The document discusses various types of adrenergic receptor antagonists including alpha blockers like prazosin and terazosin which are used to treat hypertension and benign prostatic hyperplasia, as well as non-selective antagonists like phentolamine and beta blockers like propranolol which are used to treat conditions like hypertension, angina, and arrhythmias. The mechanisms, classifications, clinical uses and side effects of these different adrenergic antagonists are explained in detail across multiple pages.
This presentation deals with the beta blockers commonly used in day-to-day practice alongwith some interesting mnemonics to remember their names & site of action
This presentation deals with the beta blockers commonly used in day-to-day practice alongwith some interesting mnemonics to remember their names & site of action
This presentation was given by me during my M.pharm.
It contains description, classification, mechanism of actions and therapeutic uses of Neuromuscular blockers.
This presentation was given by me during my M.pharm.
It contains description, classification, mechanism of actions and therapeutic uses of Neuromuscular blockers.
OVERVIEW OF ANS
SYMPATHETIC SYSTEM PREGANGLIONIC AND POST GANGLIONIC FIBERS
DISTRIBUTION OF SYMPATHETIC FIBERS
SYNTHESIS OF CATECHOLAMINES AND THERE INHIBITION AT VARIOUS LEVELS
RECEPTORS OF SYMPATHETIC SYSTEM
SYMPATHOMIMETIC DRUGS *DIRECTLY AND INDIRECTLY ACTING DRUGS*
SYMPATHOLYTIC DRUGS
USES OF THESE DRUGS
SUMMARY
ADDITIONAL INFO :ALPHA 2 RECEPTORS ARE MAJORLY PRESENT IN CNS AND DRUG USED IS CLONIDINE
General introduction about hypertension and structure activity relationship of Different types of antihypertensive drugs, and related questions that were asked in exams.
detailed SAR and mode of action of ACE inhibitors
Adrenergic Agonist & Sympathomimetic Drugs.
It includes:
Sympathetic Nervous System
Structures of the major catecholamines
Drugs acting at adrenergic neurons
Structure-Activity Relationship of sympathomimetic Amines
Structure & main clinical use of important sympathomimetic drugs
Adrenergic Receptors: Types, Nomenclature
Sympathomimetic drugs (with Recent Advances)
Beta-adrenergic blockers as a potential treatment for COVID-19 patients
Summary
Magnetically Modulated drug delivery system, Noval Drug Delivery system, New approaches to develop magnetically modulated drug delivery system and Formulation Design.
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
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.
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
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.
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
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.
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
8. MCMP 407
Autonomic Drugs
Drugs that produce their primary therapeutic effect by
mimicking or altering the functions of the autonomic
nervous system are called autonomic drugs.
These autonomic agents act either by stimulating
portions of the autonomic nervous system or by
blocking the action of the autonomic nerves.
8
10. MCMP 407
Introduction
Alpha & Beta adrenergic receptor antagonists
prevent the interaction of the endogenous
neurotransmitter norepinephrine (N.E) or
sympathomimetics (endogenous or synthetic
catecholamines, synthetic noncatecholamines)
with the corresponding adrenergic receptor.
10
11. MCMP 407
Receptor agonists activate signal transduction pathways
HO
NH3
HO CH CH2 NH2
OH
Norepinephrine
α 1 adrenergic
receptor
(+) Phospho -
Gq lipase C
PIP2
COOH IP3 Diacylglycerol
Increase Ca 2+ Activate Protein
Kinase C
Response
12. MCMP 407
Receptor antagonists block agonist binding to the receptor
HO
HO CH CH2 NH2
Antagonist NH3 OH
Norepinephrine
Phospho -
Gq lipase C
What effect would an antagonist alone
COOH
have on receptor activation?
16. MCMP 407
Alpha Blockers
Bind selectively to alpha receptors
Interfere with ability of catecholamines or other
sympathomimetics to provoke alpha responses on the heart
& peripheral vasculature
Inhibitory action of epinephrine on insulin secretion is
prevented too (insulin production is not reduced)
Side effects: orthostatic hypotension, baroreceptor-
mediated reflex tachycardia, impotence
Absence of Beta blockade allows maximum expression of
cardiac stimulation from N.E.
