Dr. Zaafran provides overview of the most common medications used to affect the sympathetic nervous system and their clinical applications.

Dr. Zaafran explores the various types of medications used to treat arrythmia. While basic pharmacology and pathophysiology are discussed, he also goes into clinical signs and symptoms and the standard of care in treatment.

Dr. Zaafran covers the key factors of anti hypertensive medications, their mechanisms, and how they are utilized in the clinical setting. Pharmacological principles are discussed for different types of agents, including:

- Adrenergic agents

- Angiotensin-converting enzyme (ACEI) inhibitors

- Angiotensin II receptor blockers

- Calcium channel blockers

- Diuretics

- Vasodilators

Presented by: Ahmed Zaafran, M.D. Dr. Zaafran presents the definition, management, and treatment of clinical hypertension.

Dr. Zaafran provides overview of the most common medications used to affect the sympathetic nervous system and their clinical applications.

Management notes

10% of the US population of 80 years of age and above suffer from atrial fibrillation. Sometimes atrial fibrillation is not noticed by the patient for a long time resulting in sufficient cardiac remodeling that establishing a sinus rhythm becomes very difficult. 

In this video talk, Dr. Syed discusses the definition, presentation, pathology, EKG, and salient points of management of the atrial fibrillation. Following aspects are discussed in detail:

1. Considerations for the treatment of the atrial fibrillation (AF.)
2. Cardioversion.
3. Anticoagulants and antiplatelets.
4. Antiarrhythmic.
5. Rate control.
6. Surgical approaches.

Considerations for Management

• Patient’s age and symptoms.
• Hemodynamic effects of the AF (LV function compromise, HF).
• Duration since the onset of the fibrillation.
  • <48 hours, unknown, >48 hours.
• Clinical stage of fibrillation.
  • Paroxysmal, persistent, permanent.
• Comorbidities.
• Risk of a cardiac incident.
• Risk of bleeding/stroke.
• Existing medication.

Electrical Cardioversion

• New onset AF associated with severe hypotension, pulmonary edema, and angina can be managed with electrical cardioversion. Usually, up to 48h of AF can be approached with cardioversion.
  • Assess the risk of stroke before cardioverting. (Use CHA2DS2-VASc score for assessment.)
    • Patients with prior embolic events, rheumatic mitral stenosis, hypertrophic cardiomyopathy with marked left atrial enlargement may not be cardioverted before careful consideration for the risk of stroke.
  • 200 Joule (sedation or anesthesia.)
    • Greater shock energy and different electrode placement may be tried if the shock fails to terminate AF.
    • If AF terminates and restarts then antiarrhythmic drugs (ibutilide) can be administered and then cardioversion attempted again.
• AF of unknown duration or greater than 48 hours must not be cardioverted. Following two choices are useful in such situations:
  • Give anticoagulants for 3 weeks before then cardiovert and then continue anticoagulants for at least 4 weeks after.
  • Perform transesophageal echocardiogram to detect a thrombus in the left atrial appendage. Cardiovert if there is no thrombus. Administer anticoagulants for at least 4 weeks after the cardioversion.
• Some patients may need continuous anticoagulation therapy instead of stopping after 4 weeks of cardioversion.

Medical Management

• Oral anticoagulants:
  • Vitamin K inhibitors.
  • Newer anticoagulants like:
    • Thrombin inhibitors (dabigatran.)
    • Factor Xa inhibitors (rivaroxaban, apixaban.)
  • Older anticoagulants like Warfarin are less used nowadays.
  • Immediate administration with Heparin is useful. This should give enough window of time to decide other therapies.
• Antiplatelet (Aspirin, Clopidogrel) have not shown efficacy for AF patients.
• Rate control:
  • Beta blockers.
  • Ca++ channel blockers. (Diltiazem, Verapamil.)
  • Na+/K+ ATPase inhibitor (Digoxin.) Especially when AV nodal blocking agent cannot be used.
• Rhythm Control (antiarrhythmic):
  • Class I
  • Class III

Anticoagulants/Stroke Prevention

• CHA2DS2-VASc score. (Indication of anticoagulants at a score of 2 or greater.)
  • Clinical Features:
    • CHF/LV Dysfunction: 1
    • HTN: 1
    • DM: 1
    • History of stroke, TIA or thromboembolism: 2
    • Vascular pathologies. History of MI, aortic atherosclerosis, PVD: 1
  • Age:
    • 65-74: 1
    • >= 75: 2
  • Sex:
    • Male: 0
    • Female: 1
• You can skip anticoagulants and antiplatelet, or administer Aspirin for a score of 0.
• Anticoagulants are administered at a score of 2 or higher, or to patients with prior history of stroke.
  • Anticoagulant may be considered even at a score of 1.
• Patients with rheumatic mitral stenosis or mechanical heart valves must receive vitamin K antagonists (Warfarin).
• Patients who have previously not received newer anticoagulants (Thrombin blocker and Factor Xa blockers) must get vitamin K antagonists as well.
• Keep in mind that 1% of the patients get intracranial hemorrhage or major bleeding that requires transfusion of fresh frozen plasma and vitamin K. (Monitoring is very important especially with the older anticoagulants.)
• Risk factors for bleeding are age >65-75 y, heart failure, anemia, excessive alcohol consumption, NSAID drugs usage, coronary stent patients on aspirin and a thienopyridine.
• Warfarin is superior to antiplatelet therapy.
  • It takes several days to achieve PT time/INR of greater than 2. Monitoring is needed. Hence newer anticoagulants are favored.
• Newer anticoagulants (dabigatran, rivaroxaban, and apixaban):
  • Shown marginal superiority over Warfarin (0.4%-0.7%.)
  • Promptly achieve the anticoagulant effect. Don’t need much dosage adjustment.
  • These are excreted by kidneys, hence severe renal failure patients cannot use these. Dose adjustment needed for modest renal failure.
  • •P-glycoprotein inducers and inhibitors also influence the excretion.
• Approach to the patient with paroxysmal AF and persistent AF is the same.
• Warfarin can be reversed by administering fresh frozen plasma and vitamin K.
• Reversing agents for the newer anticoagulants are lacking. However, they are excreted within 12 hours.
• Antiplatelet agents (aspirin, clopidogrel) are inferior to warfarin for stroke prevention in AF. Clopidogrel with aspirin is better than aspirin alone but have greater bleeding risk than aspirin alone.
• Chronic anticoagulants are contraindicated with patients with bleeding risks. In such patients, surgical removal of the left atrial appendage or catheter ablation is indicated.

Chronic Rate Control

• Usual goal is resting heart rate of <80 bpm and <100 bpm with light exertion (walking).
  • Note: if rate control is difficult then up to 110 bpm resting heart rate is acceptable provided symptoms are tolerable and ventricular function is normal.
• Rate control is important to alleviate symptoms and prevent ventricular damage due to chronic tachycardia.
• Rate control is important to also reduce the pace of or to prevent cardiac remodeling.
• Beta blockers, calcium channel blockers, and digoxin are used. Sometimes in combination.
• Rate control is incorrect if the patient experiences exertion related symptoms.
• If rate control fails with medications then catheter ablation is indicated. Sometimes AV Junction is ablated with a pace maker to manage ventricular rate. Sometimes there may be dyssynchronous ventricular rate for which biventricular pacing will be indicated.

Rhythm Control

• Rhythm control strategy includes the decision to administer antiarrhythmic or catheter ablation.
• Patient’s preference in light of risk and benefits is the guiding principle.
• Usually, the strategy is selected for following patients:
  • Symptomatic paroxysmal AF.
  • First episode of symptomatic persistent AF.
  • AF with difficult rate control i.e. patients that have structural changes.
  • AF compromising ventricular function.
  • AF aggravating heart failure.
• AV-nodal blocking agents are used.
• B-Adrenergic blockers and calcium channel blockers are used.
• These drugs help maintain sinus rhythm, improve symptoms, and have a low-risk profile. These drugs, however, have low efficacy to prevent AF episodes.
• Class I Na+ channel blockers (flecainide, propafenone, disopyramide) can be used if there is no significant structural heart change.
  • These have negative inotropic and proarrhythmic effect. Cannot be used in patients with coronary artery disease or patients with heart failure.
• Class III (sotalol and dofetilide) can be given to the patients with coronary artery disease.
  • 3% patients can develop prolonged QT and induce torsades des pointes.
  • Dofetilide should only be administered in a hospital with ECG monitors. Many physicians take the same approach with sotalol.
  • Amiodarone maintains sinus rhythm better in two-thirds of the patients.
    • It is also used after the open heart surgery to prevent a sudden onset of AF. 2g given over 2 days.
    • p-glycoprotein inhibitor.
    • Contraindicated in patients with heart block or SA node dysfunction. (Due to its class IV like behavior.)

Surgical Approach

• In patients with long standing AF (usually > 1 year) enough structural changes occur to the atrial tissue that reentrant circuits become permanent. In such patients, cardioversion will fail. If patient’s symptoms are disrupting their quality of life with permanent reentry circuits then catheter ablation is used.
• Catheter ablation can be done in two ways:
  • Usually, the tissue around the pulmonary veins is ablated trapping the reentrant signals in these areas.
  • If the restructuring is extensive, then a maze like path is formed in the atrial tissue that guides the impulse travel and prevents re-entry.
• In rare cases, catheter ablation can cause cardiac tamponade, stroke, esophageal injury, SA node injury requiring a pacemaker, and death.

Disclaimer

• All information contained in and produced by the drbeen corp., is provided for educational purposes only. This information should not be used for the diagnosis or treatment of any health problem or disease.
• THIS INFORMATION IS NOT INTENDED TO REPLACE CLINICAL JUDGMENT OR GUIDE INDIVIDUAL PATIENT CARE IN ANY MANNER.

