Pharmacology lecture notes PDF

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Pharmacology lecture notes...

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Pharmacology lecture notes Introduction Alternative therapeutic options:  Modern medicine relies heavily on drug-based therapeutics.  Other therapeutic options include procedures such as surgery, diet modification, exercise, psychological treatments and physiotherapy.  Therapeutic systems that have a basis that lie outside the domain of science are known as ‘alternative’ or ‘complementary’ medicine.  Evidence-based health care is commonly practiced in Australia. What is “pharmacology? It is the study of the effects of drugs on the function of living systems Paul Ehrlich- drug action = conventional interactions between drugs and tissues: The study of chemical agents (drugs) that interact with living systems through chemical processes, especially by binding to regulatory molecules and activating or inhibiting normal body processes. (as molecules control everything) What is “a drug? Drug = chemical other than nutrient or essential dietary ingredient. Which when administered to a living organism produces a biological effect.  A chemical applied to a physiological system that affects its function in a specific way. Pharmacology the Discipline: Pharmacodynamics: Where a drug acts in the body (site of action) {Where does the drug work}.  Biochemical, physiological and behavioural effects of drugs (mode of action) {How does the drug work} Pharmacokinetics: Time course of drug concentrations obtained in different regions of the body during or after dosing (way in which drug concentration changes with time).  Drug disposition (absorption, distribution, metabolism, excretion)  Quantitative Pharmacokinetics (measure conc of drug at various times)  Therapeutics = cure and treat  Chemotherapy = kill or weaken cells  Toxicology = poisons treatment How drugs work: 1-The majority of drugs interact with specific molecules involved in regulatory functions eg. a receptor, ion channel, pump or an active site on an enzyme (DRUG TARGET) 2-A small number of drugs interact with chemicals in the body but are not bound to a tissue component. Why do most drugs vary widely in 3-dimensional shape? Because most interact with specific sites – receptors (drug targets) Origins of Drugs 1. Some drugs are synthesised within the body (eg. hormones, autacoids, neurotransmitters) this includes insulin, oestradiol, adrenaline, testosterone. 2. Most drugs are not synthesised within the body (Toxins and poison). Physical Nature of Drugs: a. Solid  aspirin, paracetamol b. Liquid  Ethanol c. Gaseous  nitrous oxide

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These factors often determine route of administration. Some liquid drugs are easily vaporised and can be inhaled  halothane and amyl nitrate  Determines route of administration  Drugs masses of 100-1000 Daltons, which alter the body's function by interactions at the molecular level. Drug Nomenclature 1-Generic name - Official name (lower case) eg. paracetamol 2-Trade name - proprietary/brand name (first letter capitalised) Panadol®, 3-Chemical name - N-acetyl-p-aminophenol (identifies chemical structure)  

Generic name: silendafil Trade name – Viagra Generic drugs belonging to the same drug group (often)have same suffix  Phenothiazine antipsychotics ‘-azine’  Most antianxiety drugs (benzodiazepines) ‘-azepam’  Local Anaesthetics ‘-caine’  ACE inhibitors ‘-pril’  Most beta-receptor antagonists ‘-olol’ Therapeutic Drug Market:  Over 30,000 different medicinal drug products on Australian market  ~700 active ingredients  Multiple combos e.g. Panadeine = codeine + paracetamol  Tylenol sinus = paracetomal + pseudoephedrine  Delivery forms e.g. Adalat Oros = slow release nifedipine tablets (once daily)  Adalat = nifedipine tablets (twice daily)  

 On the label, R = registered, L = listed Mechanisms of Drug Action:  Most drugs vary widely in 3D shape because most interact with specific sites – receptors (drug targets)  Change in structure can change activity of drug  Type of chemical interaction with receptor can influence action of drug  High degree of specificity (affinity) can result in fewer toxic side-effects  Drug must be complementary in shape to receptor: lock and key model

Targets for Drug Action: a. Receptors: sensing elements for chemical communication (hormone, neurotransmitter, neurohormones)  E.g. D2 dopamine – agonist = dopamine, Antagonist = chlorpromazine b. Ion channels: may be blocked by a drug or the gating operation may be modulated  Local anaesthetics (eg. procaine) physically block the voltage-gated sodium channel  Benzodiazepines (eg diazepam) bind to a region of the GABA-receptor/chloride channel complex. - Most facilitate the opening of the channel by GABA c. Enzymes: drugs may be competitive (e.g. neostigmine – AchE enzyme) or noncompetitive (aspirin – COX enzyme) inhibitors of enzymes. d. Pumps: drugs may inhibit action of carrier molecules e.g proton pump inhibitor (omeprazole) Other drug effects:  Binding to DNA (cross-linking or degradation): antitumor alkylating agents (cisplatin) and cytotoxic ab’s (bleomycin)  Counterfeit substrates: antihypertensive agent alpha-methyldopa substitutes for normal substrate in synthesis of noradrenaline resulting in less active endproduct  Chemical effects: electrostatic interaction between +ve charged drug and -ve charged drug. Protamine – antagonist of the anticoagulant heparin is due to interaction of highly +ve charged protamine molecule with highly –ve charged heparin molecule  Physiological effects: Antacids e.g. AIOH3 acts as a physiological buffer (change in pH).  Cathartics (purgatives) ฀฀‫مسهل‬: ingestion of non-absorbable material (eg lactulose or MgSO4) increases water content of faeces and promotes defaecation (amount of H2O increased in the gut).

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 Transport protein can transport molecules across membranes (if drugs are not very lipid soluble) Hydrolysis of ATP can provide the energy for transport of substances against their electrochemical gradient. Drugs target either enzyme, ion channel, receptor, or pumps.

Dose-response relationships 1:

Potency and Slope: Potency: ability of drug to combine with receptors - depends on drug affinity. Important for dosage but unimportant for clinical purposes. It’s determined from the LD50 (median lethal dose). Slope or Hill slope or Hill coefficient (nH) : Relationship between change in dose and change in effect. steep slope: For some drugs a small change in dose can change a therapeutic effect into a toxic effect. Maximal Effect (Emax):  plateau in the DR-curve (DR: does response curve), Dependent on intrinsic (affinity) activity of the drug.  Potency vs. efficacy - whereas potency refers to the concentration of drug required to produce a particular effect, efficacy refers to the maximal possible effect that can be produced by the drug.  Potency is compared with the ED50  E.g. buprenorphine is lower than morphine, thus but never reaches full maximal efficacy = partial agonist

Lecture 1

Agonists and Antagonists What is an agonist?  Affinity and intrinsic activity  Drug, hormone, toxin, autacoid (local hormone not in blood e.g. Nitric oxide) or neurotransmitter that elicits a biological effect when interacts with receptors.  Magnitude of signal depends on number of receptors occupied and/or rate of formation of drug-receptor complexes....