PHARM 11: Drugs + CVS - HEART Flashcards
Describe the mechanism by which the HR is regulated
in response to sympathetic and parasympathetic stimulation:
Sympathetic response:
increased cAMP, increase If, Ica
Parasympathetic response:
decreased cAMP, increased Ik
What is a primary determinant of myocardial oxygen demand?
myocyte contraction
more work –> more O2 required
What is the effect of Beta blockers on If and Ica
what effect does this have?
decreases both If and Ica
decreases HR
What is the effect of calcium antagonists on Ica
what effect does this have?
decreases Ica
decreases HR
What is the effect of Ivabradine on If?
What effect does this have?
decreases If
decreases HR
How does Beta blockers effect contractility of the Heart?
decreases contractility
What are the 2 classes of calcium antagonists?
a) rate slowing
b) non-rate slowing
give examples of rate slowing calcium antagonists
- phenylalkylamines
- benzothiazepines
–> blocks receptors on cardiac and smooth muscle tissue
give examples of non rate slowing calcium antagonists
- dihydropyridines
- -> has powerful effect on smooth muscle
- -> but little effect on the heart itself
note: profound vasodilation can lead to reflex tachycardia
how does organic nitrate + K-channel openers influence Myocardial O2 supply/ demand
(3 ways)
- they increase coronary blood flow
- decreases amount of work heart has to do
- increases delivery of oxygen to the heart
- Organic nitrates increase NO available –> more cGMP –> relaxation + opens K+ channels
- K+ Channel Openers –> hyperpolarisation
• Both ↑ blood flow in general - Both also cause:
o Vasodilation, meaning ↓ afterload
o Venodilation, meaning ↓ preload
What two different effects of nitrates/potassium channel openers influence preload and afterload?
Vasodilation = ↓ afterload Venodilation = ↓ preload
What are medications you would use to treat angina?
- beta blockers
- calcium antagonist
- ivabradine
- nitrate (symptomatic treatment) –> immediate dilation of coronary vessels to match oxygen demand
What are some side effects of beta blockers?
why do they occur?
actions on B1:
- CO reduction –> cardiac failure exacerbation
- removes capacity to dilate –> increases vascular resistance –> increased strain on heart
- less AV node conduction –> bradycardia
action on B2:
- blockade of B2 –> bronchoconstriction
- impairs glucose control = hypoglycemia –> in diabetics
- blockade of B2 (skeletal muscle vessels) –> less peripheral vasodilation –> cold extremities
others:
- fatigue
- impotence
- depression
What are some side effects of calcium channel blockers?
Verapamil (rate limiting) –> heart consequences
- bradycardia + AV block = acts on Ca2+ channel block
- constipation = acts on gut Ca2+ channels
Dihydropyridines (non rate limiting) –> blood vessels
- ankle oedema = due to vasodilation, large amount of fluid leakage from capillaries –> enters lymph –> oedema
- headache = vasodilation –> excessive blood flow to brain / peripheries
- palpitations –> reflex tactic ardia
describe the vaughan williams classification
class 1: Na+ channel blockade
class 2: Beta adrenergic blockade
class 3: Prolongation of repolarisation
class 4: Ca2+ channel blockade
how is adenosine used as an anti-arrythmics?
- IV
- terminates supraventricular tachyarrhythmias
- short lived
2 mechanisms
a) Acts on A2 receptors in VSMC –> cause vasodilation of vascular smooth muscle
b) Acts on A1 receptors in SAN/AVN –> decreased Ca2+ channel opening, but prolonged K+ channel opening –> causes prolonged depolarisation + repolarisation (relaxation) of heart
–> decreases chronotropic + dromotropic effect
how is verapamil used as an anti-arrythmics?
- used to reduce ventricular responsiveness to atrial arrhythmias
- by depressing SA automaticity –> and subsequent AV node conduction
reduces calcium entry into tissues –>
What is an amiodarone used for?
- class 3
- used for supraventricular + ventricular tachyarrhythmias
How do amiodarones work as an anti arrythmics ?
mechanism
- multiple channel block
- prolongs Repolarisation step
- less likely to get reentry rhythm
what are some side effects of amiodarones?
- skin rashes
- hypo/hyperthyroidism
- pulmonary fibrosis
How do digoxins (cardiac glycosides) work as an anti arrythmics ?
(mechanism)
2 mechanism
a) blocks Na-K ATPase
- there is accumulation of Na+
- excess Na+ is removed by Na+/Ca2+ exchanger –> which increases intracellular Ca2+ conc –> thus causes increases inotropic effect
b) - central vagal stimulation –> increases refractory period + reduces rate of AV node conduction
What is a digoxin (cardiac glycosides) used for?
- a.fib + flutter –> can cause increase in ventricular rate –> impairs ventricular filling –> causes cardiac output
- so digoxin acts to reduce Cardiac Output
what are some side effects of Digoxin (cardiac glycosides) ?
- dysrhythmias
e. g AV conduction block
Hypokalaemia (usually a consequence of diuretic use) lowers the threshold for digoxin toxicity WHY?
if you are hypokalaemic you need to be careful with digoxin
K+ and digoxin compete for the same site on Na-K ATPase
when you are have less K+,
there is increase binding of digoxin instead —> which can cause digoxin toxicity
In SA node + AV node depolarisation = largely driven by :
calcium
describe the graph relating different channels and the action potential elicited in the heart
(ik, if, ica etc)
If = hyperpolarised causes HCN channels to open
- Na+ enters through these channels
- slow inflow of Na+
as it becomes more positive - - ca2+= channels open - and then calcium enters via the L-type channels
around 0mv
Ik = potassium K+ channels = there is depolarization –> back to resting state
how is contractility maintained
Ca2+ flows in
- initiate contraction
also directly activates RyR channels –> to increase Ca2+ release (CICR)
- Ca2+ binds to troponin –> initiates contraction
- relaxation occurs when Ca2+ unbinds form troponin
- Ca2+ = pumped back into SR for storage
- rest of Ca2+ exchanged for Na+
- Na+ gradient = maintained by Na+-K+ ATPase
what can increase myocardial work demand?
increase in
- heart rate
- preload (less effect)
- afterload
- contractility
How do calcium antagonists affect contractility
- decreases Ica
what is the effect organic nitrate
produce NO in tissues
activates guanylate cyclase
or K+ channel opens –>K+ efflux –> hyperpolarised
tissue remains relaxed for longer period of time
what is angina usually due to?
- when myocardial oxygen supply isn’t met with demand
- due to insufficient blood flow/ delivery to the heart
patients has arrhythmia associated with heart failure - what 2 MAIN drugs would you use?
why are they used?
- beta blocker
- ivabraine
- -> slows heart down to restore normal pattern of contraction
why is pindolol a good beta blocker to use for heart failure
acts on B1 + B2
restores dilating effect –> less work needed to bring blood back to the heart
why is carvedilol a good beta blocker to use for heart failure
acts on B1 + B2 + a1
has antagonistic effect on a1 –> which causes vasodilation –> less work needed to bring blood back to the heart
when should beta blockers be avoided?
asthmatics
hypoglycaemic individuals
non rate limiting Calcium antagonists –> have similar side effect profiles to:
Nitrates
rhythms disturbance due to increased HR
- tachyarrhythmias
rhythms disturbance due to decreased HR
- bradyarrhythmias
adenosine is usually used to for what type of arrhythmia?
supraventriular arrhythmias
