MP322 Master Deck

Approx how many people in UK living with a stoma?

• 130,000

Where is a colostomy usually created?

• left-hand side of the abdomen

Why do stomas require a pouch?

• stoma has no end sphincter (muscle) to control defecation so need a bag to collect waste

What is a stoma?

• procedure where part of bowel is brought to surface of abdomen to form the stoma

What is a loop colostomy for?

Is it temporary or not

• rests on the abdomen with the help of a support rod

• generally temporary

• gives bowel a temporary rest to aid in healing

When would a loop colostomy occur?

• injury, infections where part of bowel is weakened/affected and requires healing

Where is colostomy located?

Where is ileostomy located?

(typically)

• left side of abdomen

• right side of abdomen

What kind of bag for colostomy and ileostomy?

Why this kind of bag?

• colostomy = non-drainable bag (due to stool being more formed)

• ileostomy = drainable bag (stool is mainly liquid)

What is a loop colostomy procedure?

• bowel is lifted above skin level and held in place with a rod

• a cut is made on exposed bowel loop, ends are rolled down and sewed onto the skin - so actually 2 stomas that are jointed together

• temporary generally

What is end colostomy procedure?

• parts of colon/ rectum has been removed

• remaining large bowel brought to abdominal surface to form a stoma

• can be temp or permanent

Are colostomy bigger or smaller than ileostomy?

• colostomy = bigger

• ileostomy = smaller 

How does electronic spectra work?

• basically electron excitation when a light of the correct wavelength interacts with molecule resulting in the molecules reaching a higher energy state (electronic transition)

• also results in increase in the energy levels of rotational and vibrational states

What are stages of molecular absorption spectra?

• rotational

• vibrational

• electronic

• (increasing in energy as going down list)

What is Beer-Lambert Law?

• absorption is relative to concentration (strength of absorption indicate high conc in solution etc.)

What is specific absorbance equation?

• A= A(1%, 1cm).b.c

• A = absorbance

• C is in g/100ml (%w/v)

• b is in cm

• A(1%, 1cm) is the absorbance of a 1g/100ml solution in 1cm cell at a specific wavelength

When do errors due to light scattering increase?

• at shorter wavelengths

What is the downside to UV/ Vis analysis of a molecule?

• lacks specificity e.g.

• 

What is planar chromatography?

• using a flat stationary phase to separate and identify compounds in a mixture (example would be paper chromatography)

How does column chromatography work?

• mixture applied to top of column in solvent

• compounds interact with SP and are retained more/less

• 

What does infrared (IR) absorption cause transitions in?

• rotational energy levels

• vibrational energy levels

• (not electronic energy levels)

Does IR or UV/vis light absorption have less energy?

• IR has less energy

What must absorption of IR cause a change in?

• in the dipole moment of the molecule (how close/far dipoles in a molecule are from each other)

What is polymorphism?

• ability of a compound to crystallise in more than one 3d arrangement

What kinds of x-ray diffraction are available?

• powder or single crystal x-ray diffraction

• single crystal x-ray diffraction is gold standard

What is gold standard pharmaceutical analysis technique?

• single crystal x-ray diffraction

What are water soluble vitamins?

• B and C (ascorbic acid)

What are fat soluble vitamins?

• A D E K

What is vitamin B12 also called?

What is vitamin b9 also called?

• cobalamin (think hydroxycobalamin)

• folate

What are sources of vitamin B12?

Can humans self produce vitamin B12?

• animal origin - meat, fish and dairy products

• no only from diet

What are the 2 mechanisms of vit B12 absorption and how do they occur?

• passive absorption 

  • through buccal, duodenal and ileal mucosa

  • rapid but inefficient (<1% of an oral dose absorbed)

• active transport

  • occurs through ileum

  • mediated by gastric intrinsic factor

  • approx 70% of ingested amount of vit is absorbed

Describe active absorption of vit B12. 

