Antihistamine PDF

Drugs acting on the central nervous system f Unit (2) F Antihistamine 18.  Unit (2) Antihistamine  97 Unit (1) 98  Drugs act...

Drugs acting on the central nervous system f Unit (2) F Antihistamine 18.  Unit (2) Antihistamine  97 Unit (1) 98  Drugs acting on the central nervous system Antihistamine Allergy:  Allergy is a hypersensitivity disorder of the immune system. Allergic reactions occur when a person's immune system reacts to normally harmless substances in the environment.  Allergic diseases are strongly familial (genetic)  A substance that causes a reaction is called an allergen..  Allergic reactions are distinctive because of excessive activation of certain white blood cells called mast cells and basophils by a type of antibody called Immunoglobulin E (IgE). This reaction results in an inflammatory response  Types of allergies: Mild allergies like hay fever are very common in the human population and cause symptoms such as red eyes ( conjunctivitis), itchiness, and runny nose, eczema, hives ( urticaria) , or an asthma attack. - In some people, severe allergies to environmental or dietary allergens or to medication may result in life- threatening reactions called anaphylaxis.  Causes of allergies (allergins) Food allergies,/ and reactions to the venom of stinging insects such as wasps and bees are often associated with these severe reactions/ medications, / pollens ,/ dust mite ,/ latex gloves,/ animal fur  Symptoms of food allergy include abdominal pain, bloating, vomiting, diarrhea, itchy skin, and swelling of the skin during hives. respiratory (asthmatic) reactions, or rhinitis Insect stings, antibiotics, and certain medicines produce a systemic allergic response that is also called anaphylaxis; multiple organ systems can be affected, 99 Unit (1) including the digestive system, the respiratory system, and the circulatory system. Depending on the rate of severity, it can cause cutaneous reactions, bronchoconstriction, edema, hypotension, coma, and even death. This type of reaction can be triggered suddenly, or the onset can be delayed. The severity of this type of allergic response often requires injections of epinephrine, Figure 2: 1 Histamine release  Pathophysiology : In the early stages of allergy, causes a response in a type of immune cell of B cells , whose role is production of antibodies known as IgE. Secreted IgE circulates in the blood and binds to an IgE-specific receptor on the surface of other kinds of immune cells called mast cells and basophils, which are both involved in the acute inflammatory response. The IgE-coated cells, at this stage, are sensitized to the allergen. 100  Drugs acting on the central nervous system  If later exposure to the same allergen occurs, the allergen can bind to the IgE molecules held on the surface of the mast cells or basophils. Activated mast cells undergo a process called degranulation, during which they release histamine and other inflammatory chemical mediators (cytokines, interleukins, leukotrienes, and prostaglandins) from their granules into the surrounding tissue causing several systemic effects Figure 2:2  Inflammatory response: such as vasodilatation, mucous secretion, nerve stimulation, and smooth muscle contraction. This results in rhinorrhea, itchiness, dyspnea, and anaphylaxis. Depending on the individual, allergen, and mode of introduction, the symptoms can be system-wide (classical anaphylaxis), or localized to particular body systems; asthma is localized to the respiratory system and eczema is localized to the dermis. 101 Unit (1)  Histamine Histamine is a small molecule derived from the decarboxylation of the amino acid histidine Figure 2:3 Antihistamine Histamine Receptors and Receptor Antagonists: Tow histamine receptors have been identified, These different receptors are expressed on different cell types and work through different intracellular mechanisms, 1st: H1 histamine receptor: This receptors located ion bronchial smooth muscle, blood vessel, skin, stimulation of these receptors mediate acute allergic responses The intensity of reaction is proportional to the amount of histamine released 102  Drugs acting on the central nervous system 2nd H2 histamine receptors: Are located in e stomach, heart and blood vessel stimulation of these receptors cause secretion of gastric acid Histamine antagonist:  The first histamine antagonists - antihistamines - competitively blocked the binding of histamine to H1 receptors, and have been used for many years in allergy treatment, findings that the H1 antagonists did not block all actions of histamine. For example, H1 receptor antagonists do not effect secretion of gastric acid because that response is due to binding of histamine to H2 type receptors;  Inhibition of gastric acid secretion requires an H2 receptor antagonist Treatment of allergy: 1. Antiallergic drugs 2. Steroids 3. Antihistamine Antihistamine: A histamine ( H1 receptors) antagonist (commonly called an antihistamine) is a pharmaceutical