pharmokinetics Flashcards
wk 10
What is encompassed in pharmacokinetics?
How drugs are:
Absorbed in body fluids
Distributed to sites of action
Metabolised into inactive/active metabolites
Excreted by body
Why is the extent of absorption important?
Determines magnitude of response
and time of onset of action
What are the main routes of administration? And where are they?
Oral
parenteral- injection
inhalation- lungs
epithelial - via a membrane (skin, mucosa, nasal)
sublingual - under tongue
rectal
What are the four types of parenteral routes of administration?
Intravenous (via blood)
intramuscular (into the muscle)
Subcutaneous (under the skin)
intrathecal (into subarachnoid space of spine
What are the two ways that routs of administration can be divided?
Enteral
- into GI tract
-invloing/passing through intsetine
Parenteral
-not into GI tract
What are the chemical factors that affect the degree of GI absorption via oral route?
Formulation
Physical properties
Ionisation
Solubility
What are the physiological factors that affect oral administartion?
PH of GI contents
GI motility
Disorders
Presence of food
What are the advantages of Parenteral (intravenous) route of administration?
most common
-IMMEDIATE effect
-can deliver large amounts over time (infusion)
-used for drugs that can’t be orally taken or needs to be broken by first metabolism.
What are the disadvantages of Parenteral (intravenous) route of administration?
difficult to administer
-potential risk of overdose/ throbosis/ infection
what is an advantage and disadvantage of
Parenteral (Subcutaneous and intramuscular) administartion?
-A = lower rate of absorption and longer drug action
more painful and dependant on local blood flow
What is an example of Parenteral (Subcutaneous and intramuscular) administration?
insulin
What is inhalation only used for which can be a limiting factor of it’s use?
Only used for anesthetics and drugs whose site of action is the lung
What is an example of a drug that uses epithelial administration?
oestrogen patches
What is the advantage of Sublingual administartion?
Rapid absorption directly into systemic circulation without passing through liver
When is rectal administartion used (advantage)?
For drugs that have a local effect on GI tract
or
When intravenous administration is not possible
Why is lipid solubility the most important factor in drug absorption?
because drugs must be able to cross the lipid bilayer to reach their target organ.
What are the characterises of an ionised molecule vs unionsed molecule?
charged polar
water soluble
un-polar and more lipid soluble
What determines the extent of ionisation? Explan
by pH of environment that drug dissolves in.
Drug will be ionised when exposed to a pH opposite to its pKa.
When are acidic drugs more ionised?
in a basic environment: higher pH
Where is most of the drug first distributed to?
organs with a high blood supply.
what does the rate that a drug enters depend on?
permeability of capillaries for drug and perfusion
What is Volume of Distribution?
Volume of fluid needed for drug to be uniformly distributed to produce observed concentration in blood
not a rel volume
What is Volume Distribution determined by?
Relative strength of binding to tissue components VS compared to plasma proteins
(if tightly bound to plasma proteins stay in circulation) V= close to blood volume.
If the drug is tightly bound to tissues…..
= less drug in blood = drug dissolve and large volume
What is volume of distribution used for?
Indication of drug accumulation in tissue compartments
Determinants of half-life
Calculation of loading dose
What are the two processes of drug elimination?
metabolism and excretion
What is the role of lipophilic solubility in metabolism?
enhance passage through cell membranes and access to site of action
Hinder elimination from body
Most lipophilic compounds readily filtered into glomerulus of kidney and then reabsorbed across tubules
What reactions occur in Phase I of metabolism? What is this and what are the subtypes?
Functionalisation reactions
What: functional group is added/exposed
subtypes: oxidation/ reduction/ hydrolysis etc
What are the properties of Phase 1 of metabolism of drugs?
Result in loss of pharmacological activity
Form more reactive products
Important for prodrugs
What is Phase 2 of metabolism of drugs?
Covalent linkage made between functional group from drug or phase 1 metabolite
What are the properties of Phase 2 of metabolism of drugs?
Result in decrased activity
Produce more active metabolites
What are the factors that affect drug metabolism?
- Interactions between drugs
- Disease status
- eg liver and kidney disease
- Hormonal status / gender
- Age function declines with age
- Nutritional status ]
- Genetic factors
How do inetractions between drugs affect drug metabolism?
- drug induced alteration in liver enzymes
- competition for metabolic pathways
alters rates at which drugs are metabolised
What is oral administration limited by?
First-pass metabolism
Oral drugs may be inactivated in liver/intestines before enters systemic circulation = first pass metabolism
Limits oral administration because:
Higher dose needed, large and individual variation
What is bioavalaibility?
Proportion of drug that passes into systemic circulation after oral administration
What does bioavalaibility depend on?
Amount absorbed from GIT q Amount escaping extraction (first-pass metabolism) by the liver
What is elimination?
Irreversible less of a drug via metabolism and excretion
What is excretion?
irreversible loss of chemically unchanged drug in urine, bile, air or faeces
What is clearance?
Availability of individual organ or body to eliminate drug
What is Half life?
Time taken for amount of drug in the body (plasma concentration) to drop by half.
What is the relationship between Half life, clearance and Vd?
Half-life is increased by an increase in the volume of distribution or
a decrease in clearance
