Alimentary Pharmacology Flashcards
What drugs affect acid suppression in the GI tract
Antacids
H2 receptor antagonists
Proton Pump inhibitors
What drugs affect GI motility
Anti-emetics
Anti-muscarinics/spasmodics
Anti-motility
What drugs help in bowel movement in the GI tract
Laxatives
What drugs are usedin the treatment of Inflammatory bowel disease
Aminosalicylates
Corticosteroids
Immunosuppressants
Biologics
What drugs affect intestinal secretion
Bile acid sequestrate
- Cholestyramine
Urosodeoxycholic acid
What is an example of an antacid drug, what is it composed of
Maalox
containing magnesium and aluminium
What is the mechanisms of antacids
Neutralising gastric acid
to relieve symptoms
What is an example of an Alginates and its mechanism in the treatment of acid suppression
Gaviscon
Forms a vicious gel that floats on the stomach contents and reduces reflux
Name three additional muscosal protectors in acid suppression
Bismuth
Sucralfate
Misoprostol
What is an example of a H2 receptor antagonist and its mechanism
Ranitidine
Blocks histamine receptor thereby reducing acid secretion (controlling acid production)
When is H2 receptor antagonist used
Indicated in GORD
Peptic ulcer disease
What is the administration of H2 receptor antagonist and proton pump inhibitors
Orally
IV
What is an example of a Proton Pump Inhibitor and it mechanism
Omeprazole
Blocks proton pump inhibitory thereby reducing acid secretion
What is the indication for the use of Proton pump inhibitor
Used in GORD
Peptic ulcer disease
Tripple therapy treatment for PU/DU associated with H.Pylori
What are the GI upset and predisposition that can occur due to Proton pump inhibitor s
C. Diff Infections
Hypomaganesaemia
B12 deficiency
What is the mechanism of pro kinetic agents
Increase gut motility and gastric emptying
by having parasympathetic nervous system control of smooth muscle and sphincter tone via ACh
What are examples of Prokinetic agents
Metoclopramide
Domperidone/dopamine antagonist
How does Domperidone increase gut motility and gastric emptying time
blocking dopamine receptors which inhibit post-synaptic cholinergic neurones
What is Pro-kinetics used in the treatment of
GORD
Gastroparesis - allows to empty quicker
What is anti emetics, give two examples
Prevent vomiting
5- HT3 antagonists
Anti Histamines
Where do 5-HT3 antagonist work to prevent vomiting
Chemoreceptor Trigger zone (drugs/toxin)
Vomiting centre/medulla
Pharynx and GIT
(gastroenteritis, radiotherapy, some drugs)
Where do antihistamine work in the prevention of vomiting
Vestibular nuceli (motion)
Vomiting centre/medulla
Chemoreceptor trigger zone
Where does dopamine antagonist work for increasing gut motility and gastric emptying
Chemoreceptor trigger zone
Pharynx and GIT (gastroenteritis, radiotherapy, some drugs)
What is examples of anti-motlity drugs
Loperamide (immodium)
Opiods
What is the mechanism of anti-motility drugs
antagonise optiate receptors in GI tract decreasing ACh release, thereby decreasing smooth muscle contraction and increasing anal spinchter tone
What is the clinical benefit of drugs which decrease GI motility
are anti-diarrhoea
Why does loperamide have few central opiate effects
Not well absorbed across the blood brain barrier
What doe antispasmodics reduce the symptoms of
IBS
Renal colic
What is the three mechanism od anti-spasmodics
anti-cholingeric muscarinic antagonists
Direct smooth muscle relaxants
Calcium channel blockers
What is examples if anti-cholinergic muscarinic antagonists
and there mechanisms
- Hyoscine Buscopan
- Meberverine
Inhibit smooth muscle constrictions in the gut wall, producing muscle relaxation and reduction in spasm
What is an example of a CCB and its mechanism
Peppermint oil
Reduce calcium required for smooth muscle contractions
What is the 4 types of laxatives, and examples
Bulk
(e.g. Isphagula)
Osmotic
(e.g. Lactulose)
Stimulant
(e.g. Senna)
Softeners
(e.g. Arachis oil)
