Fundamentals-of-Pharmacology-dynamics.pdf

PHARMACODYNAMICS ◦Pharmacodynamics is the study of actions of the drugs on the body (what the drug does to the body) and their mechanism of action, i.e to know what drugs do and how they do it. ◦The mechanism by which drugs produce biochemical and physiologic changes in the body. ◦ e.g drugs m...

PHARMACODYNAMICS ◦Pharmacodynamics is the study of actions of the drugs on the body (what the drug does to the body) and their mechanism of action, i.e to know what drugs do and how they do it. ◦The mechanism by which drugs produce biochemical and physiologic changes in the body. ◦ e.g drugs may  or  the secretions, but they cannot change the basic function of any physiological system. Mechanism of Action ◦ Mechanism of action is a medical term that describes how a medication works in the body. For example, osmotic laxative (magnesium citrate) The mechanism of action for this medication is it pulls water into the bowel, which softens stool and increases the likelihood of a bowel movement. Dose Response The dose of medication required to achieve the desired response to the medication. As the dose increases, the response of the drug may increase, as well as the potential for toxicity. This response helps determine the therapeutic index of a drug, or the effective dose range. The measured response and dose are often graphed perpendicular to each other, with the slope of the graph’s curve representing therapeutic index (or overall dose-effect). Dose-response curves representing effective dose and toxic dose for the same drug Terminologies Receptor A binding site located on the surface/inside the effector cell that serves to recognize the signal molecule/drug and initiate the response to it, but has no other function itself. Ligand A molecule which binds selectively to a receptor site. Affinity The ability to bind with the receptor Efficacy Potential maximum therapeutic response a drug can produce “LOCK & KEY” Model of RECEPTORS Terminologies Potency Amount of drug needed to produce an effect Agonist Activates a receptor to produce an effect similar to that of the physiological signal molecule Antagonist Prevents the action of an agonist on a receptor or the subsequent response but does not have an effect of its own Partial Agonist  Activates a receptor to produce a sub maximal effect but antagonizes the actions of a full agonist Agonist – a chemical that binds to a receptor and activates the receptor to produce a biological response ( AFFINITY and INTRINSIC ACTIVITY) Antagonist – a chemical that has AFFINITY but NO EFFICACY  Receptors ◦ Intracellular receptors ◦ Located in the cytoplasm or nucleus of the cell ◦ Recognize small, hydrophobic ligands ◦ Primary target: transcription factors in the cell nucleus that regulate gene expression. ◦ Cell-surface receptors ◦ Embedded into the plasma membrane ◦ Bind to hydrophilic ligands ◦ 3 types: a. ligand-gated channels, b. G-protein coupled receptors, c. enzyme-linked receptors Ligand-gated ion channel ◦ Also know as ionotropic receptors ◦ Form channels or pores that are generally closed. ◦ Enclose ion selective channels (for Na+,K+,Ca2+ or Cl-) within their molecules. Examples: nicotinic cholinergic, GABA-A, and 5HT3 receptors G-protein coupled receptors ◦ Also know as seven-pass transmembrane receptors ; they are long proteins that have one end that sits outside the cell, then the snake-like protein dips in and out of the cell membrane seven times and finally ends on the inside of the cell. ◦ Extracellular : contains ligand-binding side ◦ Intracellular: (when activated) interacts with a G protein ( α, β, γ) Examples: Muscarinic, Dopamine D2, β-adrenergic, α1-adrenergic, α2- adrenergic, GABAB , 5-HT Enzyme-linked receptors ◦ Are usually single-pass transmembrane proteins, meaning that they have only one transmembrane segment ◦ The extracellular end of these receptors binds to medications, and their intracellular end has enzyme activity. ◦ Examples: Insulin, Epidermal growth factor (EGF), Nerve growth factor (NGF) receptors, Growth hormone, many cytokines, interferons Potency and Efficacy Potency - (strength) refers to the amount of the drug required to produce the desired effect. Efficacy - the drug’s capacity to produce an effect. Therapeutic Index ◦Is the ratio between the dosage of a drug that causes a toxic effect and the dosage that causes a therapeutic effect. ◦This value represents the margin of drug safety. ◦The larger the difference, the greater the therapeutic index.  efficacy toxicity TD50 – the minimum amount of drug that causes Minimum Maximum tolerated adverse effects in 50% of effective dose the pop’n dose ED50 – the quantity of a drug that can produce desired therapeutic effects in 50% of the pop’n  HIGH LOW  NSAIDs – aspirin,  lithium Tylenol, ibuprofen  phenytoin  Most antibiotics  phenobarbital  beta-blockers  antibiotics – genta/vanco/amik  immunosuppressive Safer drug has a higher therapeutic index and more dangerous drug has a lower therapeutic index Low TI drugs must be dosed carefully and patients should be monitored closely for signs of drug toxicity.