Hypolipidemic agents, also known as cholesterol-lowering drugs or antihyperlipidemic agents, are a diverse group of pharmaceuticals that are used in the treatment of high levels of fats (lipids), such as cholesterol, in the blood (hyperlipidemia). They are also called lipid-lowering drugs.
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
Hypolipidemic agents, also known as cholesterol-lowering drugs or antihyperlipidemic agents, are a diverse group of pharmaceuticals that are used in the treatment of high levels of fats (lipids), such as cholesterol, in the blood (hyperlipidemia). They are also called lipid-lowering drugs.
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
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.
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2019 JUNE UPDATED AMERICAN COLLEGE OF CARDIOLOGY GUIDLINES FOR MANAGEMENT OF DYSLIPIDEMIA
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TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
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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
Prix Galien International 2024 Forum ProgramLevi Shapiro
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- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
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
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
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Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
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- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
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Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
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2. CONTENTS
LIPID AND ITS METABOLISM
TYPES OF HYPERCHOLESTEROLEMIA
DIAGNOSIS
ANTIHYPERLIPIDEMIC DRUGS
3. LIPID METABOLISM
Lipids - Esters of fatty acids and alcohols
Lipoprotein - They are spherical particles that
transport neutral lipids that is TG and CH in blood.
4. Apolipoprotein : A protein that binds to lipids
Cholesteryl ester : A compound of cholesterol
and a fatty acid
Triglycerides : A compound of glycerol &
three fatty acids,
Over 93% of the fat that is consumed in
the diet is in the form of triglycerides (TG).
5. Cholesterol
• Dietary intake supplies only about 20 –25% of the
cholesterol needed everyday to:
• Build cell membranes
• Synthesize bile acids/salts
• Synthesize hormones of the adrenal glands
aldosterone , cortisol
• Synthesize the sex hormones (Estrone ,
Testosterone)
• The other 75 –80% of our daily need for cholesterol
is synthesized in the liver.
7. Source of Lipids:
I. Endogenous lipids
• Synthesized in the liver
• Liver synthesizes TG and cholesterol , packages
them as VLDLs before releasing them into the
blood
II. Exogenous lipids
• Ingested and processed in the intestine.
• Dietary cholesterol & triglycerides ,packaged into
chylomicrons in the intestine, released into
bloodstream via lymphatics.
17. Apolipoprotein B synthesis Inhibitor
• Mipomersen
Microsomal triglyceride transfer protein inhibitor
• Lopitamide
18. STATINS
Among the biggest selling class of Pharmaceutical
compounds of all time with annual sale in excess of 20.5
Billion US dollars.
It’s HMG-CoA-Reductase Inhibitors (Rate Limiting)
Production of this enzyme and of LDL receptors is
transcriptionally regulated by the content of cholesterol in
the cell.
Drugs
MEVASTATIN
ATORVASTAIN
LOVASTATIN
FLUVASTATINS
PRAVASTATIN
ROSUVASTATIN
SIMVASTATIN
PITAVASTATIN
21. 1. Stone NJ, Robinson J, Lichtenstein AH, et al. ACC/AHAguideline on the treatment of blood cholesterol to reduce athero
sclerotic cardiovascular risk in adults: a report of the AmericanCollege of Cardiology/American Heart Association Task Force1.
23. Blood Glucose
• High-dose statins led to statistically significant
increase in blood glucose level - The PROVE-IT–TIMI trial
• JUPITER trial, those randomized to rosuvastatin showed
a significant increase in HbA1c (p=0.001) and in
newly diagnosed diabetes mellitus (relative risk 1.25;
p=0.01).
Circulation: Cardiovascular Quality and Outcomes. 2009;2:279-285
Sleep
• Significant reductions in average sleep quality were seen
with simvastatin.
24. Liver
• A meta-analysis of randomized, double-blind, head-to-
head, statin comparisons showed more LFT elevations
with higher dose statins.
Interaction with Fibrates –
• Gemfibrozil , amplify the risk of rhabdomyolysis on
statins.
1)Pranav Sikka, K. K. Saxena Statin Hepatotoxicity: Is it a Real Concern?
