PHRM30003 Study Guide - Final Guide: Peroxisome Proliferator-Activated Receptor Alpha, Endosome, Lipoprotein
5 Jun 2018
School
Department
Course
Professor
Drug name
Drug class
Molec
ular target(s)
Mechanism/Function
Contradiction/AE/Notes
Dyslipidaemia
/Hyperlipidaemia
(5)
Simvastatin
Etc.
Statin
HMG
-
CoA reductase
Decrease mevalonic acid
So decrease cholesterol synthesis
compensatory increase hepatic LDL-R
increase clearance of blood LDL
Increase plasma HDL
AE is dose
-
dependent
Initial dose of statin has most effect
Poor compliance
Precautions:
- Avoid grapefruit juice
- Drug-drug interaction – CYP450
AE:
- Myopathy – minimise by UQ10
- Rhabdomyolysis – creatine kinase?
- Renal failure
- Hepatitis, liver failure
Contraindication
- Pregnancy – impair fetal
myelination
- Infection, pre-surgery, post-trauma
Cholestyramine
Colestipol
Bile acid sequestrants/resin
Bile acid
Bind to bile acid (cholesterol metabolites)
Prevent gut absorption
compensatory increase hepatic LDL-R
increase clearance of blood LDL
increase cholesterol metabolism
AE:
- GIT effects
- Decrease absorption of other drugs
Ezetimibe
Ezetimibe
As adjuvant
Sterol transporter
Inhibit cholesterol absorption
lower LDL
Not a good drug
Dietary cholesterol contributes little
Used as adjuvant
Non-specific AE
Nicotinic acid
=niacin
=vitamin B3
As adjuvant
Unclear mechanism
Decrease secretion of VLDL from liver
Decrease plasma LDL and triglycerides
Increase HDL
lower potentially atherogenic Lp-a, inhibits
thrombolysis
AE:
- Vasodilation, flushing, hypotension
- Glucose intolerance
- Uric acid retention
Combination
mAb
mAb
PCSK9
mAb
- Bind to PCSK9
- Less LDL-R degrades
- More expression of LDL-R
Normally P
CSK9
- Internalized by hepatocyte with
LDL/LDL-R complex
- Bind to LDL/LDL-R complex
