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It’s all about application, Cheat Sheet of Clinical Medicine

Centro Escolar University (CEU)Clinical Medicine

Clinical pharmacy prelims for third year students

Typology: Cheat Sheet

2022/2023

Uploaded on 07/10/2024

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Dyslipidemia
Clinical Pharmacy
3E-PH
PHA 6127
September 12, 2020
First Shifting
Ostonal, Saludes
1 of 7
LIPID
• An organic macromolecule made up of fatty acid monomer. It is
non-polar in nature therefore does not interact with water. It is oily
or greasy substance stored in the adipose tissue of the body
which supplies ener gy for different life processes. This is also
essential for different biological system as they form the cell
membrane which is the cell’s barrier from its external
environment.
• Plays various significant role i n the body such as:
1. Cellular membrane structure and function
2. Precursor of hormone
3. Cellular signaling
4. Body insulator
5. Initiate release of hormones
6. Regulation and excretion of nutrients
7. Prolonging digestive processes by decreasing the secretion of
HCl
8. Surrounding, protecting and holding or gans in place
• Can be classified either as simple, compound and derived lipids
SIMPLE LIPIDS
• Esters of fatty acid with various alcohol such as fats and waxes.
It may further be classified either as:
− Saturated Fatty Acid
o those which have sizeable effect of raising blood cholesterol
such as lauric and palmitic acid
− Mono-unsaturated Fatty Acid
o which helps in lowering of the LDL and VLDL such as ole ic
acid and palmotoleic acid
− Poly-unsaturated Fatty Acid
o are those who have hypolipidemic effects such as linoleic
acid and arachidonic acid
− Trans Fatty Acid
o who has harmful effect as it raises LDL and lowers HDL level
COMPOUND LIPIDS
• Are those that contain other groups in addition to alcohol and fatty
acids examples are phospholipid and glycolipid
DERIVED LIPIDS
• Are the hydrolysis products of simple and compound lipids
Fig. 1 Classification of Lipid
CHOLESTEROL
• A fatty substance manufactured in the liver and is carried
throughout the body in the bloodstream. It is an important
constituent of the cell membrane, steroids, bile acids and
signaling molecules. The largest source of cholesterol is the
biliary secretion and not diet. Only 50% cholesterol is absorbed
from the diet
Fig. 2. Sample of cholesterol rich foods
• An important constituent of cell membrane, steroid, b ile acid and
signaling molecules.
• Figure 3 shows as how cholesterol is synthesized to form bile and
stored in the gall bladder for release during digestion to the
duodenum to help in lipid absorption.
Fig. 3. Biliary secretion
• Bile salts are either reabsorbe d i n the GI t ract for recirculation
back to the liver through the enterohepatic circulation or excreted
thru the feces as excretion is the major pathway for cholesterol to
be eliminated from the body.
TRIGLYCERIDES
• A type of fat that is found in our blood. The body convert s excess
calories, sugar and alcohol into triglycerides.
• primary function is to store energy in adipocytes and muscle cells.
People who are overweight, inactive, smokers or heavy drinker
and those who eat very high carbohydrate diet tends to have high
triglyceride level.
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Download It’s all about application and more Cheat Sheet Clinical Medicine in PDF only on Docsity!

Dyslipidemia Clinical Pharmacy

3 E-PH PHA 612 7

September 12, 2020 First Shifting

Ostonal, Saludes 1 of 7

LIPID

  • An organic macromolecule made up of fatty acid monomer. It is non-polar in nature therefore does not interact with water. It is oily or greasy substance stored in the adipose tissue of the body which supplies energy for different life processes. This is also essential for different biological system as they form the cell membrane which is the cell’s barrier from its external environment.
  • Plays various significant role in the body such as:
    1. Cellular membrane structure and function
    2. Precursor of hormone
    3. Cellular signaling
    4. Body insulator
    5. Initiate release of hormones
    6. Regulation and excretion of nutrients
    7. Prolonging digestive processes by decreasing the secretion of HCl
    8. Surrounding, protecting and holding organs in place
  • Can be classified either as simple, compound and derived lipids SIMPLE LIPIDS
  • Esters of fatty acid with various alcohol such as fats and waxes. It may further be classified either as: − Saturated Fatty Acid o those which have sizeable effect of raising blood cholesterol such as lauric and palmitic acid − Mono-unsaturated Fatty Acid o which helps in lowering of the LDL and VLDL such as oleic acid and palmotoleic acid − Poly-unsaturated Fatty Acid o are those who have hypolipidemic effects such as linoleic acid and arachidonic acid − Trans Fatty Acid o who has harmful effect as it raises LDL and lowers HDL level COMPOUND LIPIDS
  • Are those that contain other groups in addition to alcohol and fatty acids examples are phospholipid and glycolipid DERIVED LIPIDS
  • Are the hydrolysis products of simple and compound lipids Fig. 1 Classification of Lipid

