Lec 2- Clinical pharmaceutics Flashcards
1
Q
Checklist for claims
A
-
Prove
- Statistical analysis
- Experimental design, sample size, power
- Statistical parameters
- Statistical analysis
- Demonstrate
- Indicate
- Suspect
- Claim
- State
- Imply
- Assume
2
Q
Checklist for evidence
A
- Systematic reviews and meta-analysis
- Review and analysis of all reported studies
- Randomised controlled, double-blind trials
- E.g. identical groups- one a control, one a test
- Cohort studies
- Same patients followed over time
- Case-control study
- Patients are compared on the basis of case history
- Case series
- Collection of reports of single patients with similar conditions
- Case reports (yellow cards)
- Medical history of a single patient
3
Q
Perceptions of evidence- some questions
A
- Interpretations may depend upon the observer
- Are the results or conclusions possible
- Are conclusions supported by the data
- Does missing evidence present the wrong conclusion
- Is the evidence ambiguous
- Are we excluding information by focusing too closely
- Are there hidden means in the data
- Can we extrapolate meaningfully
- Are the statistics adequate
4
Q
Two clinical trials
A
5
Q
Pharmaceutical factors influencing clinical outcomes
1) Packaging (co-amoxiclav- why an extra layer of foil)
A
- The patient feels “we care”
- Presents a quality image for the product
- Allows a premium price to be charged
- Presents a useful marketing image
- Protects from light
- Foil also reduces ingress of moisture and reduces hydrolysis
6
Q
Evidence: structure, properties and stabilities
A
7
Q
The real reason for extra packaging
A
- Compared to amoxicillin
- Clavulanic acid is much more susceptible to hydrolysis
- Therefore, give extra protection from moisture
8
Q
2a) Rifampicin adsorption
A
- TB therapy
- Almost 1/3 of humanity infected with TB
- About 2 million deaths per annum
- Anti-TB drugs
- Rifampicin and p-aminosalicylic acid (PAS)
- Bentonite added as an excipient to PAS granules- aid with flowability of formulation
- Combination therapy
- Rifampicin adsorbs to bentonite
- Bioavailability reduced
9
Q
2B) excipients and metabolism
A
- Amprenavir (Agenerase) GSK
- HIV protease inhibitor
- Available as capsules and oral solution
- Poorly water-soluble
- Propylene glycol used as the solvent
- Propylene glycol metabolised by
- Alcohol and aldehyde dehydrogenase activity
10
Q
2B) Metabolism of PG
A
- Alcohol and aldehyde dehydrogenase
- Activity low in
- Infants
- Children U4
- Pregnancy
- Patients with hepatic and renal failure
- Patients treated with disulfiram or metronidazole
- Activity low in
- Failure to metabolise PG
- Accumulation and potential adverse effects
11
Q
2C) Excipients intolerance
A
- Lactose
- Present in ~20% of formulations
- Intolerance in perhaps 5% of Europeans
- Low intestinal lactase activity
- Acts as a non-digestible, osmotic carbohydrate
- Present in ~20% of formulations
- Colouring agents
- Tartrazine
- Hypersensitivity
- Tartrazine
- Preservatives
- Contact sensitisation- eczemoid dermatitis
- Chlorocresol- in Aq cream
- Parabens- common in liquid preparations
- Contact sensitisation- eczemoid dermatitis
12
Q
3) Bioavailability
Rifampicin combinations
TB therapy
A
- Rifampicin
- Isoniazid
- Pyranzinamide
- Ethambutol
- Combination products
13
Q
Rifampicin Bioavailability
A
- Concern over poor rifampicin absorption from combination products
- Bioavailability problems with formulations with adequate dissolution profiles
- Possible in vivo stability problems
- Take on an empty stomach
- pH 1.5-2.0
14
Q
PK parameters
A
- AUC for rifampicin was substantially lower when given in combination (34-29% decrease)
15
Q
Degradation in acidic conditions
Effect of other drugs
A
