral pericardium. It consists of squamous epithelial cells that overlay connective tissues. What layer of the pericardium is this?

Epicardium

51

Cardiac myocytes form the contractile layer for the ejection of blood. The sarcomeres are the contractile units of muscle with specific arrangements of the proteins (myosin, actin, and troponin). It is divided into the subendocardial and subepicardial areas. What layer of the pericardium is this?

Myocardium

52

What is the fibrous skeleton and it's role in the heart?

Tissue that is like skeletal make-up of the heart. It's role is to prevent electrical activity.

53

What is the average pressure of the aorta?

120/80

54

What is the average pressure of the RA?

4

55

What is the average pressure of the RV?

25/4

56

What is the average pressure of the PA?

25/10

57

What is the average pressure of the LA?

8

58

What is the average pressure of the LV?

120/8

59

True or False: There is a change in shape with the LV.

True

60

The LV is how many times as thick as the wall of the RV?

3x

61

What can be followed on the surface of the heart by examining the anterior and posterior interventricular grooves?

The interventricular septum

62

Due to pressure differences between the LV and RV, is the interventricular septum pushed to the right or left?

right

63

The septum separating the RA from the LA has a shallow depression called the what?

fossa ovalis

64

The fossa ovalis in the fetal heart has an opening known as the what?

foramen ovale

65

What is the hole that goes from the right to the left side of the atrium?

Atrial Septal Defect (ASD)

66

When the foramen ovale, a flap-like opening in the septum between the RA and LA in a fetus, does not close after birth it is referred to as a what?

patent foramen ovale

67

How common is a Patent Foramen Ovale (PFO)?

Very common (about 25%)

68

What condition is a result of disorganized electrical conduction pathways in the atria, which translates into less efficient pumping of the atria?

Afib

69

True or False: Afib causes the blood to “stagnate,” which in turn may lead to the formation of blood clots.

True

70

What is a major risk factor of Afib?

Stroke

71

Where do the majority of the blood clots associated with Afib form?

left atrial appendage

72

List some treatment options for Afib:

  • Blood thinners (anticoagulants)
  • Ablation
  • Surgical procedures and implantable devices
73

The obstruction of valve leading to decrease in forward blood flow is known as what?

Stenosis

74

A leaky valve leading to backflow of blood is known as what?

Insufficiency

75

Which heart sound is the result of the mitral and tricuspid valves closing at the beginning of systole?

S1 (first heart sound/ "lub")

76

Which heart sound is the result of the aortic and pulmonic valves closing at the beginning of diastole?

S2 (second heart sound/ "dub")

77

Which valves are inlet valves?

  • Atrioventricular (AV) valves
    • Tricuspid
    • Mitral
78

Which valves are outlet valves?

  • Semilunar (SL) valves
    • pulmonic
    • aortic
79

What is the primary role of cardiac myocytes?

Contraction

80

How is the contraction from myocytes initiated?

Action potentials

81

The majority of coronary blood flow occurs in what?

Diastole

82

During ventricular what the myocardium is contracting which compresses the microvasculature within the LV?

Systole

83

True or False: Diastole is shortened when the heart rate is high.

True

84

What is a transient change in the polarization of the resting membrane potential that is transferred from cell to cell based on ionic differences?

Cardiac Action Potential

85

Why is coronary blood flow greatest in the LV?

Diastole occurs in the LV

86

True or False: Normal coronary arteries can respond with dilation, but this is not the case for diseased coronary arteries.

True

87

List the steps of the Wiggers Diagram:

  • Phase 1. Atrial Systole:

AV values open; aortic and pulmonic valves close.

  • Phase 2. Isovolumetric Contraction:

All valves closed.

  • Phase 3. Rapid Ejection:

Aortic and pulmonic valves open; AV valves remain closed.

  • Phase 4. Reduced Ejection:

Aortic and pulmonic valves open; AV valves remain closed.

  • Phase 5. Isovolumetric relaxation:

All valves closed.

  • Phase 6. Rapid Filling:

AV valves open; aortic and pulmonic valves closed.

  • Phase 7. Reduced Filling:

AV valves open; aortic and pulmonic valves closed.

88

The difference between the systolic pressure and the diastolic pressure is known as what?

Aortic pulse pressure

89

The mean can be estimated as a weighted average based on the systolic pressure and diastolic pressure. This is known as what?

