MP322 week 6 Flashcards
functional dyspepsia
non-ulcer dyspepsia
no or unknown underlying reason for symptoms
stomach protection (from acid)
- alkaline mucous gel
– both the protein content and alkalinity neutralise the hydrochloric acid in the immediate area of the epithelium
– the mucous forms a chemical barrier between the highly acidic contents of the lumen and cell surface - tight junctions between epithelial cells
– tight junctions between epithelial cells lining of the stomach limit the diffusion of hydrogen ions(H+) into underlying tissues - rapid turnover of epithelial cells (replacement of damaged cells every few days)
– replaced every few days by new cells arising by the division of cells within the gastric pits
gastric and duodenal cells secrete bicarbonate which aids in buffering acids that lies near the mucosa - PGE (prostaglandins of the E type) is important as it increases the production of both bicarbonate and the mucous layer
perforation of an ulcer
this sore can erode all the way through the stomach- this is called a perforated ulcer which is a surgical emergency
- with a perforated ulcer bacteria are able to leave the stomach and enter the peritoneum (this is called peritonitis), this bacterial infection can spread into the blood (causing sepsis) and cause organ failure and eventually death
the first sign of a perforated ulcer is sudden, intense, steady abdominal pain
- about 15% of patients die
ulcer formation
involves breaking down the mucosal barrier and exposing the underlying tissue to the corrosive action if acid and pepsin - not always clear what causes the initial damage to the barrier
acid is essential for ulcer formation- not always primary factor, many patients have normal or even sub-normal acid secretion rates
causes of ulcers include
H. pylori, NSAIDs, Pepsin, Smoking, Alcohol, Bile acids, Steroids, Stress, Changes in gastric mucin consistency (may be genetically determined)
- these can alter the mucosal defence by allowing back diffusion of hydrogen ions and subsequent epithelial cell injury
H.pylori
gram negative bacteria
first linked to gastritis in 1983 , since then research has shown it is major contributor to peptic ulcer disease, along with acid and pepsin
uses its flagella to burrow into the mucus (where the pH is more neutral)
also it neutralises the acid in it’d environment by producing large amounts of urease (an enzyme which breaks down urea present in the stomach) this breaks down urea into ammonia and carbon dioxide
causes inflammation of the gastric mucosa
infects the lower part of the stomach
40% of people are infected with h. pylori
increases gastrin release and thereby acid secretion
also causes direct damage to mucosa thus furthering disruption the physiological balance
95% of patients with gastric ulcer and 80% of those with duodenal ulcer have a h.pylori infection
almost all patients with duodenal ulcer and most with gastric ulcer have H. pylori infection
epithelial cells
- secrete mucous in response to irritation of epithelial lining and as a result of cholinergic stimulation
NSAIDs
impair mucosal resistance but do not alter acid secretion
prostaglandin
inhibition of endogenous prostaglandin synthesis leads to a decrease in epithelial mucus, bicarbonate secretion, mucosal blood flow, epithelial proliferation and mucous resistance to injury
protective factors
bicarbonate layer
mucous
blood flow
cell renewal
prostaglandins
phospholipids
damaging factors
acid, pepsin, bile salts, NSAIDs, H.pylori
symptoms of a peptic ulcer
abdominal discomfort, pain or nausea
pain is located in the epigastrium and usually does not radiate
pain may be described as burning, gnawing or as hunger pains
classically gastric ulcer pain is aggravated by meals, whereas that os a duodenal ulcer is relieved
symptoms of a peptic ulcer
abdominal discomfort, pain or nausea
pain is located in the epigastrium and usually does not radiate
pain may be described as burning, gnawing or as hunger pains
classically gastric ulcer pain is aggravated by meals, whereas that os a duodenal ulcer is relieved
diagnosis of a peptic ulcer
endoscopy
- only really done if over 55, signs of bleeding or pain when swallowing
can apply local treatments and take a sample (biopsy)
diagnostic testing for H. pylori
urea breath test (UBT) based on principle that h. pylori contains large amounts of the enzyme urease which converts urea to NH3 (ammonia) and co2 (carbon dioxide)
if h. pylori is present them co2 produced is absorbed the lining of the stomach into the blood- samples of breath are collected and the isotopic carbon (carbon 13) is measured
also stool antigen test (SAT)- this cannot determine if an infection is current or previous
who discovered propranolol and cimetidine
James black
the stomach
fundus
- upper part of stomach
- thin walled
- secretes mucus, pepsinogen and acid
antrum
-lower part of stomach
- thicker layer of smooth muscle
- responsible for mixing and grinding food
- glands here secrete little acid but contain endocrine cells which secrete gastrin
- also contain enterochomafin-like cells which release histamine
- contain D cells which release somatostatin
- both histamine and somatostatin regulate acid secretion
glands
- cells at opening secrete mucus
- lining walls of the glands are parietal cells ( which secrete acid and intrinsic factor ) and chef cells (which secret pepsinogen)
acid secretion