• vit B12 is released from food and bound to haptocorrin (transcobalamin I)

  • haptocorrin produced by salivary glands

• intrinsic factor (glycoprotein) is secreted by parietal cells

• once reached the duodenum, haptocorrin is degraded = releasing B12

• vitamin B12 is captured by intrinsic factor

• captured complex passes along intestine

• in terminal ileum, the complex is endocytosed by cubam

• intrinsic factor is degraded releasing B12

• ABC transporter releases the B12 into the blood

• B12 binds to transcobalamin II

• B12 transported in the plasma while bound to transcobalamin I, II, OR III and then taken in by cells

• Excess B12 stored in liver

  

What transcobalamin is most important for cellular uptake of B12?

• transcobalamin II

Where is excess B12 stored?

• in the liver

What kind of molecule is intrinsic factor?

• glycoprotein

What kind of anaemia occurs in B12 deficiency?

What kind of anaemia is it when it is B12 deficiency due to absence of intrinsic factor?

• megaloblastic anaemia

• pernicious anaemia

What is the cause of true pernicious anaemia?

• autoimmune response that leads to destruction of gastric parietal cells (think body attacking itself)

• parietal cells are where intrinsic factor is produced → so no intrinsic factor

  • also results in less/no gastric acid being produced (as also produced in parietal cells)

What is autoimmune atrophic gastritis and what does it cause?

• underlying cause of pernicious anaemia

• autoimmune response where antibodies attack gastric parietal cells

• immunes response directed against H+/K+ATPase

• can also be caused by antibodies directed against Intrinsic Factor

What can be causes of B12 deficiency?

• loss of gastric parietal cells

• loss of intrinsic factor

• abnormal intrinsic factor

• bacterial overgrowth in the intestine (e.g. stagnant loop syndrome)

• disorders of the ileal mucosa (e.g. resection)

• disorders of plasma transport proteins (the transcobalamins)

• dysfunctional uptake and use of B12 by cells

• inadequate dietary intake (rare)

What drugs can induce B12 deficiency?

• PPIs and H2 antagonists (less acid → less separation of B12 from food)

• oral contraceptives and HRTs

• metformin (reduces absorption)

• cholchicine (inhibits receptors in terminal ileum)

What are neurological consequences of B12 deficiency?

• paresthesia (pins and needles) in hands and feet

• sensory loss

• gait ataxia (affected walking pattern)

• weakness in legs

• subacute combined degeneration of the spinal cord (can also affect brain and peripheral nerves)

What are digestive consequences of B12 deficiency?

• Hunters Glossitis (geographic tongue)

What are cardiovascular consequences of B12 deficiency?

• angina

• venous thromboembolic disease

What is a gynaecological consequences of B12 deficiency?

• infertility

What is treatment for B12 deficiency?

Is it lifelong?

What condition requires parenteral administration?

• oral cyanocobalamin or parenteral hydroxocobalamin

• yes, lifelong treatment is necessary

• gastric intrinsic factor deficiency (pernicious anaemia)

What are sources of B9 (folic acid)?

• dark green veg

• dried legumes

• fruit/ fruit juices

• meat, seafood, poultry and eggs

• fortified breads and cereals

What is RDA of B9 per day?

What about in pregnancy?

• 200mcg/day

• in pregnancy 400mcg/day

What is RDA per day for B12?

• 1-2.5mcg/day

Where is folate mostly absorbed?

• in proximal small intestine (duodenum and jejunum)

How is folate absorbed from the lumen into the cell?

• by a proton-coupled folate transporter (PCFT)

• also via a reduced folate carrier (RCF), with folate being exchanged for organic phosphate (OP)

What is the main dietary folate?

• 5-MTHF

How do enterocytes aid in folate absorption?

• located on small intestine surface, have large surface area due to villi

• binds to folate and internalises it (into enterocyte cell) by receptor mediated endocytosis

What transporter protein exports folate and reduced from 5-MTHF, from enterocyte?

• organic anion transporter (OAT)

How does folate circulate in the blood?

What is plasma conc of folate?

• most circulates freely

• some bound to albumin

• plasma conc = 10-30nmol/L

How is folate uptaken into cells?

• same mechanisms as it being uptaken into enterocytes

  • proton-coupled folate transporter (PCFT), reduced folate carrier (RFC) and folate receptor

What are natural occurring folates found as?

