Pharmacology Flashcards
which drug classes that influence acid secretion block competitively?
- muscarinic receptor antagonist e.g. pirenzepine
- H2 histamine receptor antagonists e.g. ranitidine
which drug classes that influence acid secretion block irreversibly?
NSAIDs e.g. aspirin
which drug classes that influence acid secretion block by covalent modification?
proton-pump inhibitors e.g. omeprazole
How does drug treatment of peptic ulcers aim to promote ulcer healing by?
- reducing acid secretion
- increasing mucosal resistance
- eradicating H. pylori
which types of drugs reduce prostaglandin formation?
Non-steroidal anti-inflammatory drugs e.g. NSAIDs
what may Non-steroidal anti-inflammatory drugs cause?
trigger gastric ulceration and cause bleeding
How can gastric damage due to long term NSAID treatment be prevented?
with a stable PCE1 analogue
what are drugs that reduce gastric acid secretion used in?
- peptic ulcer
- gastro-oesophageal reflux disease
- acid hypersecretion
what are the mechanisms of anti-secretory activity?
- irreversible inhibition of proton pump
- competitive antagonism of histamine H2 receptors
- competitive antagonism of muscarinic M1 and M3 ACh receptors
- antagonism of gastrin receptors
How do proton pump (PPIs) work?
- inhibit the active H+/K+-dependant ATPase
- basic prodrugs that are inactive at neutral pH but which change conformation in a strongly acidic environment
- are absorbed from the GI tract and delivered via the systemic circulation to the secretory canaliculi of the stomach where accumulation activation and covalent modification of lumenal sulphydral groups of the membrane inserted proton-pump occurs
how do histamine H2 receptor antagonists work?
block the histamine mediated component of acid secretion and reduce secretion evoked by gastrin and ACh
what are examples of mucosal strengtheners?
surcalfate and bismuth chealate
How does surcralfate work?
binds to ulcer base and forms complex gels with mucus - provides a mucosal barrier against acid and pepsin
increases mucosal blood flow, mucus, bicarbonate and prostaglandin production
what are laxatives?
agents that are used to treat constipation
what are purgatives?
agents that cause purging, or cleansing, of bowels by promoting evacuation
when should laxatives or purgatives not be used?
when there is a physical obstruction to the bowel
How do laxatives work?
increase peristalsis and/or soften faeces causing, or assisting, evacuation
when should laxatives/purgatives be used?
- when ‘straining’ is potentially damaging to health (e.g. patients with angina) or when defaecation is painful predisposing to constipation (e.g haemorrhoids)
- to purge bowel before surgery or endoscopy
- to treat drug-induced constipation or constipation in bedridden or elderly patients
what are bulk laxatives?
indigestible polysaccharide polymers. improve stool consistency. slowly acting
what are osmotic laxatives?
poorly absorbed solutes, rapidly acting
what is the mechanism of action of bulk/osmotic laxatives?
retain H2O
increase bulk
increase peristalsis
what is a common side effect of stimulant purgatives?
abdominal cramping
what are faecal softeners?
detergent like action
how do stimulant purgatives/faecal softeners work?
increase H2O and electrolyte secretion
increase peristalsis
faecal softening
What is the treatment for irritable bowel syndrome (IBS)?
treatment is symptomatic with adjustments to diet and anti-diarrhoeals and anti-spasmodics or laxatives as requires
what is the treatment for inflammatory bowel disease (IBD)?
- glucocorticoids for acute attacks
- aminosalicylates for maintenance and mild disease
what drugs cause nausea and vomiting?
- cancer chemotherapy
- general anaesthetic
- agents with dopamine agonist properties
- morphine and other opiate analgesics
- cardiac glycosides (e.g. digoxin)
- drugs enhancing 5-HT function
what are examples of 5-HT3 receptor antagonists?
- ondansetron
- palonosetron
(drugs that end in - setron)
when are 5-HT3 receptor antagonists used?
used to suppress chemotherapy and radiation induced emesis and post-operative nausea and vomiting
how do 5-HT3 receptor antagonists work?
block peripheral and central 5-HT3 receptors
when are 5-HT3 receptor antagonists not effective?
against motion sickness or vomiting induced by agents increasing dopaminergic transmission
what are the most common unwanted effects of 5-HT3 receptor antagonists?
constipation and headaches
what are muscarinic acetylcholine receptor antagonists used for?
prophylaxis and treatment of motion sickness
what are examples of muscarinic acetylcholine receptor antagonists?
hyosine
scopolamine
how do muscarinic acetylcholine receptor antagonists work?
probably blodk muscarinic acetylcholine receptors at multiple sites
direct inhibition of GI movements and relaxation of the GI tract may contribute to anti-emetic effects
what unwanted effects do muscarinic acetylcholine receptor antagonists have? what are these a result of?
blurred vision
urinary retention
dry mouth
resulting from blockade of the parasympathetic ANS and centrally mediated sedation
What are Histamine H1 receptor antagonists used for?
prophylaxis and treatment of motion sickness and acute labyrinthitis and nausea and vomiting caused by irritants in the stomach
what are examples of Histamine H1 receptor antagonists?
cyclizine
cinnarizine
how do Histamine H1 receptor antagonists work?
blockade of H1 receptors in vestibular nuclei and NTS
what do Histamine H1 receptor antagonists normally cause?
