CV Drug Pharmacology Flashcards
What can minimise hypokalaemia caused by diuretics?
Fruit and vegetables (bananas)
Hypokalaemia caused by diuretics increases the risk of what?
Cardiac arrhythmias
Which electrolyte imbalance is a common side effect of thiazide and loop diuretics?
Hypokalaemia
What percentage of filtered sodium is reabsorbed in the distal tubule?
10%
Where in the kidneys do thiazides act? What transporter do thiazides inhibit in the kidney?
Distal tubule
Sodium-chloride transporter
What cotransporter do loop diuretics inhibit? Where do loop diuretics act in the kidney?
Sodium-potassium-chloride cotransporter
Thick ascending Loop of Henle
What percentage of sodium is reabsorbed where loop diuretics act?
~25%
Which type of diuretic is mainstay therapy due to their potency?
Loop diuretics
What can long-term diuretic treatment reduce, improving ventricular ejection?
Afterload
Diuretic enhance the excretion of what electrolyte?
Na+
Diuretics reduce what in the heart that helps reduce oedema signs?
Pre-load
What are the different classes of diuretics?
- Thiazide
- Loop
- Potassium sparing and aldosterone antagonists
What do diuretics relieve?
Pulmonary and peripheral oedema
How do diuretics increase urine output by the kidney?
Altering how kidney handles sodium
What are diuretics important in the management of?
Chronic heart failure
What is the only rationale for using ARAs instead of ACEIs?
No dry cough
What is a safety concern with ACE inhibitors and ARAs during pregnancy?
Foetal toxicity
ACE inhibitors can cause which electrolyte imbalance?
Hyperkalaemia
What enzyme does aspirin irreversibly inactivate in platelets?
COX 1
What is reduced in platelets due to aspirin’s inactivation of COX 1?
Thromboxane A2 formation
What effect does reduced thromboxane A2 formation have on platelets?
Reduces platelet aggregation
What enzyme does aspirin irreversibly inactivate in the endothelium?
COX 1
What is reduced in the endothelium due to aspirin’s inactivation of COX 1?
Prostacyclin formation
What effect does reduced prostacyclin formation have on platelets?
Increases platelet aggregation
What is the net effect of aspirin on platelet aggregation at normal doses?
Zero
Which cells can synthesize new COX 1: endothelial cells or platelets?
Endothelial cells
How do lower doses of aspirin affect platelets?
Just inhibit platelets
How do higher doses of aspirin affect platelets and endothelium?
Inhibit both
When given orally, are portal blood platelets or platelets in the systemic vasculature exposed to higher doses of aspirin?
Portal blood platelets
What type of aggregation do Clopidogrel and prasugrel inhibit? What receptor do Clopidogrel and prasugrel antagonize? Are Clopidogrel and prasugrel pro-drugs or active drugs?
ADP-induced aggregation
P2Y12 receptor
Pro-drugs
What is the effect of combining Clopidogrel/prasugrel with aspirin? Combining Clopidogrel or prasugrel with aspirin increases the risk of what?
Effects may be additive
Bleeding
What do the MHRA advise regarding the combination of clopidogrel and certain PPIs? In what condition is the combination of Clopidogrel and certain PPIs restricted to?
Should be discouraged
Acute coronary syndrome
According to one trial, is Clopidogrel slightly more or less effective than aspirin?
Slightly more effective
Is GI bleeding less common with Clopidogrel and a PPI compared to aspirin and a PPI?
No
In what situation must inpatient initiation of Clopidogrel be done?
Unstable angina
In the cardiovascular system, which cells primarily produce nitric oxide? What molecule’s formation is stimulated by nitric oxide?
Vascular endothelial cells
cGMP
What are the cardiovascular effects of nitric oxide produced by vascular endothelial cells?
- Relaxes vascular smooth muscle (vasodilation)
- Inhibits platelet aggregation
- Inhibits leukocyte-endothelial interactions (anti-inflammatory)
What effect do organic nitrates have on veins, thereby reducing preload? Do organic nitrates have a greater effect on small resistance arteries or on veins? What effect do organic nitrates have on larger muscular arteries?
Relax veins
Veins
Marked effect
What is the definition of organic nitrates?
What effect do organic nitrates have on central (aortic) pressure, thereby reducing cardiac afterload?
Drugs that mimic NO actions
Reduce central pressure
What enzyme does cGMP activate? What type of muscle do organic nitrates relax, especially?
Protein kinase G
Vascular smooth muscle
What is an important clinical consideration with frequent use of long-acting organic nitrates?
Tolerance
What are two possible initial side effects of organic nitrates? What are two important compounds of organic nitrates?
Headache and postural hypotension
Glyceryl trinitrate (nitroglycerin) and isosorbide
How is Glyceryl trinitrate absorbed to produce its effects within a few minutes? Why can’t Glyceryl trinitrate be swallowed? How long does Glyceryl trinitrate’s activity last, approximately?
Bucally
Rapidly inactivated by hepatic metabolism
30 mins
Where are b-adrenoceptors located in the heart? What type is predominantly in the heart?
Cardiac nodal tissue
β1
What causes smooth muscle relaxation in many organs?
β2 receptors
What do b-blockers bind to? What do b-blockers inhibit the binding of to b-adrenoceptors?
b-adrenoceptors
Noradrenaline and adrenaline
What physiological parameters are reduced by b-blockers?
- Heart rate
- Contractility
- Arterial pressure
- Cardiac output
Reducing O2 demand
Blockade of which receptors can cause bronchoconstriction?
β2 receptors
What condition should one take care with when prescribing b-blockers? What cardiovascular conditions are potential unwanted effects of beta-blockers?
