GI Flashcards
what are protecting groups?
- chem. modification functional group
- chemoselectivity in reaction/synthesis
what are the advantages of protecting groups?
- reaction guided to happen only at desired part
- prevent unwanted products
- protect parts from destruction
what is to be considered for choosing PGs?
- inexpensive
- commercially available
- introduction = easy & efficient
- stable & efficient removal
what must PGs do?
- react & removed selectively
- provide good yield
- no additional functionality = side reactions
- no additional stereocentres = uncontrolled stereocentres = major concern pharmaceutical chem.
what are some functional groups commonly protected?
- alcohols
- carbonyls = aldehydes, ketones & carboxylic acids
- amines
what are some PGs used for alcohols?
- silyl ethers
- benzyl ethers
what are some PGs used for aldehydes & ketones?
- acetals
- ketals
- thioketals
how is a carboxylic acid protected from further reaction?
turn into less reactive ester = allyl esters
why is amine group most susceptible to side reactions & needing protection in synthesis?
- vulnerable acid & basic conditions
- primary & secondary = prone oxidation
- N-H bond = metallation on exposure organolithium & Grignard reagents
- amino group = lone pair = react w/ electrophiles
what are some amine PGs?
- amides
- carbamates
what are some amide drugs and their uses?
- frovatriptan = anti-migraine
- brivaracetam = anti-epileptic
- axitinib = anti-cancer
what are the uses of prodrugs?
- increase solubility & stability
- improve taste & reduce toxicity
- modify the time of duration of action
- deliver drugs to specific site in the body
- alleviate pain when administered by injection
what are the 2 main classes of prodrugs?
- bioprecursor
- carrier
what is a bioprecursor prodrug?
- molecule needs modification = active compound
- rely on metabolic or chemical modification
- can involve one step/series of steps; like oxidation or reduction
what is a carrier prodrug?
- combi. active drug & carrier species = lipophilic carrier transport drug across membrane
- link between carrier & active species = group easily metabolised = ester/amide
what are some spec. uses of carrier prodrugs?
- site-specificity = hydrophilic drugs & lipophilic carrier = dihydropyridine
- minimise SE = aspirin & salicylic acid
- improve drug stability = avoid 1st pass metabolism
what are some example of drug alliances?
- sentry drugs = clavulanic acid & penicillins
- localising area of activity = adrenaline & procaine
- increasing absorption = metoclopramide & analgesics
what are antacids and what are they used for?
- treat heartburn; indigestion & upset stomach
- neutralise stomach acid
- Magnesium OH or aluminium OH
what are H2 receptor antagonists and what are they used for?
- acid-peptic disease
- block action of histamine at H2 receptors of parietal cells in stomach
what are promotility agents and what are they used for?
- treat slow movement of matter thru digestive system = gastroparesis & constipation
- enhance effect ACh
- block effect inhibitory neurotransmitter
what are laxatives and what are they used for?
- constipation & limited movement conditions
- accelerate fecal passage/decrease consistency
what is the mechanism of action of laxatives?
- increase fluid retention by hydrophilic/osmotic mechanisms
- decrease fluid absorption = manipulation electrolyte transport
- stimulation propulsive contractions/inhibition of non-propulsive contractions
what are the 2 main types of antidiarrheal drugs?
- antimotility agents = loperamide & codeine
- anticholinergic agents = atropine & scopolamine)
what are PPIs and how do they work?
- gastric ulcer treatment = omeprazole
- racemic prodrug = active metabolite in parietal cells
- inhibits gastric acid secretion by inhibiting H+, K+ -ATPase
how is PPI activated?
- PPI = weak base = pKa 4.0
- ionised strongly acidic environments
- cross parietal cell membrane when unionised
- too polar to cross back because protonation
what are immunosuppressive drugs and what are they used for?
- thiopurines 1st line & methotrexate 2nd line
- maintain remission if ICS needed after 2 or more exacerbations in 12-months
- only if aminosalicylates = not effective
- increase risk non-melanoma skin cancer
what are the 2 main classifications of antispasmodics?
- antimuscarinics
- smooth muscle relaxants
what are aminosalicylates used for?
- specialist treatment = ulcerative colitis
- consider mild-moderate proctitis & proctosigmoiditis
- topically = suppository or enema
- oral use if no remission in 4 weeks
what is the mechanisms of aminosalicylates?
- activate class nuclear receptors = control inflammation, cell proliferation, apoptosis &
metabolic function - highly express colon epithelial cells
why is oral administration ineffective with aminosalicylates?
- absorbed in small bowel = slow transit time
- effective conc. don’t make it to distal gut
- use prodrugs w/ enzyme azoreductase break down in azo cleavage reaction
which vitamins are absorbed where?
- fat soluble = vits A, D, E & K = small intestine
- water soluble = vits C & B; except B12 = mediated transport
where is vitamin B12 absorbed and why?
- in the ileum because contain cobalt
- intestinal transporter
- only complex with intrinsic factor secreted by parietal cells
what does the rate of drug absorption depend on?
- vascularisation of the site of absorption
- characteristics of formulation/dosage forms
- lipid solubility of the drug
- pH of the site of absorption
what is film coating made of?
- polymer
- plasticizer
- colorant
- solvant
what are the symptoms of GORD?
- bad breath
- nausea & vomiting
- acid reflux
- heartburn
what are the causes of GORD?
- coffee
- stress
- pregnancy
- NSAIDs
- smoking
- being overweight
what is the treatment for GORD?
- 1st line = PPI = omeprazole
- 2nd line = H2 receptor antagonist = ranitidine
what causes peptic ulcers?