In this lecture, we review the physiology of cardiac contraction and the cellular mechanisms involved in that process, including adrenergic receptors. Multiple inotropic and vasoactive agents are discussed in detail. Clinical examples are provided at the end of the lecture

In this lecture, we review the physiology of cardiac contraction and the cellular mechanisms involved in that process, including adrenergic receptors. Multiple inotropic and vasoactive agents are discussed in detail. Clinical examples are provided at the end of the lecture

Low Dose Naltrexone (LDN) - Mechanism of Action

LDN is used for chronic diseases, multiple sclerosis, autoimmune thyroid disease, and various cancers. Let's review its mechanism of action.

Disclaimer:
This video is not intended to provide assessment, diagnosis, treatment, or medical advice; it also does not constitute provision of healthcare services. The content provided in this video is for informational and educational purposes only.
Please consult with a physician or healthcare professional regarding any medical or mental health related diagnosis or treatment. No information in this video should ever be considered as a substitute for advice from a healthcare professional.

URL list from Wednesday, Feb. 2 2022

Naltrexone | Naltrexone - Bupropion Combination - Mechanism of Action
https://psychscenehub.com/psychinsights/naltrexone-naltrexone-bupropion-combination-mechanism-of-action-psychopharmacology-and-clinical-application-2/

IL-6 in Inflammation, Immunity, and Disease - PMC
https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC4176007/

Ventral tegmental area - Wikipedia
https://en.wikipedia.org/wiki/Ventral_tegmental_area

Mesolimbic pathway - Wikipedia
https://en.wikipedia.org/wiki/Mesolimbic_pathway

Striatum - Wikipedia
https://en.wikipedia.org/wiki/Striatum#Structure

Frontiers | Naltrexone Inhibits IL-6 and TNFα Production in Human Immune Cell Subsets following Stimulation with Ligands for Intracellular Toll-Like Receptors | Immunology
https://www.frontiersin.org/articles/10.3389/fimmu.2017.00809/full

In this amazing research, the researchers from the Boston Children's Hospital demonstrate for the first time ever the presence of 3D shape sensing proteins in the bacteria. These sensors help bacteria recognize the DNA packaging enzymes of the infecting bacteriophage.

Dr. Syed presents the first session on the management of type 2 diabetes mellitus. Following topics are covered: *Sources of glucose and contribution from carbs, fats, and proteins. *Is it useful to go to protein high or fat high diets? Or is it useful to cut carbs? *What is the effect of combining carbs with proteins and carbs with fats to the glucose peak that occurs after a meal? Does it matter from a therapeutic point of view? *What is the final common pathway of energy production from the three macro classes of the food - namely, proteins, fats, and carbs.

Dr. Syed discusses properties, mechanism of action, metabolism, clinical use, dosage, side effects, and contraindications for biguanides/Sulfonylureases.

Dr. Syed presents glucose absorption inhibitors. Drugs discussed are: Acarbose Miglitol Type II Diabetes Mellitus management algorithm is also reviewed.

Dr. Mobeen presents a clinician's approach to manage a type II diabetic patient. Following topics are discussed:

• Lifestyle management:
  • Couseling
  • Diet
  • Exercise (150 mins per week.)
• American diabetic academy (ADA) 2016 guidelines.
• Metformin as the first line drug.
• Discussion of mono, dual, tripple, and combination therapy with insulin.
• Why combine metrormin with meals?
• Metformin's half life.
• Metformin's dose.
• Metformin's function:
  • Hepatocyte effects.
  • Reduced gluconeogenesis.
  • Reduced lipogenesis.
  • Block lactic acid uptake.
• A visual mnemonic to remember metformin and glitazones.
• Considerations for patients that may have heart failure, renal failure, or perform rigorous exercises while taking metformin.
• Why metformin is not indicated in type I diabetes mellitus?
• B12 absorption reduction due to Ca++ channel blockade by metformin.

Dr. Mobeen presents the approach to managing a type II diabetic patient. Following classes of drugs are presented:

• Drugs that increase the levels of inuslin (insulin secretogogues).
  • Drugs that work on the beta cells.
  • Sulfonylureases.
    • Potassium channel blockade causing deploraization of a beta cell leading to the secretion of insulin.
  • Incretins.
    • GLP1
    • GIP
    • Exanatide
• Drugs that increase peripheral sensitivity to insulin.
  • Metformin
    • First line drug for managing type II diabetes mellitus.
    • Mechanism of action of metformin.
    • Actions of metformin on hepatocyte:
      • AMPK levels increased leading to the reduced cAMP levels. This reduces PKA levels. This leads to increased glycolysis and reduced gluconeogenesis.
      • FFA are reduced leading to increased insulin sensitivity.
      • Improves function of the insulin receptors.
      • Improves glucose transport inside the cell.
  • TZDs
    • Work on the lipid cells.
    • Open the genes in lipid and muscle cells leading to increased sensitivity to insulin.
    • LPL receptors are increased in density. Imprving triglyceride levels. Cholestrol levels are not improved.
    • Number of lipid cells increase. Lipogenesis increases. (Not a good effect. However, lipid storage will increase reducing glucose levels temporarily.)
• Drugs that increase ejection of the glucose from the gut. That is, reduce its absorption from the gut.
  • Alpha glucosidase enzyme's role.
  • Function of Acarbose.
  • Acarbose binding to alpha glucosidase. Preventing glucose polymer breakdown.
  • Diahrrhea, gas, discomfort, abdominal pain dur to increased glucose levels in the large intestine.
• Drugs that eject glucose in urine.
  • Sodium glucose co transporter type 2 (SGLT2) inhibitors.
  • Increased risk of UTIs especially in women.
  • Polyuria. Low blood volume leading to thirst and postural hypotension.
• Role of diet to reduce intake of glucose.
• Role of exercise to increase glucose uptake in the peripheral tissues.

Dr. Syed presents Patient groups in light of the ACC/AHA guidelines. Statin prescription intensities. Prescription approach for various groups. Criticism of the ACC/AHA guidelines. Mobeen's summary of managing a patient with dyslipidemias. Disclaimer: these lectures are to inform healthcare workers and patients for the possible management approaches. Each patient needs to be individually assessed, tested, diagnosed and treated in light of their unique presentation. These lectures do not have a prescription for any specific patient.

In this lecture Dr. Syed presents the following topics about Insulin: 
1. Structure, synthesis, and maturation of an insulin molecule. 
2. Components of a vesicle containing the insulin molecule. 
3. Immunogenic components that may be present in the insulin containing vesicle. 
4. Insulin release mechanism. 
5. Physiological factors that regulate insulin. 
6. Pharmacological factors (drugs) that regulate insulin. 
7. Glucagon-Like Peptide Hormones (GLP) 
8. Gastric Inhibitory Peptide (GIP) 
9. Effect of autonomic system on insulin release 
10. Effect of stress on insulin release

11. Effect of drugs on insulin release

In this part of the insulin therapy webinar, Dr. Mobeen presents:

• Insulin types
• Differences among various types of insulin.
• Mnemonic to remember insulin types.
• Objectives of the insulin therapy.
• Considerations for the dose adjustment.
• Insulin dose adjustment considerations for various physiological or pathological conditions. For example:
• Pregnancy
• Exercise
• Obeseity
• Various eating habits.
• Hospitialized patient.
• Patients with infections.
• Elderly.
• Patients with chronic kidney disease.
• Patients with liver disease.
• The dawn phenomenon.
• The somogyi effect.
• Dose calculation:
  • Total daily insulin (TDI)
  • Calculating basal insulin dose/units.
  • Calculating bolus insulin dose/units.
• Insulin therapy types:
  • Intensive insulin therapy.
  • Conventional insulin therapy.
  • Sliding scale insulin therapy.
• Insulin injection sites and their properties:
  • Abdomen
  • Thighs and buttocks
  • Arms
• Insulin syringes.
• Insulin mixing.
• Insulin filling in the syringe.

Ozempic and Wegovy have Semaglutide as the active agent. Semaglutide is a synthetic GLP-1 molecule that is modified to bind reversibly with albumin. This allows the slow release of these products. These drugs are also modified to escape the rapid inactivation by DPP4. Ozempic is approved for the management of type II diabetes mellitus and protection against cardiovascular events like death, stroke, and heart attacks in diabetic patients with cardiac comorbidities. Wegovy is approved for weight loss in obese and overweight individuals and also approved for protection against cardiovascular events like death, stroke, and heart attack in obese or overweight individuals with cardiovascular comorbidities.

Semaglutide helps regulate blood glucose, slows gastric emptying, produces the feeling of satiety, and acts on area postrema in medulla oblongata to cause nausea.

Objectives of this talk are:
1. What are incretins?
2. What is GLP-1?
3. What are Semaglutides?
4. Approval for Ozempic and Wegovy.
5. Blood glucose regulation by Semaglutides.
5. Slow gastric emptying (ileal brake) by Semaglutides.
6. Effects of Semaglutides on the brain tissue to produce satiety and nausea.
7. Dosage of Semaglutide for glucose regulation vs. weight loss.
8. Blackbox warning.
9. Side effects.
10. Explanation of the side effects.

