Normal Function of GI tract Flashcards
What happens when a drug is inside the body, and arrives at the site of action?
The drug binds to the receptors, usually on the outer membrane of the cells and this usually results in the activation of enzymes located within the cell
What are the 4 steps of drugs and how they act in the body?
Absorption, distribution, metabolism and excretion
Where are most receptors located and how do they work?
Receptors are typically found as integral membrane proteins at the plasma membrane - they recognise and bind to specific chemicals thereby invoking a biological response?
Receptor numbers can be…
Increased or decreased. This can happen in light of chronically high or low concentration of the agonist to optimise specificity.
What is affinity?
Affinity refers to the strength of binding to the receptor.
What is efficacy?
Efficacy refers to the intrinsic activity and how effectively a response is produced as a result of the binding.
What does an antagonist do?
It blocks the receptor from binding to the agonist - an antagonist has affinity to the receptors but does not exert efficacy.
Examples of signal transduction?
- Direct opening of ion channels
- Direct activation of an enzyme
- Indirect activation/ inactivation of enzyme or indirect opening/ closing of ion channel
How do ion channels get opened by agonists?
The agonist binds and causes a conformational change, leading to ion channel influx due to the channel opening.
Calcium is responsible for
- Muscle contraction
- Secretion
- Metabolism
- Neuronal excitability
- Cell proliferation
Calcium is a…
Secondary messenger (neither produced nor destroyed). It is moved between compartments and the effects are concentration dependant
Calcium acts via…
Activation of specific protein kinases, ion channels
Regulation of activity of many enzymes.
How does cell signalling affect the parietal cell?
Acetylcholine binds to the muscarinic acetylcholine receptor located on both the parietal cell and this results in the stimulation of acid secretion via the proton pump into the stomach.
Ranitidine acts at the…
Histamine receptors on parietal cells, to reduce gastric acid secretion.
Loperamide acts at the
Opioid receptors in the myenteric plexus - this results in reduced peristalsis and an increased tone of the anal sphincter
What is pharmaceutics?
The process of turning new chemical entity into a medication to be used safely and effectively. - It is also called the science of dosage form design
Medicines are
Drug delivery systems in normal terms - they are the same as drugs when there are no excipients in the drug formulation.
Why do medications sometimes need to be taken after meals?
Due to physiological differences between the stomach in both fasting and fed states.
What is the first pass effect?
This is where the drug has been ingested orally and due to the body perceiving the drug as a toxin, it is transported to the liver for elimination and around 50% of the drug is eliminated in the process.
Drug safety is dependant on…
its therapeutic index
At the molecular level, a drug target is a…
Biomacromolecule
What happens to COX when drugs like ibuprofen bind?
Drug binds to COX which prevents arachidonic acid from binding to COX and being converted to prostaglandins
What is the side effect of NSAID use
High prostaglandin levels increase mucosal thickness of the stomach wall, which protects it from acid degredation - non specific inhibition of COXwill result in the formation of an ulcer
Salbutamol is a
Beta-2 drug adrenoceptor-agonist which is able to mimic the affect of adrenaline and noradrenaline which is therefore able to dilate the airways
What structure of Cox enables the enzyme to perform its function?
The tertiary structure
Flurbiprofen binds in the COX active site, at a….
greater affinity than arachidonic acid.
The oral mucosa is
a major barrier to drug delivery
The gingival and palatal tissue are…
located on the gums and roof of the mouth and are keratinised/ non polar
The buccal and sublingual tissue are…
Non-keratinised and polar
Buccal delivery can be via:
- Sublingual membrane - delivered under the tongue and very fast
- Buccal membrane - delivery from the cheek and lip cavity - slower and better suited to control release
- Topical delivery from a “tablet” retained within the mouth
Absorption from the Buccal cavity avoids
First-pass metabolism which can affect the drug pharmacokinetics
A buccal drug delivery system must be designed to…
stick to the buccal surface - this “glue” is usually a polymer that adheres to a biological surface or to the mucosal surface (mucoadhesion)
Mucoadhesive glue should typically…
Become tangled in the glycoprotein surface of the cells, and bonds with glycoproteins
Physical entanglement of mucoadhesives will occur when…
The adhesive is a high Molecular weight and allows for hydration swelling
What is a solution?
