M103 T3 L14 Flashcards
(100 cards)
1
Q
What are the two ways in which drugs are designed to treat hypercholesterolaemia?
A
to inhibit cholesterol uptake from GI tract
to reduce cholesterol production in liver
2
Q
Where is cholesterol produced?
A
85% - liver
15% - food eaten
3
Q
What are two examples of statins? (SIMulATOR)
A
SIMvastatin
ATORvastatin
4
Q
What is the role of HMG CoA reductase?
A
used to synthesise CLSR in the liver
5
Q
What is the effect of inhibiting HMG CoA reductase?
A
reduces the amount of cholesterol produced by the liver
6
Q
What happens when the amount of cholesterol produced by the liver is reduced?
A
genes that produce the LDL receptor are activated
LDL particles bind to the LDL receptor on liver cells
LDL particles become internalised
7
Q
Where are the LDL receptors expressed?
A
on the surfaces of cells that require CLSR - this is usually liver cells
8
Q
When do cholesterol particles do the most harm?
A
when they are outside of cells in the bloodstream
9
Q
When do cholesterol particles do the least harm?
A
when they are inside of cells
10
Q
What are two examples of antiplatelet agents?
A
AsPiriN
cloPidogrEL
ANtiPlatELet
11
Q
What is an example of an ACE Inhibitor?
A
rAmIpril
12
Q
What are three examples of an ARB? (LOve VAlour CANDor)
A
LOS-artan
VALS-artan
CANDES-artan
13
Q
What is the end goal of an ARB?
A
to decrease the workload of the heart
14
Q
What three conditions does stable angina digress into?
A
unstable angina
NSTEMI, STEMI
15
Q
How is stable angina treated?
A
(Bonk & CoNk)
β-blockers
CCBs
Nitrates
16
Q
How is unstable angina treated?
A
stable angina treatment (Bonk & CoNk) + ANTIPLATELETS
17
Q
Why are antiplatelets added when treating unstable angina?
A
bc the atherosclerotic plaques are more likely to rupture and form a thrombus in unstable angina
18
Q
What are the antiplatelet drugs used to treat unstable angina?
A
aspirin
clopidogrel
19
Q
G What are two alternatives to clopidogrel?
A
prasugrel
ticagrelor
20
Q
What are the two phases platelets have to go through before agglutination can occur?
A
activation
aggregation
21
Q
When do platelets begin to be activated?
A
when endothelial cells are damaged
when the plaque ruptures
22
Q
Why are platelets activated when the plaque ruptures?
A
lots of substances under the endothelium drive their activation, e.g. ADP, collagen & COX
23
Q
Which two substances are key to platelet activation?
A
ADP & TXA2
24
Q
By what process does TXA2 further activate platelets?
A
positive feedback
25
How does aspirin work as an AntiplAtelet Agent?
it inhibits COX irreversibly
it prevents the production of TXA2
reduces platelet activation
26
What are three examples of ATP receptor antagonists?
(PCT)
| clopidogrel
prasugrel & ticagrelor alternatives
27
What is the effect of ATP receptor antagonists?
they prevent platelet aggregation
28
Why is the prevention of platelet aggregation beneficial?
in a patient with unstable angina
29
How does platelet aggregation cause pain?
platelets sticking together block coronary arteries
| cause the pain that's associated with an ischaemic event
30
What is special about clopidogrel?
it was the first P2 Y12 receptor antagonist to be developed
| it's a prodrug
31
What activates clopidogrel?
