Pharmacology Concepts & Calculations (Part 2) PDF

Pharmacology at a glance: concepts and calculations (Part 2) Prof David Leake Learning objectives After this lecture, and further reading as required, students will be able to: Use, with confidence, measures of drug amounts and concentration and express them in appropriate units (mo...

Pharmacology at a glance: concepts and calculations (Part 2) Prof David Leake Learning objectives After this lecture, and further reading as required, students will be able to: Use, with confidence, measures of drug amounts and concentration and express them in appropriate units (moles, molarity) as whole number and as logarithms. Give examples of complementary/alternative medicinal approaches and the questions surrounding their use. Define the set of principles that underpins Pharmacology.  Dose Volume Concentration Weight Molecular weight Molarity A B C Which beaker contains the most substance? How do you know?  Molarity (mol/l OR M): How much of the substance is available in a given volume. [Mass (g) = Concentration (mol/L) x Volume (L) x Formula Weight (g/mol)] Moles and molarity The mole is the unit that defines the amount of a given substance. One mole contains 6 x1023 molecules of a substance. The mass of one mole, in grams, is the molecular weight of that substance.  Calculating molarity By definition a 1M solution of NaCl contains 1 mole (6 x1023 molecules) in 1 litre of solution. So how would you prepare 250 ml of a 0.5mM solution? Mass Concentration Volume 58.44g 1M 1litre 58.44mg 1mM 1litre 29.22mg 0.5mM 1litre 29.22microg 0.5mM 1ml 7.3mg 0.5mM 250ml Biological assays A method of measuring the effects of a biologically active substance using an intermediate in vivo or in vitro tissue or cell model under controlled conditions. For pharmacology; test the activity of a compound against a given ‘target’. What system? Concentration response curve (CRC) Response Concentration [M] Logarithmic scales used to generate concentration response curve. Logarithmic scales A logarithm is defined as the Sigmoidal curve power to which a base (10) must be raised to produce a given number (e.g. Log 100 = 2) Log 10 molar = 1 Log 1 millimolar = -3 Log 1 micromolar = -6 Log 1 nanomolar = -9 *Further help on blackboard*  Concentration response curves Concentration-response relationship for histamine on smooth muscle contraction in the polar bear 1 Normalised Response 0 Log [Compound] (M) Therapeutic concentrations Therapeutic range Alternative medicines Migraine Asthma Epilepsy No direct evidence, after 3000 trials, that acupuncture works better than placebo. Homeopathy Based on 2 implausible principles: 1. like cures like? 2. the greater the dilution, the more potent the medicine? Samuel Hahnemann 1796 Proposed that 30C dilutions were most effective…. 30C represents a dilution factor of 1060……. Remedy for Flu is diluted 10400! Homeopathy Boots: 'we sell homeopathic remedies because they sell, not because they work' Boots, the high street chain that sells homeopathic remedies, has admitted that the products do not necessarily work. Homeopathy is a £40 million industry in the UK Photo: GETTY IMAGES By Ben Leach 7:32AM GMT 26 Nov 2009 Comment Paul Bennett, professional standards director for Boots, told a committee of MPs that the pharmacy chain stocks such items for no other reason than that they are popular. "There is certainly... Overall conclusion 33. By providing homeopathy on the NHS and allowing MHRA licensing of products which subsequently appear on pharmacy shelves, the Government runs the risk of endorsing homeopathy as an efficacious system of medicine. To maintain patient trust, choice and safety, the Government should not endorse the use of placebo treatments, including homeopathy. Homeopathy should not be funded on the NHS and the MHRA should stop licensing homeopathic products. (Paragraph 157) Evidence based medicine “Drinking beer with a straw “People who take vitamin C means it will take longer to live four times longer get drunk.” with cancer.” Clinical Trials “Salbutamol alleviates “Lidocaine causes anaesthesia.” asthma symptoms.”  Developing a new medicine $1.3 billion 12-15 Years Clinical Data Analysis Full Development Registration Studies in 100-300 Patients (Phase II) Candidate Medicine Tested in Large Amounts of 3-10,000 Patients (Phase III) Extensive Safety Candidate Medicine Studies Synthesized Studies in Healthy Volunteers (Phase I) Candidate Formulations Exploratory Development Developed Early Safety Studies Synthesis Project Team of Compounds Screening and Plans Discovery Collaborative effort Addressing attrition rates Drug Targets: Human evidence Translational Medicine Interpretation of preclinical efficacy Human tissue pharmacology Clinical biomarkers Selecting the right patient cohort Precision medicine Pharmacology principles Active ingredient (drug molecule) Selectively bind to certain molecular targets (e.g proteins) and Exerts cellular effect Exerts effect on system Produce a therapeutic effect in a concentration-related or concentration-dependent fashion Efficacy (usefulness) of drug/medicine is supported by clinical trials using agreed “outcome measures” and statistical validation