drug that inhibits the action of histamine by blocking its attachment to histamine H1 receptors , Clinically H1 antagonists are used to treat allergic reactions. It’s the most widely used drug in treatment of allergy Sedation is a common side-effect, especially in 1st generation, usually used orally, 103 Unit (1) First -generation antihistamines: - The main differences between the two generations of drugs are their propensity to cause central nervous system (CNS) sedation further limits such use. - In addition, many of these drugs also have actions which reflect their poor receptor selectivity, including an (anticholinergic)effect General uses: 1. Treatment of allergic disorder ( urticaria , hayfever , eczema) 2. Motion sickness ex ( diphenhydramine , cyclizine) 3. Antiemetic ( diphenhydramine, promethazine) 4. Enhance appetite ( cyproheptadine) 5. Eye and nose drop ( antazolin) 6. Sedative hypnotic 7. Treat Parkinson ( anticholinergic effect) Side effect: 1. Drowsiness , sedation 2. Anticholinergic effect ( dry mouth, blurred vision) 3. Interaction with alcohol and other sedative drugs (potentiation) Drugs: - Chloramphenicol ( allerfine)® 4 mg / tid - Clemastine ( tavegyl)® - Cyproheptadine ( periactin)® - Diphenhydramine ( benadryl)® oral 25 mg / tid - Promethazine ( phenergan)® from phenothiazine group , oral 75 mg / tid 104  Drugs acting on the central nervous system - Dimenhydramine Second-generation antihistamines Do not cross the blood–brain barrier, and as such are not supposed to cause drowsiness Drugs: - loratadine ( claritine)® 10 mg/ day advantage given orally once daily - Desloratadine (Aerius) ® - fexofenadine ( telfast)® - citrizine ( zyrtic) ® Table 2:1 Antihistamines First generation Second generation* Hydroxyzine Cetirizine Diphenhydramine Loratadine Chlorpheniramine Desloratadine Promethazine Fexofenadine Levocetirizine *Two earlier developed agents, astemizole and terfenadine, were withdrawn in 1986 because of cardiac toxicity adverse effects. Antiallergic drug: Mast cell stabilizers 105 Unit (1) Action: are cromone medications used to prevent or control certain allergic disorders. They block a calcium channel essential for mast cell degradation, stabilizing the cell and thereby preventing the release of histamine and related mediators.. 106  Drugs acting on the central nervous system f Unit (3) F Drugs acting on gastrointestinal tract  19. Drug therapy of peptic ulcer 20. Antiacid 21. Antiflatulent 22. Laxative and purgative 23. Antidiarrheal 24. antiemetic  107 Unit (1) Unit (3) Drugs acting on gastrointestinal - tract Drug therapy of peptic ulcer Peptic ulcer, 108  Drugs acting on the central nervous system Peptic ulcer disease is the most common ulcer of an area of the gastrointestinal tract that is usually acidic and thus extremely painful symptoms of vomiting and loss of appetite. It is defined as mucosal erosions equal to or greater than 0.5 cm. Ulcers can also be caused or worsened by drugs such as aspirin, ibuprofen, and other NSAIDs. Four times as many peptic ulcers arise in the duodenum—the first part of the small intestine, just after the stomach—as in the stomach itself. Causes: A major causative factor is chronic inflammation due to Helicobacter pylori that colonizes the antral mucosa., the bacterium can cause an increase of gastric production by that part of the stomach, that stimulates figure 3:1 Peptic ulcer the production of gastric acid by parietal cells Another major cause is the use of NSAIDs.. Although some studies have found correlations between smoking and ulcer formation, Some suggested risk factors such as diet, and spice consumption, Caffeine and coffee, and also alcohol consumption. Treatment: Treatment for peptic ulcers depends on the cause. Treatments can include several drug groups 109 Unit (1) 1st : Antibiotic medications to kill H. pylori. When H. pylori infection is present, the most effective treatments are combinations of two antibiotics (e.g. Clarithromycin, Amoxicillin, , Metronidazole) Antibiotics are important for complete eradication of H. pylori  Iether Clarithromycin, Amoxicillin  Or Amoxicillin, , Metronidazole  Or Clarithromycin, , , Metronidazole 2nd: Medications that block acid production and promote healing. Proton pump inhibitors Effect: : reduce stomach acid secretion. More powerful than H2 blocker Action: Proton pump inhibitors act by irreversibly blocking the system (the H+/K+ ATPase, or, more commonly, the gastric proton pump) of the gastric parietal cells Uses: These drugs are used in the treatment of many conditions, such as:  Dyspepsia  Peptic ulcer disease  Gastroesophageal reflux disease  Stress gastritis prevention 110  Drugs acting on the central nervous system  Zollinger-Ellison syndrome These drugs include: omeprazole (losec)®, 20 -40 mg / day ,, 10 mg for heart burn lansoprazole (lanzor)®, esomeprazole (Nexium)® pantoprazole (Protonix)®. Side effect : Common adverse effects include: headache, nausea, diarrhea, abdominal pain, fatigue, and dizziness. Figure 3: 2 Proton pump inhibitor Long-term use of proton pump inhibitors, particularly at high doses, may increase risk of hip, wrist and spine fracture. 