This document discusses various classes of antihypertensive drugs used to treat hypertension. It begins by defining hypertension and describing the different types. It then outlines the main classes of antihypertensive drugs, which include diuretics, centrally acting sympatholytics, adrenergic neuron blockers, adrenergic receptor blockers, calcium channel blockers, renin-angiotensin system inhibitors, and others. Specific drug classes and examples like beta-adrenergic receptor blockers, alpha-1-adrenergic receptor blockers, and adrenergic neuron blockers are then discussed in more detail.
In this PPTs you will get in depth information about insulin and the first class of oral hypoglycemic agents , Sulfonylurea.
useful for GPAT and Third Year B.Pharm students.
In this PPTs you will get in depth information about insulin and the first class of oral hypoglycemic agents , Sulfonylurea.
useful for GPAT and Third Year B.Pharm students.
Seretonin (5HT) and Its Antagonists PharmacologyPranatiChavan
Serotonin is a chemical that has a wide variety of functions in the human body. It is sometimes called the happy chemical, because it contributes to wellbeing and happiness.
The scientific name for serotonin is 5-hydroxytryptamine, or 5-HT. It is mainly found in the brain, bowels, and blood platelets.
Serotonin is used to transmit messages between nerve cells, it is thought to be active in constricting smooth muscles, and it contributes to wellbeing and happiness, among other things. As the precursor for melatonin, it helps regulate the body’s sleep-wake cycles and the internal clock.
It is thought to play a role in appetite, the emotions, and motor, cognitive, and autonomic functions. However, it is not known exactly if serotonin affects these directly, or if it has an overall role in co-ordinating the nervous system.
The presentation describes the mechanism action of diuretics with the class of Carbonic anhydrase inhibitors, loop diuretics, thiazides, osmotic and potassium diuretics.
Cardiovascular Drugs-Medicinal Chemistry MANIKImran Nur Manik
c) Glycosides: chemical and clinical aspects of digoxin and other digitalis glycosides
Functioning and disease of the heart, arrhythmia, atheroma, ischemia, angina pectoris,
coronary thrombosis, myocardial infarction, arteriosclerosis, atherosclerosis, hypertension and
congestive heart failure.
Introduction, classification, chemistry, mode of action, structure-activity relationship,
pharmacokineties, indications, contraindications, dose, adverse effects and drug interaction of
following individual class of drugs:
a) Cardiac glycosides.
b) Antihypertensives: -blockers, vasodilators, ca-channel blocking agents, ACE inhibitors.
c) Antiarrhythmic drugs.
Seretonin (5HT) and Its Antagonists PharmacologyPranatiChavan
Serotonin is a chemical that has a wide variety of functions in the human body. It is sometimes called the happy chemical, because it contributes to wellbeing and happiness.
The scientific name for serotonin is 5-hydroxytryptamine, or 5-HT. It is mainly found in the brain, bowels, and blood platelets.
Serotonin is used to transmit messages between nerve cells, it is thought to be active in constricting smooth muscles, and it contributes to wellbeing and happiness, among other things. As the precursor for melatonin, it helps regulate the body’s sleep-wake cycles and the internal clock.
It is thought to play a role in appetite, the emotions, and motor, cognitive, and autonomic functions. However, it is not known exactly if serotonin affects these directly, or if it has an overall role in co-ordinating the nervous system.
The presentation describes the mechanism action of diuretics with the class of Carbonic anhydrase inhibitors, loop diuretics, thiazides, osmotic and potassium diuretics.
Cardiovascular Drugs-Medicinal Chemistry MANIKImran Nur Manik
c) Glycosides: chemical and clinical aspects of digoxin and other digitalis glycosides
Functioning and disease of the heart, arrhythmia, atheroma, ischemia, angina pectoris,
coronary thrombosis, myocardial infarction, arteriosclerosis, atherosclerosis, hypertension and
congestive heart failure.
Introduction, classification, chemistry, mode of action, structure-activity relationship,
pharmacokineties, indications, contraindications, dose, adverse effects and drug interaction of
following individual class of drugs:
a) Cardiac glycosides.
b) Antihypertensives: -blockers, vasodilators, ca-channel blocking agents, ACE inhibitors.
c) Antiarrhythmic drugs.
