This document discusses the treatment of a 35-year-old man presenting with hypertension. He has a family history of hypertension, is obese, and drinks several cocktails daily. Tests show elevated cholesterol and glucose levels. The document then outlines the classification, mechanisms, and types of antihypertensive drugs and discusses how they could be used to treat this patient. It focuses on diuretics, ACE inhibitors, ARBs, and calcium channel blockers. The optimal treatment would likely involve lifestyle changes and combination drug therapy targeting his multiple risk factors.
This presentation consists of various approaches to treat hypertension depending on severity. It also include treatment according to international guidelines. Classification and brief description of each antihypertensive agent has been mentioned.
introduction to oral hypoglycemic agents with description about sulphonylurea and glinides along with their MOA, indication, side effects and brand name
This presentation consists of various approaches to treat hypertension depending on severity. It also include treatment according to international guidelines. Classification and brief description of each antihypertensive agent has been mentioned.
introduction to oral hypoglycemic agents with description about sulphonylurea and glinides along with their MOA, indication, side effects and brand name
Fibrinolytics and anti platelet agents(easy)prithvilokesh
about platelet plug formation Fibrinolytic and anti platelet agents pathology, classes of drugs with mechanism of action , adverse effects uses and novel drugs..
Proton pump inhibitors (PPIs) block the gastric H,K-ATPase, inhibiting gastric acid secretion. This effect enables healing of peptic ulcers, gastroesophageal reflux disease (GERD), Barrett's esophagus, and Zollinger-Ellison syndrome, as well as the eradication of Helicobacter pylori as part of combination regimens.Proton-pump inhibitors (PPIs) are a class of medications that cause a profound and prolonged reduction of stomach acid production. They do so by irreversibly inhibiting the stomach's H+/K+ ATPase proton pump.[1]
They are the most potent inhibitors of acid secretion available.[2] Proton-pump inhibitors have largely superseded the H2-receptor antagonists, a group of medications with similar effects but a different mode of action, and antacids.[3]
PPIs are among the most widely sold medications in the world. The class of proton-pump inhibitor medications is on the World Health Organization's List of Essential Medicines.[4][5] Omeprazole is the specific listed example.[4][5]
Mechanism of action
The activation of PPIs
Proton pump inhibitors act by irreversibly blocking the hydrogen/potassium adenosine triphosphatase enzyme system (the H+/K+ ATPase, or, more commonly, the gastric proton pump) of the gastric parietal cells.[71] The proton pump is the terminal stage in gastric acid secretion, being directly responsible for secreting H+ ions into the gastric lumen, making it an ideal target for inhibiting acid secretion.[citation needed]Because the H,K-ATPase is the final step of acid secretion, an inhibitor of this enzyme is more effective than receptor antagonists in suppressing gastric acid secretion.[72] All of these drugs inhibit the gastric H,K-ATPase by covalent binding, so the duration of their effect is longer than expected from their levels in the blood.[73]
Targeting the terminal step in acid production, as well as the irreversible nature of the inhibition, results in a class of medications that are significantly more effective than H2 antagonists and reduce gastric acid secretion by up to 99%.[2
classification , mechanism of actions, pharmacokinetics, adverse effects, uses and contra indications of antiparkinsonian drugs. with a note on other movement diorders and treatment
Fibrinolytics and anti platelet agents(easy)prithvilokesh
about platelet plug formation Fibrinolytic and anti platelet agents pathology, classes of drugs with mechanism of action , adverse effects uses and novel drugs..
Proton pump inhibitors (PPIs) block the gastric H,K-ATPase, inhibiting gastric acid secretion. This effect enables healing of peptic ulcers, gastroesophageal reflux disease (GERD), Barrett's esophagus, and Zollinger-Ellison syndrome, as well as the eradication of Helicobacter pylori as part of combination regimens.Proton-pump inhibitors (PPIs) are a class of medications that cause a profound and prolonged reduction of stomach acid production. They do so by irreversibly inhibiting the stomach's H+/K+ ATPase proton pump.[1]
They are the most potent inhibitors of acid secretion available.[2] Proton-pump inhibitors have largely superseded the H2-receptor antagonists, a group of medications with similar effects but a different mode of action, and antacids.[3]
PPIs are among the most widely sold medications in the world. The class of proton-pump inhibitor medications is on the World Health Organization's List of Essential Medicines.[4][5] Omeprazole is the specific listed example.[4][5]
Mechanism of action
The activation of PPIs
Proton pump inhibitors act by irreversibly blocking the hydrogen/potassium adenosine triphosphatase enzyme system (the H+/K+ ATPase, or, more commonly, the gastric proton pump) of the gastric parietal cells.[71] The proton pump is the terminal stage in gastric acid secretion, being directly responsible for secreting H+ ions into the gastric lumen, making it an ideal target for inhibiting acid secretion.[citation needed]Because the H,K-ATPase is the final step of acid secretion, an inhibitor of this enzyme is more effective than receptor antagonists in suppressing gastric acid secretion.[72] All of these drugs inhibit the gastric H,K-ATPase by covalent binding, so the duration of their effect is longer than expected from their levels in the blood.[73]
Targeting the terminal step in acid production, as well as the irreversible nature of the inhibition, results in a class of medications that are significantly more effective than H2 antagonists and reduce gastric acid secretion by up to 99%.[2
classification , mechanism of actions, pharmacokinetics, adverse effects, uses and contra indications of antiparkinsonian drugs. with a note on other movement diorders and treatment
hypertensive drugs in various conditions.pptxSunandaMohan
Electrolyte imbalance
Metabolic: hyperglycemia, hyperlipidemia, hyperuricemia.
