CVD Drugs Flashcards
1
Q
what is angina
A
heart temporarily deprived of oxygen
2
Q
what is a heart attack
A
heart deprived of oxygen (muscle death)
3
Q
what is dysrhythmia
A
heart rhythm disturbed
4
Q
what is heart failure
A
heart does not pump properly
5
Q
how many people in the UK have had a heart attack
A
1.5 million
6
Q
how many people have CHD and angina
A
2.3 million have CHD and 2 million have angina
7
Q
what are lipoproteins composed of
A
- lipids (triglycerides or cholesterol esters)
2. phospholipids, cholesterol and proteins
8
Q
what lipoproteins have the lowest density of all
A
chylomicrons
9
Q
what is synthesised in the hepatocytes
A
cholesterol
10
Q
increased risk of atherosclerosis diagram
A
11
Q
how does HDL decreased risk of atherosclerosis
A
increases fibrinolysis - helps break down blood clots and increases fibrin degradation
increase prostacyclin formation - decrease aggregation
12
Q
what is familial hypercholesterolaemia
A
defect in LDL receptor or ApoB protein
autosomal dominant
13
Q
what is the main component in plaque
A
foam cells (they are dark areas where the nucleus is)
14
Q
what is an example of a statin
A
atorvastatin
15
Q
how does atorvastatin reduce LDL
A
- competitively inhibits HMG-CoA reductase, rate limiting enzyme in production of cholesterol
- similar in structure
- recuses liver production of cholesterol
- lowered cholesterol leads to more LDL receptors
- increased removal of LDL from plasma
- also increased HDL and lower triglycerides
16
Q
mevalonate pathway
A
17
Q
problems with statins
A
- myositis - muscle inflammation
- rhabdomyolysis - muscle breakdown causes dark coloured urine
- myoglobin is being reduced fro muscle and released in urine
- altered liver function tests
18
Q
percentage of population taking statins in 2013
A
13%
19
Q
what is the NHS tool to see your own cardiovascular risk
A
QRISK3
20
Q
what does the QRISK3 do
A
calculates risk that you will have a heart attack or stroke in net 10 years
21
Q
what factors does the QRISK3 use
A
age, sex, ethnicity and weight
22
Q
what is the cut off for statin treatment for primary prevention
A
10% It was 20%
23
Q
how does exzetimibe work
A
inhibits intestinal cholesterol absorption
inhibits specific cholesterol transporter in gut
24
Q
what does ezetimibe result in
A
reduced LDL
reduced total cholesterol
25
when is ezetimibe used
in patients who cannot tolerate statins
26
cholesterol absorption in the intestine and how ezetimibe inhibits it diagram
27
how do anion exchange resins work
sequester bile acids in the gut, increased usage of cholesterol
28
how do fibrates work
agonists at a receptor called PRAR alpha
29
what is olestra
fat substitute
cannot be absorbed by the GI tract
Mal-absorption of fat-soluble vutamus
30
acute coronary syndromes
1 unstable angina
2 non ST elevated myocardial infarction NSTEMI
3 ST elevated myocardial infarction STEMI
31
what is angina pectoris
crushing pain in chest that may radiate to arm, neck or jaw
| the pain results from cardiac schema
32
what substrates are released as an example of referred pain
k+ , h+ and bradykinin
33
types of angina
stable and unstable
34
what are types of angina when vessels constrict/spasm
prizmental's angina
| microvascular angina
35
what is stable angina caused by
atherosclerosis of coronary arteries
36
what is unstable angina
atherosclerosis and a blood clot
| with higher risk of MI
37
NICE care pathway for stable angina
38
what do short acting nitrates do
relieve an attack
39
what does optimising angina drugs do
prevents further attacks
40
what do secondary prevention drug do
prevent progression of atherosclerosis
41
what is the surgical approach to angina
revasularisation
42
aspirin as an organic nitrate treatment
prevents platelet aggregation
43
first pass metabolism diagram
44
organic nitrate list
glyceryl trinirate
amylnitrate
isosorbide denigrate
nicroandil
45
what are pro drugs
drugs that have to be metabolised before becoming effective
46
where do organic drugs get metabolised
at their site of action and not in the liver
47
vasodilation pathway induced by an organic nitrate (prodrug)
48
how do nitrates relieve an attack of angina
- by dilating coronary arteries although less important as coronary arteries already maximally dilated by metabolises from ischaemic myocardium
- by reducing cardiac work and hence reducing the cardiac O2 demand - nitrates reduce cardiac work by reducing preload (principal effect) and after load
49
how is cardiac workload reduced
- dilation of peripheral blood vessels - capacitance veins
- heart does not have to push so hard
- less blood returned to the heart ; lower force of contraction.
50
sequence of events leading to angina
51
what do large doses of nitrates cause
arteriolar dilation
fall in peripheral resistance
reduce in cardiac after load
reduces cardiac work
52
improved coronary blood supply
53
nicorandil mechanism of action
- activator of K+ ATP channels and NO donor
- dilates both arteries and veins
- effects vs angina similar to nitrates
54
what are the unwanted effects of nicorandil
headache, flushing, hypotension, nausea and vomiting
55
reducing cardiac workload : beta blockers diagram
56
binding sites for verapamil and amlodipine
57
mechanism of vearpamil in stable angina
- blockade of Ca2+ channels in use-dependent
- more potent on heart than vascular smooth muscle
- Ca2+ channel blockade in cardiac tissue reduces heart rate and cardiac output
- dilation of orioles reduces cardiac after load
- cardiac work and O2 demand are reduced
58
amlodipine in stable angina
- blockade of Ca2+ channels and is NOT use dependent
- more potent on vascular smooth muscle than the heart
- dilatation of arteries reduces cardiac after load
- dilatation of capacitance veins reduced cardiac preload
- cardiac work and O2 demand are reduced
59
when are surgical approaches used for treating angina
if the drug options have not Brough the angina under control.
