DRUG ABSORPTION, DISTRIBUTION, Flashcards
Talk through the journey of a drug through the body
- Absorption
- Targets Site of action
- Metabolism
- Excretion
How do drugs enter the body
They have to cross barriers to be able to enter eg skin, gut walls
What happens once a drug is absorbed into the body
The blood distributes the drug to the sites of action across more barriers
Where are drugs metabolised and excreted
Kidney and or liver
What does ADME stand fro
Absorption
Distribution
Metabolism
Excretion
For which drugs is the acronym ADME relevant for
ALL DRUGS can be used to manipulate the treatment to make ti more effective
How can drugs be absorbed into the body
- Enteral
2. Parenteral
What is enteral
In or through the digestive system
Give some way s a drug can be absorbed enterally
- Oral
- Sublingual
- Buccal
- Rectal
What does parenteral mean
Taken into the body in a way other than through GIT
Give some way s a drug can be absorbed parenterally
- Subcutaneous
- intramuscularly
- intravenously
How can drugs pass through and get to their target site
- Diffuse passively
- Cells throng pores eg aqaporins
- Carrier to facilitate their transport into cells
How is insulin absorbed into the CNS
Pinocytosis or “cell drinking”
What dictates whether a drug can diffuse across a cell membrane
Lipid solubility and the concentration gradient
List some factor affecting oral absorption
- Disintegration of dosage forms
- Dissolution of particles
- Chemical stability of the drug
- Motility and mixing in the Gastrointestinal tract
- Presence and type of food
- Passage across gastrointestinal tract wall
- Blood flow to gastrointestinal tract
- Gastric emptying time
- Formulation
What is bioavailability
Is the proportion of the drug in a dosage form available to the body
When prescribing a drug what do we need to specify and why
The brand name as plasma concentration can vary between suppliers
Other than the drug type what else is important when giving medication
Mode of admin
Name the most bioavailable mode of admin
IV injection is 100%
Is bioavailability and synonymous with effectiveness
no a drug can be bioavailable but not clinically effective
What can first pass metabolism Also be called
first pass effect
What is first pass metabolism
Presystemic elimination
Where does first pass metabolism occur
The liver
What is first pass metabolism
When the liver does a thorough job metabolising some drugs that little is available to act via the systemic circulation
Give examples of drugs that are very effectively metabolised by the liver
Propranolol,
lidocaine,
GTN
`Verapamil
Does first past metabolism mean drugs have a high or lower bioavailability
low
What does a low availability mean we have to do
Give a very high oral dose compared to the amount needed to cause its beneficial effects
After absorption what happens to a drug
It is distributed to the body fluid compartments
What is volume distribution
A theoretical measure that illustrates how much volume you would need to keep the plasma concentration of a drug at a level of that administrated in the first place
How do we calculate the apparent volume Distribution of any given drug
the amount of drug present in the body divided by the concentration of a drug in the plasma
What can kidney or liver failure lead to
Fluid retention causing an increase in volume distribution so bigger doses may have to be administrated
What effect does dehydration have on volume Distribution
Dehydration conversely decreases volume Distribution so lesser doses are required to precent toxic effects occurring
Where do most drugs diffuse
Between endothelial cells that make up capillaries into the interstitial tissue space
Name the 5 body compartments
- Plasma 5%
- Interstitial 16%
- Intracellular 35%
- Transcellular 2%
- Body fat 20%
Which body compartment does heparin affect
Plasma
Which body compartment does warfarin affect
Plasma
Which body compartment does gentamicin affect
Extracellular fluid
Which body compartment does ethanol phenytoin affect
Total body water
Plasma protein drugs bind to which hormone
Albumin and Alpha 1 acid glycoproteins
What are free drugs
They are pharmacologically active and free to move to other compartments
What happens to plasma protein drugs when they are in the kidney
They are NOT filtered out by the kidney
How does blood supply affect drug effectiveness
The blood supply affects the equilibration of concentration of a lipid-soluble drug
Why do enzymes process drug molecules
To increase, decrease or otherwise change the action of a drug
How are most drugs broken down
Broken down into water soluble, inactive/less active compounds
How are pro drugs absorbed
They are absorbed in a relatively inactive form and enzyme action converts them to a pharmacologically active metabolites
What can explain variations In metabolism
Genetics
Where in the body is the prime locus of metabolism and biotransformation
LIVER
Which organs the than the liver also play a part in metabolism
Kidney
Skin
Gut
lungs
Where does the liver receive blood and absorbed compounds from
The gut bypassing the heart
How are drugs absorbed in the liver
- They enter through the gut
- Processed by the first pass effect
- Smooth endoplasmic reticulum contains the p450 enzymes
- Partially metabolised drugs re enter the systemic circulation for distribution
What does the P450 enzyme do
It controls the concentration of absorbed drugs
Name an enzyme that is abundantly expressed and used in more than half of clinically used drugs
Cytochrome P450 depended mixed function oxidases (CYPs)
How can P450 enzymes be inhibited
- Competitive inhibitor
2. Non competitive inhibition
What is competitive inhibitor
Competing fro the same enzyme
What is non competitive inhibition
When one agent binds to the enzyme and prolongs the activity of the drug
Where does most excretion of drugs occur
Via the kidneys in the urine
How can small molecular weight drugs be removed
By glomerular filtration
How are acids and bases excreted
They are actively transported in the proximal tubule
How are lipid soluble drugs reabsorbed
Reabsorbed passively across the tubule cells
Why are some drugs contraindicated in breast feeding mothers
As some drugs can travel to baby via breast milk
Does excretion occur more via urine or faeces
urine
V v little excreted in faeces unless formulation poor or patient has diarrhoea
How are volatile agents excreted
By the lungs
How are large molecular weight drugs excreted
They are conjugated and excreted via bile
What is pharmacokinetics
The study of ADME on a quantitative basis
Give some examples go how we can study pharmacokinetics
- The half life in relation to plasma concentration/time plot
- Clearance rates
- Repeated dosing regimen
What is first order kinetics
The amount of drug excreted compared to the concentration of the drug in the circulation
For the majority of drugs what is the first order kinetics
They are directly proportional ie as time goes by, more drug is excreted
What is plasma systemic clearance
It is the sum of all clearance processed of a drug
Why might a drug have a sign half life
May be due to a low clearance rate, a high volume distribution or a combo
Why might we administer multiple doses of a drug
So that the therapeutic window can be maintained without dramatic rises and fall in plasma concentration which could lead to rebound symptoms
What is a loading dose
A one off larger dose
Why might we give a loading dose
To help achieve the therapeutic target faster hastening the beneficial clinical effects of a drug
What are the limitations of Pharmacokinetics
- You cant be sure that plasma conc is actually the same as the con of a drug at its target tissue e
- Drug response depends on conc in the immediate environment of its target