3rd: Medications to reduce acid production. (H-2) blockers Effect: reduce the amount of stomach acid released into digestive tract by about 70 %, which relieves ulcer pain and encourages healing. They used orally Action: The H2 antagonists are competitive antagonists of histamine at the parietal cell H2 receptor Uses: H2-antagonists are used by clinicians in the treatment of acid-related gastrointestinal conditions, including: 111 Unit (1)  Peptic ulcer disease  Gastroesophageal reflux disease  Dyspepsia  Prevention of stress ulcer Adverse reaction: - H2 antagonists are, in general, well tolerated, except for cimetidine, cimetidine may also cause gynecomastia in males, loss of libido, and impotence, which are reversible upon discontinuation - Cimitidine may interact with many drugs and interfere with their metabolism in the liver so increase the other drugs effect ex (phenytoin , theophyllin) Drugs: - Cimitidine (Tagamet) ® 400 mg / 2 - Ranitidine (Zantac) ® 150 mg / 2 - Famotidine (pepsin)® 40 mg , 20 mg , 10 mg - Nizatadine Ranitidine and Famotidine most widely used 4th Medications that protect the lining of your stomach and small intestine. Cytoprotective agents that help protect the tissues that line stomach and small intestine. Options include sucralfate (Carafate)® and misoprostol (Cytotec)®. And bismuth subsalicylate (Pepto-Bismol)®. Patients who are taking nonsteroidal anti-inflammatory (NSAIDs) may also be prescribed a prostaglandin analogue 112  Drugs acting on the central nervous system (Misoprostol) in order to help prevent peptic ulcers, which are a side-effect of the NSAIDs. 5th antimuscarinic drugs - Parasympatholytic drugs will decrease gastric secretions ( atropine effect) - Drugs with general antimuscarinic activity not proved successfully in treatment of peptic ulcer because of the unwanted systemic effect - Pirenipine has some selectivity to decrease gastric secretions with less systemic effect - Used in duodenal and gastric ulcer 6th Antacids that neutralize stomach acid H2 receptor blocker and proton pump inhibitor are generally preferred for ulcer healing. 113 Unit (1) Antacids  Acids secreted in stomach for digestion of food  The wall of stomach is protected from acid by layer of mucous  Problem when the stomach lining is damaged or when too much acid is produced  Excess acid leading to discomfort , commonly referred to indigestion  An antacid is a substance which neutralizes stomach acidity and thus relieve pain  They are simple chemical compounds that are mildly alkaline  They have fast local effect  They are specially useful one to three hours after meal to neutralize after meal acid surge Figure 3:3 Action: Antacids are substances that reduce gastric acidity by neutralizing HCl. Uses: -Antacids are taken by mouth to relieve heartburn, -The major symptom of gastroesophageal reflux disease, or acid indigestion 114  Drugs acting on the central nervous system -Treatment with antacids alone is symptomatic and only justified for minor symptoms. The treatment of ulcers resulting from excessive acidity may require H2-receptor antagonists or proton pump inhibitors, and eradication of H. pylori Types of antacid:  Sodium bicarbonate: (NaHCO3) regular high doses may cause alkalosis (has a systemic effect), which in turn may result in altered excretion of other drugs, and kidney stones. Increased intake of sodium may be deleterious for arterial hypertension, heart failure and many renal diseases, a chemical reaction between the carbonate and hydrochloric acid may produce carbon dioxide gas. This causes gastric distension  Aluminum hydroxide: (AL (OH) 3) May lead to constipation But this is often countered by combining this one of antacid with one that contain magnesium ( Maloox)®  Magnesium hydroxide: Mg trisilicate , Mg O, Mg (OH)2 - Has a laxative properties. - They have long action - Low absorption systemic ( only local effect) - Should not be used in kidney failure  Calcium salt ( CaCO3 ) in stomach form Ca Cl2 , which cause nausea , vomiting and diarrhea 115 Unit (1) Antiflatulent An antiflatulent agent is a drug used for the alleviation or prevention of excessive intestinal gas, i.e., flatulence 1. Antifoam an antifoaming agent such as simeticone (Disflatyl)® may be taken orally. This agent will break the gas bubbles along the GIT, thereby easing the release of gas within the gastrointestinal tract via burping or flatulence. 2. Kaolin ⟶ adsorb gas 3. Activated charcoal (Eucarbon) ® ⟶ adsorb gas and toxin: Combined preparations:  Antacid + antifoaming agent (Dimethicone)  Are intended to relieve flatulent and heart burn Antispasmodic agent  An antispasmodic is a drug or a herb that suppresses muscle spasms  The effect is to prevent spasms of the stomach, intestine  Antcholinergic: Both dicyclomine and hyoscyamine (Buscopan)® are antispasmodic due to their anticholinergic action Should not be used in gastroesophageal reflux disease.  