When parietal cells are activated by acetylcholine or gastrin, there is an increase in the intracellular Ca2+ concentration, which in turn stimulates acid secretion from the H+/K+ ATPase (proton pump) on the canalicular surface
in close proximity to the parietal cells are gut endocrine cells called enterochromaffin-like cells, which also have receptors for gastrin and acetylcholine, which stimulate histamine release. Histamine binds to the H2 receptor on the parietal cell, resulting in the activation of adenylyl cyclase, which increases cAMP and activates protein kinases stimulates acid secretion from the H+/K+ ATPase (proton pump). Neural (acetylcholine), endocrine (gastrin), paracrine (histamine) mediated stimulation of acid secretion
parietal cells are stimulated to secrete acid by gastrin (acting on gastrin/cck-B receptor), acetylcholine (m3 receptor) and histamine (h2 receptor)
acid is secreted across the parietal cell canalicular membrane by the h+/K+ ATPase proton pump into gastric lumen
gastrin
secreted by astral G cells into blood vessels in response to intraluminal dietary peptides
within the gastric body gastrin passes from blood vessels into submucosal tissue of fundic glands where it binds to gastrin-cck-b receptors on parietal cells and ECL cells
the vagus nerve stimulates postganglionic neurone of the enteric nervous system to release acetylcholine which binds to m3 receptors on parietal cells and ECL cells
stimulation of ECL cells by gastrin (cck receptor) or acetylcholine (m3 receptor) stimulates release of histamine
astral D cells are stimulated to release somatostatin by the rise in intraluminal h+ concentration and by cck that is released into the bloodstream by duodenal I cells in response to proteins and fats
binding of somatostatin to receptors on adjacent antral G cells inhibits further gastrin release
acid secretion in the stomach
- carbonic anhydrase produces HCO3- and H+
- HCO3- is exchanged for CL-
- CL- diffuses into lumen
- H+ is pumped into lumen by H+/K+ ATPase
- carbonic anhydrase catalyses the reaction between CO2 and H2) to produce carbonic acid
drugs for treating peptic ulcer disease
Antacids
Antisecretory agents
Raising gastric pH (above 3) for a few hours/day promotes healing
Duration of acid suppression determines the rate of healing
Rapid healing requires suppression for 18-20 hours/day
Eradication of H. pylori infection
Pharmacological treatments
histamine receptor (h2) antagonists
H2 antagonists: cimetidine, ranitidine, nizatidine, famotidine
Act competitively on H2 receptors on gastric parietal cells
Reduce basal acid secretion and prevent the increase that occurs in response to a number of secretory stimuli
Reduce acid secretion by ~60%
Can treat both duodenal and gastric ulcers; BUT relapse is common after treatment stops
adverse effects of H2 antagonists
- diarrhoea
- headache
- confusion in elderly
- gynaecomastoa (with cimetidine because of an anti-androgen effect)
-cimetidine inhibits cytochrome P450 system (potential interactions with warfarin, phenytoin and theophylline)
PPIs
PPIs: omeprazole, lansoprazole, pantoprazole, rabeprazole, esomeprazole
Inhibition of the pump almost completely blocks acid secretion
PPIs are irreversible
Return of acid secretion is dependent on synthesis of new enzymes (H+/K+ ATPase)
Acid secretion is inhibited by ~90% for ~24 h with a single dose
adverse effects of PPIs
Gastrointestinal upset (e.g. epigastric discomfort, nausea and vomiting, diarrhoea)
Headache
Skin rashes
Omeprazole has both stimulatory and inhibitory effects on cytochrome P450 system
Long-term use may cause gastric atrophy (or stomach cancer-possibly)
eradication of H.pylori infection
patients with peptic ulcer disease and positive test for h.pylori
triple therapy- PPI, amoxicillin and clarythromycin or metronidazole
- if penicillin allergic give both clarythromycin and metronidazole with PPI
twice daily for 7 days
cytoproctective agents
Prostaglandin analogue: misoprostol
Methyl analogue of prostaglandin E1
Enhanced duodenal bicarbonate secretion
Weak inhibition of gastric acid secretion, through activation of prostaglandin receptor on parietal cells
Increased mucosal blood flow
Must not be used during pregnancy
Zollinger- Ellison syndrome
Rare disorder that can cause gastric or duodenal ulcers (usually multiple), as well as in the jejunum
Massive gastric acid hypersecretion
Due to gastrin secreting tumour in the pancreas or duodenum (gastrinoma) that stimulates acid secretion in stomach
Patients likely to have intractable ulcer disease
Treatment must control the hypersecretion and the gastrinoma
GORD
can be called GERD too
Amount of acid secretion is normal
Functionally incompetent lower oesophageal sphincter
Allows reflux of gastric contents (containing acid and pepsin into oesophagus)
Symptoms - restrosternal burning
treatment
Antacids and antacid/alginate combinations
Drugs that inhibit gastric acid secretion (H2 receptor antagonists and proton pump inhibitors)
Drugs that act on oesophageal and/or gastric motility
barret’s oesophagus
Commonly diagnosed in patients with long-term GORD
Replacement of normal stratified squamous epithelium by columnar epithelium with goblet cells
Can lead to oesophageal adenocarcinoma (>85% mortality)
a patient comes into the pharmacy to request Peptac suspension as treatment for acid reflux symptoms. Examining the patient’s medication record (PMR) you see that they are currently prescribed omeprazole 10mg gastro/resistant capsules, one to be taken in the morning
can we give peptac?
