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IPT: Cardio > Block 1 > Flashcards

Block 1 Flashcards

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1
Q

What are some advantages of Enalapril against captopril?

A

Longer T1/2

Not affected by food

Rash + loss of taste less frequent

Longer onset of action

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2
Q

What modifications must be made on a general alpha adrenergic antagonist to make it a different Rx?

A

Changes in R3

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3
Q

What is the purpose of the imidazole ring in an ARB?

A

Mimic histidine chain of angiotensin II

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4
Q

What is preload?

A

End diastolic volume that stretches the right or left ventricle of heart

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5
Q

Example of Diamnipropanol ether CCB?

A

Bepridil

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6
Q

Substitution of the “R” position of an ARB can interact with AT1 receptor through what kind of bonds?

A

Ionic

Ion-dipole

Dipole-dipole

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7
Q

What is the optimal sodium restriction goal to reduce BP?

A

<1500mg/day (loss of 5-6mmHg)

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8
Q

What is the purpose of the C2 and C3 positions of a Dihydropyridines CCB?

A

“Lock” the conformation of that compound so that the C4 ring is pendicular to the C1 position

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9
Q

What are the major effector tissues of beta 2 receptors?

A

Smooth muscles including bronchi

Liver

Skeletal muscle

Dilates bronchioles which causes GI and uterine relaxation, increase in blood sugar via glycogenolysis, and increased blood flow to skeletal muscles + increased potassium uptake

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10
Q

What is the structure of organic nitrates?

A

Look for groups of NO3

1 or 2 groups = low potency

3 groups = high potency

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11
Q

What is the purpose of neprilysin?

A

Breaks down angiotensin II

Breaks down natriuretic peptides

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12
Q

What is the relationship between length and radius to vascular resistance?

A

Poiseuille’s equation

length is proportional to resistance

radius is inversely proportional to resistance

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13
Q

Contraindications of Resperpine?

A

Depression, suicidal ideations, electroshock therapy

Ulcerative colitis or peptic ulcers

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14
Q

Example of Phenylalkylamines CCB?

A

Verapamil

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15
Q

Example of Benzothiazepines CCB?

A

Diltiazem

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16
Q

What are the adrenergic nerve blockers for HTN?

A

Reserpine

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17
Q

Cardiac muscles require calcium through L-type channels while neurons rely on what?

A

N and P type channels

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18
Q

Organic nitrates are metabolized by what?

A

Low potency = P450

High potency = ALDH-2

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19
Q

How do you calculate MAP?

A

(DBP x 2 + SBP) / 3

or

CO x SVR

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20
Q

Which group (carboxylate, phosphinic acid, or sulfhydryl) is superior in regards to binding to zinc on an ACE inhibitor?

What do the other groups utilize to compensate?

A

Sulfhydryl

Other 2 groups have a side chain mimicking phenylalanine due to lack of sulfhydryl

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21
Q

Which CCB group can either block or open channels?

A

Dihydropyridines CCBs

w/ diltiazem it can open channels

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22
Q

Ranolazine is metabolised by what?

A

Mostly CYP3A4, but has minor via CYP2D6

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23
Q

What is afterload?

A

Pressure against which the heart must work to eject during systole

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24
Q

In regards to structures, how can you modify a compound to become preferentially selective towards to the beta-1 receptor?

A

Modify the para position of the phenyl ring (opposite side)

EX: atenolol and acebutolol (that one has an addition to the ortho side as well)

