AM L5 Current therapies Flashcards
4 Lipid lowering drug classes
Statins
Fibrates
Bile acid binding resins
Other
Apart from lipid lowering what other therapies are there for ATS? (3)
Anti-inflammatory drug therapies (aspirin and cytokines)
Genetic therapy
Statins inhibit production of
HMGcoA reductase
HMGcoA reductase is part of what pathway
endogenous de novo synthesis of chol
HMGcoA reductase produces …..
mevalonate (initiation of cholesterol synthesis)
Statins may also affect the expression of …. receptors
LDL (increase LDL receptor)
Statins cause reduced…… of proteins
isoprenylation
reduces isoprenylation of proteins results in
anti-inflammatory effect
reduced function of small G proteins e.g. Rac and Rho
Statins reduces isoprenylation of proteins by….
reducing production of our old friends geranyl geranyl and farnesyl which are tads for the effector molecules
Statins causes better/worse endothelial function?
better
Statins cause increased/decreased inflammation and platelet aggregation?
decreased
Statins cause increase/decrease in circulating progenitor cells
increase
Statins cause increase/decrease in fibronolysis
increase
Statins cause increase/decrease synthetic
activity
in
osteoblasts
increased
4 minor statin side-effects
- GI disturbance
- Increased plasma concentrations of liver enzymes
- Insomnia
- Rash
2 major statin side-effects
- Severe myositis (muscle inflammation)
* Angio-‐oedema
Fibrates do what
increases synthesis of lipoprotein lipase
Fibrates side-effects (3)
- Myositis acute renal failure
- GI symptoms
- Gall stones
Fibrates act on
PPARalpha which causes increased lipoprotein lipase
Increased lipoprotein lipase results in
hydrolysis of TG in chylomicrons, fatty acids stored in fat
Do we absorb bile acid resins?
No
What do bile acid resins cause
decreased reabsorption of bile (prevent enterohepatic circulation)
Bile is synthesised from
cholesterol
Binding bile acids results in….
increased bile acid synthesis from endogenous cholesterol - therefore increased clearance of LDL cholesterol
3 e.g. of bile acid resins
Cholestyramine, colestipol
and colesevalam
negative things about bile acid resins (3)
Bind to other lipid soluble factors such as vitamins and some drugs (warfarin and throxine)
Unpalatable
Diarrhoea
Fish oil contains …. which are meant to help ATS
Highly unsaturated fatty acids
Eicosapentaenoic and docosahexaenoic acid
How is fish oil thought to help? (3)
Inhibit platelet function (increased bleeding time)
Anti-inflammatory
Reduce plasma fibrinogen
What vitamin is meant to help ATS risk
Niacin (also called nicotinic acid)
How does niacin work?
inhibits TG production and VLDL secretion (results in less LDL and ,ore HDL)
S/e of niacin (3)
flushing, palpitation and GI disturbances
How do statins produce anti-inflammatory effect? (4)
Inhibit MMPs
Decreased adhesion molecules
Decrease proinflammatory cytokines
Slow smooth muscle migration
How do fibrates produce anti inflammatory effect? (3)
decrease:
- NFkB transcription
- macrophage differentiation
- cytokine secretion
How does niacin produce anti inflammatory effect?
CRP levels are reduced
How does aspirin work?
Irreversible COX inhibition
COX usually produces (2)
platelets
Which is pro & which is anti thrombic?
TxA2
PGI2
TxA2 is pro
PGI2 is anti
Why does aspirin alter the balance of
TxA2
PGI2
Endothelial cells have nucleus - can resynthesis COX in hours.
Platelets have no nucleus - takes longer
Aspirin may also influence ATS risk through non-cox depenedent actions such as
antiimflammroty effect
Effect of aspirin is most pronounced in patients with
elevated CRP
