Flashcards in Pk Deck (18):
Advantage of parenteral administration? Risks?
Avoids first pass effect, malabsorption, vomiting.
Has 100% bioavailability
Can be used in impaired consciousness and dysphagia
Advantage of enteral administration? Disadvantages?
Cheap, painless, uninvasive
Can't be used if consciousness impaired or in dysphagia.
Affected by first pass metabolism
What factors affect plasma concentration of a drug?
Rate of uptake
First pass metabolism - metabolism occurring before the systemic circulation - gut lumen, gut wall -> hepatic portal vein -> liver
What is bioavailability? How is measured clinically?
Fraction of a drug that reaches the systemic circulation once it has overcome the barriers to absorption.
Depends on drug and route used:
Area under the curve plasma conc/time
What factors affect adoption of a drug?
Presence of active transport systems
Splanchnic blood flow - reduced in shock/HF
Destruction of gut/bacterial enzymes
What is distribution of a drug and what factors affect it?
Ability of drug to dissolve in body compartments.
Lipophilicity/hydrophobicity- if it is more lipophilic it will have a lower blood concentration as it will partition out into tissues with a high lipid content (higher volume of distribution)
Protein binding: if it binds to plasma proteins like albumin it will reduce its entry into other tissues and the amount available to exert a pharmacological effect (lower volume of distribution)
Binding to tissue proteins – drug moves from plasma to tissue – which decreases the concentration available (increases the volume of distribution)
Mass/volume of tissue and density of binding sites – varies from patient to patient depending on muscle mass, adiposity etc
What is the volume of distribution? What drugs have high Vd/low Vd
Measure of how widely a drug is distributed
(total amount of drug in body) / (plasma concentration of drug at time zero)
Dose/peak plasma conc of drug at time 0
If the drug passes into other fluid compartments (ECF, ICF) then plasma concentration will be lower, and Vd would be 10-30 litres (the volume of the respective fluid compartments)
If the drug is super lipid soluble or binds heavily to tissue protein then a lot of the drug is removed from the tissue and the plasma concentration is very low, and the Vd can appear very large (hundreds of litres)
Describe drug meatbolism
Inactivates drugs into water soluble products ready for renal elimination - particularly essential for lipophilic compounds.
Phase one reactions include oxidation and reduction, phase two reactions include conjugation (With glutathione/glucoronic acid/sulphate).
Describe phase I reactions, what carries this out? How does rate of metabolism vary?
Oxidation and reduction, this is dependent on the activity of the Cytochrome P450 enzymes
Some drugs, herbal remedies and foods (eg grapefruit juice) can induce the CYP enzymes while others can inhibit them
Everyone has a different selection of CYP enzymes and so while one drug may inhibit CYP enzymes in one person it may not in another
CYP enzymes vary greatly with race, sex, age and physical state, disease state
Everyone has different rates of metabolism so drugs may be eliminated faster in some individuals than others
What occurs in phase II metabolism? Molecules?
Conjugation with a polar molecule to make water soluble (eg glutathione, glucuronic acid, sulphate) via series of enzymes
What is the main route of elimination?
Excretion is carried out by the kidney. The ionic nature of drugs that have been metabolised increases their ability to be excreted by the kidney – they are excreted by glomerular filtration and active tubular secretion, and then can’t diffuse back across the tubule as they are ionic and not lipophilic.
What factors affect the rate of elimination?
Passive tubular reabsorption
Active tubular secretion
• Renal blood flow
• Plasma protein binding
• Tubular urinary pH
• Renal disease
What is clearance of a drug?
Measure of hepatic, renal and other forms of elimination (sweating and biliary elimination) combined
Clearance can be defined as the rate of elimination of a drug from the body.
The volume of plasma that is completely cleared of the drug per unit time.
What factors affect the rate of clearance?
• Heart – cardiovascular or circulatory factors which affect blood flow to organs of elimination
How do drugs stay in the urine to be excreted?
Metabolism makes the drug more ionic and it can then be transported by organic cation transporters (OCT) and organic anion transporters (OAT) in the kidney. Only the ionised form of the drug can enter into the filtrate and then once in there if it becomes unionised it will not be able to be reabsorbed so will be eliminated. The urine pH influences whether the drug is ionised or not in the filtrate: acidic drugs are ionised in basic filtrates and basic drugs are ionised in acidic filtrates.
What is half-life?
The amount of time over which the concentration of a drug in plasma decreases to one half of the concentration it had when it was first measured
How is half-life related to clearance?
Half-life is inversely proportional to clearance