chapter 2

• Pharmacodynamics focuses on the study of the action or effect of drugs in the body
• Pharmacodynamics includes the study of the different effects of drugs when changing the dose or concentration
• Pharmacodynamics involves the interaction of drugs with molecules in the body, specifically receptors
• Receptors are molecules in the body that drugs bind to, leading to a series of physiological events and responses
• Orphan receptors are receptors whose ligands are currently unknown, making them a target for new drug development
• Most receptors in the body are regulatory proteins that, when bound by drugs, elicit physiological responses
• Examples of substances that bind to regulatory proteins include neurotransmitters like nor epinephrine and acetylcholine
• Neurotransmitters are produced by neurons and carry messages to different organs in the body
• Hormones, another type of chemical messenger, are produced by glands like insulin from the pancreas and epinephrine from the adrenal medulla
• Enzymes, although primarily involved in speeding up chemical reactions, can also act as drug receptors by being activated or inhibited by drugs
• Examples of enzymes that interact with drugs include dihydrofolate reductase, which is inhibited by methotrexate
• Cyclo-oxygenase (COX) enzymes are inhibited by NSAIDs like aspirin and ibuprofen, leading to the inhibition of inflammatory chemicals in the body
• Transport proteins like the sodium-potassium ATPase pump regulate the exchange of sodium and potassium ions across cell membranes
• Structural proteins like tubulin contribute to cell structure and can also be targeted by drugs as receptors
• Excessive uric acid in the body, a degradation product of purines, can lead to conditions like gout due to deposits in joints causing pain and inflammation
• Class one receptors, also known as ionotropic receptors, are located in the cell membrane and have a fast action when a drug binds to them, typically in milliseconds
• Examples of class one receptors include nicotinic receptors, which are associated with ligand-gated ion channels
• Nicotinic receptors are found in the cell membrane and when nicotine binds to them, the sodium ion channel opens, leading to the cell becoming more positive and active
• Nicotinic receptors are stimulants of the central nervous system (CNS) as they make the cells more positive and active
• GABA receptors, another type of class one receptor, when activated by GABA, open chloride channels causing the cell to become more negative and depressed in function
• GABA stands for gamma amino butyric acid and is responsible for calming down the brain activity
• Benzodiazepines (BZD) are examples of drugs that act on class one receptors to slow down the firing of neurons, used for anxiety and as hypnotics
• Examples of benzodiazepines include alprazolam (Xanax) and diazepam (Valium)
• Class two receptors, also known as metabotropic receptors, are also located in the cell membrane but have a slower effect compared to class one receptors, typically in seconds
• G proteins are involved in the mechanism of action of class two receptors, with three types of G proteins: Gs, Gi, and Gq
• Gs stimulates adenylyl cyclase enzyme to produce cyclic adenosine monophosphate (cAMP) as a secondary messenger
• Gi inhibits adenylyl cyclase enzyme, leading to no cAMP production
• Gq activates phospholipase C enzyme to produce inositol triphosphate (IP3) and diacylglycerol (DAG) as secondary messengers
• Receptors can be proteins, including transport proteins, enzymes, and structural proteins
• There are four subtypes of receptors
• Class one receptors are ionotropic receptors, also known as ligand-gated receptors
• Ligands binding to ionotropic receptors open ion channels, leading to depolarization of cells
• Examples include nicotinic receptors and GABA receptors
• Class two receptors are G protein-coupled receptors (metabotropic receptors)
• These receptors are slower in their effects compared to class one receptors
• Different types of G proteins include Gs (stimulate), Gi (inhibit), and Gq (activate phospholipase C)
• G proteins lead to the production of secondary messengers like cAMP, IP3, and DAG
• Class three receptors are enzyme-linked receptors
• These receptors are much slower in their effects, taking minutes to hours to show an effect
• Examples include epidermal growth factor and atrial natriuretic peptide (ANP)