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25
Nifedipine AE?
Constipation, cardiac disturbance, flushing
26
What are the major effector tissues of beta 3 receptors?
Adipose
27
Diltiazem Nifedipine Verapamil Which one has most effect on coronary vasodilation?
Diltiazem + Nifedipine
28
What can you do to renin inhibitors to prevent renin from converting angiotensinogen into angiotensin I?
Short (non and regular) peptides with sterical structures mimicking the amino acid triad of Phe-His-Leu
29
An increase of ____ systolic BP and ____ diastolic BP doubles the risk of mortality
20mmHg - systolic 10mmHg - Diastolic
30
Diltiazem Nifedipine Verapamil Which one has the most effect on contractility?
Diltiazem - no effect Nifedipine - either increase or decreases Verapamil - decreases
31
Zinc is an important cofactor for the activity of what?
ACE
32
Diltiazem Nifedipine Verapamil Which one can cause peripheral edema?
All, but nifedipine is the worst
33
What is the purpose of the acidic groups in an ARB?
Mimic the tyrosine phenol or the aspartate carboxylate of angiotensin II Acidic groups include carboxylic acid, phenyl tetrazole, or a phenyl carboxylate
34
Diltiazem Nifedipine Verapamil Which one can cause hypotensio?
All, but nifedipine is the worst
35
What is the structure of sodium nitroprusside?
N connected to O (triple bond) N connected to C (triple bond) aka cyanide Iron
36
What are the major effector tissues of dopamine 1 receptors?
Smooth muscles, especially renal, mesenteric, and cardiac
37
Nitric oxide synthesized from what?
L-arginine via nitric oxide synthases
38
Methyldopa AE?
Sedation, positive Coombs test, hemolytic anemia
39
Clonidine AE?
Dry mouth, rebound HTN if suddenly stopped
40
What is cardiac output and how is it calculated?
Quantity of blood pumped into aorta each minute by the heart CO = stroke volume x heart rate
41
Why do arterioles have thicker walls compared to arteries?
More smooth muscle Known as resistance vessels
42
In regards to their structure, how does prazosin, terazosin, and doxazosin affect blood pressure?
They all use same structure-activity principles by having a large bulky R1 to gain affinity to the alpha receptors AND remove the hydroxyl groups on the phenyl ring to be selective alpha receptor inhibitors
43
What is the only direct renin inhibitor approved for clinical use?
Aliskiren
44
What are some counseling points to methyldopa?
Acceptable Rx for pregnant women w/ mild to moderate HTN Causes dry mouth, sedation, and drowsiness Occasionally hematologic immunotoxicity and maybe progress to hemolytic anemia Hepatotoxicity
45
What modifications must be made on a general beta-adrenergic antagonist to make it a different Rx?
Larger (but not too large) R1 additions Possible modifications to R3
46
Which antianginal can lead to renal dysfunction due to prolonged use?
Nitroprusside due to accumulation of CN and SCN
47
Methyldopa class info
Prodrug Converts to methyl Norepi in the brain Reduces BP by reducing cardiac output and vascular resistance Also decreases renin release
48
Ranolazine MOA?
Late sodium current blocker which reduces sodium and calcium overload
49
1kg of body weight loss = ___ mmHg reduction?
1kg = about 1 mmHg
50
What is arterial blood pressure?
Blood pressure that is determined by cardiac output x peripheral vascular resistance
51
AE of non-selective beta blockers?
Withdrawal syndrome after prolonged regular use Increased VLDL and decreased HDL AV block Bradycardia Respiratory issues Impotence Depression
52
Diltiazem Nifedipine Verapamil Which one has the most effect on preload?
All have about no effect
53
What is an example of a beta 1 blocker?
Metoprolol
54
Diltiazem Nifedipine Verapamil Which one possess some degree of action on vascular smooth muscle?
Diltiazem + Verapamil
55
What happens when beta 3 receptors are activated?
Increased lipolysis
56
What are the BP thresholds for Tx for those w/ no clinical CVD and 10 yr ASCVD risk under 10% and secondary stroke prevention?
≥140/90
57
What is the J-curve Phenomenon?
Excessive BP lowering may have adverse CV consequences DBP < 60 = higher risk of CV issues
58
What class does prazosin belong to?
Alpha 1 antagonist
59
Diltiazem Nifedipine Verapamil Which one has the greatest effect upon peripheral vasculature?
Nifedipine and other dihydropyridines
60
Someone w/ stage 1 HTN should be treated and assessed how often?
ASCVD risk <10% = Lifestyle modifications and 3-6 months ASCVD risk >10% = Single drug therapy + lifestyle modifications and 1 month follow-up** **change to 3-6 months if goal is met
61
What is stage 1 HTN?
130-139 SBP OR 80-89 DBP
62
What ion is an important cofactor for the activity of ACE?
Zinc
63
What are the cardioselective beta blockers?
Bisoprolol Atenolol Metoprolol tartrate and succinate
64
What is elevated BP?
120-129 SBP AND <80 DBP
65
DASH diet is expected to lose ___ mmHg
11mmHg
66
Diltiazem Nifedipine Verapamil Which one can cause constipation?
Verapamil
67
How does nitric oxide work?
