Pharmacology of Respiratory Disorders - Cough & Asthma - PDF

Pharmacology of Respiratory Disorders Cough Asthma 10/11/2024 276  Drugs Acting On The Respiratory System Many conditions affect the respiratory system. Some of the conditions are life threatening, while many are c...

Pharmacology of Respiratory Disorders Cough Asthma 10/11/2024 276  Drugs Acting On The Respiratory System Many conditions affect the respiratory system. Some of the conditions are life threatening, while many are chronic conditions which affect thousands of patients. PNEUMONIA: Pneumonia is caused by an infection of the lung. bacteria (like the pneumococcus bacterium) or viruses. ASTHMA : Asthma, a condition usually caused by allergic reactions to substances in the environment, affects many people. The allergic reactions cause the bronchioles to spasm. Hence, the flow of air into and out of the lungs becomes impaired. STATUS ASTHMATICUS: Status asthmaticus is a very sudden, continuous, and intense asthmatic attack. 10/11/2024 277  Drugs Acting On The Respiratory System… EMPHYSEMA/ Chronic Obstructive Pulmonary Disease (COPD). : – Emphysema is a condition in which the patient has large portions of the alveolar walls destroyed. – Consequently, the patient finds it necessary to breathe faster and more deeply in order to obtain the oxygen needed to live. – Emphysema is often associated with smoking. PULMONARY EDEMA: – Pulmonary edema is a condition in which fluid collects in the interstitial spaces of the lungs and in the alveoli. – Obviously, the exchange of gases in the alveoli becomes impaired. 10/11/2024 278  Pharmacotherapy of cough  Cough is a useful physiological mechanism  clear the respiratory passages of foreign material and excess secretions.  May be annoying and prevent rest and sleep.  Chronic cough can contribute to fatigue, especially in elderly patients. The cough reflex  Involves the central and peripheral nervous systems, as well as the smooth muscle of the bronchial tree.  Irritation of the bronchial mucosa  Bronchoconstriction  Stimulates cough receptors in tracheobronchial passages  Afferent fibers of the vagus nerve  cough centers in the CNS 10/11/2024 279  Cough… There are two types of cough: the useful and the useless. useful when it effectively expels secretions or foreign material from the respiratory tract, i.e. when it is productive; – it is useless when it is unproductive and persistent. Useful cough should be allowed to serve its purpose and suppressed only when it is exhausting the patient or is dangerous. Useless persistent cough should be stopped by giving the patients with antitussive drugs. 10/11/2024 280  Antitussive Agents Are agents that relieve or prevent coughing. MOA: – These agents act on the CNS to depress the cough reflex center in the medulla of the brain. – Antitussives are used to reduce respiratory irritation. – Such reduction of respiratory irritation results in the patient’s being able to rest better Codeine.  the most useful narcotic antitussive agent  aids in relieving the associated pain  S/E: drowsiness, nausea, vomiting, constipation and dependence. 10/11/2024 281  Antitussive… Dextromethorphan  nonopoid antitussive  It is found alone or in combination--usually with expectorants. S/E: gastrointestinal upset. The usual oral dosage of this drug is 10 to 30 milligrams, every four to eight hours. It is free of analgesic and addictive properties. Read its MOA 10/11/2024 282  Expectorant Agents Expectorants are agents, which facilitate the removal of secretions of the broncho-pulmonary mucous membrane. MOA: irritate gastric mucosa... stimulates secretions in the respiratory tract. – Expectorants are used to remove bronchial secretions which are purulent, viscid, or excessive. The loosened material is then moved toward the pharynx through ciliary motion and coughing. Expectorant Agents e.g.: Guaifenesin, Saturated Solution of Potassium Iodide, Ipecac alkaloid 10/11/2024 283  Mucolytics dissolve mucous in the respiratory tract. They are used by inhalation in an attempt to reduce the viscosity of respiratory tract fluid. The loosened material can then be moved toward the pharynx more easily by ciliary motion and coughing. – Like the expectorants, the mucolytics are used in the treatment of respiratory disorders in which the secretions are purulent (contain pus), viscid, or excessive. 