Asthma
Cardiac failure & bradycardia
What effect can beta-blockers have on carbohydrate metabolism? Beta-blockers can mask which condition’s symptoms such as tachycardia? Reduced cardiac output from beta-blockers can cause what symptom?
Hypoglycaemia or hyperglycaemia
Hypoglycaemia
Fatigue
Blockade of which receptors can cause cold extremities? Beta-blockers can decrease which cholesterol type and increase triglycerides? CNS effects from beta-blockers are related to what property?
β2 receptors
HDL-C
Lipid solubility
What type of channels do calcium channel blockers block? Calcium channel blockers inhibit depolarization-induced Ca2+ entry into which cells? What effect do calcium channel blockers have on myocardial contractility?
L-type channels
Muscle cells
Reduced myocardial contractility
What do L-type channels control?
Voltage-dependent Ca2+ influx
What effect do calcium channel blockers have on the heart’s conducting system? What effect do calcium channel blockers have on vascular smooth muscle cells? What kind of effects do calcium channel blockers have on heart rhythms?
Depressed electrical impulse formation
Diminished coronary vascular tone
Antidysrhythmic effects
Which calcium channel blocker exerts effects predominantly on the heart? Which calcium channel blocker has more influence on vessels and less on the myocardium? Which calcium channel blocker has intermediate effects on the heart and vessels? Which calcium channel blocker has a long half-life?
Verapamil
Nifedipine
Diltiazem
Amlodipine
Are calcium channel blockers well absorbed or poorly absorbed? Are calcium channel blockers extensively metabolised or minimally metabolised?
Well absorbed
Extensively
Do CCBs reduce mortality/morbidity after MI? What is a common vasodilator side effect of CCBs? What is a common side effect of chronic use of CCBs? What gastrointestinal side effect can calcium channel blockers cause?
May reduce
Flushing/headache
Ankle swelling
Constipation
What cardiovascular condition can CCBs cause due to vasodilation? What cardiovascular condition is a contraindication for CCBs?
Reflex tachycardia
Heart failure
Combining CCBs with which other drug class requires caution? Is renal disease a contraindication for CCB use? Does liver disease require a dose reduction when using CCBs?
Beta blockers
No
Yes
What type of heart failure are beta-blockers used in? Is the use of beta-blockers in heart failure paradoxical or expected?
Systolic dysfunction
Paradoxical (does not make sense together)
What happens to the sympathetic nervous system in heart failure? What happens to b-adrenoceptors in heart failure due to increased sympathetic tone?
Increased
Down-regulation documented
Is the mechanism for benefit in heart failure patients well or poorly understood? What is a potential mechanism of action for beta-blockers in heart failure related to sympathetic influences?
Poorly
Blockade of excessive sympathetic influences
Beta-blockers in heart failure reduce receptor what? Beta-blockers in heart failure cause attenuation of what toxicity? Is there evidence for efficacy of beta-blockers in heart failure?
Down regulation
Catecholamine toxicity
Yes
What are ACE inhibitors and Angiotensin II receptor antagonists used in? By what mechanism do ACE inhibitors and ARAs reduce preload and afterload? Is there compelling evidence for efficacy of ACE inhibitors and ARAs? What substance does ACE break down that ACE inhibitors prevent the breakdown of?
Heart failure
Blocking the formation of angiotensin II
Yes
Bradykinin
ACEi inhibits the conversion of angiotensin I to what? What is the effect of ACE inhibitors and ARAs on vascular resistance? What effect do ACE inhibitors and ARAs have on cardiac output? ACE inhibitors and ARAs promote renal excretion of what? What type of remodeling do ACE inhibitors inhibit?
Angiotensin II
Reduce resistance
Increase
Sodium and water
Cardiac and vascular
Hypotension is a safety concern especially in patients also taking which other medication?
Loop diuretics (promotes significant fluid loss, reducing blood volume)
What side effect is caused by accumulation of bradykinin from ACE inhibitors? What happens to GFR by ACE inhibitors in patients with renal artery stenosis? ACE inhibitors can cause which electrolyte imbalance?
Dry cough
Fall in GFR
Hyperkalaemia
What is a safety concern with ACE inhibitors and ARAs during pregnancy?
Foetal toxicity
Beta blockers effects on:
Brain
Heart
Kidneys
Vessels
- Reduced sympathetic outflow
- Reduced HR and cardiac output
- Reduced renin release
- Traditional b-blocker vasoconstriction but vasodilation with Nebivolol (via NO-dependent mechanism)
Beta blockers:
Compelling indications
Possible indications
Cautions
Compelling C/Is
- MI, angina
- HF
- HF (treat stable HF but can make HF worse), PVD, diabetes
- Asthma/COPD, heart block
CCBs (dihydropyridine):
Compelling indications
Possible indications
- Elderly, ISH
- Elderly, angina
CCBs (rate limiting):
Compelling indications
Possible indications
Caution
Compelling C/Is
- Angina
- MI
- Combination with beta-blockade
- Heart block, HF
What are the neurohormonal responses in the body used to increase blood pressure in heart failure? What do both end up doing?
- Activation of sympathetic system
- Renin angiotensin aldosterone system
- Vasoconstriction: increased sympathetic tone, angiotensin II, endothelins, impaired NO release
- Sodium and fluid retention: increased vasopressin and aldosterone
Further stress on ventricular wall and dilation (remodelling) leads to worsening of ventricular function
Thiazide/thiazide-like diuretics:
Compelling indications
Compelling C/Is
- Elderly, ISH, HF, stroke prevention
- Gout
Alpha-blockers:
Compelling indications
Cautions
Compelling C/Is
- BPH
- Postural hypotension, HF
- Urinary incontinence
