AM L5 Current therapies Flashcards

1
Q

4 Lipid lowering drug classes

A

Statins
Fibrates
Bile acid binding resins
Other

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2
Q

Apart from lipid lowering what other therapies are there for ATS? (3)

A

Anti-inflammatory drug therapies (aspirin and cytokines)

Genetic therapy

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3
Q

Statins inhibit production of

A

HMGcoA reductase

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4
Q

HMGcoA reductase is part of what pathway

A

endogenous de novo synthesis of chol

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5
Q

HMGcoA reductase produces …..

A

mevalonate (initiation of cholesterol synthesis)

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6
Q

Statins may also affect the expression of …. receptors

A

LDL (increase LDL receptor)

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7
Q

Statins cause reduced…… of proteins

A

isoprenylation

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8
Q

reduces isoprenylation of proteins results in

A

anti-inflammatory effect

reduced function of small G proteins e.g. Rac and Rho

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9
Q

Statins reduces isoprenylation of proteins by….

A

reducing production of our old friends geranyl geranyl and farnesyl which are tads for the effector molecules

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10
Q

Statins causes better/worse endothelial function?

A

better

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11
Q

Statins cause increased/decreased inflammation and platelet aggregation?

A

decreased

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12
Q

Statins cause increase/decrease in circulating progenitor cells

A

increase

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13
Q

Statins cause increase/decrease in fibronolysis

A

increase

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14
Q

Statins cause increase/decrease synthetic
activity
in
osteoblasts

A

increased

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15
Q

4 minor statin side-effects

A
  • GI disturbance
  • Increased plasma concentrations of liver enzymes
  • Insomnia
  • Rash
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16
Q

2 major statin side-effects

A
  • Severe myositis (muscle inflammation)

* Angio-­‐oedema

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17
Q

Fibrates do what

A

increases synthesis of lipoprotein lipase

18
Q

Fibrates side-effects (3)

A
  • Myositis acute renal failure
  • GI symptoms
  • Gall stones
19
Q

Fibrates act on

A

PPARalpha which causes increased lipoprotein lipase

20
Q

Increased lipoprotein lipase results in

A

hydrolysis of TG in chylomicrons, fatty acids stored in fat

21
Q

Do we absorb bile acid resins?

A

No

22
Q

What do bile acid resins cause

A

decreased reabsorption of bile (prevent enterohepatic circulation)

23
Q

Bile is synthesised from

A

cholesterol

24
Q

Binding bile acids results in….

A

increased bile acid synthesis from endogenous cholesterol - therefore increased clearance of LDL cholesterol

25
Q

3 e.g. of bile acid resins

A

Cholestyramine, colestipol

and colesevalam

26
Q

negative things about bile acid resins (3)

A

Bind to other lipid soluble factors such as vitamins and some drugs (warfarin and throxine)
Unpalatable
Diarrhoea

27
Q

Fish oil contains …. which are meant to help ATS

A

Highly unsaturated fatty acids

Eicosapentaenoic and docosahexaenoic acid

28
Q

How is fish oil thought to help? (3)

A

Inhibit platelet function (increased bleeding time)
Anti-inflammatory
Reduce plasma fibrinogen

29
Q

What vitamin is meant to help ATS risk

A

Niacin (also called nicotinic acid)

30
Q

How does niacin work?

A

inhibits TG production and VLDL secretion (results in less LDL and ,ore HDL)

31
Q

S/e of niacin (3)

A

flushing, palpitation and GI disturbances

32
Q

How do statins produce anti-inflammatory effect? (4)

A

Inhibit MMPs
Decreased adhesion molecules
Decrease proinflammatory cytokines
Slow smooth muscle migration

33
Q

How do fibrates produce anti inflammatory effect? (3)

A

decrease:

  • NFkB transcription
  • macrophage differentiation
  • cytokine secretion
34
Q

How does niacin produce anti inflammatory effect?

A

CRP levels are reduced

35
Q

How does aspirin work?

A

Irreversible COX inhibition

36
Q

COX usually produces (2)

A

platelets

37
Q

Which is pro & which is anti thrombic?
TxA2
PGI2

A

TxA2 is pro

PGI2 is anti

38
Q

Why does aspirin alter the balance of
TxA2
PGI2

A

Endothelial cells have nucleus - can resynthesis COX in hours.
Platelets have no nucleus - takes longer

39
Q

Aspirin may also influence ATS risk through non-cox depenedent actions such as

A

antiimflammroty effect

40
Q

Effect of aspirin is most pronounced in patients with

A

elevated CRP