Erectile dysfunction
Not effective in chronic renal disease.
More effective in elderly: also in patients with isolated systolic hypertension.
Long acting, used once a day
No tolerance and no fluid retention
Reduce calcium excretion, preferred in osteoporosis (especially older women).
Hydrochlorothiazide is one commonly used thiazide and consider as 1st choice.
the main problem with thiazide is hypokalemia and this can be avoided by K+ supplementation or using K+ sparing diuretics.
However, ACEI/ARBs should not combined with K+ sparing diuretics which cause dangerous hyperkaliemia in some pt.
Indications: HT, especially co-existing with:-
DM,
Nephropathy,
Left Ventricular Hypertrophy (LVF),
Chronic Heart Failure (CHF),
Angina,
Post Myocardial Infarction (MI) cases.
ADRs: Dry persistent cough, Fetal malformations, granulocytopenia, proteinuria (Rare).
Efficacy as monotherapy ~30-40%. Always combined with other drugs
Slow onset (1-3 weeks), well sustained action
Gradual in BP in hypertensives only.
Mech : Initially, TPR increases due to -blockade
Later TPR decreases – resistance vessels adapt to chronically decreased CO
Both systolic & diastolic BP reduced.
Also, ↓ release of NA from sympathetic nerve endings, ↓ Renin release from kidney (1).
Contraindicated in CHF, Pulmonary diseases (Bronchial asthma/COPD), Peripheral vascular disease and Variant angina.
Cardioprotective – especially helpful to prevent sudden cardiac death if given Post MI, along with ACEIs.
Hypoglycemic episodes – (1 selective less risky)
Absence of SEs like Postural Hypotension, GIT effects etc
Efficacy as monotherapy ~30-40%. Always combined with other drugs
Slow onset (1-3 weeks), well sustained action
Gradual in BP in hypertensives only.
Mech : Initially, TPR increases due to -blockade
Later TPR decreases – resistance vessels adapt to chronically decreased CO
Both systolic & diastolic BP reduced.
Also, ↓ release of NA from sympathetic nerve endings, ↓ Renin release from kidney (1).
Almost obsolete drugs
Reserpine – R.serpentina roots. Indigenous. Inhibits tpt of NA into storage granules depletion. Slow onset (2-3 wks). Also CA & 5HT depletion in brain depression, antipsychotic effect & Parkinsonism like symptoms. Not preferred as anti-HT drug now.
Guanethidine – Displaces NA from storage granules, release of NA from nerve terminals & NA reuptake inhibited depletion. Obsolete drug.
Latest guidelines (JNC8, NICE 2011): Consider:-
Age / Race: Younger patients (↑ renin) respond better to ACEIs/ARBs. Blacks & aged respond better to CCBs. Diuretics alternatives to CCBs.
If monotherapy ineffective – ACEIs/ARBs + CCBs/Diuretics.
ACEIs/ARBs + CCBs + Diuretics – 3rd step
If all fails – resistant HT – add a aldosterone antagonist or beta-blocker with vasodilator action.
BP > 140/90 in pregnancy can be risky
CKD, Diabetes & Chronic HT are risk factors for Pre-eclampsia
Aspirin
This ppt describes the anti-arrhythmic drugs pharmacology and the treatment of various arrhythmias. Novel drugs in clinical trials and older drugs with repurposed formulations also have been included. Useful for MD Pharmacology residents as well as MBBS students.
Malignant hyperthermia is a potentially fatal hyperdynamic response due to pharmacogenetic abnormalities. This ppt gives a brief description of pathology and pharmacotherapy of malignant hyperthermia.
The ppt is made for undergraduate students to have a basic understanding on Corticosteroids and its role in all feilds of medicine. This is also useful to Postgraduate students
Gout is a type of inflammatory arthritis that causes permanent disability if left untreated. This presentation focuses on the important salient points we need to remember in Gout in all aspects - diagnosis, managment (both non-pharmacological and pharmacological approaches).
This presentation is useful to both MBBS and Postgraduate students of Pharmacology.
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.
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.
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
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.
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
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
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
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
2. A CASE SCENARIO...
• A 35-year-old man presents with a blood pressure of 150/95 mm Hg.
• He has been generally healthy, is sedentary, drinks several cocktails per day, and does not smoke
cigarettes.
• He has a family history of hypertension, and his father died of a myocardial infarction at age 55.
• Physical examination is remarkable only for moderate obesity.
• Total cholesterol is 220
• High-density lipoprotein (HDL) cholesterol level is 40 mg/dL.
• Fasting glucose is 105 mg/dL.
• Chest X-ray is normal.
• Electrocardiogram shows left ventricular enlargement.
• How would you treat this patient?
3. 1. List the Classification of Anti-hypertensive drugs according to the site
of action
2. Describe the pharmacological basis for use of thiazides and other
diuretics in hypertension
3. Describe the MOA, pharmacologic effects, ADR and indications for
ACEIs and ARBs
4. List out the use of following drugs to treat hypertension ( CCB,
Ganglion blocking drugs, Adrenergic neuron blocking drugs, Beta
receptor antagonists, alpha receptor antagonists, vasodilators)
5. List out the Advantages and limitations of combining
antihypertensives
6. Describe the Pharmacological agents used in PIH and ISH
4. DEFINING HYPERTENSION
• Hypertension, also known as high or
raised blood pressure, is a condition
in which the blood vessels have
persistently raised pressure.
