The document describes the renin-angiotensin system and its role in regulating blood pressure and cardiovascular function. It discusses key components of the system, such as renin, angiotensin I and II, and angiotensin converting enzyme. It also describes how therapeutic agents have been developed that act on enzymes and receptors in the renin-angiotensin system to treat hypertension and heart failure.
This Presentation tries to make understand the System which plays a role in increasing Blood Pressure-Renin Angiotensin System & How the drugs and inhibiting Enzymes prevent this BP rise...
This Presentation tries to make understand the System which plays a role in increasing Blood Pressure-Renin Angiotensin System & How the drugs and inhibiting Enzymes prevent this BP rise...
EFFECTS OF EXCESS SALT DIET ON ANGITENSINOGEN SECRETIONS IN THE KIDNEY OVER TIMEchiehyin
Abstract
Background: Salt is an important component for normal function of cells. However, we consume more than 10 times the salt that is required. This high salt content affects the renin–angiotensin–aldosterone system (RAAS) that regulates blood pressure (BP) and water content of our body. Angiotensinogen is an oligopeptide hormone precursor serving as a substrate for renin in the formation of angiotensin I. Angiotensin I is converted to angiotensin II that causes vasoconstriction and a subsequent increase in BP. We hypothesized that angiotensinogen secretions increases in the kidney and urine with intake of high salt diet.
Methods: Dahl salt sensitive (SS) and salt resistant (SR) male rats (8 weeks old) were fed with high salt (HS) and low salt (LS) diet along with or without aldosterone (ALDO); aldosterone antagonist, eplerenone (EPL); and NADPH oxidase inhibitor, apocynin (APC) for 21 days. Urine samples and kidney were collected; total proteins isolated, and quantified using the microassay procedure and analyzed by western blot for angiotensinogen.
Results: Angiotensinogen was detected in the kidney samples of Dahl SS rat when fed either low or high salt diet, whereas angiotensinogen was detected in kidney samples of Dahl SR rats when fed with high salt diets. Angiotensinogen was not detected in urine samples.
Conclusions: In conclusion, consuming a high salt diet increases Angiotensinogen that lead to an increase in angiotensin II which may cause an increase in BP.
Acknowledgements: Vivien Thomas Summer Research Program, Morehouse School of Medicine, Atlanta, GA, USA.
Basic must know things about Anti Hypertensive drugs including the recent JNC-8 classification and protocols for treating Hypertension with various co-morbid condition.
A review of the existing evidence that supports the current practice in perioperative medicine regarding Renin-angiotensin-aldosterone system antagonists, mainly ACE inhibitors and Angiotensin type 1 receptor blockers (ARB's).
Presented as the Cleveland Clinic Hospital Medicine Grand Rounds on April 1, 2009. CME AMA Category 1 - 1 hour.
Renin Angiotensin Aldosterone System (RAAS).pptxAvinashGunjal5
The renin-angiotensin-aldosterone system (RAAS) is a critical regulator of blood volume, electrolyte balance, and systemic vascular resistance. While the baroreceptor reflex responds short term to decreased arterial pressure, the RAAS is responsible for acute and chronic alterations. The classical understanding of RAAS is that it comprises three significant compounds: renin, angiotensin II, and aldosterone. These three compounds elevate arterial pressure in response to decreased renal blood pressure, salt delivery to the distal convoluted tubule, and beta-agonism.
Hypertension or high blood pressure is a chronic medical condition in which the blood pressure in the arteries is elevated i.e. 140/90 mmHg systolic /diastolic pressure.
High blood pressure has damaging effect on the heart, brain, kidneys and eyes.
Drugs used to lower blood pressure is known as antihypertensive drugs.
Antihypertensive drug therapy has improved remarkably in the last 50 years.
Before 1950, less effective and less tolerated antihypertensive drugs were available.
Veratrum and sodium thiocyanate could lower BP, but were toxic and difficult to use.
The ganglion blockers that were developed in the 1950s were effective, but inconvenient.
Reserpine was a breakthrough, but produced mental depression.
The therapeutic potential of hydralazine was not tapped fully because of the marked side effects when it was used alone
First choice drug in all grade of essential as well as renovascular hypertension (except renal artery stenosis).
This class of medicine works by causing relaxation of blood vessels as well as a decrease in blood volume, which leads to lower blood pressure and decreased oxygen demand from the heart.
Most patient require low doses which are well tolerated.
Example - Captopril, Enalapril, Lisinopril, Ramipril, Perindopril, Benazepril, Fosinopril, Quinapril, Trandolapril.
Large hydrophobic N-heterocyclic ring increase potency.
Ring showed contain –COOH group to mimic ACE substrate.
