Pharmacology Flashcards
Bioavailability - what is definition and how to calculate it?
Bioavailability (F)
- Fraction of drug given by extravascular route (oral, IM, S/C) that is absorbed into systemic circulation
- Comparison of AUC, compared to IV AUC
- High bioavailabilty = 1, low bioavailability = 0
- Bioavailability (F) = AUC oral/AUC IV (* need to use same dose)
- Bioavailability = fraction absorbed x fraction escaping first pass clearance
AUC - definition?
AUC (Area under curve)
- How much drug patient actually gets, think serum drug presence
- For most drugs - AUC best correlated with effect
- But some drugs eg aminoglycosides- peak
DRESS - clinical features, risk medications, time?
DRESS - (Drug reaction with eosinophila and systemic Sx)
- Skin eruption, fever facial edema, lymphadenopathy, eosinophilia
- Hepatitis, nephritis, carditis
- Drugs - anticonvulsants - phenytoin, carbamazepine, lamotrogine, allopurinol, sulfonamides, NSAIDs
- HLA-B*58 (Han Chinese) - allopurine, carbamazepine
- Time -2-8 weeks after exposure
- Mx - corticosteroid
What are the phases of Clinical trials and main goals?
- Phase 1 - (20-100 subjects) - is it safe? Pharmacokinetics?
- Phase 2 - (100-200 subjects) - Does it work in patients?
- Phase 3 - (1000-6000 subjects) - Does it work, double blind?
- Phase 4 - post marketing surveillance
Clearance
Clearance = VD / Half life
What is clockwise hysteresis and anticlockwise hysteresis and causes?
Delayed distribution/anticlockwise hysteresis
- Concentration goes up then down but effect at highest
- Delay in reaching effective compartment
- Distribution delay
- Reponse delay
- Active metabolite
- Sensitisation
Clockwise hysteresis/acute tolerance
- Eg amphetamines, cocaine
- Drug concentrations soon after single dose cause greater effect than same concentration as later time
- Mechanisms - tolerance induced metabolite breakdown, minimise response, translocation receptors
- Tolerance
What are key CYP450 inducers (increase rate of metabolism?)
“COPRs”
- Carbamazepine
- OCP
- Phenytoin, phenobarbitone
- Rifampacin
- Steroid, St John’s wort
What are key CYP450 inhibitors (decrease rate of metabolism?)
“MACIC”
- Macrolides - Erythromycin, clarithromycin
- Antifungals ‘azoles’ - itraconazole, ketaconazole, fluconazole
- Calcium channel blockers - verapamil, diltiazem
- Isoniazid - TB
- Cimetidine- H2 receptor antagonist, heart burn
Key side effects gentamicin
- Nephrotoxic - 10-20%
- Ototoxic - cochlear/vestibular
- Can potential blockade of neuromuscular junction
Caffeine MOA
- Competitively antagonises bonding of adenosine to purine receptor
What is pharmacokinetics
- How drug moves in and through body - what body does to drug
- Balance between accumulation and elimination
- Factors - absorption, distribution, metabolism, elimination
- Differ in paediatric population
What is plasma concentration time curve
- Time curve - plasma concentration and time
- Area under this curve - important
- Bioavailility
- Absorption phase
- Distribution
- Elimination phase
- MEC - minimum effective concentration
What is pharmacodynamics
- Effect a drug has on human body
- Eg - effect on anti-epileptics and antihypertensive on patients
What is pharmacogenetics
- Genetic factors have major impact on drug metabolism and development of drug receptors
- Cytochrome P450 - complicated by changes in metabolic pathway and changes in development of receptors
Absorption - what is it and process
Process of absorption
- Taken into blood stream after administration by different routes:
- Oral/buccal/sublingual, IV, IM, percutaneous, rectal
- Move to sites of absorption –> cross mutliple GI membranes before passing into systemic circulation (first pass metabolism)
- Passive diffusion, sometimes due to active
- Factors affecting - pH, gastric emptying
- Different in neonates, older children and adults
- Insufficient in neonates
- Affected by maturation process of organ systems
