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Flashcards in Cardiovascular Drugs Deck (8)
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1
Q

What is the mechanism of action of GTN? What are its clinical effects? What are the indications for GTN use in the ED?

A
  1. Mechanism of action of GTN
    - Interacts with tissue sulfhydryl group -> Release nitric oxide -> Activates guanyl cyclase to produce cGMP -> Reduce intracellular Ca -> Smooth muscle relaxation
  2. Clinical effects
    A. Beneficial effects
    - Venodilation (low dose) -> Reduce preload and LVEDV -> Reduces LV wall tension
    - Reduce myocardial work load, oxygen consumption and contractility
    - Arterial dilation (high dose) -> Reduce afterload, peripheral vascular resistance, systemic BP
    - Coronary arteries vasodilation -> Increased coronary collateral flow
    B. Adverse effects
    - Reflex tachycardia
    - Hypotension
    - Headache
  3. Indications
    - Angina
    - Acute coronary syndrome
    - HTN emergency/urgency
    - APO
2
Q

By what routes can GTN be administered? Why are parenteral routes preferred? When should GTN be used with caution?

A
  1. GTN routes of administration
    - IV infusion
    - Sublingual
    - Transdermal
    - Oral
    - Buccal
  2. Parenteral routes preferred to avoid first pass metabolism which reduces oral bioavailability
  3. GTN should be avoided in
    - Hypotension
    - Sildenafil (Phosphodiesterase inhibitor)
    - Posterior and inferior MI
3
Q

What is meant by the term tachyphylaxis as it relates to GTN? What is the implication of this for the dosing and administration of GTN? What is the theoretical basis for this phenomenon?

A
  1. Tachyphylaxis is
    - Continuous exposure to nitrates reduces effectiveness
    - Smooth muscle may develop tolerance
    - Decrease in substrate to form nitric oxide
    - Seen particularly in IV infusion and long-acting preparations
  2. Drug-free days/intervals are required
    - To regenerate substrate
    - Minimum of 8 hours in between doses required
  3. Tachyphylaxis occurs due to
    - Decrease in thiol compounds and tissue sulphydryl groups which is required to produce nitric oxide
    - Increase in generation of O2 free radicals
4
Q

Describe the pharmacokinetics of GTN

A
  • Poor oral bioavailability due to first pass metabolism
  • Usually given IV, SL, transdermal, buccal to avoid first pass
  • Onset: 1 - 3 mins
  • Duration of action: 10 - 30 mins
  • Metabolism by liver
  • Excretion by kidneys
  • Tachyphylaxis with continuous exposure
5
Q

What are the effects of nitric oxide? What are potential therapeutic applications of nitric oxide?

A
  1. Effects of nitric oxide
    - Smooth muscle relaxant
    - Platelet inhibitor
    - Neurotransmitter
    - Immune regulator
  2. Potential therapeutic applications
    - Angina: Vasodilation of coronary arteries and improving collateral blood flow
    - HTN: Vasodilation reducing peripheral resistance and systemic BP
    - Anti-platelet: Inhibits platelet aggregation and adhesion
    - Respiratory: Inhalation in newborns with pulmonary HTN and ARDS
    - Atherosclerosis: Potential antioxidant effect preventing oxidation of LDL -> reduces foam cell formation
6
Q

Describe the pharmacokinetics of metoprolol. What effects does metoprolol have on the cardiovascular system?

A
  1. Pharmacokinetics of metoprolol
    - Given IV or PO
    - Well absorbed orally
    - 50% bioavailability due to 1st pass metabolism
    - Large Vd
    - Metabolised in the liver
    - Excreted in kidney
    - Half life is 3 - 4 hours
  2. Metoprolol is a selective B1-agonist and causes
    - Negative inotropy/reduce HR
    - Negative chronotropy/reduce contractility
    - Vasodilation/reduce BP
    - Slows AV node conduction
7
Q

What is digoxin’s mechanism of action? Why are patients in heart failure prone to digoxin toxicity/What factors predispose patients to digoxin toxicity? What are the features of digoxin toxicity? Describe the pharmacokinetics of digoxin. What is the antidote for digoxin toxicity and indications for its use?

A
  1. Digoxin’s mechanism of action
    - Mechanical: Blocking Na/K ATPase pump -> Intracellular Ca accumulation -> Increase myocardial contractility -> Increase CO
    - Electrical:
    + Shortens action potential -> Due to increase K conductance
    + Indirect parasympathetic stimulation on the heart -> Especially atrium + AV node -> Slows conductance -> Slows HR
  2. Patients in heart failure more likely to have
    - Poor renal function due to reduced CO -> Reduces digoxin clearance
    - Dehydration/hypovolaemia -> 3rd space loss, too much diuretics -> Affects drug distribution
    - Drug interaction -> More likely to be on other medications (ACEI, diuretics, CCB, B-blockers, Amiodarone) -> Potentiates effect of digoxin
    - Electrolytes imbalance -> Hypokalemia, hypomagnesaemia, hypercalcemia -> Diuretics
  3. Digoxin toxicity
    - Cardiac:
    + Arrhythmia -> Any arrhythmia possible EXCEPT AF due to increase automaticity -> VT, VF, SVT, bigeminy, heart blocks
    + Hypotension
    + Bradycardia
    - Hyperkalemia
    - Visual changes -> Yellow/green discolouration
    - N+V+D
    - Headache
    - Lethargy
  4. Pharmacokinetics of digoxin
    - Administered PO or IV
    - Good oral absorption and bioavailability
    - 10% of population has enteric bacteria which reduces oral bioavailability
    - Moderate Vd
    - Not extensively metabolised
    - Excreted 2/3 unchanged in kidneys
  5. Digoxin toxicity
    - Antidote: Digibind
    - Indications: CVS adverse effects/arrhythmia with instability (hypotension), refractory hyperkalemia
8
Q

Describe the pharmacodynamics of frusemide. What are the adverse effects of Frusemide? What are the pharmacokinetic properties of Frusemide?

A
  1. Frusemide is a loop diuretic
    - Blocks Na-K-2Cl co-transporter on ascending limb of Henle
    - Selectively inhibits Na-Cl reabsorption
    - Abolishes counter-currant mechanism leading to dilute urine
  2. Adverse effects of Frusemide
    - Hypokalemia
    - Hyponatremia
    - Hypomagnesenaemia
    - Hyperuricaemia -> Precipitates gout
    - Ototoxicity
    - Allergy symptoms
    - Postural hypotension
  3. Pharmacokinetic properties of Frusemide
    - Given PO or IV
    - Well-absorbed
    - Varied oral biovavailability
    - Onset of action 1 - 3 hours (oral), 15 - 30minutes (IV)
    - Duration of action 2 - 6 hours (oral), 2 hours (IV)
    - High plasma-protein binding
    - Low Vd
    - Metabolised mainly in kidneys -> Only 50% conjugated
    - Excreted in kidneys with 50% excreted unchanged