Lec 3- Distribution and elimination Flashcards
1
Q
What is drug absorption
A
- The process of drug movement from the circulation, into the tissues and organs
2
Q
What affects drug distribution- blood flow and drug partitioning
A
- Blood flow: cardiac output pushes the blood around the body. Blood flow to tissues often differs
- Rapidly perfused (clinical effect fast): Brain, liver, heart and kidney
- Slowly perfused: Muscle, bone and skin
- If the target tissue is slowly perfused, it will often result in a delayed clinical response compared to a rapidly perfused tissue
- Partitioning: from the blood into the tissues. The drug has to permeate across a lipid bilayer
- Other things can effect blood flow- such as change in cardiac output
3
Q
Important concepts- volume of distribution
A
- The volume of distribution (Vd)
- This helps you determine the right loading (Starting) dose to give to a patient
- It is actually a theoretical volume that helps you convert the dose of a drug to its systemic plasma concentration
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4
Q
Volume of distribution
A
- Vd- It helps you calculate drug concentration for different types of drugs
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5
Q
The volume of distribution example
A
- 100mg injected into 5L of blood
- Concentration= 100/5= 20mg/L
- Drug X Vd= 5-8L (very low so stays just in the blood)
- Remember: We take blood/plasma samples to determine drug concentration in the body
- If X has a large Vd it will enter into lipid and muscle
- Muscle= 100L and Blood= 5L
- 100mg/105L = 0.95mg/L
- Seems like we have a larger vol even though the actual blood volume is only 5L. TCAs bind extensively to tissue hence the large apparent volume (Vd= 2100L)
6
Q
Volume of distribution
A
- It helps you calculate drug concentration for different types of drugs
- Vd= low= IN BLOOD
- Vd= High = IN TISSUE
- Amount in body (Ab) = Vd x Cp (plasma concentration)
- High Vd= Hydrophobic
7
Q
vol
A
- Vd determine the initial concentration of a drug in patients
- Function of the drug
- Can change depending on patient (under/over/malnutrition)
- Pregnant, child, obese, bodybuilder, Anorexic
8
Q
Vol of distribution
A
- The volume is important as it can change with age and is one of the main reasons why we often give different doses of the same drug to different age groups
- Higher doses (per Kg bodyweight) for water soluble drugs as larger water volume to reach the same target concentrations in older patients
- As you get older Body water decreases: Body fat increases
9
Q
Vd
A
- 2 beakers of water 10L with identical (but known) amounts of water added and 1g of KI into each beaker (turning the water blue)
- Add charcoal to beaker B, why is the concentration different
- Volume is 20- because concentration is half, we need to double to volume to get the same amount of drug
- NB- charcoal represents tissue, blood proteins etc
10
Q
Plasma proteins
A
- Albumin- bind acid and neutral drugs
- AAG (a1- acidic glycoprotein)- Basic drugs
- Drugs are small enough to diffuse across cell membranes and reach the tissue
- Drug which are bound onto plasma proteins are unable to diffuse due to the large size of the drug-protein complex
- The clinical action of a drug is a result of the drug which is unbound/free and not the total drug concentration (which is the BOUND and UNBOUND)
- Unbound fraction (fu)
11
Q
Volume of distribution and plasma protien
A
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Low protein-bound drugs- The plasma is just like a ‘watery’ container and does not influence the drug
- Typically, these drugs can extensively distribution OUT of the circulation
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High bound drugs- These will stay longer in the circulation and also take longer to reach their target site compared to low protein bound drugs
- These drugs show a low Vd, you may need higher doses to reach therapeutic effects
- BUT as the drugs very slowly diffuse out you have less metabolism/elimination and so that clinical effect is prolonged
- Conditions that effect production of plasma proteins can effect distribution and so dose required of these drugs- hepatitis, liver cirrhosis etc
12
Q
Metabolism and excretion
A
- When administered into the body, drugs will eventually leave the body in a process often called elimination, which is a combination of metabolism and excretion
- Metabolism: the enzymatic conversion of a drug to an alternative form
- Excretion: the removal of the drug from the body
13
Q
Metabolism and excretion- dosage regimens
A
- The process control the amount of drug coming out of the body, and hence can play a direct role in governing how we decide the development of a dosage regimen
- HIGH= multiple doses daily
- LOW= Single dose daily
- A key term we used to ‘summarise’ the process of elimination is the clearance (CI) of a drug.
- This is usually either reflecting the total body clearance or can be specific for the liver (heptatic clearance) or Kidney (renal clearance)
14
Q
Metabolism and excretion- orally dosed drugs
A
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First pass effect- Lots of drugs removed on the first pass through the liver
- Once drugs enter the circulation it is then exposed to the liver and gets metabolised
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- Once drugs enter the circulation it is then exposed to the liver and gets metabolised
15
Q
Important concepts- Clearance
A
- The volume of blood or fluid from which drug is completely removed per unit time
- This is one of the most important terms in pharmacokinetics
- It governs how we design our dosage regimen (OD, BD, TDS, QDS) and is related to the elimination rate
- Definition: volume of blood or fluid from which drug is completely removed per unit time
- Tap= drug input into the body
- Beaker= the body
- Outflow= elimination
