Pharmacodynamics.pptxHow Drug Act, Basics of Molecular Pharmacology.pptx 10 Mb

How Drug Act, Basics of Molecular Pharmacology.pptx
10 Mb

1. PHARMACODYNAMICS

2. Pharmacodynamics: Pharmacodynamics is the study of how drugs act on the body and how their concentration affects the strength of the response. Drug-Receptor Interactions Most drugs work by interacting with receptors —special proteins found on the cell surface or inside the cell.

3. Drug-Receptor Complex : Key to Drug Action Every receptor is designed to recognize a specific drug or molecule, just like a lock and key. When a drug binds to its receptor: Inactive receptor (R) → Activated receptor (R) * The activated receptor triggers a response inside the cell. Example: The heart has different receptors for epinephrine (adrenaline) and acetylcholine , both of which control heart function in different ways.

4. Drug Binds to Receptor ⬇️ 2️⃣ Receptor Activation (Conformational change) ⬇️ 3️⃣ Intracellular Signaling Pathways (Second messengers, enzyme activation, ion channel modulation) ⬇️ 4️⃣ Cellular Response (Gene expression, protein synthesis, metabolic changes) ⬇️ 5️⃣ Physiological Effect (Therapeutic or adverse effects) Signal transduction When a drug binds to its receptor, it triggers a series of changes in the cell, known as signal transduction .

5. 🔹 Ligand – Any molecule (natural or drug) that binds to a receptor. 🔹 Affinity – The degree to which a substance tends to combine with another. 🔹 Intrinsic activity – Intrinsic activity is defined as ability of the agonist to activate the receptor  and produce an effect 🔹 Second messengers – Molecules that help transmit the signal inside the cell

6. Agonists: Activators of Receptors An agonist is a drug that binds to a receptor and activates it , producing a biological effect. It can either mimic the body's natural substances or produce a unique response. Types of Agonists Full Agonists 🚀 Completely activates the receptor, producing the maximum possible effect . Example: Phenylephrine activates α1-adrenoceptors , increasing blood pressure by causing blood vessels to constrict.

7. Partial Agonists ⚖️ Partially activates the receptor but can’t produce the maximum effect. Even if all receptors are occupied, it will never be as strong as a full agonist. Interesting fact: A partial agonist can act as an antagonist if given along with a full agonist. Example: Aripiprazole , used in schizophrenia, balances dopamine levels by either activating or blocking receptors. Inverse Agonists 🔄 Instead of activating the receptor, it stabilizes its inactive form , reducing its baseline activity. Opposite effect of an agonist. Example: Some drugs reduce excessive receptor activity to restore normal function.

8. Antagonists: Blockers of Receptors An antagonist is a drug that blocks the action of an agonist or natural substance without activating the receptor itself. It only works when an agonist is present. Types of Antagonists Competitive Antagonists 🏆 ( Reversible) Compete with agonists for the same binding site. Can be overcome by increasing the dose of the agonist . Example: Terazosin lowers blood pressure by competing with norepinephrine at α1-adrenoceptors

9. Noncompetitive Antagonism ( Irreversible Antagonists) 🔒 Bind permanently to the receptor, making it useless. The effect cannot be reversed , even by increasing the agonist dose. Two types: Active site binding (permanently blocks receptor). Allosteric site binding (changes receptor shape so the agonist can’t bind). 2. Functional/Physiological Antagonists ⚡ Work on a different receptor but have opposite effects. Example: Epinephrine relaxes airways, counteracting histamine , which causes bronchoconstriction (used in allergic reactions). 3. Chemical Antagonists 🧪 Directly neutralize an agonist. Example: Protamine sulfate neutralizes heparin (a blood thinner).

10. Drug Potency (EC50) Efficacy Candesartan (BP medicine) High (low dose needed) Moderate effect Irbesartan (BP medicine) Lower (higher dose needed) Same effect Dose–Response Relationships The effect of a drug depends on: 🔹 The dose given 🔹 How the body absorbs, distributes, metabolizes, and eliminates it (Pharmacokinetics) 1. Graded Dose–Response Relationship As the dose increases , the effect increases . 📈 When we plot dose vs. effect, we get: ✅ Linear graph = Hyperbola ✅ Logarithmic graph = S-shaped (Sigmoid Curve) Key Terms 🔹 Potency (Strength) = How much drug is needed for 50% of the maximum effect ( EC50 ). 🔹 Efficacy (Maximum Effect) = The highest effect a drug can achieve ( Emax ). Example of Potency & Efficacy 🔹 A very potent drug is not always the best —Efficacy matters more!

11. Quantal Dose–Response Relationships This concept explains how drug doses affect a group of people rather than just an individual. A quantal response means the effect either happens or it doesn’t (e.g., a drug lowers blood pressure by at least 5 mmHg or it doesn’t). Even continuous effects can be studied this way by setting a threshold for response. Why is this important? It helps determine the right doses for most people

12. Therapeutic Index (TI) – A Measure of Drug Safety TI = TD₅₀ / ED₅₀ TD₅₀ (Toxic Dose 50%) → Dose that causes harmful effects in half the population. ED₅₀ (Effective Dose 50%) → Dose that works for half the population. Higher TI = Safer Drug (large gap between effective and toxic doses). Lower TI = Risky Drug (small gap between effective and toxic doses).