Mean Arterial Pressure

90

What is the volume you have associated with the PVL (area under the curve)?

Stroke Work

91

The “electricity” of the heart is not electron flow but what?

ion flow

92

The contractions of the heart are initiated by ion currents that flow through specialized transmembrane protein structures called what?

ion channels

93

Describe the induction system s it flows through the heart:

SA node --> AV node --> Bundle of His --> Left and Right Bundle Branches --> Purkinje Fibers --> Ventricle

94

What are the two types of cells in the heart?

  • Cells involved with initiation and conduction
  • Cells involved in contraction cells
95

The action potential in the heart is spread how?

cell-to-cell conduction

96

What is the pacemaker of the heart found in the right atrium to the right of the superior vena cava orifice?

SA node

97

The SA node sets the what in the normal heart?

heart rate

98

What is buried beneath the endocardium in the inferoposterior region of the interatrial septum above superior to the tricuspid annulus and anterior to the coronary sinus?

AV node

99

Where is the conduction velocity fastest in the heart?

Purkinje fibers

100

List the extrinsic factors that increase conduction velocity:

  • Sympathetic stimulation
  • Muscarinic receptor antagonists
  • β-Adrenoceptor agonists
  • Circulating catecholamines
  • Hyperthyroidism
101

List the extrinsic factors that decrease conduction velocity:

  • Parasympathetic stimulation
  • Muscarinic receptor agonists
  • β-Blockers
  • Ischemia/hypoxia
  • Sodium and calcium channel blockers
102

The primary factors involved with abnormal impulse formation include:

  • Altered automaticity
  • Abnormal automaticity within the atria or ventricles
  • Triggered activity
103

This is a mechanism that results from a conducting pathway that is prematurely stimulated via a previously conducted action potential. The original action potential is delayed long enough so that the original cells can repolarize. Now repolarized, the cells can be stimulated again:

Mechanism of Reentry

104

What is a bypass or accessory pathway that runs near the mitral or tricuspid annuli (known as the Bundle of Kent) when it comes to conduction in the heart?

Wolff-Parkinson-White Syndrome

105

What does the P wave represent?

Atrial depolarization

106

What does the QRS complex represent?

Ventricular depolarization

107

What does the T wave represent?

Ventricular repolarization

108

What does the PR interval represent?

Atrial depolarization plus AV nodal delay

109

What does the ST segment represent?

Isoelectric period of depolarized ventricles

110

What does the QT interval represent?

Length of depolarization plus repolarization – corresponds to action potential duration

111

True or False: The intracellular region is negatively charged relative to the extracellular region.

True

112

A resting ventricular myocyte has a resting membrane potential (Em) of how many mV (millivolts) relative to the extracellular environment, which is considered 0 mV?

-90 mV

113

The cell in its resting state is said to be what?

polarized

114

There are four ions primarily involved in determining the membrane potential during the cardiac cycle:

  • Sodium (Na+)
  • Potassium (K+)
  • Calcium (Ca++)
  • Chloride (Cl-)
115

Which ion is the most important ion in establishing the resting membrane potential?

Potassium (K+)

116

The inverse of resistance is known as what?

conductance

117

What are the 4 factors involved in establishing cell membrane potential?

  • Type of cell
  • Ionic concentration differences
    • Chemical gradient
    • Electrochemical forces
  • Permeability of the cell membrane
  • Electrogenic pumps
118

What is simply the concentration difference across the cell membrane?

Chemical gradient

119

Which ion has a high concentration inside of the cell?

K+

120

Which ion has a high concentration outside of the cell?

Na+

121

True or False: The Em is more negative than EK.

False; less negative

122

Thus, there is a small net electromotive driving force resulting in a steady and slow leakage of K+ from the intracellular phase to the extracellular phase in the resting what?

nonpacemaker cardiomyocyte

123

A mathematical model that more reasonably reflects the multi-ion reality yields a new equation known as the what?

Goldman-Hodgkin-Katz Equation

124

The Na+/K+-adenosine triphosphate (ATPase) pump is found where?

sarcolemma

125

If for whatever reason the ATPase pump is inhibited (or fails as a consequence of hypoxia from infarction), does intracellular Na+ increase or decrease?

increase

126

Which channels (e.g., potassium, sodium, and calcium) adjust their conformations (either open or closed) as a function of the membrane potential?