• Hypertension is diagnosed if, when it
is measured on two different days,
the systolic blood pressure readings
on both days is ≥140 mmHg and/or
the diastolic blood pressure readings
on both days is ≥90 mmHg
5.
6.
7.
8.
9. A BRIEF HISTORY
• 1950s
Veratrum and Sodium thiocyanate - toxic and difficult to use
Ganglion blockers - effective but varied side effects
Reserpine - Very effective but caused Mental depression
Hydralazine - Marked side effects when used alone
• 1960s
Methyldopa, Beta blockers, Thiazides, Loop diuretics, Clonidine
1961 - Guanithidine - improvement on ganglion blockers
10. Contd..
• 1970s
Alpha 1 blocker - prazosin introduced
• 1980 - 1990s
ACE inhibitors, ARBs, CCB
• 1995
Imidazolines, Neutral endopeptidase inhibitors
• 2007
Direct renin inhibitors - Aliskiren
• Nov 2022
Baxdrostat - AAldosterone synthesis inhibitor for resistant hypertension
https://www.sciencedaily.com/releases/2022/11/221107192302.htm
Currently in Phase 2 trials
11.
12.
13.
14.
15. • THIAZIDES - Diuretic of choice
for uncomplicated hypertension;
have similar efficacy.
• Enhance the effect of other
antihypertensive agents.
• Chlorthalidone has longer t1/2 -
48hrs compared to
hydrochlorothiazide (< 24 hours)
16. ABSORPTION, FATE AND
EXCRETION:
• well absorbed from the intestine
• effect starts within one hour.
• distributed throughout the ECF and
are relatively concentrated in the
kidney.
• crosses the placental barrier.
• excreted in urine.
19. • No effect on capacitance vessels, sympathetic reflexes are not
impaired.
• Postural hypotension is rare
• Average fall in MAP - 10 mm Hg
• Potentiate other Anti-hypertensives except DHP CCB.
• Hence prevents tolerance to other agents by not allowing expansion
of plasma volume
20.
21. Thiazides should be used at low doses only because by increasing
the dose, antihypertensive effect does not increase but adverse
effects tend to increase.
Indapamide:
• Effective as an antihypertensive at lower doses than those
required for the diuretic effect (due to its direct vasodilatory
action).
• It also produces less metabolic adverse effects (hypokalemia,
hyperglycemia, hyperuricemia etc.) and can be used as an
antihypertensive in diabetic patients (whereas other thiazides
are contra-indicated).
22.
23.
24.
25.
26.
27.
28.
29. • Once a day dosing, flat dose-response curve
• No fluid retention, No tolerance
• No CNS side effects
• No postural hypotension
• More effective in patients with Isolated systolic hypertension
• Reduces risk of osteoporosis in older women and post-menopausal
women
• Low cost
30. • 1960s -70s Thiazides were used as monotherapy - dosage was 50mg/day of
HCZ / Chlorthalidone
Side effects noted were:
• Hypokalemia - muscle pain, fatigue, loss of energy, Torsedes de pointes
resulting in sudden cardiac death
• Erectile dysfunction in males
• Carbohydrate intolerance, precipitation of diabetes ( due to inhibition of
insulin release because of hypokalemia)
• Dyslipidemia - rise in total and LDL cholesterol, lowering of HDL - increases
risk of atherogenesis
• Hyperuricaemia - Inhibition of urate excretion - precipitates gout
31. ALLHAT (2002) - The Antihypertensive and Lipid-Lowering Treatment to
Prevent Heart Attack Trial - Thiazides are first choice anti-hypertensive.
Low dose Thiazides <25mg/day were very effective. Side effects were only
because of increasing the dose.
Advantages of low dose thiazides:
1. Significant hypokalemia doesn’t occur
2. Continuous ECG monitoring - no incidence of increase in arrhythmias
3. Very minimal effects on blood glucose and lipid profile - so can be used in
diabetes
4. Reduces Fatal and non fatal MI risk by 27-44%
5. Reduces stroke risk by 31-49%
6. Reduces left ventricular hypertrophy
32. • Potent, oral diuretic.
• Not recommended for long term Rx
• Indicated in severe hypertension with CHF and renal
dysfunction.
• Indacrinone can be used in patients of gout because it
inhibits reabsorption of uric acid in the nephron (other loop
diuretics and thiazides cause hyperuricemia).
33.
34.
35. • Rapidly absorbed (60-100%) from the GI
tract.
• Food reduces its bioavailability.
• The onset of action is quick and the
duration short.
• Given IV, the diuresis begins within 2
minutes and lasts for 2-3 hours.
• Excreted within 4 hours by kidney
• Fifty per cent of the dose is excreted
unchanged in urine; the rest is conjugated
with glucuronide in the kidney.
• Hence, in patients with renal insufficiency
the plasma t½ is prolonged.
37. DRUGS PROPRIETA
RY NAMES
INITIAL
ORAL
DOSAGE
DOSAGE
RANGE
ADVERSE EFFECTS COMMENTS
FUROSEMIDE LASIX 20MG BD 40-320MG IN
2-3 DIVIDED
DOSES
SAME AS
THIAZIDES. BUT
HIGHER RISK OF
EXCESSIVE
DIURESIS AND
ELECTROLYTE
IMBALANCE,
INCREASES
CALCIUM
EXCRETION
SHORT DURATION OF
ACTION. SHOULD BE
RESERVED FOR
PATIENTS WITH
KIDNEY DISEASE OR
FLUID RETENTION.
