CVR Drugs Flashcards
1
Q
What are the three main structural and functional components of the heart?
A
• Cardiac muscle (myocardium): The muscular layer responsible for contraction.
• Conduction system: Generates and transmits electrical impulses to coordinate heartbeat.
• Nerve supply: Autonomic nerves that regulate heart rate and force of contraction.
2
Q
What are the main pharmacological targets in the pathophysiology of cardiac disease?
A
• Rate and rhythm
(Involves SA and AV node action potentials, calcium currents, and the autonomic nervous system)
• Myocardial contraction
• Metabolism and blood flow
3
Q
How is cardiac output calculated?
A
Cardiac Output = Heart Rate (HR) × Mean Left Stroke Volume (SV)
(SV = volume of blood ejected from the left ventricle)
4
Q
What does autonomic control of the heart mainly regulate?
A
It mainly controls heart rate (HR).
5
Q
What is intrinsic contractility and what does it influence?
A
• It refers to the heart’s ability to contract independently of preload and afterload.
• It depends on free intracellular calcium (inotropes).
• It mainly influences stroke volume (SV).
6
Q
What are intrinsic factors that influence heart rate and rhythm?
A
Action potentials generated by the SA (sinoatrial) and AV (atrioventricular) nodes
7
Q
What are extrinsic factors affecting stroke volume?
A
Preload and Afterload
8
Q
What are the intrinsic factors affecting myocardial contraction?
What influences these factors?
A
Calcium entry across cell membrane and storage in sarcoplasmic reticulum:
• Voltage-gated calcium channels
• Intracellular sodium & Ca/Na exchange
Catecholamines and cardiac glycosides influence these mechanisms
9
Q
What are the extrinsic factors affecting myocardial contraction?
A
- PRELOAD (central venous pressure) – determined by volume of blood
• Influenced by venoconstriction and increased blood volume (congestion) - AFTERLOAD – related to peripheral resistance and arterial compliance
- AUTONOMIC SYSTEM:
• Sympathetic (inotropic effect)
• Parasympathetic (decreased HR, reduced automaticity of SA node and AV conduction)
10
Q
What is preload and what factors influence it?
A
Preload refers to central venous pressure, i.e., the volume of blood returning to the heart
It is influenced by:
• Venoconstriction
• Increased blood volume (e.g. congestion)
11
Q
What is afterload and what does it depend on?
A
Afterload is the pressure the heart must pump against
It depends on:
• Peripheral resistance
• Arterial compliance
12
Q
How do autonomic systems influence myocardial contraction (as extrinsic factors)?
A
Sympathetic system:
• Inotropic effect (increases contraction strength)
Parasympathetic system:
• ↓ heart rate
• Reduces automaticity of SA node and AV conduction
13
Q
What are the key compensatory responses to decreased cardiac output (CO) in heart failure?
A
• Increased sympathetic activity
• Activation of the renin-angiotensin-aldosterone system (RAAS)
• Myocardial hypertrophy
14
Q
What is the role of increased sympathetic activity in heart failure?
A
It helps maintain blood pressure and perfusion by increasing heart rate and contractility.
15
Q
What is the effect of RAAS activation in heart failure?
A
It promotes vasoconstriction and fluid retention, which help raise blood pressure and increase blood volume.
16
Q
Why does myocardial hypertrophy occur in heart failure?
A
It is a compensatory mechanism to cope with increased workload and maintain cardiac output.
17
Q
What are the main types of heart failure (HF)?
A
• Left heart failure (Left HF)
• Right heart failure (Right HF / Congestive HF)
• Low cardiac output (CO) HF
• High cardiac output (CO) HF
18
Q
What is the most common type of left heart failure, and what is it usually caused by?
A
Left systolic HF is the most common type
Typically caused by coronary artery disease (CAD)
19
Q
What are common causes of right heart failure (congestive HF)?
A
Usually secondary to left heart failure
Can also result from pulmonary disease
20
Q
What are the common symptoms of heart failure?
A
• Fatigue
• Reduced exercise tolerance
• Exertional dyspnoea
• Orthopnoea
• Paroxysmal nocturnal dyspnoea (PND)
• Ankle swelling
21
Q
What are the typical signs of heart failure seen on physical examination?
