Pharmacology - drug ADME Flashcards
what is pharmacodynamics
what a drug does to the body
what is pharmacokinetics
what body does to a drug eg absorption, distribution, metabolism
what is medicine
a combo of drugs and other substances for healing
what are receptors
macromolecules on/ in cells that mediate hormones
what is an agonist
binds to receptor and produces cellular response
what is an antagonist
reduces/ blocks the actions of an agonist by binding to same receptor
what is affinity
the strength of bond between receptor and agonist (slow dissociation rate = high affinity_
what is efficacy
ability to evoke a cellular response
what do antagonists have
affinity but not efficacy
what is EC50
agonist % when the response is half of it’s maximum
what is potency
lower conc = higher potency. less needed to do the job
in competitive agonists and antagonists, what does this have on EC50
shifts curve to right, more is needed to get response
in non-competitive antagonists what effect is there on EC50 if you increase conc
none, cannot increase active receptors
what is absorption
process by which a drug enters the body from it’s site of administration
what is distribution
process by which drugs enter blood and tissues
what is metabolism
conversion of drug to less active form
what is excretion
process which removed drug from body
what factors affect absorption (4)
solubility, stability (not destroyed in acid stomach), lipid to water partition coefficient (lipid soluble), degree of ionisation (unionised)
when pKa = pH what does this mean for the drug
it is 50% ionised 50% not
what is the equation for week acids
pH = pKa + log ([A-]/[AH])
what is better absorbed weak or strong acids and bases
weak
where are weak acids normally absorbed
stomach lumen
where are weak bases normally absorbed
small intestine
what is oral availability
fraction of drug that enters blood stream after ingestion
what is systemic availability
fraction that enters systemic circulation after absorption
what are some enteral drug routes
oral, sublingual, rectal
what are some parenteral drug routes
IV, IM, topical, inhalation
which drugs are more able to move around water compartments by diffusion
unionised
what is volume distribution (Vd)
volume in which a drug is dissolved (dose/ plasma conc)
a Vd of less than 10 indicates the drug is where
vascular compartment
a Vd of 10-30 means what
drug is in extracellular compartment
Vd of more than 30 indicates what
drug is in total body water
what is the MEC
minimum effective concentration
what is the MTC
maximum tolerated concentration
what is the therapeutic ratio
MTC/MEC, safe drugs have a high ratio, unsafe have a low ratio
why does a low MTC/MEC mean a drug is unsafe
because there is a risk of poisoning the patient
how is the initial concentration for a drug determined (Co)
D/Vd
mass / volume of blood
what to later concentrations depend on
elimination rate constant (Ke)
what is Ke
elimination rate constant, the fraction of a drug eliminated per unit time
what is first order kinetics
rate of elimination is proportional to drug conc (half life)
what is this half life
the time it takes for a drugs conc to half
what is the equation for t1/2
0.693/Kel
does first order kinetics change half life or Ke of a drug
no and no
what is clearance (CL)
volume of plasma cleared of a drug per unit time (norm = L/hr)
what is Cp
plasma absorption
what is the equation for the rate of elimination
CL x Cp
what is steady state
rate of drug admin = rate of drug elim
what is Css
steady state concentration of a drug
after how many half lives is Css normally achieved
5
in oral dosing what should plasma conc fluctuate around
average steady state value
what is a loading dose
an originally higher dose given at the beginning of a course to increase time to reach steady state for drugs with long half life
what is zero order kinetics
drugs eliminated at a constant rate, changes to first at low concs
what are drugs (x..)
xenobiotics, foreign chemicals
what does metabolism do
coverts parent drugs to more polar metabolites that are not as readily absorbed in renal tubules and so excreted
what organ carries out most drug metabolism
liver
what are the 2 faces of drug metabolism
1 = oxidation, reduction, hydrolysis 2 = conjunction
where does phase 1 occur
Right hand side of liver
where does phase 2 occur
left hand side of liver
what is the purpose of phase 1
makes it more polar (ionised) by adding a reactive group
what is the purpose of phase 2
adds an endogenous compound (carbon) to increase polarity
what do CYP450 proteins do
haem proteins that oxidate drugs in phase 1 by monooxygenase cycle
what is a common phase 2 reaction and what enzyme carries it out
glucuronidation, UDP-glucuronyl transferase
what are the major organs involved in drug excretion
kidneys
what are the 3 main processes involved in excretion
glomerular filtration, active tubular secretion and passive reabsorption by diffusion
drugs must be in what state to enter filtration via glomerular filtration
unbound
a drugs molecular weight (MW) must be under what to be excreted via glomerular filtration
less than 20,000
in tubular excretion, what 2 transporter systems actively secrete drugs into nephron lumen
organic anion transporter (OAT - acidic drugs) and organic cation transporter (OCT - basic drugs)
why is tubular excretion potentially the most effective (3)
1) max clearance even in bound proteins (to plasma), 2) can concentrate drugs against electrochemical gradient 3)each transporter has maximum Tm for drug
what is passive reabsorption
concentration of urine favours passive reabsorption across distal tubule by diffusion
what factors affect rate of reabsorption
lipid solubility, polarity, urine flow rate, urine pH