POOR ANTI-
HYPERTENSIVE
ACTION.
ETHACRYNIC
ACID
EDECRIN 50MG OD 50-100MG
OD OR BD
BUMETANIDE 0.25 MG
BD
0.5 - 10 MG
IN 2 OR 3
DOSES
TORSEMIDE DEMADEX,
DYTOR
5MG OD 5 - 10 MG OD EFFECTIVE BLOOD
PRESSURE
MEDICATION AT LOW
DOSAGE
37
40. (1) Aldosterone antagonist: Spironolactone,
eplerenone.
(2) Direct inhibitors of renal epithelial
sodium channels: Triamterene and Amiloride
- They have no anti-hypertensive action.
These drugs are combined with loop or
thiazide diuretics to prevent or correct
hypokalemia.
41. SPIRONOLACTONE:
• Acts by competitive antagonism of aldosterone, in the distal part of the nephron
• Prevents potassium secretion and thus decreases sodium reabsorption.
• Given orally, its full response is observed after 3-5 days.
• Short t½ of 1.6 hrs.
• Major action is due to an active metabolite, canrenone (t½ 17 hr).
• When combined with thiazide or loop diuretics it prevents loss of potassium.
• Metabolised to several inactive compounds.
42.
43. PHARMACOLOGICAL USES OF SPIRONOLACTONE:
• By itself it is not an antihypertensive agent.
• As an add-on drug, it may be particularly useful in hypertensive patients with significant
hypokalemia
• Drug of choice in primary hyperaldosteronism.
• Add-on drug in congestive heart failure.
ADVERSE REACTIONS OF SPIRONOLACTONE
• Hyperkalemia
• Endocrine effects: decreased libido, gynecomastia, impotence and menstrual
irregularity.
• Miscellaneous effects: lethargy and drowsiness.
• It may increase blood urea nitrogen and serum uric acid levels.
• Gastritis
Preparation and dosage:
Spironolactone is supplied as a microcrystalline preparation, 25 mg tablet. Dose :
100-200 mg per day (maximum 400 mg) in divided doses.
46. EPLERENONE
• Blocks the mineralocorticoid receptors in the kidney, heart, blood vessels and brain more
selectively than spironolactone.
• Metabolised by the liver - t½ of 4 -6 hours.
• Adverse reactions: GI intolerance, dizziness, hyperkalemia and
hypertriglyceridemia.
• Advantage over spironolactone is the lower incidence of endocrine side effects.
It is used to treat:
(a)Hypertension, in the dose of 50 mg OD, increased to 100 mg OD (maximum dose)
within 4 weeks, as required,
(b) Post MI CHF, in one half of the above dosage.
(c) It is also used in the combined oral contraceptive pill, Yasmin
47.
48.
49.
50.
51.
52. Absorption:
Oral Bioavailability: ~3%
Peak Plasma Time: 1-3 hr
Onset of action: Optimum effect achieved within 2 weeks
Effects are decreased when taken with a high fat meal
Metabolism:
In liver by CYP3A4
In preclinical studies, P-gp was found to be the major efflux system involved in
intestinal absorption and elimination via biliary excretion of aliskiren
Excretion:
Half-life: 24 hr
Excretion: Urine (~25%)
58. • All ACEI are prodrugs except captopril and
lisinopril
• Bioavailability of about 65%.
• Absorption is reduced by food and so it is
given 1 hour before a meal.
• Metabolism: liver (50%)
• Metabolites: captopril-cysteine disulfide
(inactive)
• Renal excretion (95%)
Dosage Forms & Strengths of captopril:
Tablet - 12.5mg, 25mg, 50mg, 100mg
61. • Dry cough - possibly due to increase in bradykinin levels
• Hyperkalemia, particularly in patients with renal insufficiency and in
those taking a potassium sparing diuretic.
• Skin rashes, disturbances of the sense of taste, vitiligo
• Headache, GI disturbances, muscle cramps and rarely leucopenia.
• Proteinuria (>1 g/day) has been described.
• Angioedema.
• Foetal toxicity in animals and should be avoided in pregnancy.
64. Status in Hypertension:
• Presently the first-line antihypertensives.
• ACE inhibitors are useful in the treatment of hypertension of all grades due to all causes.
• Addition of a diuretic potentiates their antihypertensive efficacy (90%)
CLINICAL TRIALS:
1. AIRE (1993) - Acute Infarction Ramipril Efficacy Study
2. HOPE (2000) - Heart Outcomes Prevention Evaluation
3. ALLHAT (2002) - The Antihypertensive and Lipid-Lowering Treatment to Prevent
Heart Attack Trial
All the prospective studies confirmed the anti-hypertensive and
cardioprotective effects of ACE inhibitors.
They are more effective in younger hypertensives (<55 yrs)
65. INDICATIONS:
They are specially indicated as antihypertensives in:
a. Hypertension with left ventricular hypertrophy - because hypertrophy is
gradually reversed by ACE inhibitors.
b. Patients with diabetes mellitus - because ACE-I slow the development of
nephropathy.
c. Renal diseases with hypertension - ACE inhibitors slow the progression of
chronic renal diseases like glomerulosclerosis.
d. Patients with co-existing IHD including post-MI patients.
e. In severe hypertension, they may be combined with other antihypertensives
like β-blockers, CCBs or diuretics
66. Contraindication for ACEI:
(1) Severe bilateral renal artery stenosis as they reduce GFR and may
cause renal failure,
(2) Aortic stenosis,
(3) Coarctation of the aorta; and
(4) Pregnancy.
