Carbohydrates in Pharmacy PDF

Ahmed Metwaly Associate Professor of Pharmacognosy , Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt Associate Professor, City of Scientific Research and Technological Applications (SRTA-City), Alexandria, Egypt Senior research fellow, Liaoning University of Traditio...

Ahmed Metwaly Associate Professor of Pharmacognosy , Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt Associate Professor, City of Scientific Research and Technological Applications (SRTA-City), Alexandria, Egypt Senior research fellow, Liaoning University of Traditional Chinese Medicine, China (20118-2019) Visiting scholar, School of Pharmacy, University of Mississippi, USA (2012-2014) ▪ ▪is used (by i.v. or orally) for treatment calcium deficiency. ▪These salts are characterized by being more easily absorbed than other Ca salts. ▪ Hypocalcaemia ▪ Hyperkalaemia ▪ Magnesium sulphate overdose ▪ Hydrofluoric acid burns The calcium gluconate reacts with hydrofluoric acid to form insoluble, non-toxic calcium fluoride. In addition to a 2.5% calcium gluconate gel being applied directly to the chemical burn ▪ nausea, constipation, and upset stomach. ▪ Rapid intravenous injections of calcium gluconate may cause hypercalcaemia, which can result in vasodilation, cardiac arrhythmias, decreased blood pressure, and bradycardia.  FERROUS GLUCONATE ▪ ▪ (orally or by i.v.) is used in iron deficiency. ▪ These salts are characterized by being more easily absorbed than other iron salts. ▪ An Sugar alcohol ▪ Preparation: ▪ Sorbitol is prepared by reduction of glucose  Uses: mild laxative sweetening agent in dietetic food (not absorbed), chewing gum & tooth pastes. Test of kidney function (iv), not metabolized. Mechanism of action Sorbitol exerts its laxative effect by drawing water into the large intestine, thereby stimulating bowel movements. ▪ Preparation by reduction of mannose. ▪ Osmotic diuretic osmotic diuretic that is metabolically inert in humans and occurs naturally in fruits and vegetables ▪ cerebral edema, elevated intracranial pressure, and cerebrospinal fluid Mannitol elevates blood plasma osmolality, resulting in enhanced flow of water from tissues, including the brain and cerebrospinal fluid, into interstitial fluid and plasma. As a result, cerebral edema, elevated intracranial pressure, and cerebrospinal fluid volume and pressure may be reduced. ▪ laxative, and in ▪ tests of kidney function (not metabolized if i.v.) Toxicity Mannitol overdose may result in bronchoconstriction and should be counteracted using a short-acting bronchodilator and other symptomatic and supportive care,  GLUCOSAMINE CH2OH O OH Source: strong acid hydrolysis of chitin (shells of crustaceae) H H Uses : Glucosamine is generally used over the counter in the symptomatic treatment of osteoarthritis and joint pain, frequently combined with chondroitin sulfate OH H H It is currently not approved as a prescription product by the FDA, but is widely OH available over the counter H NH2 ▪ Osteoarthritis (OA) is a progressive and degenerative joint disease marked by loss of cartilage, bone changes, and synovial membrane inflammation. ▪ provides a building block towards the synthesis of glycosaminoglycans (mucopolysaccharides), slowing the progression of osteoarthritis and relieving symptoms of joint pain. ▪ Glycosaminoglycans or mucopolysaccharides are long, linear polysaccharides consisting of repeating disaccharide units (uronic sugar and an amino sugar). hyaluronic acid (one of the Glycosaminoglycans )  ▪ Some in vitro studies show evidence that glucosamine reduces inflammation via inhibition of interferon gamma and Nuclear factor kappa B. Toxicity and side effects The oral LD50 of glucosamine in rats is >5000 mg/kg. Symptoms of an overdose with glucosamine may include nausea, vomiting, abdominal pain, and diarrhea ASCORBIC ACID Preparation: -extraction from citrus fruits - synthesis from glucose Uses: -Cure its deficiency (scurvy), cold, capillary fragility -Antioxidant in some pharmaceutical preparations CH2OH HOHC O O OH HO 1. In humans, an exogenous source of ascorbic acid is required for collagen formation and tissue repair by acting as a cofactor in the synthesis of collagens and other proteins. 2. Ascorbic acid is reversibly oxidized to dehydroascorbic acid in the body. These two forms of the vitamin are believed to be important in oxidation-reduction reactions. 