16
17. MCMP 407
Mechanism of Action (alpha
blockade)
Competitive Inhibition (reversible binding with receptors)
– Phentolamine
– Prazosin
– Yohimbine
Covalent Bond (irreversible & insurmountable blockade)
– Phenoxybenzamine
(once blockade in effect, even massive doses of sympathomimetics are
ineffective
UNTIL METABOLISM OF Phenoxybenzamine takes place
17
19. MCMP 407
α1 -adrenergic receptor antagonists
O
Acyl
Quinazoline ring moiety
Vary in half-life:
N R Prazosin 3 hrs
H3CO N N Terazosin 12 hrs
Doxazosin 20 hrs
N Piperazine ring
H3CO
Undergo extensive
metabolism, excreted
NH2
mainly in the bile
Vasodilators
Prazosin: R =
(Minipres) O Relaxation of smooth
muscle in enlarged
Terazosin: R =
prostate and in bladder
(Hytrin) O base
O “First-dose” effect
Doxazosin: R =
(Cardura)
O
20. MCMP 407
Dosage
Prazosin Terazosin
First dose 0.5mg at bed Initially 1mg at bed time
time , orally. orally.
Then 0.5mg BD or TDS , Titrate by approx. doubling
for 3-7 days. dose at weekly intervals.
Followed by 1mg BD or Usual maintenance dose is
TDS , for 3-7 days. 2-10 mg OD.
Therafter increase gradually
as required upto max. of
20mg / day.
21. MCMP 407
Mechanism Of Action
Selective blocked of postsynaptic alpha-1
adrenoseptor.
PHARMACOLOGICAL EFFECTS
CVS:
Decreases blood pressure
Only minimal changes in Cardiac output.
No reflex Tachycardia.
Kidneys:
Retension in salt & fluid when administered without a
diuretic or during long term Therapy.
22. MCMP 407
Clinical Uses
Mild to moderate chronic hypertension (more
effective when used in combination with a diuretic or
propanalol).
Acute congestive heart failure (Prazosin).
To relieve urinary obstruction ( Terazosin).
23. MCMP 407
Adverse Effect
CNS
Dizziness, headache
Resp.Tract
Nasal congestion.
GIT
GI hypermotility
Kidneys
Salt & Fluid
retension
29. MCMP 407
YOHIMBINE (Procomil, Yocon)
An alkaloid derived from the bark of the
tree Corynanthe yohimbi.It is an alpha-
adrenergic blocking agent that in excess
causes antidiuresis, increased blood
pressure, tachycardia, irritability, tremor,
sweating, dizziness, nausea, and vomiting.
It is used therapeutically to treat erectile
dysfunction.
30. MCMP 407
Blocks presynaptic alpha-2 receptors enhanced
release of N.E. from nerve endings
Toxic effect:
– Idiopathic orthostatic hypotension (rare)
– Impotence
– Crosses BBB, may cause muscle activity & tremor
– Overdosetachy, HTN, paresthesia
33. MCMP 407
Phentolamine (REGITINE)
Mechanism of Action
Non-selective alpha blockade
Inhibits response to Serotonin.
Stimulate Muscarinic receptor &, H1 H2 histamine reptor
Peripheral vasodilation (alpha-1 block) & decreased BP within
2 min (lasts 10-15 min) elicit baroreceptor- mediated
cardiac stimulation reflex
33
34. MCMP 407
Non-selective adrenergic receptor antagonists
Imidazolines
HO
Non-selective α receptor
N antagonist
N CH2 Competitive (reversible) blocker
N Potent vasodilator, but induces
H pronouced reflex tachycardia
Block of presynaptic α2 receptors
may promote release of NE
H3 C Also blocks 5-HT receptors, and is
Phentolamine (Regitine) a muscarinic and histamine
receptor agonist
35. MCMP 407
Pharmacological Effects
Glands
Stimulate Lacrimal, Slivary , Pancreatic &
Respiratory tract secreations.