67.
68. ENALAPRIL:
• It is a prodrug and is converted in the body to the active metabolite enalaprilat.
• Food does not interfere with its absorption.
• It is more potent.
• Its action is slower but lasts longer.
• It is less liable to cause taste disturbances, leucopenia and glomerulopathy
• Enalaprilat is the only drug in this class available intravenously.
69.
70. • block the AT1 receptors,
• Pharmacologic effects are similar to those of ACE inhibitors
• ARBs do not increase bradykinin levels.
• Used as first-line agents for the treatment of hypertension, especially in
patients with a compelling indication of diabetes, heart failure, or
chronic kidney disease.
• ARBs should not be combined with an ACE inhibitor for the treatment
of hypertension due to similar mechanisms and adverse effects.
• teratogenic
71.
72. • Pharmacokinetics are similar to ACEIs
• All indications, adverse effects and contra-
indications of ACEI also apply to ARB
except that incidence of cough and
angioedema is less with ARB.
• Metabolized by hepatic P450 enzyme
CYP2C9.
73. Special features of losartan:
– Produce active metabolite - 5-Carboxylic acid (E-3174) (active
metabolite; 40 times as potent as losartan in angiotensin II-blocking
activity)
– Has anti-platelet action due to competitive antagonism of TXA2.
– Mild uricosuric effect
Telmisartan has additional PPAR-δ agonistic activity. This activity
can help in patients with dysglycemia. Telmisartan is longest acting
whereas eprosartan is shortest acting ARB.
74.
75. 1. LIFE (2002) - LCZ696 In Advanced Heart FailurE
2. VALUE (2004) - Valsartan Antihypertensive Long-term Use Evaluation
Outcomes in hypertensive patients with valsartan or amlodipine.
3. SCOPE (2004) - Study on COgnition and Prognosis in Elderly
Stroke prevention with candesartan in elderly with ISH.
4. JLIGHT (2004) - Japanese Losartan therapy Intended for Global renal
protection in HyperTensive patients.
All these trials attested the favourable effects of ARBs on morbidity and
mortality in hypertensive patients.
76.
77.
78. CCB belong to 3 chemically distinct classes:
1. Phenylalkylamines e.g., Verapamil
• Least selective
• Has significant effects on both cardiac and vascular smooth muscle cells.
2. Dihydropyridines (DHP) e.g., Nifedipine, Amlodipine, etc.
Greater affinity for vascular calcium channels than the calcium channels in the heart.
They are beneficial in treating hypertension. They show little interaction with other
cardiovascular drugs, such as digoxin or warfarin.
3. Benzothiazepines e.g., Diltiazem.
Affects both cardiac and vascular smooth muscle cells.
84. • Most of these agents have short half-lives (3 to 8
hours) following an oral dose.
• Sustained-release preparations are available and
permit once-daily dosing.
• Amlodipine has a very long half-life and does not
require a sustained-release formulation
• As these drugs are metabolised by liver, dose
adjustment in patients with renal disease is less
critical.
• They are potent vasodilators.
• Calcium channel blockers do not dilate veins.
85.
86. • Nifedipine - hypertensive emergencies.
• Nifedipine and other short half-life dihydropyridines are not
recommended for long term treatment of hypertension.
• CCB are useful in impaired renal function or asthma, and in acute
hypertension during pregnancy.
• As a monotherapy particularly in moderately hypertensive patients
with diabetes mellitus.
• Diltiazem and amlodipine are as effective as diuretics, beta-blockers
or their combination, in the long term treatment of essential
hypertension.
87.
88.
89. VERAPAMIL - 1st degree AV block, constipation.
Verapamil and diltiazem - avoided in patients with heart failure or
with atrioventricular block due to their negative inotropic and
dromotropic effects.
DIHYDROPYRIDINES - Dizziness, headache, feeling of fatigue
caused by a decrease in blood pressure, Peripheral edema, gingival
hyperplasia.
CCB have no significant CNS effects. Edema of feet may be observed.
95. CLEVIDIPINE
Clevidipine is a dihydropyridine L-type calcium channel blocker, highly selective
for vascular smooth muscle.
It reduces mean arterial blood pressure by decreasing systemic vascular resistance.
Used in patients with acute hypertension who cannot take drugs orally.
Pharmacokinetics:
• Onset: 2-4 minutes
• Protein Bound: 99.5%
• Metabolized in blood and extravascular tissues
• Half-Life: Initial 1 minute; terminal 15 minutes
• Excretion: Urine (63-74%); feces (7-22%)
Dosage forms:
Intra venous emulsion - 1–2 mg/hour IV infusion.
95
96. 1. HINT, TRENT, SPRINT I & II - Increased mortality / re-infarction
in patients treated with standard nifedipine or other short acting DHPs.
Possibly because of repeated surges of adrenergic discharge and marked
swings of BP due to short action of rapidly acting DHP.
2. These were not seen in long acting DHP and Verapamil / diltiazem -
DAVIT I & II
97. contd..