Hypertension is the most common cardiovascular disease determined by increase blood pressure (pressure exerted by blood against the wall of a blood vessel )in arteries.
The onset of hypertension is defined as having a blood pressure of 140/90 mm Hg or greater .
Hypertension is the major risk factor for coronary artery disease, heart failure, stroke and renal failure.
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
This presentation contains a brief introduction of Adrenergic and cholinergic systems and their function in our body.
And a brief description of some adrenergic and cholinergic agents along with their mechanism of action along with their respective Structures.
inotropic drugs and vassopressors drugs.pptxAhmed638947
this presentation is toalking about the Sympathomimetic drugs which are agents which in general mimic responses due to stimulation of sympathetic nerves.
These agents are able to directly activate adrenergic receptors or to indirectly activate them by increasing norepinephrine and epinephrine (mediators of the sympathoadrenal system) levels.
These drugs are used clinically to treat glaucoma, anaphylactic shock, chronic obstructive pulmonary disease, hypotension, hypertension, heart failure, nasal congestion, premature labor, attention-deficit/hyperactivity disorder, narcolepsy, and acute or chronic asthma. The α or β adrenergic antagonists block or attenuate the effect of sympathomimetics on α or β receptors. Alpha blockers are used clinically to treat hypertension and benign prostatic hyperplasia. Beta blockers are used clinically to treat ischemic heart disease, essential hypertension, cardiac arrhythmias, congestive heart failure, glaucoma, hyperthyroidism, surgical removal of pheochromocytoma, nonparkinsonian tremor, migraine headache (prophylaxis), and a wide variety of anxiety situations.
Hypertension according to latest clinical advances Arbeena Shakir
This presentation is prepared for hypertension disease according to latest clinical advances and its classification is according to American heart association and seventrh report JNC 7 guidelines
This slide talks about the different pharmacological properties of Antihypertensive Drugs. The classification and examples of these drugs are also given in detail.
The National Board of Accreditation (NBA) is one of the two major bodies responsible for accreditation of higher education institutions in India, along with the National Assessment and Accreditation Council (NAAC). NBA accredits technical programmes, such engineering and management programmes, and Pharmacy earler while NAAC accredits general colleges and universities.
What is Pharm.D course?
Pharm.D course is a Professional Pharmacy doctoral programme of 6 yrs duration after 10+2 (science academic stream) which includes 5yrs of academic study + 1 year of internship or residency.
What are the eligibility criteria to join Pharm.D courses? For Pharm.D:
i) A pass in 10+2 examination with Physics and Chemistry as compulsory subjects along with one of the following subjects: Mathematics or Biology.
ii) A pass in D.Pharm course from an institution approved by the Pharmacy council of India under section 12 of The Pharmacy Act.
Opportunities of BDS in Pharmaceutical Industries.pptxDr. Manoj Kumbhare
India is the second-largest pharmaceutical market in Asia. ... A BDS graduate can have various job roles available in this sector: Principal Investigator, Co-investigator, Medical Advisor, Drug Developer, Regulatory Affairs Manager or even a Clinical Research Physician.
Career opportunities in the clinical research field are many and varied, with employment settings ranging from pharmaceutical and biotechnology, to medical device companies, contract research organizations, hospitals, educational institutions, independent contractors and more.
Many professionals with a strong science or healthcare related background — such as nurses, pharmacists, medical technologists, physicians and more — are well-positioned to join the clinical research field. Here are 10 career paths in the field.
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.
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Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
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
Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
MANAGEMENT OF ATRIOVENTRICULAR CONDUCTION BLOCK.pdfJim Jacob Roy
Cardiac conduction defects can occur due to various causes.
Atrioventricular conduction blocks ( AV blocks ) are classified into 3 types.
This document describes the acute management of AV block.
Basavarajeeyam is an important text for ayurvedic physician belonging to andhra pradehs. It is a popular compendium in various parts of our country as well as in andhra pradesh. The content of the text was presented in sanskrit and telugu language (Bilingual). One of the most famous book in ayurvedic pharmaceutics and therapeutics. This book contains 25 chapters called as prakaranas. Many rasaoushadis were explained, pioneer of dhatu druti, nadi pareeksha, mutra pareeksha etc. Belongs to the period of 15-16 century. New diseases like upadamsha, phiranga rogas are explained.
