L35 Pharmacokinetics Flashcards
(37 cards)
What is pharmacokinetics and what does it include?
non-specific, general processes including absorption from site of administration. time to onset of effect, and elimination from the body
what are the different categories of drug names?
generic name (approved or official)
trade/brand name
chemical name
use name (what they are used for eg contraceptives or anti-inflammatories)
effect name (relates to physiological or biological response in body)
what are the advantages and disadvantages for oral, intramuscular, subcutaneous and intravenous routes of administration?
oral
- convenient, safe, economical
- cannot be used for drugs inactivated by 1st pass metabolism or that irritate the gut
intramuscular
- suitable for suspensions or oily vehicle. rapid absorption from solutions or slow and sustained absorption from suspensions
- may be painful or cause bleeding at injection site
subcutaneous
- suitable for suspensions and pellets
- cannot deliver large volumes of fluid or drugs that irritate cutaneous tissue
intravenous
- bypasses absorption yielding immediate effect and 100% immediate bioavailability
- more risk for toxicity
what are the advantages and disadvantages for buccal, transdermal, inhalational, intrathecal, epidural and topical routes of administration?
buccal
- rapid absorption, avoids 1st pass metabolism
- only low doses effective, drugs must be water and lipid soluble
transdermal
- avoids 1st pass metabolism
- effective only for low doses of drug that are highly lipid soluble
inhalational
- localised effect
- particles must be correct size and dependent on patient technique
intrathecal
- local and rapid
- Requires expert administration and May introduce infection/toxicity
epidural
- targeted effect
- risk or failure or infection
topical
- non-invasive and easy
- Poorly lipid soluble not absorbed via skin or mucous membranes and slow absorption
why are using modified dose forms important?
improves patient adherence, reduces incidence/severity of GIT effects. also more control over therapeutic plasma concs (so improved treatment of chronic conditions, maintenance of therapeutic action overnight and minimised adverse effects associated with high plasma conc)
what are the problems with using modified dose forms?
Cost more per unit dose than conventional forms
Possibility of unsafe over dosage if used incorrectly or in failure of MR tablet
Rate of transit through GIT limits the maximum period for which a therapeutic response can be maintained
Variability in physiological factors e.g. GIT pH, enzymes, food etc influence drug bioavailability
What is the process of ADME through the body by oral and injection administration?
oral administered drug undergoes absorption and first pass metabolism in the liver. it is then distributed to systemic circulation, tissue spaces and cells.
injection administration goes straight to be distributed to systemic circulation, tissue spaces and cells.
both go from distribution to pharmalogical action in target tissue, metabolised in the liver or excreted via kidneys, lungs, faeces etc
what is absorption and how much of an oral drug will be absorped?
Transfer of the drug from the site of administration into the general or systemic circulation
Approx. 75% of a drug given orally will be absorbed in 1-3 hours
which factors affect oral absorption?
- particle size and formulation
- GIT enzymes/acid
- GIT motility
- physicochemical factors
- food
how does pH affect drug absorption?
drugs are either acids or bases. Acids are compounds that can dissociate to donate one or more protons
HA ↔ H+ + A-
Bases are proton acceptors
BH + ↔ B + H+
The degree of ionisation, therefore, is dependent on the pH of their environment
The lipophilic nature of the cell membrane only permits the passage of the uncharged fraction of any drug (once disassociated)
what is distribution and how does it occur?
The process by which the drug is transferred reversibly
from the general circulation into the tissues as concentrations in blood increase
from the tissues into blood as blood concentrations decrease
Mainly occurs by passive diffusion of un-ionised form across the cell membrane
what is volume of distribution and what is it for?
volume of plasma that accounts for total amount of drug
Used to determine the loading dose necessary for a desired blood concentration of a drug
Also used for estimating a blood concentration in the treatment of overdose
what are the factors affecting drug distribution?
- plasma protein binding
- specific drug receptor sites in tissues
- regional blood flow
- lipid solubility
- disease
what is drug protein binding?
Drug + Protein ↔ Drug – protein complex
Binding of drugs with albumin and glycoproteins
Reversible structure
what happens to a patients that has been administered a drug highly protein bound when already on another drug that is highly protein bound?
Results in displacement of drug already bound to protein
Produces increased unbound concentration of drug and biological activity
If drug is widely distributed in tissues, the increase in unbound drug is rapidly redistributed to body tissues and unbound plasma concentration rapidly returns to negligible amount
Changes in plasma protein binding are significant for drugs which are greater than 90% bound to plasma proteins
which drugs bind to albumin?
furosemide ibuprofen phenyltoin thiazides warfarin
which drugs are bound to glycoprotein?
chlorpromazine
propanolol
tricuclic antidepressants
lidocaine
can protein-bound drugs cross the cell membrane?
Only molecules not bound to protein can cross cell membrane
what is metabolism and what are the four roles of drug metabolism?
Process to alter drugs to facilitate their removal from the body
- activation of inactive drug
- production of active drug with increases activity from active drug
- inactivation of active drugs
- change in the nature of the activity
what is 1st pass metabolism?
metabolism occurring prior to and during absorption
what are the 4 major metabolic barriers drugs have to pass before reaching general circulation?
intestinal lumen
- gestive enzyme secreted by the mucosal cells and pancreas
- Certain enzymes break down proteins and stop them from being absorbed
intestinal wall
- rich in enzymes that further metabolise drugs
liver
- major site of drug metabolism
lung
- cells of the lung have high affinity for many drugs and are the site of metabolism for many hormones
what are the phases of metabolism?
phase 1
reaction eg oxidation, reduction, hydrolysis.
phase 2
reaction eg conjugation
lipophilic drug to more reactive drug to hydrophillic drug to be excreted by kidneys
what are the factors affecting drug metabolism?
- first pass effect
- hepatic blood flow
- liver disease
- genetic factors
- other drugs
- age
what is the CYTOCHROME P450 (CYP450) SYSTEM?
A large family of enzymes and individual one is called an isoenzyme. Isoenzymes are named using an agreed method of nomenclature
Substrate: drug metabolised by isoenzyme
Enzyme Inducers
Enhance production of liver enzymes which breakdown drugs
Faster rate of drug breakdown
Enzyme Inhibitors
Inhibit production of enzymes which breakdown drugs
Reduced rate of drug breakdown
