Flashcards in Pharmacokinetics (session 7) Deck (51):
What are the enteral methods of drug delivery into the internal environment of the body?
What are the parenteral methods of drug delivery into the internal environment of the body?
What are the methods of drug absorption on a molecular level (that we need to know about)? (3)
Secondary active transport
Which method of drug absorption do lipophilic drugs use?
True or false: Molecules (or solutes) with net ionic positive or negative charge within the GI pH range can be carried across the GI epithelia
Solute carriers (SLCs) can either be one of two types of transporters-what are these?
OAT=organic anion transporter
OCT=organic cation transporter
Which two things are SLCs pharmacokinetically important for?
Drug absorption and elimination
Where are SLCs highly expressed?
GI, hepatic and renal epithelia
True or false: SLCs can only enable drug transport in GI by facilitated diffusion
FALSE - also by secondary active transport
What do SLCs use instead of ATP in secondary active transport?
Transport is driven by pre-existing electrochemical gradient across GI epithelial membrane
Give two examples of SLCs that use secondary active transport?
1. Fluoxetine/Prozac - antidepressant co-transported with Na+ ion
2. B-lactam antibiotics/penicillin - co-transported with H+ ion
Name three physicochemical factors that affect drug absorption
Density of SLC expression in GI
Name three GI physiology related factors that affect drug absorption
Food IpH (low pH destroys some drugs)
What is 'first pass' metabolism?
Reduces availability of drug reaching systemic circulation (part of CV system that carries oxygenated blood away from heart to body and deoxygenated blood back to heart) and therefore affects therapeutic potential
What carries out first pass metabolism? (2)
GI and liver
Which two major enzyme groups are some drugs metabolised bY?
Cytochrome P450s - Phase I enzymes
Conjugating - Phase II enzymes
True or false: there is much larger expression of Phase I and II enzymes in the liver than in the GI
Fraction of a defined dose which reaches its way into a specific body compartment
What is the bioavailability reference for the CV system?
What does the first stage of drug distribution involve? (3)
1. Bulk flow - arteries to capillaries
2. Diffusion - capillaries to interstitial fluid to cell membranes to targets
3. Barriers to diffusion - interactions/local permeability/non-target binding
True or false: if a drug is largely lipophilic, it can freely move across membrane barriers
If a drug is largely hydrophilic, its journey across membrane barriers is dependent on which factors? (3)
Drug pKa and local pH
Presence of OATs/OCTs
What does a smaller Vd (apparent volume of distribution) mean?
Less penetration of interstitial/intracellular fluid compartment
Where does drug metabolism largely occur?
In the liver via phase I and II enzymes
What do phase I and II enzymes do?
Metabolise drugs - increase ionic charge and enhance renal elimination
Lipophilic drugs diffuse out of renal tubules and back into plasma and once metabolised, drugs are usually inactivated
Which enzyme carries out phase I metabolism?
Cytochrome P450 enzymes (CYP450s)
What are the two options for drugs metabolised in phase I?
Eliminated directly or go onto phase II
Give an example of when prodrugs activated by phase I metabolism activate to active species
Codeine to morphine
What carries out phase II metabolism?
True or false: phase I enzymes are versatile generalists
True or false: phase I and II metabolism decreases ionic charge
FALSE - increases ionic charge
What are the three superfamilies of cytochrome P450 enzymes?
1, 2 and 3
What is an isozyme?
Each of two or more enzymes with identical function but different structure
Complete the sentence:
If another drug in the body is metabolised by induced CYP450 isozyme then its rate of elimination will be ___________
What is an example of CYP450 induction and how does it work?
Carbamazepine (CBZ) = anti-epileptic metabolised by CYP3A4
CBZ induces CYP3A4-lowers its own levels, affecting control of epilepsy
What is an example of CYP450 inhibition and what does it inhibit?
Grapefruit juice inhibits CYP3A4
CYP3A4 metabolises Verapimil, used to treat high BP. The result of this inhibition can be reduced BP and fainting
What is the main route of drug elimination?
What are the other routes of drug elimination?
What are the three processes of renal excretion?
Active tubular secretion
Passive tubular reabsorption
What is clearance?
Rate of elimination of a drug from the body
For most drugs, total body clearance is approximately equal to what?
Hepatic clearance + renal clearance
What are the units of clearance (CL)?
What is the real plasma volume?
True or false: Clearance (CL) and Vd provide an estimate of drug half-life or t1/2
Define drug half-life
Amount of time over which the concentration of a drug in plasma decreases to a half of its original concentration
If CL stays the same and Vd increases, what happens to t1/2?
If CL increases and Vd stays the same, what happens to t1/2?
True or false: the rate of metabolism or excretion is proportional to concentration of drug
When is the rate of metabolism or excretion proportional to concentration of drug?
When there are:
Plenty of phase I/II enzyme sites
Plenty of OAT/OCT transporters
What happens when eliminated processes becomes saturated?
They become rate limited and elimination kinetics are referred to as saturated or zero order