10/11/2024 284  Mucolytics… 1. Acetylcysteine: This is a mucolytic given by inhalation Acetylcysteine has an unpleasant smell. S/E: nausea and vomiting and broncho-spasms with higher concentrations. 2. Sodium Chloride Solution This agent is used alone or in combination with other mucolytic agents. tends to decrease the viscosity of the respiratory fluid. S/E: localized irritation. 10/11/2024 285  Decongestants Reduce congestion of nasal passages, which in turn open clogged nasal passages and enhances drainages of the sinuses. MOA: – are 1 agonists; which produce localized vasoconstriction on small blood vessels of the nasal membrane. Clinical uses: – in congestion associated with rhinitis, allergic rhinitis and common cold. Drugs can be administered nasally or orally Classification: – Short acting decongestant[orally]: phenylephrine, – long acting decongestant[orally]: ephedrine – long acting [topical]: xylometazoline, oxymetazoline 10/11/2024 286  Bronchial Asthma Asthma symptoms are produced by reversible narrowing of the airway, which increases resistance to airflow and consequently reduces the efficiency of movement of air to and from the alveoli. In addition to airway obstruction, cardinal features of asthma include inflammation and hyperreactivity of the airway. 10/11/2024 287  Airway Obstruction  Factors that contribute to airway obstruction in asthma  Contraction of the smooth muscle that surrounds the airways  Excessive secretion of mucus and in some, secretion of thick, tenacious mucus that adheres to the walls of the airways 10/11/2024 288  Prevalence Most common chronic diseases globally and currently affects approximately 300 million people worldwide – Approximately 10–12% of adults and 15% of children affected by the disease – Asthma can present at any age, with a peak age of 3 years 10/11/2024 289  Disease Pattern Episodic --acute exacerbations interspersed with symptom-free periods Chronic --- daily AW obstruction which may be mild, moderate or severe ± superimposed acute exacerbations Life-threatening--- slow-onset or fast-onset (fatal within 2 hours)  Deaths from asthma are uncommon  Risks for death:- – poorly controlled disease with frequent use of bronchodilator inhalers – lack of corticosteroid therapy – previous admissions to the hospital with near-fatal asthma 10/11/2024 290  Etiology Allergic/atopic/ early onset asthma---rhinitis, urticaria, (+)skin tests, ↑IgE – Atopy is due to the genetically determined production of specific IgE antibody Idiosyncratic/non-atopic/intrinsic asthma/late onset asthma--- no allergic diseases,(-)skin tests, normal IgE – +ve FHx – more severe, persistent asthma. Adult Onset-- Occupational factors (chemicals, wood dust), – negative family history Mixed group---usually onset later in life 10/11/2024 291  Asthma Triggers Respiratory Rhinovirus, influenza, parainfluenza, Mycoplasma pneumonia infection Allergens Airborne pollens (grass, trees, weeds), house-dust mites, animal danders, cockroaches, fungal spores Environment Cold air, fog, ozone, sulfur dioxide, nitrogen dioxide, tobacco smoke, wood smoke Emotions Anxiety, stress, laughter Exercise Particularly in cold, dry environments Drugs / Aspirin, NSAIDs (cyclooxygenase inhibitors), sulfites, benzalkonium preservatives chloride, nonselective β-blockers Occupational Bakers (flour dust); farmers (hay mold); spice and enzyme workers; printers stimuli (arabic gum); chemical workers (azo dyes, anthraquinone, ethylenediamine, toluene diisocyanates, polyvinyl chloride); plastics, rubber, and wood workers (formaldehyde, western cedar, dimethylethanolamine, anhydrides) 10/11/2024 292  Pathophysiology of Asthma Exposure to antigen[eg. dust] Avoidance Antigen and IgE on mast cells Cromolyn, steroids,zileuton Mediators[LT, cytokines] B2A, LT-antag,theoph Steroids, cromolyn, LT- antag