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advances cardiovascular Flashcards

1
Q

drugs used (10)

A

lipid lowering drugs - targets hypercholesterolemia

organic nitrates - cardiac output

beta blockers/ beta adrenoreceptor antagonists - hypertension

calcium ion channels - hypertension

thienopyridines - antiplatelet

COX inhbititors - antiplatelet

positive ionotropes - heart contractivity

anti arrhythmic or ace inhibitors - multiple targets

arbs

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2
Q

lipid lowering drug example

A

atorvastatin

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3
Q

organic nitrates drug example

A

nitroglycerin

fast acting

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4
Q

beta adrenoreceptor antagonist example

A

atenolol

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5
Q

calcium channel blocker example

A

verapamil

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6
Q

thienopyridines example

A

clopidogrel

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7
Q

COX inhibitor example

A

naproxen, aspirin

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8
Q

positive ionotropes

A

digoxin

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9
Q

anti arrhythmic III drug example

A

amiodarone

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10
Q

ACE inhibitor example

A

captopril

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11
Q

ARB drug example

A

candesartan

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12
Q

novel cardiovascular therapies in lipid lowering drugs - 3

A

mipomersen

lomitapide

PCSK9 inhibitors

manage atheromatous disease

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13
Q

novel cardiovascular therapies in anginal therapies - 3

A

ivabradine

nicorandil

trimetazidine

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14
Q

novel cardiovascular therapies in heart failure therapies - 2

A

tolvaptan

cardiotrophin-1

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15
Q

novel cardiovascular therapies in hypertension therapies - 2

A

aminopeptidase A inhibitors

diminazene

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16
Q

what do lipid lowering drugs do

A

dec plasma ldl

offer endothelial protection so are prophylactic

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17
Q

nutraceuticals

A

small group of cells associated with diet, found naturally e.g. oats, yeast, rice

has some effect in dec cardiovascular risk

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18
Q

what is mipomersen/ mechanism of action

A

antisense oligonucleotide to ApoB mRNA, binds and promotes mRNA degradation

targets apolipoprotein B-100 (ApoB) which is a component of LDL and VLDL synthesis (bad cholesterol)

reduced formation of ApoB, reduced synthesis of bad cholesterol

dec of 25-40% of circulating LDL in patients

not commonly used

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19
Q

what does mipomersen target

A

liver - significant in managing plasma cholesterol level

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20
Q

mipomersen administration frequency

A

weekly injection

at lipid lowering clinic

21
Q

mipomersen side effects

A

injection site reactions

hepatic steatosis/ fatty liver due to accumulation

22
Q

lomitapide mechanism of action

A

inhibits microsomal triglyceride transfer protein (MTP) enzyme (endoplasmic reticulum of hepatocytes)

reduction in VLDL-C, LDL-C, chylomicrons

reduction in LDL-C in plasma circulation by more than 40%

23
Q

microsomal triglyceride transfer protein (MTP)

A

linked to ApoB assembly and release

24
Q

VLDL-C, LDL-C, chylomicrons

A

plasma cholesterol precursors

25
lomitapide administration
oral, uninvasive not with food, with low fat diet in clinic starts 5mg per day, up to 20 mg per day not commonly used
26
PCSK9 or proprotein covertase subtilisin/ kexin 9 inhibitors
inhibit the PCSK9's inhibitory impact on LDL receptors dec LDL-C by 60%
27
where is PCSK9 or proprotein covertase subtilisin/ kexin 9 found
liver- found in all people but at differing levels amount found correlates to cardiovascular risk in many
28
PCSK9 or proprotein covertase subtilisin/ kexin 9 - how does it work normally
binds to LDL receptor and inhibits it, thus reduced LDL recycling in liver cells
29
LDL receptor role
take in low density lipoproteins from blood via endocytosis, break it down via lysosomal degradation
30
examples of PCSK9 inhibitors - 2
alirocumab evolocumab
31
PCSK0 inhibitor administration
lipid clinic biweekly or bi monthly administration subcutaneous injection
32
PCSK0 inhibitor side effects
injection rash monoclonal antibody so minor side effects
33
novel anti-angina therapies - 3
ivabradine, nicorandil, trimetazidine often coadministered, additive effect
34
ivabradine mechanism of action
last resort targets If "funny current" in diastole/ pacemaker SA node blocks/ reduces this, thus reduces heart rate and contractivity and pressure of heart selective to cardiac muscle
35
nicorandil mechanism of action
dual action activates ATP-sensitive potassium channels causing blood vessel dilation has nitrate group - causes systemic vasodilation reduces preload and cardiac work, increases myocardial perfusion reduces major cardiovascular events e.g. cardiovascular death, unstable angina
36
nicorandil side effects - 2
flushes due to systemic vasodilation GI system upset/ vomiting
37
trimetazidine mechanism of action
modulates metabolism of cells prone to ischemic/ hypoxic conditions in ischaemia, metabolism is shifted to free fatty acids, inhibits glucose metabolism and oxidation. free fatty acid metabolism needs more oxygen than glucose metabolism trimetazidine inhibits free fatty acid metabolism, and activates glucose metabolism so less oxygen is used by cells reduced angina pain
38
aims of treating heart failure - 4
inc cardiac output by increasing contractility decrease pre-load by dec blood pressure decrease water retention and BP by increasing natriuresis inc tissue perfusion by inc vasodilation
39
novel drugs used to treat heart failure examples - 2
tolvaptan cardiotrophin-1 or CT-1
40
what is tolvaptan/ mechanism of action
vasopressin receptor 2 V2 antagonist decreases expression of aquaporin - 2 so we do not rely on electrolyte excretion less reuptake of water, less blood volume, dec pressure dec heart failure symptoms e.g. dyspnoea
41
cardiotrophin-1 or CT-1 mechanism of action
cytokine, level of IL-6 family binds to Gp-130 pro survival receptors stimulates physiological cardiac muscular hypertrophy and vessels inc cardiac output when patients cannot exercise for this effect still in studies
42
cardiotrophin-1 or CT-1 side effects
correlation with myocardial fibrosis
43
aminopeptidase A inhibitors mechanism of action
inhibit metabolism of angiotensin II to angiotensin III reduces APase aminopeptidease downregulates vasopressin release can improve and inc diuresis - removal of water from blood improves vasodilation reduces pressure on heart via SA node
44
aminopeptidase A inhibitor example
in clinical trials RB150 well tolerated prodrug CNS side effects, not fully understood inc in angiotensin II despite angiotensin III not being activated, but no effect
45
ACE-2 activator
can convert angiotensin I and II to cardioprotective peptides via Mas GPCR counteracts angiotensin II and AT1R effects already used in protozoal treatment reduces blood pressure by inc vasodilation
46
pharmacogenomic considerations - 4
HLA variants - link to ADRs drug metabolism genes encoding drug targets combined - metabolism and target can be changed by genetics
47
example of drug metabolism being relevant in pharmacogenomics
drugs with single CYP metabolism varied metabolism and plasma drug conc e.g. clopidogrel
48
variants of CYP2C19 (2) and effects on clopidogrel metabolism
loss of function CYP2C19*2 and *3 - poor metabolism, so still high risk of ischaemic events gain of function CYP2C19*17 - extensive metabolism, inc bleeding as inc platelet inhibition

342 (20 decks)

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