A mixture of 2 or more components that from a single phase that is homogenous down to the molecular level
What is dissolution?
the transfer of molecules or ions from a solid state into solution
What is solubility of a substance?
The amount that goes into a solution when equilibrium is established between the solute in solution and the excess undisssolved substance
Dissolution is the..
rate limiting step in drug absorption
What is the Noyes whitney equation?
DM/DT = DA x (Cs-C)/h
DM/DT refers to the rate of dissolution of the drug particles
D= diffusion coefficient
A= Effective surface area of the drug particles
h = thickness of the diffusion layer
Cs= the saturated solubility
C = Concentration of bulk solubility
Explain how the dissolution process occurs when a solid drug particle is amongst a solution?
The molecule detaches from the solid, and diffuses across the diffusion layer, and then leaves the diffusion layer for well stirred bulk.
Which factors affect dissolution rates
-Surface area of undissolved solid - this can be affected by the size of solid particles, the total area increases as particle size reduces and more porous particles have a bigger surface area.
-Saturated solubility of solid - solubility in dissolution medium as well as temperature can affect this
-Concentration of solute (drug) in solution - can be affected by volume of dissolution medium
-Dissolution coefficient - affected by type of dissolution medium as well as viscosity
-thickness of boundary layer - affected by degree of agitation e.g. mixing.
If you reduce particle size, what happens to the rate of dissolution?
This increases the rate of dissolution as the surface area of each particle is higher.
If you decrease porosity, what happens to the rate of dissolution?
This decreases the rate of dissolution as it reduces the surface area for each particle
If you increase solubility of the drug, what happens to the rate of dissolution?
This increases the rate of dissolution as the drug is able to dissolve much faster.
If you decrease the diffusion coefficient what happens to the rate of dissolution?
This decreases the rate of dissolution - refer to equation.
Physiological factors affecting drug dissolution include
Stomach contents - affected by food, pH, and buffer capacity
GI Motility - affetcting the emptying and transit of the stomach contents, Gastrointestinal secretions, and co-administered fluids.
How does fat affect gastric emptying?
It delays gastric emptying, due to the fat in the duodenum causing the fundus to relax, lowering intragastric pressure. It increases the feeling of fullness for a longer timeframe.
Food can….
Affect drug absorption
The villus appears curved in the GI tract and this is so….
There is a greater surface area in the GI tract which allows for a greater level of absorption
The enteric nervous system is composed of…
The myenteric plexus and submucosal plexus.
How are the CNS and ENS connected?
Via the vagus nerve, the tenth cranial nerve that runs from your brain stem down to your abdomen - lo
What neurotransmitter is produced both in the gut and the brain?
Serotonin - and this is why antidepressants which raise brain serotonin levels may be ineffective at curing depression whereas proper dietary change can help.
Afferent Neurons are…
Sensory receptor neurons which carry nerve impulses away from receptors or sense organs and towards the central nervous system.
Efferent Neurons are…
nerves which carry impulses away from the central nervous system to effectors such as muscles or glands.
The enteric nervous system is located….
within the wall of the GI tract from the oesophagus to the anus.
What does the myenteric plexus do?
Largely motor in function influencing motor activity
What does the Meissner’s plexus do?
It is largely secretory, receiving signals from epithelium and stretch receptors influencing secretory activity.
How are nerve plexuses linked tio the CNS activated by the afferent fibres?
Either due to stretch or chemical stimulation
Which part of the nervous system stimulates gut motility and secretory activity?
Parasympathetic input stimulates gut motility and secretory activity
Which part of the nervous system inhibits muscle contraction in the GI?