CHOLESTEROL

  • A fatty substance manufactured in the liver and is carried throughout the body in the bloodstream. It is an important constituent of the cell membrane, steroids, bile acids and signaling molecules. The largest source of cholesterol is the biliary secretion and not diet. Only 50% cholesterol is absorbed from the diet Fig. 2. Sample of cholesterol rich foods
  • An important constituent of cell membrane, steroid, bile acid and signaling molecules.
  • Figure 3 shows as how cholesterol is synthesized to form bile and stored in the gall bladder for release during digestion to the duodenum to help in lipid absorption. Fig. 3. Biliary secretion
  • Bile salts are either reabsorbed in the GI tract for recirculation back to the liver through the enterohepatic circulation or excreted thru the feces as excretion is the major pathway for cholesterol to be eliminated from the body. TRIGLYCERIDES
  • A type of fat that is found in our blood. The body converts excess calories, sugar and alcohol into triglycerides.
  • primary function is to store energy in adipocytes and muscle cells. People who are overweight, inactive, smokers or heavy drinker and those who eat very high carbohydrate diet tends to have high triglyceride level.

LIPOPROTEINS

  • Combination of protein and lipid. They are classified as Chylomicrons, chylomicron remnants, very low-density lipoprotein (VLDL), intermediate lipoprotein (IDL), low-density lipoprotein (LDL) and high-density lipoprotein (HDL). Figure 4 shows us the summary of the different lipoproteins. Fig. 4. Summary of Lipoprotein with their characteristics
  • Apolipoproteins − Proteins which transports lipids by binding to them. They may also serve as cell surface receptors or as enzyme cofactor. There are 6 main type of apoprotein: Apolipoprotein A, B, C, D, E, and H.
  • Lipoproteins are metabolized in the plasma in 2 pathways exogenous or endogenous (fig. 5). − In the exogenous pathway fats coming from our diet are being metabolized. When dietary cholesterol and triglyceride are absorbed from the intestine they are transported in the intestinal lymphatics as chylomicrons. In the capillaries these chylomicrons bound with Apolipoprotein CII activates in the serial lipoprotein lipase the convert 90% of chylomicron triglyceride the fatty acid and glycerol Which are then taken up by the adipocyte's and muscle cells for energy use or storage. The chylomicron remnants which are cholesterol rich then circulates back to deliver where they are cleared any process mediated by Apolipoprotein E. − In the endogenous pathway the VLDL formed in the liver and transports triglycerides to the periphery.In the capillaries the triglyceride content of VLDL-Cis removed by lipoprotein lipase after the activation of Apolipoprotein C II. The free fatty acid is then taken up by the adipose tissue and muscles. The Intermediate density lipoprotein which is comprise by approximately 50% triglyceride and 50% cholesterol ester from the HDL. This is can either return to the liver or further hydrolized and be modified to lose the triglyceride and apolipoprotein E and become LDL which is the major cholesterol carrying particle in the serum and into the extrahepatic tissues.
  • The reverse cholesterol pathway involves lipoprotein mediated transport of cholesterol from the extracellular tissue to the liver for its excretion either in the form of bile acid or biliary cholesterol. Fig. 5 Schematic diagram of the lipid metabolism pathway.