3. Syst-EUR - Systolic hypertension in Europe shows that Nitrendipine
reduces cardiovascular morbidity and mortality in elderly hypertensives
4. ACCOMPLISH (2008) and ASCOT-BPLA (2005) - Superior
efficacy of amlodipine both as monotherapy and when combined with
an ACEI for reducing CVS events in high risk HTN patients
5. ALLHAT and Syst-EUR - Stroke prevention by CCB
• CCBs are next to ACEI in slowing diabetic nephropathy
• Most useful anti-hypertensives in cyclosporine induced Hypertension
in renal transplant recipients.
98.
99.
100.
101. PHARMACOKINETICS:
• It is well absorbed after oral and parenteral administration.
• Maximal blood levels are reached within 3 to 4 hours after oral
administration.
• The drug is acetylated in the liver.
Fast acetylators → drug levels → less drug effect
Slow acetylators→ drug levels → ADR: SLE
• Elimination of the drug is almost complete within 24 hours.
• Less than 5% of an oral dose is excreted unchanged in urine. Hence, it
can be used even in the presence of renal damage.
102. PHARMACOLOGICAL ACTIONS:
• Direct relaxation of the arteriolar wall.
• The effect is slow in onset but prolonged. Even on
its IV administration, the BP falls only after 15-20
minutes.
• The fall in BP → decrease in the total peripheral
resistance
↓
compensatory tachycardia (↑ CO and SV)
• The splanchnic, coronary, cerebral and renal blood
flow may increase.
• It causes increase in plasma renin activity and
fluid retention.
• It can be given in hypertension during pregnancy
(2nd and 3rd trimesters).
103.
104. ADVERSE REACTIONS:
• Gastrointestinal irritation producing nausea, vomiting, gastric
hypersecretion, anorexia and diarrhoea.
• Cardiac effects: These include palpitation, tachycardia and anginal
attacks.
• Others like headache, nasal congestion, flushing, tremors and
dizziness.
• It causes secondary salt and water retention.
• Intolerance: The manifestations are fever, skin rash and
polyneuritis.
• GI haemorrhage and pancytopenia are serious manifestations.
• Acute rheumatoid arthritis or SLE like syndrome may develop
with large doses (over 600 mg/day) given for prolonged periods.
105.
106. Preparations and dosage:
• Hydralazine hydrochloride tablets 10,
25, and 50 mg. Maximum dose 100 mg
daily.
• Dihydralazine sulphate 25 mg tablet.
• Injection 20 mg for IM/IV use.
107. 2. SODIUM NITROPRUSSIDE:
This drug, known since 1850, has been used as a colour
indicator for acetone and aldehydes. It was regarded as a
poison because of its cyanide group.
Given by IV infusion, it is metabolised to active
compound NO which causes relaxation of arterioles and
veins.
• This results in the reduction in peripheral resistance
and venous tone, lowering the after load and the
preload.
• The myocardial oxygen consumption is reduced with
improvement in myocardial function in low output
states.
• Heart rate and the regional blood flow are little
affected.
• It increases plasma renin activity.
• It is rapidly metabolised to thiocyanate.
• The action is of rapid onset but of very short duration
108.
109.
110. THERAPEUTIC USES:
• Hypertensive emergencies.
• It is infused IV slowly in the dose
of 0.5-5 mcg/kg/min.
• In the treatment of severe
hypertension, if the BP is not
adequately controlled after 10
minutes of infusion at the maximal
rate, the drug should be stopped
immediately for fear of toxicity.
• Nitroprusside must not be stopped
abruptly during treatment of heart
failure because of the danger of
rebound hypertension.
111. ADVERSE EFFECTS:
• Hepatic dysfunction
• Thiocyanate toxicity -
Prolonged administration of sodium
nitroprusside either in high doses or in the
presence of renal insufficiency.
This results in fatigue, anorexia,
nausea, vomiting, sweating, disorientation,
psychotic behavior and muscle twitching.
Larger doses may cause ataxia,
rigidity, convulsions and metabolic acidosis.
• Nitrates have a synergistic effect with
vasodilator drugs and can lead to sudden
fall in BP and collapse.
112. PREVENTION OF TOXICITY:
• Administration of sodium
thiosulphate along with nitroprusside
prevents the accumulation of cyanide.
• Alternatively, hydroxocobalamin
may be given which combines with
cyanide to form cyanocobalamin
which is a nontoxic compound.
• Methaemoglobinaemia is also known
following infusion of nitroprusside. It
should be avoided in pregnancy.
113. AVAILABLE FORMS
• Sodium nitroprusside is supplied as 50
mg powder to be dissolved in 500 ml
of 5% dextrose in water, just prior to
administration.
• When it is exposed to light, it is
converted to cyanide; hence a brown
or black paper bag over the IV fluid
container is necessary.
• Translucent plastic tubing may need
taping.
• Only freshly prepared solution should
be used.
117. DOSAGE AND AVAILABLE
FORMS:
Minoxidil is used with a diuretic as a
reserve drug in patients with severe
hypertension who do not respond to
other drugs.
Minoxidil is started with a low dose of 5
mg daily and is gradually increased to
40–50 mg.
BALDNESS:
Activates the gene that controls the
protein of hair shaft by this it stimulates
the maturation and growth of cells of the
hair shaft. Hence it is used topically (2%
solution) for the correction of alopecia.
118. DIAZOXIDE:
Related to thiazide diuretics and is a potent arteriolar dilator.
MOA - similar to minoxidil
ADR: Hyperglycaemia, salt and water retention, palpitation and myocardial
ischaemia.
