# Pharmacology / How drugs find their targets Canonical URL: https://shipslides.com/d/catalog-health-pharmacology Raw viewer URL: https://content.shipslides.com/d/catalog-health-pharmacology/raw Category: Health Slides: 13 Updated: 2026-05-17T20:55:56.077Z Tags: catalog, health, pharmacology ## Summary Small molecules and large biologics navigating a body of 10 13 cells, looking for the one protein they were designed to bind. Key sections include: PHARMACOLOGY / How drugs find their targets; ADME — what the body does to the drug; What the drug does to the body; Receptors and ligands — keys and locks; Enzyme inhibitors — jamming the machinery; The drugs we actually take; The therapeutic window; Drug development — 10–15 years, ~$2B; Generics and biosimilars; The price of doing pharmacological business. ## Slide Outline 1. PHARMACOLOGY / How drugs find their targets 2. ADME — what the body does to the drug 3. What the drug does to the body 4. Receptors and ligands — keys and locks 5. Enzyme inhibitors — jamming the machinery 6. The drugs we actually take 7. The therapeutic window 8. Drug development — 10–15 years, ~$2B 9. Generics and biosimilars 10. The price of doing pharmacological business 11. The future of finding targets 12. Most R&D fails. The survivors transform medicine. 13. Further reading & viewing ## Slide Transcript ### Slide 1: PHARMACOLOGY / How drugs find their targets - 01 / 13 - Pharmacology · Vol. 09 - Small molecules and large biologics navigating a body of 1013 cells, looking for the one protein they were designed to bind. - A 13-slide field guide · Press → to begin ### Slide 2: ADME — what the body does to the drug - 02 / 13 - Pharmacokinetics - Every dose runs the same gauntlet. The fraction that reaches the target is often single digits. - A · ABSORPTION - Into the bloodstream - Oral, IV, transdermal, inhaled. Bioavailability varies wildly — insulin orally is ~0%. - D · DISTRIBUTION - Through tissues - Bound to plasma proteins, partitioned by lipophilicity. The blood-brain barrier turns most drugs away. - M · METABOLISM - Broken apart - The liver's CYP450 enzymes chop drugs into metabolites — sometimes activating, sometimes deactivating. - E · EXCRETION - Out - Kidneys (urine) and bile (feces) carry the remains. Half-life sets the dosing schedule. ### Slide 3: What the drug does to the body - 03 / 13 - Pharmacodynamics - Pharmacokinetics asks where the drug goes. Pharmacodynamics asks what happens when it gets there. - Almost every drug works by binding a protein — a receptor, an enzyme, an ion channel, a transporter — and changing what that protein does. - The relationship between concentration and effect is rarely linear. Doubling the dose rarely doubles the effect. Saturate the receptors and adding more accomplishes nothing… until you hit the toxicity ceiling. ### Slide 4: Receptors and ligands — keys and locks - 04 / 13 - Molecular Recognition - AgonistActivates the receptor — mimics the natural ligand. Morphine on opioid receptors. - AntagnBlocks the receptor — occupies without activating. Beta-blockers, naloxone. - PartialActivates weakly even at full saturation — ceiling effect. Buprenorphine. - InverseReduces receptor activity below baseline — rare but real. ### Slide 5: Enzyme inhibitors — jamming the machinery - 05 / 13 - Mechanism - Many of the best-selling drugs in history work by sitting in an enzyme's active site so the substrate cannot. - HMG-CoA reductase - Statins - Block cholesterol synthesis in the liver. Atorvastatin, rosuvastatin. Among the most prescribed drugs on Earth. - Angiotensin-converting - ACE inhibitors - Lower blood pressure by stopping the conversion of angiotensin I → II. Lisinopril, enalapril. - Tyrosine kinase - Kinase inhibitors - Shut off rogue growth signals in cancer cells. Imatinib (Gleevec) turned chronic myeloid leukemia into a managed condition. ### Slide 6: The drugs we actually take - 06 / 13 - Therapeutic Classes - vs. infection - Antibiotics - Penicillins, cephalosporins, macrolides, fluoroquinolones. Selectively kill bacterial machinery our cells lack. - vs. pain & inflammation - NSAIDs - Ibuprofen, naproxen, aspirin. Inhibit COX enzymes to reduce prostaglandins. - vs. severe pain - Opioids - Morphine, oxycodone, fentanyl. Bind μ-opioid receptors. Powerfully effective — powerfully addictive. - vs. depression - Antidepressants - SSRIs (sertraline, fluoxetine), SNRIs, MAOIs. Modulate serotonin / norepinephrine over weeks. - vs. clots - Anticoagulants - Warfarin, heparin, DOACs (apixaban, rivaroxaban). Prevent strokes, treat DVT — bleeding is the price. - others - Antihypertensives, antihistamines, antidiabetics… - Each class targets a different receptor, enzyme, or transporter. The categories keep multiplying. ### Slide 7: The therapeutic window - 07 / 13 - Dose — Response - Every drug has a dose where it works and a dose where it kills you. The ratio is the therapeutic index. - WidePenicillin, ibuprofen — forgiving margins, hard to overdose accidentally. - NarrowWarfarin, lithium, digoxin — therapeutic and toxic doses overlap. Blood monitoring required. - RazorChemotherapy — the toxic dose is the therapeutic dose. The art is killing tumor cells slightly faster than the patient. ### Slide 8: Drug development — 10–15 years, ~$2B - 08 / 