Pharmacology of Drugs Acting on Respiratory System PDF

# UNIT-I ## Pharmacology of drugs acting on Respiratory System. ### ANTI-ASTHMATIC DRUGS: * It is characterized by hyper responsiveness of tracheobronchial smooth muscle to a variety of stimuli, narrowing of air tubes, mucosal edema & mucus plugging. * Two principal varieties are recognized:...

# UNIT-I ## Pharmacology of drugs acting on Respiratory System. ### ANTI-ASTHMATIC DRUGS: * It is characterized by hyper responsiveness of tracheobronchial smooth muscle to a variety of stimuli, narrowing of air tubes, mucosal edema & mucus plugging. * Two principal varieties are recognized: * **Extrinsic Asthma:** Mostly episodic, less prone to status asthmaticus. * **Intrinsic Asthma:** It tends to be perennial, status asthmaticus is more common. * The inflammation in bronchial asthma is initiated by mast cells (present in lungs & infiltrate is dominated by eosinophils, lymphocytes and mast cells. ## Drugs for Bronchial Asthma | | Mast cell Stabilizers | Corticosteroids | Anti-IgE antibody | |---|---|---|---| | Leukotriene antagonists | | | Fomalizumab | | | | | | | Montelukast | | Systemic | | | | | | | | | | Hydrocortisone | Inhalational | | | | | | | | | Prednisolone | Beclomethasone dipropionate | | | | Other Glucorticoids | | | | | | | | | | | Budesonide | | | | | | | | | | Fluticasone-propionate | | | | | | | | | | Flunisolide | | | | | | | Bronchodilators | | | Ciclesonide | | | | | | | | | | | | | | | | | | | Anticholinergics | | | Be-sympathomimetics | Methylxanthines | | | | | | | | | Salbutamol | Theophylline | | | | | | | | | Terbutaline | Aminophylline | Ipratropium Bromide | | | | | | | | Bambuterol | Doxophylline | Tiotropium Bromide | | | | | | | | Salmeterol | Hydroxyethyl | | | ## Pharmacologikhil Action:- 1. **Salbutamol:** Highly selective B₂ agonist, cardiac side effects are less prominent. Inhaled salbutamol delivered mostly form pressurized metored dase inhaly produces bronchodilation with in 5 minutes and the action lasts for 2-4 hours. Palpitation, restlessness, nervousness, throat irritation and ankle edema can also occur. Oral salbutamol undergoes presysternic metabolism in the gut wall, bioavailability is 50%. It act as 4-6 hrs. 2. **Sympathomimetic Drug Action** a. **Heart:** Adrenaline increases heart rate by enhancing the pacemaker activity of SA node. Adrenaline also activates latent pacemakers in A.V node and purkinje Jibres. Arrythmias can occur with high doses that raise B.P. force of cardiac contraction is increased. Systole is shortened more than diastole. Cardiac output and oxygen consuption of the heart are enhanced. b. **Blood vessels:** Both vasoconstriction and vasodilation. Can occur depending on the drug. Vasodilation occurs through UX, 4 ₂ receptors vasoconstriction. Predominates in skeletal muscles liver and coronaris. c. **BP:** The effect depends on the amine its dose and rate of administration: Adrenaline given by slow i.v. infusion or sic injection causes rise in systolic but fall in diastolic BP. Rapid i.v. injection of Adrenaline produces a marked increase in both systolic as well as diastolic B.P. d. **Respiration:** Adrenaline and isoprenaline are potent bronchodilators. Adrenaline can directly stimulate respiratory centre. e. **Eye:** Mydriasis occurs due to contraction of radial muscle of iris but this is minimal after topical application because adrenaline penetrates cornea poorly f. **GIT:** In isolated preparations of gut, activation of both x & B receptors produces relaxation. g. **Bladder:** Destrusor is relaxed (B₂ 4B,) and trigone is constricted (X1) both actions tend to oppose bladder voiding. h. **Uterus:** - Adrenaline can both contract and relax uterine muscle, both x4 ẞ receptors. i. **Metaboli:** Adrenaline causes glycogenolysis → hyperglycemia as well as lipolysis → rise in plasma free fatty acid. 3. **Methylxanthines Action:** a. **CNS:** Caffeine and theophylline are CNS stimulants. Primarily affect the higher centres. Caffeine 150-250mg