3. The vitamin is involved in ▪ tyrosine metabolism, ▪ conversion of folic acid to folinic acid, ▪ carbohydrate metabolism, ▪ synthesis of lipids and proteins, ▪ iron metabolism, ▪ resistance to infections, ▪ and cellular respiration. LACTULOSE ▪ Galactose-b-(1,4)-fructose ▪ A semi-synthetic disaccharide (not naturally occurring) ▪ Not absorbed in the GI tract ▪ Used either as a laxative in constipation and for hepatic encephalopathy Mechanism Lactulose is not absorbed in the small intestine nor broken down by human enzymes, thus stays in the digestive bolus through most of its course, causing retention of water through osmosis leading to softer, easier-to-pass stool. Fermented by the gut flora, producing metabolites which have osmotic powers and peristalsis-stimulating effects (such as acetate), but also methane associated with flatulence. Lactulose is metabolized in the colon by bacterial flora into lactic acid and acetic acid. These partially dissociate, acidifying the colonic contents the formation of the nonabsorbable NH4 from NH3, trapping NH3 in the colon and effectively reducing plasma NH3 concentrations. (hepatic encephalopathy) There have also been studies demonstrating the capacity for lactulose to minimize the formation of gallstones. Anticancer potentiality owing to its ability to bind galactin carbohydrates involved in various tumor progressions SUCRALFATE (Aluminum salt of sucrose orasulfate) ▪ Gastro-duodenal protective agent used in the treatment of gastric and duodenal ulcers and to prevent duodenal ulcer recurrence The mechanism of action of this drug in the healing duodenal ulcers is not yet completely defined However, This drug aids in the healing of duodenal ulcers, relieving painful inflammation by creating a protective mechanical barrier between the lining or skin of the gastrointestinal tract and damaging substances. Sucralfate forms a complex that binds to protein-rich exudate found on the surface of ulcers. It binds to albumin and fibrinogen preventing blood clot lysis by stomach hydrochloric acid. In addition, sucralfate acts to increase levels of growth factors locally, and Also causes an increase in prostaglandins which are important in the healing of the mucosa (lining) of the gastrointestinal tract absorbed from the gastrointestinal tract in very minimal quantities ▪ Overdosage has never been observed with sucralfate. It is unlikely, as administering a maximum dose of up to 12 g/kg/body weight in several animal species did not result in death ▪ This drug is considered a pregnancy Category B drug ▪ Whether this drug is excreted in human milk is currently unknown. Constipation Dry mouth Nausea or gastrointestinal discomfort Gas/indigestion Drugs derived from starch Hetastarch It is hydroxyethyl starch (semisynthetic material) O OH (Starch) OH + Starch O CH2 CH2OH alkali Etylene oxide Hetastarch Used as plasma expander in case of shock but it increases bleeding time and cause allergy. Homopolysaccharides Polysaccharides in pharmacy Honey Introduction Heteropolysacchrides Mechanism of Action Ethoxylated amylopectins; colloidally expands plasma volume Pharmacokinetics Onset: 30 min Duration: 6-36 hr Half-life, Elimination: 17 days Metabolism: Enzymatically degraded by reticuloendothelial system or amylases in blood Excretion: Urine, feces (by biliary excretion) Administration: IV PAGE Homopolysaccharides Polysaccharides in pharmacy Honey 19 Introduction Heteropolysacchrides Adverse Effects Warnings Anaphylaxis (periorbital edema, Do not use in critically ill adult patients including urticaria, wheezing, mild temperature those with sepsis, and those admitted to the ICU elevation) Chills Avoid use in patients with pre-existing renal dysfunction Flu-like symptoms Myalgia Discontinue use at the first sign of renal injury Peripheral edema Headache Need for renal replacement therapy has been reported Pruritus up to 90 days after administration; continue to monitor Vomiting renal function for at least 90 days in all patients Salivary gland enlargement Avoid use in patients undergoing open heart surgery in association with cardiopulmonary bypass due to excess bleeding Discontinue at the first sign of coagulopathy PAGE Homopolysaccharides Polysaccharides in pharmacy Honey 20 Introduction Heteropolysacchrides Cyclodextrins are a family of cyclic oligosaccharides, consisting of a macrocyclic ring of glucose subunits joined by α-1,4 glycosidic bonds. Cyclodextrins are produced from starch by enzymatic conversion, Commonly cyclodextrin glycosyltransferase (CGTase) is employed along with amylas. They are used in food, pharmaceutical, drug delivery, and chemical industries, as well as agriculture and environmental engineering. Cyclodextrins are composed of 5 or more α-D-glucopyranoside units linked 1-4, as in amylose (a fragment of starch). Typical cyclodextrins contain a number of glucose monomers ranging from six to eight units in a ring, creating a cone shape: α (alpha)-cyclodextrin: 6 glucose subunits. β (beta)-cyclodextrin: 7 glucose subunits γ (gamma)-cyclodextrin: 8 glucose subunits β-cyclodextrin is ideal for complexation due to perfect cavity size, efficient drug complexation and loading, availability, and relatively low cost Some containing 9, 10, 11, 12 and 13 glucopyranose units have also been reported. Some derivatives containing the hydroxypropyl (HP), methyl (M) and sulfobutylether (SBE) substituents have been commercially used as new pharmaceutical excipients. PAGE 21  PAGE Homopolysaccharides Polysaccharides in pharmacy Honey 22 Introduction Heteropolysacchrides Cyclodextrins are cyclic oligosaccharides of a glucopyranose, containing a relatively hydrophobic central cavity and hydrophilic outer surface. Owing to the lack of free rotation around