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<200 mg/dl
<130 mg/dl
>40 mg/dl
>50 mg/dl
<150 mg/dl
Dyslipidemia Primary Cause may be due to a genetic defect of enzymes involved in liver protein or protein metabolism
Familial Hypercholesterolemia causes markedly elevated LDL level. It can also be found in young patients.
Lipoprotein lipase(LPL)
Breakdowns lipoprotein into triglyceride, cholesterol and fatty acids. This is what you find in the capillaries.
Chylomicrons are the biggest attacked by LPL VLDL acted by LPLIDL attack by LPL LDL goes to liver which would be broken down by hepatic lipase triglycerides and fatty acids
Management:
Before any form of pharmacologic treatment lifestyle modification
Caloric requirement women-1000-1200, male 1000-15002000
Dietary management
caloric restriction
Omega-3-fatty acids (fish oil) causes low triglyceride levels; tuna, salmon
NIACIN/Nicotinic acid
NIACIN (NICOTINIC ACID)
Excreted in urine
1.
Most effective agent in increasing
HDL (good cholesterol)
If the patient only presents
an increase in HDL, give niacin
2.
Only agent that reduces
lipoprotein a (LPa)
3.
Inhibits VLDL secretion
4.
Increases VLDL clearance via LPL
(lipoprotein lipase) (found in
capillaries)
5.
Decreases HDL catabolism
6.
Inhibits adipose cell LPL
o
Adipose cell: breaks down
stored cholesterol TG,
fatty acids
Adverse effects
Flushing
o
Prostaglandin mediated
vasodilation
o
Give aspirin/ibuprofen 30
mins before taking niacin
Pruritus
Abdominal discomfort
o
Patients with peptic ulcer
disease, pain is aggravated
Avoid taking
niacin
Insulin resistance
Fibrates
FIBRATES
Renal excretion
1.
Activate PPAR-alpha
Reduces triglycerides
levels
2.
Increases hydrolysis of VLDL
& chylomicron TG
3.
Increases hepatic & skeletal
muscle fatty acid oxidation
4.
Increases synthesis of APO AI
& APO AII (found in HDL)
Increasing HDL
levels
5.
Inhibits cytochrome enzyme
system (increases the levels
of statins)
a.
So, reduce the dose
of statins to avoid
toxicity
6.
Potentiate action of
coumarin
o
Coumarin: oral
anticoagulant
1.
2.
3.
II.
1.
2.
3.
4.
Drugs
Colestipol
Cholestyramine
Colesevelam
Indications or Uses
For isolated increase in LD
because these resins
upregulate LDL receptors ->
more LDL receptors -> LDL in
blood goes into the cell ->
LDL levels in blood goes
down
Prevent intestinal bile acid reabsorption
cholesterol in blood diverted
to more bile acid formation ->
cholesterol level in blood will
go down
Increase incretin secretion
incretin = "INtestinal
seCRETion of INtestine"
hormones released by
intestines after eating a high
carbohydrate meal
decreases appetite -> lowers
blood sugar
Relieves pruritus secondary to
cholestasis and bile acid accumulation
one of the symptoms of
obstructive jaundice is
Ezetimibe
Ezetimibe
o
the only agent
that inhibits
intestinal
absorption of
cholesterol
o
reduce LDL
levels
o
fecal excretion
o
levels increase
with fibrates (so
decrease the
dose)
o
levels reduced
by
cholestyramine
(so increase the
dose)
o
synergistic with
statins (problem:
very expensive)
o
may cause
hepatic
dysfunction
CEPT inhibitors
CETP Inhibitors
(Cholesteryl Ester
Transfer Protein)
1.
Torcetrapib
(withdrawn)
2.
Anacetrapib
3.
Dalcetrapib
o
normally: CETP
transfers
cholesteryl esters
from HDL to LDL
and to other
lipoproteins in
exchange to
triglycerides -> we
don't want this
MOA: Cholesteryl
esters will stay in
HDL. HDL is a
reverse
cholesterol
transporter, it
transports
cholesterol from
the periphery to
the liver and the
liver converts it to
other substances.
under
investigation
4.
LDL
Pleiotropic effects
a.
Stabilization of
atherosclerotic plaque
b.
Reduce vascular
inflammation
Used for MI and acute
coronary syndrome without
any regards on their lipid levels
Night time is the best time to
give. Because cholesterol
deposits at night.
elevation of serum
aminotransferases
myopathy
myoglobinuria
drug interaction
Elevation of serum aminotransferase
Check for CK
Drug interaction
-catabolize by cytochrome system
CYP3A4
dependent
catabolism
Lovastatin
Simvastatin
Atorvastatin
-
CYP2C9
dependent
catabolism
Fluvastatin
Rosuvastatin
Pitavastatin
Remember:
Enzyme inhibitor- increase drug level in the
body because it cannot be metabolized
Enzyme Inducer- decrease amount of drug
in the body because it increases
metabolism
Increased glucose
Dont give to patients who
are hyperglycemia
o
Acathosis nigricans:
hyperpigmentation on the
nape (sign of insulin
resistance)
Hyperuricemia
Macular edema
o
Blurring of vision
Potentiates action of
antihypertensive
o
Due to prostaglandin
mediated vasodilation
o
o
5.