Mebeverine( Duspatalin) ® is a muscolotropic spasmolytic with a strong and selective action on the smooth muscle spasm of the gastrointestinal tract , not has the side effect of anticholinergic 116  Drugs acting on the central nervous system  Peppermint oil has been traditionally used as an antispasmodic Laxative and purgative  Laxatives (purgatives,) are compounds and/or drugs taken to loosen the stool  The terms may used interchangeably, but work different,  Cathartic or Purgative is a substance that accelerates defecation, produce intense action  This is in contrast to a laxative, which is a substance which eases defecation, usually by softening feces produce mild gentle stimulation. It is possible for a substance to be both a laxative and a cathartic  Uses: most often taken to treat constipation. Certain stimulant, lubricant and saline laxatives are used to evacuate the colon for rectal and/or bowel examinations, and may be supplemented by enemas under certain circumstances.  Laxatives may be oral and/or in suppository form Types of laxative: 117 Unit (1) 1st Bulk-forming agents  A bulk-forming agent is a substance, such as fiber in food, that adds bulk and soak up water and expand to distend the rectum ,  Also known as bulking agents or roughage, these include insoluble dietary fiber. Bulk-producing agents cause the stool to be bulkier and to retain more water, as well as forming an emollient gel, making it easier for peristaltic action to move it along. They should be taken with plenty of water. Bulk-producing agents have the gentlest of effects among laxatives and can be taken just for maintaining regular bowel movements  May not be effective in elderly patient  Depend on ability of colon to respond to destination Figure 3:4 Examples:  Bran (insoluble fiber),  psyllium (Metamucil)®  methylcellulose  dietary fibre,  Agar. 2nd hyperosmotics laxative  works by the osmotic effect, which retains water in the colon, 118  Drugs acting on the central nervous system  administered orally or rectally to draw water into the feces  lactulose( dupulac)® lowering the pH through bacterial fermentation to lactic, and acetic acid, and increasing colonic peristalsis. Lactulose is also indicated in Portal- systemic encephalopathy. May used in elderly people, and for long term treatment of constipation  Glycerin suppositories work mostly by hyperosmotic action,  Solutions of electrolytes (sodium chloride, sodium sulfate) are used for whole bowel irrigation, a process designed to prepare the bowel for surgery or colonoscopy and to treat certain types of poisoning.. (intense effect)  Saline Examples: sodium phosphate, magnesium citrate, magnesium hydroxide ,magnesium sulfate (Epsom salt)®. Saline laxatives attract and retain water in the intestinal lumen, increasing intraluminal pressure and thus softening the stool. Saline laxatives may alter a patient's fluid and electrolyte balance. 119 Unit (1) 3rd Stimulant or irritant - Stimulant laxatives (also called "irritant laxatives") act on the intestinal mucosa or nerve plexus, altering water and electrolyte secretion. - They also stimulate peristaltic action and can be dangerous under certain circumstances - They are the most powerful among laxatives and should be used with care , very habit forming Table 3:1 stimulant laxative Cascara (casanthranol) Anthraquinone plant ( barbalion , emodin) Senna extract (senna glycoside) Anthraquinone Aloe vera (aloin) Anthraquinone bisacodyl (oral) ( dulcolax)® dose 5 – 15 mg before sleep, oral or supp Castor oil ricinoleic acid ( fixed oil) 4th Stool softeners (lubricant laxative) These simply make the stool slippery, so that it slides through the intestine more easily. An example is mineral oil, which also retards colonic absorption of water, softening the stool. Mineral oil may decrease the absorption of fat-soluble vitamins and some minerals. mild laxative Good for pregnancy , lactation , children 120  Drugs acting on the central nervous system Table 3:2 121 Unit (1) Figure 3:5 122  Drugs acting on the central nervous system Antidiarrheal Diarrhea is the condition of having three or more loose or liquid bowel movements per day The most common causes are - Microorganisms (bacteria, virus or ameba) - Drugs stimulate the parasympathetic nervous system - Broad spectrum antibiotic - Functional simple diarrhea , poor dietary habits and stress (anxiety) It is a common cause of death in developing countries and the second most common cause of infant deaths worldwide. The loss of fluids through diarrhea can cause dehydration and electrolyte disturbances such as potassium deficiency or other salt imbalances. Treatment:  In many cases of diarrhea, replacing lost fluid and salts is the only treatment needed. This is usually by mouth – oral rehydration therapy – or, in severe cases by parenteral infusion, Oral rehydration solutions with modest amounts of salts and are the treatment of choice  Treatment of diarrhea depends on eradication the cause by using antibiotic, anti ameba..