This document discusses the pharmacotherapy of dyslipidemia. It begins by defining dyslipidemia as disorders of lipoprotein metabolism that result in abnormal cholesterol and triglyceride levels, and describes lipoproteins. It then discusses the treatment of dyslipidemia, including lifestyle modifications and various drug therapies such as statins, fibrates, bile acid sequestrants, nicotinic acid, ezetimibe, PCSK9 inhibitors, and other newer therapies. It provides details on the mechanisms of action, uses, dosing, and side effects of these different drug classes.
SGLT2 Inhibitors (Gliflozins): A New Class of Drugs to treat Type 2 Diabetes:Naina Mohamed, PhD
Sodium-Glucose Linked Transporter 2 (SGLT2) inhibitors such as Dapagliflozin (Farxiga), Canagliflozin (Invokana) and Empagliflozin (Jardiance) are a new class of oral drugs available to treat type 2 diabetes mellitus (Type 2 DM).
SGLT2 Inhibitors (Gliflozins): A New Class of Drugs to treat Type 2 Diabetes:Naina Mohamed, PhD
Sodium-Glucose Linked Transporter 2 (SGLT2) inhibitors such as Dapagliflozin (Farxiga), Canagliflozin (Invokana) and Empagliflozin (Jardiance) are a new class of oral drugs available to treat type 2 diabetes mellitus (Type 2 DM).
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)
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)
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
Dyslipidemia management an evidence based approachDr Vivek Baliga
In this presentation by Dr Vivek Baliga, he discusses the different available statins and how you can choose the right one in different clinical situations. See articles from Dr Baliga on http://drvivekbaliga.net
Cardiovascular disease - more common in diabetic patients than in the general population
Dyslipidemia – common in patients with both types of diabetes.
Aggressive lipid treatment goals have been recommended for patients with type 2 diabetes
Diabetic Dyslipidemia is highly prevalent in the Indian diabetic population
Dyslipidemia in diabetes differs significantly with hypertriglyceridemia and small dense LDL-C
Dyslipidemia and Management of Dyslipidemia | Muhammad-Nizam-UddinMuhammad Nizam Uddin
Dyslipidemia and it's management is such a topic that one single PPT is not enough to express all sorts of problems or scopes. This PPT will give you an overview on "Dyslipidemia and it's management"
the study was a pilot study done at National Institute of Ayurveda under the Phd Research Programme with an aim to find out new avenues in the managegement of Dyslipidemia - Medoroga and Coronary Heart Disease - Hridroga, thus initiating a new concept of Preventive Cardiology through Ayurveda & Panchakarma
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.
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- 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
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
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!
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
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.
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
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
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
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
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.
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
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
2. Introduction
• Dyslipidemia – disorders of lipoprotein metabolism.
– Abnormal plasma cholesterol and/or Triglyceride (TG)
concentrations.
• Major cause of atherosclerosis and related cardiovascular
diseases.
6. Lipoprotein metabolism
• Transport of Dietary Lipids / Exogenous
Pathway
• Transport of Hepatic Lipids / Endogenous
Pathway
• Reverse Cholesterol Transport
12. Polygenic/Multifactorial
• IIb: Familial Combined (Polygenic)Hyperlipidemia
– Similar to IIa except VLDL ed
– Deficiency of LDL receptors and overproduction of VLDL by liver
• IV: Familial Hypertriglyceridemia
– Overproduction and/ or decreased removal of VLDL
13. Treatment strategies
1. Dietary and lifestyle modification (NCEP-ATP 4 guidelines)
• Aerobic exercise or brisk walking (20-60 min/d for 3-5 days/week)
• Reduce intake of cholesterol(<30% of total calories) and saturated
fats(5-6% of total calories)
• Reduce sugary beverage intake (<36 oz/wk), sweets
• Cessation of alcohol and smoking
2. Drugs
• Individualized approach
14. Drugs for dyslipidemia
A. Well established Anti-dyslipidemic therapies
– HMG-CoA (3-hydroxy-3- methyl glutaryl CoA) reductase inhibitors
– Fibric acid derivatives
– Bile acid sequestrants
– Nicotinic acid
– Inhibitor of dietary cholesterol uptake
B. Newly developed Anti-dyslipidemic therapies
– Proprotein Convertase Subtilisin/Kexin Type 9(PCSK9) inhibitors
– Inhibitor of ApoB Synthesis
– Microsomal Triglyceride Transfer Protein (MTP) inhibitors
– ApoC-III Synthesis inhibitors
– Gugulipid and fish oil derivatives
16. MOA
Inhibit HMG-CoA reductase competitively
(HMG-CoAMevalonic acid)
Inhibit biosynthesis of cholesterol
Depletion of cholesterol in hepatocytes
Activates Scap (SREBP cleavage activating protein)
Proteolytic cleavage of SREBP (Sterol regulatory element binding protein)
Translocates to nucleus
LDL-R expression on hepatocytes
ed hepatic uptake of LDL, IDL & decrease plasma LDL (20-55% )
(Major effect – dose and agent dependent
6% reduction with doubling of dose)
17. Decrease VLDL by :
• ↓ hepatic VLDL synthesis d/t ↓ in cholesterol ↓LDL-C(~25%)
Homozygous familial hypercholesterolemia (LDLR are absent)
Effect on TGs :
1. If TGs >250 mg/dL - % decrease ~ % decrease in LDL-C
2. If TGs <250 mg/dL - < 25% decrease in TG levels
in HDL ~15-20% (Rosuvastatin)
18. Pleiotropic effects:
• Improved endothelial function , NO
• Increase plaque stability
• Reduce lipoprotein oxidation
• Anti inflammatory role, ↓ CRP
• Reduce platelet aggregation, profibrinolytic activity
19. Pharmacokinetics
• Extensive first pass hepatic metabolism(uptake by OATP1B1)
• Simvastatin, Lovastatin : lactone prodrugs
• t1/2-1-4 hrs taken in evening
Atorvastatin, Rosuvastatin (~20 hrs),
Simvastatin (~12 hrs).