5. -ADRENERGICBLOCKERS
Activationof thereceptorsin heart leadsto an increasein rate andforceof
contraction.
-ReceptorBlockers reduce
(a) the heart rate,
(b) contractility
(c)arterial pressure
Dependingupontheseeffects,these
drugsreducethe work andthe oxygen
demandof heart and
improvethe oxygensupply/demand
ratio.
Prof. Dr. M.R. Kumbhare
6. -ADRENERGICBLOCKERS
-ReceptorBlockerscanbedividedinto two classdependingonthe receptorselectivity
(a)Nonselective-ReceptorBlockers(1 and2 blockingeffect) (FirstGeneration)
Propranolol,timolol, nadolol, pindolol(someexamplesof this class)
()1-SelectiveAdrenergicBlockers(cardioselective1 blockers)(SecondGeneration)
Acebutolol,atenolol, metoprolol(someexamplesof this class)
Nonselective-ReceptorBlockerswith 1 antagonisticactivity (Third Generation)
labetalol,carvedilol
Prof. Dr. M.R. Kumbhare
7. -ADRENERGICBLOCKERS
adrenergicreceptorblockersare amongthe mostwidely usedantihypertensive
drugsandalsoconsideredfor the first line treatment for glaucoma.
Cardioselective adrenergicreceptor blockershavea greater affinity for the -
receptorsin heart than for the -receptorsin other tissue.
providestwo important advantages
(next slide please)
Prof. Dr. M.R. Kumbhare
8. -ADRENERGICBLOCKERS
Cardioselective adrenergicreceptorblockershavea greater affinity for the -
receptorsin heart than for the -receptorsin other tissue.
providetwo important advantages
-Blockersdonot haveblocking
effectson-receptorson bronchi
Theycanbeusedsafelyin patients with
bronchitisor bronchial astma
-Blockersdonot haveblocking
effectsonvascular-receptors
mediatingvasodilation
Prof. Dr. M.R. Kumbhare
22. 1-ADRENERGICRECEPTORBLOCKERS
Selective1-adrenergicreceptorblockersare usedin the treatment of hypertension.
produce antihpertensive effect by blocking the vasocontricting effect of 1-adrenergic receptor
onsmooth muscle.
Thesedrugsdo not have any effect on 2-adrenergic receptors.
Examplesof selectiveadrenergic receptorblockersare Prazosin,Terazosinand Doxasozin.
Prof. Dr. M.R. Kumbhare
26. 1-ADRENERGICRECEPTORBLOCKERS
PRAZOSİN
Aminogroupat 4th positionof quinazoline ring
isveryimportant for the 1 receptor affinity
Prof. Dr. M.R. Kumbhare
Prazosineisorally usedashydrochloride salt.
Plasmahalf life is2 to 3 hours.
Sideeffectsincludedizziness,orthostatic hypotension (due to lossof reflex vasoconstriction
upon standing).
27. DOXAZOSİN
2,3-dihydrobenzo[b][1,4]dioxine
Aminogroupat 4th positionof quinazoline ring
28
(2,3-dihydro-1,4-benzodioxin-3-yl)methanone
Prof. Dr. M.R. Kumbhare
isveryimportant for the 1 receptor affinity.
Saturatedfuran
(tetrahydrofuran)
[4-(4-amino-6,7-dimethoxyquinazolin-2-yl)piperazin-1-yl]-
1-ADRENERGICRECEPTORBLOCKERS
[4-(4-amino-6,7-dimethoxyquinazolin-2-
yl)piperazin-1-yl]-(oxolan-2-yl)methanone
TERAZOSİN
30. ADRENERGİCNEURONBLOCKERS
RES
ERPINE
Prof. Dr. M.R. Kumbhare
Reserpineisan alkaloid isolated from the rootsof Rauwolfia Serpentina.
It affects the storageandreleaseof norepinephrine. It depletescatecholaminesandserotonine
from central andperipheral neuronsbyinterfering with the uptake of theseamines.
Reserpineisthe first effective antihypertensive drugin westernmedicine.
It haslargely beenreplacedbynewer agentswith fewer side effects.