DYSLIPIDEMIA

  • Disorder of lipoprotein metabolism, including lipoprotein overproduction or deficiency.
  • May be manifested by elevation of the serum total cholesterol, low density lipoprotein (LDL) cholesterol and triglyceride concentration and a decrease in the high density (HDL) cholesterol concentration. It can either by primary (familial dyslipidemia) or secondary (acquired dyslipidemia)
  • Characterized by different lipid abnormalities: − elevation of triglyceride level − elevation of low density lipoprotein (LDL) − reduction of high density lipoprotein (HDL) and 4) elevation of total cholesterol
  • Dyslipidemia may be classified as: − Hypercholesterolemia – Increase in cholesterol only − Hypertriglyceridemia – Increase in triglyceride only − Mixed or combined hyperlipidemias – Increase in both cholesterol and triglyceride − Atherogenic dyslipidemia – Raised triglyceride and small dense LDL and low HDL (Type 2 diabetes and metabolic syndrome) TOTAL CHOLESTEROL
  • Total cholesterol is a measure of the components of LDL, cholesterol, HDL-C and VLDL. It is calculated using the formula: − TC = LDL + HDL + 20% TG SIGNS AND SYMPTOMS
  • Dyslipidemia itself usually causes no symptoms but it is a risk factor for the development of 2 more serious conditions such as Coronary Artery Disease, Peripheral Artery Disease and Stroke. Several studies have been published on the linkage of dyslipidemia to the development of the said diseases. − High triglyceride and low HDL levels, is linked with CAD (Khashayar &Mohagheghi, 2010; Mahalle et.al.,(2014) − A linear relationship between the incidence of CVD and LDL-C (Daida et.al., 2014) − Lower levels of HDL-C were found to be associated with the severity of CAD (Abdelrazik et.al., 2016) − triglycerides, total cholesterol and LDL-C levels severity CAD and higher number of diseased vessels (Abdelrazik et.al, 2017) ETIOLOGY
  • Can either be of primary or secondary causes − Primacy cause / dyslipidemia – single or multiple gene mutations that result in either overproduction or defective clearance of TG and LDL cholesterol, or in underproduction or excessive clearance of HDL (fig. 6 and 7) − Secondary cause / dyslipidemia – sedentary lifestyle such as excessive dietary intake of saturated fat, cholesterol, and trans fats Fig. 6 Description of the different familial dyslipidemia

Fig. 9. SCORE – European Low Risk Chart Table 3. Interpretation of SCORE TARGET TREATMENT

  • The most recent Cholesterol Treatment Trialists’ Collaboration (CTT) meta-analysis of several trials involving .170 000 patients confirmed the dose-dependent reduction in CVD with LDL-C lowering. Every 1.0 mmol/L (40 mg/dL) reduction in LDL-C is associated with a corresponding 22% reduction in CVD mortality and morbidity. Fig. 10 Intervention strategies as a function of the total CV risk and LDL – C level TREATMENT
  • Lifestyle Modifications
  • HMG Co-A Reductase Inhibitor or Statins
  • Bile Acid Sequestrants
  • Cholesterol Absorption Inhibitors
  • Fibric acid derivatives
  • Lipoprotein synthesis inhibitor
  • Dietary Supplements Fig. 11 Impact of lifestyle modification on changes in lipid level. Lifted from ESC/ EAS Guidelines. (https://www.escardio.org/static- file/Escardio/Guidelines/publications/DYSLIPguidelinesdyslipidemi as-FT.pdf) Fig. 12. Dietary recommendations to lower TC and LDL-C levels. Lifted from ESC/ EAS Guidelines. (https://www.escardio.org/static- file/Escardio/Guidelines/publications/DYSLIPguidelinesdyslipidemi as-FT.pdf LIFESTYLE MODIFICATION Lifestyle modification as management of dyslipidemia includes decrease in the intake of saturated fats and cholesterol; increase in the proportion of dietary fibers and complex carbohydrates; and maintenance of an ideal body weight. Figure 11 shows the impact of different lifestyle modification on the lipid level while figure 12 shows dietary recommendation to lower the TC and LDL-c levels. HMG COA INHIBITOR The mechanism of action of this group of drugs is to inhibit the HMG CoA reductase in the liver and subsequently inhibit the formation of mevalonic acid which is a rate limiting step in the biosynthesis of cholesterol. This would result in the reduction of extracellular level of cholesterol and an increase in expression of the hepatic LDL receptors and enhanced receptor medicated catabolism and clearance of LDL-C from the serum (Fig. 13). The use of this group of drugs results in the reduction in the LDL-C, TC, VLDL and triglyceride with an increase in the HDL level.

