Presentation on theme: "Ischaemic Heart Disease Case E. The History Mrs TZ 60yo, takes the following medications on a regular basis. –Moduretic 50/5mg (Amiloride/Hydrochlorothiazide)"— Presentation transcript:
The History Mrs TZ 60yo, takes the following medications on a regular basis. –Moduretic 50/5mg (Amiloride/Hydrochlorothiazide) 1 M (commenced 3 weeks ago) –Norvasc (Amlodipine) 10mg 1 D –Plavix (Clopidogrel) 75mg 1 D
Estimating LDL Using Friedewald equation: LDL = TC – HDL – TG mmol/L 2.19 = 7.6 – 0.7– 3.3 2.19 Mrs TZ LDL = 5.4 mmol/L LDL > 5 mmol/L excessive even in the absence of risk factors Foundation of Oz Guidelines: –LDL > 3 risk of CVD
Medications which affect lipid levels Antihypertensive medications –Thiazide & loop diuretics VLDL & LDLs – blockers especially Propanolol – HDL & total CH/HDL CH ratio Others include: –Hepatic microsomal enzyme inducers –OCs –GCs
Is the effect of thiazide diuretics on lipid levels of clinical sig.? Thiazides tend to the production of VLDL from the liver Contains level TGs May cause in plasma TGs in some Pxs NOT usually clinically sig. v. few Px marked TGs risk vascular problems or pancreatitis Diuretics used manag. of hyperT by ing BP –Also shown to prevent: Strokes, MI & CHF
Short term studies have shown that high dose diuretics (>50mg/day) may affect lipoprotein profiles Various types of thiazide diuretics used in high doses showed: - T.CH by ~ 4% - sLDL ~10% -Lesser effects on VLDL -No in HDL High doses thiazides NOT shown greater benefit –Doses >25mg/day of hydrochlorothiazide or demonstrated rel. flat D-R curve –The likelihood of metabolic events such as CHO, e -, & lipid abnormalities may be less with lower doses aim min effect on lipid levels yet retain anti- hypoT effect –Found that indapamide 2.5mg/day is equipotent to 50mg hydrochlorthiazide but has better lipid tolerability
Is it a sustained effect? High dose thiazide diuretics sustained effect Lg scale clinical trial studies show NO effect on lipid levels after 3-5 years of use During 1st yr sCH levels may sig. –However return back to or baseline after a yr of Tx Long-term Tx w. thiazide diuretics modest elevation sCH level may occur during the 1st yr but subsides back to or baseline value after a year of therapy. Thiazide-induced seem to be D-R & may resolve w. discontinuation of Tx.
Proposed MOA Thiazide- Induced Effect on Lipid Levels The exact mechanism responsible for CH is uncertain. Many proposed mechanisms: 1.Stim. of catecholamine release in response to vol. depletion Catecholamines stimulate hepatic CH synthesis 2.Hypokalemia proposed as a cause Addition of a K+ sparing diuretic to a thiazide regimen may limit the observed elevation in CH 3.An in serum glucose or insulin secretion has also been suggested as the aetiology of the TG elevation 4.Thiazide-induced reduction in insulin sensitivity may cause an associated in hepatic production of CH However, this observation may be more related to the reduction in serum K that may occur w. dosages of thiazides
Hyperlipidaemia –Defined as an elevation in one or more of CH, cholesterol esters, phospholipids, or TG. –Can result in premature coronary atherosclerosis, leading to manifestations of IHD.
Classification of Dyslipidemias May be 1° or 2°: – 1° forms - genetically determined & classified according to lipoprotein particles raised –2° forms: - consequence of other conditions such as: DM Alcoholism, Nephrotic syndrome CRF
1° Dyslipidemias Type Lipoprotein CHTGAtherosclerosisDrug Tx IChylomicrons++++NENone IIaLDL++NEHighHMG-CoA reductase inhibitors +/- resins IIbLDL+VLDL++ HighFibrates, HMG-CoA reductase inhibitors, nicotinic acid IIIVLDL++ ModerateFibrates IVVLDL+++ModerateFibrates (+/- fish oil) VChylomicrons+++NENone (+/- fish oil) Frederickson/WHO classification of Hyperlipoproteinaemia
Clinical dyslipidemia assessment Once 2° causes & other medications have been ruled out as a cause of dyslipidemia, the Pxs lipid profile guides therapy (Based on Fredericksons classification)
Back to the Px…. What should we do? Mrs TZhyperlipidemia Recommend? –Statin –Fish oils –Non pharmacological Tx Diet fat intake Exercise Avoid smoking & alcohol