FDA Approves First Treatment to Reduce Risk of Serious Heart Problems Specifically in Adults with Obesity or Overweight | FDA
https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-reduce-risk-serious-heart-problems-specifically-adults-obesity-or

Ozempic for weight loss: Does it work, and what do experts recommend?
https://health.ucdavis.edu/blog/cultivating-health/ozempic-for-weight-loss-does-it-work-and-what-do-experts-recommend/2023/07


Semaglutide delays 4-hour gastric emptying in women with polycystic ovary syndrome and obesity - PubMed
https://pubmed.ncbi.nlm.nih.gov/36511825/

The metabolic role of vagal afferent innervation | Nature Reviews Gastroenterology & Hepatology
https://www.nature.com/articles/s41575-018-0062-1

Glucagon-like peptide-1 inhibits gastropancreatic function by inhibiting central parasympathetic outflow | American Journal of Physiology-Gastrointestinal and Liver Physiology
https://journals.physiology.org/doi/full/10.1152/ajpgi.1998.275.5.G984

Risk of Gastrointestinal Adverse Events Associated With Glucagon-Like Peptide-1 Receptor Agonists for Weight Loss | Gastroenterology | JAMA | JAMA Network
https://jamanetwork.com/journals/jama/fullarticle/2810542


Wegovy® Pen Instructions | Wegovy® (semaglutide) Injection 2.4 mg
https://www.wegovy.com/taking-wegovy/how-to-use-the-wegovy-pen.html

Wegovy: Uses, Side Effects and Weight Loss
https://www.drugwatch.com/drugs/wegovy/#:~:text=Wegovy%20carries%20a%20black%20box,same%20effects%20occur%20in%20humans.


Why Ozempic Causes Diarrhea and How to Manage Your Symptoms - GoodRx
https://www.goodrx.com/ozempic/diarrhea

Incretin - Wikipedia
https://en.wikipedia.org/wiki/Incretin

Glucagon-Like Peptide-1 Receptor Agonists for Chronic Weight Management - PMC
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10533252/

What Is an L-Cell and How Do We Study the Secretory Mechanisms of the L-Cell? - PMC
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8218725/

Enteroendocrine cell - Wikipedia
https://en.wikipedia.org/wiki/Enteroendocrine_cell#:~:text=in%20the%20duodenum.-,L%20cell,in%20the%20duodenum%20and%20jejunum.

What is ilial brake?
inslag.indd
https://scholarlypublications.universiteitleiden.nl/access/item%3A2956466/view

Cholinergic type medications are a mainstay in clinical practice today. Dr. Zaafran goes over the

• Basic physiology

• Pharmacology

• Usage of these medications in clinical practice.

Dr. Zaafran goes into clinical depth regarding respiratory drugs and their application in practice. 
Topics include: 

• Usage of bronchodilators
• Leukotriene inhibitors
• Mast cell stabilizers 
• Alpha and beta agonists 
• Cortoicosteroids 
• Anti-cholinergic agents

Dr. Zaafran goes into clinical depth regarding respiratory drugs and their application in practice. 
Topics include: 
Usage of bronchodilators
Leukotriene inhibitors 
Mast cell stabilizers
Alpha and beta agonists 
Corticosteroids
Anti-cholinergic agents.

In this lecture, Dr. Zaafran explores the clinical applications of anti-histamine medications.

What does the common cold look like?
What are the most common etiologies that lead to the common cold?
What the treatment regimens for the common cold?
What are anti-histamines and what are the types of receptors involved?
What body systems are affected by histamines and where are the receptors involved?
What is the Mechanism of Action of anti-histamines?
What are the side effects of anti-histamines?
 

In this lecture, Dr. Zaafran continues to explore the world of anti-histamines. In this presentation, he discusses:

-What are decongestants?
-What are the two main types used?
-Are there different administration modalities?
-What are the types of symptoms most often seen in patients requiring - 
 nasal decongestants?
-Discussion of cough physiology
-Different types of cough
- Mechanisms of anti-tussive (cough) medications
-What are the different types of anti-tussives?
-Review of the anti-tussive side effects

In this lecture, Dr. Zaafran continues to explore the world of anti-histamines. In this presentation, he discusses:

-What are decongestants?
-What are the two main types used?
-Are there different administration modalities?
-What are the types of symptoms most often seen in patients requiring - 
 nasal decongestants?
-Discussion of cough physiology
-Different types of cough
- Mechanisms of anti-tussive (cough) medications
-What are the different types of anti-tussives?
-Review of the anti-tussive side effects

Dr. Islam presents What is peptic ulcer disease? What causes peptic ulcer disease? What is the role of proton pump Inhibitors? What are the complications of PPIs?

Objectives:

Objectives of this lecture are:

• Pediatric vaccines and the diseases they help prevent.

• The typical primary pediatric vaccine schedule.

• Some myths about vaccination.

Mechanism of action of Penicillin and Vancomycin. Complete pharmacology of these drugs will follow later. 

Dr. Mobeen covers the following topics in this brief video: 
Penicillin-binding proteins 
Cell wall's N-acetylmuramic Acid N-Acetylglucosamine 
Bacterial defense against Penicillin
 

ICU Station and analgesia The armamentarium of the multimodule regiment for the ICU sedation while minimizing adverse effects. Definition Alpha and beta elimination. Context sensitive half-life Sedatives Analgesia Exam questions

This video presents the mechanism of action of the NO and the factors that trigger its release.

STUDY NOTES:

AUTOREGULATION - NITRIC OXIDE

Nitric Oxide is called an endothelium derived relaxing factor(EDRF) as it is released by the endothelium of the blood vessel. EDRF cause relaxation of the vascular smooth muscle, and as a result cause vasodilation of the blood vessel. The following factors contribute to the release of nitric oxide from the endothelium:

1) Blood travelling at high velocity causes a shearing effect on the wall of the blood vessels. As the endothelial cells endure a drag force produced due to friction. This results in a mechanical trigger which stimulates release of nitric oxide.

2) Vasoactive Amines are chemical mediators that mediate the release of nitric oxide.

3) The endothelium possesses Histamine H1 receptors that also take part in nitric oxide release.

4) Prostacyclins are also said to be responsible for the release of nitric oxide.

Mechanism of Action of Nitric Oxide 

Nitric oxide, when released, triggers the soluble guanylate cyclase or Guanyl cyclase to convert cGTP to cGMP. Theincreased levels of cGMP cause activation of cGMP dependent kinases which activate the enzyme Myosin Light Chain Phosphatase (MLCP). The activated MLCP enzyme in turn dephosphorylates myosin light chains which results in relaxation of the contractile apparatus. As a result, the vessels become dilated.

Atherosclerosis is the formation of fibromuscular plaques on the endothelium lining of the blood vessel. These atherosclerotic plaques render the endothelium non functional. The endothelium is therefore unable to produce sufficient amounts of nitric oxide. Consequently, the levels of cGMP reduce as less cGTP is converted to cGMP. This reduction in cGMP levels in turn leads to increased levels of Myosin Light Chain Kinases (MLCK) which are enzymes with activity opposite to that of MLCP. The contractile apparatus is activated as MLCK causes cross bridging of actins and myosin heads. The tension produced within the vascular smooth muscle as a result of the vascular smooth muscle contraction in turn causes vasoconstriction of the blood vessel.

Angiotensin II receptors are present on both the vessel endothelium and also the smooth muscle surrounding the blood vessel. Depending on the receptor activated, Angiotensin II can have vasodilating or vasoconstricting effects. At times these opposing effects are balanced out and one effect compensates for the other.   

• The vasoconstricting activity of Angiotensin II is mediated via two pathways. If Angiotensin II binds to the Gq-coupled receptors on the vascular smooth muscle, it will cause direct deactivation of MLCP enzyme. It also causes the production of IP3 which enables the release of calcium ions from the sarcoplasmic reticulum. The calcium ions activate MLCK. The activation of MLCK and inactivation of MLCP results in contraction of the smooth muscles surrounding the blood vessel. This is the vasoconstricting effect.

• The vasodilating effect of Angiotensin II occurs simultaneously to mitigate the vasoconstricting effects to some extent. This effect is mediated by binding of the Angiotensin II to its receptor on the vascular endothelium. This activation of endothelial Angiotensin II receptor cause active release of nitric oxide from the endothelium. This NO diffuses into the vascular smooth muscle and stimulates the activity of guanylate cyclase enzyme which converts cGTP to cGMP. The increases cGMP levels cause activation of the MLCP enzyme. The activated MLCP enzyme in turn dephosphorylates myosin light chains, which results in relaxation of the contractile apparatus of the blood vessel. As a result, the vessels become dilated.

Sildenafil (Viagra) is a drug that is used to treat erectile dysfunction. It is a Phosphodiesterase-5 (PDE-5) inhibitor. PDE-5 is an enzyme that binds to and cleaves cGMP. As a result, the half life of cGMP is reduced as its levels fall. Sildenafil acts by binding to PDE-5 and antagonizes its function. As a result, the cGMP levels remain high for a longer period of time. Therefore, the penile vasculature remains dilated and engorged with blood and, hence, erection is maintained.

How Dostarlimab Therapy Healed Colorectal Cancer

Link to the FDA channel: https://www.youtube.com/watch?v=DfdMsAqkneE

Disclaimer:
This video is not intended to provide assessment, diagnosis, treatment, or medical advice; it also does not constitute provision of healthcare services. The content provided in this video is for informational and educational purposes only.
Please consult with a physician or healthcare professional regarding any medical or mental health related diagnosis or treatment. No information in this video should ever be considered as a substitute for advice from a healthcare professional.

