Cardiovascular pharmacology Flashcards
(54 cards)
1
Q
Normal human heart
- A ______-chambered muscular organ
- Chambers are: _______
- A ______________ pump
- Cardiomyocytes: ______________ cells in heart
A
- Four
- Left atrium (LA); Right atrium (RA); Left ventricle (LV); Right ventricle (RV)
- Mechanical
- Contractile
2
Q
Normal heart: concept of cardiac output
- Function of heart is to ________________________ which causes _________ pressure and tissue ___________
- Cardiac output (CO): and index of cardiac __________. Defined as the amount of blood ______________ per unit time
- CO = Stroke volume x HR
A
- Pump blood into the circulation; blood; perfusion
- Activity; ejected
3
Q
Normal heart: determinants of stroke volume
Stroke volume (volume of blood ejected in each heart ___________) is determined by:
- Contractility: the intrinsic strength of muscle __________
- Preload: initial ______ of muscle fibres prior to contraction
- Afterload: the load _______ which the heart must contract to eject blood
- ________ pressure is a major component of after load for the _______
A
Contraction
- Contraction
- Stretching
- Against
- Aortic; LV
4
Q
Heart failure:
- Heart is unable to maintain a normal cardiac ______
- Common causes (n=4): _______
- 2 types
A
- Output Causes: - Ischemic Heart disease - Cardiomyopathy - Valvular disease - Hypertension
- Systolic heart failure
Diastolic heart failure
5
Q
Symptoms of heart failure
LV failure:
- Pulmonary ___________ leading to dyspnea
- Insufficient tissue ____________ leading to fatigue
RV failure:
- Systemic congestion leading to peripheral _______ (ankles), abdominal __________ (liver), _________ (GI tract)
A
- Congestion
- Perfusion
- Edema; discomfort; nausea
6
Q
Compensatory mechanisms of heart failure
- In short term: they’re ___________
- In long term: ________ load on heart which _________ heart failure
A
- Beneficial
- Increases; accelerates
7
Q
Cardiac remodelling in heart failure
Heart disease (_________ CO) leads to:
1. Increase in _________ nervous system, _____________ system (RAS) and inflammatory ______________
which lead to
2. Early stage: cardiac ___________
- Increase in mass/thickness of ___________ (increase in _________ of myocytes and no change in _______ of myocytes)
leading to
3. Late stage: heart _________
- Dilation; wall ___________; fibrosis; myocyte __________ (death of muscle cells)
A
Reduced
1. Sympathetic; renin-angiotensin; cytokines
- Hypertrophy
- Ventricle; size; number - Failure
- Thinning; apoptosis
8
Q
Drugs for heart failure (DHF)
Goals of therapy:
- To improve __________
- To slow or _________ adversity cardiac remodelling
- To prolong ________ and reduce ___________
A
- Symptoms
- Reverse
- Survival; mortality
9
Q
Drugs for heart failure: calcium is a key determinant of cardiac ____________
- Digoxin, dobutamine, milrinone cause an ______ of calcium which causes _______ in contractility
A
Contractility
- Increase; increase
10
Q
(DHF)
Positive inotropic drugs: ________
- Drugs that increase cardiac ___________
Cardiac glycosides
- Isolated from leaves of ___________ plant
- Used for over 200 years in treatment of ____________
Digoxin:
- The most extensively used _____________
- Readily absorbed ___ tract
- Excreted by __________
- Rapid _________
- __________ = 1.5 days
A
Digoxin
- Contractility
- Foxgloves
- Heart failure
- Glycosides
- GI
- Kidney
- Onset
- Half-life
11
Q
Digoxin:
- Increases ___________ in heart failure
- Increases activity of the __________ nervous system which inhibits sinoatrial node (SAN) and _______ HR
Mechanism of inotropic effect
1. Inhibition of ___________
2. Increase cytosolic ____
3. Inhibition of ____ export via Na+/Ca2+ exchanger
