Drug regulation of serum lipids Flashcards Preview

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Flashcards in Drug regulation of serum lipids Deck (31)
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1
Q

dyslipidaemia

A

abnormal lipid profile

can lead to atheroscleorsis, increased MI risk, stroke

2
Q

hypercholestrolaemia

A

elevated blood cholesterol

high risk: > 7.5mmol/L total cholesterol

treatment target: <4mmol/L

3
Q

hypertriglyceridemia

A

elevated blood triglycerides

4
Q

mixed/combined hyperlipidemia

A

hypercholesterolemia characterised by elevated LDL and TG, often accompanied by decreased HDL

5
Q
A
6
Q

The normal fasting level and target level for total cholesterol is

A

0.0-5.5mmol/L; <4.0mmol/L

7
Q

The normal fasting level and target level for TGs is

A

0.5-2.0; <2.0

8
Q

The normal fasting level and target level for HDL is

A

0.9-2.2; >1.0

9
Q

The normal fasting level and target level for LDL is

A

0.0-3.4; <2.5

10
Q

The normal fasting level cholesterol/HDL ratio is

A

0.0-5.0

11
Q

The Mediterranean diet

A
  • high in whole grain breads, cereals, fruits, vegetbles, olive oil, and fish
  • can decrease cardiovascular risk
  • does not reduce LDL levels
12
Q

Plant sterol esters

A
  • in margarine
  • reduce LDL cholesterol
  • no evidence of -CV risk
13
Q

fish oiles

A
  • reduce TGs
  • increase HDL
14
Q

Cholesterol is derived from

A
  • diet: animal (saturated) fat, eggs
  • de novo synthesis in liver
15
Q

cholesterol is used in the synthesis of

A
  • membranes
  • bile acids
  • steroid hormones
16
Q

Which lipoproteins can deposit cholesterol into arterial walls?

A

LDL, IDL, VLDL

all contain ApoB-100

17
Q

Statins

A
  • HMG-CoA reductase inhibitors
  • discovered in 1970s, Tokyo, by Kuroda and Endo
    • hypothesized that fungi (who require sterol for growth) would produce synthesis inhibitors to kill off competing microbes in their environment
    • isolated mevastatin from 6000 microbial strains (Penicillium citrinum)
      • never used clinically
  • Merck, late 1970s discovered lovastatin (Aspergillus terreus)
    • still used today
  • approved for clinical use in late 1980s
18
Q

What is the mechanism of statins?

A

e.g. lova, atorva, fluva, prava, simvastatin

  • orally absorbed
  • undergo first-pass metabolism
  • partially inhibit HMG-CoA –> -endogenous cholesterol synthesis
  • body +hepatic LDL R
  • -circulating LDL
  • +HDL
  • also -TG to a lesser extent
19
Q

Why is poor adherence common with statins?

A
  • benefit greatest after 1-2 years
  • don’t feel different - perceived lack of efficacy
20
Q

When is cholesterol synthesis greatest?

A

At night

tf we prescribe statins with shorter half-lives in the evening

21
Q

When are statins indicated?

A

hypercholesterolemiea

mixed hyperlipidaemia

22
Q

What are the precautions in statin use?

A
  • avoid grapefruit juice (p450 cytochrome enzymes)
    • common metabolic pathway, can +toxicity because they are not broken down
  • altered statin levels
    • increased by some antibiotics, antifungals, and fibrates
    • decreased by phenytoin (epilepsy), barbituates, glitazones (diabetes)
  • liver toxicity
    • elevation of serum aminotransferase/transaminase (indicator)
    • monitored every 2-4mo
  • increased creatine kinase
    • breaks down muscle, can cause pain and tenderness
    • resolved on discontinuation
23
Q

What are the common adverse effects of statins?

A

Mild GI symptoms, headache, insomnia, dizziness

no clear mechanisms of explanation

24
Q

What are the rare, serious adverse effects of statins?

A
  • myopathy (+CK, -Q10): tx w/UQ10 supplement
  • rhabdomyolysis - breakdown of muscle, myoglobin into bloodstream
  • renal failure
  • hepatitis, liver failure
25
Q

What are the contraindications for statins?

A

Pregnancy

  • statins impair fetal myelination essential for foetal nerve growth and development

Drug-drug interaction potential (e.g. w/antibiotics)

  • infection, pre-surgery, post-trauma
26
Q

What is the mechanism of bile acid sequesterants/resins in the treatment of hypercholesterolemia?

A

e.g. cholestyramine, colestipol

  • granular preparation taken orally w/liquid
  • not absorbed; excreted from the GIT
  • bind to bile acids, preventing them from emulsifying fat
  • tf -cholesterol absorption
  • ++bile acid secretion (up to 10x) and tf excretion
  • to replace it, body +hepatic LDL R
  • tf -LDL in circulation/plasma
27
Q

What are the indications for bile acid sequestrants/resins?

A

hypercholesterolaemia

mixed hyperlipidaemia

28
Q

What are the common adverse effects of bile acid sequestrants/resins?

A
  • abdominal discomfort
  • bloating
  • constipation (need to be taken with a lot of water)
  • flatulence
29
Q

What are the rare adverse effects of bile acid sequestrants/resins?

A
  • increased TGs
  • faecal impaction
  • decreased absorption of fat soluble vitamins
  • steatthorea (fatty stool)

need to drink lots of water!

30
Q

Why must bile acid sequestrants/resins be taken several hours before other drugs?

A
  • non-speciifc, tf decrease absorption of other drugs by binding to them
  • e.g. glycosides, thiazides, statins, aspirin
31
Q
A