the bonds connecting the glucopyranose units, the CDs are not perfectly cylindrical molecules but are toroidal or cone shaped. As a result it act as molecular containers by entrapping guest molecules in their internal cavity. No covalent bonds are formed or broken during drug CD complex formation. Once included in the cyclodextrin cavity, the drug molecules may be dissociated from the cyclodextrin molecules through complex dilution in the aqueous tear fluid. Since no covalent bonds are formed or broken during the guest–host complex formation, the complexes are in dynamic equilibrium with free drug and cyclodextrin molecules. PAGE Polysaccharides in pharmacy Honey 23  PAGE Homopolysaccharides Polysaccharides in pharmacy Honey 24 Introduction Heteropolysacchrides  PAGE Homopolysaccharides Polysaccharides in pharmacy Honey 25 Introduction Heteropolysacchrides They have been applied for delivery of a variety of drugs, including hydrocortisone, prostaglandin, nitroglycerin, itraconazol, chloramphenicol. The cyclodextrin confers solubility and stability to these drugs PAGE 26  PAGE Introduction Polysaccharides in pharmacy Honey 27 Chitin and chitosan Applications of CHO as delivery system in cancer Heparin Naturally occurring anionic, sulphated glycosaminoglycan Uses Heparin is an anticoagulant indicated for thromboprophylaxis and to treat thrombosis associated with a variety of conditions such as pulmonary embolism and atrial fibrillation It binds reversibly to antithrombin III (ATIII) and greatly accelerates the rate at which ATIII inactivates coagulation enzymes thrombin (factor IIa) and factor Xa. Unfractionated heparin is indicated for prophylaxis and treatment of venous thrombosis and its extension, prevention of post-operative deep venous thrombosis and pulmonary embolism and prevention of clotting in arterial and cardiac surgery. In cardiology, it is used to prevent embolisms in patients with atrial fibrillation and prevent clotting during dialysis and surgical procedures, maintain the patency of intravenous injection devices and prevent in vitro coagulation of blood transfusions and in blood samples drawn for laboratory values.  A serious side-effect of heparin is heparin-induced thrombocytopenia (HIT), caused by an immunological reaction that makes platelets a target of immunological response, resulting in the degradation of platelets, which causes thrombocytopenia. This condition is usually reversed on discontinuation, and in general can be avoided with the use of synthetic heparins. Heparin is contraindicated in those with risk of bleeding (especially in people with uncontrolled blood pressure, liver disease, and stroke), severe liver disease, or severe hypertension Acarbose Acarbose is an alpha-glucosidase inhibitor used in adjunctly with diet and exercise for the management of glycemic control in patients with type 2 diabetes mellitus Acarbose is a complex oligosaccharide that competitively inhibits the alpha- glucosidase enzymes to break down ingested carbohydrates into absorbable monosaccharides, reducing carbohydrate absorption and subsequent postprandial insulin levels Acarbose requires the co-administration of carbohydrates in order to exert its therapeutic effect, and as such should be taken with the first bite of a meal three times daily Side effects The symptoms of acarbose overdose are likely to be consistent with its adverse effect profile and may therefore include significant gastrointestinal (GI) symptoms (flatulence, distension, etc)  Hydroxypropyl methylcellulose (Hypromellose) is a semisynthetic, inert, and viscoelastic polymer that forms a colloid solution when dissolved in water. Used as an ophthalmic protectant and lubricant, in artificial tears, Promotes corneal wetting by the stabilization and thickening the precorneal tear film and prolonging the tear film breakdown time, which is usually shortened in dry eye conditions. Hypromellose also acts to lubricate and protect the eye  Hyaluronic acid is a non sulphated glycosaminoglycan Hyaluronic acid (HA) is an anionic, nonsulfated glycosaminoglycan found in connective, epithelial, and neural tissues The average 70 kg (150 lb) person has roughly 15 grams of hyaluronan in the body, one-third of which is turned over (i.e., degraded and synthesized) per day. The intra-articular preparations of hyaluronic acid are indicated for knee pain associated with osteoarthritis. Hyaluronic acid is used in cosmetic applications to prevent and reduce the appearance of wrinkles on the face, and as a dermal filler to correct facial imperfections or other imperfections on other parts of the body. It is frequently an ingredient in topical applications for wound healing and symptomatic treatment of skin irritation from various causes. Hyaluronic acid may also be indicated in ophthalmological preparations or oral capsules to treat discomfort caused by dry eyes or conjunctivitis and for its protective qualities during and before eye surgery. Finally, hyaluronic acid can be used off-label to coat the bladder for relief of interstitial cystitis symptoms.