M103 T3 L13 Flashcards
What is preload regulated by?
the sympathetic system
RAAS
What are the side effects of stable angina treatment?
Postural hypotension
Headache, Dizziness
What is an example of a stable angina treatment?
glyceryl trinitrate (GTN)
What is reflex tachycardia caused by?
the activation of the sympathetic NS
What should be done if stable angina treatment causes side effects?
should look to block effects of sympathetic NS using a beta blocker
What are the roles of beta blockers?
inhibit renin release from kidney - inhibit RAAS
What are the side effects of beta blockers?
Bronchoconstriction
Fatigue
How can CCBs reduce the heart rate?
by blocking L-type channels in the SA and AV-nodes
this slows the rate of depolarisation and of actpt generation
How can CCBs reduce the force of contraction of the ventricles?
by reducing calcium entry through L-type channels
What is the effect of Ivabradine?
blocks If in the nodal tissue of the heart
How does Ivabradin slow the rate of depolarisation of the SA node cells?
reduces Na+ entry through If channels
reduce firing frequency
reduce heart rate
What are alternative drugs to ivabradin? (Long Nights Rapping)
Long acting nitrates (isosorbide mononitrate)
Nicorandil
Ranolazine
What is the effect of long acting nitrates?
they decrease preload
Where is nitric oxide produced?
in the endothelial cells that line the blood vessel
What is one of the ways by which nitric oxide is produced in blood vessels?
stress / resistance is created between the flow of fluid against the walls of the blood vessels
the stress causes an influx of ca2+ into endothelial cells
ca2+ acts as a co factor to stimulate activity of NO synthase
NOS converts arginine to nitric oxide
What is a by product of NO production?
citrulline (amac)
What happens to NO after production?
passes across the cell membrane of the endothelial cells into the smooth muscle cell
binds to its muscle receptor - sGC
What is the function of sGC?
helps with the production of cyclic GNP
to act as a receptor for NO
What is the role of cyclic GMP?
relaxes the smooth muscle walls of the coronary vessels
How do nitrites increase oxygen supply to the heart?
they produce NO, which activates cyclic GMP
leads to muscle relaxation
What are the two effects of nitrates on the heart?
increase oxygen supply to the heart
decrease the work that the heart has to do
When can’t beta blockers be used?
if the patient is asthmatic
if the patient has poor peripheral circulation
What are alternative drugs when beta blockers can’t be used?
calcium channel antagonists
What main types of calcium channel antagonists are used for stable angina treatment?
phenyalkylamines
benzothiazepines
What effects do phenyalkylamines and benzothiazepines have on the nodal tissues?
reduce calcium entry into nodal cells
therefore slow the frequency of actpt generation
slows heart rate
What effects do phenyalkylamines and benzothiazepines have on the ventricular myocytes?
block calcium channels outside the calcium channels
reduce the force of contraction
What happens if calcium channel antagonists and some beta blockers are used together in a mixture?
severe bradycardia
heart block
Why can a mixture of calcium channel antagonists and some beta blockers be dangerous?
because they work in the same way and achieve the same effects
What are the two causes of heart block?
a delay in the time it takes for the actpt to get from the atria to the ventricles
when some of the actpts generated in the SA node don’t make it through the ATP into the ventricles
Which two heart channels does the funny current travel through?
HCN channel
pacemaker channel
Why is it called the funny current?
because most channels are opened by depolarisation,
but this one’s opened by hyperpolarization
How is glyceride trinitrate administered?
pill administered sublingually
How does glyceride trinitrate enter the body?
absorbed through the oral mucosa
straight into the bloodstream
How are Long acting nitrates administered?
orally - tablets
patch - a long slow release patch so it can be released into the blood system very slowly
What is the effect of nicorandil based on its nitrate-like properties?
can dilate some of the coronary arteries
can open some k channels
What is the effect of nicorandil based on ability to open some k channels in vascular smooth muscle cells?
dilate peripheral arterials
decrease after load by decreasing peripheral resistance
reduce myocardial oxygen requirements
What are the consequences of the late current being over expressed?
affects the actpt shape
affects the hearts’ contraction
How does the over expression of the late current affect the patient physiologically?
more na ions enter the cell in the normal healthy heart muscle cell
however lots more na ions enter the damaged cell
How does the na-ca exchange protein in the late current remove ca ions?
uses the na ion gradient across the membrane as the driving force for the removal of ca gainst its concentration gradient
Through which protein is calcium removed from the heart muscle cells?
the na-ca exchange protein
What are the amounts of na ions inside and outside of the heart muscle cells?
outside - 140 mM
inside - 5 million mM
Why is the removal of ca from the inside to the outside of heart muscle cells important?
it shortens the contraction that’s occurring in the heart muscle
What happens to the late na+ channel when cardiomyocytes are damaged and CO is compromised?
it becomes overexpressed
lots of na ions enter the cell during the actpt
they are followed by some of ca ions
However, bc there are lots of na ions inside the cell, this pump doesn’t work in the normal way
How can the late na+ channel work when it’s not working in the normal way?
less na and ca ions are removed
the pump can even work in reverse
What happens when the late na+ channel is reversed?
the na ions are removed
there is an influx of ca ions
How does the heart try to compensate when the late na+ channel is reversed?
it tries to generate more force
does more work
What happens when the heart tries to work harder to compensate for reversed late na+ channels?
can cause the pain associated with ischaemic events
What is the effect of Ranolazine?
it blocks the late na+ current
reduced influx of na ions through this current
reverses the pathological state where there is elevated intracellular ca and stronger contraction
causes contraction and intracellular ca levels to return to normal levels
How is pacemaker current calculated?
Ih/f
What are terms associated with an L-type channel?
high-voltage activated
voltage-dependent
What does the “L” stand for in L-type channel?
long-lasting - length of activation
In what condition are beta blockers contraindicated in?
patients with peripheral vascular disease
What is the term for the feedback mechanism activated in response to low bp?
Reflex tachycardia
What are features of sGC?
it’s soluble - completely intracellular
is involved in vasodilation
Which amac is NO synthesised from?
arginine
How are long acting-nitrates administered?
tabletz
Which angina medication (ivabradin alternative) benefits men more than women?
Ranolazine
What channels are targeted by CCBs?
L-type channels in the SA and AV-nodes