Sympathetic nerves cause pre-synaptic inhibition of parasympathetic-induced contraction.
Segmentation is …
The mixing of food in the GI via circular muscle contraction
Peristalsis is…
concerned mainly with the propulsion of food along tract - this relies on longitudinal contraction and circular relaxation.
What is the ideal gut transit time?
The ideal gut transit time is anywhere between and 48 hours.
How can drugs affect gut transit time?
Some drugs have side effects due to their non-specific targeting and this may impact upon gut transit time.
Examples of drugs which can cause constipation are:
Antacids, anticholinergics, and antihypertensives
How do drugs affect gut transit times?
Opioid receptors are found on locations such as the myenteric plexus, which means medications such as loperamide can decrease peristalsis, and increased tone of the anal sphincter.
Tegaserod acts as a motility stimulant due to the activation of 5-HT4 receptors of the enteric nervous system
How much saliva on average is secreted per day?
1500ml
What does saliva contain?
Mucous to help lubricate food
Alpha amylase to initiate breakdown of carbohydrate
Lysozyme (antibacterial actions)
How is saliva formed?
The isotonic fluid is produced by acinar cells (which secretes electrolytes and water) - the fluid is then modified as it flows along the salivary duct - and the final composition depends upon flow rate and neuronal input.
Saliva secretion is primarily controlled by
The autonomic nervous system
The parasympathetic nervous system helps produce…
More watery saliva, rich in amylase and mucous. It also helps increase blood flow to the salivary glands
The sympathetic nervous system promotes….
Increased output of thicker mucous
Reduced blood flow to salivary glands
Overall effects a reduction in secretion of watery saliva
Swallowing has 2 stages - the…
Voluntary stage and pharyngeal stage
Absorption in the mouth is dependant on factors such as
Drug solubility in saliva
Passive diffusion - only small lipophillic molecules are well absorbed
Properties of the oral mucosa include
- Limited surface area (200cm squared)
- Passive diffusion of molecules
- There is a rich blood supply - resulting in a rapid onset of action with similar bioavailability to I-V formulation
Oral Ulcers
Usually clear up without treatment but can require anti-inflammatories and anti-microbial mouthwash to prevent infection
Oral Thrush can be caused by
- Over-use of antibiotics, poor immune system, underlying disease, smoking, dentures
Oral Thrush can be treated by
Using antifungal gel such as miconazole and/ or nystatin.
Medications which may cause tooth decay include:
Antacids - due to sugar and sweetener content
Pain medications - due to drying out mouth and hence erosion of the tooth enamel
Antihistamines - can block release of saliva, resulting in dry mouth.
What are the functions of the stomach?
- Temporary storage of food
- Mechanical digestion by stomach movements
- Chemical digestion of proteins
- Regulation of chyme into small intestine
- Secretion of intrinsic factor - essential for absorption of vitamnin B12
Food, when mixed with gastric juice forms…
CHYME!
Chyme passes through the pyloric sphinter to the….
Duodenum
Which 3 types of cells together produce gastric juices?
- Zymogenic (chief/ peptic cells) - secrete pepsinogen
- Parietal (oxyntic) cells - secrete HCl and intrinsic factor
- Goblet (neck) cells - secrete mucous.
What other cells are in the gastric glands apart from Zymogenic, parietal and goblet cells?
G cells - which secrete gastrin
Enterochromaffin (mast like) cells - secrete histamine
D cells - secrete somatostatin.
Most parietal cells are found
In the lower body of the stomach, except from the area of the antrum
Pepsin is only active
In the acidic environment - as it is then converted from pepsinogen by HCl
Gastric lipase breaks down at pH
5-6
Describe how stomach acid reaches the stomach lumen?
What prevents the stomach from digesting itself?
- The mucosal barrier - tight junctions between mucosal epithelial cells prevents leakage of gastric juice onto underlying tissue
- Mucous secreted by epithelial/ goblet cells has higher pH, providing localised neutralisation and physical barrier to acid
- Prostaglandins increase mucosal thickness and stimulate bicarbonate production
What are the 3 phases of gastric secretion?