Nitric oxide increases cGMP and relaxes smooth muscles
68
Most of the HTN are caused by what?
Genetic factors, no cure but can be controlled
69
Which group of an ACE inhibitor traps the zinc ion?
First carboxylate group
70
What is the purpose of the first carboxylate group of an ACE inhibitor?
Trap the zinc ion
71
What is diastolic BP?
Force during cardiac relaxation/filling
72
What are some comorbidities that can cause secondary HTN?
CKD Primary aldosteronism Obstructive sleep apnea Renovascular disease
73
What is the purpose of the second carboxylate group of an ACE inhibitor?
Enable ionic interactions between the compound and amino acid residues of ACE
74
Pros and Cons of Prazosin
Good: Doesnt affect serum lipids Treats BPH Bad: Increased risk of heart failure First dose hypotension Nasal congestion Salt/water retention Orthostatic hypotension
75
What are the major effector tissues of alpha 1 receptors?
Smooth muscle Sphincters Vasoconstriction which causes mydriasis, less salivary gland secretions, bladder and prostate capsules increase contraction and ejaculation
76
What are the major effector tissues of alpha 2 receptors?
Nerve endings Inhibits release of norepi which causes vasodilation, hypotension, decrease GI motility and tone
77
Epinephrine Isoproterenol Norepinephrine Rank in order of affinity to beta receptors
Iso>Epi>Norepi
78
Someone w/ stage 2 HTN should be treated and assessed how often?
Consider 2 drug therapy + lifestyle modifications and 1 month follow-up** **Change to 3-6 months if goal is met
79
What are the applications of CCBs?
HTN Angina Arrhythmia
80
What are some drug interactions of ACEi?
Antacids Capsaicin NSAIDs K+ - sparing diuretics or potassium supplements
81
Someone w/ normal BP should be treated and assessed how often?
Treatment = maintain healthy lifestyle Reassess = 1 yr
82
Clonidine class info
alpha 2 agonist Decrease sympathetic outflow Reduces BP by reducing cardiac output due to less norepi and lowering vascular resistance Compensates by retaining salt
83
What are the ganglion-blocking drugs for HTN?
Trimethaphan; due to AE it is no longer used
84
What is the structure of Nesiritide?
32 AA peptide
85
Example of Dihydropyridines CCB?
Nifedipine
86
What happens when dopamine 1 receptors are activated?
Relaxes renal vascular smooth muscle Higher doses activates beta-1 and alpha-1 receptors
87
Calcium influx into muscle cells do what?
They go into the cytosol of muscle cells to activate calmodulin Myosin glides to lead to muscle contraction
88
What are the common and rare AE of ACEi?
Common = dry cough and fetopathic potential Teratogenic in 2nd and 3rd trimester, not 1st Rare = Angioedema Others = Hypotension, hyperkalemia, acute renal failure (constricts efferent), skin rash
89
With an ARB, what is the best possible antihypertensive therapy?
ARB + sacubitril
90
What must the nitrogen ring of a ACE inhibitor contain?
Carboxylic acid to mimic C-terminal carboxylate of ACE substrate
91
Alpha 1 antagonists block postsynaptic alpha 1 receptors and cause what?
Decrease in sympathetic nervous system Decrease of preload (veins relax) and decrease of afterload (arteries relax)
92
What are some drug interactions w/ beta blockers?
Verapamil + Digoxin Verapamil inhibits elimination of digoxin
93
Patients with moderate to severe HTN, what kind of Rx should they get?
An agent that inhibits function of sympathetic nervous system like: CNS active agent Ganglion blocking drug Adrenergic nerve blocker Adrenoceptor blocker
94
Which group of an ACE inhibitor allows the formation of a hydrogen bond between compound and amino acid residues of ACE?
Ketone group
95
What are the classes of calcium channel blockers?
Dihydropyridines Phenylalkylamines Benzothiazepines Diamnipropanol ether
96
What is the purpose of the C4 position of a Dihydropyridines CCB?
Optimizes activity and important for size/position rather than for electronic nature
97
In what muscle contraction, what is the role of calcium?
Binds to calmodulin to form MLCK MLCK phosphorylates myosin light chains that allows myosin and actin to interact
98
Changing the 1,4 Dihydropyridines structure at the meta position (C3) + replacing the ester group with other electron-withdrawing groups does what?
Makes the compound a calcium channel ACTIVATOR
99
Diltiazem Nifedipine Verapamil Which one has minimal direct cardiac effect?
Nifedipine
100
CCBs block what kind of calcium channels?
L-type voltage-gated
101
What is systolic BP?
Force during cardiac contraction
102
What kind of beta receptor should you block for someone who has asthma?
Use a selective Beta 1 blocker Also for diabetes and peripheral vascular disease
103
What are some counseling points to clonidine?
Do not suddenly d/c Will cause rebound HTN May cause sedation
104
What is a CNS-active agent?
Inhibit sympathetic outflow Selective alpha 2 agonists such as clonidine Methyldopa: converted in nerve terminal to alpha-methyl norepi aka false transmitter
105
What is isolated systolic HTN?