A
• Elevated jugular venous pressure (↑ JVP)
• Laterally displaced apex beat
• Fine bibasal crackles
• Third heart sound (S3)
• Heart murmur
• Pitting oedema (ankles or sacrum)
22
Q
What are the major drug classes used in the pharmacological treatment of heart failure?
A
• Inhibitors of RAAS
• Beta-adrenoreceptor blockers
• Diuretics
• Direct vasodilators
• Inotropic agents
• Aldosterone antagonists
23
Q
What is a major cause of cardiovascular disease (CVD) and mortality?
A
Hypertension (HTN)
24
Q
What are the two main types of hypertension?
A
• Essential/Primary hypertension – (majority)
• Secondary hypertension
25
True or False:
Secondary hypertension is more common than primary hypertension
False
Primary (essential) hypertension is more common, accounting for the majority of hypertension cases.
26
What physiological mechanisms contribute to salt and fluid retention in hypertension?
• Increased sympathetic system activity
• Activation of the RAAS
• Renal disease
27
What lifestyle factors increase the risk of developing hypertension?
• Smoking
• Obesity
• Increased salt consumption
28
What are key factors in successfully managing hypertension?
• Proper management
(e.g., medication, lifestyle changes)
• Patient compliance
29
What is the main goal of pharmacological management in hypertension?
To reduce:
• peripheral resistance
AND
• cardiac output (CO)
in order to lower arterial pressure.
30
What are the three major drug categories used to reduce peripheral resistance and cardiac output in the management of hypertension?
• Diuretics
• Aldosterone antagonists
• Vasodilators
31
What are the main types of diuretics used in hypertension management?
• Thiazides
• Loop diuretics (e.g., Furosemide)
• Potassium-sparing diuretics
32
What type of antihypertensive drug is Spironolactone?
aldosterone antagonist
33
What type of antihypertensive drug is Furosemide?
loop diuretic.
34
What are examples of vasodilators used to manage hypertension?
• ACE inhibitors (ACEIs)
• Angiotensin receptor blockers (ARBs)
• Renin inhibitors (e.g., Aliskiren)
• Alpha- and beta-receptor blockers
• Calcium channel blockers (Ca²⁺ blockers)
• Nitrates
• Hydralazine
35
Which two physiological parameters determine arterial pressure?
• Peripheral resistance
• Cardiac output (CO)
36
What type of antihypertensive drug is Aliskiren?
Renin inhibitor (vasodilator)
37
What are the components that determine cardiac output (CO)?
• Heart rate (HR)
• Cardiac contractility
• Filling pressure
38
What determines filling pressure in the heart?
• Blood volume
• Venous tone
39
What contributes to peripheral resistance in the circulation?
Arteriolar pressure
40
True or False:
Angina is caused by an imbalance between supply and demand.
True
(Read pic if you're not sure supply and demand of what exactly)
41
What causes the gnawing chest pain felt in angina pectoris?
A decrease in blood supply to the heart
42
What is the main cause of blockage of coronary arteries (CAD) ?
Atherosclerosis
43
How can CAD aggravate angina following an MI?
By causing arrhythmias
44
What are the types of angina ?
• Stable angina
• Unstable angina
• Prinzmetal’s angina
(vasospasm of coronary arteries)
45
True or False:
Angina pectoris is defined as gnawing chest pain due to an increase in blood supply to the heart.
False
Decrease
46
What are the three main components of the treatment approach for angina?
• Improvement of perfusion
• Reduction of metabolic demand
• Treatment of aggravating causes (hyperdynamic circulation)
(Read pic to understand hyperdynamic circulation)
47
Which drug classes are involved in improving perfusion in angina treatment?
• Vasodilators (including nitrates)
• Calcium channel blockers
48
Which drug classes are used to reduce metabolic demand in angina?
Cardiac depressants including:
• calcium channel blockers (CCB)
• beta-blockers
49
What are Amyl nitrite and Nitroglycerin generally used for ?
To relieve ACUTE/SEVERE attacks of angina
50
What are Isosorbide and pentaerythritol nitrate used for in angina?
They are used PROPHYLACTICALLY to prevent angina
51
What are the drugs used for the treatment of angina?