60
how does a coronary artery angioplasty work
a catheter is introduced into a large vessel in the groin or arm and is treated into the heart and guided to the place where the artery is blocked. the journey of the catheter to the blocked artery can br visualised by injection a dye out of the catheter into the blood vessel and following it using an Xray machine.
when the catheter reaches the blockage, a balloon at its tip is inflated, which opens the artery and also pushes open a metal mesh tube, called a stent. the stent will keep the artery open once the balloon is delated and the catheter is removed. stents can be either bare stainless steel or impregnanted with drugs designed to reduce inflammation
61
what are stents with drugs in them called
drug eluting stents
62
when is an angioplasty used
to treat angina that has not been controlled by drugs. it is also used as an emergency treatment in patients who have had a heart attack. in angina it can be used to reduce the frequency of angina attacks and give better control than drug treatment but t does not reduce the chance of death or of another heart attack in the usurer.
63
what are the adverse effects of an angioplasty
stroke and myocardial infarction due to the angioplasty either triggering the formation of a blood clot or dislodging one that has already formed which travels through the blood to a smaller vessel and blocks it. (embolism)
64
what is re closing of the artery called
restenosis
65
what is a coronary artety bypass graft
it is open heart surgery. it removes a non-essential blood vessel from another part of the body and uses it to restore blood flow to the part of heart in which the blood supply is compromised.
66
what are the most common blood vessels used in a CABG
internal mammary artery and the great saphenous vein from the leg
67
how long to CABG last
15 years and then need to be replaced
68
ACS classification and ECG readings
69
what is the pain treatment given in ACS
opioids
70
platelet activation and aggregation
71
what are platelets derived from
megakaryocytes (bone marrow cells)
72
what are the stimuli for platelet aggregation/activation
- thrombin
- ADP
- TxA2
73
TxA2 mechanism
synthesised from arachidonic acid by cycle-oxygenase (COX)
platelets syntheses TxA2 when activated
TxA2 is released from platelets
enhances expression of glycoprotein IIB/IIa receptors
74
how do platelets link together
through binding to fibrinogen and it is a chain reaction
75
what stops the chain reaction of platelet activation from happening
prostacyclin is released which stops the chain reaction from speeding.
demo the cells adjacent to the damage
synthesised from membrane lipids
inhibits platelet activation
76
formation of TxA2 and PGI2
thromboxane and prostacyclin
77
what is the COX1 gene
'housekeeping gene'. expressed in most cells and is involved in the synthesis of thromboxane A2 and prostacyclin.
78
what is the COX2 gene
mainly expressed in inflamed tissues and is the target of non-steroidal anti-inflammatory drugs (NSAIDS) like ibuprofen
79
what is the COX3 gene
frameshift mutation and does not produce active enzymes
80
NSAID effect on COX
NSAIDS produce their anti-inflammatory effects by acting on. COX2, most of them also have actions at COX1 and it is these COX1 effects that produce many of the side effects of NSAIDS.
81
aspirin mechanism
irreversibly blocks platelet COX enzyme, reducing TxA2 synthesis
low doses of aspirin used to avoid reducing enzyme in endothelium (source of prostacyclin)
aspirin alters the balance between platelet TxA2 and endothelial prostacyclin
82
unwanted effects of aspirin as an anti-platelet drug
extended bleeding time
indigestion
allergy
provoke asthma attacks - involves diverting membrane derived acid into pro0inflammatory signally molecules
83
what is Reye's syndrome
under 16s - liver and brain damage when aspirin is used during a viral illness
84
what is anti-platelet drug action via
modulation expression of glycoprotein IIb/IIa receptors
85
an example of an anti platelet drug and its mechanism
clopidogrel - inhibits glycoprotein IIb/IIa receptor expression on platelets by blocking the ADP receptor irreversibly
86
what does ticagrelor do
allosterically inhibits the ADP receptor
87
what does allosterically mean
In biochemistry, allosteric regulation is the regulation of an enzyme by binding an effector molecule at a site other than the enzyme's active site. The site to which the effector binds is termed the allosteric site or regulatory site.
88
what is the PLATO trail
89
clopidogrel and ticagrelor unwanted effects
- extended bleeding time
- GI tract problems
- headaches and dizziness
- gout
- breathlessness
bottom two are only ticagrelor
90
what is dipyridamole
phosphodiesterase inhibiter. prevents the breakdown of cAMP in platelets
91
mechanism diagram for dipyridamole
92
dipyridamole unwanted effects
```
GI tract problems
headaches
muscle pain
feeling hot (vasodilation)
worsen angina
decrease the flow in stenosed vessel
```
93
examples of thrombolytic drugs
reteplase
alteplase
streptokinase
94
mechanism diagram for thrombolytic drug
95
thrombus maturation -->
4.5 hour treatment window before it changes shape
96
PCI vs Thrombolysis for MI
97
what procedure has a risk of haemorrhage
thrombolysis
98
are there more PCI or thrombolysis centres
PCI centres