4. Increased intracellular _____ and ______
A
- CO
- Parasympathetic; decreases
- Na+/K+ ATPase
- Na+
- Ca2+
- Ca2+ and contractility
12
Q
Adverse effects of Digoxin
- Cardiac ________________
1. Digoxin increases _____
2. Overload of calcium in the _______
3. Afterdepolarizations
4. Cardiac arrhythmias: premature ______/______ beats and __________
Digoxin has low __________ index
Adverse effects and toxicity:
- ____________: nausea and vomiting
- _______________: blurred visions and seizures
- ____________: arrhythmias (worsened by low K+)
Treatment of digoxin toxicity:
- Antidote: Digoxin __________ (Fab)
- ____ supplements
A
Arrhythmias
- Calcium
- SR
- Atrial/ventricle; tachycardias
Therapeutic
- GI tract
- Neurologic reactions
- Heart
- Antibody
- K+
13
Q
Interaction of digoxin w/ other drugs
Digoxin toxicity can be increased by:
- Diuretics that reduce ______ in plasma which ________ binding of digoxin to Na+/K+ ATPase which further increases ___________
- Drugs that interfere with renal ____________ of digitoxin leads to __________ serum digoxin levels
- ___________ dysfunctions
A
- K+; increases; toxicity
- Clearance; increased
- Renal
14
Q
Other positive inotropic drugs
A
Dobutamine
Milrinone
15
Q
Stimulation of cardiac contraction by B-adrenergic signalling:
- Greater influx of ________
- Higher ___________ Ca2+
- Enhanced _________
A
- Ca2+
- Cytosolic
- Contraction
16
Q
Dobutamine
A synthetic ________ receptor agonist which leads to increase in cardiac _______
- Acts on B1 receptor in heart to ________ contractility
- Acts on B2 receptor to relax _________ and decrease _____________
Clinical use:
- Can _________ symptoms of heart failure which is used for __________ management of acute heart failure and cardiogenic shock
- No improvement of patient ______________
A
Beta; output
- Increase
- Blood vessels; after load
- Improve; short-term
- Survival
17
Q
Milrinone
Increases __________ levels by inhibiting PDE which can cause 2 things that will lead to increased __________
- Increased cardiac ___________
- Decrease ___________
Clinical use:
- Used for ____________ management of heart failure patients not responsive to other drugs
- Used for __________ awaiting cardiac transplantation
Adverse effects (long-term use):
- Ventricular ____________-
- Increased ____________
A
cAMP; cardiac output
- Contractility
- After load
- Short-term
- Infants
- Arrhythmias
- Mortality
18
Q
Vascular smooth muscle : Blood vessel
3 layers:
- _________ layer: endothelial cells
- _________ layer: SM cells
- _________ layer: collagen + fibroblast
Fibroblast secrete _________
Vascular SM cells:
- Contraction of smooth muscle affects vessel _______ which affects blood _______ rate
A
- Inner
- Middle
- Outer
Collagen
Diameter; flow
19
Q
Vascular SM: mechanisms of SM contraction
SM contraction:
- Initiated by increase of ______
- Ca2+ binds to ___________
- Ca2+/calmodulin complex activates _________ (MLCK)
- MLCK will then phosphorylate __________
- Phosphorylated myosin binds to actin forming _________, hence triggering ___________
SM relaxation:
- There needs to be a decrease in _________ or activation of _______________ to remove phosphate from myosin
A
- Ca2+
- Calmodulin
- Myosin Light Chain Kinase
- Myosin
- Cross-bridge; contraction
- Ca2+; MLC phosphatase
20
Q
Coronary arteries:
- First to branch off the ________
- Two of them : _________ and _________
- Supply blood to ________muscle (the heart takes up ___% of total CO and uses about ____% of total body O2 consumption
O2 supply rate to heart = (Coronary flow rate) x (O2 content)
A
- Aorta
- Left and Right coronary arteries
- Heart; 5; 11
21
Q
Coronary arteries: balance between O2 supply and demand (in normal heart)