- The cephalic phase - stimulated by sight, smell, taste, thought of food or low glucose levels
- The gastric phase - stimulated by stomach distension due to presence of food.
- The intestinal phase - stimulated by digested proteins/ fat in the duodenum - presence of fat or low pH in duodenum inhibits gastric secretion.
How does the cephalic phase occur?
The medulla oblongata cause parasympathetic neruones via the vagus nerves to increase HCl and pepsin in the stomach.
How does the gastric phase occur?
Stomach distension triggers the parasympathetic reflex leading to further HCl, pepsin and gastrin secretion
How does the intestinal phase work to decrease gastric secretion?
Chyme entering the duodenum containing fat or enough HCl to lower the pH to below 2 will trigger inhibition of gastric secretion via three main routes:
1. Neuronal impulse sent to medulla to decrease parasympathetic stimulation of gastric glands
2. Local reflexes in gut wall lead to decreased secretion
3. Release of 3 local hormones, secretin, gastric inhibitory peptide, and cholecystokynin travel via the blood to the gastric glands and inhibit secretion.
What does solubility refer to?
The amount of a substance that goes into a solution when equilibrium is established between the solute in solution and the excess (undissolved) substance
Describe the solution process
Consider 3 phases:
- Drug molecule is removed from its crystal
- A cavity from the molecule is created in the solvent
- Drug molecule inserts into this cavity
What does drug saturation refer to?
When a solution contains a drug at the limit of its solubility at any given temperature and pressure.
Factors which affect solubility of drugs (i.e. the amount of drug which can be dissolved, not the rate of dissolution)
- Temperature
- Molecular Structure of the drug
- Nature of the solvent
- Crystal characteristics
How does the surface area of the drug affect solubility?
Surface area of the drug molecule affects solubility because placing the solute molecule in the solvent cavity requires a number of solute-solvent contacts
What functional groups yield greater levels of solubility?
Polar groups such as OH which are capable of hydrogen bonding give higher solubility
Non polar groups such as methyl groups or Halogens like chlorine are hydrophobic hence not very soluble
What is the rate limiting step of drug absorption?
Dissolution
What is LogP?
Log P is the partition coefficient designed to show a measure of lipophilicity/ hydrophilicity of drugs in their unionised form
P =[Concentration in non-aqueous phase]/ [concentration in aqueous phase]
What does the LogP number suggest?
When LogP is more than 0, the drug molecule is lipophilic overall, and overall hydrophillic if less than 0
Describe crystal structures?
Crystals contain highly ordered arrays of molecules and atoms held together by non-covalent interactions - these structures vary in size, number and kind of faces depending on the drug molecule itself.
What is polymorphism in relation to crystals?
This is where molecules arrange themselves in different ways in the crystal - this however can alter the physical properties of the drug, an example of which is the ritonavir problem - the new polymorph which was discovered has a much reduced solubility.
How does digestion occur in the stomach from a mechanical perspective?
Muscularis enables food to be churned - particularly in antrum where the muscle wall is thicker
Food is mixed with gastric juice to form chyme
Chyme is then passed through the pyloric sphincter to the duodenum
How does digestion occur in the stomach from a chemical perspective
Proteins - broken down by pepsin (hydrolysing of proteins to form amino acids and to further stimulate amino acids) - (pepsin is only active in acidic form and is converted from pepsinogen via HCl)
Gastric Lipase breaks down fat at higher pH (5-6) - this initiates fat digestion and digestion of breast milk in infants
How does salivary amylase work?
It acts on carbohydrates if pH is around 6 and hence is far less active in the acidic environment of the stomach
What determines the force of stomach contraction and amount of gastric emptying?
Largely neuronal and hormonal input to the antral smooth muscle
The rate of gastric emptying is influenced by:
The physical and chemical nature of contents of stomach/ intestine
- Distension of stomach increases antral contraction
- Increased gastrin levels increase antral contraction
What does stomach emptying involve?
