Pharmacology Revision Notes (PDF)

Pharmacology  Pharmacodynamics and Pharmacokinetics Pharmacodynamics Pharmacokinetics the the effect that...

Pharmacology  Pharmacodynamics and Pharmacokinetics Pharmacodynamics Pharmacokinetics the the effect that druge have which on the body study of the way in druge move through the body during absorption distribution , , metabolism and excretion Pharmacokinetics For drugs to produce their effects they , must interact with the body. Pharmacokinetics influences decisions over the route of administration. The processes that occur after drug administration can be broken down into four distinct areas : absorption of drug A the distribution of the drug 1) molecules M metabolism of the parent drug E excretion its of the drug and metabolites - Absorption Before a drug can begin to exent any effect on the body , it has absorbed to be into the body systems. One of the most is important factors affecting the absorption process the route of.. administration  ORAL Convinient , non-sterile , good absorption most for drugs Can cause 61 innitation potential , for interactions , first pass destruction , inactivated by , acide variable absorption SUBLINGUAL Avoide first pass , fast absorption into the bloodstream , acid avoids gastric Requires patient cooperation , few preparations suitable RECTAL Avoids first pass , avoids gastric acid Les dignified for the patient INTRAVENOUS Rapid action , complete availability Painful , some patients difficult to cannulate risk tissue , of damage INTRAMUSCULAR Moderate absorption rate Painful , limited volume capacity , nish tissue of damage  SUBCUTANEOUS Slower , sustained release slower onset , smaller dose volumes INHALED Rapid action on Workbook respiratory tract , large Question 3 absorption area Few disadvantages Absorption is the process by which a drug is taken into the body and moves site administration into blood absorbed from the of the. Drugs are from the site administration of into the bloodstream and enter systemic circulation Other factors controlling the Nate and reliability of drug absorption can be said to be physiological or physico-chemical. PHYSIOLOGICAL : Blood flow to the absorbing site the better the blood supply to the area , the greater. Therefore if good circulation will the rate of absorption a person has , they have the ability to absorb the drug well for absorption Total surface area the greater the surface area , the greater Nate the. absorption intestine o The has a very large surface area , making it an ideal target for drug absorption site in Time of arrival and contact time at absorption the longer the drug is This contact with the absorbing surface , the greater the rate. of absorption is why if a diarnhora absorbed person is suffering from , the chances of a drug given onally being completely are lowered  PHYSICO-CHEMICAL is in solid dissolve. absorbed Liquid solubility if a drug form , it must before it can be forms absorb faster than solid , and drugs that dissolve easily in bodily fluids are absorbed quicker PH of absorption site druge can be effected by the pH of the surrounding environment , absorption speed influencing and effectiveness PATIENT SPECIFIC CONSIDERATIONS condition choice Patient consciousness , perfusion and haemodynamic stability influence route Patient age and body composition children , older adults , and those with different body compositions may absorb drugs at different rates , affecting how quickly the drug takes and how laste effect long it Distribution distribution Drug is how a drug moves from the tissues bloodstream to and organs in the body , action duration affecting its , , and effectiveness FACTORS AFFECTING DISTRIBUTION Blood flow and perfusion tissues with high blood flow like the brain , heart , liver and kidneys) receive drugs more quickly Plasma protein binding some drugs bind to proteins mainly albumin) I in the blood. Only the 'free' unbound drug enter tissues and have Some can an effect. drugs do not kind /e. Caffeine) (e g. Warfarin) and.. g some are highly bound. Highly protein-bound druge may have a slower onset but longer action , as they're released gradually into. tissues If a patient has now protein levels /e due to liver disease or malnutrition) there may be more free , drug g.. , increasing potency risk and of side effects Tissue kinding pot and solubility lipophilic (fat-soluble) druge , like amiodarone , are stored in fat tissues and released slowly leading , to a prolonged effect. Hydrophile/water-soluble) drugs are usually distributed more quickly , but may be eliminated faster. Obesity or higher body fat content can delay the effect of ipophilic drugs , as they take longer to reach therapeutic levels Passage through bonniers the two main examples are the placenta and the blood brain barneir (BBB). Druge must be highly lipid soluble to pass across these barriers Workbook Question Seven BIOAVAILABILITY - the proportion of the drug that enters the systemic circulation when introduced into the body and is available for therapeutic effect Metabolism metabolism and convents Doug refers to the process by which the body breaks down medications into substances that can be more eliminated easily The Liver is the main organ responsible for drug metabolism , where enzymes into inactive chemically alter drugs or more easily excreted Some also metabolised in other tissues forms. druge are such intestines as the Kidneys , lunge and The liver contains enzymes (primarily of the Cytochrome P45O family) that play a hey role in metabolising drugs. These enzymes vary in activity individuals which how is between , can influence quickly or slowly a drug processed  PHASES OF DRUG METABOLISM Phase I /Modification ( Phase 11 (conjugation ( The The drug's structure is , modified modified drug is often by oxidation , , reduction combined with another. or hydrolysis reactions This substance to make it water-soluble , can make the drug more even