- At rest, O2 supply and O2 demand are the _________
- During exercise, the _________ nervous system is activated, increasing O2 supply which consequentially increases O2 demand (so O2 supply and demand are still the __________)
A
- Same
- Sympathetic; same
22
Q
Coronary artery diseases
- Artery is ________
- Coronary blood flow rate is _______
- O2 _____________ increases and so there’s an __________ between O2 supply and demand
Angina pectoris (________ block):
- Crushing ________ pains
- Ischemia and metabolites accumulation
Myocardal infraction (\_\_\_\_\_\_\_\_\_\_\_\_\_ block) - Abbreviation: MI
A
- Blocked
- Limited
- Demand; imbalance
Partial
- Chest
Complete
23
Q
Angina pectoris
- Typical Angina (caused by ______ changes in blood vessel):
- Stable Angina
- Formation of plaque in wall of _______ and ______constriction
- Similar _______ every time it occurs (pain, triggers)
- Unstable Angina
- Rupture of ______, aggregation of ______ and ________ formation (blood clots)
- Sudden _________ in frequency and duration/severity of angina
- Precursor of Myocardal Infraction (MI) - Variant Angina (no structural change but ______ change):
- Intense ___________
- Can occur at _________
A
- Structural
- Artery; vaso
- Characteristics
- Plaque; platelets; thrombosis
- Increase - Functional
- Vasospasms
- Rest
24
Q
Antiangenal/anti-ischemic agents:
- Vasodilators (organic nitrates/nitrites and Ca2+ channel blockers)
- __________ O2 supply - Beta blockers
- __________ O2 demand
Goal of these therapies: to restore the ___________
A
- Increase
- Decrease - Balance
25
Vasodilators
Organic nitrates and nitrites: mechanisms of action
- Nitrates and nitrites can dilate __________ by releasing ___________ (NO) which is normally generated by the ____________ cells
- Blood vessels; nitric oxide; endothelial cells
26
Vasodilators: Organic nitrates and nitrites
Amyl nitrite
- Volatile __________; inhalation
- Onset: almost _________ (about 30 sec)
- Very _________ duration of action (3-5 min)
- Used for treatment of acute ________ attacks
Nitroglycerin
- _______: well absorbed by gut but rapidly metabolized by liver; sustained release for prevention
- _________: rapid absorption and used for treatment of acute angina attacks
- __________: slow release and used for prevention of angina attacks
- _________: reduces pre and after load in patients with MI or acute heart failure
- Liquid
- Immediately
- Short
- Angina
- Oral
- Sublingual
- Transdermal (ex: patches or ointments)
- Intravenous (IV)
27
Vasodilators: organic nitrates and nitrites
Antianginal actions
- Nitrates and nitrites cause the release of _____ which can lead down 2 pathways
1. Dilation of _____ -> _____ in venous return preload -> _________ in contraction and O2 demand
or
2. Dilation of large epicardial vessels of the _______ -> _________ in blood flow to ischémie areas -> _____ O2 supply
- NO
1. Veins; decrease; decrease
2. Heart; increase; increase
28
Vasodilators: organic nitrates and nitrites
Clinical uses
- To relieve _______ of an already established attack
- To prevent an ______ prior to activity/exercise
- To provide __________ prophylaxis
- Pain
- Attack
- Long-term
29
Vasodilators: organic nitrates and nitrites
Side effects and tolerance
- Excessive vasodilation -> decrease in blood pressure -> side effects (n=3): ________
Tolerance of nitrates:
- _________ administration -> decrease in vasodilation effect
Prevention of tolerance:
- _________ dose and frequency
Mechanism of tolerance:
- When nitrates/nitrites release _____, causes release of oxygen ______ radicals which _________ aldehyde dehydrogenase causing a further reduction of NO release
- Hypotension, headache, reflex tachycardia