….  Antidiarrheal drug may be provide relief , once it certain that the diarrhea is neither infection nor toxic 123 Unit (1)  Drugs: - Decrease intestinal motility by anticholinergic and opioid - Antimotility agents like loperamide (Imodium)® are effective at reducing the duration of diarrhea - Lactobacillus acidophilus, oral for simple diarrhea caused by antibiotic, infection or irritable colon - Adsorbent (kaolin, pectin) used to remove intestinal irritant - Narcotic are the most effective antidiarrhea , used when diarrhea is sever specially codeine , and Diphenoxilate Antiemetic An antiemetic is a drug that is effective against vomiting and nausea. Antiemetic are typically used to treat motion sickness and the side effects of opioid analgesics, general anesthetics, and chemotherapy directed against cancer. Antiemetic are also used for morning sickness, but there is little information about the effect on the fetus, and doctors prefer not to use them unless it is strictly necessary Types of antiemetic: 1st 5-HT3 receptor antagonists – these block serotonin receptors in the central nervous system and gastrointestinal tract. As such, they can be used to treat post-operative and cytotoxic drug nausea & vomiting. 124  Drugs acting on the central nervous system  Ondansetron (Zofran)® - administered in an oral tablet form, orally dissolving tablet form, orally dissolving film, or in an IV/IM injection. 2nd Dopamine antagonists act in the brain and are used to treat nausea and vomiting associated with neoplastic disease, opioids, cytotoxic drugs and general anesthetics. Side effects include muscle spasms and restlessness Domperidone (Motilium®)  Olanzapine (Zyprexa)®  haloperidol, ( Haldol)® 3rd Antihistamines (H1 histamine receptor antagonists), effective in many conditions, including motion sickness, morning sickness in pregnancy, and to combat opioid nausea.  Cyclizine  Diphenhydramine (Benadryl)®  Dimenhydrinate (Dramamine)®  Meclozine (Bonine, Antivert)®  Promethazine (Phenergan,)® Promethazine can be administered via a rectal suppository for adults and children over 2 years of age. 4th Cannabinoids are used in patients with cytotoxic nausea, and vomiting, or who are unresponsive to other agents. These may cause changes in perception, dizziness, and loss of coordination.  Cannabis - Medical marijuana 5th Benzodiazepines 125 Unit (1)  Lorazepam (Ativan)® is said to be very good as an adjunct treatment for nausea along with first line medications such as Compazine® or Zofran® 6th Anticholinergics  Hyoscine (also known as scopolamine) 7th Other  Ginger - contains 5HT3 antagonists gingerols  Propofol given intravenously. It has been used in an acute care setting in hospital as a rescue therapy for emesis Peppermint claimed to help nausea or stomach pain when added into a tea or peppermint candies 126  Drugs acting on the central nervous system f Unit (4) F Drugs acting on respiratory system  25. Bronchial asthma 26. Cough remedies 127 Unit (1) Unit (4) Drugs acting on respiratory system Bronchial asthma Asthma is a common chronic inflammatory disease of the airways characterized by variable and recurring symptoms, reversible airflow obstruction, and bronchospasm. 128  Drugs acting on the central nervous system Common symptoms include wheezing, coughing, chest tightness, and shortness of breath. Asthma is thought to be caused by a combination of genetic and environmental factors Symptoms can be prevented by avoiding triggers, such as allergens and irritants, (infections, exercise, various allergens, and psychological factor) Pathophysiology: Asthma is the result of: 1. Chronic inflammation of the airways edema of bronchial mucosa 2. Which subsequently results in increased contractibility of the surrounding smooth muscle. This among other factors leads to bouts of narrowing of the airway and the classic symptoms of wheezing. The narrowing is typically reversible with or without treatment. 129 Unit (1) Figure 4:1 Asthma treatment:  The correct use of drug either given regularly to prevent an attack or intermittently to relieve one 1st bronchodilator Bronchodilator help to dilate the bronchioles of people suffering from asthma and bronchitis, can either be taken when they are needed to relieve an attack or in regular basis to prevent this attack from occurring  Beta2-adrenoceptor agonists (β2 agonist) such as salbutamol (ventolin)® are the first line treatment for asthma symptoms. used to treat acute symptoms; and long- term control to prevent further exacerbation, has advantages of less effect on heart. Used: oral, injection, inhalation Drugs: sulbutamol, terbutalin (affect the heart) 130  Drugs acting on the central nervous system  Anticholinergic medications, such as ipratropium, provide additional benefit when used in combination with( β2 agonist) in those with moderate or severe symptoms  adrenergic agonists, sympathomimetic , such as inhaled epinephrine, have similar efficacy