Session 1 - Pharmacokinetics Flashcards
Define pharmacology
The study of drugs
Define pharmacokinetics
The study of what the body does to the drug
Define pharmacodynamics
The study of what the drug does to the body
Define pharmacotherapeutics
The study of how to use the right drug at the right time
What are the 4 (ADME) principles of pharmacokinetics ?
Absorb
Metabolism
Distribution
Excretion
Where does oral tablets get metabolised ?
Within the liver
Define absorption
The movement of a drug into the blood circulation
Where will orally administered drugs be absorbed ?
Some of the drug will be absorbed through the stomach lining, however most absorption occurs in the small intestines.
After a drug has been absorbed by the small intestines, where does it go ? And what happens to it
Directly to the liver
Undergo first pass metabolism
Name 4 factors that effect absorption
- Food
- Other medicines - some medicines bind together and form a large compound which makes absorption difficult .
- Controlled released drugs and enteric coated drugs
- Route of administration
Explain first pass metabolism
- Drugs absorbed by the GI tract are transported to the liver before being circulated to the rest of the body.
- The liver will metabolise a lot of the drug before it enters circulation as it sees the drug as a toxin.
- Often higher concentrations of oral drugs are required to achieve the desired effect.
What is bioavailability ?
The extent of metabolism will determine the amount of drug that appears in the circulation to preform its therapeutic task. This is known as bioavailability and is often expressed as a percentage.
Define distribution
The transfer of the drug from the general circulation into different organs in the body,
Name 4 factors that effect the distribution of a drug.
- Affinity of the drug for plasma protein.
- Size, solubility and polarity of the drug.
- Acidity of drug in solution
- Blood supply to the tissue
Define excretion
The elimination of a drug, usually by the kidneys as urine.
Explain 5 ways drugs can be eliminated
- kidneys as urine (most common)
- The lungs
- Exocrine glands (Saliva, breast milk, and tears)
- The skin
- The GI tract
Define “half life value”
Time it takes for 50% of an administered dosage to be eliminated.
What may increase a drugs half life ?
Hepatic disease.
Explain the term therapeutic range.
It is necessary to have adequate plasma concentrations of a drug within the plasma to achieve a therapeutic range
Which is why we test for drug “levels”
Define drug potency
Absolute amount of drug required to produce an effect
A more potent drug is one that requires lower dose to cause the same effect
What solubility is a polar molecule ?
Water soluble
What solubility is a non polar molecule ?
Lipid soluble
What can a polar molecule do ?
Travel within the blood stream.
Plasma contains water.
What can a non polar molecule do ?
Travel through the cell membranes phospholipid bilayer.
What can a non polar molecule not do ?
Travel within the blood stream by itself due to it “hating water” it has to be carried by a plasma protein.
Explain plasma protein binding
- Proteins such as albumin can bind to many drugs
- Only the drug which is not bound is available to the body
- If alot of the drug binds to the proteins then there is less drug available.
How much warfarin is plasma protein bound ? What does this mean ?
Warfarin is 97% plasma protein bound. Only 3% is actually active and may be excreted.
Case study
Jack is on warfarin, he has been prescribed sodium valproate. Shortly afterwards, he notices that he bleeds and bruises easier.
The sodium valproate displaces the warfarin as it has a stronger plasma protein binding. This means less warfarin is bound to the plasma protein which means there is more warfarin available to the bloodstream. The more warfarin exists as a free drug the more it effects the body, due to warfarin being a blood thinner this is what causes the increase bruising and bleeding.
What may effect protein levels within the blood ?
- liver disease - the source of protein production
- malnutrition - loss of protein
- anorexia - loss of protein
Name the factors that affect plasma protein binding and explain what it means.
- Elderly - reduced protein in the blood
- Reduction in albumin
- liver disorders
- malnutrition/anorexia
- Other drugs - competition for plasma protein
It means that a given dose of the drug will now have a greater effect as less of the drug is plasma protein bound and therefore a smaller dose may be required.
Explain the movement from of an orally administered drug to the systemic circulation.
- absorbed through the small intestines.
- the drug molecules enter the mesenteric vessels which will drain nutrient rich blood away from the intestines to the liver via the hepatic portal vein.
What is acetaminophen more commonly known as ?
Paracetamol
What is paracetamols bioavailability?
88%
Explain why morphine sulphate oral dose is 15-30mg where as it’s intravenous dose is 1-10mg (70kg adult male)
Morphine sulphates bioavailability is 24% after undergoing first pass metabolism
Name a drug that can not be given orally and explain why.
GTN (glyceryl trinitrate) undergoes high first pass metabolism so if given orally there would be given no effect of the tablet.
Sublingual administration bypasses first pass metabolism and thereby reaches the blood stream directly.
Why is a drugs half life important ?
It will inform us how frequently the drug should be administered.
What is paracetamols half life ?
2 hours
What enzymes are present within the liver ?
P450 enzymes
What do p450 enzymes do to a drug ?
Break them down
What is a prodrug ?
An inactive compound which can be metabolised to become active
What should be taken into consideration with pregnant women ?
Drug can cross into placenta and breast milk
Consideration with children
Higher proportion of water
Lower plasma protein level - more available drug
Immature liver/kidney may be metabolised or excreted slower
Considerations with older people
Body fat increases
Body water decreases
Plasma proteins decrease
What medication anti sickness medication can increase gut transit time ?
Metoclopramide
Explain phase 1 and phase 2 metabolism in terms of asprin
Phase 1 - p450 enzymes transfer asprin (inactive ) to salycilic acid (active)
Phase 2 - the drug is transformed to a water soluble drug for excretion
Explain phase 1 metabolism
Adding or removing functional groups by
- oxidation ( most common, use cytochrome p450 enzymes)
- reduction
- hydrolysis
To increase the polarity of a drug. Can convert a drug to its active metabolite.
Explain phase 2 metabolism
Known as conjugation, involves the attachment of an ionised group to the drug.
These groups include glutathione, methyl, or acetyl groups.
Makes drugs more water
What are the 2 metabolites that can be produced following metabolism ?
Active metabolite or inactive metabolite
What is an active metabolite ?
A drug that retains the same activity as the parent drug eg remains active.
Such as codeine is metabolised into morphine
What’s an inactive metabolite.
A drug that has no pharmacological activity of the original drug
What is a pro drug ?
A drug that’s administered as in inactive form which is metabolised to an active form.
What drugs can diffuse easily into the placenta ?
Drugs with a low molecular weight
Drugs with a high molecular weight are less likely to pass to the placenta