13 - From Lab to Pharmacy - For every approved drug, roughly 10,000 starting molecules were screened. Most of the cost is paying for the failures. - YR 0–3 - Discovery - Identify target. Screen libraries. Find a hit. - YR 3–6 - Preclinical - Animal toxicology, pharmacokinetics, dosing. - YR 6–8 - Phase I / II - Healthy volunteers (safety), then small patient cohorts (efficacy). - YR 8–12 - Phase III - Thousands of patients. Randomized, controlled, blinded. - YR 12–15 - FDA Approval - Review, label negotiation, post-market surveillance (Phase IV). - Phase III is where most candidates die — a drug that works in 200 people can fail in 2,000. The attrition rate from preclinical to approval is around 90%. ### Slide 9: Generics and biosimilars - 09 / 13 - Patent Cliff - A US drug patent runs 20 years from filing — effectively 8–12 years on market before competitors can copy. - When the patent expires, generic manufacturers must only prove bioequivalence: the active ingredient, the same blood concentration. They skip the discovery, the trials, the failures. - Prices typically fall 80–90% within a year. Atorvastatin went from $5/pill to under 10¢. - GenericIdentical small molecule. Same ibuprofen, different label. Bioequivalence study only. - BiosimFor biologics (antibodies, proteins) — can't be copied exactly. Must prove "no clinically meaningful difference." - BrandOften relaunches as authorized generic, or evergreens via reformulation, new indication, combination product. - Result~90% of US prescriptions are now generic. ~20% of spending. ### Slide 10: The price of doing pharmacological business - 10 / 13 - Side Effects - No drug is selective enough to bind only its intended target. Even when it is, the target does more than one thing. - Predictable - Dose-dependent - Stronger dose, stronger side effect. NSAIDs and ulcers, opioids and constipation, beta-blockers and fatigue. - Unpredictable - Idiosyncratic - Rare reactions specific to the patient — genetic variants, immune responses. Stevens-Johnson syndrome from carbamazepine. - Combinatorial - Drug-drug interactions - One drug induces or inhibits the CYP enzymes that metabolize another. Grapefruit juice does this too. - Adverse drug events cause an estimated ~100,000 US deaths annually — many from interactions in patients on 5+ medications. Polypharmacy is the silent epidemic of modern medicine. ### Slide 11: The future of finding targets - 11 / 13 - What's coming - precision - Targeted therapies - Drugs matched to a tumor's specific mutation, not its tissue of origin. Companion diagnostics required. - guided missiles - ADCs - Antibody-drug conjugates: an antibody finds the cancer cell, the linked toxin kills it. Trastuzumab deruxtecan. - code, not protein - mRNA - Deliver instructions, let the cell build the protein. COVID vaccines were the proof; cancer vaccines are next. - in silico - AI-designed molecules - Generative models propose binders for a protein structure. AlphaFold made every target druggable in principle. - Plus: gene therapies (CRISPR, AAV), PROTACs that destroy proteins instead of inhibiting them, gut-microbiome modulators, psychedelics in psychiatry. The pipeline has never been more diverse. ### Slide 12: Most R&D fails. The survivors transform medicine. - 12 / 13 - The Honest Assessment - Pharma is the only industry where 9 of every 10 products entering human trials never sell a single dose — and the model still works. - It works because the winners win enormously. Statins added years of life to entire populations. ART turned HIV from a death sentence into a chronic condition. Imatinib, GLP-1 agonists, hepatitis C cures, immunotherapy — each one rewrote a chapter of medicine. - The criticism is fair: prices are high, marketing is aggressive, the same molecule costs different amounts in different countries for opaque reasons. The replication crisis touches preclinical research too. - But the alternative — no industry willing to spend a decade and $2B on a 10% shot — is not better drugs. It is no new drugs. - A century ago, an infected cut could kill you. A bad heart meant the funeral home. Cancer meant months. The molecules in the bottle on your nightstand are the accumulated payoff of millions of failed experiments. - Pharmacology is humanity's best argument that biology is, in fact, engineerable. ### Slide 13: Further reading & viewing - 13 / 13 - Closing - Three centuries of trying to make molecules behave. Below, where to keep going. - REFERENCES - BOOKGoodman & Gilman, The Pharmacological Basis of Therapeutics - BOOKDruin Burch, Taking the Medicine: A Short History of Medicine's Beautiful Idea - BOOKBen Goldacre, Bad Pharma - PAPERDiMasi et al., "Innovation in the pharmaceutical industry" (J. Health Econ., 2016) - SITEDrugBank · PubChem · ClinicalTrials.gov - YOUTUBE - → pharmacology+basics - → drug+development+process - End of deck. Press Home to restart, ← to step back. ## Related Decks - [Pharmacology](https://shipslides.com/d/health-pharmacology) - [Aging — The Mechanics of Getting Older](https://shipslides.com/d/catalog-health-aging) - [Anatomia humana — a guided tour](https://shipslides.com/d/catalog-health-anatomy) - [Medical Breakthroughs — The Big Steps That Saved Lives](https://shipslides.com/d/catalog-health-breakthroughs)