Heart Views. 2011 Jul-Sep; 12(3): 104–106
2)Wiggins BS1, Saseen JJ Gemfibrozil in Combination with Statins-Is It Really Contraindicated?
Curr Atheroscler Rep. 2016 Apr;18(4):18
25.
26.
27.
28. CHOLESTEROL ABSORPTION
INHIBITOR
EZETIMIBE
• Inhibits the luminal cholesterol uptake by
inhibiting cholesterol transport protein Nieman Pick
C1 like 1 protein.
• Dosage -10 mg orally once a day
• ↓ LDL-C 10-18%
30. Despite the established cholesterol-lowering benefits of
ezetimibe, significant controversy exists with respect to
ezetimibe’s vascular and clinical benefit.
31. FIBRATES
These are ligands for peroxisome proliferator
activated receptors (PPARs) increase expression of
lipoprotein lipase .
Activating Lipoprotein lipase, hence increasing
hydrolysis of TG in chylomicrons and VLDL particles
Dosage: 150mg once a day
Produce a modest decrease in LDL ( 10%) and
increase in HDL (~ 10%).But, a marked decrease in
TGs (~ 30%).
33. Adverse effects
• GIT disturbances.
• Gall stones increased billiary cholesterol
excretion.
• Muscle pain and myopathy , specially when
combined with statins
• Potentiate effects of oral anticoagulants
• Contraindicated in pregnancy, lactating women,
renal and hepatic dysfunction, gall stones.
34.
35. NICOTINIC ACID
Vitamin B3
Lipid-lowering properties require much higher
doses than when used as a vitamin.
• Vitamin dose -15-35 mg/day;
• Antihyperlipidemic activity 1-2 g, 3xtimes
day
Effective, inexpensive, often used in
combination with other lipid-lowering agents
38. Adverse effects
• Skin flushing
• Pruritus
• Abdominal discomfort
• Hepatotoxicity (rare but may be severe),
• Nausea
• Peptic ulcer
• Atrial fibrillation
• Glucose intolerance
Flushing can be diminished by taking an 350mg
aspirin about 30min before niacin
39. BILE ACID SEQUESTRANTS
They sequester bile acids in the GIT.
Prevent their reabsorption and enterohepatic
recirculation.
Drugs - Cholestyramine,
Colestipol
Colesevelam
Dosage - 1.875 g (3 tablets) PO q12hr with
meals
41. THERAPUTIC USES:
• Type IIA and IIB hyperlipidemias (along with
statins when response to statins is inadequate or
they are contraindicated).
• Useful for Pruritus in biliary obstruction (↑ bile
acids).
• Second generation BAS such as colesevelam and
colestimide have a glucose-lowering effect
42. ,
MD, PhD Franklin J. Zieve etal. Results of the glucose-lowering effect of WelChol study (GLOWS): A randomized, double-blind,
placebo-controlled pilot study evaluating the effect of colesevelam hydrochloride on glycemic control in subjects with type 2 diabetes.
clinthera.2007.01.003
,
43. CETP INHIBITORS (Cholesteryl
Esteryl Transport Protein) Inhibitors
Drugs
• Torcetrapib
• Dalcetrapib
• Evacetrapib
• Anacetrapib
CETP transfers cholesteryl ester from HDL to
VLDL or LDL .
Inhibition of this process results in higher HDL
levels and reduces LDL levels
49. APOLIPOPROTEIN B SYNTHESIS
INHIBITORS
• Antisense oligonucleotides
• ↓ LDL-C 21%, TC 19%, apo B 24%, and non-HDL-C 22%
in patients with HoFH.
• Dosing of 200 mg per week subcutaneously
MIPOMERSEN
52. ADVERSE EFFECTS
• Can cause increases in transaminases (ALT,AST).
• Causes increase in hepatic fat (steatosis) with or
without concomitant elevated transaminases,
which may be a risk for progressive liver
diseases.
