Clinical Pharmacology of Alimentary Flashcards
List the main drug classes used in the treatment of acid suppression.
- Antacids
- H2 receptor antagonists
- Proton pump inhibitors
List the main drug classes used to affect GI motility.
- Antiemetics
- Anti-muscarinics/other antispasmodics
- Anti-motility
- Laxatives
List the main drug classes used in the treatment of IBD.
- Aminosalicylates
- Corticosteroids
- Immunosuppressants
- Biologics
List the main drug classes used to affect intestinal secretions.
- Bile acid sequestrates
- Ursedeoxycholic acid
Describe antacids and give an example.
- Used in treatment of acid suppression
- Contain magnesium or aluminium
- Neutralise gastric acid
- Taken when symptoms occur
e. g. Maalox
Describe alginates and give an example.
- Used in treatment of acid suppression
- Form a viscous gel that floats on stomach contents and reduced reflux
e. g. Gaviscon
Describe mucosal protectors and give examples.
- Used in treatment of acid suppression
e. g. bismuth, sucralfate, misoprostol
Describe H2 receptor antagonists and give an example.
- Used in treatment of acid suppression
- Block histamine receptor thereby reducing acid secretion
- Indicated in GORD/peptic ulcer disease
- Given orally or intravenously
e. g. Ranitidine
Describe proton pump inhibitors and give an example.
- Used in treatment of acid suppression
- Block proton pump thereby reducing acid secretion
- Indicated in GORD/peptic ulcer disease
- Oral or IV administration
- Widely used (overused?)
- Triple therapy treatment of PU/DU associated with H. pylori
- Problems with GI upset and predisposition to C. difficile infection, hypomagnesaemia, B12 deficiency
e. g. Omeprazole
Describe prokinetic agents and give examples.
- Increase gut motility and gastric emptying
- MoA: not clear but involves parasympathetic nervous system control of smooth muscle and sphincter tone (via ACh)
- Also stop vomiting
e. g. gastroparesis, GORD, antiemetics, Metoclopramide and Domperidone (dopamine antagonists - habit post-synaptic cholinergic neurons)
Describe classes of drugs that decrease GI motility and give examples.
- Can be used for clinical benefit (anti-diarrhoea) or cause unwanted effects (constipation)
- MoA: decrease ACh release via opiate receptors, decrease in smooth muscle contraction, increase in anal sphincter tone
e. g. Loperamide (Immodium), Opiods - Loperamide has few central opiate effects as it is not well absorbed across the blood-brain barrier
Describe anti-spasmodics and give examples.
- Can be used to reduce symptoms in IBS, renal colic
Three mechanisms;
- Inhibit smooth muscle constriction in gut wall –> muscle relaxation –> reduces spasm
e. g. anti-cholinergic muscarinic antagonists (hyoscine, buscopan, mebeverine) - Direct smooth muscle relaxants
- CCBs (peppermint oil) reduce Ca –> smooth muscle relaxation
Describe laxatives and give examples.
- Pharmacological treatment may not be needed
Four types;
- Bulk e.g. Isphagula
- Osmotic e.g. Lactulose
- Stimulant e.g. Senna
- Softeners e.g. Arachis oil
- Work by increasing bulk or drawing fluid into gut
Issues;
- Obstruction
- Route of administration: oral or rectal
- Need for other measures: osmotic laxatives will not work without adequate fluid intake
- Misuse
Describe aminosalicylates and give examples.
- Treatment of IBD
- MoA: unclear but anti-inflammatory
- Oral or rectal administration
- Chemically related to salicylates so avoid if allergic
- Caution in renal impairment
e. g. Mesalazine, Olsalazine
Adverse effects;
- GI upset
- Blood dycrasias
- Headches
- Renal impairment
Describe corticosteroids.
- Treatment of IBD
- Anti-inflammatory effects
- Given orally, IV or rectally
Concerns and contraindications;
- Osteoporosis
- Cushingoid features e.g. weight gain, DM, HT
- Increased susceptibility to infection
- Addisonian crisis with abrupt withdrawal
Describe immunosuppressants and give an example.
- Treatment of IBD
- Prevent formation of purine required for DNA synthesis –> reduce immune cell proliferation
- Numerous drug interactions
- Specialist use and close monitoring required
e. g. Azathioprine
Adverse effects;
- Mainly bone marrow suppression
- Azathioprine hypersensitivity
- Organ damage (lung, liver, pancreatitis)
Describe biologics (anti-TNFA antibodies) and given an example.
