Pharmacokinetics Flashcards
What is the process of Pharmacokinetics?
Dose administered - drug in bloodstream - drug in tissues- drug metabolised or excreted
OR
- Drug binding at site of action
- toxicity or efficacy
What is the therapeutic range?
- aims to keep concentration of drug in the plasma within a certain range
- minimum toxic concentration . above this = toxicity
- Min therapeutic concentration = below = no beneficial effect
How do drugs move across membranes?
- Through passive diffusion
- small molecules move faster
-solubility in the lipid bilayer - Inside - lipid bilayer = hydrophobic (not too much tho!)
- Facilitated Transport (carrier mediated)
- Passive
- Bidirectional
- Relies upon conc gradient
- slc (solute carrier) = Organic Anion/Cation Transporters
- Active transport
- If drug is a substrate for transporter/carrier which pumps drugs back into lumen
- ATP-driven pumps
(ABC superfamily like P-glycoprotein - Can also occur in the kidney, brain`
What is the effect of pH in the stomach/intestine for weak acids?
- Many drugs are weak acids
- Charged drugs do not cross membranes
- Low PH = h+ = high, EQUILIBRIUM GOES TOWARDS HA
- VERY little ionised = lots absorbed
- High pH, H+ = low. More ionised, less absorbed
- Charged ions do not pass the membrane
What is the effect of pH in the stomach/intestine for weak bases?
Low pH= High H+ = equilibrium goes towards BH+
- Lots ionised
- Little absorbed
- High pH , less ionised , more absorbed
What is the effect of pH in the kidney?
Weak bases
- Charged drugs do not cross membranes
- At low pH , [H+] is high, equilibrium goes towards BH+
- Lots ionised = little absorbed
= At high pH [H+] is low
- Less ionised = more absorbed
What are the principles of Pharmacokinetics ?
- Absorption from the site of administration
- Distribution within the body
- Metabolism
- Excretion
How is the rate of absorption into systemic circulation modified?
- site of administration
- drug formation
What is the definition of absorption?
- The transfer of drug from the site of administration to the systemic circulation
What is Bioavailability (F)?
F = Quantity of drug reaching systemic circulation as intact drug/ Quantity of drug administered (i.e. does)
What is bioequivalence?
- If the drug preparation contains the same active ingredient
AND - When the rates and extents of bioavailability of the active ingredient in the two products are not significantly different.
What factors affect absorption from the gut?
- Gastric emptying ( taking meds on an empty stomach)
- Gastrointestinal motility
- Blood flow
- Particle size and formulation
- Physiochemical factors e.g. solubility, molecular weight, binding to calcium (esp. in milk) or fat in food
- Metabolism ( enzyme-catalysed reactions)
What is the first pass effect?
- When drugs are metabolised by enzymes in the gut wall or liver
What may metabolism in the gut or liver lead to?
- Activation of pro drug- one that is converted to an active form by enzymes in the liver
OR
-Inactivation - when a drug converted to inactive metabolites.
What are the routes of absorption from the GI tract?
- Mouth,Rectal - avoids first pass metabolism
– Sub-lingual
– Buccal - Oral
- Duodenal
What is the sub-lingual (glyceryl trinitrate) route of administration?
- undergoes first pass metabolism
- Needs a quick response (does not go into stomach)
- given as a spray or tablet under tongue
- given for angina
What are sub-cutaneous routes of adminstrations (Examples)?
- Local anaesthetics, that act locally
- Can be given with vasoconstrictor to delay systemic absorption
What are intra-muscular depot preparations?
- Contraceptives
- Gradual release, sustained concentrations
- Convenience
What are examples of rectal adminstered drugs?
Anti-epileptic drugs
- Diazepam for epilepsy when there is continuous fittings
What are examples of topic drugs?
- Anti-inflammatories
- Ibuprofen, avoids irritation to stomach
- Corticosteroids, avoid systemic side effects
What are examples of intra-articular anti-inflammatories?
- Corticosteroids, direct to target, avoids systemic side effects.
What is the effect of plasma protein binding on distribution?
- Can slow down the elimination of the drug
How are drugs distributed?
- Different drugs distributed in different ways
- Lipid soluble/water soluble drugs have a smaller distribution in the body = slower elimination in the body.
What is the volume of distribution (Vd)?
The volume of plasma that would contain the total body content of the drug at a concentration equal to that of plasma.
- concentration = mass/ volume
