Clinical Pharmacology of the Alimentary System Flashcards
What are the main types of drugs used in alimentary disease?
- Acid suppression
- Drugs affecting GI motility
- Laxatives
- Drugs for IBD
- Drugs affecting intestinal secretions
What can be used for acid suppression?
- Antacids
- H2 receptor antagonists
- Proton pump inhibitors
What type of drugs can affect GI motility?
- Anti-emetics
- Anti-muscarinics/other anti0spasmodics
What types of drugs can be used for IBD?
- Amino salicylates
- Corticosteroids
- Immunosuppressant’s
- Biologicals
What types of drugs can affect intestinal secretions?
-Bile acid sequestrants and ursodeoxycholic acid
What is the mechanism of action of antacids?
Act on hydrogen ions pumped into the stomach lumen to neutralise them
What is the mechanism of action of PPIs?
Inhibit the proton pump that pumps H ions into the stomach lumen to prevent decrease in stomach pH
What is the mechanism of action of H2 antagonists?
Prevents stimulation of the proton pump which decreases the number of H ions being pumped into the stomach lumen, preventing decrease in pH
What do antacids such as Maalox contain?
Magnesium or aluminium
What do antacids do?
Neutralise gastric acid
When are antacids taken?
When symptoms occur
Give example of a well-known alginate.
Gaviscon
What do alginates do?
Forma viscous gel that floats on stomach contents and reduces reflux
Give 3 examples of other mucosal protectors apart from antacids and alginates.
- Bismuth
- Sucralfate
- Misoprostol
Give an example of a H2 receptor antagonist and a common brand that its found in.
Ranitidine found in Zantac
What do H2 receptor antagonists do?
Block histamine receptor thereby reducing acid secretion
When are H2 receptor antagonist indicated?
- GORD
- Peptic ulcer disease
How are H2 receptor antagonists administered?
- Orally
- IV
Give an example of a proton pump inhibitor.
Omeprazole
What do PPIs do?
-Irreversibly block proton pump and thereby reduce acid secretion
When are PPIs indicated?
- GORD
- Peptic ulcer disease
How are PPIs administered?
- Orally
- IV
What can long term PPI use predispose you to?
- C diff infection
- Hypomagnesaemia
- B12 deficiency
What can PPIs be given with antibiotics as triple therapy for?
Ulcers associated with H pylori
What do pro-kinetic agents do?
Increase gut motility and gastric emptying
What are pro-kinetic agents used for?
- Gastro paresis
- GORD
- Anti-emetics
Give 2 examples of pro-kinetic agents.
- Metoclopramide
- Domperidone
What is the mechanism of action of pro-kinetics?
Mechanism of action is not clear but involves parasympathetic nervous system control of smooth muscle and sphincter tone (via ACh)
How does domperidone probably work?
By blocking dopamine receptors which inhibit post-synaptic cholinergic neurones
How can motion induce vomiting?
- Vestibular nuclei
- Vomiting centre in the medulla
How can the smell and sight of vomit induce vomiting?
- Cerebral cortex
- Vomiting centre in the medulla
How can drugs and toxins induce vomiting?
- Chemoreceptor trigger zone
- Vomiting centre in the medulla
How can gastroenteritis, radiotherapy and some drugs induce vomiting?
- Pharynx and GIT
- Vomiting centre in the medulla
What types of drugs act on the pharynx and GIT to prevent vomiting?
- 5HT3 antagonists
- Dopamine antagonists
What type of drugs act in the vestibular nuclei to prevent vomiting?
Anti-histamines
What type of drugs act on the chemoreceptor trigger zone to prevent vomiting?
- Dopamine antagonists
- 5HT3 antagonists
- Cannabinoids
What type of drugs act on the vomiting centre in the medulla to prevent vomiting?
- Anti-muscarinics
- Anti-histamines
What can drugs which decrease motility be used for?
Clinical benefit (anti-diarrhoea) however, the may cause unwanted effects (constipation)
What is the mechanism of action for drugs which decrease GI motility?
- Via the opiate receptors in the GIT to decrease ACh release
- Decrease in smooth muscle contraction
- Increase in anal sphincter tone
Why does loperamide have few central opiate effects?
It is not well absorbed across the blood-brain barrier
What can anti-spasmodics be used for?
Reduce symptoms due to IBS and renal colic
What are the 3 mechanisms of anti-spasmodics?
- -Anti-cholinergic muscarinic antagonists (hyoscine, buscopan, meberverine) that inhibit smooth muscle constriction in the gut wall, producing muscle relaxation and reduction spasm
- Direct smooth muscle relaxants
- Calcium channel blockers reduce calcium required for smooth muscle contraction
What is an example of a calcium channel blocker?
Peppermint oil
What are the 4 types of laxatives and an example?
- Bulk: isphagula
- Osmotic: lactulose
- Stimulant: senna
- Softeners: arachis oil
How do laxatives work?
Work by increasing bulk or drawing fluid into gut
What are the issues with laxatives?
- Obstruction
- Route of administration (oral or rectal)
- Need for other measures (osmotic laxatives will not work without adequate fluid intake)
- Misuse
What is the mechanism of action of aminosalicylates?
Unclear but anti-inflammatory
How can aminosalicylates be administered?
- Oral
- Rectal
What are aminosalicylates chemically related to?
Salicylates
What are the possible adverse effects of aminosalicylate?
- GI upset
- Blood dyscrasias
- Renal impairment
Give 3 examples of aminosalicylates.
- Mesalazine
- Olsalzine
- Sulfasalazine
What effect for corticosteroids have?
-Anti-inflammatory
How can corticosteroids be administered?
