MDU - Gastrointestinal System

- Define Oral Liquid Dosage Form - The API is combined with a suitable lquid vehicle for oral administration - Describe the advantages of liquid dosage forms - Good absorption - Less GI irritation - No expensive drying step required when manufacturing - Phase separation isn't a concern with solutions - Describe the disadvantages of liquid dosage forms - There's taste making issues - Susceptible to microbial contamination - There's dose uniformity issues with some types of liquid dosage forms such as suspensions and emulsions - It's not as convenient as tablets or capsules - For some large liquid bottles, there are transportation issues - Define 'Pharmaceutical Solution' - A homogenous mixture of one or more solutes, dispersed in a solvent - An API as an aqueous solution offers the greatest degree of bioavailability - Why are solutions developed ? - This is because it doesn't undergo disintegration or dissolution - There's 7 - API - A vehicle - Co- solvents to improve solubility - Buffer - Sweeteners/ taste masking agents/ flavouring agents - Preservatives - Antioxidants if needed - What are the formulation components of an oral solution ? - Cimetidine - Lactulose - Give 4 examples of an oral solution ? 1 / 15 - Dexamethasone - Ondansetron - What is a syrup ? - An aqueous solution saturated with high proportions of sugar - What are the properties of syrups ? - Suitable for water soluble drugs - Dual masking effect - The drug is present with flavour and/or colorant - Concentrated sugar solutions are resistant to microorganisms due to low water content - Minimum preservatives used due to osmotic effects of high sugar concs - In low sugar concentrations, high osmotic pressure is maintained with sorbitol, glycerol and propylene glycol - Why are preservatives included in syrups ? - To counteract the consequences of surface dilution (microorganism growth) - How can you minimise crystallisation in - Polyhydric alcohols such as sorbitol, syrups ? glycerol and propylene - Occurs on and around screw caps used to seal the container - Forms a solid plug which impedes - How does crystallisation work in syrups syrup flow ? - Crystallisation is minimised by invert syrup (glucose- fructose mixture) and Polyhydric alcohols - What is an elixir ? - A sweetened solution of the API in a mixture of water and ethanol - More suitable for water soluble and alcohol soluble API's - They are less sweet and viscous than syrups 2 / 15 - Why are oil based solutions used ? - Aqueous or hydroalcoholic solutions are unsuitable when drugs are hydrophobic - This is because hydrophobic drugs are soluble enough in polar solvents like water or alcohol - Oil based solutions taste and feel deegusting orally so they can be used to formulate injections - What is the most common reason for seeking an alternative formulation ? - The instability of the API in aqueous solution - Storage temperature - Microbial contamination leading to pH change - Evaporation of a volatile co-solvent - What are the 4 factors affecting physical - Degradation to a compound with restability of a pharmaceutical solution ? duced solubility - All these factors come ability to disperse the components of the solution, leading to crystallisation or precipitation - Why are solutions a challenge in regards to chemical stability ? - They are highly mobile - Therefore more susceptible to degradation than other oral dosage forms via hydrolysis and/or oxidation - What is a tincture ? - An alcoholic or hydroalcoholic solution containing API or extracts from plant materials - Alcohol content ranges from 15-80% - What is a suspension ? - A dispersion of a solid within a liquid or gas - Useful for delivering liquid doses of poorly soluble/ insoluble drugs - Suspension classification - A Coarse suspension = particles > 1 micrometers 3 / 15 - A colloidal suspension = particles <1 micrometers - Oral - Topical - Injectable - Otic - Rectal - Different routes/ types of suspensions ? - The API (usually a water insoluble drug dispersed in an aqueous suspension - Wetting agents= Drugs with a hydrophobic surface are difficult to disperse in an aqueous medium. Wetting agents form a coating around the API molecule and act to reduce surface tension - Suspending agents= added to increase viscosity of the medium - What components does a suspension - Flocculating agents= neutralises the usually have ? high charge density of certain particle types therefore preventing