- Constriction of lower oesophageal Sphincter
- Contraction of gastric muscularis
- relaxation of pyloric sphincter
What things can inhibit gastric emptying?
Distension of duodenum
Presence of fat
Increased HCl
This is known as the enterogastric reflex and can have implications for oral drug absorption.
Why does high fat meals delay gastric emptying?
Fat in the duodenum causes the fundus to relax, lowering the intragastric pressure, and it also increases the feeling of fullness
What is a gastric ulcer?
This is where the mucosal layer of the stomach has been eroded, causing inflammation and damage to underlying tissue.
Acid may not be the initial damaging feature. It is however noted that acute or chronic ulceration of the GI tract in close proximity to acid producing cells.
What was the main cause of Gastric and duodenal ulcers?
95% duodenal ulcers and 85% gastric ulcers are associated with H. Pylori infection. The remainder are believed to be linked to NSAID use.
How is acid secretion controlled?
How is gastric ulceration managed?
- Explanation and reassurance
- Dietary control
- Drug therapy - aimed at maintaining the balance between the damaging and protective factors of the intestinal mucosa. Control of acid production
- Eradication of H. Pylori
Explain the function of the pancreas
The pancreas primarily has an exocrine effect (via 99% of the cells) - it acts as an accessory organ to digestion and secretes enzyme- rich fluid into the duodenum, to allow the breakdown of all categories of digestible food.
1% of cells do have an endocrine effect - they release hormones into the bloodstream which affect carbohydrate metabolism
Which pancreatic cells exert an endocrine effect?
Islet Beta cells release insulin,
Islet alpha cells release glucagon, and Islet delta cells release somatostatin.
What do Acinar cells do?
Secrete enzymes and fluid into the duct system
What do duct cells do?
They fuse with the bile duct on entry to the duodenum and are responsible for expressing high levels of carbonic anhydrase and HCO3- secretion.
What are pancreatic juices made of?
They have a aqueous component and a highly potent enzymatic component hence making the pancreas a dangerous organ to injure
What is the aqueous component and what does it do?
Aqueous component is made up 200-800ml of fluid, is secreted each day, is rich in bicarbonate (pH of 8), and helps neutralise acidic chyme - its secretion is stimulated by secretin
What does the enzymatic component do?
Produces proteolytic enzymes, pancreatic amylase, and lipolytic enzymes
How is pancreatic secretions controlled?
Underlying nervous and hormonal control - nervous reflex involves medulla and vagal innervation, gastrin is released in response to stomach distension, secretin and cholecystokinin are secreted by the mucosa in response to presence of chyme in duodenum (intestinal phase)
What is pancreatitis?
This is where the pancreatic enzymes are activated within the pancreas itself, causing the enzymes to attack the organ. This can be acute or chronic, but becomes chronic when pancreatic tissue is destroyed and scarring develops.
What causes pancreatitis?
Gallstones, alcoholism, and various other causes which are unknown (idiopathic)
What is the function of the liver?
Processing digested food from intestine
Making bile
Storing high levels of monosaccharides by converting them to glycogen
Storing iron, vitamins and other essential chemicals
Break down of fat, glycogen or protein to form glucose,
Metabolising drugs and break down poisons
Bactericidal activity (kupffer cells)
How is the liver structured
Cells are arranged in radial pattern around central vein, Hepatocytes make up functional units called lobules, and lobules form lobes of liver.
How do hepatic blood supplies work?
Receives double blood supply - oxygenated from the hepatic artery and deoxygenated from the portal vein
What is bile?
Bile is a digestive secretion produced via liver metabolism
What do bile salts do?
Bile salts emulsify fat into small droplets, and makes bile cholesterol soluble.
What gives faeces and urine their colour?
Bile pigments (bilirubin) which is yellow/brown in colour. Absorbed from the blood.
What does the gallbladder do?
