3. pharmacodynamics by Dr Jamal UOH.pptx

**Title: Pharmacodynamics: Understanding Drug Actions and Effects**

**Description:**

Welcome to this detailed presentation on pharmacodynamics. This PowerPoint aims to provide a comprehensive overview of how drugs exert their effects on the body, including the interactions between drugs and their target sites, and the subsequent physiological responses.

**Key Topics Covered:**
- **Introduction to Pharmacodynamics:** Definition and importance of studying drug actions in the context of therapy and drug development.
- **Drug-Receptor Interactions:** Explanation of how drugs bind to receptors and the types of receptors involved (e.g., G-protein coupled receptors, ion channels).
- **Dose-Response Relationship:** Exploration of how the dose of a drug influences the magnitude of its effect, including concepts like EC50 and maximum efficacy.
- **Pharmacological Agonists and Antagonists:** Distinctions between agonists, antagonists, partial agonists, and inverse agonists, and their clinical implications.
- **Mechanisms of Drug Action:** Overview of various mechanisms through which drugs produce their effects, including enzyme inhibition, ion channel modulation, and receptor activation.
- **Therapeutic and Adverse Effects:** Discussion on how pharmacodynamic principles relate to therapeutic effects as well as potential side effects and toxicity.
- **Pharmacodynamic Modeling:** Introduction to methods used to predict and analyze drug effects using mathematical and computational models.
- **Clinical Relevance:** How pharmacodynamic concepts are applied in drug selection, dosage determination, and treatment planning.

This presentation is designed for students, healthcare professionals, and anyone interested in understanding the science behind drug actions. It combines fundamental theories with practical examples, providing valuable insights into the complex interactions between drugs and their biological targets.

1. Dr Jamal Tariq PT

2. Pharmacodynamics (PD) is the study of the effects of drugs on the body, including the physiological and biochemical changes that occur after drug administration. Importance in physical therapy Understanding pharmacodynamics is crucial for physical therapists to: - Anticipate potential side effects and interactions with physical therapy interventions - Optimize patient outcomes by adjusting physical therapy plans accordingly - Collaborate effectively with healthcare teams, including physicians and pharmacists Relevance to physical therapy Physical therapists often work with patients taking medications that affect the musculoskeletal, cardiovascular, and nervous systems. Understanding pharmacodynamics helps physical therapists design safe and effective treatment plans.

3. Binding to receptors: Drugs bind to specific receptors on cell surfaces, triggering responses. Example: Morphine binds to opioid receptors, reducing pain perception.

4. Activation or inhibition of enzymes Drugs can activate or inhibit enzymes, affecting biochemical pathways.

5. Alteration of membrane permeability: Drugs can change cell membrane permeability, affecting ion flux and cellular activity. Example: Local anesthetics block sodium channels, reducing pain transmission. Other examples: Calcium channel blockers (CCBs), Potassium channel openers (KCOs) Stimulation or inhibition of hormone production: Drugs can influence hormone production, impacting various physiological processes. Example: Beta blockers reduce adrenaline production, slowing heart rate and blood pressure Hormone examples: Insulin (glucose regulation), Thyroxine (metabolism regulation)

6. Receptor binding - Agonists: - Activate receptors, mimicking natural ligands - Example: Albuterol (Ventolin) binds to beta-2 receptors, relaxing airway smooth muscle - Antagonists: - Block receptors, reducing or eliminating natural ligand effects - Example: Naloxone (Narcan) binds to opioid receptors, reversing opioid overdose effects - Partial agonists: - Activate receptors partially, producing a reduced response - Example: Buprenorphine (Subutex) binds to opioid receptors, providing analgesia with reduced risk of addiction

7. RECEPTOR Pharmacology defines a receptor as any biologic molecule to which a drug binds and produces a measurable response. enzymes, nucleic acids, and structural proteins can be considered to be pharmacologic receptors. the richest sources of therapeutically exploitable pharmacologic receptors are proteins that are responsible for transducing extracellular signals into intracellular responses.

8. These receptors may be divided into four families: 1) ligand-gated ion channels, 2) G protein–coupled receptors, 3) enzyme–linked receptors/ Tyrosine Kinase-Linked Receptors and 4) intracellular receptors/Ligand-Activated Transcription Factors.

9. Hydrophilic ligands interact with receptors that are found on the cell surface. hydrophobic ligands can enter cells through the lipid bilayers of the cell membrane to interact with receptors found inside cells

10. Ligand-gated ion channels Also known as ionotropic receptors responsible for regulation of the flow of ions across cell membranes Response to these receptors is very rapid, enduring for only a few milliseconds. These receptors mediate diverse functions, including neurotransmission, cardiac conduction, and muscle contraction.

11. For example, stimulation of the nicotinic receptor by acetylcholine results in sodium influx, generation of an action potential, and activation of contraction in skeletal muscle. Benzodiazepines, on the other hand, enhance the stimulation of the γ-aminobutyric acid (GABA) receptor by GABA, resulting in increased chloride influx and hyperpolarization of the respective cell.

12. G protein–coupled receptors: Also called metabotropic receptors. These receptors comprise a single α helical peptide that has seven membrane spanning regions. The extracellular domain of this receptor usually contains the ligand-binding area. Intracellularly, these receptors are linked to a G protein (Gs, Gi, and others) having three subunits, an α subunit that binds guanosine triphosphate (GTP) and a β and γ subunit . Binding of the appropriate ligand to the extracellular region of the receptor activates the G protein so that GTP replaces guanosine diphosphate (GDP) on the α subunit.

