This document provides information on hyperlipidemic drugs. It begins with an introduction to hyperlipidemia and its causes. It then discusses various drug classes for treating hyperlipidemia, including their mechanisms of action, effects on lipid levels, pharmacokinetics, therapeutic uses, adverse effects and interactions. The major drug classes discussed are HMG-CoA reductase inhibitors (statins), bile acid sequestrants, fibrates, and niacin. For each class, specific drugs are highlighted and their properties compared.
It is a anti- hypertensive drug. It is non-selective beta blocker drug. Hence it is beta blocker drug so it has many side effect.Not only Propranolol but also Timolol,Atenolol are beta blocker drugs.
It is a anti- hypertensive drug. It is non-selective beta blocker drug. Hence it is beta blocker drug so it has many side effect.Not only Propranolol but also Timolol,Atenolol are beta blocker drugs.
A detailed information about the cholesterol types, its absorption, conversion and drugs used to lower the levels of LDL, VLDL and Triglycerides - classification, mechanism of action, side effects, dosage and indications.
This a is a slide set (42 slides) covering clinically used drugs for lipid lowering. This is an updated version of the lecture series for the 2021-2022 academic year. Suitable for intermediate level learners
Hyperlipidemia , dyslipidemia , and drug therapy
also Fat transport and metabolisim and pathophysiology of lipoprotein
clincal importance of
1. Hypertriglycredemia
2. Hypercholesterolemia
3.Combined hyperlipidemia
4. Some other lipoprotein disorders
Including disorder of HDL_C
the aim of sharing this material to help students and provide delayed information regarding topic.You all are most welcome for you suggestion to make i more easy, graspable and attractive.(easy to learn in creative way)
Introduction
Generic Name: Atorvastatin
Brand Names: Lipitor,Atorvast,Divastin,Lipicut
Atorvastatin a group of drugs called HMG CoA reductase inhibitors, or "statins."
Atorvastatin reduces levels of "bad" cholesterol or LDL and triglycerides in the blood, and also increasing levels of "good" cholesterol or HDL.
4Mechanism of action
Statin drugs competitively inhibit HMG-CoA, which is an enzyme that catalyzes the synthesis of HMG-CoA in to cholesterol. Therefore, it effectively the synthesis of new cholesterol. It leads to an increase in LDL receptor on Liver cells to take in more LDL, effectively decreasing LDL in the body
5Pharmacokinetics
Absorption
Atorvastatin undergoes rapid absorption when taken orally, with an approximate time to maximum plasma concentration of 1–2 h
Distribution
The mean volume of distribution of atorvastatin is approximately 381 L. It is highly protein bound (=98%), and likely secreted into human breast milk.
8Metabolism
Atorvastatin metabolism is primarily through cytochrome P450 3A4 hydroxylation to form active ortho-and parahydroxylatedmetabolites. The ortho-and parahydroxylatedmetabolites are responsible for 70% of systemic HMG-CoA reductase activity. The ortho-hydroxymetabolite undergoes further metabolism via glucuronidation.
9ExcretionAtorvastatin is primarily eliminated via hepatic biliary excretion, with less than 2% recovered in the urine. Bile elimination follows hepatic and/or extrahepaticmetabolism. Atorvastatin has an approximate elimination half-life of 14 h.
10Medical Uses
Hypercholesterolemia to reduce total cholesterol, LDL-C, apo-B, as well as increase HDL levels.
Hypertriglyceridemia
Primary prevention of heart attack, stroke.
Secondary prevention of myocardial infarction, stroke, unstable angina.
Myocardial infarction and stroke prophylaxis in patients with type II diabetesInteractions
Grapefruit juice can increase the blood levels of atorvastatin. This can increase the risk of side effects such as liver damage.
Interactions with clofibrate, fenofibrate, gemfibrozil, usually in combination with statins, increase the risk of myopathy.
Barbiturates, carbamazepine, oxcarbazepine, rifampin, and rifamycin, which are CYP3A4 inducers, can decrease the plasma concentrations of atorvastatin.
12Precautions to be taken Before taking this medicine
Liver disease
Muscle pain or weakness
History of liver disease
History of kidney disease
History of stroke
If you are pregnant or breast-feeding
A thyroid disorder
If you drink more than 2 alcoholic beverages daily.
Side Effects
Cough
Difficulty with swallowing
Fast heartbeat
Fever and dizziness
Itching
Muscle cramps, pain, stiffness, swelling, or weakness
Puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
Skin rash
Tightness in the chest
Unusual tiredness or weakness
Lipids are a heterogenous group of
water –insoluble ( hydrophobic ) organic
molecules. Presentation on how they affect the body and what to do to prevent their effects.