III.
a)
b)
c)
d)
intense pruritus
Bind digitalis glycosides
Adverse Effects
Constipation and bloating
o
improve bowel movement by:
Ingesting more
fibers
Taking laxatives
esp. fiber-rich ones
(e.g.
Psyllium
fiber)
Vitamin K malabsorption
o
if taking warfarin or other
anticoagulant, adjust the
dose
o
PTT with INR to see if right
dose
Impairs absorption of drug
o
should be given 1 hr before
the drug or 2 hours after
giving the resin (not
simultaneously)
Avoid in patients with diverticulitis
o
since it causes constipation
and bloating, it can aggravate
diverticulitis
markedly increase
HDL and reduces
LDL *Niacin
increases HDL too
IV.
Drug Combinations
a.
If failure of monotherapy
b.
Mixed hyperlipoproteinemia
c.
Markedly increased in VLDL during treatment of hypercholesterolemia with a resin
d.
Use the lowest effective dose
e.
Monitor for toxicity
Seatwork: Case
Cholesterol
Triglycerides
HDL
LDL
Normal SGOT / SGPT
205 mg/dl
1,067 mg/dl
35 mg/dl
100 mg/dl
Increased
markedly increased
decreased
slightly increased
NSAIDS
Low-dose ASA
DOC: Fibrates
1.
It is the best drug for lowering triglycerides
2.
Promotes HDL synthesis
3.
Prevents the risk of having acute pancreatitis
Effects on
PGI
(antithrombo
tic)
Effects on
TXA
(prothrombot
ic)
Conventional
(Nonselective)
NSAIDS
COX-2
inhibitors
No effect
Thrombotic
Risk
(may be
due to renal
effects and
not due to
of PGI )
( because
of PGI-2)
Goals of treatment:
1. Relief of pain and maintenance of function
2. Slowing/ arrest of tissue-damaging process
NSAIDS
-
I. Non-acetylated
Salicylates
- nonselective cox inhibitors
- anti-inflammatory >
analgesic
- safer but weaker against pain
- desirable in px with asthma,
bleeding tendencies, and renal
dysfunction
DMARDS
given to RA patients with no relief from NSAIDS
- slow down/ reverse joint damage
- slow-acting: benefit seen after 6 wks- 6 months
-usually toxic
- MOA; suppress T-cells, B-cells, cytokines and TNF
- immunomodulating agents
Arachido
nic Acid
COX-1
(Constitutiv
e) Pathway
COX-2
(Inducibl
e)
Pathway
I.Thromboxa
Biologic DMARDS
PGI
-MC side ne
effect: infection
PGE-1
(prostacyclin)
- may also cause malignancies
& PGE-2
-screen px for TB
-Hemostasis
may reactivate TB
Cytoprote
1.
Abatacept: T cell modulator
pain, fever
renal
2.
Rituximab : B-cell cytotoxicctive
and
protecti
3.
Toclizumab: anti_IL6 receptor antibody
inflammati
4.
TNF-blocking agents:
on
on
adalimumab, certolizuman, Etarecept, Golinumab, Infliximab
GOUT
Agents are used for the relief of acute gouty attacks and prevent recurrent gout and ureate lithiasis
Asymptomatic gout = with or without treatment
Symptomatic = give treatment
Arachidonic
Acid
blocked by
Nonselective
and COX-2
NSAIDS
sodium
retention
(Most common)
Peripheral
edema
Acute Renal
Failure
Hyperkalemia
Prerenal
azotemia and
decreased
bloodflow
Type 4 Tubular
Necrosis
Hyponatremia
HPN
CHF
Acute Tubular
Necrosis (ATN)
Gout could be the Swelling of the first metatarsal joint, tophi etc.
Purine diet
o
Not a factor for gouty arthritis
o
The sudden change in the uric acid level is the factor for gouty arthritis
ACUTE GOUT
Colchicine
Magic drug
Hepatic cirrhosis
Route of administration:
Can be given IV
o
But withdrawn from the
because it causes death
NSAIDS
Oxaprozin
Uricosuric agent
Glucocorticoids
Causes
GI
bleeding,
hyperglycemia,
immune
suppression
Oral: Prednisone
</=7.5mg/day not to be
given in a long period of time,
gradual redcution
Intra-articular
injection
of
Triamcinolone acetonide
Interleukin-1
Inhibitor
investigational
Canakinumab
Anakinra
Rilonacept
For
those
refractory
NSAIDS and colchicine
to
market
Allopurinol
Drug Interactions:
Toxicity:
Febuxostat
Hepatic metabolism
Renal excretion
Adverse effect:
o
liver function abnormality
o
CARDIOTOXIC at high doses
Pegloticase
Given IV