Pharmacology 4 - Pharmacokinetics Flashcards
List the stages that occur between drug administration and removal
- Absorption
- Distribution
- Metabolism
- Excretion
Why are pharmacokinetics important?
- It determines the dose of a drug available to tissues
- The journey a drug takes through the body
List possible methods of drug administration
- Dermal
- Intramuscular
- Subcutaneous
- Intraperitoneal
- Intravenous
- Inhalation
- Injestion
Compare entral and parentral administration
- Parentral is outside GI tract (dermal, intramuscular, subcutaneous, intravenous, inhalation)
- Enteral is gastroinestinal administration (via injestion)
How do drugs move around the body?
- Bulk flow transfer in the bloodstream
- Diffusional transfer (molecule by molecule over short distances)
- Have to transverse both aqueous and lipid environment
How do drugs cross lipid barriers (cell membrane)?
- Simple diffusion (lipid soluble)
- Carrier process
- Pinocytosis
- Diffusion across aqueous pores (least relevant- has to be very small)
What lipid membranes are crossed when oral route of administration is used?
- Small intestine to ECF to intestinal capillary
- Target tissue capillary to target cell, where it binds to receptor
Describe the general structure of most drugs, and how it is effected?
- Most drugs are weak acids or weak bases.
- They exist in ionised and non-ionised forms, and the ratio depends on pH
Why does pH affect drug transport across lipid membranes?
As the non-ionised form of drugs are more lipid soluble and can cross lipid membranes and be transported easier.
- Therefore the form at physiological pH is important.
How is dissociation constant determined? Write down the equation for a weak base and weak acid
Henderson-Hasslebalch equation
List the factors affecting drug distribution
- Regional blood flow (highly metabolically active tissues have denser capillary networks)
- Extracellular binding (plasma-protein binding)
- Capillary permeability
- Localisation in tissues
How does extracellular binding affect distribution?
- If a drug is bound to a plasma protein it is going to stay in the blood for a long time
- Eg. warfarin 90% bound to plasma protein - dose must be adjusted so the warfarin available is enough to produce an effect.
- Seen more in acidic drugs
- If taking multiple drugs that bind to plasma protein, this can result in displacement and altered percentage reaching target tissue
How does capillary permeability affect distribution?
- Affects how easy it is for the drug to reach the tissue (water soluble drugs)
- Continuous capillary - need to be small enough to fit through gaps or have mechanism to cross the cells
- Blood brain barrier - tight junctions very hard for drugs to get across
How does localisation in tissues affect distribution?
- The drug can sit in some tissues, such as adipose tissue. Only a small amount of the drug passes through there (2% blood supply)
- Very fat soluble drugs can be stored in fat (75%) and gradually secreted into the blood (eg. general anaesthetic)
What are the two major routes of drug excretion?
- Kidney is responsible for most elimination, lost in urine
- Liver is responsible for some drugs, usually large molecular weight conjugates found in bile and lost in faeces