It stores and concentrates bile by extracting water and ions - it can lead to increased insoluble cholesterol levels
Bile enters the gallbladder by the cystic duct when the small intestine is empty.
Bile is then ejected into the duodenum when protein/fat rich chyme enters the duodenum, as CCK causes the gallbladder to contract and the sphincter of oddi to relax which allows bile to enter the duodenum
What is a gallstone?
Crystalline deposits that accumulate when there is too much cholesterol and not enough bile salts.
This can be dissolved but if severe, can cause gall bladder to be removed.
Why do gallstones cause jaundice
This blocks the bile duct, meaning there is increased levels of bilirubin in the blood plasma, which then causes skin discolouration.
Which factors affect the concentration of drugs in solution in GI fluids?
Complexation
Adsorption
Chemical stability
Micellar Solubilisation
What is complexation?
This is where a component such as mucin which is present in the GI fluids forms complexes with some drugs and reduces the absorption and bioavailability
What is Adsorption?
This is where the co-administration of drugs and medicines containing solid adsorbents may result in the adsorbents which interfere with the absorption of drugs from the GI tract.
What is the issue with chemical stability?
This is where drugs that breakdown in the GI fluids will have reduced absorption and bioavailability
Instability can be caused by:
-Stomach pH (acidic hydrolysis)
-Enzyme degredation
What is micellar solubilisation?
This increases the solubility of drugs in the GI tract.
What are micelles?
Micelles initiates via surfactant molecules which have a hydrophobic tail and hydrophillic head
What happens to micelles once added to water?
They will be found on the surface of water as the hydrophillic heads will create an interface
What can act as surfactants in the GI
bile salts - such as either glycochenodeoxycholic acid or taurochenodeoxycholic acid
What is log D
Log D is the distribution coefficient
It takes into account ALL forms of drug - e.g. ionised and unionised
Log D is pH dependant and is always less than Log P
How to calculate Log D with known log P and known pH and Pka
Log D = Log P + Log (Funionised)
(Funionised) for acids = [1/ (1+10^pH-pka)]
(Funionised) for bases = [1/ (1+10^pka-pH)]
How does the body react to different formulations when either in the fed or fast states?
when fed - Liquids and pellets/ distintegrated tablets empty with food - controlled release are retained for longer.
When fasting, there is little discrimination between formulation types.
How does food affect pH?
Carbs do not affect pH significantly
Proteins elevate the pH
Liquid mixed meals do elevate the pH but levels return to basal numbers.
What happens to pepsin above pH 5?
Gets denatured and the acid production is reduced.
The intestines are composed of:
Small:
Duodenum
Jejunum
Ileum
Large:
Caecum
Colon
Rectum
What is the structure of the intestinal wall?
What is the structure of the small intestinal villi
What do the small intestinal villi do
They have folds of mucosa and submucosa which increase the surface area for absorption
The microvilli increase the surface area further
Each villus has:
-arteriole
-capillary bed
-venule
-lymphatic
They contain vessels for transporting of nutrients
How are the intestinal juices produced?
Secretion is regulated by reflex stimulated by the presence of chyme
CCK and secretin are also responsible for stimulating secretion
How does digestion work in the small intestines mechanically?
Segmentation - allows mixing of chyme/ food
Peristalsis - concerned with propulsion of food along tract, via longitudinal contraction and circular contraction
How does digestion occur from a chemical perspective in the intestine?
Digestive process started by salivary amylase and stomach pepsin
Process is completed in small intestine by combined actions of:
- pancreatic juice
-bile - intestinal juice
How are carbs digested in small intestine?
starch Conversion to dissacharides by pancreatic amylase
Dissacharides (maltose, sucrose) converted to monosaccharide (glucose, fructose) by glycosidase
Monosaccharides then absorbed
How are proteins digested in small intestine?
Polypeptides arrive from stomach catabolised by pancreatic trypsin and chymotrypsin
Digestion completed by peptidases released from glandular epithelium
Peptidases cleave peptides.