- Treatment of IBD
- Mouse-human chimeric antibody to TNF-alpha
- Prevents action of TNF-alpha (key cytokine in inflammatory response)
- Also used in psoriasis, RA
- Addresses inflammatory response but not underlying disease process so course of disease after discontinuation is unclear
e. g. Infliximab
Describe infliximab and its cautions/contraindications and adverse effects.
- Biologics used in treating IBD
Cautions/contraindications;
- Current TB or other serious infection
- Multiple sclerosis (can cause onset too)
- Pregnancy/breast feeding
Adverse effects;
- Risk of infection, particularly TB (screen all patients)
- Infusion reaction (itch, fever)
- Anaemia, thrombocytopenia, neutropenia
- ?Demyelination
- Pleurodenia
- Malignancy
Describe cholestyramine.
- Affects biliary secretion
- Pruritis from biliary cause
- Reduces biliary salts by binding with them in the gut and then excreting insoluble complex
- May affect absorption other drugs so should be taken separately
- May affect fat soluble vitamin absorption so may decrease vitamin K levels (affecting clotting and Warfarin)
Describe ursodeoxycholic acid.
- Affects biliary secretion
- Used to treat gallstones and primary biliary cirrhosis (PBC)
- Inhibits an enzyme involved in formation of cholesterol, altering amount in bile and slowly dissolving non-calcified stones
Describe the problems with absorption.
- GI symptoms may necessitate a change in route of administration
- Absorption (rate and total): pH, gut transit, transit time
Describe the problems with distribution.
- Low albumin –> decreased binding and increased free drug concentration
Describe the problems with metabolism.
- Liver enzymes (may be inhibited or reduced but generally toxic)
- Increased gut bacteria (metabolise drugs so increases doses needed)
- Liver blood flow (drugs with high extraction ratio)
Describe the problems with excretion.
- Biliary excretion (increased toxicity if hepatobiliary disease)
Describe GI adverse effects.
- GI upset very common with medication (20-40% of ADRs)
Diarrhoea/constipation;
- Acute/chronic
e. g. cholinergic, NSAIDs, antimicrobials, opioids, anti-cholinergic - Multiple mechanisms
GI bleeding/ulceration;
- 6.5% of hospital admissions due to ADRs
e. g. low dose aspirin, NSAIDs, warfarin - Mechanisms include ulcer causation and increased bleeding tendency
- Other drugs implicated e.g. SSRIs
Changes to gut bacteria;
- Mainly antibiotics
- Loss of OCP activity
- Reduced vitamin K absorption (increased prothrombin time)
- Overgrowth of pathogenic bacteria e.g. C. difficile
Describe drug-induced liver injury.
Type A ADR: intrinsic hepatotoxicity (predictable, dose–dependent, acute)
Type B ADR: idiosyncratic hepatotoxicity (unpredictable, not dose dependent, and may occur at any time – may be part of a hypersensitivity reaction);
- May be due to drug, herbal product or active metabolite
- Can range from asymptomatic increase in LFTs to fulminant liver failure and death
- Generally hepatitis or cholestasis, but can mimic any pattern of acute or chronic liver disease
Describe the risk factors of drug-induced liver injury.
- Age: elderly
- Sex: female
- Alcohol consumption
- Genetic factors
- Malnourishment
Consider the severity of liver disease.
- Child-Pugh classification
- Individual scored summed and grouped as <7 = A, 7-9 = B, >9 = C
Describe prescribing in liver disease.
Care with avoidance of;
- Drugs that can be toxic due to changes in pharmacokinetics: liver metabolism, therapeutic index, biliary excretion (if biliary/cholestatic disease)
- Hepatotoxic drugs e.g. methotrexate, azathioprine
- Drugs that may worsen the non-liver aspect of disease (e.g. encephalopathy) e.g. benzodiazepines
Particular drugs;
- Warfarin/anticoagulants: clotting factors already low
- Aspirin/NSAIDs: increase bleeding time, in combo with low clotting factors, NSAIDs can worsen ascites due to fluid retention
- Opiates/benzodiazepines: may precipitate encephalopathy by increasing sedation
