principles of pharmacokinetics Flashcards
define pharmacology
the study of how medicines work and how they affect our bodies
what is pharmacology split into
- pharmacodynamics
- pharmacokinetics
define pharmacodynamics
the biochemical, physiological and molecular effects of a drug on the body
define pharmacokinetics
the fate of a chemical substance administered to a living organism
the action of drugs in the body
whats the difference between pharmacodynamics and pharmacokinetics
pharmacodynamics is what the drug does to the body whereas pharmacokinetics is what the body does to the drug
define sub competency
the general skills and behaviours that are required to be able to complete a particular competency
what are the 4 sub-competencies of prescribing to ensure safe and effective decisions
- understand the actions of drugs (and medicines) on the body
- make prescribing decisions appropriate for individual patients
- undertake appropriate monitoring - for efficacy and adverse reactions
- avoid/anticipate drug interactions
what are the 4 processes of pharmacokinetics
absorption
distribution
metabolism
excretion
define absorption
the process of transfer from the site of administration into the general or systemic circulation
give all the routes of drug administration
- oral
- intravenous
- intra - arterial
- intramuscular
- subcutaneous
- inhalational
- tropical
- sublingual
- rectal
- intrathecal
whats different about IV and IA administration
100% of the dose reaches systemic circulation without crossing any membranes whereas for any other route the drugs most cross at least one membrane to reach systemic circulation
what are the 4 mechanisms for drugs to pass across membranes
- passive diffusion through the lipid layer
- diffusion through pores or ion channels
- carrier-mediated processes
- pinocytosis
which drugs use passive diffusion
lipid-soluble drugs
which drugs use diffusion through ion channels
small molecules, water-soluble drugs
which drugs use facilitated diffusion using carrier proteins
nutrients eg glucose and some amine neurotransmitters
which drugs use active transports
lots of them
which 2 factors affect drug absoprtion
- lipid solubility
- drug ionisation
define ionisation
a basic property of most drugs that are either weak acids or weak bases
why are ionisable groups essential for drug action
as ionic forces are part of the ligand-receptor interaction
which form of drugs are regarded as more water soluble
ionised = because has poor lipid solubility and therefore is poorly absorbed
which form of drugs are regarded as more lipid soluble
un ionised
what does the proportion of ionisation depend on
the ph of the aqueous environment
what gives rapid and complete absorption of oral drugs
large SA and high blood flow of small intestine
give 4 obstacles a drug needs to overcome to reach systemic circulation
drug structure
drug formulation
gastric emptying
first pass metabolism
why is drug structure an obstacle
drugs need to be lipid soluble to be absorbed from the gut
;ipid soluble molecules diffuse down conc gradient
some drugs are unstable at low pH or in the presence of digestive enzymes so have to be given by alternative route
large or hydrophilic molecules are poorly absorbed
why is drug formulation an obstacle
the capsule/tablet must disintegrate and dissolve to be absorbed
some are formulated to dissolve slowly or have a coating that is resistant to the acidity of the stomach
why is gastric emptying an obstacle
the rate of gastric emptying determines how soon a drug taken orally is delivered to small intestine
can be slowed down via food and drugs or sped up via gastric surgery
why is first pass metabolsim an obstacle
drugs taken orally have to pass 4 major metabolic barriers to reach circulation
1. intestinal lumen
2. intestinal wall
3. liver
4. lungs
give 5 factors that affect oral drug absoprtion in the stomach
- gastric enzymes - drug molecule may be digested (peptides, proteins)
- low pH - molecule may be degraded
- food - full stomach will slow it down
- gastric motility - altered by drugs and disease state
- previous surgery - eg gastrectomy
give 3 factors that affect oral drug absorption in the intestine
- drug struture
- medicine formulation
- P - glycoprotein
give 3 types of absoprtion
intradermal and subcutaenous absoprtion
intramuscular absoprtion
inhalational absoprtion
what does P glycoprotein do
substrates are removed from intestinal endothelial cells back into lumen
describe Intradermal and subcutaneous absorption
- Avoids barrier of stratum corneum
- Mainly limited by blood flow
- Small volume can be given
- Use for local effect or to deliberately limit rate of absorption
describe intramuscular absoprtion
- Depends on blood flow and water solubility
- Increase in either enhances removal of drug from injection site
- Can make a depot injection by incorporating drug into lipophilic formulation which releases drug over days or weeks
describe inhalational absorption
- Large SA and blood flow but limited by risks of toxicity to alveoli and delivery of non-volatile drugs
- Largely restricted to volatiles such as general anesthetics and locally acting drugs such as bronchodilators in asthma
- Asthma drugs non-volatile so given as aerosol or dry powder
describe protein binding
- Many drugs can bind to plasma or tissue proteins
- may be reversible or irreversible
-The most common reversible binding occurs with the plasma protein albumin - Binding lowers the free concentration of drug and can act as a depot releasing the bound drug when the plasma concentration drops through redistribution or elimination
- Some drugs bind irreversibly and cannot re-enter the circulation and is equivalent to elimination
describe drug distribution
- Lipid soluble drugs easily pass from blood to brain
- The brain does little metabolizing and drugs are removed by diffusion into plasma, active transport in the choroid plexus or elimination in the CSF
- Lipid soluble drugs readily cross placenta
- Large molecules do not cross placenta
- Foetal liver has low levels of drug metabolizing enzymes, so relies on maternal elimination
describe elimination
- The removal of a drugs activity from the body
- May involve metabolism – the transformation of the drug molecule into a different molecule
- Or excretion – the molecule is expelled in liquid, solid or gaseous waste
describe metabolism
- Necessary for the elimination of lipid soluble drugs
- They are converted to water soluble products that are readily removed in the urine (if they remained lipid soluble they would be reabsorbed)
- Metabolism produces one or more new compounds which may show differences from the patent drug
- Drug metabolism may be divided into two phases
what are phase 1 metabolism reactions
these reactions involve the transformation of the drug to a more polar metabolite
- done by unmasking or adding a functional group
- oxidations are the commonest reactions catalyzed by CP450
what are phase 2 metabolism reactions
involves the formation of a covalent bond between the drug or its phase 1 metabolite and an endogenous substrate
- Resulting products are usually less active and readily excreted by the kidneys
what 3 things can drugs and metabolites be excreted in
fluids
solids
gases
whats excreted in fluids
important for low molecular weight polar compounds (urine, bile, sweat, tears, breast milk)
Urine excretion: Total excretion = glomerular filtration + tubular secretion – reabsorption
whats excreted in solids
faecal elimination
whats excreted in gases
expired air important for volatiles
what is the blood brain barrier
a membrane that seperated foreign substances in the blood from the CNS
it is a continuous layer of endothelial cells with tight junctions
efflux pump removes water soluble molecules
role of BBB
maintains a stable environment and protects the brain but poses a challenge for treating CNS conditions
give 3 ways for drugs to reach the CNS
- high lipid solubility
- intrathecal administration
- inflammation - causes barrier to become leaky
what are the 4 compartments in the body
fat
plasma
interstital fluid
intracellular fluid
which drug properties will influence ability to move between compartments
molecule size
lipid solubility
protein binding
define volume of distribution
the theoretical volume a drug will be distributed in the body
it is the volume of plasma required to contain the administered dose
which drugs will have a high Vd
drugs that are well distrbuted
which drugs will have a low Vd
drugs that are poorly distributed