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
MANAGEMENT OF ATRIOVENTRICULAR CONDUCTION BLOCK.pdfJim Jacob Roy
Cardiac conduction defects can occur due to various causes.
Atrioventricular conduction blocks ( AV blocks ) are classified into 3 types.
This document describes the acute management of AV block.
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
2. Introduction
Hyperlipidemia is a condition excess
of fatty substances called lipids,
largely cholesterol and triglycerides,
in the blood.
It results from abnormalities in lipid
metabolism or plasma lipid transport
or a disorder in the synthesis and
degradation of plasma lipoproteins.
3. Serum Lipid Level (mg/dL) and Risk of
CAD and IHD based on NCEP Guidelines
2001
5. Current cigarette smoking Defined
as smoking within the preceding 30
days
Age Male >45 years of age or
female >55 years of age
Family history of premature CHD A first-
degree relative (male <55 years of age or
female <65 years of age when the first CHD
clinical event occurs)
6. Hypertension Blood pressure
140/90 or use of
antihypertensive medication,
irrespective of blood pressure
Low HDL-C <40 mg/dL
(consider <50 mg/dL as "low" for
women)
Obesity
Body mass index >25 kg/m2
and waist circumference >40
inches (men) or >35 inches
(women)
Type 2 diabetes mellitus
7. Hyperlipoproteinaemias
Primary: due to:
(a) A single gene defect: is familial and
called ‘monogenic’ or genetic
(b) Multiple genetic, dietary and
physical activity related causes:
‘polygenic’ or multifactorial.
9. Secondary: associated with
Diabetes,
Myxoedema,
Nephrotic syndrome,
Chronic alcoholism,
Drugs (corticosteroids, oral
contraceptives, β blockers) etc.
10. Lipids- Hterogenous group of compounds
related to fatty acids, which are insoluble in
fatty acids and are source of energy.
Lipoproteins- Spherical particles of water
soluble proteins, that transport neutral lipids
through body fluids.
13. • Life style modification.
Regular exercise.
• Obesity reduction.
• Stop smoking &
alcoholism.
• Diet.
• Restrict intake of saturated
fat.
Fish intake-oily sea fish.
Eg-Tuna & Mackarel.
• Plenty of fruits &
vegetebles.
• TREAT THE UNDERLYING
Treatment strategies
14. Clinical guidelines
recommend the drug
therapy to be started along
with lifestyle changes in
patients with IHD or in
patients with having LDL
greater than 130mg/dl.
18. Primary prevention involves
management of risk factors to prevent a
first-ever CHD event.
Secondary prevention patients are
those who have had a prior CHD event
and whose risk factors are treated most
aggressively.
Recently, the concept of primordial
prevention has been applied to CHD
19. The primordial prevention guidelines include
150 minutes/week of moderate-intensity exercise (walking
20-30 minutes/day.
Dietary recommendations include
reducing total calories from fat to <30% and saturated fat to
<7% to avoid trans fat;
consuming <300 mg of cholesterol/day,
a variety of oily fish twice a week or more often, and
oils/foods rich in -linolenic acid (canola, flaxseed, and
soybean oils; flaxseed; and walnuts);
restricting sugary beverages to <36 oz/week for a person
consuming 2000 Kcal daily
20. HYP0LIPIDEMIC
DRUGS
Several different classes of drugs are
used to treat hyperlipidemia. These
classes differ not only in their
mechanism of action but also in the
type of lipid reduction and the
magnitude of the reduction.
21. Classification of Hypolipidemic
Drugs
First Line Therapy
1. HMG-CoA reductase inhibitors (Statins): Lovastatin,
Simvastatin, Pravastatin, Atorvastatin, Rosuvastatin,
Pitavastatin
2. Bile acid sequestrants (Resins):
Cholestyramine, Colestipol
3. Inhibitors of Intestinal Absorption of
Cholesterol: Stanol Esters, Ezetimibe.
4. CETP Inhibitors: Torcetrapib,
Anacetrapib
22. Second Line Therapy
Lipoprotein lipase activators (PPARα
activators, Fibrates): Clofibrate,
Gemfibrozil, Bezafibrate, Fenofibrate
Lipolysis and triglyceride synthesis
inhibitor: Nicotinic acid (Niacin)
Miscellaneous Agents: Gugulipid and
Fish oil Derivatives.
23. HMG-CoA REDUCTASE
INHIBITORS (Statins)
The statins are the most effective and
best-tolerated agents for treating
dyslipidemia.
These drugs are competitive inhibitors of
HMG-CoA reductase, which catalyzes an
early, rate-limiting step in cholesterol
biosynthesis.
