Alimentary Pharmacology Flashcards
Liver disease: Identify patients with impaired liver function
- Use albumin and PT to establish synthetic function of the liver
- These parameters tend to decrease in the advanced stages of liver failure
- NOTE: PT and INR may be decreased due to Vitamin K deficiency
- LFR tests do not provide information on synthetic abilty, only on damage
Liver disease: Discuss how pharmacokinetic parameters alter due to liver disease
Absorption:
- Decreased due to decreased GI motility
- Decreased first pass metabolism causes increased bioavailabilty
Distribution:
- Ascites and oedema change distribution
- Hypoalbuminaemia: Decreased transport
Metabolism:
- Decreased levels of hepatic metabolic enzymes
- Lipid soluble drugs not metabolised to water soluble
- Drugs with high extraction ratio will experience decreased clearance
- Extraction ratio: The amount of parent drug that is irreversibly removed from the blood with each pass through the liver
- Determined by blood flow through the liver
Excretion:
- Reduced renal clearance. For drugs with narrow therapeutic window this is particularly detrimental
Liver disease: Describe how pharmacodynamic properties may alter and list 3 medicines affected
↑ response, ↓ effect, ↑ toxicity (RET)
- Benzodiazopines (sedatives)
- anticoagulants
- Opiates
- diuretics
- nephrotoxic medicines
Liver disease: List 5 medicines/medicine classes to use with caution or avoid in patients with impaired liver function
- Electrolyte disturbing medicines e.g. diuretics
- Constipating medications
- Herbal medicines
- Encephalopathy inducing medicines e.g. diuretics
- Hepatotoxic medicines
- Nephrotoxic medicines
- Medicines with haematological effects e.g. warfarin
Liver disease: List general considerations for prescribing in patients with impaired liver function
- Age
- Gender
- Alcohol abuse
- Nutritional status
- Systemic disease
- Other medications
Adverse drug reactions: Define ADR
ADR: An unwanted/unpleasant effect that occurs at the desired dose of a medication
☆Toxicity occurs above the desired dose
Adverse drug reactions: Discuss what types of ADR can occur
On-target: Occur due to the action of the drug on its target receptor
Off-target: Occur due to the action of the drug on an unintended target
A-E classification:
- Augmented: Exaggeration of effects (on-target) can be reduced with dose. Predictable and preventable
- Bizarre: Not predictable. Normally very serious
- Continuing: Persist for long periods
- Delayed: Occur following use of a medication
- End of use: Associated with withdrawal of medicines
Adverse drug reactions: State 2 types of ADR and distinguish between them
Bizarre: Unpredictable. Anaphylaxis to beta-lactams.
Augmented: Linked to on-target, e.g. ACE inhibitors acting at receptors in other regions
Adverse drug reactions: Identify factors which predispose patients towards developing an ADR
- Polypharmacy
- Decreased hepatic/renal function
- Age
Adverse drug reactions: Outline how the safety of medicines is tested and monitored
Tested: Laboratory tests, testing on healthy individuals, clinical tests of small group large group clinical trial, drug licensed and marketed
Monitored: Pharmacovigilance. Yellow card scheme to report side-effects
Adverse effects: Suggest ways to avoid ADRs
- Low doses
- Avoid polypharmacy
- Short courses
- Low first dose
- Avoid in women of child bearing age
Drug interactions: State the pharmacokinetic and pharmacodynamic mechanisms that underlie most drug interactions
Pharmacokinetics:
- Absorption: Presence of food, GI emptying, chelation,
- Metabolism: CytP450 can be affected by food and medications
- Distribution: Displacement from binding protein, increases bioavailabilty
- Excretion: Changes in GFR