THERAPEUTIC USE: It is used intravenously in hypertensive
emergencies where monitoring of infusion is not possible.
Diazoxide has a long duration of action (24 hours) and is suitable in such
situations.
120. Fenoldopam:
It is a D1 dopamine receptor agonist, brings about dilation of
peripheral arteries and also loss of sodium.
It has a short t½ of 10 minutes and is given as an IV infusion.
USES:
Useful in hypertensive emergencies and postoperative
hypertension, particularly when there is impaired renal function.
Started with a low dose of 0.1 μg/kg/min, it is gradually increased
every 20 minutes till adequate response is attained. (maximum dose
1.6 μg/kg/min).
Adverse effects: include flushing, headache, palpitation and
hypotension. It should be avoided in patients with glaucoma since it
can raise the intraocular pressure.
Fenoldopam has efficacy similar to sodium nitroprusside but is
devoid of thiocyanate-related complications.
121.
122.
123.
124. Peripheral vascular alpha-
receptors are of two types
• Postsynaptic α1 receptors
which are stimulatory in
nature; their activation causes
vasoconstriction and
• Presynaptic α2 receptors
(auto-receptors), which are
inhibitory in nature; their
activation inhibits NA release.
125.
126.
127. NON SELECTIVE ALPHA BLOCKERS
PHENOXYBENZAMINE
Cyclizes spontaneously to highly reactive
ethyleniminium intermediate.
Competitive block:
Blockade is slow onset & longer duration
(3-4 days). Also inhibits reuptake of NE. Shifts blood
from pulmonary to systemic circuit. Shift fluid from
extravascular to vascular compartment - relaxation of
postcapillary vessels.
PHARMACOKINETICS - Preferred ROA- i.v.
Lipid soluble -penetrates brain. Mainly excreted
through urine in 24 hrs. Accumulates in adipose
tissue on chronic administration.
Dose - 20-60 mg/d oral; 1mg/kg/1hr slow i.v
infusion.
Uses - Pheochromocytoma, occasionally 2° shock,
PVD
PHENTOLAMINE
More potent α-blocker
Duration of action is shorter (min).
Equally blocks α1 & α2 receptors- NA
release ↑sed.
Uses - Δsis & intraop.management of
pheochromocytoma.
HTN due to clonidine withdrawl, cheese
reaction.
Dermal necrosis due to extravasated i.v
NA/DA.
Given S.C as local infiltration.
128.
129.
130. ALPHA 1 BLOCKER
Prazosin
• Highly selective α1-blocker , α1: α2 selectivity 1000:1
• Fall in BP with only mild tachycardia.
• Dilates arterioles more than veins
• Postural hypotension occurs as 1st dose effect, minimized by starting with low
doses at bed time.
• Also inhibits PDE- ↑se cAMP in smooth muscle.
PK
• Effective orally, BA- 60%.
• Highly bound to plasma proteins (α1 acid glycoprotein).
• Metabolized in liver, excreted in bile.
• t1/2 – 2-3hrs, effect lasts for 6-8hrs.
Uses
• Primarily as antihypertensive.
• LVF not controlled by diuretics & digitalis.
• Raynaud’s disease
• BPH
• Scorpion sting
131.
132. FIRST DOSE EFFECT
• Occurs in 1% patients
• Due to profound postural hypotension
• Lose consciousness 30-60 min after receiving 1st dose
• Minimized by given first dose of the drug at bedtime or in very low
initial doses (less than 1mg)
• Adviced patients not to drive or do any hazardous activities after
taking the dose for 12-24hrs.
138. BETA BLOCKERS
• They are the first-line antihypertensive drugs in mild to moderate
hypertension with cardiac problems.
• β-blockers are effective and well-tolerated and are of special value in
patients who also have arrhythmias or angina.
• They should not be used alone.
• Suitable for combination with other antihypertensives, particularly
with drugs that cause tachycardia as their side effect (e.g.
vasodilators).
• Beta blockers are avoided in patients with peripheral arterial disease.
139.
140.
141.
142.
143.
144.
145.
146.
147.
148.
149.
150. Atenolol is the preferred β-blocker because of the advantages like once
a day dosing, absence of CNS side effects and β1 selectivity.
β-blockers should always be tapered while withdrawing.
Metoprolol may be given as a sustained release preparation for twice
daily use. It is particularly preferred in patients with concurrent
hypertension and heart failure.
Esmolol is a short-acting β1-blocker with a half life of about 10 min. It
is given intravenously as a loading dose of 0.5–1 μg/kg followed by an
infusion (50–300 μg/kg/min). Esmolol is suited for use in intraoperative
and postoperative hypertension and in hypertensive emergencies.
151.
152.
153. ALPHA + BETA BLOCKERS
Labetalol and carvedilol block
α1- and β- receptors. They are
used IV in the treatment of
hypertension in
pheochromocytoma and in
hypertensive emergencies.
159. CLONIDINE
MECHANISM OF ACTION:
It is a selective α2-agonist. Stimulation
of α2 autoreceptors in the CNS (in the
vasomotor centre and hypothalamus)
decreases central sympathetic outflow,
blocks the release of noradrenaline from
the nerve terminals leading to a fall in BP
and bradycardia
160.
161.
162.
163. Pharmacological actions:
Given IV it produces a transient hypertensive response followed by a prolonged fall in both
systolic and diastolic BP accompanied by bradycardia. Initial hypertensive effect is not seen
after its oral administration.
