Pharmacology Flashcards
What are the classes of antiarrhythmic drugs?
I: Sodium channel blockers II: beta-adrenergic blockers III: prolong ERP IV: calcium channel blockers Adenosine Digoxin
What are tachyarrhythmias?
Increased HR due to:
(1) ***re-entry/retrograde
(2) enhanced automaticity in non-pacemaker cells
(3) after potentials
What are the main actions (and classes) of antiarrythmic drugs?
- Suppress enhanced automaticity – classes 2 + 4
- Prolong effective refractory period – class 3
- Slow conduction in tissue – class 1 + 2
- Depress resting membrane potential – adenosine
How do sodium channel blockers affect the myocardial action potential? What are the adverse affects?
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
How do beta1-adrenoceptor blockers work?
Affects the beta-AR linked sodium and calcium channels - reducing HR and slows contraction
What is commonly used to treat angina, heart failure, HTN and risk of sudden death after MI? what are some examples?
Beta1-AR blockers
- metoprolol
- atenolol
How do the classIII drugs prolong AP duration and ERP?
Prolong AP: by blocking K+ channels and prolonging repolarisation and preventing re-entrant arrhythmias
How does adenosine affect the myocardial AP?
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
What are the strategies of anti-hypertensive drugs?
(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
How does the renin-angiotensin system work?
- 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)
How does ACE-inhibitors decrease BP?
Inhibit the conversion of AT1 to AT2, preventing vasoconstriction and reabsorption
How do Beta-AR and Alpha-AR blockers work to reduce blood pressure?
Beta-AR: Reducde HR and contractility
Alpha-AR: suppress vasconstriction and decrease peripheral vascular resistance
What are the main types of calcium channel blockers?
(1) cardioselective - verapamil
(2) vascular smooth muscle selective - dihydropyridines
- - both: diltiazem
How do thiazides work?
They are diuretics that prevent sodium reabsorption in the loop and DCT - e.g. amiloride
What are some K+ sparing diuretics and how do they work?
- aldosterone antagonist, spironolactone, eplerenone
- they allow the kidney to reabsorb potassium but still excrete more fluid
Drugs acting early in the tubule ____ more Na+ reabsorption than those acting later
Prevent
What is the clinical use of antihypertensives?
- 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
What are the drug strategies for managing heart failure?
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
How does digoxin work?
- 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
What are the signs of digoxin toxicity?
Cardiac: serious arrhythmias
Neurological: nausea, confusion, visual
What is the consequence of digoxin in hypokalaemic patients?
If there is low K+ then digoxin occupies more ATPase sites
This reduces sodium and potassium exchange - leading to increased arrhythmias
How is angina treated?
Reduce HR and contractility - beta-AR blockers and calcium channel blockers
Dilate resistance vessels - calcium channel blockers and nitrates (GTN)
What are anti-platelet drugs used for? and what are some examples?
All coronary artery diseases
- aspirin, clopidogrel, prasugral and ticagrelor, LMW heparin
What is used for early management for acute coronary syndromes?
- Antiplatelet/anti-coag therapy
- Beta-AR blockade
- ACE inhibition
What is the longterm management of CAD?
• 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
In asthma, what is the airway narrowing due to?
(1) Thickness of airway wall increased
(2) Increased mucous in lumen
(3) constriction of airway smooth muscle
What are the therapeutic goals in asthma?
- Preventing/relieving bronchoconstriction (eg beta-2-adrenoceptor agonists)
- Suppressing inflammation – controllers such as inhaled corticosteroids (ICS)
- Inhibiting mucous hypersecretion
What beta2-AR agonists are used in asthma and how do they work? (reliever)
- Salbutamol and terbutaline
- stimulate beta2-AR on airway smooth muscle to induce relaxation
Onset: 5-10mins
short acting: 4-6 hours
What are some longer acting beta2-AR agonists? (reliever) and what are they often conjugated with?
Eformoterol and salmeterol - actions last 12-24 hours EF onset: 5-10mins SA onset: 15-20mins - often used in conjunction with inhaled corticosteroids
What is the frontline therapy in maintenance of mild, moderates and severe asthma? (controller)
Inhaled corticosteroids:
- inhalation
- regulate gene transcription of proteins like cytokines, chemokines
- must be taken prophylactically
- beclomethasone, budenoside
How do leukotriene receptor antagonists work in asthma?
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)
How to anti-IgE antibodies manage asthma?
Omalizumab - binds free IgE
- used to treat moderate to severe allergic asthma in patients with raised IgE and who are on ICS
How do statins work?
They inhibit HMG CoA reductase
What is the relevance of PCSK9 in cholesterol levels?
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