Pharmacodynamics:
Toxicity
Drug interactions: Recogise which drugs are likely to pose a problem
Warfarin
Insulin
Lithium
Digoxin
C
A
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Outline the physiological mechanisms in nausea and vomiting and the transmitter involved
Triggers:
- Severe emotion, disturbing site etc. Th frontal cortex signals to the vomiting centre
- The CTZ may signal to the vomiting centre
- Signals from the stomach (via vagus) to the vomiting centre
- Signals from the vestibular centre to the vomiting centre
CTZ: D2, 5-HT (CDS)
Vestibular centre: H1, Muscarinic
Vomiting centre: Muscarinic, 5-HT, H1 (M&S H)
Stomach: Vagus through release of 5-HT
Anti-emetics: H1 antagonists
- Effective against most causes of emesis, particularly vestibular
- Some antimuscarinic action
- Example: Cyclizine
ADR:
- Sedation, antimuscarinic effects
Anti-emetics: D2 antagonists
- Effective against CTZ and GIT receptor induced emesis
- Some of this group also have antimuscarinic and antihistaminic effects
ADRs:
- EPSE (problems with movement e.g. dystonia)
- Dizziness
- Drowsiness
Anti-emetics: Antimuscarinics
-
More effective than antihistamines but less well tolerated
- Due to antimuscarinic side effects e.g. dry mouth, drowsiness, blurred vision and urinary retention
- Effective for motion sickess and post-operative vomiting
Example: hyoscine butylbromide
Anti-emetics: Serotonin antagonist (5-HT)
- Highly effective against cancer chemotherapy induced emesis
- Post-operative
Mild side effects:
- Constipation
- Flushing
- Headache
- Fatigue
Anti-emetics:
Dexamethasome, neurokinin 1-receptor antagonists, nabilone, benzodiazepines
Dexamethosone: Chemotherapy and post-operative
Neurokinin 1-receptor antagonists: Cisplatin
Nabilone
Benxodiazepenes: Anticipatory N&V
Constipation: List drugs that commonly cause constipation
- Iron salts
- Antimuscarinics
- Calcium channel blockers
- Opiates
- Diuretics
- Calcium
Laxatives: Bulk-forming laxatives
MOA:
- Addition of indigestable polysaccharides
- Causes the retention of fluid in faecal mass and subsequent stretching
- This activates stretch receptors and promotes peristalsis
- Example: Husk
Notes:
- Take several days to work
- Adequate fluid intake essential
Side effects:
- Flatulence
- Abdominal distension
- Bloating
- DO NOT USE WITH OPIATES
Laxatives: Osmotic laxatives
MOA:
- Semisynthetic disaccharide or poorly absorbed ions
- Draw in fluid via osmotic effect, increasing faecal volume
Notes:
- Takes 2-3 days to work
- Need to take regularly
- Requires high fluid intake
Side effects:
- Bloating
- Flatulence
- Cramps
- Electrolyte disturbances
Laxatives: Stool softeners
MOA:
- Reduce the surface tension of faeces, increasing the amount of fluid able to be taken into the faeces
- Soften the faeces
Notes:
- Effect occurs after 1-3 days
Laxatives: Stimulant laxatives
MOA:
- Directly stimulate the colonic nerves, prompting propulsive movements
- Example: Senna
Notes:
- Effect within 8-12 hours
- Use with opioids
Side effects:
- Abdominal crmap
- Caution with long term use
- Avoid in intestional obstruction
Diarrhoea: List drugs that cause diarrhoea
- Beta-blockers
- Digoxin
- Antibiotics
- Metformin
- Antacids with magnesium
- PPIs
Management of diarrhoea: Fluid replacement
Oral rehydration therapy
Management of diarrhoea: Racecadotril
- Prodrug
- Enkephalinase inhibitor
- Inhibits the breakdown of endogenous opioids → reducing intestinal secretions
- Used for uncomplicated diarrhoea
Management of diarrhoea: Anti-motility agents
Examples: Opioids, Codeine, loperamide
- Eluxadoline: Used for irritable bowel syndrome
MOA: Enhance segmental contractions in the colon. Prolong transit time by inhibiting propulsive movements of the small intestine and colon.