any other qs
- yes can give peptac - however not within 2 hours of omeprazole
- how long have they been on omeprazole?- it can take a few days to work
Scenario 2- a patient comes into the pharmacy with a prescription for Arcoxia (etoricoxib) 90mg, one tablet to be taken in the morning. The doctor has chosen this medication as it is less likely to cause GI irritation than other non-steroidal anti-inflammatory drugs (NSAID). While the patient is waiting for their prescription you over hear them requesting treatment for a mouth ulcer from the medicine counter assistant.
oral ulceration if a very common side effect
if ulcer caused by this medication it will not be self limiting - needs to come off meds
is this the first prescription/ first time in a while- ulcer won’t be caused by the medication
this is a cox 2 inhibitor- meaning it doesn’t cause GI irritation but still have analgesic effect
a patient requests a supply of ibuprofen to treat epicondylitis. On examining the patient’s Patient Medication Record (PMR) you see that that they have been prescribed ranitidine 150mg tablets, one to be taken twice a day
- Epicondylitis- a painful condition that occurs when tendons in the elbow are overloaded – usually by repetitive motions ie tennis elbow
ranitadine- used for gastric ulceration and GORD
- if they have GI issues they shouldn’t use NSAIDs
should recommend a non NSAID like paracetamol for pain management
a patient requests a supply of lactulose to treat constipation. On examining the patient’s PMR you see that that they have been prescribed co-codamol 15/500 tablets, two to be taken four times a day.
- constipation is a side effect of pain killers
- ask how long she’s been taking the co-codamol and how long she has been constipated- could be completely unrelated
- safe to give lactulose- drink plenty fluids and remind them it b=may take 2-3 days to work
can you supply a CD to a doctor in an emergency without a prescription
yes
when you supply a CD to a doctor in an emergency without a prescription, how long do they have to provide a prescription
24 hours
What is the legal limit on the number of Paracetamol tablets / capsules you can you sell?
No more than 100 non effervescent tablets
No legal limit on effervescent just professional judgement, why would they need more?
What are the licensing restrictions for OTC sales of codeine and dihydrocodeine?
Short term use only (3 days), max pack size 32, can cause addiction on packaging, acute pain that is not relived by paracetamol, ibuprofen or aspirin alone
What are the different means by which you can help people who have run out of their medication in Scotland?
Unscheduled care PGD
Emergency supply
Cant give schedule 1, 2 or 3 through these- only phenobarbital (when indicated for epilepsy)
if an emergency supply is made at the request of the prescriber how long do they have to provide a prescription
72 hours
Can you make an emergency supply for a person when their prescriber resides in EEA or Switzerland?
yes but all the same the conditions apply and you would need to be sure of all the
relevant information – dose, form etc
Can you make an emergency supply for a person when their prescriber resides in EEA or Switzerland?
yes but all the same the conditions apply and you would need to be sure of all the
relevant information – dose, form etc
Can you accept a faxed prescription?
no, not legal – could be forged, where is it coming from? How do we check that
Are there any legal restrictions on children collecting a prescription?
case by case basis, table to help with decision making (do you know them?, age, maturity, what is being collected?, prior arrangement, etc.)
