Pharmacokinetics 1 Flashcards
What does pharmacology mean?
Origin, nature, chemistry, effects and uses of drugs
What does toxicology mean?
Study of the adverse effects of chemical, physical or biological agents
What does pharmacodynamics mean?
What the drug does to the body
What does pharmacokinetics mean?
What the body does to the drug
What are the 5 stages that a drug will undergo pharmacokinetically as it passes through the body?
(Liberation) Absorption Distribution Metabolism Excretion
(Write some on routes of drug administration)
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What is the bioavailability of a drug?
Fraction of unchanged drug that reaches the systemic circulation
IV injection gives 100% bioavailability
What are the four ways that small molecules cross cell membranes?
1) Diffusing directly through the lipid
- Lipid solubility highly importan
2) Diffusing through aqueous pores
- More likely important for diffusion of gases
3) Transmembrane carrier protein
- e.g. solute carriers
4)
Pinocytosis
- Mostly macromolecules, not drugs
Describe the solubility of hydrophilic and lipophilic drugs
Hydrophilic drugs are soluble in aqueous, polar media.
Lipophilic drugs are soluble in fats and non-polar solutions
What parts of the cell will hydrophilic and lipophilic drugs pass through respectively?
Blood plasma, cytosol and interstitial fluid are aqueous, polar media.
The interior of the lipid bilayer and fat are non-polar.
Why is drug absorption linked to ionisation?
Many drugs are weak acids or bases
• Ionised:unionised ratio depends on pH
• Ionised drugs have low lipid solubility
What are the pH ranges of areas of the body?
Gastric acid (pH 1.0–3.0) Large intestine (pH 8.0) Small intestine (pH 5.0–6.0) Plasma (pH 7.4)
In what situations will there be barriers to drug absorption?
The route of administration is affected by both drug and by patient factors so unless the drug is injected directly to the systemic circulation, there are always going to be barriers to absorption
What are the main drug properties that affect absorption?
lipophilicity and ionisation
What factors affect drug distribution?
Degree of drug ionisation Lipid solubility pH of compartments Cardiac output and blood flow Capillary permeability Plasma protein binding
According to compartment model what step does an intravenous dose Q skip to reach peripheral compartment (k12->
Absorption (kabs) ->Volume Vd a single well-stirred compartment
What do biphosphonates travel to?
Phosphonate groups have a high affinity for calcium
Quickly distributed to the skeleton
Give an example of a couple of biphosphonates up to no good in my neighbourhood
Oral alendronate
– Daily/weekly
IV zoledronate
– Yearly
Used to treat bone diseases like osteoporosis
What is required for a drug to take effect on the body
A drug must be free to distribute widely or bind to its receptor
Discuss protein binding in pharmacokinetics
A drug must be free to distribute widely or bind to its receptor
Many drugs bind to plasma proteins
Fraction of unbound drug can be as low as 1%
• Competition for binding sites can cause big increases in free drug concentrations
What are some drugs that bind to plasma proteins?
– Albumin
– α-1 acid glycoprotein
– Lipoproteins
– Globulins
What relationship do warfarin and aspirin have in common?
98% of warfarin bound to albumin Aspirin has high affinity for albumin
What effect does the relationship between aspirin present in the body have on administered warfarin
Less warfarin is able to bind to albumin so there is a greater percentage of unbound warfarin
Where is body water distributed?
To four main compartments - specialist compartments exist and factors such as perfusion influence distribution
What impacts the distribution between the compartments that contain body water?
The degree of distribution between these compartments depends on tissue- and drug- dependent factors
Why is an understanding of drug distribution important?
Side-effects of some drugs can be minimised by limiting their distribution via the route of administration
Give an example of some muscarinic ACh receptor agonists?
Pilocarpine Non-selective muscarinic agonist Constriction of pupils (miosis) Glaucoma (to decrease IOP) Xerostomia (following head/neck radiotherapy)
Bethanechol
Non-selective muscarinic agonist
Bladder and gastrointestinal hypotonia
What are the learning outcomes of this section?
To define the four main criteria of ADME.
To list the major routes of drug administration plus their benefits and drawbacks.
To relate the general chemical properties of a drug to its subsequent absorption and distribution throughout the body.
To explain the general concept of pharmacokinetic compartments.
To discuss the effects of protein binding upon the distribution and availability of drugs within the body.
To identify the major physiological factors affecting drug absorption and distribution.