Voltage-gated ion channels

127

Which channels interact with chemicals to open and close (e.g., the neurotransmitter acetylcholine can bind to a receptor that opens a special type of potassium ion channel (IK, Ach) that is present)?

Receptor-gated ion channels

128

Which ion channels are voltage and receptor gated?

Slow Na+ (If)

129

Which ion channels are receptor gated?

  • ATP-sensitive
  • ACh activated
  • Calcium activated (IK,Ca)
130

Which ion channels occur in phase 0 of myocytes?

Fast Na+ (INa)

131

Which ion channels are slow inward, long-lasting current; phase 2 of myocytes and phases 4 and 0 of SA and AV nodal cells?

L-type (ICa)

132

Which ion channels contribute to phase 4 pacemaker current in SA and AV nodal cells?

Slow Na+ (If)

133

Which ion channels are transient current; contributes to phase 4 pacemaker current in SA and AV nodal cells?

T-type (ICa)

134

Which ion channels maintain negative potential in phase 4; closes with depolarization?

Inward rectifier (IK1)

135

Which ion channels contribute to phase 1 in myocytes?

Transient outward (Ito)

136

Which ion channels involve phase 3 repolarization?

Delayed rectifier (IKr)

137

Which ion channels are inhibited by ATP; open when ATP decreases during cellular hypoxia?

ATP-sensitive (IK,ATP)

138

Which ion channels are activated by acetylcholine and adenosine; Gi-protein coupled; slows SA nodal firing?

Acetylcholine activated (IK,ACh)

139

Which ion channels are activated by high cytosolic calcium; accelerates repolarization?

Calcium activated (IK,Ca)

140

For the sodium ion channel, the loop between which domains is believed to be the inactivation gate?

3 and 4

141

Which channel has 4 domains that are not bonded together by peptide bonds?

Potassium (K+)

142

Which channels have 4 domains covalently bonded together by peptide bonds?

  • Sodium
  • Calcium
143

Whether an ion channel is in the open or closed state depends on what?

Em

144

Which cells are “triggered” by APs in adjacent cells with depolarizing currents?

Nonpacemaker ("fast response") APs

145

Which phase of the nonpacemaker cardiac AP is being described?

  • This is the repolarization phase of the AP. The downward slope of the curve is a result of two events: The gK+ conductance increases and initiates an outward K+ current through the potassium delayed rectifier (IKr), and the gCa++ conductance decreases.

Phase 3

146

Which cells are different from nonpacemaker cells in that they can spontaneously generate their own APs spontaneously?

Pacemaker ("slow response") APs

147

Which phase of the nonpacemaker cardiac AP is being described?

  • This repolarization is the result of the opening of a special type of K+ channel, the transient outward K+ channel (Ito), in combination with the inactivation of the Na+ ion channel. Also, the gCa++ is increased, and there is a slow movement of Ca++ into the cardiomyocyte via the L-type calcium channel (ICa). The L-type calcium channel is known as the slow inward, long-lasting current.

Phase 1

148

Which phase of the nonpacemaker cardiac AP is being described?

  • The equilibrium is maintained by a high gK+ through the inward rectifying potassium channel (IK1) compared in comparison to low gNa+ and gCa++. This is a true resting potential.

Phase 4

149

Which phase of the nonpacemaker cardiac AP is being described?

  • This is characteristic of the nonpacemaker cardiac AP. The inward movement of Ca++ is through the long-lasting (L-type) voltage-gated calcium ion channel (ICa). This is the major pathway for entry of Ca++, which open when the Em is depolarized to -40 mV.

Phase 2

150

Which phase of the nonpacemaker cardiac AP is being described?

  • When a threshold potential of -70 mV is reached, a rapid depolarization begins. The cell membrane goes from a state of polarization to a state of depolarization. The rapid depolarization is due to the temporal increase in sodium ion conductance (gNa+) of the voltage-gated fast ion Na+ channels (INa). This results in a rush of Na+ from the extracellular environment to the intracellular environment.

Phase 0

151

The ventricular cells are unexcitable (refractory) during which phases?

Phases 0, 1, and 2

152

The ventricular cells unexcitable during phases 0, 1, and 2 is known as what?

Absolute refractory period (ARP)

153

What includes ARP and some of Phase 3. Only localized action potentials can be generated, but they cannot be propagated?