to (β2 agonist) They are however not recommended due to concerns regarding excessive cardiac stimulation  Methyl Xanthines :  Promot muscle relaxant by direct effect on muscle  Action: inhibit the enzyme phisphodiesterase in the bronchial muscle ⤍ causing to relax  Drugs:  Aminophylline , Theophylline  Although they are effective , they require careful use as there are a small differences between the therapeutic and toxic dose  Aminophyllin ⤍ used by injection, slow intravenous infusion Aminophyllin is a salt converted in the body to theophylline Aminophylline, Theophylline ⤍ used orally (slow release preparations)  Adverse effect: nausea, anxiety, tachycardia, arrhythmia , convulsion Adverse effect may be controlled by regulating the dose and checking blood level 131 Unit (1) 2nd Antinflammatory: Effect: drugs that prevent and inhibit inflammation and swelling of mucosa  Corticosteroids  are generally considered the most effective treatment available for long-term control ,Inhaled forms such as beclomethasone (becotide)® are usually used It is usually recommended that inhaled formulations be used once or twice daily, depending on the severity of symptoms  Inhalations enable maximum concentration to be obtained in the bronchi with minimal systemic effect  Side effect candida infection in the mouth , horse voice  Leukotriene antagonists (such as montelukast) Leukotriens are substances produced by inflammatory white cells which cause spasm of bronchial muscle Drugs are becoming available which prevent spasm by blocking action of leukotriens , so prevent inflammation  Mast cell stabilizers (such as cromolyn sodium) and ketitofen ( zaditin)® Prevent asthmatic attack by stopping the release of substance from mast cell ( histamine) which responsible for bronchospasm Uses: used by inhalation for prophylactic from asthmatic attack. 132  Drugs acting on the central nervous system Cough remedies A cough is a reflex and natural response to irritant which helps to clear the large breathing passages from secretions, irritants, foreign particles and microbes. Common causes: infection of respiratory tract, inflammation, exposure to irritant substances, allergy Cough may be: … productive that is phlegm producing, as inflammatory secretion …. Or maybe dry usually allergic So their are two main group of cough remedies, according to whether cough productive or dry 133  Unit (1) 1st productive cough Mucolytic and expectorant are the groups of drugs most commonly recommended for productive cough Mucolytic: Alter the consistency of phlegm (mucous) making it less sticky and easier to cough up 1. steam inhalation : liquified the sputum and enable it to be cough up 2. Ambroxol (mucosolvon)® , dose 15 mg / 3 3. Bromohexine (Bisolvon)® dose 8mg / 3 Expectorant: 134  Drugs acting on the central nervous system Are drugs that are frequently included in over the counter cough and cold remedies, these are said to encourage the production of phlegm , but the over all benefit of such drugs are doubtful Action: expectorant loosen the sputum and thus aid its ejection from the bronchial tree  They are nearly all emetic if given in large doses Drugs: 1. ammonium chloride (NH 4 Cl) , dose (300 – 500 ml x 3) (Benylin)® (Polaramine expectorant)® 2. Ipecacuana Alkaloid Emetin / expectorant , emetic 3. Guaphensin 2nd Dry cough Drugs used for dry cough are given to suppress the coughing mechanism by depress the cough center in the brain , also called antitussive All cough suppressants have a generally sedating effect on the brain and nervous system and commonly cause drowsiness Action: suppress the cough center in modularly oblongata Antitussive: 1) Narcotic cough suppressant 135 Unit (1)  Morphine , codeine ,  Side effect: drowsiness , constipation , miosis , urinary retention , dependence  Pholcodeine -Stronger effect than codeine as cough suppressant  Dextromethorphan D.M, used widely with cough remedies (Actifed DM)® has effective antitussive effect used with antihistamine 2) Antihistamine Has antitussive effect, cause sedation 3) Demulcent Benzoin tincture , simple tincture Cough mixtures: every formulary is replete with combination of antitussive , expectorants , mucolytic , bronchodilators and sedative Precaution Its important to select the correct type of medication for cough to avoid the risk that may makes the condition worse (using cough suppressant for productive cough may prevent getting rid of excess mucous and may delay the recovery) 136  Drugs acting on the central nervous system f Unit (5) F Vitamins and minerals  27. Hematonic 28. Vitamins 29. The parental nutrition 30. Mineral 137 Unit (1) Unit (5) Vitamins and minerals Hematonic: A hematinic is a medicine that increases the hemoglobin content of the blood. Hematinics are used to treat iron- 138  Drugs acting on the central nervous system deficiency anemia. Hematinics are usually vitamins or minerals that are essential for normal erythropoiesis. 