24. History
Statins were isolated from a mold,
Penicillium citrinum, and identified
as inhibitors of cholesterol
biosynthesis in 1976 by Endo and
colleagues.
The first statin studied in humans
was compactin, renamed
mevastatin, which demonstrated
the therapeutic potential of this
25. Alberts and colleagues at Merck
developed the first statin approved for
use in humans, lovastatin (formerly
known as mevinolin), which was
isolated from Aspergillus terreus.
Pravastatin and simvastatin are
chemically modified derivatives of
lovastatin.
Atorvastatin, fluvastatin,
rosuvastatin, and pitavastatin are
structurally distinct synthetic
26. They competitively inhibit
conversion of 3-Hydroxy-3-
methyl glutaryl coenzyme A
(HMG-CoA) to mevalonate
(rate limiting step in CH
synthesis) by the enzyme
HMG-CoA reductase.
28. LDL is also reduced by
enhancing the removal of
precursors of of LDL. Eg;
VLDL and IDL.
Reducing hepatic VLDL
production also leads to
reduction in the level of
LDL. This also reduced the
level of TG.
29. Therapeutic doses reduce CH synthesis by
20–50%. This results in compensatory
increase in LDL receptor expression on liver
cells → increased receptor mediated uptake
and catabolism of IDL and LDL.
Over long-term, feedback induction of HMG-
CoA reductase tends to increase CH
synthesis, but a steady-state is finally attained
with a dose-dependent lowering of LDL-CH
levels.
30. Actions
Effect on Lipid Levels
Effect of TG:
• Significant reduction in TG Level (35-45%)
if the TG > 250mg/dl.
• If TG <250 mg/dl – maximum reduction is
<25%
• LDL is also reduced.
31. Effect on LDL-C
• Depending upon the statin its dose the degree
of reduction in the level of LDL ranges from
20-55%Statins Dose Range
Fluvastatin 20-80mg 20 35
Pravastatin 10-40mg 20 35
Lovastatin 10-80mg 20 40
Cervistatin 0.2-0.8mg 20 40
Simvastatin 10-80mg 26 50
Atorvastatin 10-80mg 31 55
Rosuvastatin 5-40mg 36 55
Percentage Reduction in LDL-C in
Min Dose Max Dose
32. Effect on HDL-C
• Increased irrespective of the dose and statins
used but if the HDL-C <35mg/dl- the effect
may be variable.
• Simvastatin produces greater increase in HDL-
C and apoA-1 level than Atorvastatin and
Rosuvastatin.
Level of Lp(a) is not affected by the Statins.
34. Effect on Endothelium
Hypercholestroleamia depresses the
acetylcholine induced vasodilatation in coronary arteries.
Statins increase the synthesis of endothelial NO by stabilization of
endothelial synthase mRNA.
Endothelial dysfunction is also reversed by statins.
35. Effect on Plaque Stability
Inhibits the infilteration of monocytes in
arterial wall.
Inhibits the secretion of metalloproteinases secreted
by macrophages.
The metalloproteinases degrade matrix and weaken
the fibrous cap of atherosclerotic plaque.
Statins also appear to modulate the cellularity of the
artery wall by inhibiting proliferation of smooth muscle
cells and enhancing apoptosis.
Reduced proliferation of smooth muscle cells and
enhanced apoptosis- retard initial hyperplasia and
restenosis.
36. Effect on Inflammation
C- Reactive Protein – marker for high risk
CAD.
Statins Reduces the baseline CRP.
37. Effect on Lipoprotein Oxidation
Oxidative changes in LDL
occurs and important in
the uptake of lipoprotein
cholesterol by
macrophages,
cytotoxicity with lesions.
Statins inhibits the
oxidative changes and
thus subsequent effect.
38. Effect on Coagulation
Statins decrease platelet
aggregation and also reduce the
level of fibrinogen.
Increased level of fibrinogen may
be involved in increased incidence
of CAD
39. Atorvastatin
This newer and most popular statin is more
potent and appears to have the highest LDL-CH
lowering efficacy at maximal daily dose of 80 mg.
At this dose a greater reduction in TGs is noted if
the same was raised at baseline.
Atorvastatin has a much longer plasma t½ of 18–
24 hr than other statins, and has additional
antioxidant property.
40. Rosuvastatin
This is another newer, commonly used and
potent statin (10 mg rosuvastatin ~ 20 mg
atorvastatin), with a plasma t½ of 18–24 hours.
Greater LDL-CH reduction can be obtained in
severe hypercholesterolaemia; partly due to its
longer persistence in the plasma.
