Pharmacokinetics and Pharmacodynamics Flashcards
Define Pharmacokinetics
What the body does to the drug
Define Pharmacodynamics
What the drug does to the body
Which is the only type of drug that can elicit an effect on the body?
Only free drug can elicit a pharmaceutical response
What is bioavailability?
The fraction of an orally administered drug that reaches the systemic circulation as intact drug (F)
What is the bioavailability of an IV drug?
100%
How do you calculate bioavailability?
Bioavailability = AUC oral x100%
AUC IV
What factors affect bioavailability?
-
Absoprtion
- Formulation
- Age
- Food (chelation, gastric emptying)
- Vomiting/ Malabsorption (Crohn’s)
- First pass metabolism
Identify on the curve, absorption, distribution and elimination
What are modified release preparations?
Standard preparations have to be administered several times a day
Modified release are taken less often and are absorbed over a longer period
- Plasma concentration determination shifts more towards the rate of absorption
What factors affect the distribution of therapeutic agents?
- Blood flow (to target organ) , capillary structure
- Lipophilicity and hydrophilicity
- Protein binding
What are the different types of proteins that drugs can bind to
- Albumin- acidic drugs
- Globulins - hormones
- Lipoproteins - basic drugs
- Glycoproteins - basic drugs
Explain the one compartment model of distribution
Drug only distributed in one compartment, no equilibrium established
Explain the 2 compartment model of distribution
Slower distribution across the different compartments of the body
Equilibrium established between the different body compartments
Elimination can start to happen before an equilibrium in body tissues is established
How can drug-protein binding affect distribution if a second drug is administered?
When is this clinically important?
Bound drug can be displaced from a binding site → now free drug that can elicit a response
Clinically important if:
- highly protein bound
- narrow therapeutic index
- low Vd
What is volume of distribution? (Vd)
The apparant volume of drug in the body releative to its concentration in plasma
Low Vd= mainly in plasma
High Vd= well distributed throughout body compartments
How do you calculate Vd?
Vd= Dose/ [Drug] plasma
How do you calculate a dose based on Vd?
Vd x [Drug] plasma = dose
What are the 2 phases of metabolism?
Phase 1: CYP450s → oxidation reaction → forms lipophilic metabolites
Phase 2: Conjugation reaction → excretion by kidney to urine or gall bladder in bile
What are the main isoenzymes of CYPs? How are these induced/inhibited
CYP1A - induced by smoking
CYP2C - many inhibitors
CYP2D - metabolises many drugs
CYP2E - Alcohol metabolism
CYP3A - ~50% therapeutics
What are pro-drugs?
Drugs that are adminstered inactively, and are activated by CYP450 enzyme metabolism
e. g. perindopril → dopamine
e. g. codeine → morphine
What factors can affect the activity of CYP450s?
- age
- hepatic disease
- blood flow
- alcohol
- cigarette smoking
Which CYP does grapefruit inhibit?
CYP3A4
Effects statin metabolism - CYP3A4 inhibited so statin levels remain high
What are the routes of drug elimination from the body?
- Primarily via the kidneys
- Other routes:
- Fluids- sweat, tears, genital secretions, saliva, breast milk
- Solids- faeces, hair
- Gases- volatile compounds
By which routes are low molecular weight and high molecular weight metabolites respectively excreted?
Low molecular weight polar metabolites- by the kidneys
High molecular weight metabolites- by hepatic route
What factors affect Renal clearance?
- Glomerular filtration affected by GFR & Protein binding
- Tubular secretion affected by Competition for transporters
- Tubular reabsorption affected by lipid solubility, pH, flow rate
Briefly explain the principles of hepatic clearance
- Drug conjugated with glucoronic acid in the liver
- Congugated drug enters gut with bile
- Eliminated in faeces or reabsorbed into enterohepatic circulation
What is first order metabolism?
Elimination of drug is concentration dependent
e.g. more drug= faster elimination
What is zero order metabolism?
Elimination of drug is at a fixed rate, regardless of concentration (e.g. alcohol)
What is half life?
Time taken for the concentration of drug to half
(independent of concentration)
Give the equation to calculate T1/2
t1/2 = 0.693 / k
How do you calculate clearance?
Clearance = Rate of elimination from body/ drug concenration in plasma
What is clearance?
The volume of bood cleared, per unit time (mL/min)
What is the equation for haf life, with clearance?
t1/2 = 0.693 x Vd
CL
How does t 1/2 vary in first order vs zero order drugs?
Most drugs are first order- t1/2 is constant
Zero order- dose can change giving unpredictable [plasma] → t1/2 is not calculable (important for dosing and toxicity)
Approximately how many t1/2 does it take to reach steady state concentration?
Steady state (Css) reached in ~5 t1/2
(and will take ~5 t1/2 for drug to be elimated from system after termination)
How do you calculate steady state concentration?
Css= Rate of infusion/ CL
For orally administered drugs at steady state administration = elimination.
Give the equation for steady state plasma concenration for an oral drug?
Css = Dose (D) x Oral Bioavailability (F)
Frequency of administration (t) x Clearance (Cl)
What is a loading dose?
A dose given when rapid onset is required or drug has a long half life meaning it would take too long to reach Css
How do you calculate a loading dose?
Loading dose = Css x Vd
How can different drugs exert their action at receptors?
Agonists - activate receptors
Partial agonist - partial response even if all receptors occupied
Inverse agonist - binds to receptors preventing basal response happening
Competitive antagonists
Non- competitive antagonist