How is fat digested in the Small intestine?
Bile plays an essential role
Fat globules in the duodenum coated with bile salts to create emulsion and disperse fat globules into smaller entities
Emulsification allows breakdown of triglycerides by increasing the surface area for water soluble pancreatic lipases to act upon and produce monoglycerides and free fatty acids
By what mechanisms does absorption occur via the intestinal mucosa
Active transport
and diffusion
How are monosaccharides absorbed?
Glucose absorbed via Epithelial cell by co-transport with Na+ via sodium-glucose transporters then leave epithelial cell and enter blood via facilitated diffusion via the GLUT transporters
Fructose just absorbed in and then leaves to go to blood via GLUT’s
How are peptides absorbed?
Uptake into epithelial believed to be H+ linked. Then broken down to amino acids inside epithelial cell
Amino acids are uptaken into epithelial cells by Na+ dependant co-transport (active)
They leave the epithelial cell via facilitated diffusion
How are fats absorbed in small intestine?
Monoglycerides and free fatty acids associate with bile salts to form micelles/ emulsions
These diffuse passively into epithelial cells
Bile salt remains in the lumen of the gut until terminal ileum then re-cycled via enterohepatic circulation
Lipids accumulate in vesicles of smooth ER of epithelial cells to form chylomicrons.
These leave the cell by fusing with the plasma membrane
Chylomicrons leave intestine in the lymph since they are too large to enter circulation immediately. They are eventually delivered into venous circulation.
What does the lymphatic system do?
Absorbs nutrients (primarily fat), electrolytes, fluid and protein from interstitial spaces.
Removal of haemorrhaged red blood cells from tissue and invading bacteria.
It also allows uptake of chylomicrons due to the size preventing them from entering systemic circulation
Advantages of lymphatic flow
Bypasses the liver and nutrients/drugs are delivered into systemic circulation close to the heart
It is high capacity - can process 100g of triglycerides per day
How does the lymphatic system affect drugs?
The lymphatic system gets involved if the solubility of drugs in triglycerides is 50mg/ml or greater
What happens to digestive juices in the GI tract?
Although 7-8 litres are secreted, almost all is re-absorbed.
Most electrolytes are actively absorbed along the intestine
How are vitamins absorbed?
Fat soluble ones such as A, D, E and K must be absorbed in micelles
Water soluble vitamins (B and C) are absorbed by diffusion
Vitamin B12 requires intrinsic factor- produced by the stomach
What is segmentation?
It is rhythmic contraction and relaxation of the intestine
Mixes chyme in both directions
Allows full contact of contents with intestinal juices for digestion and the intestinal wall for absorption
Where is skeletal muscle found in the GI tract?
Upper third part of oesophagus and lower part of large intestine - contraction is under voluntary control
Which ion is responsible for generating force and contraction?
Calcium - removal of calcium from the cytosol is required for relaxation
How are smooth muscle cells connected?
Gap junctions
How is segmentation initiated?
Via the electrical activity of interstitial cells of cajal (pacemaker cells) in circular smooth muscle
How is Smooth muscle contraction regulated?
Via neurotransmitters released by autonomic nerve endings - no specialised motor end plate but swollen regions of axon (known as varicosites) contain NT’s
It can also be regulated by hormonal or mechanical input via receptor activation
How does E-C coupling occur in smooth muscle?
No troponin involved - instead, contractile proteins regulated by Ca2+/ CaM activation of myosin light chain kinase resulting in phosphorylation of myosin.
Which neurotransmitters are excitatory and inhibitory for the smooth muscle of the GI tract?
Acetylcholine and serotonin - excitatory
VIP and Noradrenaline - inhibitory
Which disorders can cause a fast Small intestine motility and transit time?
Diarrhoea, thyrotoxicosis, Irritable bowel syndrome, chronic pancreatitis
Which disorders slow the small intestine motility and transit time
Constipation, myxoedema, pseudo-obstruction, ileal resection, partial gastrectomy, jejunal bypass, and diabetes.
