Pharmacology Flashcards
bioavailability
proportion of administered drug that reaches the systemic circulation
pharmacokinetics
what the body does to the drug
pharmcodynamics
what the drug does to the boyd
to measure bioavailability
% of proportion measured relative to IV dose
IV administration mean
drug is 100% bioavailable
on a graph of bioavailability the area under it
is an indicator of total body exposure to the drug
factors which influence bioavailability
- nature of the drug (chemical, peptide)
- GI transit and digestion
- first pass metabolism
- route of admin
- lipophilicity
Bioavailability and GI transit and digestion
Patients with vomiting and diarrhoea have faster transit through GI tract- therefore tablets many not be totally absented.
patients who are sick
may not absorb any of the drug
drugs can be broken don by
enzymes in the GI tract
what is first pass metabolism
breakdown of drug by liver before it reaches systemic circulation
-blood flow from GI tract passes through liver via hepatic portal vein
route of admin e.g
- IV
- orally
IV
straight into the bloodstream
Oral
easy and well tolerated
IM
via capillaries/lympathic system- slower absorption
respiratory
across plasma membrane- rapid absorptions
administrations which involve
the drug accessing a blood supply quickly are the quickest
why is oral administration not perfect
due to first pass metabolism decreasing bioavailability
lipohilicity
the more lipophilic/hydrophobic molecules are the more that can pass through the phospholipid bilayer of cells, increasing conc of drug in tissues
many drugs are
weak acids
many drugs are weak acts so
are in equilibrium between ionised and unionised form
e.g.Uncharged + lipophilic or charged and lipophobic
the lower the pKa the
stronger the acid
pKa
pH at which [ionised]= [unionised
pl
isoelectric point
pl is
the pH at which there is no net charge
volume of distribution
represent the volume in which total amount of drug would need to be dissolved to match plasma concentration
the higher th vd
the lower drug vol in the plasma= more in tissue
after absorption
drug equilibrate between plasma and tissues e.g. adipose tissue
calculating Vd
amount of drug in the body (dose) (mg)/ plasma concentration (mg/mL)
factors affecting Vd
- drug size
- lipophilicity
- lasma protein binding
- body composition
- patients, age, gender
- diff body fat composition
Vd and plasma protein bidning
if drug bound to proteins in plasma, its generally not going to enter the tissue as proteins done bass into tissues
Vd and body composition
e. g. inhale anaestheics- very fat soluble- drug absorbed into fatty tissue the back into body, very diff to control level of anaesthesia
- why obese people are asked to lose weight before surgery
how is Vd measured
measured experimentally following iv administration of known amount of drug
high plasma [drug] =
ow Vd= drug not widely distributed, restricted to plasma compartment
low plasma [drug]=
high Vd= drug widely distributed in other tissues
clearance is
the volume of plasma cleared of the active compound per unit time
hepatic clearance
by liver- metabolism
renal clearance
by kidney- excretion -predominant route
zero order
linear e.g. alcohol
-
first order
exponential- most drugs
-constant proportion of drug cleared per unit time
clearance can not be increased regardless of how much more drug you add if
all enzymes are saturated
clearance=
[drug in urine] x urine flow rate/ [drug in plasma]
clearance units
mL/min
factors affecting renal clearance
- kindey function
- lipophilicity
- plasma protein binding
plasma half life
-time taken for plasma conc of a drug to reduce by half
drug targeting
targeting of drug delivery to site of action
why is drug targeting important
- reduces side effects
- allows a lower does to be given
- more predictable side effects
drug targeting exploits
property of target tissue
sometime high bioavailability isn’t desirable
systemic effect not desirable or necessary
direct application: suppositiories/enemas
anti-inflammatory drugs
oral drugs
- enteric coated- delayed release 9time/ pH release)
- prodrugs converted by gut bacteria
sulfalazine
uses prodrug converted by gut bacteria
targeted inflamed tissue
monoclonal antibodies against cytokines
prodrugs are good because
they will prevent damage to the stomach
