cardio: HLD Flashcards
statins that must be taken at night
lovastatin, simvastatin, pravastatin, fluvastatin
statin that must be taken with food
lovastatin
lipophilic statins
atorvastatin, pitavastatin, simvastatin, fluvastatin, lovastatin
high intensity statin
atorvastatin 40-80mg, rosuvastatin 20-40mg
moderate intensity statin
atorvastatin 10-20mg, rosuvastatin 5-10mg, simvastatin 20-40mg
pravastatin 40-80mg, lovastatin 40-80mg, fluvastatin XL 80mg, fluvastatin 40mg BD, pitavastatin 1-4mg
low intensity statin
simvastatin 10mg
pravastatin 10-20mg, lovastatin 20mg, fluvastatin 20-40mg
statin potency
fluvastatin, pravastatin, lovastatin < simvastative < atorvastatin < rosuvastatin
exogenous cholesterol pathway
chylomicrons transport TG and cholesterol from intestine to the tissues > subsequently stored, oxidized to bile acids or secreted in bile unchanged
endogenous cholesterol pathway
cholesterol and newly synthesised TG are transported from liver as VLDL to muscle and adipose tissue > TG are hydrolysed and resulting fatty acids enter the tissues > during this process, lipoprotein particles become LDL > cells take up LDL by endocytosis via LDL receptors that recognise LDL apolipoproteins
are statins safe in pregnancy and lactation?
no!!!
SAMS: myalgias
muscle aches and pain, CK normal
SAMS: myositis/myopathy
muscle pain and weakness interfering with daily activities, CK > 10xULN with concerning sx or objective weakness
SAMS: rhabdomyolysis
muscle breakdown, CK>40xULN + renal injury
- occurs when damaged muscle tissue releases its proteins and electrolytes into the blood. These substances can damage the heart and kidneys and cause permanent disability or even death
SAMS: statin-associated autoimmune myopathy
HMGCR antibodies, incomplete resolution
- very rare form of muscle damage caused by the immune system in people who take statin medications
risk factors for SAMS
- age > 75yo
- female
- low BMI
- Asian descent
- impaired kidney function (CKD stage 3-5) or liver impairment
- surgery with high metabolic demands, consider holding off before
- acute infection
- high level of physical activity
- excess alcohol
- drug abuse
- dietary effects (excessive grapefruit, cranberry juice)
- hypothyroidism: untreated or undertreated
- genetic factors: CYP450 or drug transporter related mutations
myoglobinuria
myoglobin (muscle proteins broken down) > goes to kidney and bound to renal tubules
if no muscle sx present but CK is raised
consider checking thyroid function or muscle related
?clinical significance
DDI with statins: amiodarone
do not exceed:
- simvastatin 20mg
- lovastatin 40mg
DDI with statins: macrolide antibiotics
do not exceed:
- atorvastatin 20mg, with clarithromycin
- pravastatin 40mg, with clarithromycin
- pitavastatin 1mg, with erythromycin
DDI with statins: amlodipine
do not exceed simvastatin 20mg
DDI with statins: colchicine
caution with lovastatin, simvastatin, fluvastatin, pitavastatin, pravastatin
DDI with statins: gemfibrozil
CI with simvastatin
avoid with: L,P,P,A,F
do not exceed R 10mg (use only if needed, avoidance recommended)
DDI with statins: other fibrates
caution with all statins
DDI with statins: verapamil
do not exceed:
- simvastatin 10mg
- lovastatin 20mg
niacin and fibric acid drugs can rarely cause rhabdomyolysis or liver failure when used alone, but…
- combining them with statins incr risk of rhabdo or liver failure
- gemfibrozil should not be combined with statins
- other fibric acids and niacin are used, with caution, in combi with statins
coadm of statins with bile salt binding resins, how is it done?
statins should be taken 1hr before or 4h after bile salt binding resins eg. cholestyramine
- bile salt binding resins bind statins in the intestine and reduce their absorption into the body
statins and warfarin, ok?
statins incr effect of warfarin
- monitor blood clotting ability carefully
statins and red yeast rice, ok?
should not be combined!!!
- red yeast rice contains chemical that is similar to statins, can lead to serious side effects such as rhabdomyolysis
ezetimibe MOA
selective inhibitor of cholesterol transoirt protein, Niemann-Pick-C1-like1 (NPC1L1) protein - in walls of GIT and decr uptake into body
BUT effective in absence of dietary cholesterol: can saturate and still block transporters that takes up biliary cholesterol!!!!!
ezetimibe ADR
URTI, sinusitis, arthralgia, limb pain, diarrhea
PCSK9i
Proprotein Convertase Subtilisin/Kexin type 9 inhibitors
- evolocumab, alirocumab
PCSK9i MOA
bines plasma PCSK9, thus incr LDL receptors on the cell surface > incr cellular uptake of circulating LDL from plasma
PCKSK9i adm
injectibles, every other week or monthly
PCSK9i place in therapy
due to exorbitant costs, likely to be cost effective only in the very high-ASCVD
evolocumab labelled for
homozygous familiar hypercholesterolemia
PCSK9i adr
itching at site, flu-like sx, early concerns of neurocognitive function changes, incr DM risks shown not to be an issue
can PCSK9i be used in pregnancy and lactation?
use with caution, unknown!
concern with LT use of PCSK9i treatment?
autoantibodies
cholestyramine MOA
bile-acid exchange resins, not absorbed or altered by digestive enzymes
- binds bile acid, prevents reabsorption of drug and cholesterol into body
-> large portion of bile acids removed from enterohepatic circulation
-> liver synthesises more hepatic cholesterol
-> incr hepatic demand for cholesterol
-> incr LDLR expression
cholestyramine ADR
flatulence, constipation, dyspepsia, nausea: use small doses, ingest ample fluids, incr dose gradually
may cause incr TG
niacin
- incr HDL by stimulating production of ApoA1 production in liver
- upregulate lipoprotein lipase resulting in incr catabolism of VLDL
WITHDRAWN FROM SG
cholestyramine must be adm ____ before and ____ after other drugs
4h, 1h
metabolic syndrome
- FBG > 5.6mmol/L
- large waist size (central obesity)
- high BP>130/85mmHg
- TG>1.7mmol/L
- low HDL
hallmarks of familial hypercholesterolemia
fatty deposits around eye cornea, eye, feet, muscle joints
heterogyenous familial hypercholesterolemia (HeFH)
- typically develop CAD before 55yo (M) and 66yo (F)
- risk for CAD is definite or probably and incr at least 10x
- critical to diagnose early and treat appropriately
homogynous familiar hypercholesterolemia (HoFH)
- develop CAD by 20yo and die before 30yo
- identification of these children is critical
- treatment with statins/plasma apheresis
what hyperlipidemia meds to use for pregnant women?
only bile acid sequestrants
- statins, fibrates, ezetimibe, niacin are ci
- no data with pcsk9i
when should we stop statin relative to cessation of contraception?
4 weeks prior
fibrates MOA
incr activity of lipoprotein lipase > incr peripheral clearance
how often should we monitor for lipid profile?
8+/- 4 wks, after starting tx and after adjustment until goal is reached
how often should we monitor for ALT?
8-12wks after starting and after dose incr
- routine ALT repeat not reco if on sttatin, consider if on fibrates
- annually will do
how often should we monitor for ck?
routine monitoring not necessary, recheck if pt develops myalgia
- check for baseline, if ck>4xULN then do not start therapy, recheck
how often should we monitor for hba1c?
regular checks for pt at high-risk of diabetes or high-dose statins