produces a sense of alertness, Jatigue thinking becomes clear. Vomiting at high doses is due to both gastric imitation and CTZ stimulation. b. **CVS:** It direct stimulates the heart and increase force of myocardial contractions. They tend to increase heart rate by cardiac action, but cercase it by causing vagal stimulation. c. **Smooth muscles:** - All smooth muscles are relaxed most prominent effect is exerted on bronchi in asthmatins Theophylline is more potent bronchodilator than Caffeine. d. **Kidney:** - Mild idiuretics. They act by inhibiting tubular reabsorption of Nat and water as well as increased sencal blood flow. e. **Skeletal musdes:**- Coffeine enhances contractile power of Skeletal muscles. f. **stomach:** Methylxanthines ernharice secretion of acid and pepsin in stomach even on parenteral injection g. **Mast cells & inflammatory cells:** - Theophylline dececases release of histamine, other mediators and cytokines from mast cells and activated inflammatory cells. ## Mechanism of Action: * ATP Aderylcyclese CAMP Phosphodiesterase 5-AMP GTP guanyleydase CGMP Inhibited by theophylline 5-GMP. ## Pharmacokinetics: * Well absorbed orally. It is distributed in all tissues. Crosses Uplacenta & is secreted in milk, 50% plasma protein bound & extensively metabolized in liver by demethylation & oxidation. T ½ in adults is 7-12 hrs. Only 10% is excreted unchanged in urine ## Adverse effects: - * Theophylline has a narrow margin of safety. Headache, Nervousness and hauser are early symptoms, the irritant property of theophylline is reflected in gastric pain, rectal inflammation if pain at site of sim, injection. # * EXPECTORANT & ANTITUSSIVE * ## Expectorant: * Are the dangs used to increase bronchial scretion or reduce its viscosity, facilitating and its semoval by coughing considered. * Sodium and potassium citrate are to increase bronchial selection by salt action. * Potassium iodide is secreted by bronchial gland and can joritate the Lisway mucosa. * Guaiphenesin vasaka a tolu balsam are plack product which are supposed to enhance bronchial secretion. ## Expectorant | | Secretion enhancers | Mucolytics | |---|---|---| | | | | | | Potassium citrate | Bromhexine | | | Sodium citrate | Ambroxol | | | Tolu balsam | Acetylcysteine | | | Vasaka | Carbocisteine | | | Ammonium Chloride | | ## Mucolytics: * **Bromhexine:** A derivative of the alkaloid vasicine obtained from Adhatoda vasica (vasaka) is a mucolytic & mucokinety capable of inducing thin copious bronchial ## Side effect: * Lacrimation, nousca, gastric irritation hypersensitivity. * **Ambroxol:** Ambroxol is a metabolite of bromhexine having similar mucolytic action. * **Acetylcysteine:** It opens disulphide bonds in mucoprotein present in sputum & makes it less viscid. * It can be administered orally (200-600mg TDS) as well as by inhalatiod of 10-20%. nebulized solution ## Antitussive: * These are the drugs which suppress the cough production * These are the doug that act in the CNS to raise the threshold of cough centre or act peripherally in the respiratory tract to reduce tusd impulse or both. These actions. ## Antitussive | | Antitussive | Peripherally acting dangs | |---|---|---| | | | | | | i) Narcotic/opoid antitussive | | | | →codeine, hydro | | | | | | | | | i) Mucosal anesthetic | | | | →Benzo | | | ii) Non-narcotic/non-oboid antitussive | | | | → Dextromethomorphan, Diphenhydramine | | | | | | | | | ii) Hydrating agent | | | | → steam, Aerosol. | | | iii) Miscellaneous | | | | →Bromhexine, | | # * ANTIULCER DRUGS / PEPTIC ULCER * * Peptic ulcer occurs in that part of the gastrointestinal tract (gist) which is exposed to gastric acid & pepsin, ive. the stomach and duodenum. * It probably due to an imbalance between the aggressive (acid, pepsin, bile & Hopylori) and the defensive (gastric mucus, nitric oxide, bicarbonate secretion, prostaglandins etc.) factors * Duodenum ulces - high production of acid ## Classifications: 1. **Reduction of gastric acid secretion:** a. **H₂ antihistamines :** Cimetidine, Ranitidine, Jermotidine, Roxatitine, Lafutidine b. **Proton pump inhibitors:** Omeprazole, Pentoprazole, (ions) Rabeprazole, Esomeprazole, Lansoprazole c. **Anticholinergics :** Pirenzipine, Propantheline, oxyphenonium. d. **PG (Prostaglandin) analogue:** Misoprostol. 