URL list from Wednesday, Jun. 8 2022

Rectal Cancer Disappears After Experimental Use of Immunotherapy | Memorial Sloan Kettering Cancer Center
https://www.mskcc.org/news/rectal-cancer-disappears-after-experimental-use-immunotherapy

PD-1 Blockade in Mismatch Repair–Deficient, Locally Advanced Rectal Cancer
https://www.nejm.org/doi/pdf/10.1056/NEJMoa2201445?articleTools=true

Study of Induction PD-1 Blockade in Subjects With Locally Advanced Mismatch Repair Deficient Solid Tumors - Full Text View - ClinicalTrials.gov
https://clinicaltrials.gov/ct2/show/NCT04165772

Dostarlimab - Wikipedia
https://en.wikipedia.org/wiki/Dostarlimab

Programmed cell death protein 1 - Wikipedia
https://en.wikipedia.org/wiki/Programmed_cell_death_protein_1

Structures of PD-1 with its ligands: Sideways and dancing cheek to cheek - PMC
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2492504/

Ectodomain - Wikipedia
https://en.wikipedia.org/wiki/Ectodomain

Treatment | Global Colon Cancer Association
https://www.globalcca.org/treatment

Colorectal Cancer Stages | Rectal Cancer Staging | Colon Cancer Staging
https://www.cancer.org/cancer/colon-rectal-cancer/detection-diagnosis-staging/staged.html

Potential New Killer Cells for Cancer Immunotherapy

This amazing find by the scientists from Memorial Sloan Kettering Cancer Center holds a lot of potential for immunotherapy of solid tumors. Let's review

Disclaimer:
This video is not intended to provide assessment, diagnosis, treatment, or medical advice; it also does not constitute provision of healthcare services. The content provided in this video is for informational and educational purposes only.
Please consult with a physician or healthcare professional regarding any medical or mental health related diagnosis or treatment. No information in this video should ever be considered as a substitute for advice from a healthcare professional.

URL list from Monday, Apr. 25 2022

FastStats - Older Persons Health
https://www.cdc.gov/nchs/fastats/older-american-health.htm

Trends in Causes of Death among Older Persons in the United States (October 2005)
https://www.cdc.gov/nchs/data/ahcd/agingtrends/06olderpersons.pdf

Cancer Immunosurveillance by Tissue-Resident Innate Lymphoid Cells and Innate-like T Cells: Cell
https://www.cell.com/cell/fulltext/S0092-8674(16)00003-9

Programme of self-reactive innate-like T cell-mediated cancer immunity | Nature
https://www.nature.com/articles/s41586-022-04632-1

Scientists identify potential new 'soldier' for cancer immunotherapy -- ScienceDaily
https://www.sciencedaily.com/releases/2022/04/220420133616.htm

About Us | Sloan Kettering Institute
https://www.mskcc.org/research/ski/about

New T cell immune response discovery points to ‘out-of-box’ cancer therapy options – Endpoints News
https://endpts.com/new-t-cell-immune-response-discovery-points-to-out-of-box-cancer-therapy-options/

Programme of self-reactive innate-like T cell-mediated cancer immunity
https://en.x-mol.com/paper/article/1516862209619566592

Immune Checkpoint Inhibitors - National Cancer Institute
https://www.cancer.gov/about-cancer/treatment/types/immunotherapy/checkpoint-inhibitors

nci-vol-10396-150.jpg (1500×1200)
https://www.cancer.gov/sites/g/files/xnrzdm211/files/styles/cgov_enlarged/public/cgov_image/media_image/2019-09/nci-vol-10396-150.jpg?h=30063a04&itok=DGHB7TA1

Immune checkpoint blockade therapy for cancer: An overview of FDA-approved immune checkpoint inhibitors - PubMed
https://pubmed.ncbi.nlm.nih.gov/29990692/

Definition of CTLA-4 - NCI Dictionary of Cancer Terms - National Cancer Institute
https://www.cancer.gov/publications/dictionaries/cancer-terms/def/ctla-4

776560.jpg (3120×2400)
https://nci-media.cancer.gov/pdq/media/images/776560.jpg

USCS Data Visualizations - CDC
https://gis.cdc.gov/Cancer/USCS/#/Demographics/

FCER1G - Wikipedia
https://en.wikipedia.org/wiki/FCER1G

Story of Ivermectin Nobel Prize

Ivermectin is a more effective modified form of Avermectin. Avermectin was discovered by Satoshi Omura and William C Campbell. They were awarded the Nobel prize in Physiology or Medicine 2015. Let's review the fascinating story of Ivermectin discovery and its benefit to humanity.

Press release
https://www.nobelprize.org/prizes/medicine/2015/press-release/

CDC
https://www.cdc.gov/parasites/lymphaticfilariasis/index.html

Filariasis (Elephantiasis and Hydrocele)
https://en.wikipedia.org/wiki/Wuchereria_bancrofti

River blindness (Onchocerciasis)a
https://en.wikipedia.org/wiki/Onchocerciasis
https://en.wikipedia.org/wiki/Onchocerca_volvulus

Streptomyces - the benefactor of the human race
https://en.wikipedia.org/wiki/Streptomyces

Disclaimer:
This video is not intended to provide assessment, diagnosis, treatment, or medical advice; it also does not constitute provision of healthcare services. The content provided in this video is for informational and educational purposes only.
Please consult with a physician or healthcare professional regarding any medical or mental health related diagnosis or treatment. No information in this video should ever be considered as a substitute for advice from a healthcare professional.

In this talk we will discuss the following topics:
Opioid receptor structure.
Second messenger system overview.
Desensitization: an immediate effect of opioid use on the receptors and the second messenger system.
Tolerance: days to a week after opioid use disorder the mechanism for sensitization to kick in.
Dependence: a need for opioid use due to severe pains leading to dependence. (See DSM-4 for an exhaustive diagnostic criteria)
Addiction and withdrawal: an addictive state. (See DSM-4 and DSM-5 for an exhaustive diagnostic criteria.)
Opioid receptor disposition.
Adaptation of intracellular signaling mechanism.
System level counteradaptation.
Differential tolerance development.

References:

Effects of Acute and Chronic Opiate Receptor Activation
Brunton, Laurence; Knollman, Bjorn; Hilal-Dandan, Randa. Goodman and Gilman's The Pharmacological Basis of Therapeutics, 13th Edition (Goodman and Gilman's the Pharmacological Basis of Therapeutics) (p. 1362). McGraw Hill LLC. Kindle Edition.

Receptor specificity of endogenous opioids and effects of receptor activation on neurons.
Brunton, Laurence; Knollman, Bjorn; Hilal-Dandan, Randa. Goodman and Gilman's The Pharmacological Basis of Therapeutics, 13th Edition (Goodman and Gilman's the Pharmacological Basis of Therapeutics) (p. 1358). McGraw Hill LLC. Kindle Edition.


FDA's recommendations for OUD:
Information about Medication-Assisted Treatment (MAT) | FDA
https://www.fda.gov/drugs/information-drug-class/information-about-medication-assisted-treatment-mat

Diagnostic criteria for opioid use dependence and opioid use disorder
The ASAM National Practice Guideline for the Treatment of Opioid Use Disorder – 2020 Focused Update
https://www.asam.org/quality-care/clinical-guidelines/national-practice-guideline?gclid=CjwKCAiAg9urBhB_EiwAgw88mZm1lh6sE-rLtgkJP3w3ij1KSUJ4PkKqNrISFpagDzlQbRitsIJFBhoCQJIQAvD_BwE

npg-jam-supplement.pdf
https://sitefinitystorage.blob.core.windows.net/sitefinity-production-blobs/docs/default-source/guidelines/npg-jam-supplement.pdf?sfvrsn=a00a52c2_2

Psychiatry Online | DSM Legacy
https://dsm.psychiatryonline.org/dsmPreviousEditions

APA_DSM_Changes_from_DSM-IV-TR_-to_DSM-5.pdf
https://www.psychiatry.org/File%20Library/Psychiatrists/Practice/DSM/APA_DSM_Changes_from_DSM-IV-TR_-to_DSM-5.pdf
 

Omega 3 is typically anti-inflammatory and omega 6 is typically proinflammatory. In this talk we will discuss the ratio of omega 6 to omega 3 and the nuances. We will also dive deep in understanding why omega 3 is anti-inflammatory and why omega 6 is proinflammatory. Finally, we will review why a continuous balance of omega 6 and 3 is needed instead of a short-term intervention.

Disclaimer:
This video is not intended to provide assessment, diagnosis, treatment, or medical advice; it also does not constitute provision of healthcare services. The content provided in this video is for informational and educational purposes only.
Please consult with a physician or healthcare professional regarding any medical or mental health related diagnosis or treatment. No information in this video should ever be considered as a substitute for advice from a healthcare professional.

The importance of the ratio of omega-6/omega-3 essential fatty acids - ScienceDirect
https://www.sciencedirect.com/science/article/abs/pii/S0753332202002536?via%3Dihub

The omega-6/omega-3 fatty acid ratio: health implications | OCL - Oilseeds and fats, Crops and Lipids
https://www.ocl-journal.org/articles/ocl/full_html/2010/05/ocl2010175p267/ocl2010175p267.html#:~:text=A%20target%20of%20omega%2D6/omega%2D3%20fatty%20acid%20ratio,evolutionary%20aspects%20of%20diet%2C%20neurodevelopment%20and%20genetics.

Serum Omega-6/Omega-3 Ratio and Risk Markers for Cardiovascular Disease in an Industrial Population of Delhi - PMC
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5598746/

Omega-3 versus Omega-6 fatty acid availability is controlled by hydrophobic site geometries of phospholipase A2s - PubMed
https://pubmed.ncbi.nlm.nih.gov/34474084/

Omega-3 comes in three molecular forms. Alpha linolenic acid (ALA) which can then be converted to docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). ALA is less directly important while DHA and EPA are essential for omega-3 effects. ALA conversion to DHA and EPA is less than 5%. Let's review some of the sources of EPA and DHA and compare the quantities needed for 1 g daily DHA and EPA.

Disclaimer:
This video is not intended to provide assessment, diagnosis, treatment, or medical advice; it also does not constitute the provision of healthcare services. The content provided in this video is for informational and educational purposes only.
Please consult a physician or healthcare professional regarding any medical or mental health-related diagnosis or treatment. No information in this video should ever be considered as a substitute for advice from a healthcare professional.
 

