git physiology Flashcards

Question

what are the secretions that increase the small intestine ph

Answer 1

1– Brunner's glands • They are located in the duodenum • They are responsible for the secretion of bicarbonate which neutralizes the acid emptied from the stomach. 2– Intestinal cells • They are present throughout the small intestine. • They secrete mucus and enzymes. • The enzymes, hydrolases and proteases, continue the digestive process 3• Pancreatic secretions: – The pancreas is a large gland which secretes about 1-2 L of pancreatic juice per day into the small intestine via a duct. – The components of pancreatic juice are sodium bicarbonate and enzymes. – The enzymes consist of proteases, principally trypsin, chymotrypsin and carboxypeptidases, which are secreted as inactive precursors or zymogens and converted to their active forms in the lumen by the enzyme enterokinase. – Lipase and amylase are both secreted in their active forms. – The bicarbonate component is largely regulated by the pH of chyme delivered into the small intestine from the stomach. 4-bile

Answer 2

1– Brunner's glands • They are located in the duodenum • They are responsible for the secretion of bicarbonate which neutralizes the acid emptied from the stomach. 2– Intestinal cells • They are present throughout the small intestine. • They secrete mucus and enzymes. • The enzymes, hydrolases and proteases, continue the digestive process 3• Pancreatic secretions: – The pancreas is a large gland which secretes about 1-2 L of pancreatic juice per day into the small intestine via a duct. – The components of pancreatic juice are sodium bicarbonate and enzymes. – The enzymes consist of proteases, principally trypsin, chymotrypsin and carboxypeptidases, which are secreted as inactive precursors or zymogens and converted to their active forms in the lumen by the enzyme enterokinase. – Lipase and amylase are both secreted in their active forms. – The bicarbonate component is largely regulated by the pH of chyme delivered into the small intestine from the stomach. 4-bile

Answer 3

Bile – It is secreted by hepatocytes in the liver into bile canaliculi, – It get concentrated in the gallbladder and hepatic biliary system by the removal of sodium ions, chloride and water. – It is delivered to the duodenum. – Bile is a complex aqueous mixture of organic solutes (bile acids, phospholipids, particularly lecithin, cholesterol and bilirubin) and inorganic compounds (plasma electrolytes; sodium and potassium). – Bile pigments, the most important of which is bilirubin, are excreted in the feces. – The enterohepatic recirculation: the bile acids are absorbed by an active process in the terminal ileum  They are returned to the liver via the hepatic portal vein and resecreted in the bile

Answer 4

– Promoting the efficient absorption of dietary fat, such as fatty acids and cholesterol, by aiding its emulsification and micellar solubilization – The provision of excretory pathways for degradation products

Answer 5

• The colon is the final part of the gastrointestinal tract. • It stretches from the ileocaecal junction to the anus and makes up approximately the last 1.5 m of the 6 m of the gastrointestinal tract. • It is composed of – The caecum: ~85 mm in length – The ascending colon: -200 mm – The hepatic flexure – The transverse colon: usually greater than 450 mm – The splenic flexure – The descending colon: ~300 mm – The sigmoid colon ~400 mm – The rectum The colon has no specialized villi.

Answer 6

– The microvilli of the absorptive epithelial cells – The presence of crypts – The irregularly folded mucosae. s approximately 1/30th that of the small intestine

Answer 7

The main functions of the colon are: – The absorption of sodium ions, chloride ions and water from the lumen in exchange for bicarbonate and potassium ions. – Thus, the colon has a significant homeostatic role in the body. – The storage and compaction of feces

Answer 8

• This large bacterial mass is capable of several metabolic reactions including: – Hydrolysis of fatty acid esters – The reduction of inactive conjugated drugs to their active form. • The bacteria rely upon undigested polysaccharides in the diet and the carbohydrate components of secretions such as mucus for their carbon and energy sources. • They degrade the polysaccharides to produce shortchain fatty acids (acetic, proprionic and butyric acids), the gases hydrogen, carbon dioxide and methane These fatty acids lower the luminal pH. – The pH of the caecum is around 6-6.5. – This increases to around 7-7.5 towards the distal parts of the colon. • Recently, there has been much interest in the exploitation of the enzymes produced by these bacteria with respect to targeted drug delivery to this region of the gastrointestinal tract

Answer 9

• Transit through the oesophagus is dependent both upon the dosage form and posture and adhesion • Transit of liquids has always been observed to be rapid, and in general faster than that of solids. • Most dosage forms are taken in an upright position. In this case, they transit through the oesophagus quickly  usually in less than 15 seconds. • Tablets/capsules taken in the supine position (especially if taken without water) are liable to lodge in the oesophagus. • Adhesion to the oesophageal wall can occur as a result of partial dehydration at the site of contact and the formation of a gel between the formulation and the oesophagus. • The chances of adhesion will depend on the shape, size and type of formulation.

