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
Describe the process of drug excretion in the kidney
- Glomerular filtration (dependent on molecular weight)
- Active secretion of basic/acidic drugs (dependent on transport proteins)
- Passive reabsorption of lipid soluble drugs (dependent on urine pH and extent of drug metabolism)
Describe the process of drug excretion from the liver
- Liver has discontinuous structure
- Biliary excretion (large molecular weight molecules)
- Active transport systems transport the molecules into bile
Describe enterohepatic cycling
- Drug/metabolite excreted into the gut via bile
- Gut bacteria break down the conjugate to lipid soluble form, so the drug is reabsorbed
- Taken to the liver
- Excreted again
- Leads to drug persistence
Define bioavailability
Proportion of the administered drug that is available within the body to exert its pharmacological effect
- Linked to absorption
Define apparent volume of distribution
The volume in which a drug appears to be distributed - an indicator of the pattern of distribution
Define biological half-life
- Time taken for the concentration of a drug (in the blood/plasma) to fall to half its original value
- Linked to metabolism/ excretion
Define clearance
- Blood clearance is the volume of blood/plasma cleared of a drug (where the drug is completely removed) in a unit of time
- Related to excretion
Compare systemic and local drug administration
- Systemic reaches the entire organism (cannabis, aspirin, nicotine patch)
- Local affects one organ/tissue (salbutamol, antacid, betnovate)
Compare aspirin and morphine at physiological pH
- Aspirin is a weak acid (proton donor)
- Morphine is a weak base (proton acceptor)
Write the equation used to determine the proportion of a drug ionised and unionised
Rearranged henderson-hasslebach
10^(pKa - pH)
- Acids ratio unionised/ionised
- Bases ratio ionised/unionised
Describe the relationship between pH and pKa with regards to ionisation
- In acids as pH is higher above pKa there are more ionised molecules (less lipid soluble)
- In bases pH above pKa more unionised (more lipid soluble)
How is aspirin effective?
- More unionised in the stomach so can easily enter the bloodstream
- Less ionised in the blood so less easily cross lipid membranes
Why might treatment with IV sodium bicarbonate increase aspirin excretion?
- Sodium bicarbonate will increase urine pH
- Aspirin will be more ionised
- Then aspirin will not be reabsorbed into the urine
List the non-major routes of excretion
- Lungs (alcohol test)
- Skin
- GI secretions
- Saliva
- Sweat
- Milk
- Genital secretions
How does bioavailability affect efficacy?
- Increase bioavailability increases efficacy
- This is because there is a larger concentration of drug available to cause its physiological effects
