Principles of Pharmacology Flashcards
Pharmacology Definition
The study of drug action
Therapeutics Definition
Drug prescribing and the treatment of disease (more focused on the patient)
Pharmacodynamics
what the drug does to the body
Pharmacokinetics
what the body does to the drug
Main 3 questions for pharmacodynamics
- Where is this effect produced?
- What is the target for the drug?
- What is the produced response after interaction with the target?
What are the 4 main drug targets?
- Receptors
- Enzymes
- Ion channels
- Transport proteins
Selectivity
- lock and key model
- necessary for a drug to be an effective therapuetic agent
What is a factor that impacts dosage?
The selectivity of the drug, however it is difficult to accurately predict how much of a drug might bind to the desired target protein
What are the 4 ways drugs can interact with target receptors?
- Electrostatic
- Hydrophobic
- Covalent
- Stereospecific
What is an electrostatic interaction?
MOST COMMON
involves hydrogen bonds and Van der Waals forces
What is a hydrophobic interaction?
Involved with lipid-soluble drugs
What is a covalent interaction?
LEAST COMMON
tendency to be irreversible
What is a stereospecific interactions?
due to the presence of stereoisomers and interact stereospecifically with receptors.
Describe the relationship between drug+receptor and the drug-receptor complex
Proportional, at equilibrium
Agonists
drugs that bind and activate receptors
Antagonists
drugs that only bind tot he receptors
Affinity
determines the strength of the binding of the drug to the receptor, and therefore the drug-receptor complex
A high affinity leads to…
High receptor occupancy
Efficacy
the ability of an individual drug molecule to produce an effect once bound to a receptor
Difference between antagonists, partial agonists and full agonists
The size of the response caused by the binding of the drug molecule to the receptor
Potency
concentration or dose required to produce a defined effect.
Measure of potency
the concentration/dose required to produce a 50% tissue response EC/D50
(half maximal effective concentration/dose)
A highly potent drug…
produces a large response at relatively low concentrations
A highly efficacious drug…
produces a maximal response, irrelevant of the drug concentration
What are the 4 major pharmacokinetic factors?
- Absorption
- Distribution
- Metabolism
- Excretion
Absorption
the passage of a drug from the site of administration into the plasma
Bioavailability
the fraction of the initial dose that gains access to systematic circulation
Difference between absorption and bioavailability
absorption is the process, whereas bioavailability is the outcome of the transfer
What are the main forms of drug administration?
- IV administration (100%) Lower than 100%: - Oral - Inhalational - Dermal (percutaneous) - Intra-nasal
What are the 2 main forms of drug transfer?
- Bulk Flow transfer (bloodstream - 100%)
- Diffusional transfer
(molecule by molecule - <100%, lipid membrane)
2 unlikely routes for diffusion
- pinocytosis
- diffusion across aqueous route
2 most likely routes for drug transport
- diffusion across lipid membranes (only possible if lipid soluble)
- carrier mediated transport (including a transmembrane protein)
The solubility of most drugs is…
water soluble not lipid soluble
What is the impact of ionisation on solubility?
The unionised form of the drug retains more lipid solubility, and therefore more likely to diffuse across lipid membranes.
What does ionisation depend on?
- The dissociation constant (pKa) of the drug
- The pH of the part of the body
if the pKa (of the drug) and the pH (of the tissue) are equal…
The drug will be equally dissociated between the 2 forms
What pKa do most weak acids have?
Between pKa 3-5
For weak acids, as pH decreases…
The unionised form starts to dominate
For weak acids, as the pH increases…
The ionised form starts to dominate
Factors that effect tissue distribution
- Regional blood flow
- Plasma protein binding
- Capillary permeability
- Tissue localisation
Regional blood flow by organs
- Liver: 27%
- Heart: 4%
- Brain: 14%
- Kidneys: 22%
- Muscles: 20%
changes depending on circumstance (exercise or food)
Factors affecting plasma protein binding
- the free drug concentration
- the affinity for the protein binding sites
- the plasma protein concentration
What is the plasma concentration required for a clinical effect in the majority of drugs?
A maximum of 1.2mmol/l
the same as the binding capacity fo albumin alone
Saturation and plasma protein binding
Plasma proteins are NEVER fully saturated
What causes the difference in the extent of plasma protein binding?
Due to the particular affinity for the protein binding sites for that particular drug
What nature of drugs bind better to plasma proteins?
Acidic drugs bind well to albumin.
Why do drugs dissociate from plasma proteins?
Only free drug is able to diffuse out of blood and into tissues.
What are the different types of capillary structure?
- H2O filled gap junction, continuous
- Tight junction (blood brain barrier)
- Continuous, discontinuous and fenestrated
Transport through continuous membranes.
- Very lipid soluble: diffuse across endothelial cells
- Carrier proteins
What are the benefits of the discontinuous capillaries in the liver?
Allows for drugs to easily diffuse out of the bloodstream and match the high metabolic demands of the liver
The glomerulus of the kidney and fenestrated capillaries
Main function of the kidney is excretion
What is the impact Tissue localisation on drug transport in the BBB?
Drugs move down the concentration gradient, the brain has a high concentration of lipids, the blood has a higher water content. Equilibrium means water soluble drugs are retains in the plasma and vice versa.
