REVIEW AND ASSESSMENT NOTES Flashcards
The 2013 ACC/AHA cholesterol guidelines recommend moderate- or high-intensity statin therapy for primary prevention of CV disease for individuals with an estimated 10-year risk of?
≥7.5%.
simvastatin is metabolized primarily by cytochrome P450 CYP3A4, which if inhibited by other medications leads to an augmented serum simvastatin level and the potential for increased toxicity, including myositis and rhabdomyolysis
The FDA advises that gemfibrozil not be prescribed concurrently with simvastatin, and that the dosage of simvastatin should not exceed 10 mg daily for patients who also take verapamil, diltiazem, or amiodarone
moderate intensity regimens recommended by the 2013 ACC/AHA guidelines include
atorvastatin 10-20 mg daily or rosuvastatin 5-10 mg daily.
Optional high-intensity r mens include
atorvastatin 40-80 mg daily or rosuvastatin 20-40 mg daily.
Reduction of dietary sodium intake to <100 mmol/d (2.4 g of sodium or 6 g sodium chloride) decreases systolic BP approximately
2 to 8 mm Hg
Adoption of the DASH (Dietary Approaches to Stop Hypertension) eating planrich in fruits, vegetables, and low-fat dairy products and low in total and saturated fat—has been shown to reduce BP by .
11.4/5.5 mm Hg
Ethanol consumption of no more than——–
(24 oz beer, 10 oz wine, 3 oz 80-proof liquor for a normal-size man and less for a woman) is associated with decreased cardiac mortality, but excessive alcohol intake exerts a pressor effect, so that alcohol abuse is actually a cause of reversible hypertension.
1 oz/d
Fibromuscular renovascular disease arises primarily in women aged 20-60
aged 20-60
The second, and less common, form of renal artery stenosis is fibromuscular dysplasia,
nvolves mainly the distal two thirds of the main renal artery,
involvement of the media is most common.
Renovascular disease is one of the most common causes of secondary hypertension and has two main etiologies. The most common cause (80% to 90% of cases) is athero sclerotic disease affecting the——– of the main renal artery, typically seen in older men
proximal third
A renovascular etiology of hypertension should be suspected in patients who develop high blood pressure ———- with the abrupt onset of severe and resistant hypertension
before age 30, or after age 50
Renal parenchymal disease is the most common cause of secondary hypertension
t
Essential hypertension accounts for approximately 90% of patients with elevated blood pressure. 1 Renal parenchymal disease is the second most common cause, responsible for approximately 5%
T
Grouped together, coarctation of the aorta, Cushing disease, and pheochromocytoma contribute to <1%.
t
. Primary aldosteronism accounts for ~1% of h tension in the general population but a higher percentage (~11%) in patients with resistant hypertension
the
Pure “white coat” hypertension, in which blood pressures taken in the office are persistently elevated but outof-office readings are not, is found in—– of patients.
20% to 30%
Most patients with white coat hypertension are found to be free of target organ damage and have an excellent 10-year prognosis with respect to cardiovascular disease.
T
The cuff bladder should encircle and cover —— of the length of the arm
two thirds
WHAT IS THE LIFE TRIAL?
However, in the LIFE trial, the ARB losartan was compared with the beta-blocker atenolol in high-risk hypertensive patients with electrocardiographic LVH, the majority of whom were also treated with a diuretic. Despite a similar reduction in blood pressure, the individuals who received losartan demonstrated reduced cardiovascular morbidity and mortality compared with those who received the beta-blocker. 2
The use of oral contraceptives (OCs) is a cause of secondary hypertension in young women. The likelihood of such patients developing hypertension is increased by
alcohol consumption
age >35 years
Obesity
probably related to the estrogen content of the agent.
Because estro gen increases the hepatic production of angiotensinogen, a probable mechanism for hypertension induced by oral contraceptives is activation of the
renin-angiotensin system with subsequent sodium retention and volume expansion.
BP normalizes within 6 months of initiating OC therapy in approximately 50% of patients.
t
Most pheochromocytomas arise in the adrenal medulla, where —— are bilateral and —– are malignant.
10%
Approximately —— of pheochromocytomas are extra-adrenal (paragangliomas).
15%
The most reliable screening test for pheochromocytoma is the——- , the catecholamine metabolite least affected by interfering substances.
24-hour urine assay for metanephrines
Approximately 10% of pheochromocytomas are familial, and may be inherited alone or in combination with other abnormalities, most commonly multiple endocrine neoplasia (MEN) type 2A or 2B.
TRUE
The most common side effect is an annoying dry cough that occurs in in 5-20% of patients taking ACE inhibitors, likely related to increased
bradykinin.
The cough from ACE-I may persist for —— after discontinuation of the medication
more than 3 weeks
Calcium channel blockers vasodilate and lower blood pressure by interacting with plasma membrane L-type calcium channels in vascular smooth muscle and cardiac myocytes. A common side effect is ankle edema (———why?— Less common adverse effects include ——
which arises because of arterial > venous vasodilation).
headache, flushing, and gingival hyperplasia.
Hydralazine is a direct vasodilator with potential adverse effects that include
These side effects can be prevented, and the antihypertensive effect increased, by co-administration of a beta-blocker.
tachycardia, flushing, and headaches.
Verapamil and diltiazem can also impair —-
cardiac conduction and cause bradycardia.
Minoxidil is a direct vasodilator that is occasionally used in patients with renal failure and severe hypertension. Its side effects include
reflex increase in cardiac output
fluid retention
hirsutism.