CVS
Vasodilation through both alpha-adrenoceptor
blokade & an additional non-adrenergic action on
vascular smooth muscle
Decrease Peripheral resistance & Increase Venous
capacitance
Cardiac stimulaiton through Reflex effect & alpha-2-
36. MCMP 407
Phentolamine
(Clinical Uses)
Acute HTN emergencies
– Intraop manipulation of PHEOCRHOMOCYTOMA
– Autonomic NS Hyperreflexia
» 30 to 70 mcg/kg IV (prompt/transient dec in BP)
» Drip may be desirable to maintain steady state
Accidental extravascular injection of
sympathomimetic drug
– Local infiltration of phentolamine-containing solution
(2.5 to 5mg in 10ml)
Frost Bite.
36
To cause erection in male sexual Dysfunction.
37. MCMP 407
Adverse Effects
CVS Precautions
Severe tachycardia, Pts with coronary artery
arrhythmias, angina, disease.
postural hypotension. Pts with peptic ulcer.
GIT
Diarrhea , Increased
gastric acid production.
39. MCMP 407
α-ADRENOCEPTOR
ANTAGONISTS
Interaction with receptors:
A) Reversible B) Irreversible
• Phentolamine Phenoxybenzamin
• Tolozoline
• Prazosin
• Labetolol(both
alpha & beta )
• Ergot alkaloids
40. MCMP 407
LABETALOL ( Mixed alpha
& beta)
Labetalol (Normodyne, Trandate) is a mixed alpha/
beta adrenergic antagonist, which is used to treat
high blood pressure.
41. MCMP 407
Non-selective adrenergic receptor antagonist
β-Haloalkylamines
Non-selective α receptor
antagonist
CH3 Also blocks acetylcholine,
histamine, and serotonin
O receptors
N
Irreversible antagonist resulting
from covalent modification of
receptor
Cl
Phenoxybenzamine (Dibenzyline)
42. MCMP 407
Irreversible blokade long Duration (14-48 hrs)
Phenoxybenzamine(Dibenzyline)
Non-selective (alpha-1 & alpha-2 blocker) covalent
bond
Alpha-1 block > Alpha-2 block
Slow onset (up to 60 min to reach peak) IV or PO.
Long time required for structural change of the
molecule needed to render drug active
Elimination half-time: 24 hr (cumulative effect with
repeated doses)
Note:
Block can be overcome only by the synthesis of new
adrenoseptors.
42
43. MCMP 407
Mechanism of Action
It bind covalently to alpha adrenoceptors (alpha-1 >
alpha-2)
It inhibits reuptake of released nor-epinephrine by
presynaptic adrenergic terminals.
It also blocks histamine (H1) , acetylcholine, &
serotonin receptors.
44. MCMP 407
Non-selective adrenergic receptor antagonist
β-Haloalkylamines: Mechanism of receptor inactivation
R R
R R R R Cl- R R Cl-
N
N N N
Nu Nu
Aziridinium ion
Cl receptor alkylated
receptor
45. MCMP 407
Cliniclal uses
To relieve vasospasm in Raynaud’s phenomenon
To relieve urinary obstruction
To control autonomic hyperreflexia due to spinal cord
transection.
– Preoperative treatment of HTN of pt with
PHEOCHROMOCYTOMA (0.5-1 mg/kg PO)
» With chronic alpha blockaderelieving intense peripheral
vasoconstriction, allows expansion of IV volume as reflected by a
drop in Hct
– Given to Pt with excessive vasoconstriction with associated
tissue ischemia (eg. hemorrhagic shock) but only after IV
fluid volume is replenished.
46. MCMP 407
Adverse Effect
CNS GIT
Fatigue, Sedation Nausea & vomiting
Eye (with oral
admisinstration)
Miosis
Reproduction
CVS
Inhibition of
Postural hypotension, ejaculation.