What are synthetic folates made up as?

• polyglutamate folates

• monoglutamate folates

What does intracellular folate exist as and why?

• polyglutamate folate

• because is more negatively charged so is less likely to leak out of cell membrane (think phopholipid bilayer)

Why is folate crucial (bio molecularly)?

• crucial for the transfer of one-carbon units to amino acids, nucleotides and other biomolecules

What are causes of folate deficiency?

• inadequate dietary intake

• defects in the uptake system (problem with the transporters)

• intestinal disease (e.g. IBD, coeliac)

• drug interactions (sulfasalazine, trimethoprim, methotrexate, metformin)

• chronic alcohol use

• increased cellular requirement (e.g. pregnancy)

What are symptoms of folate deficiency?

• sore tongue (glossitis)

• GI symptoms (nausea, vomiting, abdominal pain, diarrhoea especially after meals)

• neurologic (cogn impairment, dementia and depression

• neural tube defects in foetus

What is treatment of folate deficiency?

• oral folic acid for 1-4 months

• treated until recovery occurs

What is malabsorption?

• inadequate absorption of nutrients form the GI tract

Where does most absorption occur?

• through the small intestine walls

What is the difference between mucosal and pre-mucosal malabsorption?

• mucosal = relating directly to small intestine wall (something wrong with the adsorptive surface of the wall)

• pre-mucosal = before reaching small intestine and is because the nutrients arent available for adsorption (e.g. because food source hasnt been broken down enough)

What are conditions that cause mucosal malabsorption?

• crohns, coeliac and certain kinds of surgery

What are conditions that cause pre-mucosal malabsorption?

• pancreatitis

• cystic fibrosis

• lactase deficiency

What is Crohn’s disease’ effect on absorption?

Is Crohn’s mucosal or pre-mucosal malabsorption?

• abnormal epithelium → deficient absorption

• mucosal (problem with small intestine itself)

Why does surgical resection effect absorption?

Is this mucosal or pre-mucosal?

• shortens bowel = less surface area for absorption

• is mucosal (small intestine itself)

Why do cystic fibrosis, pancreatitis and lactase deficiency effect absorption?

Is this mucosal or pre-mucosal malabsorption?

• because there are insufficient quantity of digestive agents →macronutrients cant get broken down so cant get absorbed

• pre-mucosal (as not to do with small intestine directly, but before it)

What are typical deficiencies associated with Crohns?

• iron deficiency anaemia

• B12/ folate deficiency

• Vit D and calcium deficiency

What is a drawback to treating crohns/ IBD with steroids?

• steroids over long-term can cause negative effect on bones causing bone loss

What is villous atrophy?

What condition does this result in?

• villi become inflamed and flattened → worst case can disappear completely

  • body cant absorb nutrients properly

• coeliac

What is coeliac disease?

• gluten causes abnormal mucosal response = chronic inflammation, damage to small intestine and villous atrophy

What are symptoms of coeliac disease?

How is coeliac diagnosed?

• fatigue, gastric upset, weight loss

• via serological testing

What deficiencies/conditions can occur in patients with coeliac?

• anaemia, osteoporosis (due to vit D and calcium deficiency)

Is short bowel syndrome mucosal or pre-mucosal malabsorption?

Why do certain drugs need to be delivered in higher doses to patients with short bowel syndrome?

• mucosal due to lest surface are available for absorption

• if drug is mainly absorbed in small intestine, require higher dose as these patients have smaller surface area so less absorption takes place, why they need a higher dose

What sex is more affected by pancreatitis?

What does pancreatitis lead to?

• men (any age)

• deficiency in pancreatic enzymes

What is chronic pancreatitis?

What is it associated with pancreatitis?

• chronic inflammation of pancreas leading to impaired function of the organ (pre-mucosal malabsorption)

• long term excess alcohol consumption

What is steatorrhea and what condiditon is associated with it?

• presence of excess fat in faeces (cystic fibrosis)

What is cystic fibrosis?

What can cystic fibrosis lead to?

