Pharmacology

Question 1

What are the classes of antiarrhythmic drugs?

Answer 1

I: Sodium channel blockers
II: beta-adrenergic blockers
III: prolong ERP
IV: calcium channel blockers
Adenosine
Digoxin

Question 2

What are tachyarrhythmias?

Answer 2

Increased HR due to:

(1) ***re-entry/retrograde
(2) enhanced automaticity in non-pacemaker cells
(3) after potentials

Question 3

What are the main actions (and classes) of antiarrythmic drugs?

Answer 3

• Suppress enhanced automaticity – classes 2 + 4
• Prolong effective refractory period – class 3
• Slow conduction in tissue – class 1 + 2
• Depress resting membrane potential – adenosine

Question 4

How do sodium channel blockers affect the myocardial action potential? What are the adverse affects?

Answer 4

Delays the time taken to raise the membrane potential to threshold (conduction time delayed) so myocardial contraction rate is slower
Adverse affects: enhanced risk of arrhythmia as conduction in latent circus is slowed so timing falls into critical range

Question 5

How do beta1-adrenoceptor blockers work?

Answer 5

Affects the beta-AR linked sodium and calcium channels - reducing HR and slows contraction

Question 6

What is commonly used to treat angina, heart failure, HTN and risk of sudden death after MI? what are some examples?

Answer 6

Beta1-AR blockers

• metoprolol
• atenolol

Question 7

How do the classIII drugs prolong AP duration and ERP?

Answer 7

Prolong AP: by blocking K+ channels and prolonging repolarisation and preventing re-entrant arrhythmias

Question 8

How does adenosine affect the myocardial AP?

Answer 8

Adenosine opens the K+ channels which decreases the resting membrane potential so the stimulus cannot raise the potential to threshold - ectopic impulses cannot conduct
Adenosine receptors are on the atrial and AV conducting tissue

Question 9

What are the strategies of anti-hypertensive drugs?

Answer 9

(1) Reduce cardiac output - beta-AR blockers, Ca2+ blockers
(2) Dilate resistance vessels - Ca2+ blockers, RAS blockers, alpha-AR blockers, nitrates
(3) Reduce vascular volume - diuretics , RAS blockers

Question 10

How does the renin-angiotensin system work?

Answer 10

• Drop in blood pressure
• Renin released from kidney
• Renin converts forms angiotensin 1 from angiotensinogen
• ACE from the lungs converts AT1 to AT2
• AT2 causes vasconstriction and stimulates kidney to release aldosterone (increases reabsorption)

Question 11

How does ACE-inhibitors decrease BP?

Answer 11

Inhibit the conversion of AT1 to AT2, preventing vasoconstriction and reabsorption

Question 12

How do Beta-AR and Alpha-AR blockers work to reduce blood pressure?

Answer 12

Beta-AR: Reducde HR and contractility

Alpha-AR: suppress vasconstriction and decrease peripheral vascular resistance

Question 13

What are the main types of calcium channel blockers?

Answer 13

(1) cardioselective - verapamil
(2) vascular smooth muscle selective - dihydropyridines
- - both: diltiazem

Question 14

How do thiazides work?

Answer 14

They are diuretics that prevent sodium reabsorption in the loop and DCT - e.g. amiloride

Question 15

What are some K+ sparing diuretics and how do they work?

Answer 15

• aldosterone antagonist, spironolactone, eplerenone

- they allow the kidney to reabsorb potassium but still excrete more fluid

Question 16

Drugs acting early in the tubule ____ more Na+ reabsorption than those acting later

Answer 16

Prevent

Question 17

What is the clinical use of antihypertensives?

Answer 17

• Thiazide diuretic or ACEI or AT1 blocker
• Both thiazide diuretic and ACEI or AT1 blocker
• Add calcium channel blocker
• Add alpha1 adrenoceptor blocker or beta blocker

Question 18

What are the drug strategies for managing heart failure?

Answer 18

ACE-I or AT1 blocker - reduce PVR/aldosterone driven remodelling
Aldosterone antagonists
Beta-adrenoceptor blocker - counter affects of symp stim
Loop diuretic - counter aldosterone driven Na retention
Digoxin - increase cardiac contractility
Nitrates
Oxygen

Question 19

How does digoxin work?

Answer 19

• Competes with K+, thereby blocking Na+/K+ATPase
• Less efficient calcium exchange = increased IC Ca2+ and more efficient myocyte contraction
• decreases HR and increases contractility

Question 20

What are the signs of digoxin toxicity?

Answer 20

Cardiac: serious arrhythmias
Neurological: nausea, confusion, visual

Question 21

What is the consequence of digoxin in hypokalaemic patients?

Answer 21

If there is low K+ then digoxin occupies more ATPase sites

This reduces sodium and potassium exchange - leading to increased arrhythmias

Question 22

How is angina treated?

Answer 22

Reduce HR and contractility - beta-AR blockers and calcium channel blockers
Dilate resistance vessels - calcium channel blockers and nitrates (GTN)

Question 23

What are anti-platelet drugs used for? and what are some examples?

Answer 23

All coronary artery diseases

- aspirin, clopidogrel, prasugral and ticagrelor, LMW heparin

Question 24

What is used for early management for acute coronary syndromes?

Answer 24

• Antiplatelet/anti-coag therapy
• Beta-AR blockade
• ACE inhibition

Question 25

What is the longterm management of CAD?

Answer 25

• Anti-platelet agents • Anticoagulants • Risk factor management • Beta adrenergic blockade • ACE inhibition or ARB • Specific interventions – revascularization, rhythm etc Risk management: diabetes, BP, lipids, smoking

Question 26

In asthma, what is the airway narrowing due to?

Answer 26

(1) Thickness of airway wall increased (2) Increased mucous in lumen (3) constriction of airway smooth muscle

Question 27

What are the therapeutic goals in asthma?

Answer 27

1. Preventing/relieving bronchoconstriction (eg beta-2-adrenoceptor agonists) 2. Suppressing inflammation – controllers such as inhaled corticosteroids (ICS) 3. Inhibiting mucous hypersecretion

Question 28

What beta2-AR agonists are used in asthma and how do they work? (reliever)

Answer 28

- Salbutamol and terbutaline - stimulate beta2-AR on airway smooth muscle to induce relaxation Onset: 5-10mins short acting: 4-6 hours

Question 29

What are some longer acting beta2-AR agonists? (reliever) and what are they often conjugated with?

Answer 29

``` Eformoterol and salmeterol - actions last 12-24 hours EF onset: 5-10mins SA onset: 15-20mins - often used in conjunction with inhaled corticosteroids ```

Question 30

What is the frontline therapy in maintenance of mild, moderates and severe asthma? (controller)

Answer 30

Inhaled corticosteroids: - inhalation - regulate gene transcription of proteins like cytokines, chemokines - must be taken prophylactically - beclomethasone, budenoside

Question 31

How do leukotriene receptor antagonists work in asthma?

Answer 31

LT mediate inflammation by binding to LT receptors in airways and inducing airway narrowing and promotes secretion of mucous, blood leakage and eosinophil influx (this is inhibited)

Question 32

How to anti-IgE antibodies manage asthma?

Answer 32

Omalizumab - binds free IgE | - used to treat moderate to severe allergic asthma in patients with raised IgE and who are on ICS

Question 33

How do statins work?

Answer 33

They inhibit HMG CoA reductase

Question 34

What is the relevance of PCSK9 in cholesterol levels?

Answer 34

Mutations in PCSK9 can cause high or low cholesterol in people though gain of function (high) or loss function (low) so it is a target for treatment