Sesh 5: Pharmacokinetics : Absorption And Distribution

Question 1

Drug distribution

Answer 1

Depends on how lipid soluble a drug is, need to be lipid soluble to pass through a biological membrane and need to not bind to blood proteins such as albumin because if all bound hard to have biological efficacy

Question 2

There is a point in whereby if increase drugs it doesn’t not produce a stronger effects so need to consider safety

Answer 2

X

Question 3

Example of dose response curve explained

Answer 3

So for example would only need a small increase in dose of hydromorphine in order to produce a substantial increase in effect whereas

Aspirin for example need a higher dose to produce a more effect

Question 4

What does Margin of safety ?

Answer 4

The range of doses is referred to as the margin of safety of a drug. The margin of safety of a drug is a concept that tells us how safely we can use a drug for therapeutic purposes without risking too many adverse effects at the same time.

Question 5

What is therapeutic index ?

Answer 5

The therapeutic index is a quantitative measurement of the relative safety of a drug.

Question 6

What is ED99?

Answer 6

The Margin of Safety (MOS) is usually calculated as the ratio of the toxic dose to 1% of the population (TD01) to the dose that is 99% effective to the population (ED99).

Question 7

Diff Routes of administration ?

Answer 7

Orally 
Rectally
Inhalation
Topical (e.g creams or gels)
Parentally :
Intravenous (into the vein)
Intramuscular (into the muscle)
Subcutaneous ( under the skin) 
Intraperitoneal  (within or administered through the peritoneum. The peritoneum is a thin, transparent membrane that lines the walls of the abdominal (peritoneal) cavity and contains/encloses the abdominal organs such as the stomach and intestines. )

Question 8

An oral drug must ;

Answer 8

Be soluble in gastric fluid 
Stable in gastric fluid 
Enter intestine 
Penetrate through gut epithelium 
Enter blood stream

Question 9

Parental drug ;

injection

Answer 9

Fast acting 
Travels across fewer body compartments 
Delivers a more accurate dose 
More likely overdose 
Once drug been injected cannot be recalled

Question 10

In terms of safety and convenience what’s the highest route of administration

Answer 10

Oral , subcutaneous , intramuscular then IV

Question 11

What drugs have a higher cost , high bioavailability , high speed of onset and compliance ?

Answer 11

IV
IM
SC
ORAL

Question 12

Passing of drugs

Answer 12

Drug goes through plasma it needs to pass through capillary endothelium, then interstitial fluid then majority of drugs need to pass through plasma membrane of the cell and then the intracellular fluid

Question 13

Drug movement across cellular barriers: What determines permeability?

Answer 13

Drug molecules need to cross the cell lipid membrane

What determines permeability?
Permeability coefficient 
Concentration difference 
liphophilicity
ionisation

Question 14

Lipid soluble

Answer 14

A drug needs to be lipid soluble to penetrate membranes unless there is an active transport system or it is so small that it can pass through the aqueous channels in the membrane.

Strongly ionized drugs cannot cross membranes so they are not absorbed orally and cannot cross the blood-brain barrier.1

Question 15

What is PKA

Answer 15

pKa is a number that shows how weak or strong an acid is

Question 16

Drug characteristic for absorption ;

Answer 16

Low molecular size
Non polar
Charged
High lipid solubility (disadvantage of this it means insoluble and hard to get into aqueous solutions)

Question 17

Passive diffusion and active transport

Answer 17

Passive diffusion - from high conc to low through lipid bilayer

Active transport from low to high and requires energy

Question 18

Pinocytosis

Answer 18

Pinocytosis involves absorption of fluid or particles following their encapsulation by a cell. The membrane of the cells closes and fuses to form a complete vesicle, which later detaches and moves into the inside of the cell. This process also requires energy to occur.

Important process for large and complex drugs e.g insulin

Question 19

Factors affecting drug distribution ;

Answer 19

Affecting rate of distribution -
Membrane permeability and blood perfusion

Affecting extent of distribution;
Plasma protein and intracellular binding 
Regional differences in pH
Lipid solubility 
Available transport mechanisms

Question 20

Bioavailability

Answer 20

Quantity of drug in systemic circulation vs the quantity of drug administered

Need high bioavailability to have high efficacy

Question 21

Pharmacokinetics vs pharmacodynamics

Answer 21

pharmacokinetics is ‘what the body does to the drug’.

Pharmacodynamics is ‘what the drug does to the body’

Question 22

Fluoxetine

Answer 22

Fluoxetine is a selective serotonin reuptake inhibitor used to treat major depressive disorder

Fluoxetine increases the plasma concentration of amitriptyline by inhibiting its metabolism

Question 23

Tramadol

Answer 23

Tramadol is a centrally-acting opioid agonist used for moderate to severe pain in adults.

Question 24

Vasopressin

Answer 24

Vasopressin also helps maintain the body’s internal temperature, its blood volume, and the proper flow of urine from the kidneys.