Effective Refractory Period (ERP)

154

During what period are there weaker than normal APs may be generated and conducted?

Relative Refractory Period (RRP)

155

During which period are there weaker than normal stimuli being able to generate APs?

Supranormal period

156

If the fast response Na+ channels are blocked pharmacologically or inactivated by depolarization, the action potential upstroke is reduced. This change can lead to what?

arrhythmias

157

During Phase 3 or early Phase 4, nonpacemaker cells may start generating spontaneous depolarizations called what?

afterdepolarizations

158

When the membrane potential rises to approximately how many mV, essentially all of the fast Na+ channels are inactivated by the closure of the h gate?

-55 mV

159

True or False: The pacemaker cells in the heart have no true resting potential.

True

160

The pacemaker AP is divided up into which 3 phases?

  • 0
  • 3
  • 4
161

Which phase of the pacemaker cardiac AP is being described?

  • The inward movement of Ca++, through the long-lasting (L-type) voltage-gated calcium ion channel (ICa), is the major depolarizing current. These long-lasting (L-type) voltage-gated calcium ion channels (ICa) opens when the Em is approximately -40 mV. The current flow is much slower than for fast sodium ion channels. There is a simultaneous decrease in potassium ion channels currents.

Phase 0

162

Which phase of the pacemaker cardiac AP is being described?

  • There are four events happening: (a) The gK+ is decreasing. (b) The gCa++ is increasing in the second half of phase 4 due to transient (T-type) Ca++ channels. (c) There is a pacemaker current (If) known as the “funny” sodium ion current. (d) The L-type Ca++ ion channels start to open.

Phase 4

163

Which phase of the pacemaker cardiac AP is being described?

  • In phase 3 repolarization begins due to a decrease in gCa++ and an increase in gK+.

Phase 3

164

List the factors that can increase the SA node firing rate:

  • Sympathetic stimulation
  • Muscarinic receptor antagonist
  • β-Adrenoceptor agonists
  • Circulating catecholamines
  • Hypokalemia
  • Hyperthyroidism
  • Hyperthermia
165

List the factors that can decrease the SA node firing rate:

  • Parasympathetic stimulation
  • Muscarinic receptor agonists
  • β-Blockers
  • Ischemia/hypoxia
  • Hyperkalemia
  • Sodium and calcium channel blockers
  • Hypothermia
166

What are the 3 mechanisms that can modify the SA node AP?

  • Change slope of Phase 4
  • Alter the threshold voltage
  • Change the hyperpolarization
167

What is the primary pacemaker site?

SA node

168

What is the order of dominance in pacemaker AP?

SA node > AV node > Bundle of His > Purkinje fibers

169

Which beta blockers bind B1 and B2?

Non-selective/ 1st generation

170

Cardioselective/2nd generation beta blockers are selective for which receptor?

B1

171

Which drugs are non-selective beta and alpha-1 blockers?

  • Labetalol (Trandate/Normodyne)
  • Carvedilol (Coreg)
172

Which beta blocker is selective for B1 + NO?

Nebivolol (Bystolic)

173

List the non-selective/1st generation beta blockers:

  • Propranolol (Inderal)
  • Nadolol (Corgard)
  • Timolol (Biocadren)
  • Pindolol (Visken)
  • Penbutolol (Levatol)
174

List the Cardioselective/ 2nd generation beta blockers:

  • Atenolol (Tenormin)
  • Metoprolol (Lopressor/Toprol XL)
  • Acebutolol (Sectral)
  • Betaxolol (Kerlone)
  • Bisoprolol (Zebeta)
  • Esmolol (Brevibloc)
175

What are the effects of beta blockers on cardiac muscle?

  • ↓ inotropy = ↓ contraction strength
176

What are the effects of beta blockers on the SA and AV nodes?

  • ↓ chronotropy = ↓ heart rate (HR)
177

What are the overall effects of beta blockers?

  • ↓ stroke volume (SV)
  • ↓ heart rate (HR)
178

When is beta blocker selectivity lost?

At high doses

179

What is a side effect of beta blockers with membrane stabilizing activity?

Anesthetic side effects

180

Intrinsic sympathomimetic activity can occur with beta blockers. What does this mean those beta blockers have?

partial agonist activity

181

Which beta-blocker is being described?

  • non-selective for β receptors and selective for α1 receptors (vasodilating); unique cardioprotective, anti-ischemic and antioxidant properties

Carvedilol

182

Which beta blocker is being described?

