PK PD Pharacokimetics And Pharmacodynamics Flashcards
(34 cards)
What’s the difference between pharmacokinetics, pharmacogentics and pharmacodynamics?
Pharmacokinetics - what the body does to a drug
Pharmacogenetics - how individuals differences affect metabolism
Pharmacodynamics - what the drug is doing at receptor level
What can happen to a free drug in the body?
Protein- bound drug
Metabolised -> active/ inactive
Excreted
Distributed to tissues reservoirs
Interact with receptors -> (therapeutic) effect
Key factors affecting pharmacokinetics?
Bioavailability Half-life Drug elimination Inter-subject variability (clinical trials) Drug- drug interactions
Renal function Stress Pyrexia Alcohol Smoking Occupational exposure Lactation Albumin level Circadian/ seasonal variations
What is oral bioavailability? What affects it?
Measure of the amount of drug that gets into systemic circulation relative to IV route (=100%/ 1)
Measure of drug absorption where it can be used
<1 = lower bioavailability
Absorption Formulation Age Food Vomiting/ malabsorption First pass metabolism (gut lumen, gut wall, liver)
How to calculate bioavailability from a time, plasma concentration of drug graph
(Area under curve oral/ AUC IV) X 100%
How does the rate of absorption dictate visibility of distribution and elimination phases?
Fast absorption means a more obvious distribution phase
Whereas slow absorption means gradual plasma conc increase
Give an example of an extended release modified release preparation
Meteor in can be altered through tweeted preparation to change the pharmacokinetic parameters -> slower absorption so can be taken once a days rather than 3 but more expensive, less Gi discomfort, increased adherence
What affects distribution of a drug?
Blood flow Capillary structure Lipophilicity Hydrophilicity Protein binding
Which type drugs tend to bind to which proteins?
Albumin - acidic drugs
Globulins - hormones
Lipoproteins - basic drugs
Glycoproteins - basic drugs
When is displacement of a drug from binding sites resulting in protein binding drug interactions important?
- highly protein bound
- narrow therapeutic index
- low Vd
When is a sceond drug displacing a first drug from binding proteins important?
Results in more free first drug to elicit a response, potentially causing harm
- pregnancy (fluid balance)
- renal failure
- hypoalbuminaemia
How to calculate Vd?
Dose/ drug plasma conc
If you give a dose of 100mg, the plasma concentration is measured as 20mg/ L and the Vd as 5L what does this mean?
To achieve a plasma conc of 20mg with 100mg dose you need 5L for it to be dissolved into
What does the Vd tell you about where the drug is in the body?
In general
A smaller apparent Vd suggests a drug confined to plasma and extracellular fluid
A larger apparent Vd suggests drug is distributed throughout tissues
Compare where drugs are found if there Vd is <12L compared to >200L
<12L - found mostly in plasma
> 200L majority distributed, sequestered into other tissues
Describe the stages of metabolism
Drug
Phase 1 enzymes
Oxidation/ dealkylation/ reduction/ hydrolysis
Phase 2 enzymes
Glucoronide/ sulphate/ glutathione/ N-acetyl
Conjugates
-> gall bladder -> bile
OR
-> kidney -> urine
Explain how cytochrome P450 isoenzymes are affected by exogenous substances
CYP1A - induced by smoking CYP2C - many inhibitors CYP2D - metabolises many drugs CYP2E - alcohol metabolism CYP3A - 50% therapeutics
Majority of phase 1 catalysed reactions utilise the P450 system
How do CYP450 enzymes work on most drugs and how else can they work?
Active -> inactive (most)
Inactive -> active (perindorpril -> perindoprilat/ levodopa -> dopamine)
Active -> active (codeine-> morphine/ diazepam -> oxazepam)
Induced/ inhibited by endogenous/ exogenous compounds affecting phase 1 metabolism e.g. age, hepatic disease, blood flow, alcohol (antibiotics), cigarette smoking
What effect does grapefruit juice have on statin therapy?
CYP3A4 inhibition -> increased statin (simvastatin/ lovastatin) plasma concentration -> more likely time get side effects
How is CYP 2D6 affected by genetic variations, substrates and other drugs?
CYP 2D6
- Absent in 7% Caucasians
- Hyperactive/ increased induction in 30% East Africans
- substrates include beta blockers, many SSRIs, some opioids
- inhibited by some SSRIs, other antiarrhythmic agents and other antidepressants
How are drugs eliminated?
Primarily via kidney
Fluids (sweat, tears, genital secretions, saliva, breast milk)
Solids (faeces, hair)
Gases (volatile compounds e.g. alcohol)
What Drugs are normally renally metabolised? What affects this?
Typically low molecular weight polar metabolites
Affected by: GFR, protein binding (gentamicin), competition for transporters (penicillin), lipid solubility/ PH/ flow rate (aspirin)
What is clearance? How do you calculate it?
Clearance of drug from the body - clearance from all routes, both metabolism and excretion taken together (mL/ min), mostly GFR
- volume of blood cleared per unit time (mL/ min)
Rate of elimination from body (mg/min) / drug concentration in plasma (mg/ mL)
What drugs are normally hepatically metabolised? What affects this?
Typically high molecular weight - conjugated with glucuronic acid (phase 2)
Bile -> faeces or reabsorbed -> enterohepatic circulation
Antibiotic drug interactions (manipulate gut biome, change rate of reabsorption)