Early response Late response bronchoconstrition inflammation 10/11/2024 Early response Early response 293 bronchoconstrition bronchoconstrition  Goals of Therapy Acute Asthma attack Correct significant hypoxemia Rapid reversal of airflow obstruction Reduce likelihood of relapse or future recurrence of severe obstruction General Measures – Monitor pt to assess severity, detect sign of improvement or deterioration – In the absence of Blood gas monitoring , clinical evaluation …V/S , e.g. RR, PR, use of accessory muscles, color, paradoxical mov’t of diaphragm , speech , level of consciousness. – Humidified oxygen by mask at high conc. – Rehydration 10/11/2024 294  Goals of Therapy…Chronic Asthma Reduce impairment – prevent chronic, troublesome symptoms – require infrequent use (≤ 2 days a week) of inhaled SABA for quick relief of symptoms – maintain (near-) normal pulmonary function – maintain normal activity levels – meet patients’ & families’ expectations of and satisfaction with care 10/11/2024 295  Goals of Therapy Reduce risk – prevent recurrent exacerbations – minimize need for visits/hospitalizations – prevent loss of lung function – prevent reduced lung growth in children – minimal adverse effects of therapy 10/11/2024 296  Treatment Early recognition of deterioration & aggressive treatment are vital – patient/family education Primary therapy – short-acting β2-agonist (SABA) Additional therapy depending on severity – systemic corticosteroids – inhaled anticholinergic – O2 Antibiotics should not be given routinely unless there is convincing evidence for bacterial respiratory infection 10/11/2024 297  Drug groups in Asthma  -adrenergic receptor agonists  Anticholinergics  Methylxanthines  Glucocorticoids  Leukotriene inhibitors  Chromones  Anti-immunoglobulin E (IgE) 10/11/2024 298  -adrenergic receptor agonists  Selective 2-receptor agonists.  They are mostly delivered directly to the airways via inhalation.  Classified as  Short-acting agonists: used only for symptomatic relief of asthma.  Long-acting agonists: used prophylactically in the treatment of the disease. 10/11/2024 299  -adrenergic RA… MOA  Stimulation of 2-AR on bronchial smooth muscle cells activates adenylate cyclase consequently increasing cytosolic cAMP  bronchial relaxation 10/11/2024 300 Short-Acting 2-AR Agonists[SABA]  Drugs in this class include albuterol, levalbuterol, metaproterenol, terbutaline, and pirbuterol.  Used for acute treatment of bronchospasm… inhalation/oral  Inhalation drugs has rapid onset of bronchodialation (1-5 min) which lasts for about 2 to 6 hours.  Are the preferred treatment for rapid symptomatic relief of dyspnea associated with asthmatic bronchoconstriction.  Are used on as-needed basis 10/11/2024 301 Long-Acting 2-AR Agonists[LABA]  Drugs in this class include Salmeterol and formoterol  Bronchodilation lasts over 12 h with inhalation salmeterol.  The higher lipophilicity of the drugs may be responsible for the extended effect. 10/11/2024 302  -adnergic RA…  Side effects  Increased heart rate  cardiac arrhythmias  CNS effects associated with -AR activation. 10/11/2024 303 Oral Therapy with -AR Agonists  Not generally recommended for routine use due to adverse effects  Situations where oral therapy is used In children (< 5 yrs) who can not manipulate MDI(albuterol or metaproterenol syrups) In some severe asthma exacerbations, aerosols can worsen cough and wheezing by causing local irritation 10/11/2024 304  Albuterol: Adult – Bronchospasm: 2 puffs every 4-6 hours PRN…MDI Oral: 2-4 mg/dose 3-4 times/day…fast release 8 mg every 12 hours; maximum dose not to exceed 32 mg/day (divided doses)…extended release – Exacerbation of asthma (acute, severe) 4-8 puffs every 20 minutes for up to 4 hours, then every 1-4 hours as needed…..MDI – Exercise-induced bronchospasm (prevention): – 2 puffs 5-30 minutes prior to exercise 10/11/2024 305 Dosing: Pediatric Bronchospasm: – Children 2-6 years: 0.1-0.2 mg/kg/dose TID (maximum: 12 mg/day) – Children 6-12 years: 2 mg/dose 3-4 times/day (maximum: 24 mg/day) – Children >12 years: 2-4 mg/dose 3-4 times/day (maximum: 32 mg/day) Oral, extended release: – Children 6-12 years: 4 mg every 12 hours (maximum: 24 mg/day) – Children >12 years: 8 mg every 12 hours (maximum: 32 mg/day) 10/11/2024 306  Dosing: Pediatric…. MDI(90 mcg/puff): – Children ≤4 years: 2 puffs every 4-6 hours PRN – Children 5-11 years: 2 puffs every 4-6 hours PRN – Children ≥12 years: 2 puffs every 4-6 hours PRN Exacerbation of asthma (acute, severe) MDI(90 mcg/puff): – Children 4 years: 2 puffs 5-30 minutes prior to exercise 10/11/2024 308  Glucocorticoids MoA in Asthma do not directly relax airway smooth muscle and thus have little effect on acute bronchoconstriction Have anti-inflammatory effect in part by inhibition of production of inflammatory mediators; they also potentiate the effects of - receptor agonists and inhibit the lymphocytic- eosinophilic airway mucosal inflammation 10/11/2024 309  Corticosteroids used in asthma Class Agent Route Oral Prednisone Oral corticosteroids Methylprednisolone oral Parenteral Methylprednisolone IM, IV corticosteroids Hydrocortisone IV Inhaled Triamcinolone acetonide Inhal. corticoseteroids Beclomethasone dipropionate Flunisolide budesonide 10/11/2024 fluticasone 310  Inhaled corticosteroids … Inhaled glucocorticoids are superior to inhaled b2-agonists for symptom control. The most frequent side effects are local and include oral candidiasis, sore throat and throat irritation, and coughing. Special delivery systems (e.g., devices with spacers) can minimize these side effects. 10/11/2024 311  Pharmacokinetics of Inhaled Corticosteroids 10/11/2024 312  Inhaled Corticosteroids (ICS) Use: cornerstone of chronic asthma therapy – improve lung function – reduce severe exacerbations – only therapy shown to reduce risk of asthma death Low systemic activity ?? Response delayed for several weeks 10/11/2024 313  ADRs and contraindications ICS – Candidiasis – Dysphonia Rinsing the mouth and throat with water after each use Employing spacer or reservoir devices attached to the dispenser to decrease drug deposition in the oral cavity 10/11/2024 314  ADRs and contraindications… Systemic: – Treatment for brief periods (5 to 10 days) causes relatively little dose-related toxicity. – The most common adverse effects during a brief course are mood disturbances, increased appetite, impaired glucose control in diabetics, and candidiasis. – Adrenal suppression, growth retardation, osteoporosis, and increased susceptibility to infection. 10/11/2024 315  Anti-IgE therapy Omalizumab is a recombinant humanized monoclonal antibody targeted against IgE. MOA: IgE bound to omalizumab cannot bind to IgE receptors on mast cells and basophils, thereby preventing the allergic reaction at a very early step in the process 10/11/2024 316  Anti-IgE therapy…  Pharmacokinetics  Delivered as a single SC injection every 2 to 4 weeks.  It has a bioavailability of about 60%.  The serum elimination half-life is 26 days.  The elimination of omalizumab-IgE complexes occurs in the liver.  Some intact omalizumab is also excreted in the bile.  Adverse effects  Generally well tolerated.  A/E: injection-site reactions (e.g., redness, stinging, bruising), anaphylaxis  Possibly malignancies??? 10/11/2024 317  Chromones  Drugs: Cromolyn sodium and nedocromil  Both administered by inhalation and have very good safety profiles, making them particularly useful in treating children.  MOA  Inhibiting mediator release from mast cells, suppressing the activating effects of chemotactic peptides on human neutrophils, eosinophils, and monocytes,  Inhibit cough reflexes and inhibiting leukocyte trafficking in asthmatic airways.  The exact MOA in asthma is not known. 10/11/2024 318  Chromones…. Pharmacokinetics  Administered by inhalation  Pharmacological effects result from the topical deposition of the drug in the lung, since only about 1% of an oral dose of cromolyn is absorbed.  Once absorbed, the drug is excreted unchanged in the urine and bile in about equal proportions. 10/11/2024 319  Chromones…. Adverse effects  Generally well tolerated  Include bronchospasm, cough or wheezing, laryngeal edema, joint swelling and pain, angioedema, headache, rash, and nausea.  