31. ADRENERGİCNEURONBLOCKERS
RES
ERPINE
Prof. Dr. M.R. Kumbhare
Asindole derivatives, it issensitiveto decompositionbylight andoxidation, especially in
solution.
Reserpineisusedorally or parenterally for the treatment of hypertension.
32. ADRENERGİCNEURONBLOCKERS
Guanethidinepreventsthe releaseof norepinepherinefrom the postganglionic
neuronsin responseto sympatheticnervestimulation andcausesdepletionof it in
adrenergicneurons.
İt isusedorally for antihypertensive therapy.
Prof. Dr. M.R. Kumbhare
2-[2-(azocan-1-yl)ethyl]guanidine
GUANETHIDINE
Ocane:Suffixes for fully saturated
eight membered ring without nitrogen
34. CENTRALL
YACTINGSYMP
A
THOL
YTICDRUGS
Centrallyacting sympatholyticdrugsare 2-adrenergicreceptor agonists.
Prof. Dr. M.R. Kumbhare
Thesedrugscausea decreasein sympathetic outflow from the central nervoussystem.
Therefore, they decreasethe peripheral vascularresistance, bloodpressureandheart
rate andcontractility.
Clonidine,-methyldopa, guanabenzandguanafacineare examplesof thisclass.
37. What istautomerization ?
Tautomerization isthe processof isomerizationof onetautomer into anothertautomer.
REMINDER
Tautomersare two formsof the samecompoundwhichdiffer bypositionsof a hydrogenatom and a pi bond.The
Equilibriumarrow isusedto showthe tautomerequlibrium.
Forexampleketonesandenolsare tautomers:
ketone enol
N
H
N
H
N
Cl
Cl
N
H
H
N
N
Cl
Cl
Clonidinetautomerscanbedrawnasfollows
Prof. Dr. M.R. Kumbhare
39. it existsto a significantextent in the nonionizedform.
Thenonionizedform canpassthe membranesand/ orBBB
(BloodBrainBarrier).
N
H
N
H
N
CENTRALL
YACTINGSYMP
A
THOL
YTICDRUGS
CLONIDINE
Asa centrally actingdrug,at physiologicalpH,
Cl
Cl
Cl
H
N
N
N
H
Cl
Guanidine
Prof. Dr. M.R. Kumbhare
40. Asa centrally actingdrug,at physiologicalpH,
it existsto a significantextent in the nonionizedform
Howcanwe explainthisdilemma ?
Guanidine(strongbasic)
(pKa=13.6)
ionizedat physiologicalpH
Clonidinebearsa guanidine moiety
CENTRALL
YACTINGSYMP
A
THOL
YTICDRUGS
CLONIDINE
Cl
N
H
N
N
H
Cl
Prof. Dr. M.R. Kumbhare
41. H
N
CENTRALL
YACTINGSYMP
A
THOL
YTICDRUGS
CLONIDINE
Asa centrally actingdrug,at physiologicalpH,
Cl
it existsto a significantextent in the nonionizedform.
N
N
H
Cl
pKaof clonidineismuchmorelower than guanidine’spKa.
Guanidine(strong basic)
(pK
a=13.6)
Clonidine
(pKa=8.0)
Becauseof the inductiveand
resonanseeffectsof dichlorophenyl
ring
Thebasicityof clonidine is
decreased
43
44. HO
HO
CH2 COOH
NH2
C*
H
L-DOP
A
Dopa is the precursor of the catecholamines
[dopamine, norepinephrine (noradrenaline)
andepinephrine (adrenaline)].
Alsousedasantiparkinson drug.
Flyingwedgeprojectionof L-Methyldopa
L-Methyldopahas Sconfiguration
CENTRALL
YACTINGSYMP
A
THOL
YTICDRUGS
METHYLDOPA
*
?
Prof. Dr. M.R. Kumbhare
45. FromIUP
ACGoldBook
D/ LCONVENTIONIN STEREOCHEMISTRY
REMINDER
Anarbitrary conventionaccordingto which(+)-glyceraldehydewasnamedD-
glyceraldehyde (with the enantiomer L-glyceraldehydeandits racemate DL-
glyceraldehyde).