URL list from Friday, May. 17 2024 16:13 PM

Omega-3 Fatty Acids - Health Professional Fact Sheet
https://ods.od.nih.gov/factsheets/Omega3FattyAcids-HealthProfessional/

Omega-3 Fatty Acids - Consumer
https://ods.od.nih.gov/factsheets/Omega3FattyAcids-Consumer/#:~:text=The%20U.S.%20Food%20and%20Drug,DHA%20combined%20from%20dietary%20supplements.

Study links omega-3s to improved brain structure, cognition at midlife - UT Health San Antonio
https://news.uthscsa.edu/study-links-omega-3s-to-improved-brain-structure-cognition-at-midlife/

Are all n-3 polyunsaturated fatty acids created equal? - PMC
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3224740/

Merck’s Molnupiravir (EIDD-281) Effective Against SARS-COV-2

Molnupiravir is a nucleoside analog. It has shown to be able to cause mutations accumulation and the RNA replication errors during the virus replication in vitro and in mouse models (in-vivo).

Let’s look at the following
What is Molnupiravir?
What is EIDD-281?
What is a nucleoside and a nucleotide?
How is positive mRNA is replicated to a negative sense RNA and back again during the viral replication?
How does EIDD-281 disrupt this process?
Why is it better performing than Remdesivir?
It’s therapeutic dose is non cytotoxic.
Concerns about its toxicity in humans.

References
https://stm.sciencemag.org/content/12/541/eabb5883
https://en.wikipedia.org/wiki/Molnupiravir
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6848974/
https://en.wikipedia.org/wiki/Nucleoside
https://en.wikipedia.org/wiki/Nucleotide
https://www.reuters.com/article/us-health-coronavirus-merck-co/merck-says-study-shows-covid-19-drug-causes-quick-reduction-in-virus-idUSKBN2AY07U
https://clinicaltrials.gov/ct2/show/NCT04405739

Maraviroc Mechanism of Action (MOA)

Maraviroc is a potential antiviral drugs for the HIV-1 (R5 strain). Let’s review it’s mechanism of action. (See the side effects in the video and the description below. Also, review the references.)

About serious side effects of Maraviroc (Reference: https://clinicalinfo.hiv.gov/en/drugs/maraviroc/patient)
Note: Maraviroc can cause serious, life-threatening side effects. These include liver problems and severe skin rash and allergic reactions.

References:
Maraviroc
https://en.wikipedia.org/wiki/Maraviroc
Book: Goodman and Gilman
Maraviroc blocks the binding of the HIV outer envelope protein gp120 to the CCR5 chemokine receptor
Brunton, Laurence; Knollman, Bjorn; Hilal-Dandan, Randa. Goodman and Gilman's The Pharmacological Basis of Therapeutics, 13th Edition (Goodman and Gilman"S the Pharmacological Basis of Therapeutics) . McGraw-Hill Education. Kindle Edition. 
Location 54074

CCR5
https://en.wikipedia.org/wiki/CCR5
On monocytes
https://journals.lww.com/shockjournal/Fulltext/2019/11000/CCR5_Positive_Inflammatory_Monocytes_are_Crucial.16.aspx
CCR5 and Cytotoxic T cells
https://pubmed.ncbi.nlm.nih.gov/31034775/
CCR5 Receptor Antagonists
https://en.wikipedia.org/wiki/CCR5_receptor_antagonist#Drug_development
HIV.Gov
https://clinicalinfo.hiv.gov/en/drugs/maraviroc/patient
G-protein coupled receptors
https://en.wikipedia.org/wiki/G_protein-coupled_receptor
CCL5
https://en.wikipedia.org/wiki/CCL5

Low Histamine Diets for MCAS and Long COVID Patients

Let’s continue our discussion about the post-COVID syndrome (long haul syndrome.) In the talk today we will discuss foods that we can avoid and the foods that we should add to our routine to help identify histamine related triggers.

References:
https://eatbeautiful.net/low-histamine-low-oxalate-food-list-printable/
https://www.histamineintolerance.org.uk/private/treatment/
https://en.wikipedia.org/wiki/Histidine
https://en.wikipedia.org/wiki/Diamine_oxidase

IVIg A High Level Overview

Some KoolBeens have been asking about the IVIg and how do these products work. Today we will briefly talk about IVIg.

Mixing Vaccine Types - Oxford University Study

Oxford University is conducting vaccine type mixing for prime dose and the booster dose. In a preliminary data set they have printed the side-effects of mixing the vaccine types. Let’s review the initial reactogenicity data published in Lancet.

Some news: CDC says mask not required for fully vaccinated in certain situations. https://www.cdc.gov/coronavirus/2019-ncov/vaccines/fully-vaccinated.html

British airway is trialing highly intelligent 25 seconds saliva based coronavirus test. https://news.sky.com/story/covid-19-ultra-rapid-25-second-coronavirus-test-hailed-as-a-game-changer-in-british-airways-trial-12305272

Now to today’s topic 
Initial reactogenicity data printed in lancet
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)01115-6/fulltext

Link with the study protocols
https://comcovstudy.org.uk/study-protocol
Study protocol V5.0
https://comcovstudy.org.uk/files/com-covprotocolv5026-apr-2021finalpdf
Study protocol V2.1
https://comcovstudy.org.uk/files/com-cov2protocolv2123-apr-2021cleanpdf

Administration of Second Dose Of Moderna Vaccine After An Immediate Hypersensitivity Reaction to The First Dose

Immunologist have reported administration of the second dose of Moderna vaccine in a graded fashion with protective antibody titers to the patients that had immediate hypersensitivity reaction to the first dose.

Link to the case reports
https://www.acpjournals.org/doi/10.7326/L21-0104

Nasal Spray for Virus/SARS-COV-2 Reduction

A Canadian company has successfully run trials and tests to show that nitric oxide based nasal spray can reduce viral replication by 99.99% in 72 hours. Let’s look at this spray, the test results, and its mechanism of action for viruses.

Pre-read/watch
DrBeen’s discussion about N-AcetylCysteine
https://youtu.be/K8kKWgsGIU8

About Cysteine and Cystine
https://www.sciencedirect.com/topics/chemistry/sulfur-containing-amino-acid

saNotize nasal spray site.
https://sanotize.com/covid-19/

About NO
https://sanotize.com/why-nitric-oxide/

About neuraminidase inhibitors
https://en.wikipedia.org/wiki/Neuraminidase_inhibitor

About neuraminidase
https://en.wikipedia.org/wiki/Neuraminidase

About NO from Goodman Gillman for reference
Platelet activation and coagulation do not normally occur within an intact blood vessel. Thrombosis is prevented by several regulatory mechanisms that require healthy vascular endothelium. Nitric oxide and prostacyclin synthesized by endothelial cells inhibit platelet activation

Produced by activated helper T (TH) and natural killer (NK) cells, IFN-γ enhances the microbicidal activity of macrophages by inducing mammalian inducible nitric oxide synthase (iNOS, also called NOS2), thereby increasing their production of nitric oxide (NO) and their capacity to kill intracellular pathogens.

Brunton, Laurence; Knollman, Bjorn; Hilal-Dandan, Randa. Goodman and Gilman's The Pharmacological Basis of Therapeutics, 13th Edition (Goodman and Gilman"S the Pharmacological Basis of Therapeutics) . McGraw-Hill Education. Kindle Edition. 

How is AstraZeenca's COVID vaccine made?
DrBeen's series on coronavirus vaccines explained. In this brief review we will check out the production steps of the AstraZeneca vaccine.

AstraZeneca (Oxford college’s partner) has released the interim results for the trials conducting in the UK and Brazil.

https://www.astrazeneca.com/media-centre/press-releases/2020/azd1222hlr.html

Safety data study
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)32466-1/fulltext

AstraZeneca Vaccine is 62% and 90% Effective

AstraZeneca (Oxford college’s partner) has released the interim results for the trials conducting in the UK and Brazil.

https://www.astrazeneca.com/media-centre/press-releases/2020/azd1222hlr.html

Safety data study
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)32466-1/fulltext

AstraZeneca Vaccine Efficacy Update

AstraZeneca’s original trial results are here. Let’s check their latest updates, especially, for the vaccine efficacy.
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)32661-1/fulltext

COVID-19 Vaccine AstraZeneca confirms 100% protection against severe disease, hospitalisation and death in the primary analysis of Phase III trials
https://www.astrazeneca.com/media-centre/press-releases/2021/covid-19-vaccine-astrazeneca-confirms-protection-against-severe-disease-hospitalisation-and-death-in-the-primary-analysis-of-phase-iii-trials.html

DrBeen’s AstraZeneca vaccine videos

AstraZeneca Vaccine is 62% and 90% Effective
https://youtu.be/tDpSbYUZos8

AstraZeneca and our nucleus
https://youtu.be/wYz-7zB_AAw

How Is AstraZeneca Vaccine Made?
https://youtu.be/C_kzjxQfAJo

Is There Fetal Tissue In AstraZeneca Vaccine?
https://youtu.be/vWMWM4YyS6M

A Koolbeen’s message about the AstraZeneca efficacy:
“Don Phelps  • 2 hours ago 
Dear Dr, There has been published recent update on AstroZenica vac.
The different efficacy rates turned out to be due to time interval between first and second shot, and delay period before efficacy measured.  I belive I saw it WhiteBoard Doctor.  But I also watch TrialSiteNews and medcram. So please update your review. Hope that is helpful.  I do love and appreciate you and this channel. Yours, Don”

Oxford’s article
https://www.ox.ac.uk/news/2021-02-02-oxford-coronavirus-vaccine-shows-sustained-protection-76-during-3-month-interval

Latest paper from AstraZeneca
https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3777268

All news for AstraZeneca vaccine
https://www.research.ox.ac.uk/Area/Search/vaccine_development

Is It Safe to Delay a Second COVID Vaccine Dose?
https://www.scientificamerican.com/article/is-it-safe-to-delay-a-second-covid-vaccine-dose/

After Admitting Mistake, AstraZeneca Faces Difficult Questions About Its Vaccine
https://www.nytimes.com/2020/11/25/business/coronavirus-vaccine-astrazeneca-oxford.html

A good table for various vaccines here:
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)00306-8/fulltext

Why did a German newspaper insist the Oxford AstraZeneca vaccine was inefficacious for older people—without evidence?
https://www.bmj.com/content/372/bmj.n414

Something of interesting. Vaccine mixtures are being tested as well.
https://www.research.ox.ac.uk/Article/2021-02-04-oxford-leads-first-trial-investigating-dosing-with-alternating-vaccines
https://www.research.ox.ac.uk/Article/2020-12-08-first-peer-reviewed-results-phase-3-coronavirus-vaccine
https://www.research.ox.ac.uk/Article/2020-12-08-phase-3-trial-data-publication-faq
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)00306-8/fulltext

#drbeen #koolbeens #COVID

AstraZeneca Vaccine And Our Nucleus

In the talk today we will discuss how the adenovirus that makes AstraZeneca vaccine will enter our cells, reach our nucleus, and insert its genetic material into our nucleus. We will discuss the events that transpire in our cell’s nucleus once the adenovirus DNA is in there.