CNS depression and sedation - drowsiness may affect performance of skilled tasks
What are examples of dopamine receptor antagonists?
domperidone and metoclopramide
what are dopamine receptor antagonists used for?
drug induced vomiting and vomiting in GI disorders
how do dopamine receptor antagonists work?
centrally block dopamine D2 (and D3) rceptors in CTZ
peripherally exert a prokinetic action on the oesophagus, stomach and intestine
what are phenothiazines used for?
severe nausea and vomiting
what unwanted effects may arise metoclopramine but are less likely in domperidone and why?
disorders of movement
domperidone does not cross the BBB
when are NK1 receptor antagonists used?
in combination to 5-HT3 receptor antagonists and dexamethasone in acute phase of highly emetogenic chemotherapy
how do NK1 receptor antagonists work?
antagonism of substance P (which causes vomiting and is released by vagal afferents) is assumed
what is an example of an NK1 receptor antagonist?
aprepitant
when are cannabinoid (CB1) receptor agonists used?
used ideally in in-patient setting for treatment of cytotoxic chemotherapy that is unresponsive to other anti-emetics
how do cannabinoid (CB1) receptor agonists work?
decrease vomiting induced by agents stimulating the CTZ.
what unwanted effects of cannabinoid (CB1) receptor agonists are there?
drowsiness
dizziness
dry mouth
mood changes
how do opioids work on the alimentary tract?
- inhibition of enteric neurones
- creased peristalsis, increased segmentation
- increased fluid absorption
- constriction of pyloric, ileocaecal and anal sphincters
- increased tone of large intestine
what are the major opioid agents used in diarrhoea?
- codeine
- diphenoxylate (low CNS penetration, low water solubility)
- loperamide (low CNS penetration, low solubility in water)
what is the best treatment for symptomatic stones?
laproscopic cholecystectomy
who may ursodeoxycholic acid be suitable for?
patients with unimpaired gall bladder function who have small/medium sized radiolucent stones (CH stones) which it dissolves
what is a adverse effect of ursodeoxycholic acid?
diarrhoea
what may happen if morphine is given for biliary colic?
pain may worsen due to constriction of sphincter of oddi and increased intrabiliary pressure
what are alternatives to morphine for biliary colic?
buprenorphine and pethidine
what might biliary spasms be relived by?
atropine and glyceryltrinitrate (GTN)
what are examples of bile acid sequestrants (resins)?
colveselam
colestipol
colestyramine
how do bile acid sequestrants work?
act by binding to bile acids, preventing their reabsorption
how do bile acid sequestrants indirectly lower plasma LDL-cholesterol?
- promote hepatic conversion of cholesterol to bile acids
- increase cell surface expression of LDL-Receptor in hepatocytes
- increase clearance of LDL-cholesterol from plasma
what are clinical uses of bile acid sequestrants?
hyperlipidaemia
cholestatic jaundice
bile acid diarrhoea
what are limitations and adverse effects of bile acid sequestrants?
- unpalatable, inconvenient (large dosages)
- frequently causes diarrhoea
- reduced absorption of fat-soluble vitamins and some drugs
what is the main organ of drug metabolism?
liver, but the GI tract, lungs and plasma alos have activity
what does drug metabolism act to do?
- convert parent drugs to more polar metabolites that are not readily reabsorbed by the kidney, facilitating excretion
- concert drugs to metabolites that are usually pharmacological less active than parent compound.
- less frequently, metabolites may; be converted to active compounds or gain activity, have unchanged activity or posses a different type, or spectrum of action
what are the two phases that are often present in drug metabolism?
phase I (oxidation, reduction, hydrolysis) - makes drug more polar, adds a chemically reactive group permitting conjunction
phase II (conjunction) - adds an endogenous compound increasing polarity
what are the main gene families in the human liver?
CYP1, CYP2, CYP3
What mediates oxidation reactions (phase I) in the liver?
haem proteins located in the endoplasmic reticulum of liver hepatocytes
what is glucuronidation?
transfer of glucuronic acid to electron-rich atoms of the substrate
how to you teat hepatic failure?
- lactulose
- antibiotics (neomycin, rifamixin)
what happens during hepatic failure?
detoxification of ammonia, via the urea cycle to urea fails, blood ammonia levels rise exerting toxic effect upon the CNS that causes incoordination, drowsiness, coma and death.
how do you treat allergic oesophagitis?
steroids/chromoglycate/montelukast
what drugs can be used for treatment of GORD?
antacids
H2 antagonists
proton pump inhibitors
why are antacids used for GORD?
symptomatic relief
no benefit in healing/preventing complications
what two H2 antagonists are used in GORD?
cimetidine - symptom relief
ranitidine - poor at preventing relapse and complications
what drugs function is acid suppression?
intravenous omeprazole
which methods achieve haemostasis?
terlipressin endoscopic variceal ligation sclerotherapy sengstaken-blakemore balloon TIPS
what is sulphasalazine?
a combination of sulphapyridine and 5-ASA
what does 5-aminosalicyclic acid act as?
anti-inflammatory
what side effects of sulphasazine are due to the sulphapyridine moiety?
oligospermia headache heinz body aneamia megaloblastic aneamia lung fibrosis
what are common 5-ASA side effects?
GI upset headache agranulocytosis pancreatitis interstitial nephritis
what types of 5-ASA drugs are there?
sulphasalazine
mesalazine
olsalazine
what are the therapy options for ulcerative colitis?
5ASA (mesalazine)
steroids
immunosuppressants
anti-TNF therapy
what are the therapy options for crohn’s disease?
steroids
immunosuppressants
anti-TNF therapy
what do 5ASAs reduce the risk of?
colon cancer
what are the steroid side effects?
muscoskeletal -avascular necrosis, osteoporosis
GI
cutaneous - acne, thinning of skin
metabolic - weight gain, diabetes, hypertension
neuropsychiatric - cataracts, growth failure
what are the side effects of azathioprine?
pancreatitis
leucopaenia
hepatitis
small risk of lymphoma, skin cancer
