Pharmacokinetics Flashcards
Window of therapeutic index?
Safer is window is as big as possible
If above window then TOXIC
If lower doesn’t meet effective concentration
ADME
- Absorption
- Distribution
- Metabolism
- Excretion
Compliance
Patients willingness to take drugs
Routes of drug administration
- Enteral (oral rectal)
- Parenteral (subcutaneous/ intramuscular/ intravenous)
- Percutaneous (inhalation/ Sublingual/ topical)
Absorption depends on:
Route of administration
Blood flow at site of administration
Drug solubility
Active vs passive diffusion
Dose of drug
What is bioavailability
Fraction of the total dose administered that reaches the plasma
Does drug diffuse directly to target organs?
No. Drug randomly diffuses.
Chemical properties of a drug:
Chemical nature
Molecular weight
Solubility
Partition coefficient
What affects the absorption of drugs from gastrointestinal tract :
- formulation of drug
- stability of drug (digestive enzymes)
- time available for absorption (tansit time, diarrhoea)
- lipid solubility
- interaction with food
- conc of drug
- blood flow
Pharmaceutical interventions influencing absorption:
- particle size (dry powder inhaler)
- coating of tablets
What is enteric coating of tablets?
Slow-release
Solid core around it and water diffuses in and releases drug
Factors affecting transdermal (through skin) absorption:
- lipid solubility
- formulation
- skin thickness
- hydration
- blood flow
Pinocytosis?
Facilitated diffusion and active transport
Lipophilicity?
Strongly decides whether a compound an pass through membrane
Distribution depends on:
- lipid solubility
- diffusion barriers
- tissue binding
- plasma protein binding (albumin)
One compartment model?
Assume the body is one whole compartment
Pharmacokinetics view of the body (specific properties):
- how many membranes
- pH value
- circulation
- size of surface area
- any diffusion barriers
- any inactivating enzymes
Special highly regulated diffusion barriers?
- Blood brain barrier
- Placenta
AVD
Apparent volume of distribution
The notional volume of fluid required to dilute
the absorbed dose to the concentration found in plasma
How extensively a drug is distributed in the body
What is the AVD of drug that is heavily plasma protein bound?
Low ~ 6 litres
AVD if drug heavily tissue bound?
High ~ More than 70 litres
Bcs concentration of drug in the blood is lower
AVD= drug mass/ conc
Two compartment model?
Central and periphery compartments
The central compartment (compartment 1) consists of the plasma and tissues where the distribution of the drug is practically instantaneous. The peripheral compartment (compartment 2) consists of tissues where the distribution of the drug is slower.
Ion trapping?
Many drugs exist in eqm btw ionised and unionised forms
Only unionised form is lipid soluble and infuses through membranes
Charged molecules can’t diffuse back out so traps them
Protonisable groups?
COOH
NH2
Where will drugs tend to accumulate?
In area where ionisation is favoured
Where weak acidic drugs absorbed and accumulate
Tend to be well absorbed from acidic environments and accumulate in basic environments
Where Basic drugs absorbed and accumulate
Well Absorb from basic environments and accumulate in acidic environments
Why are basic drugs secreted into the stomach?
Because of ion trapping
pH is acidic in stomach
And basic drugs accumulate in acidic environments
Were are acidic drugs excreted?
In urine
First pass metabolism?
Drug gets metabolised at a specific location in the body that results in reduced concentration of the active drug upon reaching site of action
Which administrative route has a high first pass metabolism effect?
Orally
How does plasma protein binding affect distribution of drug?
Unbound drugs free to diffuse into tissue
Med with low plasma protein binding distributed readily
Med with high binding has a longer duration of action
Where does metabolism occur?
Liver (first pass metabolism)
Kidney
Skin/ lungs
Microbiome
Why is knowledge of first pass metabolism important ?
Can assist the prescriber when deciding on doses and dose schedules
to ensure correct dosing by correct route for optimum effect
In bio transformation is there reduction and oxidation of drugs?
No.
Mainly oxidation (via cytochrome p450 enzymes) - addition of hydroxyl groups
conjugation (attaching small polar molecules on drugs) - addition of small polar groups
What does metabolism do to drug?
Usually inactivates drug but can activate them too
Ways of Excretion of drugs?
- Kidney - into urine
- Liver - into bile, enterohepatic circulation
- Lungs - exhalation
- Saliva, sweat, milk
What bodily fluids are usually used for drug analytics
Urine
Saliva
Blood
Preclinical outcomes of studying pharmacokinetics
- Select drugs with max potential for reaching target
- Select appropriate route of administration to deliver drug
- Blood levels relate to efficacy/ toxicity so an select safe doses
- decide Frequency and duration of dosing
What drugs have high volumes of distribution
Lipophillic
Basic drugs
What drug is heavily plasma protein bound?
Acidic drugs
What drug is heavily tissue bound?
Basic drugs
What is the definition of pharmacokinetics
Study of the movement of drugs in the body
What does it mean if AVD is high
Less drug stays in blood (vascular space)
More drugs absorbed into organ systems
What does it mean if AVD is low
More drug stays in vascular space
Distribution in two compartment models
Distribution takes time
Not instantaneous like one compartment model
AVD of two compartment model
AVD becomes larger until eqm is reached and as drug distributes further
Why has two compartment model got a bi exponential decline
Initially decline is plasma drug conc due to elimination and distribution (steep)
Later decline in plasma drug conc due ONLY to elimination (slower)
What is the AVD for one compartment model
Constant from beginning
Why is one compartment model mono exponential
Decline in plasma drug corn is ONLY due to elimination