2. **Neutralization of gastric acid (Antacids)** a. **Systemic :** Sodium bicarbonate, sodium citrate b. **Non-systemic :** Magnesium hydroxide, magnesium trisilicate, Aluminium hydrowde. Magaldrate, cakium carbonate. 3. **Ulcer protectives:** - Sucralfate, colloidal bismuth Subcitrate (CBS) 4. **Anti H. Pylori drugs:** - Amoxicillin, clarithromycin, Metronidazole, Tinidazole, tetracyclin, CBS * **H₂ receptor antagonist :-** eng :- Cimetidine * Acid is generated by the carbonic anhydrase -mediated catalysis of CO₂ & H₂O to foom H+ & HCO₃ * H+ jons are then exchanged fox kt by H+ k + ATPase pump & later coupled with Cl- ions entering the parietal cell from the blood in exchange for HLD₃. There are 13 regulatory molecules that stirradate acid secretion (Ach., histamine & gastrin) * **Anticholinergic drugs:** - e.g.- Piperazine which is a anti-cholinergic drugs inhibit acetylcholine action on muscarinic receptors decrease HCl secretion. * **Prostaglandins analogue:** - e.g:- Misoprostal which increase mucous & bicarbonate secretion show cytoprotective action by increase mucosal blood supply increase healing by increase blood supply and decrease HCl secretion. ## Pharmacological Action: 1. **H₂ Blockade :** - These drugs block histamine induced. gastric secretion, cardiac stimulation, uterine relaxation. → No effect on Ha responses because they are selective. 2. **Gastric secretion:** - The only significant in vivo action of H₂ blockers is marked inhibition of gastric secretion. * All phases are suppressed dose dependently * H₂ blocker have no direct effect on gastric or oesophagal motility or on lower esophageal sphincter tone. ## Mechanism of Action:- [Diagram of the stomach cell with all parts labelled] ## Pharmacokinetic:- * Absorbed orally, biovailability 60-80% undergass first pas metabolison. * About 2/3 of dose is excreted unchanged in urine / bile. * Elimination ty½ is 2-3 hrs * Dose reduction is needed in renal failure. ## Adverse effects: * Meadache, d'arshes, dizziness, dry mouth, bradycardia (cocur when administered as iv.) # * DRUGS FOR CONSTIPATION:- * ## Laxatives: * These are drugs that promote evacuation of bowels. a. **Laxative or aperient :** milder action, elimination of soft but formed stools. b. **Purgative or cathartics:** stronger action resulting in more fluid and forcesful evacuation * Many drugs in low doses act as for laxative and in larger doses as purgative. ## Classification of drugs for constipation | | Bulk forming agents | Stool softner | Osmotic purgatives | |---|---|---|---| | | | | | | | Dietary fibre: bran | Docusates | Mag. sulfate | | | | | Mag. hydroxide | | | Psyllium | | + liquid paraffin | | | | | Sod. sulfate | | | Ispaghula | | | | | | | Sod, Phosphate | | | Methyl cellulose | | | | | | | Lactulose | | | | | Lactitol | | | Stimulant purgatives | | | |---|---|---|---| | | | | | | | Diphenylmethanes | Anthraquinones | 5-HTY agonist | | | | | | | | Bisacodyl | Senna | Pucalo-analogu | | | | Cascara sagrada | | | | Sod. picosujate | | | ## Mechanism of Action: * All purgatives increase the water content of the faceces by a. A hydrophilic or osmotic action, retaining water and electrolytes in the intestinal lumen - increase volume of colonic content and make it easily propelled b. Acting on intestinal mucosa, decrease net absorption of water and electrolyte ; intestinal transit is enhanced indirectly by the fluid bulk. allowing less time for absorption of salt I and water as secondary effect. ## Bulk purgatives:- * Dietary fibre : bran * Dietary fibre consists of unabsorable cell wall & other constituents of vegetable food - cellulose, lignins, gums, pectins, glycoproteins and other polysaccharides. * Bran is the residual product of flour industry