The Zn2+binding group may be
sulfhydryl (-CH2SH) like captopril
Di-carboxylate like in enalapril, lisinopril and quinapril
Phosphate like fosinopril
Sulfhydryl group shows superior binding to Zn ion and produces side effect like skin rash, taste disturbance etc.
Esterification of carboxylate or phosphate produce orally bioactive prodrug.
Large heterocyclic ring and hydrophobic ring generally N-containing increase potency and alter pharmacokinetic parameter.
Generally pyrrolidine ring is present (E.g. – Captopril, Enalapril)
The N-group must contain –COOH group to mimic the C-terminal carboxylate of ACE substrate.
X is usually methyl to mimic the side chain of aniline . This type of drug do not require prodrug for oral activity.
Drugs are : Losatran, Candesartan, Irbesartan, Valsartan, Telmisartan
The most prominent action of angiotensin II is vasoconstriction.
The two types of angiotensin II receptors are AT1 and AT2 , most of the action of angiotensin II are mediated by AT1 receptor.
Angiotensin receptor blockers do not affect bradykinin production.
Oral bioavibility – 33% (1st pass metabolism) It is partially carbonylated in liver to an active metabolism (E3174).
All ARB prevent and reverse all known effect of angiotensin-II including slow CNS effect, release of catecholamine, secretion of aldosterone, direct and indirect renal effect.
Telmisartan has additional PPAR-ϒ agonistic activity. This activity can help patient with dysglycemia.
There are thee functional groups that are the most important part f
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
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.
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
Anti ulcer drugs and their Advance pharmacology ||
Anti-ulcer drugs are medications used to prevent and treat ulcers in the stomach and upper part of the small intestine (duodenal ulcers). These ulcers are often caused by an imbalance between stomach acid and the mucosal lining, which protects the stomach lining.
||Scope: Overview of various classes of anti-ulcer drugs, their mechanisms of action, indications, side effects, and clinical considerations.
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New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
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.
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
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
2. Chapter Overview
Describes the role renin-angiotensin
system plays in regulating the
cardiovascular system
Critical role in the mechanism of
hypertension and congestive heart failure
Development of therapeutic agents that act
on the various enzymes and receptors
associated with the renin-angiotensin
system
3. Chapter Overview
Renin-angiotensin system influences
normal physiological function
Components of the system such as renin,
angiotensin I and II, and angiotensin-
converting enzyme
4. Renin-Angiotensin System
and Hypertension
Renin-Angiotensin system – is a hormonal
system that plays a central role in the
control of sodium excretion and body fluid
volume. Interacts closely with the
sympathetic nervous system and
aldosterone secretion in the regulation of
blood pressure.
5. Renin-Angiotensin System
and Hypertension
Renin – a kidney extract produced a potent
vasopressor response.
- An aspartyl protease (MW 35,000 –
40,000).
- Primary source is kidney.
- Cleaves the Leu-Val bond from the
aspartic acid end of the angiotensinogen
polypeptide molecule to release the
decapeptide angiotensin I
6. Renin-Angiotensin System
and Hypertension
Angiotensin – hypertensive substance
isolated and identified as decapeptide
- is a glycoprotein (MW 58,000 – 61,000).
- synthesized primarily in the liver and
brought into the circulatory system
7. Biochemical Conversion
The Cleavage of a dipeptide (His-Leu)
from the carboxyl terminal of angiotensin
converting enzyme to form octapeptide
which is angiotensin II (a potent
vasoconstrictor)
Angiotensin III is formed by removal of
the N-terminal aspartate residue of
angiotensin II a reaction catalyzed by
glutamyl aminopeptidase
8. Biochemical Conversion
In contrast to angiotensin II, angiotensin
III has a less potent but significant
regulatory effect on sodium excretion by
the renal tubules
This is primarily resulting from the effect
angiotensin III has in stimulating
aldosterone secretion, a potent
mineralcorticoid.
9. Vasoconstrictive effects
of angiotensin II
Angiotensin II – stimulates the release of
vasopressin from the hypothalamus.
Vasopressin – also known as antidiuretic
hormone (ADH)
- This peptidic hormone is typically
released to conserve water when body is
dehydrated.
10. Vasoconstrictive effects
of angiotensin II
Endothelin – a 21 amino acid peptide that
is produced in the vascular endothelium
and plays a role in the regulation of
smooth muscle contraction and contributes
to blood pressure regulation.
Aldosterone – secreted by adrenal cortex
and elicits its effects at various sites.
Responsible for the absorption of sodium
in the bloodstream
11. Regulatory action of the
renin-angiotensin system,
- In controlling sodium and potassium
balance and arterial blood pressure is
modified by vasodilators called kinins.