Minoxidil is a direct vasodilator that is occasionally used in patients with renal failure and severe hypertension. Its side effects include
reflex increase in cardiac output
fluid retention
hirsutism
EFFECTS OF THIAZIDES
LOWERS THE FF
HYPOKALEMIA
HYPOMAGNESEMIA
HYPONATREMIA
EFFECTS OF THIAZIDES
INCREASES THE FF
HYPERCALCEMIA
HYPERURICEMIA
higher dosages (≥50 mg daily) may increase the total blood cholesterol, LDL, and triglyceride levels
statins increase the cell surface expression of LDL
By reducing the i lular cholesterol concentration, the expression of cellsurface low-density lipoprotein (LDL) receptors is increased (resulting in enhanced removal of LDL particles from the circulation) and the hepatic production of very-lowdensity lipoprotein (VLDL), the precursor of LDL choles terol, is reduced.
Myonecrosis, consisting of muscle aching or weakness in association with a serum creatine kinase level >10 times normal occurs in <0.5% of patients. This adverse effect should prompt immediate discontinuation of the statin. The risk of myopathy is increased when there is concurrent therapy with other drugs that interfere with cytochrome P-450 metabolism of many of the statins. Examples of such drugs include
erythromycin, cyclosporine, and antifungal agents.
P450 INHIBITORS
SICKFACES.COM Sodium valproate Isoniazid Cimetidine Ketoconazole Fluconazole Alcohol..binge drinking Chloramphenicol Erythromycin Sulfonamides Ciprofloxacin Omeprazole Metronidazole Grapefruit juice
P450 Inducers
CRAP GPS induces me to madness!!
Carbemazepines
Rifampicin
Alcohol (chronic)
Phenytoin
Griseofulvin
Phenobarbitone
Sulphonylureas
Effect of Drugs on Lipid Profile
Beta-blockers, particularly non–beta 1 -selective agents, . Thiazides
Hormonal replacement therapy with estrogen
Protease inhibitors, for patients with human immunode ficiency virus infection,
BB: increase triglyceride levels and lower high-density lipoprotein (HDL) levels
t: tend to increase triglyceride levels
E: increases both HDL and triglyceride levels.
P: dyslipidemic syndrome characterized by elevated triglyceride and total cholesterol levels with decreased HDL levels
.is an autosomal co-dominant disorder that results from defects in the LDL receptor gene.
Corneal arcus, tendinous xanthomas, and xanthelasmas are common.
Familial hypercholesterolemia
is one of the most common familial lipoprotein disorders. It is a polygenic condition with abnormalities that include elevations of LDL and/or triglycerides, a reduction in HDL, and ele vated apo B levels.
Patients with FCH have an increased risk of coronary artery disease (CAD)
Physical findings such as corneal arcus or xanthomas are rare.
Familial combined hyperlipidemia (FCH)
is also a polygenic disorder and is characterized by elevated triglycerides with normal or low LDL levels and reduced HDL. Patients do not develop xanthomas or xanthelasmas, and the relationship with CAD is not as strong or consistent as with FCH.
Familial hypertriglyceridemia (type IV hyperlipoproteinemia)
encodes a protease that binds to the LDL recep tor and targets it for lysosomal degradation. Gain-of-function mutations in this gene decrease the availability of the LDL receptor, which causes higher plasma LDL cho lesterol levels and an increased risk of ischemic heart disease. 3 Loss-of-function mutations in this gene result in lower LDL-cholesterol and coronary event rates.
The proprotein convertase subtilisin/kexin type 9 gene (PCSK9)
Niacin (nicotinic acid) is a B vitamin with lipid-lowering effects when taken at pharmacologic doses. Its primary action is to
decreases the release of free fatty acids from adipocytes (which are used by the liver for triglyceride synthesis), thus reducing triglyceride levels.
reduce very low-density lipoprotein secretion from the liver, which causes a subsequent reduction in intermediate-density lipoprotein and low-density lipopro tein (LDL) levels.
reduces LDL cholesterol by 10% to 25% and triglycerides by 20% to 50%, and increases high-density lipoprotein (HDL) cholesterol by 15% to 35%.
NIACIN
NIACIN Despite these effects on the lipid profile, its widespread use has been limited historically because of side effects, including
flushing, hepatotoxicity, hyperuricemia, hyperglycemia, and gastritis.
owever, in more recent trials of patients treated aggressively with statin therapy (AIM-HIGH 2 , HPS2-THRIVE 3 ), the addition of niacin did not further lower cardiovascular risk compared to the statin alone.
(AIM-HIGH 2 , HPS2-THRIVE 3
Niacin also reduces c lating levels of lipoprotein (a
T
In the ACCORD trial, type 2 diabetic patients already treated with simvastatin achieved a marked reduction in triglycerides with the addition of fenofibrate. However, compared with placebo, clinical outcomes (fatal cardiovascular events, nonfatal myocardial infarction, or stroke) were not reduced by the addition of fenofibrate. 3
ACCORD trial
is the major protein in high-density lipoprotein (HDL) and its concentration is inversely correlated with angiographic evidence of coronary disease
Apo AI
two forms of apoprotein B arise from a single gene that displays a unique editing mechanism that allows for synthesis of both proteins.
(apo B48 and apo B100)
is the primary apoprotein of low-density lipoprotein (LDL), allowing recognition of the particle by the LDL receptor on cell surfaces.
Apo B100
is found in very-low-density lipoproteins (VLDL) particles as well as in chylomicrons, in intermediatedensity lipoprotein (IDL) particles, and, to a small extent, in HDL.
Apoprotein E
(also termed dysbetalipoproteinemia or broad beta disease) are homozygous for the apoprotein E2/2 genotype.
type III hyperlipoproteinemia
one of the few interventions that can significantly reduce Lp(a); statin drugs do not. However, no study yet has shown that targeted pharmacologic reduction of Lp(a) improves cardiovascular outcomes.
Niacin