• Amyl nitrite
• Nitroglycerin
• Isosorbide nitrate
• Pentaerythritol nitrate
• Calcium channel blockers (CCB)
• Beta-blockers
52
What are the non-pharmacological treatments for heart failure?
Surgical and lifestyle changes
53
What are the pharmacological treatments for heart failure?
• Diuretics
• Vasodilators
• Inotropic agents
• Aldosterone antagonist
54
What are the types of diuretics used in heart failure treatment?
• Thiazides
• Loop diuretics (e.g. Furosemide)
• K+ sparing diuretics
55
List the vasodilators used in heart failure treatment.
• ACE inhibitors (ACEIs)
• ARBs
• β-receptor blockers
• Ca²⁺-channel blockers
• Nitrites/nitrates
• Hydralazine
(Read pic if you want to know how these cause vasodilation)
56
Name the inotropic agents used in heart failure treatment.
• Cardiac glycosides (Digoxin, Digitoxin)
• Amrinone
• Dobutamine
(Read pic if you want to know how they produce inotropic effects)
57
What type of drugs are Digoxin and Digitoxin?
Cardiac glycosides (inotropic agents)
58
What is the aldosterone antagonist used in heart failure treatment?
Spironolactone
59
In which conditions are diuretics described as very effective?
• Heart failure (HF)
• Hypertension (HTN)
60
How do diuretics act in the kidney?
What does that result in?
By promoting the renal excretion of salt and water through blocking tubular reabsorption via Na⁺/Cl⁻ channels
RESULTING IN:
Fluid loss → reduces ventricular filling (↓ preload)
61
What transporter do thiazide diuretics inhibit?
The Na⁺/Cl⁻ symporter
62
Name the examples of thiazide diuretics
• Chlorthalidone
• Metolazone
• Hydrochlorothiazide
63
Chlorthalidone, Metolazone, and Hydrochlorothiazide are what types of drugs?
Thiazide diuretics
64
In which patients are thiazide diuretics less effective?
Patients with reduced glomerular filtration rate ( ↓ GFR )
65
What effect do thiazides have when combined with loop diuretics?
Synergistic action:
• reduce plasma volume AND ↓ blood pressure (relax the vascular smooth muscle)
66
Why is close supervision required with thiazide diuretics?
Because associated metabolic side effects are more likely
67
What are the contraindications of thiazide diuretics?
• Hepatic failure
• Renal impairment
• Electrolyte imbalance
68
What transporter do loop diuretics inhibit and where?
The Na⁺/K⁺/Cl⁻ symporter in the thick ascending limb of the loop of Henle
69
Name the examples of loop diuretics
• Furosemide
• Bumetanide
• Torsemide
70
Furosemide, Bumetanide, and Torsemide are what type of drugs?
Loop diuretics
71
What effect do loop diuretics have on vascular smooth muscle in the renal system?
Relaxation, which reduces peripheral resistance, BP, and plasma volume
Thus, increasing renal blood flow
72
What is the effect of loop diuretics on renal blood flow?
Increases renal blood flow
73
How fast do loop diuretics act?
Rapid action
74
What electrolyte imbalance and metabolic effect can result from loop diuretics?
• Potassium loss (K⁺ loss)
• Hyperuricemia
75
What are the adverse reactions for loop diuretics?
• Prerenal azotemia
• Hypokalemia
• Skin rash
• Ototoxicity
(Read pic if you want to know what the first and last one mean)
76
True or False:
Potassium-sparing diuretics are weak diuretics when used alone.
True
77
What are two examples of potassium-sparing diuretics
• Amiloride
• Spironolactone
78
What do potassium-sparing diuretics act on ? And what is their effect?
The distal tubule → reduce K⁺ secretion
79
What are potassium-sparing diuretics used as adjuncts to?
Thiazide and loop diuretics
80
What electrolytes are spared by potassium-sparing diuretics?
• Potassium (K⁺)
• Magnesium (Mg²⁺)
81
What are the contraindications for using potassium-sparing diuretics? And why?
• Use with ACE inhibitors
• Use with ARBs
• Diabetes
(Due to risk of hyperkalemic acidosis and renal impairment)
82
What does the renin-angiotensin-aldosterone system (RAAS) regulate?