Answer 10

delay a drug's onset of action or cause damage or irritation to the oesophageal wall, – Potassium chloride tablets. – Bisphosphonates: alendronate (Fosamax® ), risedronate (Actonel® ), and ibandronate (Boniva® ). – Tetracyclines : particularly doxycycline – NSAIDs – Iron – Alprenolol – Pinaverium

Answer 11

Gastric residence time, gastric emptying time or gastric emptying rate: it is the time a dosage form takes to traverse the stomach

Answer 12

1• The dosage form 2• The fed/fasted state of the stomach. – Normal gastric residence times usually range between 5 minutes and 2 hours – Much longer times (over 12 hours) have been recorded, particularly for large single units.

Answer 13

the electrical activity of the stomach 4 phases in the fasted stage – Phase I (the basal state): a relatively inactive period of 40-60 minutes with only rare contractions occurring – Phase II (the preburst state): characterized by increasing frequency and strength of contractions  ~ 30 – 45 minutes – Phase III (the burst state): characterized by strong contractions. Physiologically, this phase serves to clear out the stomach of any undigested material or saliva and thus, contractions in this phase are called (housekeeper waves)  ~ 5 – 15 minutes – Phase IV: a short transitional period between the powerful activity of phase III and the inactivity of phase I  ~ 5 minutes The cycle repeats itself every 2 hours until a meal is ingested and the fed state or motility is initiated.

Answer 14

here gastric emptying is delayed by the presence of food in the stomach, – After ingesting typical meal  the motor activity of the stomach starts to resemble phase II in the fasted state – Typically, last for 3 – 4 hours (depends on the caloric value of the meal) – The pyloric sphincter allows liquids and small food particles to empty while other material is retropulsed into the antrum of the stomach for further size reduction before emptying Thus, in the fed state: liquids, pellets and disintegrated tablets will tend to empty with food • Large sustained or controlled release dosage forms can be retained in the stomach for long periods of time. • In the fasted state: the stomach is less discriminatory between dosage form types

Answer 15

– The type of dosage form – The presence of food – The composition of the food – The postural position – The effect of drugs and disease state

Answer 16

• Metoclopramide: it is a drug that ↑ gastric emptying rate  ↑ the rate of absorption of paracetamol. • Proprantheline: it is a drug that delays gastric emptying  it delays the absorption of paracetamol

Answer 17

– Dosage forms that release their drug slowly (e.g. controlled- sustained- prolonged-release systems) as they pass along the length of the gastrointestinal tract – Enteric-coated dosage forms which release drug only when they reach the small intestine – Drugs that dissolve slowly in intestinal fluids – Any drugs that are absorbed by intestinal carrier-mediated transport systems.

Answer 18

• The type of dosage form • Diet • Eating pattern • Disease state.

Answer 19

1. Propulsive contractions or mass movements: which are associated with the aboral (away from the mouth) movement of contents 2. Segmental or haustral contractions: which serve to mix the luminal contents and result in only small aboral movements Segmental contractions: are brought about by contraction of the circular muscle  they are the predominant contractions • Propulsive contractions: are due to contractions of the longitudinal muscle  occur only 3-4 times daily in normal individuals.

Answer 20

– The drug needs to remain in solution. – The drug should not become bound to food or other material within the gastrointestinal tract. – The drug needs to be chemically stable in order to withstand the pH of the gastrointestinal tract – The drug must be resistant to enzymatic degradation in the lumen. – The drug then needs to diffuse across the mucous layer, without binding to it, across the unstirred water layer The drug should cross the gastrointestinal membrane (its main cellular barrier)  no efflux – After passing through this cellular barrier, the drug encounters the liver before it reaches the systemic circulation.

Answer 21

Gastric fluid is highly acidic, normally exhibiting a pH within the range 1-3.5 in healthy people in the fasted state. – Following the ingestion of a meal, the gastric juice is buffered  Typical gastric pH values following a meal are in the range 3-7. – Depending on meal size  the gastric pH returns to the lower fasted-state values within 2-3 hours. • Thus, only a dosage form ingested with or soon after a meal will encounter these higher pH values.