Very rare instances of anaphylaxis  Can cause a bad taste. Clinical Use  Main use: to prevent asthmatic attacks in individuals with mild to moderate bronchial asthma.  Ineffective in treating ongoing bronchoconstriction 10/11/2024 320  Muscarinic receptor antagonists:  Drugs include ipratropium and tiotropium  Competitively inhibit effect of acetylcholine at muscarinic receptor  Competitive antagonists at all muscarinic sites.  M3 is responsible for the bronchial relaxing effect block contraction of air way smooth muscle and the increase in secretion of mucus that occurs in response to vagal activity Systemic adverse effects as a result of rapid absorption include: Urinary retention Tachycardia loss of accommodation agitation Local effects like dryness of mouth limit the quantity of atropine used 10/11/2024 321  Muscarinic receptor antagonists… Ipratropium bromide:  is poorly absorbed and does not enter CNS thus permits the delivery of high doses; it can be used for bronchial asthma Muscarinic antagonist drugs appear to be less effective than -agonists in reversing asthmatic bronchospasm The antimuscarinic agents appear to be significant value in chronic obstructive pulmonary diseases more than asthma They are useful as alternative therapies for patients intolerant of - agonists. 10/11/2024 322  Methylxanthines  The three important methylxanthines are theophylline, theobromine, and caffeine from beverages of tea, cocoa, & coffee, respectively.  Theophylline: Not frequently used nowadays, due to the greater effectiveness of 2-agonists and glucocorticoids. Its lower cost is the main reason behind its use.  Aminophylline: theophylline-ethylenediamine complex. 10/11/2024 323  Xanthines…  MOA  Inhibits PDE enzyme, thus causing increased cytosolic levels of cAMP and cGMP Cardiac stimulation Smooth muscle relaxation Decreased release of inflammatory mediators from mast cells 10/11/2024 324  Xanthine derivatives: Bronchodilator Agents Directly relax the smooth muscle of the bronchi and pulmonary blood vessels. They may also reduce the fatigability and thereby improve contractility in patients with chronic obstructive airway disease. Xanthine derivatives are often used in the treatment of apnea and bradycardia of prematurity in infants. 10/11/2024 325  Xanthine derivatives: Bronchodilator Agents… Aminophylline: is a xanthine derivative containing ~80% theophylline. It is prescribed as a bronchodilator to treat asthma. It will also relieve bronchospasms associated with emphysema and bronchitis. Aminophylline is generally administered intravenously (I.V.) to relieve acute bronchospasms or status asthmaticus resistant to adrenergic drugs. 10/11/2024 326  Xanthine derivatives: Bronchodilator Agents… Theophylline: is often prescribed as the xanthine of choice for oral administration (tablets, capsules, elixir, syrup, or solution). One must take care when dispensing theophylline products. Theophylline is a drug with a very narrow therapeutic index. For this reason, patients should have their theophylline blood levels monitored on a routine basis. 10/11/2024 327  Xanthine derivatives: Bronchodilator Agents…  Nowadays has less prominent role primarily because of the modest benefits it affords, its narrow therapeutic window, and the required monitoring of drug levels.  Toxicity and adverse effects  It has a narrow therapeutic window 5–20 mg/L is associated with improvement in pulmonary function. 15 mg/L: Anorexia, nausea, vomiting, abdominal discomfort, headache, and anxiety in some patients and become common at concentrations greater than 20 mg/L. Higher levels (> 40 mg/L) may cause seizures or arrhythmias 10/11/2024 328  Mast cell stabilizers Cromolyn and nedocromil: is a unique product that works by inhibiting the release of histamine and other spasm-causing compounds from mast cells located in the lungs and prevents bronchoconstriction. It used in exercise and antigen induced asthma and occupational asthma. It has no role once mediator is released and is used for casual prophylaxis. 