In patients with raised TG levels, rosuvastatin
raises HDL-CH by 15–20% (greater rise than
other statins).
41. Potency of Statins
Potency Order for reduction in LDL-C:
Rosuva > Atorva > Simva > Lova > Prava >
Fluva
Potency Order for reduction in TG:
Atorva >Prava > Rosuva > Simva > Lova
>Fluva
Potency Order for increase in HDL-C:
Prava >Simva > Rosuva = Fluva = Lova >
Atorva
42. HMG-CoA reductase activity is
maximum at midnight, so all statins are
administered at bed time to obtain
maximum effectiveness.
However, this is not necessary for
atorvastatin and rosuvastatin, which
have long plasma t½.
All statins, except rosuvastatin are
metabolized primarily by CYP3A4.
44. Interactions
Enzyme inducers (Phenytoin, Rifampicin,
Greisofulvin, Phenobarbitone)
Reduces the plasma concentration of statins
metabolized by CYP3A4 (Lovastatin,
Simvastatin, Atorvastatin)
Simulataneous consumption of grape or its juice
Increases the plasma levels of statins.
46. Therapeutic Uses
Primary hyperlipidaemias with raised LDL and
total CH levels, with or without raised TG
levels (Type IIa, IIb, V),
Secondary hypercholesterolaemia- (diabetes,
nephrotic syndrome)
47. Bile Acid Sequestrants
Mechanism of Action
Bile acid sequestrants are polymeric compounds
that serve as ion-exchange resins.
Bile acid sequestrants exchange anions such
as chloride ions for bile acids.
By doing so, they bind bile acids and sequester
them from the enterohepatic circulation.
The liver then produces more bile acids to
replace those that have been lost.
Because the body uses cholesterol to make bile
acids, this reduces the amount of LDL
cholesterol circulating in the blood.
48. Pharmacokinetics
Bile acid sequestrants are large polymeric
structures, and they are not significantly
absorbed from the gut into the bloodstream.
Thus, bile acid sequestrants, along with any
bile acids bound to the drug, are excreted
via the feces after passage through the
gastrointestinal tract.
51. Interactions
Cholestyramine and
colestipol bind and interfere
with the absorption of many
drugs
They reduce the absorption
of vitamins
Thiazides
Furosemide
Propranolol
L-thyroxine
Digoxin
Warfarin,
Statins(Pravastatin
and Fluvastatin).
Vitamin K
Folic Acid
Ascorbic Acid
Severe
Hypertriglyceridemi
a- Increase TG
levels
Contraindications
53. Mechanism of Action
Fibrates reduce TG- activate a nuclear receptor-
PPAR alpha
Stimulates beta oxidation of Fatty Acids
Increase LPL synthesis
Reduce production of Apo C3
Inhibits Lipolysis and receptor mediated clearance.
VLDL clearance is enhanced
54. Fibrate-mediated increases in HDL-C are due to
PPAR stimulation of apoA-I and apoA-II
expression, which increases HDL levels.
PPARα may also mediate enhanced LDL
receptor expression in liver seen particularly with
second generation fibrates like bezafibrate,
fenofibrate.
Fibrates decrease hepatic TG synthesis as well.
55. Pharmacokinetics
All of the fibrate drugs are absorbed rapidly and
efficiently (>90%) when given with a meal but
less efficiently when taken on an empty
stomach.
The ester bond is hydrolyzed rapidly.
Peak plasma concentrations -within 1-4 hours.
The t1/2 ranges from 1.1 hours (gemfibrozil) to
20 hours (fenofibrate).
The fibrate drugs are excreted predominantly
as glucuronide conjugates; 60-90% of an oral
dose is excreted in the urine.
59. Niacin –Pyridoxine-3-
carboxylic acid
Water soluble vitamin B
complex group
One of the oldest drug used in
the treatment of dyslipidemia
LIPOLYSIS AND TRIGLYCERIDE
SYNTHESIS INHIBITOR (Niacin)
60. Mechanism of Action
In adipose tissue, niacin inhibits the lipolysis of
triglycerides by hormone-sensitive lipase- reduces
transport of free fatty acids to the liver and
decreases hepatic triglyceride synthesis.
Acting on GPR109A, niacin stimulates the Gi–
adenylyl cyclase pathway in adipocytes, inhibiting
cyclic AMP production and decreasing hormone-
sensitive lipase activity, triglyceride lipolysis, and
release of free fatty acids.
Niacin also may inhibit a rate-limiting enzyme of
triglyceride synthesis, diacylglycerol
acyltransferase-2.
61. In the liver, niacin reduces triglyceride synthesis
by inhibiting both the synthesis and
esterification of fatty acids, effects that increase
apoB degradation.