  • non-selective for β receptors and highly selective for α1 receptors (vasodilating)

Labetalol

183

Which beta-blocker is being described?

  • selective for β1 receptors, increases NO (vasodilating)

Nebivolol

184

Which beta blockers would you expect to have "vivid dreams" as a specific side effect?

  • Penbutolol
  • Propranolol
185

β2 receptor agonism causes what in the lungs?

bronchodilation

186

β-blockers cause what in the lungs?

bronchoconstriction

187

Asthma and COPD can be treated with what?

β2 AGONISTS

188

True or False: Beta blockers could cause hyperkalemia.

True

189

What would happen to blood glucose levels if we block β2 receptors in the liver?

decrease blood glucose levels and lead to hypoglycemia

190

What would happen to blood glucose levels if we block β2 receptors in the pancreas?

Levels would increase due tot he pancreas not releasing insulin the way it should (this could lead to diabetes)

191

Which generation of β-blockers antagonize α1 receptors or release NO → vasodilation, increased blood flow and delivery of glucose to cells?

3rd

192

List some common side effects of beta-blockers:

  • Bradycardia
  • Hypotension
  • CNS side effects
  • Hyperkalemia
  • Masks the symptoms of hypoglycemia
  • Pulmonary issues
  • Erectile dysfunction, likely from decreased SNS activity
  • Do not abruptly discontinue!
    • Use of β-blockers causes upregulation of receptors
    • Discontinuation of β-blockers results in increased sympathetic activity
193

List the non-selective alpha blockers:

  • Phentolamine (Regitine)
  • Phenoxybenzamine (Dibenzyline)
194

List the selective (alpha-1) blockers:

  • Prazosin (Minipress)
  • Terazosin (Hytrin)
  • Doxazosin (Cardura)
195

What are alpha-1A selective blockers used for?

BPH

196

List some alpha-1A selective blockers:

  • Tamsulosin (Flomax)
  • Alfuzosin (Uroxatrol)
  • Silodosin (Rapaflo)
197

What prevents the release of NE leading to decreased sympathetic activity including negative chronotropic and inotropic effects?

Alpha2 Agonists

198

What are some side effects of alpha-2 agonists?

  • Bradycardia
  • Dry mouth (inhibition of SNS-mediated salivation)
  • Sedation
  • Withdrawal symptoms with abrupt discontinuation
199

What are the two types of Calcium channel blockers?

  • Nondihydropyridines (Non-DHP)
  • Dihydropyridines (DHP)
200

Non-DHP affect the what?

myocardium

201

DHP affect the what?

Peripheral vascular tissue

202

List some Non-DHP:

  • Verapamil (Isoptin, Calan, Verelan)
  • Diltiazem (Cardizem)
203

List some DHP:

  • Nifedipine (Procardia, Adalat)
  • Nicardipine (Cardene)
  • Amlodipine (Norvasc)
  • Isradipine (Dynacirc)
  • Felodipine (Plendil)
  • Nisoldipine (Sular)
  • Clevidipine (Cleviprex)
  • Nimodipine (Nimotop)
204

What are the different types of Voltage-Gated Calcium channels?

  • L-type: “long” acting, high voltage activation
  • N-type: “neural”, on central and peripheral neurons
  • T-type: “transient”, low voltage activation
205

True or False: The L-Type Calcium channel is voltage-gated.

True

206

Under normal conditions, what is the function of the L-type calcium channel?

increasing calcium entry into cells

207

In regards to the L-type calcium channel, once calcium enters the cell Calcium then stimulates which receptor in the sarcoplasmic reticulum causing an intracellular increase in calcium?

Ryanodine receptor

208

What is the overall effects of the L-type calcium channel?

  • Increased contraction
  • Positive inotropic/chronotropic effects
209

Is vasodilation stronger in DPH or non-DPH?

DPH

210

What is stronger in non-DPH?