Answer 22

– The chemical stability of the drug in the lumen – The drug dissolution – The drug ionization and absorption • Chemical degradation due to pH-dependent hydrolysis can occur in the gastrointestinal tract. – The result of this instability is incomplete bioavailability  as only a fraction of the administered dose reaches the systemic circulation in the form of intact drug.

Answer 23

– Penicillin G (benzylpenicillin) – Erythromycin – Proton pump inhibitors (e.g. omeprazole)

Answer 24

– The primary enzyme found in gastric juice is pepsin. – Lipases, amylases and proteases are secreted from the pancreas into the small intestine in response to ingestion of food. – These enzymes are responsible for most of nutrient digestion. – Pepsins and the proteases are responsible for the degradation of protein and peptide drugs in the lumen. – Other drugs that resemble nutrients, such as nucleotides and fatty acids, may also be susceptible to enzymatic degradation. – The lipases may also affect the release of drugs from fat/oil-containing dosage forms. – Drugs that are esters can also be susceptible to hydrolysis in the lume

Answer 25

These enzymes have been utilized when designing drugs or dosage forms to target the colon. • Sulphasalazine, for example, is a prodrug of 5- aminosalicylic acid linked via an azo bond to sulphapyridine. • The sulphapyridine moiety makes the drug too large and hydrophilic to be absorbed in the upper gastrointestinal tract – And thus permits its transport intact to the colonic region • In the colon the bacterial diazoreductase enzymes reduce the azo bond and release the active drug (5- aminosalycylic acid) for local action in colonic diseases such as inflammatory bowel disease The prodrug reach the colon as such because: • There is no diazoreductase activity in the upper parts of the GIT • There is limited absorption of the prodrug in the small intestine.

Answer 26

1. Complexation of drugs with components in the diet 2. Alteration of pH 3. Alteration of gastric emptying 4. Stimulation of gastrointestinal secretions 5. Competition between food components and drugs for specialized absorption mechanisms 6. Increased viscosity of gastrointestinal contents 7. Food-induced changes in presystemic metabolism 8. Food-induced changes in blood flow

Answer 27

Tetracycline: forms non-absorbable complexes with calcium and iron • Patients are advised to not take products containing calcium or iron, such as milk, iron preparations or indigestion remedies, at the same time of day as the tetracycline.

Answer 28

– Gastrointestinal secretions (e.g. pepsin) produced in response to food may result in the degradation of drugs that are susceptible to enzymatic metabolism. – The ingestion of food, particularly fats, stimulates the secretion of bile. • Bile salts are surface active agents and can increase the dissolution of poorly soluble drugs  thereby enhancing their absorption. • However, bile salts have been shown to form insoluble and hence non-absorbable complexes with some drugs, such as neomycin, kanamycin and nystatin.

Answer 29

– It happens in the case of those drugs that have a chemical structure similar to nutrients required by the body for which specialized absorption mechanisms exist – There is a possibility of competitive inhibition of drug absorption. – Example of such drugs are: • Peptide-like drugs: penicillins, cephalosporins, angiotensin-converting enzyme inhibitors (ACE) and renin inhibitors  they rely on the peptide transporters for their efficient absorption • Nucleosides and their analogues for antiviral and anticancer drugs  depend on the nucleoside transporters for their uptake. • L-dopa and -methyldopa: transported by the carrier-mediated process for amino acids.

Answer 30

– The presence of food in the gastrointestinal tract provides a viscous environment which may result in a reduction in the rate of drug dissolution. – In addition, the rate of diffusion of a drug in solution from the lumen to the absorbing membrane lining the gastrointestinal tract may be reduced by an increase in viscosity. – Both of these effects tend to decrease the bioavailability of drug.

Answer 31

– Certain foods may increase the bioavailability of drugs that are susceptible to presystemic intestinal metabolism by interacting with the metabolic process. – Example: Grapefruit juice is capable of inhibiting the intestinal cytochrome P450 (CYP3A family) • If it is taken with drugs that are susceptible to CYP3A metabolism  it is likely to result in their increased bioavailability. • Clinically relevant interactions exist between grapefruit juice and the antihistamine terfenadine, the immunosuppresant cyclosporin, the protease inhibitor saquinavir and the calcium channel blocker verapamil.