10/11/2024 329  Mast cell stabilizers… Leukotriene modifiers The production of leukotrienes (immunologic proteins) and the binding of leukotriene receptors appears to be responsible for:  Airway edema, Smooth muscle constriction and  Altered inflammatory processes contributing to the signs and symptoms of asthma. For this reason, several new agents have been developed: Zafirlukast, montelukast and zileuton. 10/11/2024 330  Respiratory drugs cont’d TREATMENT OF STATUS ASTHMATICUS Very severe and sustained attack of asthma which fails to respond to treatment with usual measures Management includes: – O2 adm. – Frequent adm. of aerosolized 2-agonist like salbutamol – IV systemic corticosteroids like hydrocortisone – Iv infusion to avoid dehydration – Antibiotic in the presence of evidence/suspect of infection 10/11/2024 331  Treatment of acute asthma attacks in adults First line Salbutamol, MDI: 200 micrograms by aerosol inhalation. – every 20 minutes for the first hr. – S/Es: headache, nervousness, dizziness, palpitation, tachycardia. – C/Is: cardiac Arrythmias Alternatives Aminophylline, 5mg/kg by slow I.V. push over 5 minutes. – S/Es: GI disturbances, headache, irritability, nervousness, insomnia, and tremor – C/Is: HNT, IHD, epilepsy, hyperthyroidism, CHF 10/11/2024 332  Treatment of acute asthma attacks in adults… Adrenaline, 1:1000, 0.5ml sc. – Repeat after ½ to 1 hour if patient doesn’t respond. S/Es: headache, nervousness, dizziness,Arrythmia – C/Is: cardiac arrythmias – Dosage forms: injection, 0.1% in 1 ml ampoule 10/11/2024 333  If response to initial therapy is poor: First line Establish intravenous line and start Aminophylline, PLUS Hydrocortisone, 200 mg IV as a single dose. Further IV doses are needed only if oral dosing is not possible. OR Prednisolone, 40-60 mg P.O. Alternatives – Nebulized Salbutamol Plus – Hydrocortisone, 200 mg IV as a single dose. OR Prednisolone, 40-60 mg P.O 10/11/2024 334  Maintenance therapy for chronic asthma in adults: 1. Intermittent asthma: First line – Salbutamol, inhaler 200 microgram/puff,1- 2 puffs PRN but not more than 3-4 times a day, or tablet, 2-4mg 3-4 /d Alternative – Ephedrine + Theophylline (11mg + 120mg) P.O. BID OR TID 10/11/2024 335  2. Persistent mild asthma: First line – Salbutamol, inhaler, 200 micro gram/puff 1-2 puffs PRN but not more than 3-4 times/day, or tablet, 2-4mg 3-4/d PLUS – Beclomethasone, oral inhalation 1000mcg QD for two weeks Plus Prednisolone, 5-10 mg P.O. QOD….if required Alternative Ephedrine + Theophylline (11mg + 120mg, P.O. two to three times a day PLUS Beclomethasone oral inhalation 1000mcg QD for two weeks. 10/11/2024 336  3. Persistent moderate asthma: First line – Salbutamol, inhalation 200microgram/puff 1-2 puffs as needed PRN not more than 3-4 /d PLUS – Beclomethasone, 2000mcg, oral inhalation QD for two weeks and reduce to 1000 mcg if symptoms improve. PLUS Prednisolone, 5-10 mg P.O. QOD...if required 10/11/2024 337  4. Severe persistent asthma: Salbutamol, inhalation , 200 micro gram/puff 1-2 puffs not more than 3-4 times a day PLUS – Beclomethasone, 2000 mcg, oral inhalation daily PLUS – Prednisolone, 5-10 mg P.O. QOD…. ( if required) 10/11/2024 338  General:- Stepwise Approach for Asthma Management OCS LABA LABA LABA ICS high dose ICS high dose ICS low dose ICS low dose Short Acting B2-Agonists as needed for symptom mngt[SABA] Mild Mild Moderate Severe Very Severe Intermittent Persistent Persistent Persistent Persistent 10/11/2024 339  Patient Education Appropriate inhalation technique is vital for optimal drug delivery and therapeutic effect – up to 30% cannot master MDI technique Rinse mouth after inhaled corticosteroids (ICS) < 4 years old usually need to attach a face mask to the inhalation device 340 10/11/2024  Cardiovascular Pharmacology 10/11/2024 386  Brainstorming Be in groups and discuss….. A. What is cardiovascular system [Physiology??] B. What are the common CVS disorders? C. What is Hypertension? I. BP? II. Factors affecting BP? III.Treatment protocol? 