Drug Distribution Total Session Time: 120 minutes
Session 2: Drug Distribution
Total Session Time: 120 minutes
Prerequisites
None
Learning Tasks
By the end of this session students are expected to be able to:
Describe the distribution of drugs in various compartments of the body
Describe factors affecting/determining distribution of drugs
Describe Volume of distribution
Calculate Volume of distribution
Explain clinical applications of volume of distribution
Resources Needed:
Flip charts, marker pens, and masking tape
Black/white board and chalk/whiteboard markers
Computer and LCD Projector
SESSION OVERVIEW
Step
Time
Activity/
Content
Step
Time
Activity/
Content
Step
Time
Method
Content
Method
Method
1
1
05 minutes
05 minutes
Presentation
Introduction, Learning Tasks
Introduction, Learning Tasks
2
2
10 minutes
10 minutes
Presentation/
Distribution of Drugs in Various
Distribution of Drugs in Various
2
2
10 minutes
10 minutes
Buzzing
Compartments of the Body
Compartments of the Body
Buzzing
Compartments of the Body
Compartments of the Body
3
3
30 minutes
30 minutes
Presentation/
Factors Affecting Distribution of Drugs
Factors Affecting Distribution of Drugs
3
3
30 minutes
30 minutes
Brainstorming
Factors Affecting Distribution of Drugs
Factors Affecting Distribution of Drugs
Brainstorming
4
4
20 minutes
20 minutes
Presentation
Volume of Distribution
Volume of Distribution
4
4
20 minutes
20 minutes
Presentation
Presentation/
5
5
30 minutes
30 minutes
Small Group
Calculation of Volume of Distribution
Calculation of Volume of Distribution
Discussion
6
6
15minutes
15minutes
Presentation
Clinical Application of Volume of
Clinical Application of Volume of
6
6
15minutes
15minutes
Presentation
Distribution
Distribution
Distribution
Distribution
7
7
05 minutes
05 minutes
Presentation
Key Points
Key Points
8
8
05 minutes
05 minutes
Presentation
Evaluation
Evaluation
PST 05104 Pharmacology & Therapeutics 11 NTA Level 5 Semester 1 Facilitator Guide
SESSION CONTENTS
STEP 1: Presentation of Session Title and Learning Tasks (5 minutes)
READ or ASK students to read the learning objectives and clarify
ASK students if they have any questions before continuing.
STEP 2: Distribution of Drugs in various Compartments of the Body (10 minutes)
Activity: Buzzing (5 minutes)
ASK students to pair up and buzz on the following question for 2 minutes
What is distribution process of drugs in the body?
ALLOW few pairs to respond and let other pairs add on points not mentioned
WRITE their response on the flip chart/board
CLARIFY and SUMMARIZE by using the content below
Once in the systemic circulation drugs will distribute into sections/units called compartments.
The following are the compartments for governing drug distribution: o Plasma compartment (Vascular compartment)
Drugs with very large molecular weight or those binding extensively to plasma
proteins are effectively trapped within the plasma (vascular) compartment because such drugs are too large to move out through the endothelial slit junctions of the capillaries.
Extracellular fluid
o Observed in drugs with low molecular weights but also hydrophilic, such drugs can move through the endothelial slit junctions of the capillaries into the interstitial fluid. However, these hydrophilic drugs cannot move across the membranes of cells to enter the water phase inside the cell.
Total Body Water
o Observed in drugs with low molecular weight and are hydrophobic, such drugs can not only move into the interstitium through the slit junctions, but can also move ,through the cell membranes into the intracellular fluid.
Other sites
o In pregnancy, the foetus may take up drugs and thus increase the volume of distribution.
PST 05104 Pharmacology & Therapeutics 12 NTA Level 5 Semester 1 Facilitator Guide
STEP 3: Factors Affecting Distribution of Drugs (30Minutes)
Activity: Brainstorming (5 minutes)
Ask students to brainstorm on the following question:
What are the factors determining distribution of drugs?
ALLOW few students to respond
WRITE their responses on the flip chart/ board
CLARIFY and SUMMARISE by using the content below
Distribution of drugs in the body is dependent on the following factors:
Organ Blood Flow
o Organs with high blood flow will have larger amounts of drug delivered to them per unit time.
o Organs with high blood flow will experience initial high concentrations of drug, but these high concentrations will diminish as the drug is redistributed throughout the body to sites with lower blood flow.
Barriers to diffusion
o There are special barriers which restrict drug entry to some organs o Blood Brain Barrier ―BBB‖ is a special case
o In general, the BBB restricts the movement of hydrophilic drugs into brain; however, the BBB is ―broken‖ by ischemia and inflammation.
o The BBB can be exploited to develop drugs with reduced CNS adverse effects
Adipose tissue
o Lipophilic drugs will distribute into adipose (fat) tissue.
o Distribution of lipophilic drugs into fat may necessitate a larger initial bolus of drug to achieve the desired effect.
o Large depots of drug in fat may necessitate a longer period of time for drug to be removed from the body.
o The distribution of lipophilic drugs will be different in thin versus obese patients
Plasma protein Binding
o Drugs bound to protein are pharmacologically inactive.
o Only when the protein molecules release the drug can the drug diffuse into the tissues, interact with receptors, and produce a therapeutic effect.
o Some drugs are highly bound (> 90%) to plasma proteins.
o Acid drugs bind to albumin and basic drugs bind to alpha1-acid glycoprotein.
o Binding of drugs by plasma proteins limits the distribution of drugs out of the vascular compartment, necessitating more drug initially to achieve the desired effect
PST 05104 Pharmacology & Therapeutics 13 NTA Level 5 Semester 1 Facilitator Guide
Displacement of a highly plasma-protein bound drug by another drug may lead to drug-drug interactions because of a rapid increase in the availability of ―free‖
(unbound) drug.