Use of HMG Co-A reductase may result in Myositis, myalgia, elevated hepatic transaminases Fig. 13. Mechanism of Action of HMG Co-A Reductase inhibitor Fig. 14. Clinical Pharmacokinetics of HMG Co-A Reductase Inhibitor BILE ACID SEQUESTRANTS There are 3 drugs included in this category namely: cholestyramine, colestipol and colesevalam. It is the drugs of choice for women who are or are planning to become pregnant. It is administered either 4 h before or 1 h after other drugs. It is to be given with meals to increase their efficacy. They may also increase TGs, so their use is contraindicated in patients with hypertriglyceridemia. Side effects of this drugs includes unpalatability, bloating, constipation, and heartburn. It also decreases the absorption of other drugs. Bile acid sequestrant are anion exchange resins that binds bile acids in the intestine forming complex. This results in the loss of bile acids in the stools thus increasing the conversion of cholesterol into bile acids in the liver. It also decreases the concentration of intrahepatic cholesterol which results in the compensatory increase in LDL receptors, thus increasing the hepatic uptake of circulating LDL and decrease the serum LDL cholesterol levels. The mechanism of action of bile acid sequestrant is presented in fig. 15. Fig. 15. Mechanism of action of bile acid sequestrants CHOLESTEROL ABSORPTION INHIBITOR Ezetimibe is a novel drug that acts by inhibiting intestinal absorption of cholesterol and phytosterols. It can be used as second-line therapy in association with statins when the therapeutic target is not achieved at maximal tolerated statin dose. It can be taken without regard to food intake. No dosage adjustment necessary for patient with hepatic or renal insuffiency and it can be administered with statin at any dose. Its side effect includes moderate elevation of liver enzymes and muscle pain. Ezetimibe lowers plasma cholesterol levels by inhibiting the absorption from intestine Increase expression of hepatic LDL receptors. This cause a decrease in the cholesterol delivery to the liver which in turn clears more cholesterol from the blood. It has a selective action, it does not interfere with TGs, and lipid- soluble vitamins absorption. Figure 16 shows the mechanism of action of cholesterol absorption inhibitor, ezetimibe. Fig. 16 Ezetimibe mechanism of action FIBRIC ACID DERIVATIVE Fibrates significantly lower plasma triglycerides and LDL and elevate HDL. They shift the distribution of the LDL subfraction from small, dense LDL to larger, less dense LDL. Termed the atherogenic phenotype, small, dense LDL is associated with a nearly threefold increase in the risk of acute myocardial infarction. The larger, less dense LDL is more readily cleared by hepatic mechanisms. Its side effect includes nausea, skin rashes, myopathy, liver enzyme elevation and cholelithiasis. Fibrates also improve the lipid profile through a mechanism involving peroxisome proliferator activator receptors (PPARs). Fibrate-activated PPARs reduce plasma levels of apolipoprotein C- III (Apo C-III). Consequently, fibrates: facilitate lipoprotein lipase clearance of triglyceride-rich very low density lipoprotein (VLDL), a process usually inhibited by Apo CIII, and stimulated by apolipoprotein C-II (Apo C-II); activate expression of acyl-coenzyme A synthetase, which in turn stimulates oxidation of fatty acids; and therefore,reduce triglyceride synthesis in the liver and VLDL secretion. PPARs may also increase the transcription of genes for the major apolipoproteins of HDL, apolipoprotein I and apolipoprotein II. Fibrates inhibits triglyceride synthesis thus reducing VLDL release into the circulation. It increases lipoprotein lipase activity, which catabolizes chylomicron and VLDL. It also increases catabolism of triglyceride-rich VLDL, thereby lowering serum VLDL levels. It increase HDL through improved Apo A-I and Apo- II synthesis (fig. 17). Fig. 17. Mechanism of action of fibrates

