Fichas
Pharmacokinetics
Fichas del conjunto (62)
- 1define pharmacokineticswhat the body does to the drug
- 2pharmacodynamicswhat the drug does to the body
- 34 main criteria of ADME(liberation)
absorption
distribution
metabolism
excretion - 4liberationthe process of release of a drug from the pharmaceutical formulation
- 5absorptionprocess of substance entering the blood circulation
- 6distributiondispersion of substance through fluids/tissues of the body
- 7metabolismrecognition by organism that a foreign substance is present and irreversible transformation of parent compounds into daughter metabolites
- 8excretionremoval of the substance from the body
- 9oral route advantages and disadvantagesa - Convenient
d - First-pass effect, many variables and barriers. - 10Sublingual adv and disa - no first pass effect
d - Inconvenient, small dose limit, taste - 11inhalationa - fast, rapid delivery to blood
d - Requires special properites of drug (e.g. atomised, vapourised) - 12topicala - Convenient, localised
d - Only local - 13transdermala - Prolonged release
d - Skin very effective barrier - 14intramusculara - Rapid for aqueous, slow for oil
d - Painful, requires trained personnel - 15intravenousa - direct, total dose, rapid
d - Requires professional, infection risk, rapid response - 16how does bioavailability differ between iv and oral doese?- iv gives 100% bioavailability
- oral is much lower - 17define bioavailabilityFraction of unchanged drug that reaches the systemic circulation
- 18what are the 4 ways in which small molecules can cross cell membranes1) Diffusing directly through the lipid
-Lipid solubility highly important - need to be uncharged and lipophilic
2) Diffusing through aqueous pores
- More likely important for diffusion of gases
3) Transmembrane carrier protein
e.g. solute carriers - drugs can hijack these
4) Pinocytosis
– Mostly macromolecules, not drugs - 19what is the solubility of ionised drugs?- low lipid solubility
- 20what are the main drug properties that affect absorption ?- lipophilicity
- ionisation - 21list some factors that affect distribution- Degree of drug ionisation
- Lipid solubility
- pH of compartments
- Cardiac output and blood flow
- Capillary permeability
- Plasma protein binding - 22what do phosphonate groups have a high affinity for?calcium
- 23what drugs are quickly distributed to the skeleton?- bisphosphonates due to phosphonate having high affinity for calcium
- 24name some bisphosphonatesOral - alendronate – Daily/weekly
IV- zoledronate – Yearly - 25what do drugs have to be free to do?- to distribute widely or bind to its receptor
- 26what are the plasma proteins that drugs can bind to?– Albumin
– α-1 acid glycoprotein
– Lipoproteins
– Globulins - 27what can cause big increases in free drug conc?- competition fro binding sites on albumin /plasma proteins
- 28how low can the percentage of unbound drug be?as low as 1%
- 29why is taking aspirin with warfarin dangerous?-98% of warfarin is bound to albumin
- aspirin has a high affinity for albumin
- aspirin fights for binding sites and displaces some of the warfarin = creating or unbound warfarin = more of a pharmacological effect on the patient - 30why does unbound warfarin have to be kept within a tight limit?too much unbound warfarin will mean the blood with be too thin
not enough and the blood will clot - 31how is body water distributed?Body water is distributed in to four main compartments
- specialist compartments exist and factors such as perfusion influence distribution - 32what does the degree of distribution between these compartment depend on ?tissue and drug dependent factors
- 33how can the side effects of some drugs be minimised?y limiting their distribution via the route of administration
- 34describe first stage of metabolismPhase I metabolism
• Generally oxidation, reduction or hydrolysis – Introduce/reveal a reactive chemical group
– “Functionalisation”
• Products often more reactive - 35stage 2 metabolismPhase II metabolism
• Synthetic, conjugative reactions
• Hydrophilic, inactive compounds generated (usually)
- makes drug more dissolvable in water- excreted better by kidneys - 36which stage produces reactive products1
- 37which stage produces hydrophilic products2
- 38what is the function of cytochrome P450 enzymes?Throughout the body, extensively in the liver
• Biosynthesis of steroids, fatty acids and bile acids
• Metabolism of endogenous and exogenous substrates - 39paracetamols small therapeutic windowthe toxic metabolites are combined with glutathione which are then conjugated and excreted
but when glutathione is delepletd the toxic metabolites combine with hepatic enzymes and this leads to toxicity - 40why can you not take phenobarbital land warfarin together?phenobarbital increases expression of CYP450s
warfarin is metabolised by CYP450s
=reduction in effectiveness of warfarin - 41grapefruit juice and statins- statins metabolised by CYP3A$
- grapefruit juice blocks this enzyme
= statins not metabolised - 42what do different routes of metabolism allow?allow for patient- specific choices to be made
– E.g. Genetic variability, disease state, other treatments - 43what is the aim of drug metabolites?that they can be excreted
- 44what are the 2 things metabolites can be?active or toxic
- 45metabolic enzymes- Genetic variability in metabolic enzymes occurs,
- expression of metabolic enzymes can be induced and/or inhibited
- Competition for metabolic enzymes occurs and metabolic pathways can be saturated - 46how can metabolism affect drugs?their bioavailability
- 47how are drugs eliminated?- either unchanged or as metabolites
- 48which drugs are eliminated more readily?hydrophilic rather than lipophilic
- 49list some possible sources of excretion• Breath
• Urine
• Saliva
• Perspiration
• Hair
• Feces
• Milk
• Bile - 50what is the important organ in elimination of drugs?kidneys
- 51what is the therapeutic window?a ratio between minimum effective concentrations (MEC) to the minimum toxic concentration (MTC)
- 52onset of actiontime between taking drug and reaching minimum effective concentration
- 53duration of actiontime spent above ineffective zone
- 54peak plasma concentration and time to peak plasma concentrationCmax (peak of the graph) horizontal line
Tmax (vertical line) down from Cmax - 55absorption half lifeamount of time it takes to absorb half the peak concentration of drug
- half cmax - 56effect of absorption half lifepeak plasma conc of drug decreases a step absorption like increases
a longer half life = longer duration of action, and a longer onset of action - 57plasma clearance (elimination) half lifego to Cmax, go to half way point,
then calculate how long it take to get from Cmax to that half way point.
= amount of time it takes to elimination half the Cmax. - 58repeated dosesnot waiting required time in between does = summation of drug conc, can push yourself towards the probability of getting to the toxic conc
- 59describe the plasma drug concentration during IV infusionPlasma concentration increases during infusion until rate of input equals rate of output
- there is a plateau - called a steady state Css - 60factors that can affect pharmacokinetic parameters- age
-sex
- pregnancy
- body weight
-genetic variability
- diet
-disease
-other medications
- ethnicity - 61what are the 5 body fluid compartments?- plasma water5%
- interstitial water16%
- fat 20 %
- intracellular water 35%
- transcellular water 2% - 62what 4 things change movement between the 5 body compartments?• Permeability across tissue barriers
• Binding within compartments
• pH partition
• Fat:water partition
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- Descripción
- Pharmacology Fichas sobre Pharmacokinetics, creado por hazel wilkie el 03/05/2017.
- Creado por
- hazel wilkie
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