Prof. Dr. M.R. Kumbhare
D-glyceraldehyde
(R)-2,3-dihydroxypropanal
L-glyceraldehyde
46. REMINDER
Achemicalnameisconsistedof fourparts in the IUPACNomenclature System
IUPACNOMENCLATURE
PREFIX PARENT LOCANT SUFFIX
indicatethe location
andidentity of substituent(s)
Definesthe main part of the molecule
andindicatethe longestcarbonchain
orthe ring, etc.
identifies the primary functional group
FromFundamentalof Organic
ChemistrybyJ.McMurry
givesthe locationof the
primary functionalgroup
Prof. Dr. M.R. Kumbhare
50. METHYLDOPA
CENTRALL
YACTINGSYMP
A
THOL
YTICDRUGS
HO
HO
Methydopa isused only by oral route, because its zwitterionic character limits its
solubility.
Methyldopa absorptionislimited andrange 8%to 62%.
Its absorption appears to involve an amino acid transport system. Therefore its absorption
isaffected by food and about 40% of absorbed drug isconverted to O-sulfate conjugate by
the intestinalmucosal cells.
CH2
NH3
C COO-
CH3
Prof. Dr. M.R. Kumbhare
+
51. Methyldopa isunstablein the presenceof oxidizingagents(alsoair), alkaline pH and
light.
METHYLDOPA
CENTRALL
YACTINGSYMP
A
THOL
YTICDRUGS
HO
HO
CH2
NH3
C COO-
CH3
Prof. Dr. M.R. Kumbhare
+
Catecholisverysusceptibleto oxidation
52. Theethyl esterof methyldopaisknownasMethyldopate.
Thehydrochloridesalt of methyldopateishighlywater solubleanddeveloped to
makeparenteral solution.
Methyldopate ishydrolyzedto methydopain the bodyby esterases.
METHYLDOPA
CENTRALL
YACTINGSYMP
A
THOL
YTICDRUGS
METHYLDOP
A
TE
Hydrochloridesalt of
METHYLDOP
A
TE
Prof. Dr. M.R. Kumbhare
54. DIRECTV
ASODILA
TORS
TheseDrugsreducearterial smoothmuscletonebydirect action onthe vasculature
without interference from the autonomic innervation.
Theyproducevasodilationandlower the blood tension.
Theycancauseincreasein heart rate andcardiacoutputbyincreasedsympathetic
reflex activity.
Hydralazine, dihydralazineandsodiumnitroprussideare the examplesof this class.
Prof. Dr. M.R. Kumbhare
62. POTASSIUMCHANNELAGONISTS
Prof. Dr. M.R. Kumbhare
Thesedrugsare alsoknownasPotassiumChannelOpeners.
TheseagentsactivateATP-sensitiveK+-channelsin vascularsmoothmuscle.
Openingpotassiumchannelsleadsto a decreaseof intracellularCa+2 andresultsin
hyperpolarizationof the membrane.
Thisprocessproducesaninhibitory influenceonthe membraneexcitation and
causesvasodilation
Minoxidil anddiazoxideare the examplesof thisclass.
65. POTASSIUMCHANNELAGONISTS
DIAZOXIDE
It isa rapidly acting antihypertensiveagent for emergencyreductionof blood pressure
in hospitalizedpatient (with accelerated or malignant hypertension)byintravenous
injection.
Water solublesodiumsalt isusedfor injectable formulation.
Prof. Dr. M.R. Kumbhare
66. H2N NH2
N 1
O
6
5
4
2
N 3
POTASSIUMCHANNELAGONISTS
MINOXIDIL
piperidine
2,6-diamino-4-(piperidin-1-yl)pyrimidine 1-oxide
N
pyrimidine
N
N
N
H2N NH2
3
OSO-
MinoxidilSulfate
Prodrug
S
ulfotransferase
enzyme
ActiveMetabolite
Prof. Dr. M.R. Kumbhare
(in theliver)
67. POTASSIUMCHANNELAGONISTS
MINOXIDIL
N
N
N
H2N NH2
sodiumandwater retention, reflex tachycardia.
Minoxidileisusedfor severehypertensionuncontrolledbyother
drugs.It isthe onlydirect-acting vasodilatorthat requires
metabolicactivation to produceits antihypertensive effect.
It hascharacteristicsideeffectsof directvasodilatoryagentssuchas
O
Minoxidiletopical solutionisusedto treatalopeciaandrogenitica. It isbelievedto
increasecutaneousbloodflow stimulating hair growth.