- Continuous
- Decreasing
- NO; free; inhibit
30
Vasodilators: calcium channel blockers (CCBs)
```
Dihydropyridine class (-dipine)
- n=2
```
- Amlodipine (longest half-life at 40hrs) and Felodipine (14 hrs)
31
Vasodilators: calcium channel blockers (CCBs)
Mechanism of action
L-type Ca2+ channels:
- Expressed in cell membrane of: vascular ____ cells, cardio_________, SAN and AV node cells
- Allow _____ influx into cells
- Blockage by CCB -> _______ Ca2+ influx -> vaso____
T-type Ca2+ channels:
- Expressed in ______ and _______ tissue
- Is not blocked by ______
- SM; myocyte
- Ca2+
- Reduced; dilation
- Heart; vascular
- CCBs
32
Vasodilators: calcium channel blockers (CCBs)
Antiangenial actions
Dihydropyridine drugs cause ______ of coronary artery which ________ O2 supply
Non-dihydropyridine drugs can do dihydropyridine action or they can cause _________ in HR and contractility which leads to _________ in O2 demand
Dilation; increase
Decrease; decrease
33
Vasodilators: calcium channel blockers (CCBs)
Clinical uses:
- ___________ of variant angina
- ___________ of typical angina
- ___________ of exercise endurance
- Used for atrial _____cardia
Adverse affects:
- Vaso______ and ____tension are associated with: headaches, peripheral edema, dizziness
- Relaxation of gut _____ is associated with constipation
- Prevention
- Treatment
- Improvement
- Tachy
- Dilation; hypo
- SM
34
Vasodilators: B blockers (-olol)
B blockers used for angina (n=4)
1. Atenolol
2. Metoprolol
3. Nadolol
4. Propanolol
35
Selective B1 blockers (atenolol, metoprolol): block B1 receptors in _______ which ________ HR and contractility, leading to ______ O2 demand
1. Prevents _______ angina
2. Prevention of _____cardia induced by vasodilators
Non-selective (nadolol, propanolol): Block B1 receptors, but also block B2 receptor in ________ leading to smooth muscle _________
- _____________: in airways of lungs
- ___________________: in arteries of skeletal muscle
B blockers have no direct effect on coronary _______
Heart; reduces; reduced
1. Typical
2. Tachy
SM; contraction
- Bronchoconstriction
- Reduced blood flow during exercise
Arteries
36
New drugs for angina:
Ivabradine:
- _______ funny currents (determine HR) in SAN pacemaker cells
- selectively _______ HR which ______ O2 demand of heart
- Used for treatment of _______ angina and heart failure
Ranolazine:
- ________ late Na+ currents in cardiomyocytes
- _________ diastolic wall tension (reduces O2 demand, and improves blood supply)
- Treatment of _______ stable angina (increases exercise capacity and reduces anginal frequency)
Trimetazidine:
- _________ B-oxydation and reduces FA metabolism
Leads to
- __________ in glucose metabolism
Leads to
- __________ O2 consumption/demand of the heart
- Inhibits
- Decreases; reduces
- Chronic
- Inhibits
- Reduces
- Chronic
- Inhibits
- Increases
- Reduces
37
Blood pressure
- Pressure of circulating ________ on blood vessel wall
- Not stable, it fluctuates
1. ___________: peak pressure (during contraction)
2. ___________: lowest pressure (during relaxation)
- Blood
1. Systolic pressure
2. Diastolic pressure
38
Hypertension:
- Systolic pressure (>___ mmHg) or Diastolic pressure ( > ___ mmHg)
- Is a risk factor for other _____ diseases: coronary heart disease, stroke, heart/renal failure
- 2 types:
1. _______ hypertension
2. ________ hypertension
- Chronic kidney disease
- Aldosterone-secreting tumors
- 140; 90
- Heart
1. Primary
2. Secondary
39
Short-term regulation of blood pressure (fast response)
Barorecetpro reflex
1. Pressure _________
2. __________ of vessel wall stretch and baroreceptor input
3. ___________ symp. NS and ______ of parasymp. NS (vagal nerve)