AstraZeneca vaccine EUA in UK
https://www.astrazeneca.com/content/astraz/media-centre/press-releases/2020/astrazenecas-covid-19-vaccine-authorised-in-uk.html

AstraZeneca vaccine authorization in India and six other countries
https://www.astrazeneca.com/content/astraz/media-centre/press-releases/2021/serum-institute-of-india-obtains-emergency-use-authorisation-in-india-for-astrazenecas-covid-19-vaccine.html

Adenovirus replication (keep in mind that the adenovirus in AstraZeneca vaccine is not able to replicate.)
https://www.cronodon.com/BioTech/Adenovirus.html

Adenovirus
https://en.wikipedia.org/wiki/Adenoviridae

How an adenovirus enters, and reaches the nucleus of our cells?
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3578361
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4429625/

How various viruses replicate?
https://en.wikipedia.org/wiki/Viral_replication

Adenovirus related article
https://www.bbc.com/news/health-55308216

A good article about the adenovirus based vaccines
https://www.news-medical.net/health/What-are-Adenovirus-Based-Vaccines.aspx

Virus based vectors to carry genes for vaccines and cancers
https://en.wikipedia.org/wiki/Viral_vector#Adenoviruses

Is India Mistaken To Approve Covaxin Vaccine?

Vero cell line (for virus culture)
https://en.wikipedia.org/wiki/Vero_cell

Beta-propiolactone (for inactivating the virus)
https://en.wikipedia.org/wiki/Beta-Propiolactone

How is the COVAXIN like vaccines made?
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7202686/

Bharat Biotech, ICMR publish Covaxin Phase 1 data showing safe, enhanced immunity to Covid-19 disease
https://www.firstpost.com/india/bharat-biotech-icmr-publish-covaxin-phase-1-2-safety-data-in-an-interim-report-in-lancet-9229311.html

Press Information Bureau Government of India
https://pib.gov.in/PressReleseDetail.aspx?PRID=1685761

Regulatory approval of COVID-19 vaccine for restricted use in clinical trial mode
https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(21)00045-1/fulltext

India begins COVID-19 vaccination amid trial allegations
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)00145-8/fulltext

Watch | 'Mistake to Authorise Covaxin Without Phase 3 Data': Dr Ashish Jha
https://thewire.in/health/mitali-mukherjee-ashish-jha-bharat-biotech-covaxin

Scientists Urge Govt to Release Covaxin Phase 3 Trial Data Before Rollout
https://science.thewire.in/health/bharat-biotech-covaxin-vaccine-data/

How COVAXIN works?
https://www.nytimes.com/interactive/2021/health/bharat-biotech-covid-19-vaccine.html

Sputnik Vaccine is 91.6% Effective

Safety and efficacy of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine: an interim analysis of a randomised controlled phase 3 trial in Russia
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)00234-8/fulltext

Sputnik V COVID-19 vaccine candidate appears safe and effective
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)00191-4/fulltext

About this vaccine
https://sputnikvaccine.com/about-vaccine/

Wikipedia article
https://en.wikipedia.org/wiki/Sputnik_V_COVID-19_vaccine

Interferon Beta- A New Study

Excerpt from Wikipedia
Interferons (IFNs, /ˌɪntərˈfɪərɒn/[1]) are a group of signaling proteins[2] made and released by host cells in response to the presence of several viruses. In a typical scenario, a virus-infected cell will release interferons causing nearby cells to heighten their anti-viral defenses.

A small study shows good results with interferon beta 1
https://www.sciencemediacentre.org/expert-reaction-to-announcement-by-synairgen-that-their-drug-sng001-has-had-positive-results-in-initial-trials-on-covid-19-patients/

Trial for the interferon beta
https://clinicaltrials.gov/ct2/show/NCT04385095

Interferons
https://en.wikipedia.org/wiki/Interferon#:~:text=Interferons%20(IFNs%2C%20%2F%CB%8C%C9%AA,heighten%20their%20anti%2Dviral%20defenses.

Interferon Beta
https://en.wikipedia.org/wiki/Interferon_type_I#IFN-.CE.B2

An invitro study on SARS-COV-1 (not 2)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3322919/

Vitamin D, Dust and COVID-19

Vitamin D’s effect is reduced by dust. Hence, the severity of COVID-19 is increased. Let’s see how?

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7326088/

Erratum: the spelling of Regeneron is incorrect in the title slide due to human error. We are fixing this error. 

Antibody cocktail
https://investor.regeneron.com/news-releases/news-release-details/regenerons-regn-cov2-antibody-cocktail-reduced-viral-levels-and

https://science.sciencemag.org/content/369/6506/1010

https://science.sciencemag.org/content/sci/369/6506/1010.full.pdf

Azithromycin is an antibiotic used for the treatment of a number of bacterial infections.[3] This includes middle ear infections, strep throat, pneumonia, traveler's diarrhea, and certain other intestinal infections.[3] It can also be used for a number of sexually transmitted infections, including chlamydia and gonorrhea infections.[3] Along with other medications, it may also be used for malaria.[3] It can be taken by mouth or intravenously with doses once per day.[3]

https://en.wikipedia.org/wiki/Azithromycin

Macrolides

https://en.wikipedia.org/wiki/Macrolide#:~:text=The%20mechanism%20of%20action%20of,well%20as%20inhibiting%20ribosomal%20translation.

Effect of Azithromycin on NK cells

https://pubmed.ncbi.nlm.nih.gov/22410149/

Famotidine (H2 Receptor Antagonist)

Famotidine (H2 Receptor Antagonist) 

https://youtu.be/TtN0gwP16cc

MATH+ '+' protocol advocates the use of Famotidine based on the study showing reduction in the risk of intubation and death in COVID-19 patients.

Famotidine, sold under the brand name Pepcid among others, is a medication that decreases stomach acid production.[2] It is used to treat peptic ulcer disease, gastroesophageal reflux disease, and Zollinger-Ellison syndrome.[2] It is taken by mouth or by injection into a vein.[2] It begins working within an hour.[2]

Common side effects include headache, intestinal upset, and dizziness.[2] Serious side effects may include pneumonia and seizures.[2][3] Use in pregnancy appears safe but has not been well studied while use during breastfeeding is not recommended.[4] It is a histamine H2 receptor antagonist.[2]

Famotidine

https://en.wikipedia.org/wiki/Famotidine

Gastrin

https://en.wikipedia.org/wiki/Gastrin

Enterochromoaffin-like cells

https://en.wikipedia.org/wiki/Enterochromaffin-like_cell

Norepinephrine (NE)

Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic chemical in the catecholamine family that functions in the brain and body as a hormone and neurotransmitter.

Norepinephrine

https://en.wikipedia.org/wiki/Norepinephrine

Catecholamines

https://en.wikipedia.org/wiki/Catecholamine

Management of Critically Ill Adults With COVID-19

https://jamanetwork.com/journals/jama/fullarticle/2763879

Organization of the sympathetic system

https://en.wikipedia.org/wiki/Sympathetic_nervous_system

Chromaffin cells of the suprarenal glands that release catecholamines

https://en.wikipedia.org/wiki/Chromaffin_cell

Interleukin 6

https://en.wikipedia.org/wiki/Interleukin_6#:~:text=IL%2D6%20can%20be%20secreted,%2Dlike%20receptors%20(TLRs).

Shock

https://en.wikipedia.org/wiki/Shock_(circulatory)

Cytokines and shock

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4378830/

Cytokines causing vasoactivity

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2730638/#:~:text=Cytokines%20induce%20macrophage%2Dtype%20NOS%20in%20VSMCs.&text=TNF%2D%CE%B1%20(produced%20by%20macrophages,to%20the%20hyperemia%20of%20inflammation.