What is the overall mechanism of laxatives
Work by increasing bulk or drawing fluid into the gut making it easier for stool to pass
What is potentially issues of laxatives
Can cause obstruction
Osmotic laxatives will not work without adequate fluid intake
Misuse
Route of administration: oral or rectal
What is the problems of anti-motility drugs
Can cause constipation
Cannot take it there is an obstruction
Prevent diarrhoea - infection isn’t “flushed out”
What drugs are used in treating inflammatory bowel disease
Aminosalicylates
Cortiscosteroids
Immunosuppressants (azathioprine)
Biologics
(Anti-TNFα antibodies)
What is examples of aminosalicylates that treat IBD
and how are they administrated
Mesalazine
Olsalazine
(Sulfasalazine original drug but side effect problems)
Administrated either Orally or IV
What is the mechanism of aminosalicylates in treating IBD
Unclear but has anti-infammatory properties
What cautions should be taken when taking aminosalicylates for the treatment of IBD
Chemically related to salicylates so avoid if allergic
Be careful if have renal impairment
What is the adverse effect of aminosalicylates
GI upset
Blood dyscrasias
Renal impairment
What is the administration and mechanism of cortiscosterioids
Given: Orally, IV, Rectal
Anti-inflmammatory effects
What is the concerns of taking corticosteroids in IBD
Can cause:
-Osteoporosis -Cushingoid features (weight gain, diabetes mellitus, HT)
Have an increased susceptibility to infection
If abrupt withdrawal causes addisonian crisis
Define addisonian crisis
Medical emergency as symptoms that indicate severe adrenal insufficiency caused by insufficient levels of the hormone cortisol
How does the immunosuppressant azathioprine work in the treatment of IBD
Prevents the formation of purines required for DNA synthesis so reduces immune cell proliferation
What is the adverse effects of azathioprine that means it requires close monitoring
Bone marrow suppression
azathioprine hypersensitivity and organ damage to lung,liver, pancreatitis
Drug interaction
What is an example of a Biologic that treats IBD, and its mechanism
Infliximab
- mouse human chimeric antibody to TNFα
Prevents the actions of TNFα preventing cytokine occurring in an inflammatory response
What is infliximab also used in the treatment of
Psoriasus
Rheumatoid arthritis
What are the cautions and contradictions of Infliximab treatment in IBD
Current TB/serious infection
Multiple sclerosis
Pregnancy/ breast feeding
What is the adverse effect of Infliximab
Risk of infection,
Infusion reaction (fever, itch)
Anaemia, thrombocytopenia, neutropenia
Demyelination
Malignancy
What should all patients taking Infliximab be screened for
TB
What are 5 examples of other biologics that can be used in the treatment of IBD
Certolizumab
Adalimumab
Natalizumab
Golimumab
Vedolizumab
What is the mechanism of Bile acid sequestrate’s
Cholestyramine
Reduces bile salts by binding with them in the gut and then excreting as insoluble complex
- preventing reabsorption
What should be considered when taking Cholestyramine
May affect the absorption of other drugs - take separately
May affect fat soluble vitamin absorption so may decrease vitamin K levels (affecting clotting and warfarin)
What does chlestyramine treat
Pruitits from biliary cause
What does Ursodeoxycholic Acid treat
Gall stones
Primary Biliary cirrhosis
What is the mechanism of Ursodeoxycholic Acid
Inhibits an enzyme involved in the formation of cholesterol, altering amount in bile and slowly dissolving non-calcified stones
Gastrointestinal or liver disease can effect what process of drugs
Absorption
Distribution
Metabolism
Excretion
What might change the route of administration of drugs
GI symptoms
What facts affect the absorption of drugs in the GI
Change in pH
Gut length:
- extra stomach time
- slow time to small intestine
Transit time
- dependant on bacteria
- diarrhoea, increases transit time, decreases absorption