Reflex tachycardia.
Local
Resp.Tract
Local tissue irritation by
Nasal stifness injection.
48. MCMP 407
Clinical pharmacology of α -adrenergic
receptor antagonists
Route of
Drug Receptor admin. Clinical uses
Phenoxybenzamine α1, α2 Oral Pheochromocytoma, hypertensive crisis
Phentolamine α1, α2 Parenteral Pheochromocytoma, hypertensive crisis,
male impotence
Prazosin α1 Oral Hypertension, benign prostatic
hypertrophy
Terazosin α1 Oral Hypertension, benign prostatic
hypertrophy
Doxazosin α1 Oral Hypertension, benign prostatic
hypertrophy
Side effects of α 1 receptor antagonists:
Orthostatic hypotension, inhibition of ejaculation, nasal stuffiness, tachycardia
49. MCMP 407
Beta Blockers
Bind to Beta adrenergic receptors and block effects of
catecholamines & sympathomimetics on the heart &
smooth muscles of the airways & blood vessels
Beta blockers should continue during periop period to
avoid reflex SNS hyperactivity
49
56. MCMP 407
Classification
Nonselective for beta1 & beta2 receptors (propanolol,
nadalol, timolol, pindolol)
Cardioselective for beta1 receptors (esmolol,
metoprolol, atenolol, acebutolol, betaxolol)
Beta receptor selectivity is dose-dependent
Beta receptor selectivity is lost when large doses of
antagonist is given
56
58. MCMP 407
β -adrenergic receptor antagonists
Pharmacological effects
CH3
CH
Decreased cardiac output and
O N heart rate
H CH3
OH Reduced renin release
Increase VLDL, Decrease HDL
Inhibit lipolysis
Propranolol Inhibit compensatory
(Inderal) glycogenolysis and glucose
release in response to
hypoglycemia
Increase bronchial airway
resistance
Therapeutic uses for β-adrenergic receptor antagonists:
Hypertension, angina, cardiac arrhythmias, migraine, stage fright,
thyrotoxicosis, glaucoma, congestive heart failure (types II and III)
59. MCMP 407
Propanolol (Inderal la, INNOPRAN XL)
First Beta antagonist introduced clinically.
Nonselective for beta1 & beta2 receptors (equal
antagonism)
Pure antagonist (lacks sympathomimetic intrinsic
activity).
Mechanism of Action
Blocks both Beta 1 and Beta 2- Adrenoceptor
59
60. MCMP 407
Clinical use
Hypertension (most often used with either a diuretic
or a vasodilator).
Angina pectoris & prophylaxis of myocardial
infarction.
Supraventricular & ventricular arrhythmias.
Ventricular ectopic beats, esp if precipitated by
catecholamines.
Obstructive cardiomyopathy (to increase stroke
volume)
Dissecting aortic aneurysm (to decrease rate of
development of systolic pressure).
63. MCMP 407
Contraindication:-
Cardiogenic shock
Right ventricular failure secondary to pulmonary
hypertension.
Congestive cardic failure
Asthma
Greater than 1st degree heart block
Hypotension
Raynaud’s phenomenon
Pts on MAO inhibitors.
64. MCMP 407
Precautions
Dose Precaution
20-80mg TDS or QID, Pts with asthma.
orally. Pts with diabetes
In emergency treatment mellitus esp IDDM.
of dysarrhythmias
1mg over 1 min, IV;
repeated at 2 min.
interval to a maximum
of 10mg
65. MCMP 407
Non-selective β -adrenergic receptor antagonists
CH3 Less lipophilic than propranolol
CH Long half-life: ~20 hours
O N Mostly excreted unchanged in urine
H CH3
HO OH Administered: Oral
Uses: Hypertension, angina, migraine
HO
Nadolol (Corgard)
CH3 Thiadiazole nucleus with
morpholine ring
C CH3
O N Administered: Oral, Ophthalmic
H CH3
O OH Uses: Hypertension, angina,
N N migraine, glaucoma
N S How will β-blockers affect
Timolol (Timoptic, Blocadren) pupil size?