• Only available through REMS program ( Risk
Evaluation and Mitigation Strategy )
53. Microsomal triglyceride transfer
protein (MTTP) INHIBITORS
LOMITAPIDE
• FDA Aproved_ dec 2012
• Dosage: Cap 5mg to 60mg once daily
• ↓ Up to LDL-C 40%, TC 36%,apo B 39%, TG 45%,
and non HDL-C 40%
54. MECHANISM OF ACTION MTTP INHIBITOR
MTTP INHIBITOR
•Inhibits the microsomal triglyceride transfer protein which is
necessary for VLDL assembly and secretion in the liver.
55.
56. PCSK9 INHIBITORS
A new era of lipid lowering therapy
PCSK9 is a secreted serine protease that binds to
the extracellular domain of the LDL receptor
and targets the LDL receptor to the lysosomal
compartment for degradation.
Consequently, PCSK9 prevents recycling of the LDL
receptor to the cell surface, thereby attenuating
LDL clearance
Drugs - Bococizumab , Evolocumab ,Alirocumab
Inclisiran
58. • Bococizumab is a monoclonal antibody that
inhibits PCSK9, a protein that interferes with the
removal of LDL.
• Failed in phase 3 clinical trial due to higher level of
immunogenicity and higher rate of injection site
reactions and no benifits over placebo.
BOCOCIZUMAB
59.
60. ALIROCUMAB
• It is a human monoclonal antibody
• FDA aproved_ july 2015
• Dosage: 75 mg SC every 2 weeks
may increase to 150 mg SC q2weeks
• Common side effects: nasopharyngitis, influenza, UTI
, diarrhea, bronchitis, and myalgia
61.
62. Evolocumab
• Evolocumab is a humanized monoclonal antibody
• FDA APROVED _ August 2015
• Dosage 140 mg subcutaneously every 2 weeks
or
420 mg subcutaneously once a month
• It cost about $14,300 USD per year
63.
64. Inclisiran
• Long-acting, synthetic, small-interfering RNA
molecule directed against PCSK9 .
• Subcutaneously delivered
• Comleted phase 2 clinical trial
• A single 300-mg injection of inclisiran plus statin
therapy achieved a mean 51% reduction in LDL
cholesterol and a second subcutaneous 300-mg
dose resulted in a 57% reduction in LDL
65.
66. Uses of PCSK9 INHIBITORS
• PCSK9 inhibitors should be considered for use in
combination with statin therapy for LDL-C lowering
in individuals with FH.
• PCSK9 inhibitors should be considered in individuals
with clinical cardiovascular disease who are unable
to reach LDL-C/non-HDL-C goals with maximally
tolerated statin therapy.
•They should not be used as monotherapy except In statin
intolerant individuals.
67. Take Home Message
Statins are wonder drugs that
have shaped the treatment of
hypercholesterolemia and
associated cardiovascular
diseases.
• Beyond statins many new agents
with promising results have
emerged but they are not in reach
68. MCQ
Q. White woman with diabetes 48 yr of age Total cholesterol
180 mg/dl, HDL cholesterol 55mg/dl,Systolic blood pressure
130 mm Hg ,Non smoker with calculated 10-yr risk of CHD
or stroke 1.8%, which of the following are to be started?
1. Atorvastatin 80mg
2. Rusovastatin 40mg
3. Atorvastatin 10mg
4. Fibrates
69.
70. Q. Which of the lipid lowering agents have
additional benefits in diabetes mellitus?
1 . Statins
2. CETP inhibitors
3. Bile acid sequestrants
4. Pcsk 9 inhibitors
71. Q Torcetrapib a CETP inhibitor having
promising antilipid effects was withdrawn
from trials for which of the following reasons?
1. High cost
2. No change in incidence of ASCVD
3. Hypertension
4. None of these
72. Q. Which of the following is a synthetic PCSK9
inhibitor?
1. Bococizumab
2. Inclisiran
3. Evolocumab
4. Alirocumab
73. Q. Skin flushing is a side effect of which of the
following?
1. Bile acid sequestrants
2. CETP inhibitors
3. Statins
4. Niacin
74. Q. PCSK 9 causes which of the following effects
in liver?
1. Increases LDL receptors
2. Decreases LDL receptors
3. Can cause both
4. Has no effects on LDL receptors