Tissue protein binding
Some drugs are highly bound to tissue proteins.
Binding of drugs by tissue may necessitate a larger initial bolus of drug to achieve the desired effect.
Large depots of drug in tissue may necessitate a longer period of time for drug to be removed from the body.
In general Tissue bindings sites: Increase the apparent volume of distribution, represent potential sites for drug interactions, result in sequestration of drug in the
tissue, may release the drug back into the circulation as the plasma concentration falls.
Thus tissue binding may represent a reservoir of drug that can extend the duration of action of the drug.
Ion trapping
Ion trapping can be used to distribute drugs into the urinary compartment to increase the urinary excretion of poisons.
Example:
Alkalinisation of the urine with systemic administration of sodium bicarbonate is useful for the treatment of overdoses of aspirin and phenobarbital.
Example:
Acidification of the urine with systemic administration of ammonium chloride is useful for the treatment of amphetamine overdoses.
STEP 4: Volume of Distribution (20minutes)
Volume of distribution is used to describe or predict the extent of drug distribution in the body.
The volume of distribution (Vd) is a hypothetical volume of fluid into which the drug is disseminated.
o It is referred to as an apparent volume
Fig 2.1 Drugs appear to distribute in the body as if it were a single compartment.
PST 05104 Pharmacology & Therapeutics 14 NTA Level 5 Semester 1 Facilitator Guide
Rang and Dale pharmacology seventh
edition
The magnitude of the drug‘s distribution is given by the apparent volume of distribution
(Vd)
(Apparent) Volume of Distribution: Volume into which a drug appears to distribute with a concentration equal to its plasma concentration
Vd is not a real volume with an independent existence. In this regard, the word
―volume‖is used in a metaphorical sense.
However Vd is important clinically
Values of Vd have been measured for many drugs
STEP 5: Calculation of Volume of Distribution (30 Minute)
Activity: Small Group Discussion (30 minutes)
DIVIDE students into small manageable groups
ASK students to discuss on the following question
ALLOW students to discuss for 15 minutes
ALLOW few groups to present and the rest to add points not mentioned
CLARIFY and SUMMARIZE by using the contents below
PST 05104 Pharmacology & Therapeutics 15 NTA Level 5 Semester 1 Facilitator Guide
The apparent Vd of the drug is 0.5L or 500ml
STEP 6: Clinical Application of Volume of Distribution (15minutes)
Volume of distribution has importance in the following situations:
Determining the loading dose
o A delay in achieving the desired plasma levels of drug may be clinically unacceptable.
o Therefore, a "loading dose" of drug can be injected as a single dose to achieve the desired plasma level rapidly
CP[target] is a target plasma concentration
From the formula above if we know the Vd and bioavailability of a drug and predict our target plasma concentration to be obtained when a drug is administered then we can predict the high dose (loading dose) to be administered.
Fig 2.2 shows the effect of using loading dose for digoxin that help to achieve the required therapeutic concentrations immediately in contract to the use of normal dosing regime which may require up to 10 dats to achieve therapeutic concentration
Rang and Dale pharmacology seventh
edition
Apparent volume of distribution will predict whether the drug will reside in the blood or in the tissue.
Water-soluble drugs will reside in the blood, and fat soluble drugs will reside in cell membranes, adipose tissue and other fat-rich areas.
PST 05104 Pharmacology & Therapeutics 16 NTA Level 5 Semester 1 Facilitator Guide
Volume of Distribution also relates to whether a drug is Free / protein bound
Protein bound drugs form macromolecular complexes that cannot cross biological membranes and remain confined to the bloodstream.
STEP 7: Key Points (5 minutes)
Various body compartments are involved in the distribution of drugs
Distribution of drugs is affected by many factors
The volume of distribution is a hypothetical volume but of clinical importance in the determination of a loading dose.
STEP 8: Evaluation (5 minutes)
What is the meaning of Volume of distribution?
What are factors affecting drug distribution?
What is the clinical application of Volume of distribution?
List drugs with a large volume of distribution
What is the relationship between volume of distribution and elimination?
PST 05104 Pharmacology & Therapeutics 17 NTA Level 5 Semester 1 Facilitator Guide
References
Katzung, B. G. (2018). Basic and clinical pharmacology. New York: Mcgraw Hill Education.
Santos, R. R., Rang, H. P., Dale, M. M., Ritter, J. M., & Flower, R. J. (2007). Rang & Dale Farmacologia. Rio de Janeiro: Elsevier.
Tripathi, K. (2018). Essentials of Medical Pharmacology. Place of publication not identified:
Jaypee Brothers Medical P.
Ministry of Health and Social Welfare. (2013). Standard Treatment Guidelines & National Essential Medicines List Tanzania Mainland (4th ed.). Dar es salaam, Tanzania government printers.
Sally S.R, Jeanne C.S. (2000). Introductory Clinical Pharmacology (6th ed) New York, Lippincott Williams and Wilkins.
School of Pharmaceutical sciences. (2011).Tanzania Pharmaceutical Handbook (2nd ed.).
Dar es Salaam, ARDHI University press.
The Royal Pharmaceutical Society of Great Britain. (2007). Martindale, the Extra Pharmacopoeia (5TH ed). London, pharmaceutical press.
The Royal Pharmaceutical Society of Great Britain. 2009. British National Formulary (59th ed). London, BMJ Group and RPS Publishing.
PST 05104 Pharmacology & Therapeutics 18 NTA Level 5 Semester 1 Facilitator Guide
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