need to think about consequences to the patient if we dont supply
legal class of: morphine
CD schedule 2
legal class of: codeine
CD schedule 5 (CD invoice must be kept for 2 years)
legal class of: dihydrocodeine
CD schedule 5 (CD invoice must be kept for 2 years)
legal class of: buprenorphine
CD schedule 3
legal class of: ibuprofen
GLS, P, POM depends on pack size and strength
legal class of: hydrocortisone
GSL, P, POM - depends on strength
legal class of: aspirin
GLS, P, POM depends on pack size and strength
legal class of: paracetamol
GLS, P, POM depends on pack size etc
referral for gastric disorders and ulceration
prolonged, severe, unresponsive to therapy danger symptoms
omeprazole mechanism of action
ionised by acid
this allows it to diffuse through the fatty secretariat canals of parietal cells (where the pH is 1)
parietal cells are full of protons- this means omeprazole is ionised inside the cell
at low pH a chemical conversion occurs and omeprazole becomes active (sulphonamide)( a permanently charged quaternary ammonium salt) which fits into ATPase enzyme
this is why the drug acts specifically in the parietal cells
because of this low pH it cannot move out of the cell as it cannot become unionised again
this is known as ion trapping
sulphonamide reacts with thiol groups in H+, K+ -ATPase enzyme which forms a stable disulphide complex- no more acid is produced until new enzyme is made which results in a long duration of inhibition of gastric acid production
omeprazole formulaiton
in hard gelatine capsules to prevent conversion to active form (sulphonamide) whilst in the stomach
omeprazole in treatment of ulceration
omeprazole works for a long while- 40mg dose affects acid secretion for 72 hours
duodenal ulcer- 20mg daily doses for 2-4 weeks
gastric ulcer - 20mg daily doses for up to 8 weeks
omeprazole stereochemistry
has chirality of S enantiomer which was much more effective in inhibiting acid secretion than R enantiomer
chiral centre is at the sulphur
- sulphur has a lone pair of electrons
H2 receptor antagonists
stomach acid is produced by H2 receptor
inhibit the H2 receptor and stop acid production
ranitidine is an example
omeprazole
- discovered via initial observations and iterative process
- pkas of 4 and 8.7
- log d and log p = 2.3 at physiological pH
log p
a measure of lipophilicity/ hydrophilicity in an unionised state
log p of 3 means- for every 1 molecule that stays in water, 1000 molecules will cross membranes into organic phase
lower log p - more likely to cross membrane
log p is for each functional group- not a whole molecule
acids and bases
acids donate protons
the more dissociated the molecule the more acidic
log D
also takes into account the environment - pH
always less than log p
higher log d - more absorption
calculations- refers to drug molecule not environment
give 2 examples of alginates and a medical condition which they shouldn’t be used with
peptac and gaviscon
rafting agents- these create a floating barrier on top of acid to stop it splashing up
hypertension
Give 5 examples of PPIs
omeprazole
lansoprazole
esomeprazole
pantoprazole
rabeprazole
indications for PPI’s
ulcer disease
h. pylori eradication
dyspepsia
GORD
prevention of NSAID damage
re- bleed after surgery
PPI cautions
increased risk of bone fracture on prolonged usage
increased risk of C. diff infection
mark symptoms of cancer
rebound hyper secretion of acid on cessation
PPI interactions
esomeprazole and omeprazole decrease antiplatlet effect of clopidogrel
pantoprazole may increase anticoagulant effect of warfarin
PPI side effects
common- abdominal pain, headaches
uncommon- arthralgia, parasthesia
rare- confusion, gynaecomastia
pharmaceutical care of GORD+ peptic ulcer disease
H2 receptor antagonists
chelates
prostaglandin analogues
pro-kinetic drugs- affect gastric emptying
raft forming alginates
name 4 H2 receptor antagonists
ranitidine
cimetidine
famotidine
nizatidine
H2 receptor antagonists cautions/ side effects
mask symptoms of cancer
common- diarrhoea, dizziness
uncommon- erythema
rare- hepatitis, confusion
H2 receptor antagonist drug interactions
cimetidine increases blood concentration of erythromycin
famotidine and ranitidine- reduce plasma concentration of atazanavir
medication stability lab
- ## safe medications will be within 5% of the stated dose
uv/vis
uv/vis works using the linear relationship of absorbance with concentration
– the stronger the concentration the greater the absorbance
(only linear at certain concentrations)
the best method for analysis of the stated content of a drug forumulation
uv/vis
A11 value
if 1g of drug in 100ml should give absorbance of A11 value
these values can vary and so needs to be calculated for each machine- meaning literature values are not always appropriate for use
inflammatory bowel disease
Ulcerative Colitis and Crohn’s Disease