4. _____________ in HR, contractility, vascular contraction
1. Increases
2. Increase
3. Decrease; Increase
4. Decrease
40
Long-term regulation of blood pressure (slow response)
Angiotensin II
- Generated by _________________ enzyme (ACE) from ______________
- Causes vaso____________
- Stimulates secretion of ___________
- Angiotensin-converting; angiotensin I
- Constriction
- Aldosterone
41
Antihypertensive drugs: Diuretics
1. ___________ renal sodium excretion
2. ___________ blood volume
3. ___________ filling pressure
4. ___________ preload
5. ___________ stroke volume
1. Increase
2. Decreases
3. Decreases
4. Decreases
5. Decreases
42
Antihypertensive drugs: Urine formation
- ____________ of water, ions and other small molecules into tubular fluid
- ____________ of substances back to the blood
- ____________ of substances into tubular fluid
Diuretics ________ reabsorption of Na+ -> _________ osmolarity of tubular fluid -> ____________ urine volume
-> _____________ blood volume and blood pressure
- Filtration
- Reabsorption
- Secretion
- Inhibit; Increase; increase; decrease
43
Antihypertensive drugs (diuretics): Thiazide Diuretics
Drugs: Hydrochlorothiazide and indapamide
Most commonly used diuretics for ______________
Economic
Mechanism of action:
1. _________ Na+/Cl- cotransporter in early distal tubule
2. __________ Na+ and osmolarity of tubular fluid causing _______ of urine volume (diuresis)
3. ____________ of K+ secretion (hypokalemia - loss from blood)
Adverse effects:
- Hypokalemia: low serum _____ which causes cardiac arrhythmias and skeletal muscle weakness
- __________ blood levels of glucose, lipids and uric acid in some patients
Hypertension
1. Inhibits
2. Increases; Increase
3. Stimulation
- K+
- Increased
44
Antihypertensive drugs: Loop diuretics
Drug: furosemide
- ____________ Na/K/Cl cotransporter into ascending limb of Loop of Henle
- Has powerful _________ effect
- Side effect: _____________
Clinical uses:
- Used when intensive ___________ is required
- Used in __________ patients when thiazides aren't effective
- Inhibits
- Diuretic
- Hypokalemia
- Diuresis
- Hypertension
45
Antihypertensive drugs: potassium-sparing diuretics
Drug: amiloride
- _________ Na+ channels in distal tubule and collecting duct which __________ Na+ reabsorption and causes _________
Effects:
- Has mild natriuretic effects
- ________ K+ secretion so often used for prevention of ________________
- Blocks; reduces; diuresis
| - Reduces; hypokalemia
46
Antihypertensive drugs: Renin-Angiotensin-Aldosterone system
Renin:
- A protease that generates ______________
- Secreted by ____________ cells in kidneys
- Its secretion is stimulated by:
- _______ pressure in renal afferent arteriole
- _______ NaCl content in distal tubule
- _______ outflow of symp. NS
3 types of angiotensin inhibitors:
1. ACE: _________________ inhibitor
2. ARB: _________________
3. Renin __________
- Angiotensin I
- Juxtaglomerular
- Reduced
- Reduced
- Increased
1. Angiotensin-converting enzyme
2. Angiotensin receptor blockers
3. Inhibitors
47
Antihypertensive drugs: ACE inhibitors
Mechanism of action:
1. Ace inhibitors ________ angiotensin II levels which causes:
- ____________ vasoconstriction which leads to ___________ blood pressure
OR
- __________ aldosterone, leading to __________ sodium retention and blood volume which causes _________ in blood pressure
1. Decrease
- Decrease; decreased
- Decreased; decrease; decrease
48
Antihypertensive drugs: ACE inhibitors
Captopril:
- ________ ACE inhibitor ever developed
- _________ absorption in gut
- Side effects: dry ________, rash, _____ taste sensation
Enalapril
- _________ sulf-hydril group (doesn't reduce taste sensation)