Blood pressure (BP) and water (fluid) balance
83
Heart failure leads to the activation of the RAAS system via 2 mechanisms :
• In response to decreased renal perfusion → juxtaglomerular cells secrete RENIN into circulation.
• Renin release by same cell via activation of sympathetic & β receptors
84
Briefly explain the steps of the RAAS system
(Know it step by step - important)
85
What enzyme converts angiotensinogen into angiotensin I?
Renin
86
What enzyme converts angiotensin I into angiotensin II?
Angiotensin-converting enzyme (ACE), found in the lungs
87
What are the effects of angiotensin II?
• Potent vasoconstrictor
• Increases blood pressure
• Stimulates aldosterone secretion
88
What does aldosterone do to blood volume and pressure?
• Increases tubular reabsorption of water and Na⁺
• Increases fluid volume
• Further increases blood pressure
89
What condition results if RAAS is too active?
Hypertension (HTN)
90
What interrupts the RAAS system and is beneficial in HF, RF, and diabetes?
ACE inhibitors (ACEIs) and ARBs
91
Where is aldosterone secreted
Adrenal cortex
92
Which drug classes inhibit the renin-angiotensin-aldosterone system (RAAS)?
• ACE inhibitors (ACEIs – the “-prils”)
• ARBs (the “-sartans”)
• Aldosterone antagonist (Spironolactone)
93
In which conditions are RAAS inhibitors (ACEIs, ARBs, Spironolactone) considered beneficial?
• Heart failure (HF)
• Hypertension (HTN)
94
What is the effect of RAAS inhibitors on preload, and how do they achieve it?
They reduce preload by reducing the amount of blood returning to the heart
95
What are the two mechanisms by which RAAS inhibitors act?
• Vasodilation (ACEIs, ARBs)
• Diuresis (reduces preload)
96
What effect do RAAS inhibitors have on the heart by reducing preload?
• Reduce the size of ventricles
• Increase ejection fraction
• Increase efficiency of the heart
97
What type of vasodilators are ACEIs and ARBs?
MIXED vasodilators
(they dilate both arteries and veins)
98
Lisinopril, Benazepril, Enalapril
Are what type of drugs?
ACEIs
(Hint: "pril")
99
Losartan, Valsartan, Irbesartan
Are what type of drugs?
ARBs
(Hint: "sartan")
100
What are examples of balanced (mixed) vasodilators
ACEIs
ARBs
Na-nitroprusside
Prazosin
101
What is afterload?
The resistance against which the heart has to pump
102
How do arterial dilators like nifedipine and minoxidil affect afterload?
• Reduce afterload
• Increase efficiency of the heart
• Cause reflex increase in CO and HR
103
What type of drugs are Nifedipine and Minoxidil?
Arterial dilators
104
What do ACE inhibitors (ACEIs) inhibit?
The conversion of angiotensin I to angiotensin II (a potent vasoconstrictor)
105
What is the effect of ACEIs on aldosterone and sodium/water retention?
Decrease the release of aldosterone, reducing Na⁺ and water retention
106
ACEIs can be used with which types of diuretics, and which type should they not be used with?
Can be used with thiazide and organic acid diuretics
Should NOT be used with K⁺-sparing diuretics
107
Why are ACEIs considered safe in terms of side effects?
• low incidence of adverse effects
• do not interfere with mental or renal function
108
How do ARBs compare to ACEIs in terms of effects and adverse effects?
Similar effects as ACEIs
BUT they have less incidence of side effects when compared to ACEIs
109
What are Diazoxide and Na-nitroprusside used for?
They are potent vasodilators used in heart failure (HF) and hypertensive crisis
110
What is the mechanism of action of ARBs?
ARBs block angiotensin II from binding to AT₁ receptors, preventing its vasoconstrictive and aldosterone-secreting effects.
111
What is the action of Hydralazine?
Potent arteriolar vasodilator; directly relaxes arterioles and arteries, reduces peripheral vascular resistance and after-load.
112
What type of drugs are α-adrenergic blockers and hydralazine?
Potent arteriolar vasodilators.
113
Give an example of an α-adrenergic blocker and its action.
Prazosin – arterial and venous smooth muscle relaxant.
114
What is the primary effect of Ca²⁺-channel blockers?
Or
What is it's affect on the afterload ?
Reduce afterload.