flocculations and caking following sedimentation - Preservatives= Prevents microbial growth - Sweeteners= Masks unpleasant taste of the API - Flavours= Increases patient compliance with the suspension - Colorants= Makes it pretty - What is flocculation? - When particles of a liquid suspension forms relatively weak bonds to create loose, light fluffy flocs held together by weak van der waals forces - How does flocculation occur ? - Idk tbh pls explain it to me if you understand :( - What is aggregation ? - When the particles of a liquid suspension are held together by strong inter particles forces and therefore aggregate 4 / 15 - Leads to crystallisation which forms a thin solid layer of precipitate known as cake - What is easier to resuspend, suspensions which aggregate or suspensions which floc? - Flocculation/ flocculating agents - = Increased API bioavailability - Increased drug stability compared to aqueous solutions - Has prolonged drug action - What are the advantages and disadvantages of emulsions ? - = Emulsions are thermodynamically unstable, leading to possible flocculation, creaming, coalescence and breaking - More complex to formulate than solutions - Define Malnutrition - A deficiency or excess or an imbalance of energy, protein and other nutrients - Reasons for Malnutrition - Inadequate/ unbalanced food intake - Patients having increased requirements - Defects in food absorption or digestion - What are the signs of malnutrition? - Loss of muscle and fat mass - Impaired immune response and ability to deal with illness - Poor wound healing - Define PN - Parenteral nutrition= administered centrally, by IV to the central vein - Nutrients are delivered directly into the superior vena cava or right atrium - = Passes into systemic circulation and bypasses the GI tract. Avoids first pass metabolism by the liver - Macronutrients - Fat - Carbs - Protein 5 / 15 - Micronutrients - Vitamins - Minerals - What are the components of PN ? - Carbs in the form of glucose - Fat emulsion - Amino acid solutions - Electrolyte solutions - Vitamins (fat soluble and water soluble) - Trace elements - Water - What are the 3 main groups of lipids ? - Triglycerides - Phospholipids - Sterols - Minimum fat requirements ? - 0.3g/kgBW to ensure that essential fatty acid requirements are met - What physiological functions are involved with vitamins ? - Anabolism - Energy metabolism - Amino acids metabolism - Nucleotides biosynthesis - RBC formation - Protection against oxidation - What are examples of fat soluble vitamins ? - Vitamins A, D, E and K - They are stored in the adipose tissues - Vitamin C and B - What are examples of water soluble vitamins ? - These vitamins aren't stored - Coalescence= dispersed droplets merge together to form large particles - Flocculation= Dispersed particles form - Inadequate physical stability of an weak interactions with each other and emulsion can lead to what 4 phenomeform flocs na? - Creaming= The upward movement of dispersed droplets leading to obvious phase separation. Opposite movement 6 / 15 downwards= sedimentation and the difference in direction is a result of density differences. - Breaking= The complete separation of the emulsion into its component phases - They provide substrate for protein syn- Why are amino acids essential in par- thesis, leading to diminished catabolism, enteral solutions ? improved hormone functioning, tissue repair and preserve lean body mass - They can't be broken down - Why aren't proteins suitable for parenteral nutrition solutions ? - Protein requirements vary and range from 0.15-3g of nitrogen per day - Preserves intracellular and extracellular fluid balance - What is the main role of electrolytes ? - Provides minerals essential for tissues turnover - What is a Suppository? - A solid unit dosage form that goes in the rectum - = Can also be used to administer drugs for systemic absorption, can promote evacuation of the bowel, can be used in unconscious patients, avoids GI irrita- Advantages and disadvantages of rection, avoids first pass metabolism tal route of administration? - = May be unacceptable to certain patients, difficult to self administer for arthritic, elderly or immobile patients - How do suppositories work? - 1) Melting of the suppository base at body temp - 2) Dissolution of the suppository base in surroundings fluids - 3) Dispersion of the suppository base in surrounding fluids 7 / 15 - The quantity of fluid available= dictates