- Is a pro_______ and is metabolized by body into its ________ form
- Has a longer duration of ________ (24h) than Captopril (6-12hrs)
Clinical effects:
- Excellent anti_____________ action
- Used for management of _______ to _______ hypertension
Adverse effects:
- Dry _______ (ACE inhibitors reduce activity of ACE, increasing bradykinin and causing dry cough)
- Fetal/neonatal injury and death (not to be used during ____________)
- First
- Rapid
- Mouth; reduces
- Lacks
- Drug; active
- Action
- Hypertension
- Mild to severe
- Cough
- Pregnancy
49
Antihypertensive drugs: Angiotensin receptor blockers (ARBs)
- Angiotensin II causes __________ of angiotensin receptors which __________ free calcium levels in vascular SM which causes vaso__________
- Drugs: Losartan and Valsartan
Action and clinical effects:
- Directly blocks ___________ receptors
- Similar effects as ______ inhibitors (used for treatment of hyper_________)
- Rarely cause dry _________
Adverse effects:
- Fetal and neonatal __________ and death (same as ACE inhibitors)
- May _________ blood levels of liver aminotransferase enzymes
- Activation; increased; constriction
- Angiotensin
- ACE; tension
- Cough
- Injury
- Increase
50
Antihypertensive drugs: Renin inhibitor
Drug: Aliskiren
- The ___________ renin inhibitor developed
- ____________ defective
_____________ of renin activity -> ___________ production of angiotensin I and II -> ___________ blood pressure
- First
- Orally
Inhibition; reduced; reduced
51
Antihypertensive drugs: Drugs on sympathetic nervous system
B1 receptor blockers in heart and kidney:
Action:
- ___________ HR and contractility
- ___________ renin secretion in kidneys
a1 receptor blockers in blood vessels:
Drug: Prazosin
Action:
- Arteriolar ___________ -> __________ vascular resistance -> ___________ blood pressure
Side effect:
- Reflex ____________ sympathetic nervous system causes _____________ HR and contractility
Uses:
- Not used for initial treatment of ______________
- Can be added to other _____________
a2 receptor agonists in vasomotor center in brainstem medulla
Drug: Clonidine
- ____________ sympathetic outflow leads to arteriolar _______________ which causes ___________ blood pressure
Uses:
- Not recommended for chronic treatment of __________
- Can be used for hypertensive ___________ (has a rapid onset, a single dose can reduce BP to normal levels)
Hypertensive urgencies:
- Systolic BP > ___ mmHg or
- Diastolic BP > ___ mmHg w/ no evidence of target organ damage
- Reduce
- Reduce
- Dilation; reduced; reduced
- Activation; increased
- Hypertension
- Drugs
- Reduced; dilation; reduced
- Hypertension
- Urgencies
- 180
- 120
52
Antihypertensive drugs: Vasodilators
Calcium channel blockers (CCB)
- ______________ of vascular SM -> Arteriolar ____________ -> ____________ of vascular resistance and BP
Uses:
- Mostly recommended for initial treatment of __________
- Protects against stroke; coronary ________ disease and kidney __________
- Relaxation; dilation; decrease
- Hypertension
- Heart; disease
53
Antihypertensive drugs: Vasodilators
Sodium Nitroprusside
- Releases _______________ (NO) -> vaso___________
- IV infusion for hypertensive ____________; has a ___________ onset
- Action lasts for up to ______ minutes
Side effects:
- _______tension
- Cyanide _________
- Nitric oxide; dilation
- Emergencies; rapid
- 10
- Hypo
- Toxicity
54
4 types of drugs for hypertension:
1. ____________: increase renal sodium/water excretion
2. ___________: reduce production of aldosterone (etc.)
3. ___________: B blockers and a1 blockers
4. ____________: can directly relax SM in arteries to reduce BP
1. Diuretics
2. Angiotensin inhibitors
3. Sympathetic nervous system inhibitors
4. Vasodilators