1st Iron compound Physiological importance of iron:  Present in hemoglobin ( 70 % of body iron)  Present in mioglobin ( 5% of body iron)  Present in enzymes ( cytocrome 0.2 %)  Stored in reticuloendothelial system and bone marrow as ferritin and hemosederin ( 25 %)  2 % lies in the labile iron pool ( part of body iron which is ready available) Pharmacokinetics:  Absorbed from small intestine ,(10%) the amount absorbed increased in anemia  Ferrous Fe++ is better absorbed than ferric Fe+++  food impaired absorption and vitamin C enhance it  pregnant lady needs during third trimester 5 mg daily uses:  Iron compounds is used in iron deficiency anemia which result from the following: - excess demand - reduced stores - defective absorption Iron preparations: Oral iron: ferrous sulfate, ferrous chloride, ferrous gluconate 139 Unit (1) - Dose 180 – 210 mg / day - They are effective easily administered and cheap - Side effect : nausea , epigastric pain and constipation Parenteral iron: - uses : mal absorption Continuous blood loss Anemic pregnant women just before term - Side effect include: gray brown staining of the skin , fever headache , vomiting , arthralgia , urticaria , bronchospasm 2nd Vitamin B 12 cyanocobalamine physiological importance: - Required for normal erythropoesis and maturation of other cell types - Required for certain biochemical reaction - Facilitate entrance of folic acid to the cell figure 5:1 Pharmacokinetics: - Normal body store 3mg - Synthesized in small intestine by normal flora (5 mg / day) 140  Drugs acting on the central nervous system - The absorption needs the presence of intrinsic factor Uses: - Used in pernicious anemia that result from : - Deficiency of intrinsic factor ( genetic) - Nutritional deficiency - Mal – absorption - It can be given orally or injection in a dose of 300 – 1000 mg /day 3rd Folic acid  Present in a wide varieties of plants and animal tissue  Required for normal erythropioses and many biochemical reaction  Deficiencies lead to megaloplastic anemia  Its used in folate deficiency which result from : 141 Unit (1) Figure 5:2 - Nutritional deficiency (children , old age , alcoholism) - Mal absorption (diseases from small intestine) - Excessive utilization (pregnancy, hemolytic anemia, malignant diseases, chronic inflammatory diseases) - Drugs as, phenytoin, phenobarbitone, nitrofurantoin. Vitamins A vitamin is an organic compound required by an organism as a vital nutrient in limited amounts ,its is called a vitamin when it cannot be synthesized in sufficient quantities by an organism, and must be obtained from the diet.. 142  Drugs acting on the central nervous system Figure 5:3 vitamines List of vitamins: 143 Unit (1) A riboflavinosis: angular stomatitis , sore throat , dermatitis , itching and burning of eyes, neuropathy, mild anemia Beri beri : CNS (fatigue, paralysis, , cardiovascular (edema , cardiac enlargement heart failure) Vitamin B6 : used in nausea and vomiting in pregnancy (Navidoxin )® = cyclizin + pyridoxine Pellagra: diarrhea , dermatites , dementia Scurvey: anemia , joint pain , hemorrhage from mucous membrane in mouth , GIT and skin , delay in wound healing 144  Drugs acting on the central nervous system The parental nutrition:  Normal saline injection ( NaCl 0.9%) : Uses: 1. hypotention 2. dehydration 3. nutrition 4. after surgery  Dextrose injection 5 % Uses: nutrition Hypoglycemia , as in high insulin dose  Amino acids Uses: GIT disease Coma Post surgery in patient not allow to swallow ( NPO)  NaHCO3 Used in acidosis Minerals: 145 Unit (1) 1) calcium Uses: 1. used to treat tetany (acute hypocalcemia), require systemic IV therapy by Ca gluconate 2. Ca gluconate tablet to treat hypoparathyrodism 3. Rickets ( children) + VIT D also in osteoporosis 4. Pregnancy + lactation 2) potassium Dietary source , from green leafy vegetables , orange , potato , and banana Uses: 1. With diuretic as thiazide and furosamide 2. To treat digoxin toxicity 3. Deficiencies 146  Drugs acting on the central nervous system f Unit (6) F Dermal preparations  - Drugs affect the skin 147 Unit (1) Unit (6) Dermal preparations Drugs affect the skin  Locally acting drugs are applied onto the skin and sometimes on mucous membranes, 148  Drugs acting on the central nervous system  The term topical preparations  the benefits include: 1. Concentration of drug at site of application is high 2. Systemic absorption is negligible 3. Adverse effects are minimum as compared to systemic preparation Figure 6:1  Types of applications most commonly used bases or vehicles  Tinctures  Wet dressings  Lotions  Gels  Aerosols  Powders  Pastes  Solution  Creams  Ointments 149 Unit (1)  Collodions  Active ingredient in preparations: 1) antibiotic ,,,, for bacterial infection 2) antifungal 3) local corticosteroid 4) antiviral 1. Demulcents Means to ‘smooth down’. These are protective agents applied over throat and mucous membrane to treat irritation. Uses: lozenges , gargles Examples:-  Gum acacia, Tragacanth  Glycyrrhiza  Synthetic cellulose, Methyl cellulose, Carboxy methyl cellulose  