Glenmark's FabiFlu approved for coronavirus treatment in India, costs Rs 103 per tablet

Mumbai-based Glenmark Pharmaceuticals have launched a new antiviral drug - Favipiravir with brand name FabiFlu - for the treatment of mild to moderate Covid-19 patients. The firm has become the first Indian company to commercially launch the antiviral drug.

https://www.indiatoday.in/india/story/coronavirus-treatment-drug-glenmark-fabiflu-favipiravir-launch-india-rs-103-per-tablet-reduce-viral-load-1691066-2020-06-20

Coronavirus replication

https://www.ncbi.nlm.nih.gov/books/NBK554776/figure/article-52171.image.f1/

RdRp is the main enzyme of transcription-replication complex

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2322833/

Favipiravir mechanism of action and its study

https://www.biorxiv.org/content/10.1101/2020.05.15.098731v1.full.pdf+html

Experimental Treatment with Favipiravir for COVID-19: An Open-Label Control Study

https://www.sciencedirect.com/science/article/pii/S2095809920300631?via%3Dihub

Potential coronavirus drug approved for marketing

Favipiravir, an antiviral that has shown potential in treating the novel coronavirus, was approved for marketing, the Taizhou government of Zhejiang province announced Sunday.

https://www.chinadaily.com.cn/a/202002/17/WS5e49efc2a310128217277fa3.html

Therapeutic options for the 2019 novel coronavirus (2019-nCoV)

Therapeutic options in response to the 2019-nCoV outbreak are urgently needed. Here, we discuss the potential for repurposing existing antiviral agents to treat 2019-nCoV infection (now known as COVID-19), some of which are already moving into clinical trials.

https://www.nature.com/articles/d41573-020-00016-0

Fujifilm Announces the Start of a Phase III Clinical Trial of Influenza Antiviral Drug Avigan (favipiravir) on COVID-19 in Japan and Commits to Increasing Production

https://www.drugs.com/clinical_trials/fujifilm-announces-start-phase-iii-clinical-trial-influenza-antiviral-avigan-favipiravir-covid-19-18505.html

Iodine and its medical uses

Iodine and Its Medical Uses 

https://youtu.be/F4pn-YEdfOU

Iodine is a chemical element with the symbol I and atomic number 53. The heaviest of the stable halogens.

Donate to support my work:

https://paypal.me/mobeensyed?locale.x=en_US

Thyroid hormones

https://en.wikipedia.org/wiki/Thyroid_hormones

Iodothyroinine deiodinase

https://en.wikipedia.org/wiki/Iodothyronine_deiodinase

Antiseptics and Disinfectants: Activity, Action, and Resistance

Antiseptics usually mean the biocides applied to skin

Disinfectants usually mean the biocides applied to surfaces

These terms are interchangably used as well

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC88911/

Iodine

https://en.wikipedia.org/wiki/Iodine

Povidone Iodine

https://en.wikipedia.org/wiki/Povidone-iodine

Potassium Iodide

https://en.wikipedia.org/wiki/Potassium_iodide

Jod-Basedow Phenomenon

https://en.wikipedia.org/wiki/Jod-Basedow_phenomenon

Grave’s disease

https://en.wikipedia.org/wiki/Graves%27_disease

Hashimoto’s Thyroiditis 

https://en.wikipedia.org/wiki/Hashimoto%27s_thyroiditis

Anterior Pituitary

https://en.wikipedia.org/wiki/Anterior_pituitary

Dexamethasone

Errata: Th1 and Th2 are reversed in the diagram and narration.

Oxford RECOVERY Trial statement

https://www.recoverytrial.net/files/recovery_dexamethasone_statement_160620_v2final.pdf

Statnews article for dexamethasone results

https://www.statnews.com/2020/06/16/major-study-finds-common-steroid-reduces-deaths-among-patients-with-severe-covid-19/

WHO Statement for Dexamethasone

https://www.who.int/news-room/detail/16-06-2020-who-welcomes-preliminary-results-about-dexamethasone-use-in-treating-critically-ill-covid-19-patients

Warning: abrupt withdrawal can cause acute adrenal insufficiency

Aspirin has antithrombotic, anti-inflammatory, analgesic, and anti-pyretic effects.

Aspirin plus Vitamin D trial for COVID-19

The LEAD COVID-19 Trial: Low-risk, Early Aspirin and Vitamin D to Reduce COVID-19 Hospitalizations (LEAD COVID-19)

https://clinicaltrials.gov/ct2/show/NCT04363840

Aspirin

http://tmedweb.tulane.edu/pharmwiki/doku.php/aspirin

Leukotrienes and allergies

https://en.wikipedia.org/wiki/Leukotriene#:~:text=Leukotrienes%20are%20a%20family%20of,the%20enzyme%20arachidonate%205%2Dlipoxygenase.

Magnesium takes part in more than 300 reactions in our body. It is the second most abundant intracellular cation.

It is anti-inflammatory, excitable membrane stabilizer, and helpful in biomolecule synthesis.

Magnesium in COVID-19

https://www.medrxiv.org/content/10.1101/2020.06.01.20112334v1

Effects of oral magnesium supplementation on inflammatory markers in middle-aged overweight women

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3685774/

Magnesium and electrolyte imbalances

http://www.mgwater.com/schroll.shtml

Magnesium functions

https://www.ncbi.nlm.nih.gov/books/NBK519036/

Magnesium

https://ods.od.nih.gov/factsheets/Magnesium-HealthProfessional/#:~:text=Magnesium%20is%20a%20cofactor%20in,%2C%20oxidative%20phosphorylation%2C%20and%20glycolysis.

Magnesium deficiency and endotoxin damage

https://pubmed.ncbi.nlm.nih.gov/8001362/

Magnesium

https://en.wikipedia.org/wiki/Magnesium

Melatonin is a safe over the counter medication. It has anti-inflammatory, antioxidant, and anti-viral (other than COVID-19) effects. MATH+ protocol suggests melatonin to be given at almost all the stages of the disease. Here we discuss the synthesis and the mechanism of action of melatonin.

COVID-19: Melatonin as a potential adjuvant treatment

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7102583/

Difference between oxidative, aerobic and anaerobic glycolysis.

https://www.crossfit.com/essentials/understanding-the-warburg-effect-the-metabolic-requirements-of-cell-proliferation

Warburg effect

https://en.wikipedia.org/wiki/Warburg_effect_(oncology)

Melatonin

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7211589/

Tocilizumab
https://en.wikipedia.org/wiki/Tocilizumab

interleukin 6 
IL-6 in Inflammation, Immunity, and Disease

https://en.wikipedia.org/wiki/Interleukin_6

How to decode loci on chromosomes
https://en.wikipedia.org/wiki/Locus_(genetics)

Neutrophils
https://en.wikipedia.org/wiki/Neutrophil

Th17 Cells
https://en.wikipedia.org/wiki/T_helper_17_cell

IL6 Receptor blocker study
https://www.sanofi.com/en/media-room/press-releases/2020/2020-04-27-12-58-00

IL6 Receptor blocker study from France (in the French language)
https://www.aphp.fr/contenu/le-tocilizumab-ameliore-significativement-le-pronostic-des-patients-avec-pneumonie-covid

COVID-19 Insights. An Invitro VIRAL BLOCKER Camostat Mesylate

Links to the news

Acute MI incidence reduced during the lockdown. It will increase once the lockdown lifted.
https://www.nejm.org/doi/full/10.1056/NEJMc2015630
Infection can spread by aerosol
https://www.nejm.org/doi/full/10.1056/NEJMc2009324
CDC thinks that the virus spreads more from humans to humans than the fomites.
https://www.cdc.gov/coronavirus/2019-ncov/prevent-getting-sick/how-covid-spreads.html


Links to the studies and medical concepts

The Impact of Camostat Mesylate on COVID-19 Infection (CamoCO-19)
From https://clinicaltrials.gov/ct2/show/NCT04321096
Study that proves Camostat Mesylate blocks viral (SARS-COV-2) entry into the cells
https://www.eurekalert.org/pub_releases/2020-03/dpp-pso030520.php

How serine proteases cut the proteins
https://en.wikipedia.org/wiki/Serine_protease

Camostat mesylate
https://en.wikipedia.org/wiki/Camostat
Camostat invitro study
https://pubmed.ncbi.nlm.nih.gov/32142651/
Camostat dosage
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7188520/
Camostat trials
https://clinicaltrials.gov/ct2/show/NCT04321096
https://clinicaltrials.gov/ct2/show/NCT04353284

Spike protein priming
https://link.springer.com/chapter/10.1007/978-3-319-75474-1_4

Six helices for the S2 subunit of the Spike protein
https://www.researchgate.net/figure/The-fusion-core-structureThe-fusion-core-is-a-six-helix-bundle-with-three-HR2-helices_fig3_23986117

WHO's list of essential medicines: safest and most effective drug needed in the health system.

Used for acetaminophen/paracetamol overdose and to loosen thick mucus.
Appears to be safe in pregnancy

How does NAC break disulfide bonds?
https://www.researchgate.net/figure/Structural-formula-of-N-acetylcysteine-NAC-A-Disulfide-bonds-in-proteins-P-can-be_fig1_299401240

It increases the levels of glutathione in paracetamol overdose.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5241507/

Role of glutathione in immunity and inflammation in the lung
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3048347/

Disulfide bond reduction of vWF
https://www.ncbi.nlm.nih.gov/pubmed/20946172

N-Acetylcysteine as an antioxidant and disulfide breaking agent: the reasons why
https://www.tandfonline.com/doi/full/10.1080/10715762.2018.1468564

NAC functions
https://www.sciencedirect.com/topics/chemistry/cysteine

Passive antibody therapy

Antibodies are gamma globulin proteins that make up 20% of the plasma proteins.

Immunoglobulins can be induced actively in the host (through vaccines for example), or acquired passively from other people’s plasma that have the needed antibodies.

1 person may donate plasma that will be useful for about two doses of treatment for COVID-19. It is not sufficient. So, the process is slow.

Passive immunity is used to neutralize toxins of diphtheria, tetanus, botulism. We also have passive antibodies for viruses like rabies, hepatitis A and B viruses, etc.

Plasma contains fibrinogen (for clotting) and albumin (to keep plasma in the blood vessels.) Plasma transports proteins, nutrients, antibodies, etc. to the tissues of the body. Plasma will also wash away the waste products produced by the cells.

