Flashcards
Pharmacokinetics
Flashcards do conjunto (44)
- 1What is pharmacokinetics?How the body effects the drug
- 2What factors are considered in pharmacokinetics?Administration - Delivery of the drug to the body
Absorption - Movement of the drug across the membrane
Distribution - The drugs movement into different compartments of the body
Metabolism - Chemical alteration of the drug
Elimination - How the drug is removed from the body - 3What are the two ways in which a drug will travel through the body?Bulk flow - via bloodstream
Diffusion - Molecule by molecule via membranes - 4What mode of movement is most important to the structure of the drug?Diffusion - The structure of the drug will determine for example if it is non-polar enough to be able to pass through a lipid membrane
- 5What is the number of molecules crossing the membrane determined by?The concentration difference across the membrane (high to low)
The permeability coefficient (p) - 6What is the permeability coefficient determined by?How lipid soluble the drug is
Diffusivity - A constant value for how well two molecules can diffuse - 7Outline what is meant by ionisation trappingDrugs exist as weak acids or weak bases. When they are in a pH of similar value (eg an Acid in an acidic environment) it is said to be in the unionised form. This form can permeate through membranes.
When the drug is in a pH of opposite value (eg an Acid in alkaline) it is said to be in the ionised form and cannot permeate membranes and is hence said to be trapped - 8When will a weak acid ionise?In a high pH (alkaline conditions)
- 9When will a weak base ionise?In low pH (acidic conditions)
- 10Using a diagram outline the ionisation trapping effect on aspirinnotes
- 11What is the effect of ionisation?The rate of permeation though membranes
The distribution of drugs between compartments - 12When will a drug become trapped in a compartment of the body?If the compartment forces the drug into the ionised form, the drug can therefore theoretically not move anywhere
- 13Why does ion trapping rarely occur in the body?pH is rarely in equilibrium
In practise, membranes are not totally impermeable to ionised drug - 14When however is ion trapping relevant?Renal system and blood brain barrier
- 15How can ion trapping be manipulated for use?Increasing the acidification of the urine will increase the speed of excretion of weak bases.
Increasing the plasma pH (by administering bicarbonate) will enable the extraction of weak acid drugs from the CNS - 16Where might drug be wrongly absorbed?Plasma proteins - At therapeutic concentrations, large majorities of drug are bound to plasma proteins. Only unbound drug is active.
Body Fat - The ease with which drug enters body fat is determined by its fat:water partition coefficient. Most drugs have a low value and so do not move in easily. Also body fat has a low blood supply and hence delivery of the drug to fat is low.
The only real significance is in chronic treatment where over time the drug may accumulate in fat. - 17Where does chloroquine accumulate?The malaria drug accumulates in melanin, which can lead to ocular toxicity
- 18Why do we not need to know the mechanics of absorption for intravenous injection?Because the primary target for any drug is the blood stream. Intravenous drugs directly enter the blood stream
- 19Other than IV injected drugs, what is the main sight for absorption?The small intestine
- 20What factors effect absorption of drug into the small intestine?Occurs via passive diffusion
Level of ionisation - Acids greater than pH3 and bases greater than pH10 are ionised
Carrier Mediated transport
Gastrointestinal motility - An increased digestion rate will increase absorption speed
Splanchnic blood flow - Impaired blood flow will lead to impaired absorption
Particle size and formation of drug
Physicochemical factors - 21How much of an orally administered drug will be absorbed and how long does this take?75% from 1-3 hours
- 22Define bioavailabilityThe amount of drug that reaches the systemic circulation in comparison to the amount administered
- 23What factors effect drug distribution?Membrane permeability of compartments
Plasma bound levels
pH and ion trapping
fat:water partition - 24During which circumstances would the brain be susceptible to drug absorption?Inflammation
Chemoreceptor Trigger Zone - 25Why is the BBB susceptible to drug absorption during inflammation?The BBB loses integrity and hence drugs can penetrate through
- 26Why is the BBB susceptible at the chemoreceptor Trigger zone?The BBB is weak here and as such some uptake of drug is possible here
- 27What kind of drugs can cross the placenta?Lipid soluble, not highly polar or large
- 28What are the two phases of drug metabolism?Phase 1 - Catabolic
Phase 2 - Anabolic - 29Outline the initial stage of Phase 1Initially a reactive group is added in a process known as functionalisation. The drug then undergoes oxidation via the hepatic P450 system
- 30Outline the main part of Phase 2The drug combines with P450 (which contains Fe3+)
NADPH - P450 reductase then donates an electron
The Fe3+ is reduced to Fe2+ (with drug)
The Fe2+ can now be combined with oxygen (Fe2+o2 + drug)
NADPH - P450 or cytochrome b5 donates a H+ or e-
Fe2+OOH + drug is formed
Another H+ is added to form ferric oxene (FeO)3+ + Drug
This ferric oxene is capable of removing a H+ from the drug to oxidise it
The drug is now oxidised - 31What is the most important point of Phase 1?The formation of ferric oxene to oxidise the drug
- 32What are the 3 cytochrome p450 enzyme families?CYP1
CYP2
CYP3 - 33Outline Phase 2?This takes place in the liver and involves the covalent bonding of a group to the phase 1 product which leaves the product of phase 1 pharmacologically inactive
- 34What is the aim of drug metabolism?To render the foreign drug useless which is achieved by making it less lipid soluble and also by making it pharmacologically inactive
Phase 1 will oxidise, reduce and hydrolyse, whilst phase 2 results in an inactive polar molecule - 35Which are excreted quicker, metabolites or parent drug?Metabolite
- 36What 3 process are involved in the renal excretion of drugs?Glomerular Filtration
Reabsoprtion
Tubular Secretion - 37Outline glomerular filtration stageDrugs of molecular weight below 20,000 will pass through.
Proteins bound to drug will prevent the drug being filtered - 38Outline reabsorption phaseThis stage underlines why the body does Phase 1 and 2 reactions.
99% of a non-polar, lipid soluble drug will be reabsorbed and taken out of the kidney - 39Outline tubular secretionThis is the most effective stage of excretion. 80% of a drug is taken into the nephrons here via the proximal tuble using special transporters
- 40Which capillary delivers drugs from the proximal tuble?Peritubular
- 41What are the two transporters in the proximal tuble?Organic anion transporters (OAT) - acidic drugs
Organic cation transporters (OCT) - organic bases - 42Why is the proximal tubule drug clearance so high compared to the glomerulus?Only 20% of drug is absorbed via the glomerulus because a large amount will be bound to serum protein.
The transporters in the proximal tubule can achieve maximal clearance despite when the drug is bound to protein - 43Define renal clearance and give the equationThe volume of plasma containing the total amount of drug that is removed from the body
CLr = (Cu x Vu) / Cp - 44What are the one and two compartment models?One compartment - The body is one compartment
Two compartment - The body is 2 compartments (plasma and organ) and (fat and bone)
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- FlashCards sobre Pharmacokinetics, criado por ajanxi em 25-04-2015.
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- ajanxi
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