CHD AND RISK EQUIVALENTS

  1. CHD: MI, coronary artery bypass graft, percutaneous coronary intervention with or without stent, acute coronary syndrome
  2. Other clinical forms of atherosclerotic disease (PAD, abdominal aortic aneurysm, and symptomatic carotid artery disease)
  3. Diabetes mellitus
  4. 10-year risk of CHD is more than 20% based on Framingham. MAIN POSITIVE RISK FACTORS (EXCLUSIVE OF LDL-C) THAT MODIFY LDL-C GOALS
  5. Cigarette smoking
  6. Hypertension (BP 140/90 mm Hg or higher or taking an antihypertensive drug)
  7. Low HDL-C (less than 40 mg/dL)
  8. Family history of premature CHD a. CHD in male first-degree relative younger than 55 years b. CHD in female first-degree relative younger than 65 years
  9. Age (men 45 years or older; women 55 years or older)

RISK ASSESSMENT

  1. For patients with two or more risk factors, perform Framingham 10 - year CHD risk assessment.
  2. For patients with zero or one risk factor, Framingham 10-year CHD risk assessment is not required.
  3. Ten-year CHD risk assessment is based on Framingham tables (Fig. 21) − Sex − Age − TC − Smoking − HDL-C − Systolic BP Fig. 23 Statin Doses and LDL lowering effect END OF REVIEWER

Coronary Artery Disease Clinical Pharmacy

Asst. Prof. Michelle D. Bartolome, MSc PHA 6127

October 19, 2020 Second Shifting

Bautista, N., Ostonal, Saludes 1 of 7

WHO FACT SHEET

  • Cardiovascular diseases are the number 1 cause of death globally
  • Estimated 17.9 million people died from CVD in 2016

  • 75% of CVD deaths occur in low and middle income countries

  • 85% of all CVD deaths are due to heart attack and stroke

ANATOMY OF THE CORONARY ARTERY

▪ DEOXYGENATED BLOOD

  • blood that no longer has oxygen
  • comes in from superior and inferior vena cava then - > right atrium

    • right ventricle - > pulmonary arteries - > then lungs

  • Once the deoxygenated blood reaches the lungs, there will be an exchange of gas, therefore the deoxygenated blood will be receiving oxygen
  • From the lungs, blood will go back into the heart through the Pulmonary Veins
  • Superior and Inferior vena cava > Right atrium > Right Ventricle

    Pulmonary arteries > Lungs > Pulmonary Vein

  • Pulmonary veins go directly into the left atrium. The oxygenated blood goes into the left ventricle
  • From the left ventricle, it will be pumped to the aorta, where it is being distributed into the different organs Figure 2. The illustration of the heart highlighting the coronary arteries
  • The heart being an organ itself, needs oxygenated blood for it to function properly
  • From the aorta, the oxygenated blood will go into the coronary arteries

▪ CORONARY ARTERIES

  • From the aorta the oxygenated blood travels to the arteries including the coronary artery, which supplies blood to the cardiac muscles. The coronary artery branches to the left and right coronary artery (Figure 2)
  • Supplies oxygenated blood to the heart so that it would be able to pump
  • Branches: − the Left Coronary Artery o Left Circumflex Artery (LCA) – supplies blood into the left atrium, to the side and back portion of the left ventricle o Left Anterior Descending Artery (LDA) – supplies blood for the front, bottom parts of the left ventricle and front part of septum − the Right Coronary Artery o Right Marginal Artery (RMA) - provides blood to the branch of the right ventricle o Posterior Descending Artery / Distal Right Coronary Artery – provides blood to the right ventricle, bottom part of the left ventricle, and the back portion of the septum
  • Collateral Circulation – network of tiny blood vessels which are formed to reroute the blood around a blocked area − If there is an occlusion in one area, tiny blood vessels will form a network allowing the detour of the blood to bypass the blocked area

CORONARY ARTERY DISEASE

  • Also known as Coronary Heart Disease (CHD) or Ischemic Heart Disease (IHD)
  • Condition wherein the vascular supply (coronary artery) to the heart is impended by narrowing of the blood vessels: − Atheroma: degenerating artery walls due to accumulation of fats − Thrombosis: formation of a blood clot − Spasm of the coronary artery: temporary tightening of the coronary artery
  • This impairs the supply of the oxygenated blood to the cardiac tissue thus causing myocardial ischemia (Figure 1)
  • If there is narrowing of the blood vessel, there would be lesser supply of blood to be received by our cardiac muscles. − Since our heart is also a muscle, it needs oxygenated blood to function properly
  • Any occlusions or blockages may cause myocytes (cardiac cells) to die Figure 1. Illustration of the cause of coronary artery disease