What therapies affect GI tract dysmotility?
How does the large intestine mechanically digest chyme?
Chyme enters through the ileocaecal valve
Haustral churning occurs
Peristalsis occurs slowly - due to mass movement
How does the large intestine digest chyme chemically?
Chemically there is limited action - there is only bacterial enzymes, which ferment the remaining carbs to produce flatus and they also break down remaining amino acids
Describe the motility patterns in the large intestines
Segmental contractions occur more often - propulsive movements are only seen 3-4 times a day
Slow peristaltic contractions facilitate and retard movement through colon
Mass movements - giant migrating contraction. Intense and prolonged peristaltic contractions which cab clear sections of the colon of all contents.
How does defecation occur?
The reflex is initiated by distention of the rectum (parasympathetic input to open internal anal sphincter).
Therefore the pressure in the rectum increases - causing longitudinal muscles to shorten
Voluntary contractions of diaphragm and abdomen
External anal sphincter opens.
What are the disadvantages of using Sodium bicarbonate for neutralising stomach acid?
Used in the body as a buffer to maintain plasma pH is an advantage - but if used excessively can risk alkalosis
Why can we not use drugs which block muscarinic acetylcholinergic receptors?
They are likely to produce unwanted side effects - and the receptors are found throughout the parasympathetic nervous system and involved in cardiac respiratory control
Why do antihistamines not reduce acid secretion by parietal cells?
Antihistamines act on H1 receptors, but parietal cells predominantly have H2 receptors.
Which virus is responsible for cold sores?
Herpes simplex
What stages are there for cold sore infections?
- Tingle stage - slight tingle or itch around mouth or nose
- Blister stage - this is where the small raised blotch swells and forms a blister
- Weeping stage - blisters collapse and join together to form a large weeping sore
- Scab stage - scab forms and later falls off.
How does impetigo get treated?
Antibiotics and creams such as fusidic acid.
What is the referral criteria for dry mouth?
- Severely dry
- Medications being used which may be causing it
- If cause is unclear
- Difficulty swallowing
What is the referral criteria for gingivitis?
Bleeding, foul taste, severe symptoms
What can the cause of mouth ulcers be?
Stress, food, trauma, genetics, and nutritional deficiencies.
Referral criteria for ulcers?
Apart from minor aphthous ulcers, refer all the time.
Refer for minor Aphthous when symptoms last more than 14 days, when child is under 10, or adult over 40
Note: Aphthous ulcers are almost always round.
Referral criteria for Oral thrush?
symptoms more than 3 weeks, no apparent risk factors, or when diabetic, when severe, treatment did not work, immunocompromised.
What are fillers used for in tablet prep and examples of fillers?
Fillers are used to add necessary bulk.
Lactose, glucose, and mannitol - water soluble
Cellulose - water insoluble
What are binders and examples?
Binders promote adhesion of the particles
Solution binders include starch, sucrose, gelatin as well as PVP, cellulose derivatives.
Dry binders include microcrystalline cellulose.
What are glidants and examples?
Glidants improve the flowability and they reduce friction between particles.
Colloidal Silica and Talc are an example of these.
What do lubricants do and example:
Lubricants are responsible for reducing friction between particles and the die wall
Magnesium Stearate is an example.
How does colon targeting work?
This is where the drug core needs to be coated with the extended-release membrane - exposure to bacterial enzymes generates holes in the coating, which results in the drug core being released
Ethylcellulose is an example of a component which is stable in the stomach, and is only digested by colonic bacteria.
Example of gastro-resistant coatings?
Acrylic polymers, phthalate polymers
Advantages of film coating vs sugar coating:
- Less volume increase
- Better stability of the tablet
- Better mechanical strength
- One step process.
Describe the structure of the rectum:
What are the advantages and disadvantages of rectal drug delivery?
Examples of rectal formulations:
Enema (solution, foams, gels, creams, ointments, and suppositories