10/11/2024 387  Introduction  Cardiovascular (Circulatory) system – heart & blood vessels  Arteries – transport blood to tissues  Capillaries – sites of exchange, fluid, O2, CO2, nutrients etc.  Venules – collect blood from capillaries  Veins – transport blood back to heart  Blood moves within vessels – from higher to lower pressure  Resistance to flow depends on:  vessel diameter,  length and  viscosity of blood 10/11/2024 388  Cardiac blood flow The mammalian heart is a double pump in which: i. the right side  Is a low-pressure system delivering de-oxygenated blood to the lungs, ii. while the left side  Is a high pressure system delivering oxygenated blood to the rest of the body. The walls of the right ventricle are much thinner than those of the left, – because the work load is lower for the right side of the heart. The ventricular muscle is relatively stiff, and it would take some time to fill with venous blood during diastole. 10/11/2024 389  Regulation of cardiac output ≈5L /minute; depend on: i. Heart rate ii. Stroke volume iii. Preload iv. Afterload 10/11/2024 390  Ctnd… Starling’s Law Ventricular contraction is proportional to muscle fiber stretch. Aortic output pressure rises as the venous filling pressure is increased. Increased venous return – increase cardiac output – up to a point! 10/11/2024 391  Cardiac electrical activity Cardiac muscle does not require any nervous stimulation to contract. Each beat is initiated by spontaneous depolarization of pacemaker cells in SA node. 10/11/2024 392  Ctnd… These cells trigger the neighboring atrial cells by direct electrical contacts and a wave of depolarization spreads out over the atria, eventually exciting AV node. Contraction of atria precedes that of ventricles, forcing extra blood into ventricles. The electrical signal from the AV node is carried to ventricles by a specialized bundle of conducting tissue (the bundle of His) The conducting tissues are derived from modified cardiac muscle cells, the Purkinje fibers. 10/11/2024 393  Ctnd… Most commonly encountered CVS disorders are: 1. Hypertension  is an elevated blood pressure(BP). 2. Angina pectoris  Is pain on the chest associated with an imbalance b/n oxygen demand and supply to the heart. 3. Congestive heart failure(CHF)  heart is unable to pump as to the body’s blood and oxygen demand. 4. Cardiac Arrhythmia (Dysrythmia)  Is loss of normal rhythm of the Heart. 10/11/2024 394  1. Hypertension or High Blood Pressure Is a medical condition in which constricted arterial blood vessels increase the resistance to blood flow, – causing an increase in blood pressure against vessel walls. The heart must work harder to pump blood through the narrowed arteries. If the condition persists, – damage to the heart and blood vessels is likely, – increasing the risk for stroke, heart attack, and kidney or heart failure. Often called the “silent killer,” – hypertension usually causes no symptoms until it reaches a life-threatening stage. 10/11/2024 395  Pathophysiology of hypertension Elevated blood pressure Results from: – increased peripheral vascular smooth muscle tone and – reduced capacitance of the venous system. Hypertension is the most common cardiovascular disease. More than 90-95% of patients have primary or essential hypertension. 10/11/2024 396  Problems of elevated blood pressure Brings a complication to end organs: heart kidney brain liver Stroke and failure of these vital organs Because it damages the endothelial cells of these organs. 10/11/2024 397  Types of hypertension =2 types 1. Primary or essential hypertension The cause is not identified Accounted for about more than 90-95% cases It is a chronic progressive disorder We cannot totally cure but we can control 10/11/2024 398  Ctnd… 2. Secondary hypertension Comes due to different disorders CVS disorders Kidney disorders (chronic renal diseases) Diabetes It can be treated by treating the causes. 10/11/2024 399 Blood Pressure Classification Systolic pressure, the higher number of a blood pressure reading, is the pressure as the heart pumps. Diastolic pressure is the pressure when the heart relaxes between beats. 1. Normal blood pressure:  systolic