- NSAIDs
- H. pylori
what is the treatment for peptic ulcer caused by NSAIDs & H. pylori?
- NSAIDs = stop it & PPI
- H. pylori = amoxicillin + clarithromycin + PPIs
- 2nd line = levofloxacin + metronidazole + PPIs
- pen-allergic = metronidazole + clarithromycin + PPIs
what is a side effect of quinolones?
- tendon damage
- QT-prolongation
how do you diagnose for H. pylori?
- carbon 13 urea breath test
- stool & blood test
what causes treatment failure?
- patient compliant
- prior use antibiotics
- bacteria resistant
what are the GI defenses to infections?
- mucus secretion
- lysozyme
- acid
- gut flora
what are the 3 types of symbiotic relationships?
- mutualistic
- commensalism
- parasite
what are the functions of normal gut flora?
- defense
- metabolism = fiber fermentation, absorb minerals & sterols
- structural = enhance epithelial barrier
how do bacteria damage host cells?
- toxins
- enzymes
- hypersensitivity = trigger exaggerated immune response = damage tissue
what are the types of toxins?
- exotoxins
- endotoxins
- cytotoxins
- neurotoxins
- enterotoxins = interfere GI lining
what are the A & B enterotoxins?
- cholera = diarrhoea
- e.coli = block protein synthesis host cell
- c. diff = diarrhoea
what is the pathogenesis of C. diff?
- flora is disrupted by antibiotics
- ingest c. diff
- colonisation in the colon by bacterium
- A & B released = formation pseudomembrane
what is the treatment for C. diff?
- vancomycin
- give hydration
what are the causes of ceoliac disease?
- immune response to gluten
- thyroid disease
- diabetes type 1
what is the treatment for diverticular disease?
- stop NSAIDs
- lifestyle
- laxatives
- paracetamol
what are the 2 causes of diverticular disease?
- NSAIDs
- smoking
- obesity
- genes
what is the treatment for diverticulitis?
- antibiotics = co-amoxiclav
= trimethoprim & metronidazole
what are the factors that cause vomiting?
- toxic substances
- pregnancy
- palliative care & meds
what are the risk factors of ulcerative colitis?
- non smoker = smoking crohns
- no appendicectomy = appendicectomy crohns
- NSAIDs
- family history
what is the main complication of UC?
- toxic megacolon = dilation colon
what are the severe symptoms of UC that require hospitalisation?
- bloody diarrhoea
- fever
- tachycardia
- hypotension
what is the main side effect of aminosalycilates?
- blood dyscrasia = leukopenia
= bleeding, bruising, sore throat
what are the progressive complications of GORD?
- ulcers on oesophagus = bleed & swallowing painful
- oesophagus becoming scarred and narrowed
- changes in the cells lining oesophagus
what are the progressive complications of peptic ulcers?
- bleeding ulcer site & stomach lining split open
- ulcer blocking food movement through the digestive
system = gastric obstruction
what are the red flag symptoms of GORD?
- unintentional weight loss
- stomach pain/difficulty when swallowing
- persistent vomiting & jaundice
how is omeprazole converted to a prodrug?
- omeprazole = sulphonamides
- sulphonamides bind to cysteine residue on pump
- disulphide bonds with cysteine
how does h. pylori lead to a peptic ulcer?
- h. pylori attack stomach lining w/ urease
- make stomach acid less acidic = weaken mucosal lining
- bacteria stick stomach lining & stim. acid secretion
what are progressive complications of IBD?
- primary sclerosing cholangitis = bile ducts inside the liver become damaged
- risk developing bowel cancer
- poor growth & development = children & young people
what are the symptoms for UC & Crohn’s disease?
- diarrhoea = w/ blood, mucus or pus UC
- abdominal pain
- empty bowel frequently = UC
- bloody stool, fatigue & weight loss = Crohn’s
what is the treatment for diarrhoea?
- antimotility = loperamide
- anticholinergic = atropine
why is azathioprine a high-risk medication?
- immunosuppressant
- SE related to SNP in gene for TMPT = degradation and efficacy of AZA
- can increase types cancer
what are some counselling points for azathioprine?
- regular blood tests = before & during treatment
- more likely get infections
- use sunscreen = photosensitivity
what are the 3 phases of digestion?
- cephalic
- gastric
- intestinal
what is the role of TPMT in treating IBD?
- direct correlation bw. TPMT gene polymorphisms & toxicity AZA
- need TPMT genotyping
what is cholescytokinin?
- stim. release pancreatic juices from gall bladder
- inhibit gastric emptying
- release by I-cells
what is gastrin?
- stim. HCL secretion
- cause growth gastric & colonic mucosa
- release from G-cells
what are the functions of histamine, gastric & somatostatin & secretin in HCl secretion?
- somatostatin & secretin = inhibit
- histamine & gastric = increase
what is a filler?
- increases bulk volume for compression
- lactose
what is a buffer?
- sodium bicarbonate
- maintains pH
what is a disintegrant & superdisintegrants?
- swell up when in contact H2O
- friction between that and drug particles
- starch & crospovidone
what is a lubricant?
- reduce friction
- magnesium stearate
what is a glidant?
- improve flowability
- colloidal sillica
what is a binder?
- improve cohesiveness
- starch
what is secretin?
- stim. growth of exocrine pancreas
- inhibit gastric acid secretion
- secrete bicarbonates to small intestine = neutralise chyme from stomach
- released S cells = duodenum
what is GIP?
- secreted from duodenum cells & proximal jejunum
- in presence glucose = stim. secretion insulin by endocrine pancreas