115
What generation and type of drugs are Ca²⁺-channel blockers like Nifedipine?
First-generation calcium antagonists.
116
What do Ca²⁺-channel blockers block?
Ca²⁺-channel (Ca²⁺-influx) into heart and arterial blood vessels.
117
What is the result of Ca²⁺-channel blocker action?
Arteriolar vasodilation and relief in Prinzmetal’s angina, HF, and HTN.
118
What is the main effect of Nifedipine?
Mainly arteriolar vasodilation with minimal effect on cardiac conduction.
119
What is a contraindication for Nifedipine?
Acute MI in HTN patients.
120
What does Verapamil do to cardiac function?
Slows atrioventricular conduction, decreases HR, BP, and oxygen demand.
121
Why is Verapamil contraindicated in some cases?
Due to cardiac depression from negative inotropic effect and decreased Digoxin effect.
122
What are the effects of Diltiazem compared to Verapamil?
Similar effects.
123
What does Diltiazem dilate?
Peripheral and coronary arteries.
124
Where is Diltiazem beneficial?
In Variant (Prinzmetal’s) angina.
125
What are the cardiac effects of Diltiazem?
Causes negative inotropic and positive chronotropic effects.
126
What are Calcium Channel Blockers used to treat?
Angina, HF, HTN, and supraventricular arrhythmias.
127
List side effects of Calcium Channel Blockers.
Excessive vasodilation, hypotension, cutaneous flush, headache, nausea, drowsiness, dizziness, and constipation.
128
True or False:
There is considerable evidence supporting the use of β-blockers (Metoprolol, Carvedilol, Nebivolol) in patients with chronic stable heart failure.
True
129
When should β-blockers not be used?
In patients receiving diuretics, requiring IV inotropic agents, and in heart block.
130
What conditions are β-blockers effective in?
HF, HTN, and Angina.
131
What is the preferred first choice treatment for preventing angina?
β-blockers.
132
How do β-blockers help prevent angina?
They slow the heart rate and reduce force, lowering blood and oxygen demand.
133
What are the most common side effects of β-blockers?
Fatigue, cold hands & feet, slow heartbeat, diarrhea, and nausea.
134
What are less common side effects of β-blockers?
Sleep disturbances, nightmares, and impotence.
135
What is a contraindication for β-blockers?
Not suitable for patients with asthma or chronic obstructive pulmonary disorder (COPD)
136
True or False:
Non-selective β-blockers are safe for use in asthma and diabetes.
False
They are contraindicated as they suppress insulin release.
137
What are the cardiac effects of non-selective β-blockers?
Negative inotropic effect (reduces contractility of the myocardium) and negative chronotropic effect (decreases heart rate).
138
What is Propranolol (Inderal)?
A prototypical non-selective β-blocker mainly used in the treatment of HTN.
139
What are the CNS side effects of Propranolol and why?
Dizziness, confusion, and depression due to its lipid solubility.
140
What is Atenolol used to treat?
High BP, angina, and to help prevent additional MIs in MI patients.
141
What are additional uses of Atenolol?
To correct irregular heartbeat, prevent migraine headaches, and treat tremors.
142
What drugs are used for patients who cannot tolerate ACEIs?
Isosorbide mono- & di-nitrate (and Hydralazine).
143
How do nitrates work on vascular smooth muscle?
They release NO, stimulating guanylate-cyclase and increasing intracellular cGMP.
144
What is the effect of nitrates on veins and arteries?
Cause vasodilation of both, reducing pre- and afterload.
145
What is the result of nitrate use on myocardial oxygen demand and BP?
Rapid decrease in myocardial O₂ demand and decrease in BP.
146
What conditions do nitrates provide rapid relief for?
Acute Angina, HF, and MI.
147
What are common adverse effects of nitrites/nitrates due to vasodilation?
Vasomotor flushing, dizziness, and headache.
148
What may occur with sudden vasodilation when nitrates are used for angina?
Postural hypotension, fainting, and tachycardia (HR > 100/min).
149
What precaution should be taken when administering nitrates sublingually or via inhalation?
The patient should be seated.
150
What is a major contraindication with nitrates?
Sildenafil (phosphodiesterase V inhibitors) and other vasodilators due to increased hypotensive action.
151
Where are potassium channel activators mainly present?