CYP2C19
32
How does prasugrel work?
it undergoes hydrolysis by an esterase to form an intermediate compound, then an active compound
33
What is a disadvantage of both prasugrel and clopidogrel?
they both are irreversible
34
What is a consequence of the irreversibility of prasugrel and clopidogrel?
if bleeding occurs, it's very difficult to reverse the effects of the drugs quickly
35
Which P2 Y12 receptor antagonist is reversible?
ticagrelor
36
What is the pathway of ticagrelor?
it's absorbed from the gut
some gets metabolised
some is absorbed as the active ingredient
binds to the ATP receptor
37
What symptoms are used to diagnose a heart attack?
pain that does not go away with rest
sweating
tachycardia
cold clammy skin
38
What do the symptoms of a heart attack indicate about the NS?
that there is a problem with the sympathetic NS
39
What causes the symptoms of a heart attack?
heart has becomed damaged
cardiac output is impaired
bp drops and is detected by baroreceptors
they send signals to the medulla oblongata
activates the sympathetic system
40
What is the treatment for a heart attack?
pain relief, oxygen
aspirin / GTN
fibrinolytics
41
What is an example of a pain relief drug for treating a heart attack?
diamorphine
42
What is an example of a clot busting drug?
tenecteplase
43
What is the number one option for heart attack treatment?
pain relief
44
What is the specific type pain common in patients who have had a heart attack?
a pain radiating through the shoulder and down the the arm
45
What is the main reason for giving painkillers to patients with the radiating pain down the arm?
most people will think this pain is due to actively having a heart attack thanks to the media
this will cause anxiety
46
What is the effect of anxiety on a patient who's recently had a heart attack?
anxiety drives the sympathetic NS
it will make the heart work harder
the muscle cells are being asked to contract to relax much more forcibly and frequently than they would do normally
can cause ischaemia in the tissues - more likely to die bc they can't get the neccessary oxygen supply for this activity
47
What is the effect of diamorphine?
it decreases pain, anxiety & sympathetic activity
| it increases vasodilation in the coronary arteries
48
Why is oxygen administered to patients who have had a heart attack?
so that any blood that bypasses the blockage is maximally oxygenated
therefore it's helping the tissue downstream of that blockage as best it can to to survive
49
Why is GTN administered to patients who have had a heart attack?
it dilates coronary blood vessels
| it reduces the workload of the heart
50
Why is aspirin administered to patients who have had a heart attack?
to prevent any more thrombi from forming
51
What is the effect of tenecteplase?
acts as a fibrinolytic - degrades clots
| produces plasmin which breaks down fibrin
52
What three types of drug are used to treat heart attacks? (Anti B.ACE)
Anticoagulant
Beta blockers
ACE inhibitors
53
What is the effect of beta blockers?
they decrease cardiac workload
| they prevent arrhythmias
54
Why is metoprolol used in the hospital as a short term solution?
the hospital can adjust the dose very carefully bc of its short half life
55
What is the effect of anticoagulants for patients in long term bed rest?
prevents thrombus formation
56
What are examples of anticoagulants? (WAR.DabiL)
```
warfarin
apixaban
rivaroxaban
dabigatran
LMWHs
```
57
What is the effect of beta blockers against adrenaline?
they try to prevent adrenaline affecting the damaged heart muscle cells
58
What is an example of a LMWH?
TINZAparin
59
How does digoxin work?
it binds to the Na+/K+ ATPase and inhibits its action
this increases Na+ levels in the cardiomyocytes
AAR the Na+/Ca2+ exchanger is inhibited
build up of Ca2+ inside the muscle cell
leads to a stronger contraction
60
What is digoxin used to treat?
HF that may develop from a heart attack
61
What is the effect of digoxin?
it will ics the force of contraction of the heart
| ics cardiac output
62
What drug is used to treat dysrhythmias?
Amiodarone
63
What type of drug is amiodarone?
a K+ channel blocker drug
64
How does amiodarone work to reduce arrhythmias?
blocks some of the K+ channels
the actpts last longer - so the refractory period of ventricular myocytes is increased
can terminate arrhythmias
65
What is heroin otherwise known as?
diamorphine
66
What are ARBs otherwise known as?
Angiotensin receptor blockers
| Ang II receptor antagonists
67
What are ARBs used to treat?
high bp and HF
| chronic kidney disease
68
What medication is prescribed following a heart attack?
Angiotensin receptor blockers - ARBs
69
*Google* How is unstable angina treated?