how rapidly the API can dissolve - Properties of rectal mucus= Slows drug absorption - What physiological factors affect rectal - Rectal content= Affects drug absorption drug absorption? and spreading of the suppository mass - Rectal wall motility= Increased contractile activity of the rectal wall increases the spreading of the suppository—> increases bioavailability - What are suppositories composed of ? - 1) A vehicle (base) - 2) Co formulation additives - 3) API - What are the 2 types of base that can be used for the suppository? - Fatty hydrophobic bases - Water soluble hydrophilic bases - What characteristics does the base - Needs to melt at physiological temperneed to make it suitable for suppository ature formulation ? - Needs to dissolve - An agent added to stabilise emulsions - One of the most commonly utilised class of emulsifiers= surfactants - What is an emulsifier? - Hydrophobic tail of the surfactant is protected from water. When surface is occupied, they start to form micelles. - Micelles are spheres of surfactant molecules, arranged so polar beads are on the external surface of the sphere and the hydrophobic tails are protected within - Micelles contain the dispersed phase which can lead to very stable dispersions 8 / 15 - Enemas - 2 formulations - An evacuant enema= Used as a bowl stimulant to treat constipation (volume of evacuant enemas may reach up to 2 litres - They should be warmed to body temperature before administration - Retention enema= A medicated dosage form designed to be retained within the rectum to provide a local effect or to be absorbed to provide a systemic effect like a suppository - volume doesn't exceed 100ml - Rectal foams - Used in certain conditions such as ulcerative colitis - Injected into and expands to fill the cavity. Distributes the API around the rectum and demonstrates improved retention characteristics compared to traditional liquid enemas - The API is dissolved in a low bp solvent containing preservatives and buffering agents - 1) In cephalic phase of secretion, vagus nerve releases ACh, stimulating m1 muscarinic receptors on parietal and paracrine cells - 2) Gastric Phase =food in stomach. - What is the mechanism for Gastric Acid Stimuli such as proteins + stomach disproduction ? tension triggers gastric release from G cells. Gastric acid stimulates muscarinic and gastric receptors on parietal cells. This causes intracellular Ca2+ increases. Therefore, H+/K+ ATPase pumps are activated . 9 / 15 - Muscarinic and gastrin receptors on nearby paracrine cells causes release of histamine. Histamine stimulates H2histamine receptors on parietal cells, increasing intracellular cAMP production -> Maximising gastric acid production. - What is Dyspepsia and how is it treated ? - A general term relating to problems such as hyperacidity, indigestion, bloating and heartburn. - Antacids - More severe cases= proton pump inhibitors or H2- receptor antagonists - How do Antacids work? - Neutralises gastric acid in the stomach lumen - Raises pH - however acid rebound can occur - What is acid rebound ? - When reduction in gastric acid stimulates more gastrin release - This causes more gastric acid to be produced - Sodium bicarbonate= Water soluble and rapid onset of action - Unfortunately the CO2 produced in the reaction stimulates gastrin release, can cause acid rebound effect. Sodium bicarbonate can be absorbed by the intestine, frequent/ large dose can cause systemic alkalosis - Describe the different types of Antacids ^This NOT recommended to be used. - Magnesium hydroxide= insoluble in water. Rapidly reacts with HCL. Poorly absorbed by intestine, low risk of alkalosis. Can cause diarrhoea. - Aluminium hydroxide= Not well ab10 / 15 sorbed by intestine, neutralises HCL over a period of hours. Causes constipation. - Therefore, aluminium hydroxide and magnesium hydroxide are combined together. - Alginates - What is sometimes given with Antacids - Increases mucus viscosity, supporting ? the barrier forming nature of the mucus - also mucus and mucous are different - What are peptic ulcers and how are they treated ? - When the gastric mucousal barrier is breached and gastric wall becomes damaged. This damage can also occur if pepsin and acid are present in high concs. Or if a different problem can reduced the normal protective mechanisms of the mucus. - H2- receptor agonists - proton pump inhibitors - Burning pain high up in the abdomen - Base of ulcer= surrounded by rim