Male-pattern baldness
Prof. Dr. M.R. Kumbhare
73. RENIN-ANGIOTENSIN SYSTEM INHIBITORS
AngiotensinI Angiotensin II
AngiotensionConverting Enzyme
AC
E
decapeptide Octapeptide
a potent vasoconstrictor
Significantregulatory effect onsodiumexcretionbyrenal tubes
Prof. Dr. M.R. Kumbhare
Glu-AP
(Glutamyl aminopeptidase)
Angiotensin III
Lesspotent asvasoconstrictor
74. RENIN-ANGIOTENSIN SYSTEM INHIBITORS
Renin
Angiotensinogen AngiotensinI AngiotensinII
Cardiacand Vascular
Hypertrophy
Systemic
Vasocontriction
IncreasedBlood
Volume
RenalSodiumand
FluidRetention
Aldosterone
Kidney
ELEV
A
TEDBLOOD
PRESSURE
AngiotensionIII
AC
E Glu-AP
Prof. Dr. M.R. Kumbhare
75. RENIN-ANGIOTENSIN SYSTEM INHIBITORS
Renin
Angiotensinogen AngiotensinI AngiotensinII
Cardiacand Vascular
Hypertrophy
Systemic
Vasocontriction
IncreasedBlood
Volume
RenalSodiumand
FluidRetention
Aldosterone
Kidney
ELEV
A
TEDBLOOD
PRESSURE
AngiotensionIII
AC
E Glu-AP
Prof. Dr. M.R. Kumbhare
77. A
CEINHIBITORS
Prof. Dr. M.R. Kumbhare
Captopril,Lisinopril,Enalapril, Benazepril,Quinapril,Ramipril, Fosinopril and
Trandoprilare the examplesofAngiotensionConvertingEnzyme(ACE)
Inhibitors.
Enalapril, Benazepril,Quinapril,Ramipril, FosinoprilandTrandoprilare
prodrugs.
78. PHAR406PHARMACEUTICALCHEMISTRYIV
EMU-SPRINGTERM
A
CEINHIBITORS
Prof. Dr. M.R. Kumbhare
Becauseof the importancein regulating kidneyfunction,aldosteronerelease,
electrolyte balanceandbloodvolume,the renin-angiotensionsystemisvery
important drugtarget in the managementof highbloodpressureandhearth
failure.
Theyare usedin hypertensionandhearth failure
Acommonsideeffect ofACEinhibitorsisa drycoughappearingin about 10%
of patients(it appearsto berelated to the elevationin bradykinin).
81. PHAR406PHARMACEUTICALCHEMISTRYIV
EMU-SPRINGTERM
David W.Cushman,Miguel A. Ondetti, Designof angiotensin converting
enzyme inhibitors, Nature Medicine , Volume 5, Number 10,p.1110-1112,
October 1999.
Proposed binding to the active site of ACEby asubstrate or venom peptide inhibitor with
terminal sequence Phe–Ala–Pro,by succinylamino acids, and by captopril.
Prof. Dr. M.R. Kumbhare
82. PHAR406PHARMACEUTICALCHEMISTRYIV
EMU-SPRINGTERM
CONCLUSION
Theactivesitemodelthat we describedin our originalstudiesusedsimple
chemicalconceptsguidedbya hypothetical ‘paper andpencil’modelof
substrateandinhibitor bindingto the enzyme.
Thisrational designapproachhasled to a classof structurallysimple
compoundsthat caninhibit the actionof the enzymewith greatpotencyand
specificity,propertiesthat translate in vivointo effective antihypertensive
activity with aremarkablylow level of unwantedsideeffectsor toxicity.
82
Prof. Dr. M.R. Kumbhare
86. ACE INHIBITOR PRODRUGS
Enalapril, Benazepril,Quinapril,Ramipril, FosinoprilandTrandoprilare examples
of thisclass.
Enalaprilisthe first andthe prototype of this class.
Thesedrugsdonot havethiol group(nocommonsideeffects!)
Exceptfosinopril(containingphosphorus),all of them sharethe (S)-2-amino-4-
phenylbutyricacidethyl estermoiety. Whyester formation?