more water-soluble and prepare enabling easier elimination it excretion from the body usually futher , for or via unine or bile processing in phase I FIRST PASS METABOLISM The initial processing of a drug by the liver immediately after it is absorbed from the gastrointestinal tract ① When is absorbed a drug taken onally , it is from the 61 tract to the portal , ve i n which carries it directly to the liver ② In river (CYP450) metabolise broken the , enzymes the. drug A significant portion of the drug may be circulation down or inactivated here before it ever reaches the systemic ③ First-pass metabolism can reduce the bioavailability of the drug meaning less of it reaches the systemic bloodstream to exent its therapeutic effects EXAMPLE extensive metabolism in the liver which is GTN undergoes first : pass , instead why its typically given sublingually of onally , bypassing the liver initially circulation directly and allowing more of the drug to enter CLINICAL IMPLICATIONS : druge with high first-pass metabolism may require higher ora doses or alternative routes to achieve therapeutic levels in the bloodstream workbook Question Four  SECOND PASS METABOLISM Additional metabolism that occurs after a drug has already circulated through the body and returned to the. liver This second pass' can involve further breakdown of the drug ① absorbed into After the drug has been and circulated , it can be excreted the bil and released into the. There intestines it be reabsorbed back into the bloodstream , may and returned to the liver ② this second On pase through the liver , the drug or its metabolites may undergo additional processing , futher altering its structure and preparing it for excretion ③ This additional cycle of nabsorption and metabolism can prolong the drugs presence and in effect the body EXAMPLE initial , : After metabolism morphine and its active metabolite may undergo enterohepatic. recirculation This recycling can extend its analgesic effects CLINICAL IMPLICATIONS : Drugs that undergo second-pass metabolism active the sometimes may stay longer in body , requiring modified dosing In patients with liver impairment , reduced second-pass metabolism accumulation with of toxicity lead can to , increasing the risk , especially for druge active metabolites Workbook Question Five Excretion The kidneys are the primary organs for excreting drugs , especially water-soluble. compounds Drugs are fittered from the blood into wine in the. hidneye This filtration proces active molecules metabolites circulation removes drug and from and its wine E.. morphine g metabolites are primarily excreted in , so  elimination patients with midney impairment may have slower and prolonged effects of the drug Drugs not excreted by the kidneys may undergo biliary. excretion After being metabolised the liver by , some released into intestine drugs are secreted into bil , which is the eliminated in wa and. Drugs faces excreted bile may also undergo enterohepatic. circulation be This process allows the drug to reabsorbed in the intestine , prolonging its effects. E. g. antibiotics such as doxycycline can be excreted in bile , extending their duration of action Caseous and volatile like anaesthetic excreted drugs , agents , are through This rapid elimination the. lungs allows of these drugs after administration stops FACTORS AFFECTING DRUG EXCRETION Kidney function impaired Midney function can slow the excretion of drugs that rely on renal elimination , increasing risk the of accumulation and toxicity Liver function patients with liver disease have difficulty eliminating druge that require may hepatic metabolism and. This lead to accumulation and biliary excretion can drug prolonged effects Half-life a drug's half-life is the time taken for its concentration in the blood to reduce by half. Druge with short holy-lives are excreted more quickly , while drugs with long holy-lives remain frequent dosing and in the body longer may require less Womboon Question Six  Pharmacodynamics - Mechanism of action Pharmacodynamics refere to how a drug affects the body , focusing on the mechanisms of action , effect on specific receptors , and resulting physiological changes. Understanding pharmacodynamics is essential for choosing appropriate drugs , knowing how they will interact with a patients body in critical situations and complications , recognising possible side effects or Agonist and antagonist actions Agonist and antagonist drugs are terms used to describe how drugs interact with in activate certain cellular responses receptors the body to either or block L X AGONIST ANTAG ONIST These are drugs that kind to receptor and These are drugs that kind to receptor but do not activate them , producing a response similar activate them. Instead , they response to the body's own chemicals /e. g. block or dampen the receptor's activity by neurotransmitted) preventing hormones or. They are often other substances from binding. action unwanted used when the body needs more a o This blocking can reduce specific action , like increasing Nate heart responses , like high blood. pressure Beta blockens such E. g. Salbutamol is a Beta-2 agonist. E.. g as Antenolol which It selectively binds to Beta-2 receptors in They block Beta-1 receptors in the heart , bronchodilation lunge causing reduces heart blood by the rate and , pressure and smooth muscle decreasing the effect of adrenaline and relaxation noradrenaline on the heart PARTIAL ACONISTS These kind to receptor and activates it but to limited extent Even a , only a. doses produce maximum at high , partial agonists cannot the some response that a full agonist can. They are useful in situations where a full response isn't desired , and their effects can be , making self-limiting them safer in some cases · when they bind to a receptor , partial agonists produce a moderate response , regardless the dose of in partial agonist the full agonist functional · a act presence of , a can as a Antagonist by competing for the same receptors and reducing the overall response , as it prevents the fur agonist from binding fully. Buprenorphine E opioid. g is a partial agonist at without receptors , providing pain relief producing as strong an effect as full opioids like morphine Often used in pain management and opioid addiction treatment. Because it only partially opioid activates receptors , it has a 'ciling effect' that lowers the risk of respiratory depression and overdose INVERSE AGONISTS An inverse agonist kinds to the same receptor as an agonist but has the opposite effect. agonist agonist - While an activates a receptor to produce a response , an inverse reduces the receptor's baseline activity. In other words , it suppresses any natural or 'background activity that the receptor might have , even when no agonist is present. level baseline activity · receptors have some of even in the absence many , of a binding. molecule Inverse agonists kind to these receptors and actively reduce their intrinsic agonist activity creating , an effect opposite to what an would produce unlike antagonists inverse activity · , agonists actively decrease the receptors below its normal baseline Workbook Question Eleven  certain /such E.. g types of Beta-blockers as propanol) act as inverse agonists at beta-adrenergic receptom reducing , their intrinsic activity and leading to a more pronounced decrease in heart rate and blood. pressure Synergists is A drug that enhances the effect of another drug called a synergist some interactions dramatic increase in intended drug-drug may cause a the aspirin-warfarin interactions effect of the primary drug , as seen in addition with In to interacting with another drug , some drugs may also interact intamine , minerals and/or herbal suppliments. For example , tetracycline is compromised when it is taken with daiy products containing calcium …not all drug actions are receptor-type interactions… interactions inhibit Enzyme some drugs enzymes that break down specific neurotransmittens or other chemicals , prolonging certain. their action E.. g druge stop enzymes that break down seratonin adrenaline their neurotransmittens like or , intensifying effects Ion channel modulation drugs can open or close in channels , altering the ions which impulses flow of across cell membranes , influences neve , muscle contractions heart rhythm E lidocaine sodium , or... g blocks channels , stabilising cardiac tissue , and helping manage arhythmias Influences on pharmacodynamic effects POTENCY this refers to the drug's strength , or the amount needed to achieve desired a effect. A highly potent drug requires a smaller dose to be. effective For example , fentanyl is more potent than morphine , meaning hower doses are needed similar pain relief for EFFICACY this refers to the maximum effect a drug can produce regardless , of dose. Some drugs (like full agonists) have high efficacy , achieving a complete therapeutic effect , while others /like partial agonists) have lower efficacy producing , less than the maximum effect even at higher dose Dose-response relationship This explains how a drug's effect changes with various doses , which is crucial in determining the safest and most effective amount for patient treatment Therapeutic dose : the dose that produces the desired effect Ceiling effect : at a certain dose , increasing the amount of the drug not increase its effect may Toxic dose : the dose at which adverse toxic effects become or likely Therapeutic index This is the natio of a drug's toxic dose to its therapeutic dose , providing a. safety margin with wide therapeutic index /e ibuprofen) while Drugs a. g. are generally safer , those with therapeutic /e. morphine) a narrow index have a higher rish of toxicity g. Drug-response time Onset of action how quickly a drug starts working after administration Peak the time it takes to reach maximum therapeutic effect effect Duration of action how long the drugs effect last  Side effects and adverse reactions SIDE EFFECTS These are predictable often , mild , and usually non-life-threatening effects of a drug , based on its pharmacological. action For example , morphine commonly causes drowsiness and nausea due to its CNS depressant effects ADVERSE DRUG REACTIONS These unexpected potentially harmful and be than side effects are , , can more severe. They immediate For can sometimes be life-threatening and may require intervention. example , severe hypotension from GTN due to its vasodilation effects Workbook & Question Eight and nine  Coagulation Coagulation , or blood clotting , is a critical process in preventing excessive bleeding after injury Clotting cascade clotting cascade or secondary The , hoemostasis is a series of steps in response activate to bleeding caused by tissue injury , where each step the next and ultimately produces blood clot a There two of haemostasis : are phoses ① hoemostasis Primary forms an unstable platelet plug at the site of injury ② The clotting cascade is activated to stabilise the plug , stopping blood flow necessary repairs time and allowing increased to make cascade which injury. The clotting is a process by the body stops bleeding after an involves specific protine of biochemical nactions It a sequence where , known as clotting factors , activated blood elot are in a step-by-step manner to form a main intrinsic and extrinsic which The cascade clotting has two pathways converge into a common pathway. Each pathway is a series of enzymatic reactions activate that clotting factors in a domino effect , ultimately leading to the formation of a stable clot blood INTRINSIC PATHWAY inside activated by damage · blood direct contact vessels or of blood foreign /e with a surface. exposed g. collagen in a blood vessel wall) activation begins with the Factor XII · of involves and several steps leading to the activation of Factor X intrinsic crucial in maintaining long · the is but role