Dosing
• advisable to start each patient on a dose that will achieve the
patient's target goal for LDL-C lowering
20. Statins dose (mg) Required to Achieve Various
Reductions in LDL-C from Baseline
21. Adverse effects
• Myopathy:
o Myopathy–rhabdomyolysis–myoglobinuria–renal shut down
o High dose / Old age/ Perioperative period
o Hepatic/ renal dysfunction, Hypothyroidism
o Drugs: fibrates, especially gemfibrozil (OATP1B1 inhibition,
interferes with glucuronidation), erythromycin, cyclosporine,
itraconazole (CYP3A4)
o Fluvastatin (2C9) and pravastatin (unchanged) – less risk of
myopathy
o Niacinenhanced inhibition of skeletal muscle cholesterol
synthesis
22. • Hepatotoxicity :
• Elevation of transaminases.
• Severe hepatitis rare
• Monitoring recommended before starting therapy and at 2-3
months, then annually.
C/I : pregnancy & lactation.
• Pravastatin in children >8 yrs.
• Atorvastatin, Simvastatin and Lovastatin >11 yrs.
23. Use
• DOC for hypercholesterolemia
• Statins + Niacin = ed effectiveness but risk of myopathy
• Statins + resins = 20-30% greater reduction in LDL-C
• Statins + fibrates = useful when LDL associated with TG
• Atorvastatin and Rosuvastatin : max TG lowering effect
• Statin + resins + Niacin = 70% reduction in LDL-C
• Simvastatin + Ezetimibe = 60% reduction in LDL-C
24. Activators of PPARα – gene transcription regulator (expressed
primarily in liver and brown adipose tissue)
!st generation - Gemfibrozil (600-mg BD, 30 minutes
before morning and evening meals)
2nd generation - Clofibrate (~500 mg QID)
Fenofibrate (~145 mg OD)
Bezafibrate( ~200 mg TDS)
Fibric Acid Derivatives
25. MOA
• LPL synthesis : clearance of TG-rich lipoproteins
• Reduce expression of apoC-III (an inhibitor of lipolytic processing
and R-mediated clearance) thereby clearance of VLDL
• Reduce TGs (upto 50%) by stimulation of fatty acid oxidation
• in HDL-C(~15%): stimulation of apoA-I & apoA-II expression
• Misc. effect : inhibition of coagulation and fibrinolysis
26. Therapeutic Uses
• DOC
– Type III familial dysbetalipoproteinemia
– Severe hypertriglyceridemia
– Chylomicronemia syndrome
• Familial hypercholesterolemia type IIa
• Familial combined hypercholesterolemia type IIb
• triglycerides and low HDL-C levels associated with the
metabolic syndrome or type 2 diabetes mellitus
27. Adverse effects
• Abdominal discomfort/ Diarrhea/ Nausea.
• Increased risk of gallstones (clofibrate).
• Prolonged prothrombin time
• Myopathy :
• high risk when combined with statins (followed at 3 months).
• Gemfibrozil : highest incidence.
• Fenofibrate safer: glucuronidated by enzymes that are not
involved in statin glucuronidation
C/I
• Children & pregnant women
• Renal failure
28. • Safest as not absorbed from intestine
• Cholestyramine, colestipol, colesevelam
• MOA:
– Highly positively charged molecules that bind negatively
charged bile acids
– Due to large size, resins are not absorbed and bound bile acids
are excreted in stool
– Pool of bile acids is depleted
Bile Acid Sequestrants
29.
30. • The resin-induced decrease in BA is a/w in hepatic TG
synthesis. Monitoring (every 1-2 weeks) of fasting TG levels is
needed or their use in such patients should be avoided.
• 12-18% reduction in LDL-C.
• 40 – 60% reduction in LDL-C when used along with statin/ niacin
• 4-5% rise in HDL-C.
31. Therapeutic Uses:
• Heterozygous familial hypercholesterolemia
• Drug of choice for children and females in reproductive age group.
Dose :
• Cholestyramine 4g packet
• Colestipol 5g packet / 1g tab.
