Pharmacokinectics Flashcards
What is Pharmacokinetics?
What the body does to the body
Branch of pharmacology
What is a drug?
Any substance used for the treatment, relief, diagnosis or prevention (prophylaxis) of disease
What are the 3 main sources of drugs?
1) plant origin- e.g. Digoxin (foxglove)
2) animal origin- e.g. Insulin previously from pigs
3) mineral origin- e.g. Magnesium
What are the 2 main routes of administration?
Parenteral
Enteral
What is the definition of enteral?
Anything involving the digestive tract
From the mouth to the rectum
What is the definition of parenteral?
‘To avoid the gut’
Any route other than via the GI tract
What are examples of enteral administration?
Oral
Rectal
Sublingual (under the tongue)
What are examples of parenteral administration?
Subcutaneous
Intramuscular
Intravenous
What are the 4 stages of pharmacokinetics?
1) absorption
2) distribution
3) metabolism
4) excretion
What is drug absorption?
From administration though to the time it reaches the tissues and so is available to us
May involve getting into the circulation
Oral drugs must be converted into a solution via Dissolution to be absorbed
Quicker a drug is converted into soluble state, faster it can be absorbed across cell membranes
What processes allow absorption across cell membranes?
Passive transport and active transport
What is the process of passive transport?
Requires no energy (ATP)
Movement of substances down conc. gradient from high to low concentration
E.g. High in GI tract to low in bloodstream (oral drugs)
What is the process of active transport?
Requires energy (ATP)
Movement of substances from a low to a high conc. (against conc. gradient)
E.g. Levodopa- treats Parkinson’s disease
Carrier molecules may be involved
How can distribution take place?
Bloodstream transports the drug to its site of action
How does blood flow to a tissue affect a distribution?
Drugs will ultimately get to all tissues
Drugs initially may reach higher conc. in tissues with a good blood supply e.g. Brain/heart
Reduced flow to tissues and organs affect distribution
Blood brain supply (prevents bacteria/toxins entering the brain)
What is the function of the brain blood barrier?
Prevents any substances from entering the CNS
Some substances are blocked from entering brain tissue- acts as protective mechanism- prevents harmful substances entering the brain
What is a free drug?
The part of the drug that is not bound
Can exert its effects on tissues
Distribution depends on properties of the drugs e.g. Lipid solubility etc
The free drug is the only active part- small enough to leave the bloodstream
What is metabolism?
Involves transforming drug so it is more water-soluble and can be excreted
Main site- liver (other tissues involved- plasma, kidneys, lungs and intestinal mucosa)
What is the function of metabolism?
Drugs metabolised into inactive metabolites and excreted
Some metabolites are already active so exert own action and then undergo further metabolism or are excreted unchanged
Some metabolites require altering to become active
What is the function of liver cells in metabolism?
Attempt to break down the drugs into constituent parts so they can be eliminated
What is the First Pass Effect?
Shows effect liver metabolism has had on the drug during its first passage through the liver (how much drug has been broken down in the liver)
How much of the drug has been inactivated
The drug always has to first pass through the liver to be broken down before it is able to circulate the rest of the body
What are the 3 determinations that can be made from the first pass effect?
1) amount of drug reaching general circulation
2) half-life of drug (time taken for half the drug to be eliminated from the plasma)
3) whether the drug undergoes ‘biotransformation’
What is biotransformation?
The conversion of molecules from one form to another within an organism, often associated with change in pharmacologic activity
May involve drug being changed from an inactive to an active state
‘Pro drugs’
What is excretion?
Involve active or inactive drugs
Requires removal from site of action
Main organ- kidney
What are the main organs involved in elimination of drugs?
Kidney Gut Skin Lungs Salivary glands Sweat glands
What is bioavailability?
Used to describe the fraction of an administration dose of the drug reaching the systematic circulation
E.g. If bioavailability is 50%, half the dose reaches the systematic circulation
If low- higher dose is required and excess will remain in the GI tract
What factors affect bioavailability?
Route of administration
Properties of drugs
Absorption
Blood flow to administration site
First pass effect
What is the definition of onset?
Time from administration to when the therapeutic effect occurs and is affected by routes of administration and pharmacokinetics
What is the effect of intravenous administration?
Gives the quickest route
Most brief pain control
Most CNS side effects
What is the effect of oral administration?
Maximises duration of analgesia
Minimises CNS side effects
Longest time to onset of relief
What dictates the timings of repeat doses?
1) rate of absorption
2) metabolism of the drug
3) excretion
What is the definition of steady state?
Reached when rate of infusion is equal to rate of elimination
What is the function of modified released drugs?
Designed to slowly release drug into GI tract over a period of time
What are the benefits of modified release oral preparations?
1) dose frequency is reduced- increased compliance
2) peak plasma level reduced- less side effects
3) less peaks and troughs in plasma levels- more sustained therapeutic effect
Give 2 examples of modified release preparations…
Propranolol
Ibuprofen
What is the definition of therapeutic range?
Optimum plasma levels in which it has its therapeutic effect
What is the therapeutic window?
Describes levels in plasma at which a drug can act
Aiming for drug concentration to be within this window
Narrow- require monitoring
What does MTC and MEC stand for?
MTC- maximum tolerated concentration
MEC- minimum effective concentration
What does Iatrogenic mean?
Illness caused by medicine, examination or treatment
How do pharmacokinetic changes affect older people?
Most important is the reduction of kidney function so care must be taken with drug toxicity and its effect on the kidney
How do pharmacodynamics affect old people?
They are more sensitive to drugs acting in CNS and drugs causing side effects in the stomach/intestine
What is drug tolerance?
Describes the decrease in pharmacological effect when a drug is given repeatedly
Causing progressively higher doses required to produce the same effects
Various pharmacokinetics/pharmacodynamics mechanisms- tolerance
E.g. PK mechanisms- increased metabolism of drug
E.g. PD mechanisms- reduced receptor numbers at cell surface
What does the term drug dependence mean?
A compulsion/compulsive need to take a drug in order to function normally (even if it causes harm)
Lead to withdrawal symptoms e.g. Diahorrea, shivering, muscle ache, dilated pupils, sweating and abdominal cramps
Body adapts to the drug and so stabilises
Causes the body to overcompensate for the drug which is no longer present