SA and AV suppression

211

List the effects of CCBs:

  • Decreased dromotropic and chronotropic effects - CCB blocks L-type channel in SA and AV nodes
  • Decreased inotropic effect - blocking L-type channel prevents calcium influx and calcium-mediated calcium release from intracellular stores.
  • Smooth muscle vasodilation - decreased intracellular calcium results in a decrease in calcium-calmodulin complex. This complex is needed to activate myosin light chain kinase. Without this activation, there is no contraction.
212

List some side effects of CCBs:

  • Hypotension
  • Exacerbation of GERD
  • Bradycardia (non-DHP)
  • Prolonged QTc (non-DHP)
  • Many drug-specific effects including headaches, constipation
  • Drug interactions
    • Verapamil is a P-glycoprotein inhibitor and blocks elimination of drugs that are cleared by P-gp like digoxin
213

List some examples of ACE inhibitors:

  • Captopril (Capoten)
  • Enalapril (Vasotec, Enalaprilat)
  • Lisinopril (Prinivil, Zestril)
  • Ramipril (Altace)
  • Quinapril (Accupril)
  • Trandolapril (Mavik)
  • Fosinopril (Monopril)
  • Benazepril (Lotensin)
  • Moexipril (Univasc)
  • Perindopril (Aceon)
214

List some examples of ARBs:

  • Losartan (Cozaar)
  • Valsartan (Diovan)
  • Irbesartan (Avapro)
  • Candesartan cilexetil (Atacand)
  • Telmisartan (Micardis)
  • Eprosartan mesylate (Teveten)
  • Olmesartan medoxomil (Benicar)
  • Azilsartan medoxomil (Edarbi)
215

What is an example of Renin inhibitors?

Aliskiren (Tekturna)

216

What are Ang II actions at AT1?

  • Vasoconstriction
  • Aldosterone release
  • Vasopressin (ADH) release
  • SNS activation
  • Inhibition of renin release
  • Renal Na/H2O reabsorption
217

AT1 is coupled to which G protein?

Gq

218

AT2 is coupled to which G protein?

Gi

219

What are the actions of Ang II at AT2?

  • Vasodilation
  • Antiproliferation
  • Apoptosis
  • Antidiuresis/antinatriuresis
  • Bradykinin production
  • NO release
220

Which drugs inhibit AT1?

  • ACEIs
  • ARBs
221

AT2 is stimulated by what?

ARBs

222

Which drugs block Ang II binding to AT1 receptor?

ARBs

223

What inhibits renin = prevents conversion of Ang I from angiotensinogen?

DRI

224

What inhibits ACE (↓ Ang II, ↑ bradykinin activity)?

ACEIs

225

ACE inhibition leads to increased Bradykinin. What is a common side effect do to the increase of Bradykinin?

dry cough

226

People who have high Renin HTN should be started on low doses of ACEIs. Why?

  • ACEIs cause rapid drop in AgII which can cause hypotension
227

List the summary of effects of DRIs:

  • DRIs inhibit renin activity, but renin is still released from JG cells
  • Ang I and Ang II levels may increase initially before decreasing eventually
  • Ang II inhibits renin release from JG cells via a negative feedback mechanism. Without Ang II, this inhibitory effect on renin is lifted, resulting in increased renin levels
  • Decreases effects of Ang II:

↓ SNS activity

↓ Vasoconstriction (i.e., DRI causes vasodilation)

↓ Aldosterone release (hyperkalemia?)

↓ ADH release = diuresi

228

List the summary of effects of ACEIs:

  • ACE inhibition = ↑ bradykinin + ↓ Ang II
  • ↑ bradykinin = vasodilation, bronchoconstriction = cough
  • ↓ Ang II = ↓ SNS, vasodilation, ↓ Na+/water retention (↓ ADH, ↓aldosterone)
  • In kidney, ↓ AngII = vasodilation of efferent arteriole, ↓ GFR
  • Patients with high-renin HTN may develop hypotension
229

What happens when aldosterone is not produced?

No NaK channels --> we cannot reabsorb Na and can't kick out K+ --> leading to hypokalemia

230

List the summary of effects of ARBs:

  • ARBs antagonize AT1, reducing effects of Ang II
  • ↑ AngI, Ang II, Ang (1-7) without bradykinin accumulation
  • ACE is still active and degrades Ang (1-7) = preventing Ang (1-7) binding to AT2
  • However, increased Ang II concentrations, and blockage of AT1, causes Ang II to bind to AT2 resulting in positive AT-2 effects
  • Overall result: diuresis, decreased SNS activity, vasodilation, etc.
231

What are complications associated with ARBs?

Hyperkalemia due to turning off Aldosterone still (like ACEIs)

232

RAAS effectors reduce what activity to reduce BP?

Ang II