• Colesevelam 1.875 g packet/ 625 mg tab. (3 tab.)BD with meal
C/I- Hypertriglyceridemia
Mixed with water or
juice. Ideally, patient
should take resins BBF
and before supper,
starting with one
packet twice daily
32. Adverse effects
• Heart burn, dyspepsia, bloating, gritty sensation (suspending
powder in liquid several hours before ingestion)
• Malabsorption of Vitamin K, folic acid etc.
• Constipation (adequate water intake and psyllium)
• Rarely can cause hyperchloremic acidosis.
D/I:
• Binds to digoxin, warfarin, thyroxine, some statins, furosemide,
thiazides; prevents absorption 1 hr before or 3-4 hrs after
bile acid sequestrants.
33. Niacin (Nicotinic Acid)
• Oldest, effective, inexpensive, often used in combination
• Best agent available for increasing HDL-C (25-30%)
• Lowers TGs (40%), LDL-C (20-25%) in dose of 1.5-3 g/day
• Reduces Lp(a) levels significantly.
34. • LPL activity, clearance of chylomicrons and VLDL
• Inhibit a rate-limiting enzyme of TG synthesis, Diacyl Glycerol Acyl Transferase-2
Inhibits lipolysis of TGs by HS Lipases by inhibiting
adipocyte adenylyl cyclase
Decrease fractional
clearance of
Stimulates expression
of SR-CD36 & ABCA1
1.
2.
3.
4.
35. Therapeutic uses:
• Hypertriglyceridemia and high LDL-C associated with low HDL
• DOC for Familial combined hypertriglyceridemia
• Familial dysbetalipoproteinemia (type 3)
• Severe mixed hypertriglyceridemia(type 4)
• Heterozygous familial hypercholesterolemia (+ resins/statins)
Niacin Starting Dose Maximal Dose
Immediate release 100 mg TDS 1 g TDS
Sustained release 250 mg BD 1.5 g BD
Extended release 500 mg HS 2 g HS
36. Side effects
• Flushing, warmth (PGD2 & E2)
• Pruritus, rashes
• Dyspepsia
• Skin dryness
• Acanthosis nigricans
• Liver dysfunction (flu like fatigue)
• Hyperglycemia, Hyperuricemia
• Risk of myopathy if combined with
statins. (dose not >25% of
maximum)
C/I
• Peptic ulcer disease
• Gout
• DM
• Pregnancy
37. Ezetimibe
• Inhibition of cholesterol absorption by jejunal enterocytes (NPC1L1
transport protein) decrease in hepatic cholesterol
upregulation of LDL-R.
• Lowers LDL-C by 15-20%
• HDL-C by ~2% and decrease TGs by ~5%
• 10 mg tablet/day with statins
• Bile-acid sequestrants inhibit absorption of ezetimibeshould not
be co-administered
• ADRs: rare allergic reactions
39. • Alirocumab & Evolocumab (Approved in 2015)
– Heterozygous FH
– Lower LDL-C by 50-72% (effect persists for 2-4 weeks after
single S.C. injection)
– Lower PCSK9 activity upto 80%; Reduce Lp(a)
– Alirocumab: 75 mg SC q2weeks; If the LDL-C lowering response
is inadequate, may increase to 150 mg SC q2weeks
– Evolocumab: 140 mg SC q2weeks
• Bococizumab (Phase III)
• PCSK9 also involved in degradation of many receptors that are
also receptors for viruses (human rhinovirus and hepatitis C
virus) viral infections need to be monitored in patients on
PCSK9 inhibitors
40. Inhibitor of ApoB Synthesis: Mipomersen
• Antisense oligonucleotide that inhibits ApoB-100 synthesis in liver
decrease VLDL & LDL-C
• Useful in heterozygous and homozygous FH who lack LDL-R
• 200 mg SC weekly: reduces apoB(33-54%), LDL-C(34-52%),
Lp(a)(24%)
• ADRs: severe injection site reaction, flu-like reactions, headache,
hepatotoxicity
• Approved for t/t of homozygous FH with restriction due to
hepatotoxicity available through restricted Risk Evaluation &
Mitigation Strategy(REMS) program
41. Microsomal Triglyceride Transfer Protein (MTP) inhibitors:
Lomitapide
• Bind and inhibit MTP from transferring TG to apoB in liver
decrease in VLDL & LDL-C
• Useful in homozygous FH who lack LDL-R
• Reduces LDL-C (42-50%)
• Dose: Initially orally 5mg/day 10, 20 40 upto 60 mg
• Approved for t/t of homozygous FH with restriction
hepatotoxicity available through restricted Risk Evaluation &
Mitigation Strategy(REMS) program
50. Disorders of reduced HDL-C
• Gene deletion in APO A5-A1-C3-A4 locus and coding mutation in
APOA1
• Tangier Disease (ABCA1 deficiency)
• Familial LCAT deficiency
51. 2. Therapies that HDL
– Cholestryl ester transfer protein (CETP) Inhibitors:
Dalcetrapib, Torcetrapib, Evacetrapib, Anacetrapib