69. MCMP 407
Effect of chronic β-receptor blockade
Na+
Presynaptic neuron
Tyrosine
Na+
Dopamine
Tyrosine
Action Potential
H+ O
DA MA
NE NE
Ca2+
Uptake 1
Na+, Cl-
NE
NE NE NE
Effector organ
70. MCMP 407
Effect of chronic β-receptor blockade:
Receptor up-regulation Na+
Tyrosine
Na+
Dopamine
Tyrosine
Action Potential
H+ O
DA MA
NE NE
Ca2+
Uptake 1
Na+, Cl-
NE
NE NE NE
Effector organ
71. MCMP 407
Selective β1 -adrenergic receptor antagonists
CH3
CH
O N CH3
H “Cardioselective”
OH
Less bronchconstriction
Moderate lipophilicity
Half-life: 3-4 hours
R Significant first-pass
Metoprolol (Lopressor, Toprol) metabolism
R= CH2 O CH3 Administered: Oral,
Bisoprolol (Zebeta) CH3 parenteral
R= O CH2 CH Uses: Hypertension,
CH2 O CH3 angina, antiarrhythmic,
congestive heart failure
72. MCMP 407
Selective β1 -adrenergic receptor antagonists
CH3
CH
O N
CH3
OH
H “Cardioselective”
Less bronchconstriction
Low lipophilicity
NH2
Half-life: 6-9 hours
Administered: Oral,
O parenteral
Atenolol (Tenormin) Uses: Hypertension,
angina
73. MCMP 407
Selective β1 -adrenergic receptor antagonists
CH3 Very short acting
CH Half-life: 9 minutes
O N Rapid hydrolysis by
H CH3
OH esterases found in red blood
cells
Administered: Parenteral
O
Note: incompatible with
CH3 sodium bicarbonate
O
Uses: Supraventricular
Esmolol (Brevibloc) tachycardia, atrial
fibrillation/flutter,
perioperative hypertension
77. MCMP 407
Adrenergic β3 Receptors
Antagonists
SR 59230A is a selective antagonist of the
beta-3 adrenergic receptor.
L-748,337 Selective β3 antagonist .
SR 59230A hydrochloride Potent and selective β3
antagonist.
Adrenergic receptor located primarily in the small
intestine, adipose tissue and vascular endothelium
79. MCMP 407
Mixed adrenergic receptor antagonists
Non-selective β receptor
antagonist, with potency
OH somewhat lower then that
H of propanalol.
N 1'
1 α1 receptor antagonist,
HO
CH3 with potency less then that
CONH2
of phentolamine.
β-blocking activity prevents
Labetalol (Normodyne, Trandate)
reflex tachycardia normally
associated with α1 receptor
antagonists
Administered: Oral,
parenteral
Uses: Hypertension,
80. MCMP 407
Mixed adrenergic receptor antagonists
OCH3
O
O N
H
OH
N Carvedilol (Coreg)
H
Non-selective β receptor β-blocking activity prevents
antagonist reflex tachycardia normally
α1 receptor antagonist associated with α1 receptor
Both enantiomers antagonize α1 antagonists
receptors Administered: Oral
Only (S)-enantiomer possesses Uses: Hypertension, congestive
β-blocking activity heart failure (Types II and III)
81. MCMP 407
Pharmacologic manipulation of the adrenergic system
Na+
Presynaptic neuron
Tyrosine
Na+
1
Dopamine
Tyrosine
2
Action Potential
H+ O
DA MA
NE NE
Ca2+
Uptake 1
3 Na+, Cl-
NE
NE NE NE
β
Effector organ
83. MCMP 407
Adrenergic Neuron Blocker
Drugs that reduce storage or release of NE
H Possess guanidino moiety
N NH2
N C (pKa > 12)
NH Effects can be blocked by
transport blockers
Guanethidine (Ismelin) Uses: Hypertension
84. MCMP 407
Mechanism of Action:
It inhibits nor epinephrine release from
sympathetic nerve endings.