PHARMACOKINETICS:
Bioavailability: Immediate release (75-85%)
Protein bound: 20-40%
Duration: 6-10 hr.
Metabolism in Liver.
Elimination Half-life: 12-16 hr.
Excretion: Urine
164. Other Uses
1. In opioid withdrawal: Most withdrawal symptoms in opioid addicts
are of sympathetic overactivity and can be benefited by treatment with
clonidine.
2. Diabetic neuropathy: Clonidine controls diarrhoea by improving
absorption of NaCl and water in the gut by stimulation of α2 receptors
in the intestines.
3. With anaesthetics: Clonidine given preoperatively reduces the dose
of the general anaesthetic needed due to its analgesic effects.
165.
166.
167. Preparations:
Clonidine hydrochloride 0.1 mg tablets. A transdermal preparation is
also available; its effect lasts for 7 days.
Guanfacine and Guanabenz are related to clonidine and have actions
similar to clonidine. Their duration of action, however, is prolonged.
New drugs like moxonidine and rilmenidine are congeners of
clonidine with longer half lives. These drugs are selective for
imidazoline receptors that modulate the central α2 receptor activity.
168. AVAILABLE DOSAGE FORMS:
Abrupt discontinuation of clonidine therapy can lead to
rebound hypertension - Rx with phentolamine
169. ALPHA METHYL DOPA
• An analog of dopa, is a prodrug.
• It is metabolised in the body to alpha
methyl norepinephrine which is an α2-
agonist and acts like clonidine.
• It reduces central sympathetic outflow
leading to a fall in BP.
• Renin levels also fall but renal blood flow
is well maintained.
• Onset of action is about 4–6 hr
• Duration of action 12–24 hr.
• Left ventricular hypertrophy is reversed in
about 12 weeks of treatment.
170.
171. USES:
Methyldopa is used in mild to moderate hypertension along with a diuretic.
It is safe in hypertension during pregnancy and is the preferred antihypertensive
in such patients. Started with 250 mg twice daily, the dose may be increased to a
maximum of 750 mg BD.
ADVERSE EFFECTS:
Sedation, dryness of mouth and nose, nightmares, depression, vertigo,
extrapyramidal signs, raised prolactin levels, headache, postural hypotension,
impotence, hemolytic anemia
On prolonged use, salt and water retention may blunt the antihypertensive effect
(called pseudotolerance) and needs a diuretic to be added.
172.
173.
174.
175. • These drugs inhibit the NN type of nicotinic receptors that
are present on the autonomic ganglia (both sympathetic and
parasympathetic).
• The therapeutic effect (decrease in blood pressure) is due to
the decrease in neurotransmission through sympathetic
ganglia whereas decreased transmission through
parasympathetic ganglia is responsible for the adverse
effects like urinary retention and dry mouth.
• Hexamethonium and trimethaphan are the drugs in this
group and are used as antidotes for nicotine poisoning.
176. • Trimethaphan is given intravenously to produce controlled
hypotension during certain surgical procedures due to its rapid and
short action (15 minutes)
• Trimethapan is used along with nitroprusside as a slow i.v. infusion for
hypertensive emergencies in aortic dissection.
177. Guanethidine:
depletes the stores of
noradrenaline in the
adrenergic neurons and also
blocks its release.
Because of the adverse
effects like postural
hypotension, diarrhoea and
sexual dysfunction,
guanethidine is not used.
178. Reserpine
It is an alkaloid obtained from Rauwolfia
serpentina (Sarpagandhi) that grows in India.
MECHANISM OF ACTION:
• In the adrenergic neurons, it binds to the
vesicles that store monoamines like
noradrenaline, dopamine and 5-HT and
destroys these vesicles.
• Reserpine thus depletes the stores of these
monoamines and reduces BP.
• Depletion of monoamines particularly
dopamine is thought to be responsible for
the antipsychotic effects of reserpine
179. USES:
Hypertension
Initial - 0.5 mg daily for 1 or 2 weeks
Maintenance - 0.1-0.25 mg PO OD
Use higher dosages cautiously occurrence of mental depression
or other adverse reactions may increase
Psychiatric Disorders
0.5 mg daily, but may range from 0.1 to 1 mg; titrate dose
according to patient response
Tardive Dyskinesia
0.25 mg q6hr; may increase by 0.1-0.25 mg to a total of 5 mg
daily
180. ADVERSE EFFECTS:
drowsiness, depression,
nightmares, parkinsonism, postural
hypotension, oedema, weight gain,
gynaecomastia and sexual
dysfunction
AVAILABLE FORMS AND
DOSAGES:
tablet - 0.1mg, 0.25mg
It is not currently in clinical
practice
198. CASE SCENARIO ANSWER
The patient has Joint National Committee stage 1
hypertension.
The strong family history suggests that this patient has
essential hypertension.
Need to do ECHO, LFT, RFT, Sr. electrolytes
Non-Pharmacological management - behavioral,
including dietary changes and aerobic exercise.
198
199. CONTD..
Thiazide diuretics in low doses are inexpensive, have relatively few
side effects, and are effective in many patients with mild hypertension.
Other first-line agents include angiotensin-converting enzyme
inhibitors, angiotensin receptor blockers, and calcium channel
blockers.
A single agent should be prescribed and the patient reassessed in a
month.
If a second agent is needed, one of the two agents should be a
thiazide diuretic. Once blood pressure is controlled, patients should be
followed periodically to reinforce the need for compliance with both
lifestyle changes and medications.
199