Answer 32

Blood flow to the gastrointestinal tract and liver increases shortly after a meal  thereby increasing the rate at which drugs are presented to the liver. – The metabolism of some drugs (e.g. propranolol, hydralazine, dextropropoxyphene) is sensitive to their rate of presentation to the liver: • The faster the rate of presentation  the larger the fraction of drug that escapes first-pass metabolism. • This is because the enzyme systems responsible for their metabolism become saturated by the increased rate of presentation of the drug to the site of biotransformation. • For this reason, the effects of food serve to increase the bioavailability of some drugs that are susceptible to first-pass metabolism.

Answer 33

– Reduced absorption – Delayed absorption – Increased absorption – Accelerated absorption – No effect on absorption

Answer 34

– Local diseases can cause alterations in gastric pH that can affect the stability, dissolution and/or absorption of the drug. – Gastric surgery can cause drugs to exhibit differences in bioavailability than that in normal individuals. • Partial or total gastrectomy results in drugs reaching the duodenum more rapidly than in normal individuals. • This increased rate of presentation to the small intestine may result in an increased overall rate of absorption of drugs that are primarily absorbed in the small intestine. • However, drugs that require a period of time in the stomach to facilitate their dissolution may show reduced bioavailability in such patients

Answer 35

The unstirred water layer or aqueous boundary layer is a more or less stagnant layer of water, mucus and glycocalyx adjacent to the intestinal wall. – It is ~ 30-100 m in thickness. – This layer can provide a diffusion barrier to drugs (non-polar drugs). – Some drugs are also capable of complexing with mucus, thereby reducing their availability for absorption

Answer 36

– It separates the lumen of the stomach and intestines from the systemic circulation. – It is the main cellular barrier to the absorption of drugs from the gastrointestinal tract. – This barrier has the characteristics of a semipermeable membrane  allowing the rapid transit of some materials and impeding or preventing the passage of others. – It is permeable to amino acids, sugars, fatty acids and other nutrients. – It is impermeable to plasma proteins. – It can also be viewed as a semipermeable lipoidal sieve • Allows the passage of lipid-soluble molecules across it • Allows the passage of water and small hydrophilic molecules (ions) through its aqueous por

Answer 37

– There are counter-transport efflux proteins that expel specific drugs back into the lumen of the gastrointestinal tract after they have been absorbed. – One of the key counter-transport proteins is P-glycoprotein. – P-glycoprotein is expressed at high levels on the apical surface of columnar cells (brush border membrane) in the jejunum. – It is also present on the surface of many other epithelia and endothelia in the body, and on the surface of tumour cells. P-glycoproteins were originally discovered because of their ability to cause multidrug resistance in tumour cells  by preventing the intracellular accumulation of many cytotoxic cancer drugs by pumping the drugs back out of the tumours. • Certain drugs with wide structural diversity are susceptible to efflux from the intestine via Pglyocprotein. • Usually, co-localized with the enzyme CYP3A4 More efficient presystemic metabolism may be achieved as the drug is repeatedly absorbed back into the enterocytes and thus exposed for longer to the degradation enzymes • Such efflux may have a detrimental effect on drug bioavailability. • These efflux proteins pump drugs out of cells in a process that requires energy  – They can work against a concentration gradient – They can be competitively inhibited by structural analogues – They can be inhibited by inhibitors of cell metabolism – It is a saturable process. • Example of drugs that are susceptible to efflux by Pglycoprotein: Cyclosporine, Nifedipine, Verapamil, Paclitaxel, Celiprolol, Digoxin

Answer 38

It will result in a low bioavailability of those drugs which are rapidly metabolized by the liver. • The bioavailability of a susceptible drug may be reduced to such an extent as – To render the gastrointestinal route of administration ineffective, or – To necessitate an oral dose which is many times larger than the intravenous dose – For example: propranolol  Although it is well absorbed, only about 30% of an oral dose is available to the systemic circulation owing to the first-pass effect. The bioavailability of sustained-release propranolol is even less: – As the drug is presented via the hepatic portal vein more slowly than from an immediate-release dosage form  the liver is therefore capable of extracting and metabolizing a larger portion. • Other drugs which are susceptible to a large first-pass effect are – The cholesterol lowering agent atorvastatin – The anesthetic lidocaine – The tricyclic antidepressants imipramine – The analgesics pentazocine, morphine, demerol – Other: buprenorphine, diazepam, midazolam, and cimetidine