13. Dissociation of the G protein occurs, and both the α-GTP subunit and the βγ subunit subsequently interact with other cellular effectors, usually an enzyme, a protein, or an ion channel. These effectors then activate second messengers that are responsible for further actions within the cell. Stimulation of these receptors results in responses that last several seconds to minutes. G protein–coupled receptors are the most abundant type of receptors, and their activation accounts for the actions of most therapeutic agents. Important processes mediated by G protein–coupled receptors include neurotransmission, olfaction, and vision.

14. Second messengers: These are essential in conducting and amplifying signals coming from G protein–coupled receptors. A common pathway turned on by Gs , and other types of G proteins, is the activation of adenylyl cyclase by α-GTP subunits, which results in the production of cyclic adenosine monophosphate (cAMP)—a second messenger that regulates protein phosphorylation. G proteins also activate phospholipase C, which is responsible for the generation of two other second messengers, namely inositol-1,4,5-trisphosphate (IP3) and diacylglycerol (DAG) . IP3 is responsible for the regulation of intracellular free calcium concentrations , and of other proteins as well. DAG activates several enzymes such as protein kinase C (PKC) within the cell leading to a myriad of physiological effects.

15. Enzyme-linked receptors A third major family of receptors consists of a protein that spans the membrane once and may form dimers or multi subunit complexes. Duration of responses to stimulation of these receptors is on the order of minutes to hours. Metabolism, growth, and differentiation are important biological functions controlled by these types of receptors .

16. Typically, upon binding of the ligand to receptor subunits, the receptor undergoes conformational changes , converting kinases from their inactive forms to active forms. Enzyme-linked receptors

17. Intracellular receptors The fourth family of receptors differs considerably from the other three in that the receptor is entirely intracellular , and , therefore, the ligand must diffuse into the cell to interact with the receptor.

18. The receptor ligands are lipid soluble, they are transported in the body attached to plasma proteins such as albumin . The primary targets of these ligand -receptor Complexes are transcription factors . The activation or inactivation of these factors causes the transcription of DNA into RNA and translation of RNA into an array of proteins . For example, steroid hormones exert their action on target cells via this receptor mechanism. Intracellular receptors

19. Dr.Rahma Fazeel

20. The activated ligand –receptor complex migrates or translocates to the nucleus, where it binds to specific DNA sequences, resulting in the regulation of gene expression. The time course of activation and response of these receptors is much longer than that of the other mechanisms. Because gene expression and, therefore, protein synthesis is modified, cellular responses are not observed until considerable time has elapsed (30 minutes or more), and the duration of the response (hours to days) is much greater than that of other receptor families. Intracellular receptors

21. Drug potency refers to the strength or effectiveness of a drug in producing desired therapeutic effect or response. It is a measure of the drug’s ability to bind to its target site (receptor, enzyme etc.) and trigger a biological response. Higher potency drugs require lower doses to achieve the desired effect, while lower potency drugs require higher doses. Potency is different from efficacy, which refers to maximum effect a drug can produce. A drug can b highly potent but have limited efficacy, or vice versa

22. Drug Interactions Synergism: - Enhanced effect when two or more drugs are combined - Example: Combining acetaminophen (Tylenol) and ibuprofen (Advil) produces greater pain relief than either drug alone- Antagonism: - Reduced effect when two or more drugs are combined - Example: Combining a beta blocker (metoprolol) with a calcium channel blocker (verapamil) reduces the effectiveness of both drugs - Potentiation: - Increased duration or intensity of drug effect when combined with another drug - Example: Combining a muscle relaxant (cyclobenzaprine) with a benzodiazepine (diazepam) increases the risk of respiratory depression

23. Pharmacodynamics in Physical Therapy Pain management: - Analgesics (acetaminophen, ibuprofen) - NSAIDs (aspirin, naproxen) - Opioid analgesics (morphine, fentanyl) Inflammation management: - Steroids (prednisone) - NSAIDs (ibuprofen, naproxen) Muscle tone management: Muscle relaxants (cyclobenzaprine, baclofen) Benzodiazepines (diazepam, clonazepam) Cardiovascular management: Beta blockers (metoprolol, atenolol) Diuretics (furosemide, hydrochlorothiazide) Calcium channel blockers (verapamil, diltiazem)

24. Case Study Patient with knee osteoarthritis - Physical therapy plan: - Exercise (strengthening, flexibility) - Manual therapy (joint mobilization, soft tissue mobilization) - Pharmacological interventions: - Analgesics (acetaminophen) - NSAIDs (ibuprofen) - Corticosteroid injections (triamcinolone) - Potential interactions and side effects: - Increased risk of gastrointestinal bleeding with NSAIDs - Potential for analgesic dependence or addiction - Increased risk of muscle toxicity with corticosteroid injections

25. Conclusion - Pharmacodynamics is essential for physical therapists to understand - Appropriate use of drugs can enhance physical therapy outcomes - Awareness of potential interactions and side effects is crucial for safe and effective patient care - Physical therapists should collaborate with healthcare teams to optimize patient care