Pharmacokinetics 1 Flashcards
What is pharmacokinetics?
The variation of the concentration of drugs in the body by the processes of absorption, distribution, metabolism and excretion
Why do we consider pharmacokinetics?
-effective targeting
-bioavailability
-ensuring the dose gives a plasma conc within a therapeutic range
What may call for close monitoring?
Individual variability in response and narrow therapeutic range
What causes individual variability in response ?
Membrane carrier systems
CYP enzymes
What’s a CYP enzyme ?
Cytochrome p450
What is pharmacogenetics for?
Working towards personalised medidcne
What is achieved with a dosing interval ?
Steady state plasma concentration and therapeutic range
what is bioavailability
Amount of drug reaching the systemic circulation
What. Determines the CHOICE of route of administration?
Factors influencing bioavailability by various routes
What factors determine the route of administration ?
- patient compliance
- chemical nature
- formulation of drug
- accessibility of target
-speed of onset and duration of action
Why are cell membranes important for drugs ?
Barriers between body compartments
Must be crossed by drugs so they reach their target
What affects a drugs ability to penetrate hydrophobic barriers ?
-molecular size
-lipid solubility
-polarity/charge/degree of ionisation
- access to membrane carrier systems
What is the lipinski rule of 5
-no more that 5 hydrogen bond donors
- no more than 10 hydrogen bond acceptors
- molecular weight below 500
- ClogP not greater than 5
What are enteral routes of administration?
Oral, sublingual, buccal, rectal
What is an enteral route of administration influenced by ?
- formulation of drug
- presence of food in stomach
- pH variation in GI tract
- stability to acid and enzymes
- lipid solubility
- first pass elimination effect
- motility of gut
What state can a drug cross a membrane ?
Unionised
What determines the amount of unionised drug ?
- pH of surroundings
- pKa value of drug (pH at which 50% is ionised)
What is the Henderson-hasselbach equation ?
In what state is a drug likely to exist in its ionised state ?
If the pH of surroundings is further away from its pKa value
Explain the pH influence on aspirin ?
pKa= 3.5 (weak acid)
- absorption from stomach favoured due to low pH
- high proportion of drug in unionised form
- slower uptake into plasma (higher pH, more Ci)
Explain the influence of pH on pethidine ?
(pKa = 8.6)
- weak base
- large proportion as Ci in stomach
- poorly absorbed
- can only be given paternally or via SR capsule
What are the routes of parenteral administration? (5)
- intravenous
- intramuscular
- subcutaneous
- intrathecal (space between spinal chord and lining)
- topical
- inhalational
How does an IV route of administration differ from an oral route graphically ?
Give an example of a topical route
- slow release dermal patch