What factor affect distribution of drug in the GI tract
Low albumin (decreased binding and increased free drug concentration)
What factor affect the metabolism of drugs in the GI tract
Liver enzymes (decrease in disease, drugs toxicity increase)
Increased gut bacteria (metabolise drugs so increased dose needed)
Gut wall metabolism (disease may reduce first pass metabolism)
Liver blood flow (Blockage in flow means drugs will have a high extraction ratio)
What factor affects the excretion of drugs in the GI tract
Biliary excretion due to an increased toxicity if hepatobilliary disease
What are the pharmacodynamic effects with drug examples In Liver disease
Exaggerated response e.g. sedation with benzdiaepines
Reduced response e.g. reduced dieresis with loop diuretics
Increased toxicity e.g. nephrotoxicity with amino-glycosides
What is the GI adverse effects of drug treatment
GI upset
Diarrhoea/constipation
GI bleeding/ulceration
Changes to gut bacteria
Drug induced liver injury
What drugs causes the adverse reaction of diarrhoea/constipation
Cholinergics, NSAIDs, Antimicrobials
Opioids, Anticholinergics
What are the mechanism of the drug treatment that cause diarrhoea
osmotic, secretory, shorted transit time,
protein losing, malabsorption,
What is the main aetiology of drug induced diarrhoea
antimicrobials
What are two example of drug induced GI bleeding/ulceration
Low dose aspirin/NSAIDS
Warfarin
What is the mechanism of drug induced GI ulcers
Ulcer causation and increases bleeding tendency due to impaired platelet aggregation
Implication of other drugs e.g. SSRI and Platelet function
What is NSAID pathology to GI Bleeding
Affect COX1 (Impairing the defence) and COX 2 (impairing the healing) and causes epithelial damage (impairing platelet aggregation)
resulting in local and systemic effect through prostaglandins
Changes to the gut bacteria is mainly due to what drugs
Antibiotics
What is the affect of changes to gut bacteria
Loss of oral contraceptive pill activity
Reduced Vitamin K absorption (increased prothrombin time)
Overgrowth pathogenic bacteria (eg C.diff infection)
What is the two forms drug induced liver injury
Intrinsic hepatoxocity (predictable, dose dependant)
Idiosyncratic hepatotoxicity (unpredictable, not dose dependant)
What causes drug induced liver injury
The drug itself
or its active metabolite
What is the diverse affect of the drug induced liver injury
From asymptomatic increase in LFTS to liver failure and death
Generally causes
- Acute/chronic hepatitis
- cholestasis
(gall stone in bile duct)
What is the risk factors for drug induced liver disease
Age (elderly at risk)
Sex (female at risk)
Alcohol consumption
Genetic factors
Malnourishment
What are examples of drugs causing drug induced liver disease (hepatotoxicity)
Paracetamol, isoniazid = acute
Diclofenac, methyldopa = chronic
ACE inhibitors, co-amociclav = acute cholestasis
Methotextrate = fibrosis/cirrhosis
What is assessed for child-pugs classification scoring the severity of liver disease
High Bilirubin Low albumin PTs Encephalopathy Ascites
When prescribing in Liver disease what drug properties should be avoided
Drugs which can be toxic due to changes in pharmokinetics
Drugs which are hepatotoxic
Drugs which may worsen with non liver aspects of liver disease e.g. encephalopathy
What are the pharmokinetics that change that can cause toxicity of drugs
Liver metabolism
Therapeutic index
Bilary excretion
What is examples of drugs that are hepatotoxic
Methotrexate
Azathioprine
What is an example of a drug which can worsen encephalopathy in liver disease
Benzodiazepine
What particular drugs should be avoided when prescribing in liver disease and why
Warfarin/anti-coagulants
- clotting factors already low
Aspirin/NSAIDS
- Increase bleeding time
- worsen ascites due to fluid retention
Opiates/benzodiazepines
- precipitate encephalopathy by increasing sedation