- Oral
- IV
- Rectal
What are the usual concerns and contrainidications for corticosteroids?
- Osteoporosis
- Cushingoid features including weight gain, DM, HT
- Increased susceptibility to infection
- Addisonian crisis with abrupt withdrawal
Give an example of an immunosuppressant.
Azathioprine
How do immunosuppressant’s work?
Prevent the formation of purines required for DNA synthesis so reduces immune cell proliferation
What adverse side effects are related to immunosuppressants?
-Mainly related to bone marrow suppression but also azathioprine hypersensitivity and organ damage (lung, liver, pancreatitis)
Give an example of an anti-TNFa antibodies biological?
Infliximab
How do anti-TNFa antibodies work?
- Mouse-human chimeric antibody to TNFa
- Prevents action of TNFa (key cytokine in inflammatory response)
- Addresses inflammatory response but not underlying disease process so course of disease after discontinuation is unclear
What are biologicals used in outside of the GIT?
- Psoriasis
- Rheumatoid arthritis
What cautions/contraindications are there for infliximab?
- Current Tb or other serious infection
- Multiple sclerosis
- Pregnancy/breast feeding
What are the adverse effects of infliximab?
- Risk of infection, particularly TB so all patients should be screened
- Infusion reaction
- Anaemia, thrombocytopenia, neutropenia
- Demyleination
- Pleurodynia
- Malignancy
Other than infliximab give examples of 5 other biologicals.
- Certolizumab
- Adalimumab
- Natalizumab
- Golimumab
- Vendolizumab
Certolizumba
Fab fragment of humanized anti-TNFa monoclonal antibody
Adalimumab
Humanized recombinant antibody to TNF
Natalizumab
Anti-integrin monoclonal antibody
Vendolizumab
Binds to integrin a4B7
What drugs affect biliary secretions?
- Cholestyramine
- Ursodeoxycholic acid
What is cholestryamine given to relieve?
Prurutus from biliary cause
How does cholestyramine work?
Reduces bile salts by binding with them in the gut and then excreting as insoluble complex
What may cholestyramine affect?
- Absorption of other drugs so should be taken separately
- Fat soluble vitamin absorption so may decrease vitamin K levels (affect clotting and warfarin)
What is ursodeoxycholic acid used to treat?
- Gallstones
- Primary biliary cirrhosis
How does ursodeoxycholic acid work?
Inhibits an enzyme involved in the formation of cholesterol, altering amount in bile and slowly dissolving non-calcified stones
GI or liver disease ca affect the processes of drug …
- Absorption
- Distribution
- Metabolism
- Excretion
What is absorption dependent on?
- pH
- Gut length
- Transit time
What problems are there with distribution in chronic liver disease?
-Low albumin (decreased binding and increased free drug concentration)
What problems with metabolism are there in chronic liver disease?
- Liver enzymes (variability in effects but generally toxicity)
- Increased gut bacteria (metabolise drugs so increased dose needed)
- Gut wall metabolism (disease may reduce first pass metabolism)
- Liver blood flow (drugs with a high extraction ratio)
What problems with excretion are there in chronic liver disease?
Biliary excretion (increased toxicity if hepatobiliary disease)
How does liver disease affect sedation with benzodiazepines?
Exaggerated response
How does liver disease affect diuresis with loop diuretics?
Reduced response
How does liver disease affect aminoglycosides?
Increased nephrotoxicity
What GI adverse effects can there be with medication?
- Diarrhoea/constipation
- Bleeding/ulceration
- Changes to gut bacteria
- Drug induced liver injury
What are the mechanisms for diarrhoea/constipation as an adverse drug reaction?
Multiple mechanisms
- Osmotic
- Secretory
- Shortened transit time
- Protein losing
- Malabsorption
What are the most common causes of GI bleeding/ulceration as an adverse drug effect?
- Low dose aspirin
- NSAIDs
- Warfarin
What drugs are mainly responsible for changes to gut bacteria?
Antibiotics
What do changes in gut bacteria lead to?
- Reduced vitamin K absorption (increased prothrombin time)
- Overgrowth of pathogenic bacteria
What type A ADR can occur with drug induced liver injury?
Intrinsic hepatotoxicity (predictable, dose dependent, acute)
What type B ADR can occur with drug induced liver injury?
Idiosyncratic hepatotoxicity (unpredictable, not dose dependent and may occur at any time- may be part of hypersensitivity reaction)
Describe type B ADR drug induced liver injury.
- May be due to the drug itself or an active metabolite
- Can range from asymptomatic increase in LFTs to fulminant liver failure and death
- Generally hepatitis or cholestasis but can mimic any pattern or acute or chronic liver disease
What are the risk factors for ADR?
- Age
- Female
- Alcohol consumption
- Genetic factors
- Malnourishment
What is the most common reason for withdrawal of a drug from the marker?
Hepatotoxicity
What scale is used to consider the severity of liver disease?
Child-Pugh classification
What drugs should there be extra care/avoidance with in liver disease?
- Drugs which can be toxic due to changes in pharmokinetics: (Liver metabolism, therapeutic index, biliary excretion)
- Drugs which are hepatotoxic
- Drugs which may worsen the non-liver aspects of liver disease
Why should warfarin/anti-coagulants be avoided in liver disease?
Clotting factors are already low
Why should aspirin/NSAIDs be avoided in liver disease?
- Can increase bleeding time, in combination with deficiency in clotting factors
- NSAIDs can worsen ascites due to fluid retention
Why should opiates/benzodiazepines be avoided in liver disease?
-May precipitate encephalopathy by increasing sedation