Kallikrein – is activated in plasma by
noxious influences to act on a kinin,
callidin, which is converted to bradykinin
by tissue enzymes.
12. Regulatory action of the
renin-angiotensin system,
Bradykinin – enhances release of the
prostaglandins PGE2 and PGI2 within
certain tissues to produce a vasodilatory
effect.
- Converted to inactive products by ACE
and other carboxypeptidases.
13. ACE – a membrane bound enzyme
anchored to the cell membrane through a
single transmembrane domain.
- Zinc containing glycoprotein (MW
130,000)
- A non specific peptidyldipeptide
hydrolase, widely distributed in mamalian
tissues.
- Is a tripeptide with a free carboxylate
group.
14. Active sites of ACE
Important binding points
- Cationic site to attract a carboxylate ion
- Zinc ion that can polarize a carbonyl
group of an amide function to make it
more susceptible to hydrolysis.
In the active site, there is a nucleophilic
attack of the amide carbonyl by the y-
carbonyl group of a glutamic acid
residue to cause hydrolysis of peptide.
15. Important role of renin
angiotensin system
Regulating kidney function
Aldosterone release
Electrolyte balance
Blood volume
16. Renin-Angiotensin system
inhibitors
Captopril – 1-[(2S)-3-mercapto-2-methyl-
1-oxopropionyl]proline (Capoten)
- Blocks the conversion of angiotensin I to
angiotensin II by inhibiting the
converting enzyme.
- Was designed with a carboxyl group on a
proline and a thiol group was introduced
to enhance binding to zinc ion of ACE.
17.
18. Lisinopril – 1-[N2-[S-1-carboxy-3-phenylpropyl]-
L-lysyl]-L-proline dihydrate (Privinil, Zestril)
- A lysine derivative of enalaprilat, active
metabolite of enalapril.
- Like all ACE inhibitors, it is an active site-
directed inhibitor of the enzyme, with the zinc
ion used in an effective binding interaction at a
stoichiometric ratio of 1:1
- Pharmacological effect are similar to those of
captopril and enalapril.
19.
20. ACE-Inhibitors ProDrugs
- Available for the treatment of
hypertension following the clinical
effectiveness of enalapril
- These drugs, like the prototypical drug
captopril, are used in the treatment of
mild to moderate hypertension, either
alone or in conjunction with diuretics or
calcium channel blockers
21. Enalapril Maleate - 1-[N[(S)-1-carboxy-3-
phenylpropyl]-L-alanyl]-L-proline 1-ethyl
ester maleate (Vasotec)
- Is a long-acting ACE inhibitor.
- Is devoid of the side effects of rash and loss
of taste seen with captopril
- The absence of the thiol group in enalapril
maleate may free it from these side effects.
- The half-life is 11 hours.
22.
23. Benazepril Hydrochloride - (3S)-3-[[(1S)-1-
carbethoxy-3-phenylpropyl]amino]-2,3,4,5-
tetrahydro-2-oxo-1H-1-benzazepine-1-acetic
acid 3-ethylester hydrochloride (Lotensin)
- Metabolized rapidly to the active diacid
benazaprilat.
- No mutagenicity has been found, even
though these drugs cross the placenta.
24.
25. Quinapril Hydrochloride - (S)-[(S)-N-[(S)21-
carboxy3-phenylpropyl]alanyl]-1,2,3,4-
tetrahydro-3-isoquinolinecarboxylic acid 1-
ethyl ester hydrochloride (Acuretic)
- forms the diacid quinaprilate in the body. It is
more potent than captopril and equipotent to
the active form of enalapril.
26.
27. Ramipril - (2S, 3aS, 6aS)-1-[(S)-N-[(S)-1-
carboxy-3phenylpropyl]alanyl]
octahydrocyclopenta[b]-pyrrole-2-carboxylic
acid 1-ethyl ester (Altace)
- Is hydrolyzed to ramiprilat, its active diacid form,
faster than enalapril is hydrolyzed to its active
diacid form.
- Peak serum concentrations from a single oral
dose are achieved between 1.5 and 3 hours.
- ramiprilate formed completely suppresses ACE
activity for up to 12 hours, with 80% inhibition
of the enzyme still observed after 24 hours.
28.
29. Fosinopril Sodium - (4S)-4-cyclohexyl-1-
[[[(RS)-1-hydroxy-2-methylpropoxy](4-
phenylbutyl) phosphinyl]acetyl]-L-proline
sodium salt (Monopril)
- Phosphorus-containing ACE inhibitor.
- It is inactive but serves as a prodrug, being
completely hydrolyzed by intestinal and liver
enzymes to the active diacid fosinoprilat