Pharmacology Flashcards
Partiel agonist
Promotes a stimulatory respons, that is lower than the maximal respons (elicited by the full agonist). The partial agonist is an antagonist compared to the full agonist.
Invers agonist
A drug that binds to the same receptor as an agonist but induces a pharmacological response opposite to that of the agonist. (<12%)
Affinity
How well the ligand is binding to the receptor. Is expressed as KD and/or Bmax.
KD
The dissociation constant, is commonly used to describe the affinity between a ligand and its receptor. Therefore, Kd can be used as a measure of binding affinity (how tightly a ligand binds to a receptor).
The ligand concentration (X-axis) that gives 50% of the maximum specific binding. A higher KD means that you require a higher concentration of ligand to bind 50% of the target (high KD = low affinity)
IC50
Antagonist concentration that inhibits 50% of the max agonist response.
Bmax
Maximal binding capacity ( fx the number of receptors per cell or per mg membrane protein) - only important in experimental conditions.
Potency
The amount of agonist needed for a given response. Measured as EC50 (the agonist concentration that elicits 50% of max. activation)
EC50
The concentration of an agonist that produces 50% of the maximal response for that agonist.
Efficacy
The degree of activation (effect).
The maximum response that can be achieved with a drug. Expressed as Emax (the maximal achievable response for a given agonist).
Therapeutic window/index
Describes the dosage range between a minimum effective therapeutic concentration, and the minimum toxic concentration.
Is calculated by TD50/ED50.
ED50 and TD50
ED50: the dose required to produce a therapeutic effect in 50% of the population
TD50: the dose required to produce a toxic effect in 50% of the population.
Therapeutic range
The plasma drug concentration that has the intended therapeutic effect with minimal side effects.
Allosteric binding
When an effector molecule binds to a site that is different from the agonist binding site.
Competitive antagonist
A competitive antagonist binds to the same site as the agonist but does not activate it, thus blocks the agonist’s action. (If there are both an agonist and competitive antagonist present, then there will be a change in potency, but no change in Emax).
Noncompetitive antagonist
A non-competitive antagonist binds to an allosteric (non-agonist) site on the receptor to prevent activation of the receptor. (If there are both a agonist and a noncompetitive antagonist present, then there will be bo change in potency, but a change in Emax).
Tachyphylaxis
A rapid response to a large initial dose of a drug. To protect itself, the cell desynthesizes itself to how much drug is out there. The cell can do this by:
1. Decrease the synthesis of the receptor (less receptor to bind to).
2. Enzymes can phosphate residues to the receptors, and thereby inhibit or inactivate the receptor.
3. Endocytosis of the receptor.
Tolerance
A chronic response to a drug, the signal is weakened within days and weeks.
The cell protects itself by endocytosis of receptors and by stopping the synthesis of receptors.
There is an increase in metabolic enzymes, that work to break down the drug. When they break down the drug, it will reduce the efficacy of the drug, that will reduce the response that the drug will produce in the body. It is possible to overcome the activity of the enzyme if the enzyme gets oversaturated, so an increase in dose, can overcome the decreased response/effect.
Desensitization
When the effect of the drug is weakened within minutes after activation.
Resistance
When the activity of the drug disappears (e.g. resistance to chemotherapy).
First pass effect
The phenomenon where orally administered drugs are eliminated on the first pass by the (1) gut epithelia, (2) liver, or (3) lungs. Majority of the first pass effect are due to the liver.
Bioavailability (F)
It is the proportion of the drug that is absorbed and can then be distributed. IV will have a bioavailability of 1 and all other routes are measured compared to this.
(F = AUC p.o. / AUC i.v)
Factors that affect the bioavailability
Solubility - hydrophobic and small drugs have a high bioavailability, the opposite has a low.
Instability - drugs can be degraded by e.g. HCl in the stomach.
First pass effect - low first pass effect, increased bioavailability
What can affect the absorption of a drug?
pH - easier to absorb a non polar drug.
Blood flow - a decreased blood flow to a particular organ, results in a decreased absorption.
Total surface area + contact time - diseases that destroy the vili and microvili, the surface area all decrease and decrease the absorption.
P-glycoprotein - this protein will transfer the drug right back to the GIT. Then the drug will not be absorbed.
Types of administration
Topical (skin or mucous surface) - slow effect and can cause local irritation.
Oral - easy and convenient, but there is higher first pass effect and can cause irritation.
IV - low first pass effect and fast absorption.
Rectal - absorption can be unreliable but can be rapid and more complete than following oral administration. Less first pass effect than oral.
Sublingual - rapid response, low first pass effect as the drug won’t be degraded by gastric pH or be rapidly metabolized by the liver. Potentially poor absorption.
Pulmonary - fast absorption, high first pass effect.