13. Examples: Safe vs. Risky Drugs Warfarin (Narrow TI – Risky) Works by preventing blood clots but can easily cause bleeding if the dose is slightly too high. Small changes in dose make a big difference → Careful monitoring needed. Penicillin (Wide TI – Safe) Can be given in much higher doses than needed without harm. No need for strict monitoring → Safe for most people.

14. Four Major Types of Receptors Drugs work through different receptor types based on their chemical nature: 1 . Ligand-Gated Ion Channels (Fast Response - Milliseconds) These receptors control ion flow across the cell membrane. When a ligand binds, the channel opens, allowing ions to enter the cell. Example: Nicotinic receptors open sodium channels → Muscle contraction. 2. G Protein-Coupled Receptors (GPCRs) (Seconds to Minutes) The most common receptor type. They work by activating G proteins , which then trigger second messengers . Example: β-Adrenoceptors → Activated by epinephrine → Increases heart rate. GABA Receptors → Activated by benzodiazepines → Produces a calming effect.

15. 3. Enzyme-Linked Receptors (Minutes to Hours) These receptors have built-in enzyme activity. When a ligand binds, it activates enzymes inside the cell. Example: Insulin receptors → Control glucose metabolism. 4. Intracellular Receptors (Slow Response - Hours to Days) These receptors are found inside the cell. The drug must cross the cell membrane to bind. Example: Steroid hormones (like cortisol) bind to their receptors → Affect gene

16. Receptor Type Response Speed Function Example 1. Ligand-Gated Ion Channels ⚡ Fast (milliseconds) Allow ions (charged particles) to enter the cell Nicotinic receptors → Muscle contraction 2. G Protein-Coupled Receptors (GPCRs) 🔄 Medium (seconds to minutes) Activate internal signals β-Adrenoceptors → Heart rate increase 3. Enzyme-Linked Receptors ⏳ Slow (minutes to hours) Control metabolism & cell growth Insulin receptors → Regulate blood sugar 4. Intracellular Receptors 🐢 Very slow (hours to days) Affect genes & long-term changes Steroid hormones → Control inflammation Four Major Types of Receptors

17. Tolerance Tolerance happens when the body gets used to a drug after repeated use, so a higher dose is needed to get the same effect. Common with CNS drugs like painkillers (morphine), sedatives (barbiturates), and alcohol. Cross-tolerance: If two drugs are similar, tolerance to one may also apply to the other (e.g., morphine and methadone). Causes of Tolerance: Receptor Changes: The body’s receptors become less sensitive, so more drug is needed. Enzyme Induction: The liver produces more enzymes to break down the drug faster, reducing its effect. Decreased Absorption: The body absorbs less of the drug over time, making it less effective. Tolerance can lead to dependence, where stopping the drug suddenly causes withdrawal symptoms.

18. Tachyphylaxis This is a fast-developing tolerance where repeated doses of a drug stop working, even if the dose is increased. Happens quickly (unlike regular tolerance, which develops over time). Example: Ephedrine (used for nasal congestion) loses effectiveness if taken repeatedly in a short period.

19. Variation in Drug Responsiveness Not everyone responds to a drug in the same way. Even the same person may respond differently to a drug at different times. This variation can be due to several factors, including genetics, metabolism, disease conditions, and drug interactions.

20. Types of Variations in Drug Response Unusual (Idiosyncratic) Responses Some people experience rare or unexpected drug effects. Often caused by genetic differences or allergic reactions. Quantitative Variations Some people may need higher doses (hyporeactive) or lower doses (hyperreactive) for the same effect. If a drug response decreases over time, tolerance develops. If tolerance happens very quickly , it's called tachyphylaxis .

21. Factors Affecting Drug Response Drug Levels in the Body Absorption, metabolism, distribution, and excretion affect how much drug reaches the target. Liver, kidney function, age, weight, and genetics play a role. Some cells pump drugs out using special transporters (MDR genes), making them resistant (e.g., cancer cells resisting chemotherapy). Natural Body Substances (Endogenous Ligands) If a person has high levels of a natural substance, a drug may have a stronger effect. Example: A heart rate-lowering drug (like propranolol) works better in someone with high adrenaline levels but has little effect on an athlete with low resting heart rate.

22. Receptor Number & Function More receptors = Stronger response Fewer receptors = Weaker response Long-term drug use can increase (upregulation) or decrease (downregulation) receptor numbers. Stopping certain drugs suddenly can cause severe withdrawal effects due to receptor changes. Example: Stopping clonidine (a blood pressure drug) suddenly can cause a dangerous rise in blood pressure. Changes After the Receptor (Post-Receptor Effects) A drug’s effect depends on how well the body’s systems respond. Disease conditions and compensatory body mechanisms may reduce drug effectiveness. Example: Some patients develop resistance to blood pressure drugs due to kidney compensation.

23. Pharmacogenetics & Personalized Medicine People have different drug responses due to genetic differences. Some cancer treatments work better in patients with specific genetic mutations. Doctors may use genetic testing to select the best drug for each patient.