- both include inflammation, swelling and ulceration of intestinal tissue
- chronic diseases with periods of remission
- symptoms include stomach pain and cramps, weight loss, diarrhoea (blood and mucus) and tiredness
- also can cause joint pain, inflamed eyes and rashes
ulcerative colitis
only affects the large bowel and the inflammation is on the inner lining
Crohn’s disease
can affect any area of the GI system and all layers of tissue can be inflammed
diagnosis of IBD
- symptoms presented
- blood tests for anaemia, vitamin deficiencies and inflammatory markers
- x-ray examination< CT and MRI scans
- sigmoidoscopy and colonoscopy
- for crohns
– small bowel enema
– small capsule endoscopy
what causes IBD
- genetic links
- autoimmune disease
- environmental
- previous infection
prevlance of IBD
- most common in late teens/ early 20s
- more common in white than other ethnicities
- more common in women
- in uk about 1 in every 350
aims of treatment for IBD
- induce and maintain remission
- reduce symptoms and improve quality of life
- reduce inflammation - steroids, ahminoglycosides, cytokine modulators
- reduce autoimmune response - immunosuppressant drugs
corticosteroids
- administered orally or rectally
- GR or MR formulations or enemas and foams
– hydrocortisone
– beclomethasone
– budesonide
– prednisolone
if longer than 2 weeks need to taper due to adrenal suppression
pharmacology of steroids
reduce inflammation mediators directly and also have effects on expression of genes associated with inflammatory and anti-inflammatory proteins
corticosteroid cautions
cognitive heart failure
hypothyroidism
osteoporosis
untreated infection
corticosteroids side effects
insomnia
dyspepsia
Cushing’s syndrome
impaired healing
adrenal suppression with long term use
corticosteroids interactions
grapefruit juice increases plasma concentration of oral budesonide
also antagonise diuretic effects
aminosalicylates
administered orally or rectally
MR tablets/ capsules, granules, suspensions or foam, suppository, enemas
– balsalazine
– mesalazine
– olsalazine
– sulfalazine
aminosalicylates side effects
- rare
– blood disorders- patients to report unexplained bleeding, bruising, purport, sore throat, fever or malaise during treatment - renal function should be checked before starting oral therapy then 3/12 then annually
- salicylate sensitivity
Suggests bone marrow suppression- blood disorders
Need to advise patients on what to look out for
salfasalazine
- colours urine and contact lenses orange
- decreases concentration of digoxin (moderate) and absorption of folates (moderate)
cytokine modulators
- monoclonal antibodies which inhibit pro-inflammatory cytokine, tumour necrosis factor alpha
- administered bu subcutaneous administration
– infliximab, adalimumab, golimumab, vedolizumab - stop the extension of activated T cells by interrupting the calmodulin-calcineurin cascade
immunosuppressants
- t - cell effects
- administered orally or by injection
- care when handling in pharmacy
– azathioprine, ciclosproin, metcaptopurine
– methotrexate - anticancer drugs with blood toxicity and liver toxicity so require regular monitoring of blood counts and organ function for safe use
methotrexate
- weekly dosage
- follow up dose of folic acid to reduce s/e
- only use 2.5mg tablets
- report sore throat, bleeding, bruising, mouth ulcers
- regular monitoring- FBC, renal and liver
- methotrexate safety card
- high risk drug in CMS
how are IBD drugs used
mild disease in rectum and recto-sigmoid is treated with local steroid or aminosalicylate
- diffuse or unresponsive IBD is treated orally as above (alone or in combination)
- move to parenteral administration in severe cases (steroid, immunosuppression and antibody therapy)
none drug treatment of IBD
- smoking cessation
- attention to diet
– lose residue diet
– trigget foods - surgery
– stoma operations
– resection operations
role of the pharamacist in IBD
- could be IP
- diagnosis
- investigation
- selecting appropriate treatments
- selecting appropriate doses
- selecting best treatment for special groups eg breast feeding, renal impairment
- adherence to guidelines
- monitor outcomes
pharmaceutical care
overall responsibility to ensure that patient is able to take the prescribed medication in a safe and effective manner to ensure that the patient derives maximum treatment benefit
Is the prescription legal and has it been dispensed accurately
is the dose safe
any other clinical issues (eg interactions, side effects)
explain how to take/ use the medication
additional cautions
what side effects to look out for and what to do
provide advice in regimen (why a dose or medication has changed)
explain how the drugs work in language the patient will understand
poor symptom control (OTC requests)
must be able to explain condition being treated
lifestyle advice
advice and signpost to support eg Crohn’s and colitis UK