Serum on the other hand is plasma minus the clotting factors. Serum is obtained after blood clotting. Serum contains the antibodies, hence one of its use is to test for antibodies.

Antibodies are IgG, IgM, IgA, IgD, and IgE (GAMED)

Immunoglobulins (Igs) act to neutralize the toxins. They help opsonize the pathogens. Activate complement system. And, they help prevent the attachment of the pathogens to mucosal surfaces.

Monoclonal vs. polyclonal antibodies.

Immunoglobulins are glycoproteins. They consist of a light (L) chain, and a heavy (H) chain. Simplest antibody molecule is a Y shaped complex.

Light chains’ heavy region can be either kappa or lambda. But, in one molecule of an immunoglobulin only one type of light chain will be present (either containing kappa or lambda.)

Light chains have one variable and one heavy domain.

Heavy chains have one variable and three or four heavy domains. IgG and IgA have 3, IgM and IgE have 4.

Variable regions of both the chain are for the antigen binding.

Constant region of the heavy chain is for the biological functions like binding to a cell/surface and complement activation.

GM makes classic cars. IgG and IgM activate complement.

IgG looks pregnant. It passes through the placenta.

IgA is always away to the outdoors. It sits in the surface mucosal fluids.

IgD is only a receptor on the B cells.

IgE is on the mast cells and takes parts in allergies. We don’t want too much of this unless there are worm infections.

IgG also helps opsonize (see it has a pac man like open mouth? Phagocytes have receptors for the IgG heavy chains.)

IgM can activate complement. Which in turn produces C3b which is also a opsonizing molecule. Because phagocytes also have the receptors for C3b.

IgM is usually found as five molecules joined with a J chain. Hence, it has ten binding sites (two sites on each protein.) It is the most efficient immunoglobulin and is produced as the first response.

Genes to form the heavy chains are arranged as (VVVV-D-JJJJ-HMHDHGHEHA)

Genes to form the light chains are arranged as (VVVV-D-JJJJ)

All B cells first produce IgM and IgD. Then the class switching allows them to produce IgG, IgE, and IgE. Various cytokines can influence the switching to various Immunoglobulin types.

Once a specific heavy chain has been spliced out, that immunoglobulin cannot be made any more by this B cell.

Every new encounter with the antigen improves the response. This is because of somatic hypermutation and affinity maturation.

FDA approves blood plasma therapy

https://www.fda.gov/vaccines-blood-biologics/investigational-new-drug-ind-or-device-exemption-ide-process-cber/revised-information-investigational-covid-19-convalescent-plasma

FDA has a form 3926 to fill and send. Response within 4 to 8 hours.

Emergency response needed, call operations at 1-866-300-4374 to seek verbal authorization.

https://www.uscovidplasma.org/

FDA will send an IND number (investigational new drug number.)

https://youtu.be/dZ0xDq7UlD8

First patient to receive plasma in Colorado is a doctor (Dr. Michael Leonard)

https://youtu.be/VvE9TuwbVDo

Mt. Saini

Dr. Jeffery Jhang. Using plasma infusion.

https://youtu.be/4UrigBGv-Q8

Mayo clinic

https://youtu.be/97XVn-PxAxY

Dr. Michael Joyner

https://youtu.be/sBHlCYIj3Cw

Takeda pharma making this product

https://youtu.be/T5vAln2X_YM

A science journalist's take

https://youtu.be/oFZwE6azptM

Androgens - Physiological and Pharmacological Aspects (Lecture 1)

As we prepare to discuss anti-androgen drugs, it is essential for us to understand at a high level the function of androgen hormones. Let's start our first topic in this series. We will discuss genitalia formation and maturation. Viewer discretion is advised.

Today we will discuss the following topics:
High level physiological effects of androgens.
High level pharmacological effects of androgens.
Cellular signaling mechanism of the androgen hormones.

References:
https://www.frontiersin.org/articles/10.3389/fonc.2019.00858/full
https://en.wikipedia.org/wiki/Androgen
https://en.wikipedia.org/wiki/Dihydrotestosterone
https://pubmed.ncbi.nlm.nih.gov/17077643/
https://www.ncbi.nlm.nih.gov/books/NBK499854/
https://www.ncbi.nlm.nih.gov/books/NBK279291/

Disclaimer:
This video is not intended to provide assessment, diagnosis, treatment, or medical advice; it also does not constitute provision of healthcare services. The content provided in this video is for informational and educational purposes only.
Please consult with a physician or healthcare professional regarding any medical or mental health related diagnosis or treatment. No information in this video should ever be considered as a substitute for advice from a healthcare professional.

Androgens - What Controls Androgen Release? (Lecture 2)

Continuing with our series about androgen hormones. The goal is to present the overview of the functions and release of the androgen in a context to discuss the pharmacology of pro-androgen and anti-androgen therapies.

How is the testosterone release controlled?
How are the androgens released from the suprarenal controlled?
High level overview of the hypothalamic involvement in the control of androgens.
High level overview of the pituitary and its role in the control of androgens.

Reference: Guyton and Hall Textbook of Medical Physiology (14th Edition.)
Interesting articles:
https://synergenxhealth.com/how-low-t-treatment-works-for-high-cholesterol/
https://www.webmd.com/cholesterol-management/high-cholesterol-in-men

Disclaimer:
This video is not intended to provide assessment, diagnosis, treatment, or medical advice; it also does not constitute provision of healthcare services. The content provided in this video is for informational and educational purposes only.
Please consult with a physician or healthcare professional regarding any medical or mental health related diagnosis or treatment. No information in this video should ever be considered as a substitute for advice from a healthcare professional.

Antiandrogens - A High-Level Overview (Lecture 3)

Continuing with our discussion of androgens. Today we will discuss the antiandrogen drug classification, indication, side effects, and mechanism of action. Let's dive in.

References:
Brunton, Laurence; Brunton, Laurence; Knollman, Bjorn; Knollman, Bjorn; Hilal-Dandan, Randa; Hilal-Dandan, Randa. Goodman and Gilman's The Pharmacological Basis of Therapeutics, 13th Edition (Goodman and Gilman"S the Pharmacological Basis of Therapeutics). McGraw-Hill Education. Kindle Edition. 

https://pubmed.ncbi.nlm.nih.gov/12537774/
https://www.mdpi.com/2072-6694/13/2/327/htm
https://clincancerres.aacrjournals.org/content/19/6/1335
https://en.wikipedia.org/wiki/List_of_antiandrogens
https://en.wikipedia.org/wiki/Antiandrogen

Disclaimer:
This video is not intended to provide assessment, diagnosis, treatment, or medical advice; it also does not constitute the provision of healthcare services. The content provided in this video is for informational and educational purposes only.
Please consult with a physician or healthcare professional regarding any medical or mental health-related diagnosis or treatment. No information in this video should ever be considered as a substitute for advice from a healthcare professional.

Study - Antiandrogens Reduce COVID Hospitalization, Deaths, And Disease Progress

Let's review the role of antiandrogenic therapy in reducing COVID caused hospitalization, deaths, and disease progression.

References
https://clinicaltrials.gov/ct2/show/study/NCT04446429
https://www.futuremedicine.com/doi/10.2217/fon-2020-0571
https://pubmed.ncbi.nlm.nih.gov/34089595/
https://pubmed.ncbi.nlm.nih.gov/32977363/
https://www.nature.com/articles/s41467-021-24342-y
https://www.cureus.com/articles/50511-early-antiandrogen-therapy-with-dutasteride-reduces-viral-shedding-inflammatory-responses-and-time-to-remission-in-males-with-covid-19-a-randomized-double-blind-placebo-controlled-interventional-trial-eat-duta-androcov-trial---biochemical
https://www.news-medical.net/news/20210322/Anti-androgen-drugs-may-help-disarm-coronavirus-spike-protein-stop-progression-of-COVID-19.aspx
https://onlinelibrary.wiley.com/doi/10.1111/jdv.17249
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7557269/
https://pubmed.ncbi.nlm.nih.gov/34089595/

Disclaimer:
This video is not intended to provide assessment, diagnosis, treatment, or medical advice; it also does not constitute provision of healthcare services. The content provided in this video is for informational and educational purposes only.
Please consult with a physician or healthcare professional regarding any medical or mental health related diagnosis or treatment. No information in this video should ever be considered as a substitute for advice from a healthcare professional.

Study - Antiandrogens (Dutasteride) For Mild COVID Cases

Let's review the role of antiandrogenic therapy in reducing COVID caused hospitalization, deaths, and the disease progression.

References
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7885746/
https://www.futuremedicine.com/doi/10.2217/fon-2020-0571
https://pubmed.ncbi.nlm.nih.gov/34089595/
https://pubmed.ncbi.nlm.nih.gov/32977363/
https://www.nature.com/articles/s41467-021-24342-y
https://www.cureus.com/articles/50511-early-antiandrogen-therapy-with-dutasteride-reduces-viral-shedding-inflammatory-responses-and-time-to-remission-in-males-with-covid-19-a-randomized-double-blind-placebo-controlled-interventional-trial-eat-duta-androcov-trial---biochemical
https://www.news-medical.net/news/20210322/Anti-androgen-drugs-may-help-disarm-coronavirus-spike-protein-stop-progression-of-COVID-19.aspx
https://onlinelibrary.wiley.com/doi/10.1111/jdv.17249
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7557269/
https://pubmed.ncbi.nlm.nih.gov/34089595/

Disclaimer:
This video is not intended to provide assessment, diagnosis, treatment, or medical advice; it also does not constitute provision of healthcare services. The content provided in this video is for informational and educational purposes only.
Please consult with a physician or healthcare professional regarding any medical or mental health related diagnosis or treatment. No information in this video should ever be considered as a substitute for advice from a healthcare professional.