(S)-ethyl 2-amino-4-phenylbutanoate
86
Prof. Dr. M.R. Kumbhare
97. ANGIOTENSIN II ANT
AGONIS
TS
97
Prof. Dr. M.R. Kumbhare
Thesedrugsare the angiotensionII receptor blockers.
Thereare four subtypesof angiotensionII receptorsidentified to date, namely
AT1, AT2,AT3and AT4
AT1receptors of angiotensionII haveimportancein managingspesific
cardiovasculardiseases.
98. Stimulation ofAT1receptorsof angiotensionII cause
(a) vasocontriction
(b) increasedaldosteronesynthesisand secretion
(c) increasedvasopressin secretion
(d) decreasedrenal blood flow
(e) increasedrenal tubular sodium reuptake
(f) Other physiological events
98
Prof. Dr. M.R. Kumbhare
ANGIOTENSIN II ANT
AGONIS
TS
99. ANGIOTENSINII ANT
AGONISTS
CompetetiveantagonistsofAT1receptorsof angiotensionII produce
vasodilatory effects.
Thesedrugsare usedin the treatment of hypertensionandheart failure in a
similarmannerasACEinhibitors.
Because they do not inhibit ACE,they do not cause an increase in bradykinin,
which contributes to the some of the side effects of ACEinhibitors (cough and
angioedema).
Losartan, valsartan, candesartan, irbesartan and telmisartan are the
examplesof this class.
99
Prof. Dr. M.R. Kumbhare
101. ANGIOTENSIN II ANT
AGONIS
TS
N
HOH2C C4H9
CH2
N
N
N
HN
L
OS
ART
AN
101
Prof. Dr. M.R. Kumbhare
2-butyl-4-chloro-1-[4-[2-(1H-tetrazol-5-yl)phenyl]benzyl]imidazole-5-methanole
1
2
N3
Cl
4
5
Losartanisthe first angiotensionII A
T1receptorantagonist
Potassiumsalt isusedorally. How??Fromwhere canit give
Ksalt?Brandname :Cozaar
Tetrazoleringhasacidiccharacter and
resemblesthe acidicfunctionof
angiotensionII duringreceptor
interaction.
102. ANGIOTENSIN II ANT
AGONIS
TS
N
N
HOH2C C4H9
CH2
N
N
N
HN
L
OS
ART
AN
Cl
Extensivefirst-pass metabolism
N
N
Cl
C4H9
CH2
N
N
N
HN
HOOC
Thismetabolite isclosely15 times more
potent than the parent compound
oxidation
102
Prof. Dr. M.R. Kumbhare
109. CALCIUMCHANNELBLOCKERS
CalciumChannelBlockerscanbeclassifiedaccordingto their chemical
structures as follows:
BenzothiazepineDerivatives
Diltiazem
Aralkylamine Derivatives(DiphenylalkylamineDerivatives)
Verapamil
1,4-DihydropyridineDerivatives
Nifedipine,nicardipineamlodipineand others
Theeffects of thesethree classesonmyocardiumandthe arteries vary from
oneclassto the other
Prof. Dr.ErçinERCİY
AS,May 8,2018
109
Prof. Dr. M.R. Kumbhare
110. CALCIUMCHANNELBLOCKERS
Benzothiazepines(diltiazem) andAralkylamines(verapamil) affect boththe
hearth and arteriols
BenzothiazepineDerivatives
Diltiazem
Aralkylamine Derivatives(DiphenylalkylamineDerivatives)
Verapamil
1,4-DihydropyridineDerivatives
Nifedipine,nicardipine,amlodipineand others
Therefore, benzothiazepines(diltiazem) andAralkylamines(verapamil) are used
clinicallyasantianginal, antiarrhythmicand antihypertensive
114
Prof. Dr. M.R. Kumbhare
111. CALCIUMCHANNELBLOCKERS
Dihydropyridines have much less affect on cardiac tissues and higher
specificityfor the arteriols.
BenzothiazepineDerivatives
Diltiazem
Aralkylamine Derivatives(DiphenylalkylamineDerivatives)
Verapamil
1,4-DihydropyridineDerivatives
Nifedipine,nicardipine,amlodipineand others
Therefore, Dihydropyridines are used frequently as antianginal and
antihypertensive
111
Prof. Dr. M.R. Kumbhare