Reduction of triglyceride synthesis reduces
hepatic VLDL production-reduced LDL levels.
Niacin also enhances LPL activity-promotes
clearance of chylomicrons and VLDL
triglycerides.
62. Niacin raises HDL-C levels by decreasing the
fractional clearance of apoA-I in HDL rather than
by enhancing HDL synthesis.
This effect is due to a reduction in the hepatic
clearance of HDL-apoA-I, but not of cholesteryl
esters, thereby increasing the apoA-I content of
plasma and augmenting reverse cholesterol
transport.
64. Interactions
Postural hypotension may occur in patients on
antihypertensives when they take nicotinic acid.
Risk of myopathy due to statins is increased.
Contraindication
s
Diabetes Mellitus
Peptic Ulcer
Pregnancy
Gout
65. It is a novel drug that acts by inhibiting
intestinal absorption of cholesterol and
phytosterols.
Ezetimibe
( Cholesterol Absorption Inhibitor)
N
OH
O
F
OH
F
EZETIMIBE
66. Mechanism of action
Lowers plasma cholesterol levels by inhibiting the
absorption from intestine
This cause a decrease in the cholesterol delivery to
the liver which in turn clears more cholesterol from
the blood.
Selective action (( not interfere with TGs, lipid-
soluble vitamins absorption))
67. • Monotherapy or in combination with HMGRI for
reduction of elevated total cholesterol.
Therapeutic uses
Important Points
Should not be given
with Resins
Should not be given in
pregnancy
69. LDL oxidation inhibitor:
Probucol
Acts by inhibiting the synthesis of sterols.
Inhibits atherogenesis- Antioxidant action
Reduces LDL as well as HDL.
Used in patients of severe atherosclerosis with
hypercholestrolemia.
Cardiotoxicity
HDL-C is decresed.
70. Gugulipid
Guggul is made from the sap (gum resin) of the
Commiphora mukul tree, which is native to India.
Reduces the sectretion and enhances the
excretion of cholesterol.
VLDL,LDL,TG are reduced.
HDL is incresed
Used is type 2b and Type 4 hyperlipidemia.
73. CETP-INHIBITORS
The cholesteryl ester transfer protein (CETP)
facilitates exchange of CHEs with TGs
between HDL particles and chylomicrons,
VLDL, LDL, etc.
It plays an important role in the disposal of
HDL-associated CH.
Inhibitors of this protein, torcetrapib,
anacetrapib, etc. markedly raise HDLCH and
lower LDL.
74. They were presumed to have
antiatherosclerotic action.
However, during a large randomized clinical
trial, torcetrapib was found to increase
cardiovascular events like angina, MI, heart
failure and death.
The trial and further development of the drug
was stopped in 2007.
Whether other CETP inhibitors will have
therapeutic value is being investigated, but
75.
76. Statin + Niacin- Type 2a and 2b
Can be used for incresed LDL and decreased
HDL levels.
Statins + Ezetimibe- Synergistic combination for
Primary Hypercholestrolemia and Type2a
Statins + Fibrates- High risk patients on Statin
therapy having increased TG levels as their main
lipid abnormality.
Patient treted with this combination must be
observed for Myopathy.
77. Bile Acid Binding Resin + Fibrates- Type 2b.
Increased risk of Cholelithiasis.
Bile Acid Binding Resin + Niacin- Type 2a and
2b.
Resin has neutralizing action which
reduces gastric irritation caused by niacin.
Resin + Statins- Reduces LDl-C in Type 2a
Statins should be given one hour before or
four hours after the resin to ensure proper
absorption.
Resin+ Statin +Niacin- Used in severe disorders
due to increased levels of LDL- Type 2a and
2b.
Learning Outcomes
29.1 Explain the importance of triglycerides and cholesterol and their role in atherosclerosis.
aIf pretreatment LDL-C is near or below LDL-C goal value, then a statin dose sufficient to lower LDL-C by 30-40% should be prescribed. bPatients in this category include those with a 10-year risk of 10-20% and one of the following: age >60 years, three or more risk factors, a severe risk factor, triglycerides >200 mg/dL and HDL-C <40 mg/dL, metabolic syndrome, highly sensitive C-reactive protein (CRP) >3 mg/L, and coronary calcium score (age/gender adjusted) >75th percentile. cPatients include those with any severe single risk factor, multiple major risk factors, 10-year risk >8%.
By inhibiting intracellular isoprenoids formation, statins suppress vascular and myocardial inflammation
they also reduce T-cell activation, macrophage infiltration, vascular wall inflammation, and promote plaque stabilization