• genetic condition where decreased Cl secretion, increased Na absorption = thick mucus in pancreas mainly → inhibits absorption

• osteoporosis, malnutrition, weight loss, intestinal obstruction

  • treat with pancreatic enzyme supplements (Creon capsules), fat soluble vit replacement and calorie replacement

What is small intestine bacterial overgrowth (SIBO)?

What does SIBO result in?

• when after an incident, passage of food and waste products in GI tract slows, creating a breeding ground for bacteria

• diarrhoea, weight loss and malnutrition

Is fat malabsorption pre-mucosal or mucosal?

In what conditions is fat malabsorption common?

What deficiencies does fat malabsorption result in?

• pre-mucosal as problem with digestion

• in Crohn’s and Coeliac

• deficiencies in fat-soluble vitamins (A,D, E, K as cant be absorbed without dissolving (i think?))

What does vitamin D deficiency result in?

What does vitamin K deficiency result in?

• rickets, osteoporosis

• clotting problems

What is treatment options for malabsorption of protein, fat and carbohydrates (when pancreatitis or cystic fibrosis)?

What is problem with pancreatic enzyme replacement therapy?

• supplementation of pancreatic enzymes (lipase, amylase and protease)

  • Creon

• derived from pork, so muzzys and veggies need to reconsider some stuff blah blah blah

Specific signs and symptoms linked to malabsorption conditions (list them)

Nutrients	Main signs/symptoms of malabsorption
Fat	Steatorrhoea
Protein	Muscle wasting, malnutrition, oedema
Carbohydrate	Bloating, flatulence, diarrhoea
Vitamin D +/- calcium	Bone problems – osteoporosis, fractures
Vitamin E	Neurological problems
Vitamin K	Coagulation (bleeding) problems
Vitamin A	Night blindness

What does MCR stand for?

• medicines care and review service

What were the main drivers for MCR being introduced?

• prescribing, dispensing errors

• compliance/concordance of patients (not adhering to meds)

• workload

What kind of patient conditions can be aided with MCR?

• registered with a Scottish GP permanently

• at least one long term condition that requires medication

• new medications

• high risk medication e.g. warfarin, methotrexate, lithium

• smoking cessation

• gluten free foods

What patients are eligible for MCR?

• at least one long term condition

• permanently registered with Scottish GP

What sorts of drugs are excluded from MCR?

• drugs subject to dose titrations

• CD 2-4 and cytotoxic drugs (eg methotrexate)

• drugs that require close monitoring (may not be suitable)

• patients subject to frequent medication changes

How does kaolin work as a treatment for acute diarrhoea?

• acts as an adsorbent and is bulk forming

What are examples of anti-motility drugs used to treat acute diarrhoea?

• diphenoxylate and atropine (called co-phenotrope)

• codeine

• morphine (with kaolin)

• loperamide

• racecadotril

How do codeine and morphine act as antimotility drugs?

• act on mu opioid receptors as agonists, causes decrease in ACh release → less peristaltic activity → slows transit time through gut

Which receptors does ACh bind to?

• nicotinic and muscarinic acetylcholine receptors

What is co-phenotrope composed of?

How does co-phenotrope act as an antimotility drug?

• diphenoxylate and atropine

• 

• atropine acts as an inverse agonists on muscarinic receptors (baseline activity of receptor lowered)

• diphenoxylate acts similarly to codeine by binding to mu opioid receptors as an agonist → decrease in ACh release → decrease in peristaltic activity

How does atropine affect muscarinic acetylcholine receptors?

• is an inverse agonist on the receptor (lowers baseline activity)

• 

Where is racecadotril molecule cleaved to become thiorphan (prodrug→active drug)?

• cleaved between the ester bond (ester hydrolysis via esterases)

• 

Why is raceacadotril/thiorphan not formulated as a salt?

• due to there being no ionisable groups (is an overall neutral molecule)

What salt is loperamide made into?

• loperamide hydrochloride

What salt is diphenoxylate made into?

What salt is atropine made into?

• diphenoxylate hydrochloride

• atropine sulphate

What salt is codeine made into?

• codeine phosphate