Lipids

Cholestrol : diperlukan untuk steroid, cell membrane, syn bile acid

TG : source of energy, (glycerol + 3 fatty acid)
Phospholipid : emulsifiers

Transported via Lipo protein. Made of cholesterol and tg, made of phospholipid and
apolipoproteins (kilomikron, VLDL, LDL, HDL)

Kilomikron : tg, less cholesterol, produksi di gut from diet.

VLDL : most tg, less cholesterol, produced in hepar.
Both job to transfer energy to cell. By lipoprotein lipase then transferred to tissue.

Kalo tg kurang, vldl jadi LDL (to transfer cholesterol to cells). Mostly in liver for production of
bile acids.

Excess cholesterol is transferred back to liver by HDL.

PROBLEM, high LDL, accumulate in tunica interna and cause atherosclerosis.

HDL prevent atherosclerosis and reduce vascular inflammation.

Obat 1 : Statins : HMG Coa Reductase inhibitors

Reduce mevalonic acid, and therefore concentration of cholesterol in liver cells. This will be
compensated by increasing LDL receptors. Decrease secretion of VLDL (turunkan VLDL), dan
bisa turunkan HDL juga
Side effect : elevate liver enzyme, muscle related problem, myopathy, rhabdomyolysis.

Obat 2 : Nicotinic Acid, niacin

Works in adipose tissue. Hambat hormone sensitive lipase. Hambat perubahan TG kepada
fatty acid. Sehingga produksi VLDL dan LDL dari hepar berkurang. Increase HDL.
Side effect : flushing niacin induced prostaglandin release vasodilation, hyperuriciemia,
gout, liver toxicity

Fibrates : tempel ke PPAR Alpha.

Increase secretion of lipoprotein lipase, sehingga TG di sirkulasi ganti ke fatty acids.
Decrease secrete apo CIII, inhibit lipoprotein lipase activitiy. Increase apo I dan apo II
- Gemfibrozil
- finofibrate
Side effect : GI disturbance, myopathy, rhabdomyolysis, gale stone

Bile acid sequestrants : prevent secretion and increase excretion. Increase LDL receptors,
decrease LDL. Prevent reabsorption of cholesterol via enterohepatic circulation, therefore
synthesis of bile acid will come from reserved cholesterol in the liver.
- Cholestyramine
- Colestipol
- colsevelem
Side effect: bloating, constipation, decrease absorbtion of ADEK, dpt meningkatkan TG.
Cholestrol absorption inhibitors.
Bind with npc1l1. Hambat endocytosis. Reduce delivery of intestinal cholesterol.
Ezetimibe
Efek samping : Good untuk pasien not responsive statin

LIPID LOWERING DRUG

PCSK9 inhibitors
Reduce removal of LDL in circulation. Monoclonal antibodies. Decrease LDL.
Evolocumab, alirocumab
Efek samping : inject side reaction, flu like
Pertimbangkan dlm pasien hiperkolestrolemia familial.

Omega 3 fatty acids  used for TG lowering effect. Inhibition of VLDL and TG synthesis in
the liver
Obat : DHA and EPA., icosapent ethyl
Side effect : diarrhea, fishy taste, increase risk of bleeding

Bile salt emulsifies fat, pancreatic lipase pecah TG kepada monoglyceride, fatty acid dan
glyceril. Masuk ke enterocyte, dan form TG lagi. Packaged dengan cholesterol dan bergerak
melalui kilomikron. Masuk ke lymph kemudian pembuluh darah. Kilomikron nempel ke LPL
di pembuluh darah untuk transfer fatty acid dan glycerol (hydrolized TG) ke sel untuk energi
atau storage.

Fat juga bisa terproduksi oleh hepar (VLDL) dan akan berfungsi sama seperti kilomikron +
LPL.

Fat stores di adipose tissue bisa pindah ke pembuluh darah melalui hormone sensitive lipase
(eg. Epinephrine)

Fatty acid bisa berubah kepada acetil coa, yang berperan terhadap penghasilan ATP melalui
siklus asam sitrus. Access acetyl coa diverted kepada ketone bodies. Ini sgt penting pada
glucose starvation. Akan tetapi acidic.

DIABETES

Insulin  glucose update in cell. Liver and skeletal muscle as glycogen, other cell convert it
to ATP.

Blood glucose low  Alpha pancrease release glucagon. Turn glycogen to glucose.

1. Insulin/Analogs (subcutan injection)

a. Rapid/short acting : lispro, asport, glulisine regular insulin
 b. Intermediate acting : NPH
c. Long acting : Detemir, Glargin, Degludec
d. SE : Hypoglycaemia, lipodystrophy.
2. Synthetic Amylin
a. Amylin is to delay gastric emptying, decrease glucagon, increase satisfaction.
b. Pramlintide
c. SE : hypoglycaemia, weight loss
3. Incretin mimetics (exenatide, liraglutide)
a. GLP I analong
b. Slow gastric emptying, increase satisfy
c. SE : weight loss, GI problem, may damage pancrease
4. DPP4 inhibitors : increase insulin secretion, decrease gastric empting and decrease
glucagon release
a. Alogliptin
b. Linagliptin
5. Sulfonylureas
a. Hambat ATP sensitive potassium channel. Causes insulin secretion. Increase
sensitivity beta to glucose
b. Glimepiride, Glipizide
c. SE : weight gain, hypoglycaemia, interacts with many drugs CYP450, increase
risk of infarction of the heart
6. Biguanides (Metformin)
a. Reduction of hepatic glucose production, increase glucose sensitivity
b. Decrease hepatic intake of lactate
c. SE : loss of appetite, nausea, diare, vomiting, increase risk of lactic acidosis (in
congestive heart failure and renal impairment)
7. SGLT2 inhibitors
a. Inhibit glucose reabsorption in the kidney.
b. Osmotic diuresis
c. SE : decrease in blood pressure and weight loss, sering kecing, haus
d. Canagliflozin, Dapagliflozin.
8. Alpha glucosidase inhibitors
a. Break carbohydates into sugar is BLOCKED
b. Acarbose, Miglitol
c. SE : abdominal cramp, bloating, flatulence, diarrhea