pharmacokinetics Flashcards
what are the 6 rights of prescribing?
- Right patient
- Right drug
- Right route
- Right dose
- Right time
- Right outcome
what is pharmacokinetics? 5
what the body does to the drug
- Facilitates safe and effective use of medicines
- Determines optimal dosage regimen (dose, route, dose interval, duration of treatment)
- Predicts potential drug interactions
- ADME (absorption, distribution, metabolism, excretion)
what is absorption?
- Drug transfer from its site of administration to the systemic circulation (blood)
what are the routes of drug administration? 6
- Enteral
- parenteral
- topical
- transdermal
- inhalation
- intrathecal
describe the enteral routes of drug administration? 4
- Oral
- Rectal
- Sublingual
- Buccal
what factors influence enteral absorption? 6
- GI motility
- Absorptive area
- GI blood flow
- Drug particle size and formulation
- Drug physicochemical properties
- Drug binding
describe druge physiochemical properties- solubility? 4
- Lipid soluble= non-ionized molecules (NaCl)
- Hydrophilic (polar)= ionized molecules (Na+, K+)
- So:
- The more lipid soluble a drug the greater the absorption
- The more water soluble a drug the less the absorption
describe drug physiochemical properties pH? 7
- Acidic drugs are better absorbed in acidic media
- Basic drugs are better absorbed in basic media
- Acidic (aspirin) better absorbed in the stomach
- Basic (diazepam) better absorbed in intestines
- Acidic drugs are better excreted in basic media
- Basic drugs are better excreted in acidic media
- This can be important in poisoning?
what are the different parenteral routes of drug administration? 4
- intramuscular
- subcutaneous
- intravenous
- intradermal
describe bioavailability? 2
- Fraction of the administered (oral) dose of a drug that reaches the systemic circulation
- Oral AUC/ IV AUC (AUC= under the curve)
describe first pass metabolism?
refers to the metabolism of the drug prior to reaching system circulation
what is bioequivalence?
two drugs are considered bioequivalent when there is no significant difference in the rate or extent of bioavailability at the same molar dose and under the same conditions
describe relevance?
different formulations from different companies and different batches of drugs from the same company
where do most drugs end up after absorption?
systemic circulation
describe drug distribution? 2
- Process by which the drug is transferred reversibly from the systemic circulation into the tissues as concentrations in the blood increase, and from the tissues into the blood when blood concentrations decrease during elimination
- Distribution of the drug into vascular, interstitial and intracellular compartments
how does distribution occur? 3
- Most drugs transfer by passive diffusion
- Across capillary walls down a concentration gradient
- Into interstitial fluid until concentration of free drug molecules into interstitium is equal to that in plasma
describe plasma protein binding of drugs? 5
- Drugs bind non-specifically to albumin in plasma
- Drug and protein- drug-protein complex
- Reversible and saturable
- Unbound or free fraction distributes
- Unbound portion is responsible for the clinical effect
name some highly protein bound drugs? 7
- Warfarin
- Phenytoin
- Aspirin
- Thyroxine
- Ibuprofen
- Heparin
- Furosemide
what are the different body fluid compartments? 3
- plasma volume= 3L
- interstitial fluid= 12L
- intracellular fluid volume= 25L
what factors can influence drug distribution? 6
- Drug physicochemical properties
- Lipid solubility
- Water solubility
- Drug particle size
- Drug protein binding
- The environment- blood flow; pH
describe the apparent volume of distribution? 4
- A concept that seeks to predict how extensively a drug is distributed throughout the body
- Volume into which a drug appears to be distributed with a concentration equal to that of plasma
- Drugs that have a large Vd will need to be administered in larger doses to achieve a target concentration in the plasma
- Apparent volume of distribution (Vd)= dose/ concentration
what do we do mean if a drug has a low Vd? 2
in the middle? 4
high? 2
- Vd<10L
- Highly protein bound drug so retained in the plasma
- Vd= 10-30L
- Water soluble drugs, low lipid solubility
- Distributed into interstitial fluid but not cells
- Dose on ideal body weight to avoid toxicity
- Vd>100L
- Fat soluble drug distributes into tissues
describe the two phases of drug metabolism?
Phase 1: the drug can become active (pro-drug), inactive or toxic due to oxidation (P450 cytochrome, reduction and hydrolysis)
Phase 2: drug solubilisation by conjunction- glucuronidation, acetylation, sulfation, methylation elimination in urine or bile
what is a prodrug?
a drug or compound that is metabolised into a pharmacologically active drug
describe rapid cytochrome P450 inhibitors? 8
- Amiodarone
- Ciprofloxacin
- Erythromycin/ clarithromycin
- Metronidazole
- Fluconazole
- Isoniazid
- Alcohol
- Grapefruit juice
describe slow cytochrome P450 inhibitors? 4
- Carbamazepine
- Phenytoin
- Rifampicin
- Alcohol
what is a therapeutic index?
the ratio of concentration associated with toxicity vs concentration associated with efficacy
explain what can lead to potential fr an adverse drug interaction?
- A drug metabolised by CYP450 with a narrow therapeutic index/ window + cytochrome P450 inhibitor
describe genetics and drug metabolism? 6
- Genetic polymorphisms are multiple genetic variants (allele combinations) which result in different phenotypes
- Polymorphisms of drug metabolising enzymes can affect drug handling
- Extensive metaboliser= two active normal alleles
- Intermediate metaboliser= one normal and one abnormal allele
- Poor metaboliser= two abnormal alleles
- Ultrarapid metabolisers= duplication of normal alleles
describe codeine phosphate and CYP2D6? 2
- CYP2D6 polymorphism with ultrarapid metaboliser effect causes opiate toxicity in some individuals even at a low dose. This causes an exaggerated response to codeine
- CYP2D6 polymorphism with poor metaboliser effect causes inadequate pain relief by codeine in some individuals
describe how the activity of N-acetyltransferase is genetically determined? 3
- Fast acetylators at increased risk of isoniazid hepatoxicity
- Slow acetylators at increased risk of isoniazid neuropathy
- Slow acetylators at increased risk of drug induced lupus with hydralazine
describe the rate of drug metabolism in non-saturable metabolism and saturable metabolism?
- rate of drug metabolism is proportional to drug concentration (first order kinetics)
- the rate of drug metabolism is independent of drug concentration in saturable metabolism (zero order kinetics)
describe drug clearance? 3
- The sum of all the drug-eliminating processes, principally determined by hepatic metabolism and renal excretion
- It can also be defined as the theoretical volume of fluid from which a drug is completely removed in a given period of time
- Kidneys are the main drug excreting organ with urine
what are the components of renal excretion? 3
- Glomerular filtration- glomerulus
- Secretion- proximal convoluted tubule
- Reabsorption- distal convoluted tubule
name some other excretory methods? 5
- Bile
- Sweat
- Exhaled air
- Saliva
- Breast milk
what are causes of low drug clearance? 7
- Normal variation
- Renal impairment
- Liver impairment
- Enzyme inhibition
- Genetic poor metaboliser
- Neonate
- Old age
what are the causes of high drug clearance? 4
- Normal variation
- Increased renal blood flow
- Genetic hypermetabolism
- Enzyme induction
what is half life?
what does if provide information on? 3
Time for the concentration of drug in plasma to halve
- Time course of drug elimination
- Time course of drug accumulation
- Choice of dose interval
describe the dosing of drugs? 3
- Loading dose is determined by the volume of distribution
- Maintenance dose is determined by the clearance
- Dose interval is determined by the half life
what is the equation for half life?
proportional to- volume of distribution / clearance
