Sesh 5: Pharmacokinetics : Absorption And Distribution Flashcards
Drug distribution
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
There is a point in whereby if increase drugs it doesn’t not produce a stronger effects so need to consider safety
X
Example of dose response curve explained
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
What does Margin of safety ?
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.
What is therapeutic index ?
The therapeutic index is a quantitative measurement of the relative safety of a drug.
What is ED99?
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).
Diff Routes of administration ?
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. )
An oral drug must ;
Be soluble in gastric fluid Stable in gastric fluid Enter intestine Penetrate through gut epithelium Enter blood stream
Parental drug ;
injection
Fast acting Travels across fewer body compartments Delivers a more accurate dose More likely overdose Once drug been injected cannot be recalled
In terms of safety and convenience what’s the highest route of administration
Oral , subcutaneous , intramuscular then IV
What drugs have a higher cost , high bioavailability , high speed of onset and compliance ?
IV
IM
SC
ORAL
Passing of drugs
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
Drug movement across cellular barriers: What determines permeability?
Drug molecules need to cross the cell lipid membrane
What determines permeability? Permeability coefficient Concentration difference liphophilicity ionisation
Lipid soluble
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
What is PKA
pKa is a number that shows how weak or strong an acid is
Drug characteristic for absorption ;
Low molecular size
Non polar
Charged
High lipid solubility (disadvantage of this it means insoluble and hard to get into aqueous solutions)
Passive diffusion and active transport
Passive diffusion - from high conc to low through lipid bilayer
Active transport from low to high and requires energy
Pinocytosis
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
Factors affecting drug distribution ;
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
Bioavailability
Quantity of drug in systemic circulation vs the quantity of drug administered
Need high bioavailability to have high efficacy
Pharmacokinetics vs pharmacodynamics
pharmacokinetics is ‘what the body does to the drug’.
Pharmacodynamics is ‘what the drug does to the body’
Fluoxetine
Fluoxetine is a selective serotonin reuptake inhibitor used to treat major depressive disorder
Fluoxetine increases the plasma concentration of amitriptyline by inhibiting its metabolism
Tramadol
Tramadol is a centrally-acting opioid agonist used for moderate to severe pain in adults.
Vasopressin
Vasopressin also helps maintain the body’s internal temperature, its blood volume, and the proper flow of urine from the kidneys.