Clinical Uses
Moderate to severe hypertension ( usually with
a diuretic & a vasodilator)
85. MCMP 407
Adverse Effects
CVS: Contraindication
Orthostatic hypertension Pheochromocytoma
& syncop esp. during
exercise.
Severe coronary
artery disease.
GIT:
Cerebrovascular
Diarrhea
insufficiency.
Sk,muscle
During MAO
Aching , weakness
inhibitor
Reroduction administration.
Delayed Ejecullation
86. MCMP 407
Catecholamine depleters
H3CO N
H
N OCH3
H H O
H OC OCH3
H3CO2C
OCH3 OCH3
Reserpine (Serpasil)
Indole alkaloid obtained Slow onset of action
from the root of Rauwolfia Sustained effect (weeks)
serpentina Used in the treatment of
Block vesicular monoamine hypertension
transporters May precipitate depression
Deplete vesicular pool of NE
87. MCMP 407
Mechanism of Action
Reserpine blocks the ability of adrenergic
transmitter vesicles to take up & store biogenic
amines by interfering with an uptake
mechanism that depend on Mg & ATP ,
Depletaion of nor epinephrine, dopamine &
serotonin in both central & peripheral neurons.
Also exerts a direct vasodilating effect on
vascular smooth muscle when administer
intraarterially.
88. MCMP 407 HO CH2 CH NH2 TYROSINE
COOH
Inhibition of nor HO
X tyro sine hydroxyla s e
Metyrosine
epinephrine synthesis HO CH2 CH NH2 DOPA
COOH
aromatic L-amino a cid de carboxyla s e
HO
HO CH2 CH2 NH2 DOPAMINE
dopamine β -hydroxyla s e
HO
HO CH CH2 NH2 NOREPINEPHRINE
OH
phenylethanolamine-
HO N-methyltran sfera s e
HO CH CH2 NH EPINEPHRINE
OH CH3
89. MCMP 407
Drugs that reduce storage or release of NE
Na+
Tyrosine
Na+
Dopamine
Reserpine Tyrosine
Guanethidine
Action Potential
H+ O
MA
NE NE
Ca2+
NE
Guanethidine, Guanethidine
Bretylium
β
Effector organ
93. MCMP 407
Methyldopa
Mechanism of Action
Converted into alpha methylnorepinephrine which is
stored in adrenergic nerve granules, where it is
stoichiometrically replaces norepinephrine &, is
released by nerve stimulation to interact with
presyneptic central alpha adrenoseptors, Decrease
sympathetic outflow Decrease arterial presure.
Inhibit Dopa decarboxylase decrease stor of
norepinephrine in the sympathetic nervous system.
Decrease BP.
94. MCMP 407
Clinical Uses:-
Mild to moderate severe hypertension.
Dosage
1-2 g orally in divided doses.
97. MCMP 407
2) CLONIDINE
Mechanism of Action
It stimulates presyneptic alpha-receptor in vasomotor
center of brain Decrease sympathetic outflow to
the peripheral vessels.
Dosage
0.2 - 1.2 mg/day
Clinical Uses
Fall in BP, decrease in cardiac output & heart rate.
Decrease plasma Renin activity
100. MCMP 407
Mechanism of Action
Decrease of aqueous humor production
Side Effects
Ocular irritation, contraindicated in
patients with asthma, obstructive air
disease, bradycarida, and congestive heart
failure.
101. MCMP 407
Side effects of β -blockers:
Bradycardia, AV block, sedation, mask symptoms
of hypoglycemia, withdrawal syndrome
May alter airway resistance, carbohydrate/lipid
metabolism, distribution of extracellular ions
Cross CNS/placenta
GI: N/V/D
Fever, rash, myopathy, alopecia,
thrombocytopenia with chronic use