≥ 140 SBP AND <90 DBP More common in elderly; decreased flexibility of arterial wall
106
What is the structure of hydralazine?
Double benzene ring with 1 nitrogen connected to a hydrazine (NHNH2)
107
Which part of the heart is known as the pacemaker?
Sinoatrial (SA) node
108
What is the purpose of the ketone group of an ACE inhibitor?
Form hydrogen bonds between compound and amino acid residue of ACE
109
What is the neutral endopeptidase that sacubitril can inhibit? What are the consequences of that?
Neprilysn Increases Angiotensin II and activates angiotensin receptors
110
Which CCB group blocks both Calcium and Sodium channels?
Diamnipropanol ether Not available in the US
111
Diltiazem Nifedipine Verapamil Which one will worsen CHF?
Verapamil
112
Zinc may bind to a carboxylate (carboxylic acid) group of an ACE inhibitor. What else may they bind to?
Sulfhydryl or phosphinic acid
113
ACEi AE?
Cough + renal damage in pre existing renal disease and in the fetus
114
What is stage 2 HTN?
≥140 SBP OR ≥90 DBP
115
Diltiazem Nifedipine Verapamil Which one should be cautious when given with beta blockers?
Verapamil
116
Someone w/ elevated BP should be treated and assessed how often?
Treatment = lifestyle modifications Reassess = 3-6months
117
Diltiazem Nifedipine Verapamil Which one has the highest chance of headaches?
Nifedipine, small chance for verapamil
118
What is the structure of ranolazine?
Benzene ring with 2 nitrogens aka piperazine
119
An ACE inhibitor mimics three AA. What are they?
Ring = Phenylalanine Methyl group = Alanine Ring with nitrogen = Leucine
120
What are the major effector tissues of beta 1 receptors?
Cardiac muscles Kidney Increases HR and contraction which causes increased renin
121
Which ACEi's bioavailability is reduced w/ food?
Captopril Give it 1hr before meals
122
How does changing the R1 side of adrenergic agonists affect its binding?
R1 is larger than methyl (isopropyl and t-butyl), alpha binding is dropped. T-butyl will make activity switch to a beta-2 receptor R1 is really bulky, alpha receptor gets restored WITHOUT agonist activity
123
Reserpine class info
Extracted from indian plant, Rauwolfia serpenina Depletes Norepi from nerve endings and blocks the transport of it Reduces BP by reducing sympathetic tone and peripheral vascular resistance
124
Diltiazem Nifedipine Verapamil Which one depresses HR and contractility?
Diltiazem + Verapamil
125
What happens if you replace the N1 position or use of oxidized (pyridine) or reduced (piperidine) ring of a 1,4 Dihydropyridines?
Abolishes or decreases activity N1 position is supposed to have a nitrogen with a hydrogen
126
What is the dietary potassium goal to reduce BP?
3500 to 5000mg/day (loss of 4-5mmHg)
127
Which ACEi is a prodrug?
Enalapril
128
CCBs AE?
Cardiac depression (cardiac arrest, bradycardia, AV block , and heart failure)
129
What is orthostatic hypotension?
SBP decreases >20 AND DBP decreases >10 from supine to standing
130
What are the amino acids found in angiotensionogen? Purpose?
Phenylalanine Histadine Leucine Mediates recognition and binding of renin to angiotensinogen
131
In what period of life is cardiac output increased?
Children + young adults
132
ARB AE?
Renal damage in pre existing renal disease and in the fetus
133
Which group of an ACE inhibitor enables ionic interactions between compound and amino acid residues of ACE?
Second carboxylate group
134
What is white coat and masked HTN? Who's at a higher risk?
White coat - BP is high in office but not at home or community Masked - BP is lower in office than other settings Higher risk in masked due to missed diagnosis
135
Dihydropyridines CCB are inactivated by what CYP protein?
CYP3A4 except on clevidipine
136
What produces an orally bioavailable prodrug of an ACE inhibitor?
Esterification of the carboxylate or phosphinate
137
Diltiazem Nifedipine Verapamil Which one has the most effect on afterload?
Nifedipine decreases the most
138
What are the applications of ACEi?
Antihypertensive CHF Diabetic Nephropathy
139
If a Rx has intrinsic sympathomimetic activity, what does that mean?
Decrease BP and systemic vascular resistance, but HR and cardiac output are maintained
140
Epinephrine Isoproterenol Norepinephrine Rank in order of affinity to alpha receptors
Epi>Norepi>Iso
141
In regards to their structure, how does dichloroisoproterenol, pronethalol, and propranolol affect blood pressure?
They all use same structure-activity principles by having a sufficiently large R1 group (not bulky) to increase binding affinity to beta receptors AND removal of hydroxyl groups on phenyl ring to become selective beta receptor inhibitors
142
What are the beta blockers with intrinsic sympathomimetic activity?
Penbutolol Acebutolol Pindolol
143
Diltiazem Nifedipine Verapamil Which one has the most effect on AV conduction?
Verapamil - decreases the most Diltiazem - decreases it Nifedipine - no effect

IPT: Cardio (4 decks)

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