of inflamed tissue - Symptoms of peptic ulcers ? - Factors leading to peptic ulcers= alcohol, smoking, long term NSAID use, chronic gastritis, corticosteroid use, stress, Zollinger- Ellison syndrome (overproduction of gastrin). - Drugs such as cimetidine and raniti- How do Histamine H2- receptor antagdine antagonise H2- receptors on parionists work? etal cells. This reduces gastric acid. - PPI drugs such as lansoprazole and omeprazole ( pro drugs= activated only at very low pH) are inactive when admin11 / 15 istered, but activated in acid. - Irreversibly inhibits H+/ K+ ATPase - How do proton pump inhibitors work ? pumps on parietal cells, causes almost no gastric acid to be produced. - More detailed - What is H. pylori ? - Passes through membrane as un ionised lipophilic bases. Becomes protonated in acidic environment. Can't cross back over membrane, accumulates in canaliculi. - Protonation triggers acid catalysed conversion, which activates drug, causing it to bind to exposed cysteine residues of proton pumps and blocks the pump to prevent release of HCL - Contributes to ulcer formation by producing inflammatory toxins that weaken the gastric mucosal barrier - Survives harsh acidic environment in stomach - Detected via a stool antigen test or urea breath test. - H. pylori triple therapy treatment ? - A proton pump inhibitor and 2 antibiotics are given for initially one week - Mucosal protectants ? - Alginates - Bismuth Chelate= high affinity for exposed mucosal glycoproteins and necrotic tissue in ulcers. This forms protective layer. Can blacken teeth, tongue and faeces. - Misoprostol= Reduces gastric acid production and increases protective mucus secretion - Bulk forming laxatives - What is the treatment of constipation ? - Osmotic laxatives - Stimulant laxatives- Faecal softeners 12 / 15 - Antidiarrhoeal treatments - Oral Rehydration Therapy= solutions of electrolytes and glucose. - How is Diarrhoea treated ? - More diarrhoea treatments ? - Antimotility Treatments= Loperamide. - Hybrid molecule which is lipophilic, slowly absorbed and metabolism prone. Antagonises opioid receptors in the GI tract, causes K+ ion channels to open. Leads to hyper polarisation of the cell, inhibits neurotransmitter release, therefore reduces bowl motility. - Adsorbents= Kaeolin } a pure form of natural clay. Either adsorb microbes or their toxins, coat and protect intestinal mucosa. Or adsorbs excessive fluid in the bowel. - Usually administered as a suspension on its own or as a mixture with other drugs like morphine - Obesity treatment ? - How is vomiting caused ? - Lipase Inhibitors - Orlistat - Lipases normally digest dietary lipids into fatty acids and glycerol which can then be absorbed - Orlistat inhibits lipase so fat can't be digested effectively, therefore reducing calorific intake - Co- ordinated by area in lateral reticular formation of the medulla - CTZ (chemoreceptor trigger zone) communicates with vomiting centre and detects chemical stimuli. - Vomitting centre also receives info from these sources: 13 / 15 - Limbic cortex, nucleus solitarius and spinal cord. - Antiemetic drugs ? - Antimuscarinics= Hyoscine directly antagonises muscarinic receptors - H1- Histamine receptor antagonists= Cyclizine for example, Antagonises H1 receptors on the vomiting centre - Dopamine D2 receptor antagonists= Antipsychotic phenothiazine's such as prochlorperazine blocks dopamine D2 receptors on the CTZ and also antagonises muscarinic and histamine receptors - Crohn's disease= affects any part of GI tract - 2 forms of IBS ? - Ulcerative Colitis= Only affects your bum - Management for Crohn's disease ? - Anti diarrhoeas such as Loperamide - Nutrition advice about low fat diets - Glucocorticoid anti inflammatory treatment such as oral prednisolone - if unable to take glucocorticoids, 5-aminosalicylates are taken - Aminosalicylates - Mechanism of action unknown - Suppositories= Site of action, rectum. Treats proctitis. - Ulcerative Colitis - Foam= Site of action, Sigmoid colon. Treats Proctosigmoiditis. - Enemas= Site of action, descending colon to splenic fixture. Some cases, distal part of transverse colon. Treats left sided colitis 14 / 15 - proctitis ? - Affects rectal mucosa - Proctosigmoiditis? - Affects Rectum and Sigmoid Colom - Left sided Colitis ? - Affects Rectum, Sigmoid colon and descending colon up to splenic fixture - Pancolitis / extensive Colitis ? - Affects Rectum and up past the splenic fixture 15 / 15