Glycerin  Starch 2. Emollients External protective which provide lubrication. they are used for dry skin they soothe and smooth the skin , may used as vehicle for another drugs Examples:-  Animal fat, lanolin  Vegetable oils: , Olive oil , Cotton seed oil , Theobroma oil  Paraffin , Vaseline 150  Drugs acting on the central nervous system 3. Astringents These are locally applied protein precipitants i.e. when applied over skin, they cause precipitation of proteins present over surface but do not destroy cells. They just cause contraction of tissues and wrinkling of tissues. Stretch the skin, decrease secretions, may also used antiperspiration.. Examples - Calamine - Alum - Zinc oxide - Tannic acid 4. Counter Irritants, Rubifacient  Its topical applied analgesic , applied in intact skin  Those locally acting drugs used over skin cause feeling of hotness and burning so that they mask the pain,( stimulate nerve ending)  The best counter irritants are physical agents , especially heat  Many drugs however used for this purpose  Used : in rheumatic or muscle pain 1. Camphor 2. Black mustard 3. Salicylate 4. Turpentine oil 5. Menthol 6. Capsaicin 7. Eucalyptous oil → Topical NSAIDs are used to relieve musculoskeletal pain 151 Unit (1) 5. Protective and absorbent:  Contain water repellent substances and may be used to protect the skin, may absorb moisture ,  Talc and ZnO may cool by increasing the effective surface area of skin and they reduce friction between skin surfaces.  Physical barrier preparations Example: Talc, starch , Zinc oxide , dimethicone , cotton , Cellulose, bandage, gauze, plaster, collodions 6.Caustics Topical agents which destroy upper thick layer of skin, and are thus not commonly used. Examples: Phenol ,.AgNO3 Uses: 1. Destroy warts (viral infection causing raised thick layer over skin) 2. Keratosis 3. Fungal infections & Eczema 7. Keratolytics Desquamating agents, can cause desquamation of dermis, destroy unwanted tissue, great care necessary to avoid ulceration. 152  Drugs acting on the central nervous system Characteristics: Softening & removing horny layer of skin Uses: 1. Fungal infections 2. Warts & Corns 3. Eczema & certain forms of acne 4. Psoriasis These agents are applied to reduce thickness. Examples: 1. Podophyllin (for wart) 2. Salicylic acid 3. Resorcinol 4. Tar (applied to patients of psoriasis) 5. Trichloroacetic acid As damage to skin occurs, these are carefully applied to warts especially salicylic acid. 8. Anti Acne Drugs 153 Unit (1) Figure 6:2 acne Management of acne  Topical preparations for acne, keratolytic, sulfur + antiseptic for cleansing  Oral antibiotics  Hormonal treatment  Retinoic acid & vitamin A derivatives  Isotretinoin (Roacutane)® systemic effect  astringent 9. Melanizing Agents In hypopigmentation caused by vertiligo, psoralens as methoxsalen ( lotion) ,Trioxsalen (Systemic) is applied over 154  Drugs acting on the central nervous system skin but requires direct sunlight for action, patient is asked to sit in sun after applying cream over lesion. 10. Anti Pigmentation Drugs (bleaching agent) These preparations contain: 1. Hydroxyquinones (Eldoquin)® Side Effects: Irritation of skin, patient is asked to apply small quantity gradually increasing strength. Inactivated by exposure to light, applied before going to bed. 11. Sunscreens Sunscreens :Absorb UV light. Sunblock : physical barrier UVA ⤍ cause skin aging and cancer UVB ⤍ cause sun burn and tanning Chemical compounds: 1. P-aminobenzoic acid 2. Benzophenones 3. Titanium dioxide  Performance of sunscreen is expressed as SPF (sun protection factor) 155 Unit (1)  If SPF = 10 , means that the dose of UVB required to cause erythema must be 10 times grater in protected than non protected skin  Very fair people require up to 15 SPF, below this level are not effective. 12.Psoriasis White silvery spots over skin especially over extensor surfaces, knees, elbows, scalp due to rapid turn over of epidermis. Figure 6:3 Management: 156  Drugs acting on the central nervous system - moisturizers, mineral oil, and petroleum jelly may help soothe affected skin and reduce the dryness that accompanies the build-up of skin on psoriatic plaques. - Medicated creams and ointments applied directly to psoriatic plaques can help reduce inflammation, remove built-up scale, and clear affected skin of plaques. Ointment and creams containing coal tar, dithranol (anthralin), corticosteroids like desoximetasone, and retinoids are routinely used. - Activated vitamin D and its analogues can inhibit skin cell proliferation, (for example, calcipotriol) 13. Eczema: also known as atopic dermatitis is a form of chronic inflammation of the skin. These include dryness and recurring skin rashes that are characterized by: redness, skin edema (swelling), itching and dryness, crusting, flaking, blistering, cracking, oozing, or bleeding. 157 Unit (1) figure 6:4 eczema Management: - Corticosteroids - antihistamine, - Moisturizers ,eczema can be exacerbated by dryness of the skin. 158