which consists of ~40% dietary Fibre. * It absorbs water in the intestine, swells, increases water content of faeces - softens it and facilitates colonic transit. * Increased intake of dietary Fibres is the most appropriate method for prevention of functional constipation, particularly if the diet is deficient in fibre ## Drawbacks: * Bran is generally safe, but it is unpalatable - large quantity (20-40g/day) needs to be ingested. Full effect requires daily intake for at least 3-4 days. * As such, bran is useful for prevention of constipation. # * DRUGS FOR DIARRHOEA :-* ## Diarrhoea: * Diarrhoea is too frequent, often too precipitate passage of poorly formed stools. * Diarrhoe is defined by WHO as three or more loose or watery stools its a 24 hrs period. * In pathological terms, it occurs due to passage of excess water in faeces. This may be due to: * Decrease electrolyte and water absorption. * Increase secretion by intestinal mucosa. * Increase luminal osmotic load * Inflammation of mucosa & exudation into lume. ## Classifications :- | | Antimicrobial drugs. | Probiotics | Drugs for inflammatory bowel disease | |---|---|---|---| | | | | | | | Norfloxacin | Lactobacillus sp. | | | | Ciprofloxacin | Enterococcus sp. | | | | | Bacillus clausis | | | | | | | | | Ofloxacin | Nonspecifict antidiarrhoeal drugs | Glucocorticoids | | | | | | | | Rifaximin | 5-ASA Compound | Sulfasalazine | | | | | Prednisolone | | | Tetracycline | | Mesalazine | | | | | Hydrocortisone | | | | | Balsalazide | | | | | | | | Ethromycin | | | | | | | Immunosuppress-ant | | | | | | | | Absorbants | Antisecretory drugs | Antimotility | | | | | | | | | Ispaghula | · Bismuth subsalicylate | Codorne | Azathioprine | | | | | | | | | Methylcellulose | Anticholinergics | Loperamide | Methotrexate | | | | | | Cyclosporin | | | | Racecadotril. | Diphenoxylate | | | | | | | | | | | | | INF inhibitor | | | | | | | | | | | | Infliximab | # * EMETICS & ANTIEMETICS : * ## Emetics: * These are the drugs used to evoke vomiting. a. Act on CTZ : Apomorphine b. Act reflexly & on CTZ : Ipecacuanha * Vomiting needs to be induced when an undesirable substance (poison) has been ingested. Powdered mustard. suspension or strong salts solution may be used in emergency. They act reflexly by imitating the stomach. * **Apomorphine:** It is a semisynthetic derivative of morphinen; act as a dopaminergic agonist on the CTZ. It should not be used if respiration is depressed, because it has inherent respiratory and CNS depressant actions. Apomorphine has a therapeutic effect in parkinsonism, but is not used due to side effects. ## Antiemetics: * These are drugs used to prevent or suppress vorriting. This is known as entiemetics ## Classifications of antiemetics :- | | Anticholinergics | Neuroleptics (D2 blockers) | Prokinetic deng | Nky recepto antagonists | |---|---|---|---|---| | | | | | | | | Hyoscine | Chlorpromazine | Metoclopramide | Aprepitant | | | Dicyclomine | Triflupromazine | Domperidone | | | | | Prochlorperazine | Cisapride | Fosaprepitan | | | | | Mosapride | | | | | | | | | | H₂ antihistamine | Levosulpride | | | | | | | Cinitapride | | | | | | | | | | Promethazine | | | | | | | | | | | | Diphenhydramine | | | | | | | | | | | | Dimenhydrinate | | | | | | | | | | | | Doxylamine | | | | | | | | | | | | Meclozine | | | | | | | | | | | | | 5-HT₃ antagonists | | | | | | | | | | | | Ondasetron | | | | | | Granisetron | | | | | | Palonoseton | | | | | | Ramosetron | | | | | | | | | | | | Adjuvant antiemetics | | | | | | | | | | | | Dexamethasone | | | | | | Benzodiazepines | | | | | | Dronabinol | | | ## Mechanism of action: [Diagram of the stomach cell with all parts labelled] ## Pharshacokinetic: * Well absorbed orally / copter lin * Distension & other stimuli trigger 5-HT release from the enterochromaffin cells located in the enteric mucosa stimulates intrinsic & extrinsic primary afferent neurons of the enteric nervous system through peripheral variant of 5-HT, receptor & 5-HT₃ receptor. ## Pharmacokinetic: * Well absorbed orally, enter in blood, placenta, secreted in milk. t/2=3-6 after 24 hers excreted out. * liv. 2 min, Jim lo min & orally - 1/2 her ## Uses:- * emetics, dispepsia, gastro-oesophageal reflux # * Nasal decongestant :-. * ## Nasal decongestant * Nasal decongestant agents that constrict dilated blood vessel in the nasal mucosa by stimulating X-adrenergic nerve receptor in vasculatory smooth muscle. ## Drugs:- | | Adrenergic | Intranasal steroids | |---|---|---| | | | | | | Topical & oral route | Topical route | | | | | | | → Ephedrine | → Beclomethasone | | | | → fluticasone | | | | →Mometasone | | | | | | | →Naphozoline | | | | | | | | → Oxymetazoline | | | | | | | | →Phenylephrine. | | | | | | | | →Praldoephedrine. | | # * (Analeptics) * Respiratory stimulant : * are those which stimulate respiration & have resuscitative value in coma or fainting. * Situations in which analepties are used:- * Respiratory depression cdue to hypnotic drug poisoning * suffocating on drowing * failure Oto ventilate spontaneously after general anesthesia. ## Drugs: * Doxapram * Prethcamide * Modafinil * Reflex setimulant :- Ammonia of alcatiol vapoure. ## Doxapram: * 1.5-4 mg/min iv. is given as respiratory stimulant along with assisted mechanical ventilation. # * Appetite stimulant 4 suppressants :- * ## Appetite stimulant : * These are substances intended to promote digestion of food. * A no. of proteolytic, amylolytic and lipolytic enzyme are marketed in combination formulation and promoted for dyspeptic symptom & as appetite stimulant. a. **Pepsin:** may be used along with Hd in gastric achiyflia be due to along atrophic gastritis Carcinoma etc. b. **Pepain:** It is proteolytic enzyme obtained From raw papaya c. **Pancreatin:** It is mixture of pancreatic enzymes obtained from dreng beg fi big pancreas. It contains amylasex trypsin & lipase and is indicated in chronic pancreatitis fat and nitre may be reduced & diaishola stools may be prevented. d. **Diastase:** These are amylalytic enzyme obtain from the fungus Aspergillus oтурка * Vigrously promoted for dyspeptic symptom & as appetite stimulant or health tonics. * They are accassionaly beneficial, only when elaboration of enzyme in goist. Vis deficient. * Their routine use in tonic & appetite improv mixtures is irrational. ## Eng:- Megesterol acetate :- * Appears to act via CNS to enhance appetite. * mechanism of action is not fully known. * Stabilizus or increase body weight. * Any weight gain = fat accumulation (drug enhance expresion and activity of lipogenic enzyme) * Possible side Effect (edema). ## Appetite suppressants :- * An anarectic or anarexic is a drug which reduces appetite resulting in lower food consumption leading to weight loss. ## Drugs used in appetite suppressants :- * Benzphetamine * Mazindol * Diethylpropion * Phentermine. # * Carminative :-* * Carminative is a preparation intended to either prevent formation of a gas in the GIT or facilitate the expulsion of Saidagas there by combatting flatulence. ## Drug used in carminative: * Sodium bicarbonate 0.6-1.5g * Peppermint oil 0.06-0.1ml * Tincture cardamom 1-2ml * Oil of oil 0.06-0.2ml * Tinchise ginger 0.6-Iml ## Uses:-. * flatulent dyspepsia. * To prevent segurgitation of milk in infants. # * Digestants :- * ## Digestants * These are the substances intended to promote digestion of food. A no. of proteolytic, amylolytic and lipolytic enzyme are marked in combination formulation and promoted for dyspeptic symptom & as appetite stimulant. a. **Pepsin:** - may be used along with Hd in gastric achiyflia be due to along atrophic gastritis Carcinoma etc. b. **Pepain:** - It is proteolytic enzyme obtained From raw papaya c. **Pancreatin:** - It is mixture of pancreatic enzymes obtained from dreng beg fi big pancreas. It contains amylasex trypsin & lipase and is indicated in chronic pancreatitis fat and nitre may be reduced & diaishola stools may be prevented. d. **Diastase:** - These are amylalytic enzyme obtain from the fungus Aspergillus oтурка