In vascular and other smooth muscles.
152
What is Nicorandil and how does it work?
It combines ATP-sensitive K⁺-channel agonist activity with nitrovasodilator (NO) properties and is used as an anti-anginal medicine.
153
What type of dilator is Nicorandil?
Arterial and venous dilator.
154
What is the main effect of inotropic drugs on the heart?
Enhance cardiac muscle contractility and thus increase cardiac output (CO).
155
How do inotropic drugs increase cardiac contractility?
By increasing cytoplasmic calcium concentration via different mechanisms.
156
What are the three main classes of inotropic drugs?
1. Cardiac glycosides
2. β-adrenergic agonists
3. Phosphodiesterase inhibitors
157
What are cardiac glycosides (e.g., Digoxin, Digitoxin) used to treat?
Heart failure (HF) and atrial fibrillation.
158
How does Digoxin act as a positive inotrope?
By inhibiting Na⁺/K⁺-ATPase, increasing [Na⁺], which is exchanged for [Ca²⁺].
159
What effect does increased [Ca²⁺] have in the heart?
Induces actin-myosin interaction, increasing myocardial contractility.
160
What additional effects does Digoxin have on the autonomic system?
Reduces sympathetic activity, heart rate, and circulating renin.
161
What is a key elimination property of Digoxin?
Water-soluble and eliminated mostly unmetabolized by the urinary tract.
162
How is Digitoxin different from Digoxin?
More lipid-soluble, requires metabolism, and has a longer half-life.
163
What is the purpose of “digitalization” in acute CHF?
To rapidly attain effective therapeutic concentration.
164
What does hypokalemia do in relation to cardiac glycosides?
Predisposes to drug toxicity and can cause cardiac arrhythmias.
165
How does hyperkalemia affect cardiac glycosides?
Decreases their action.
166
What effect does hypercalcemia have on cardiac glycosides?
Increases their action
167
What are the cardiac effects of cardiac glycosides?
Bradycardia, ectopic beats, and potentially life-threatening arrhythmias.
168
What is the primary predisposing factor for cardiac glycoside toxicity?
Decrease in intracellular potassium.
169
What are the GI and CNS side effects of cardiac glycosides?
Anorexia, nausea, vomiting, headache, confusion, blurred vision, and altered color perception.
170
In which patients must Digoxin levels be closely monitored?
Patients with renal insufficiency
171
How can Digoxin toxicity be reversed?
By giving potassium supplements, antiarrhythmic drugs, and antibodies to Digoxin.
172
What effect do corticosteroids, thiazide diuretics, and loop diuretics have on potassium?
They decrease blood potassium levels.
173
What drugs can increase Digoxin concentration during concurrent therapy?
Erythromycin, Quinidine, Tetracycline, and Verapamil.
174
What is the combined effect of decreased potassium and increased Digoxin concentration?
Enhanced potential for cardiotoxicity.
175
How do sympathomimetics (Dobutamine, dopamine) exert their effects?
Positive inotropic and vasodilator effects via activation of adenylate cyclase.
176
What are sympathomimetics used for?
In combination (counterbalance) for cardiac arrest and low BP.
177
What is the action of β-adrenergic agonists?
Improve cardiac performance by causing positive inotropic effects and vasodilation.
178
Which β-adrenergic agonist is most commonly used and how?
Dobutamine, given as IV infusion in hospital for acute HF.
179
How do β-adrenergic agonists enhance cardiac contraction?
By increasing Ca²⁺ entry into myocardial cells.
180
What causes the vasodilator effect of inotropic agents?
Direct relaxant effect on vascular smooth muscle, reducing both pre- and afterload.
181
What is the use of centrally acting sympathetic drugs (clonidine, α-methyldopa)?
For HTN with renal disease; also beneficial in HF & angina.
182
Why does α-methyldopa have special clinical value?
It is safe to use in pregnant women with HTN.
183
Why do centrally acting sympathetic drugs have a limited role?
Due to development of tolerance
184
What is the role of phosphodiesterase inhibitors (Inamrinone)?
Symptomatic relief in refractory HF; long-term use increases mortality.
185
What are the contraindications for Dobutamine and Dopamine?
Dobutamine – acute MI; Dopamine – pheochromocytoma.