(antiplatelet agents) clopidogrel + aspirin (up to 12 months) + an ACE inhibitor
70
For how long is unstable angina treated using clopidogrel + aspirin?
up to 12 months - most benefit occurs during the first 3 months
71
*G* What are alternatives to clopidogrel in certain patients? (PT)
prasugrel or ticagrelor
72
*NHS* What substance is used to treat stable angina?
GTN
73
*NHS* What is the most common type of angina?
stable angina
74
*NHS* How is GTN administered?
tablets (sublingual administration)
| GTN mouth spray
75
*NHS* What is the NHS advice for people having an angina attack?
Stop what you're doing and rest.
Use your GTN medicine.
Take another dose after 5 minutes if the first one does not help.
Call 999 if you still have symptoms 5 minutes after taking the 2nd dose
76
*NHS* When can GTN be used by patients at risk of angina attacks?
prophylactically before e.g. exercise
77
*NHS* What might patients experience soon after using GTN prophylactically?
headache, flushing or dizziness
78
*NHS* What is the difference between sublingual and buccal administration?
sublingual - drug placed under tongue to dissolve and absorb into the bloodstream through the tissue there
buccal - drug placed between gums and cheek, where it also dissolves and is absorbed into the bloodstream
79
*NHS* When do GTN tablets expire?
about 8 wks after the packet is opened
80
*NHS* When do GTN spray expire?
3 years
81
What is the chemoreceptor of ADP?
P2Y12 receptors
82
What happens when endothelial cells are damaged?
platelet activation: ADP < P2Y12 receptors (on platelets) < GPIIb/IIIa receptors expressed
fibrinogen binds to these GPIIb/IIIa receptors to crosslink different platelets
83
How does ADP activate platelets?
it acts on P2Y12 receptors on the platelets, stimulating the expression of GPIIb/IIIa receptors
84
Where are P2Y12 and glycoprotein IIb/IIIa receptors located?
on platelets
85
How does COX indirectly activate platelets?
it produces TXA2
86
By what processes are platelets activated?
ADP *pathway
| COX *pathway
87
What substance does aspirin inhibit?
COX, irreversibly
88
How does clopidogrel and prasugrel work as ADP antagonists?
by blocking ADP's receptors on platelets, P2Y12 receptors
89
What does the expression of GPIIb/IIIa receptors on platelet surfaces allow for?
agglutination via these GPIIb/IIIa receptors
fibrinogen and blood proteins bind to the receptors on two different platelets, causing them to stick together [crosslink]
90
What is clopidogrel's relationship with CYP2C19?
it needs CYP2C19 to activate it
| but the CYP2C19 has lots of polymorphisms, most of which reduce the activity of clopidogrel
91
What is a consequence of the polymorphisms in CYP2C19 on the dosage / effectiveness of clopidogrel?
for a given dose of clopidogrel, the amount of the active compound in the bloodstream is far less than the prodrug dose initially given
92
Why was prasugrel developed after clopidogrel was made available?
bc of the polymorphisms in CYP2C19 which activate clopidogrel, it needs a much higher dosage than it should
prasugrel works by a different pathway that doesn't involve CYP2C19
93
What is the difference between stable and unstable angina?
stable: angina symptoms during moderate+ physical activity, which go away with rest and/or medication
unstable: angina symptoms while doing very little or resting
94
How do beta blockers work?
they block the release of the adr + noradr in certain parts of the body
95
What happens to b-adrenergic receptors signalling pathways AAR of HF?
they undergo several adaptive and sometimes maladaptive regulatory changes
96
What activities are beta-adrenergic receptors responsible for when activated?
modulating the heart rate and myocardial contractility
97
What is the difference between arrhythmia and dysrhythmia?
nothing - they're the same
98
What is TXA2 produced by?
activated platelets during haemostasis that produce COX-1 isoform (from which TXA2 is synthesised)
99
What is the role of TXA2?
has prothrombotic properties - it stimulates activation of new platelets and increases platelet aggregation via Glycoprotein (GP) IIb/IIIa receptors
100
What is the difference between agglutination and aggregation?
agglutination - the joining of platelets only, without other cells and debris
aggregation - platelets, cells and debris clumping all together
