Pharmacodynamics - Drug Interactions and Effects PDF

Pharmacodynamics - How a drug interacts and affects the body, including its mechanism of action, effect of specific receptors and the resulting physiological changes Agonist -- binds to a receptor and activates it, creating a response similar to the body's own Partial Agonist -- binds t...

Pharmacodynamics - How a drug interacts and affects the body, including its mechanism of action, effect of specific receptors and the resulting physiological changes Agonist -- binds to a receptor and activates it, creating a response similar to the body's own Partial Agonist -- binds to a receptor activating it to a limited extent. Does not produce a response as strong as the body not matter the dose. In the presence of a full agonist it will act as a functional antagonist, reducing the response. Inverse Agonist -- binds to a receptor and reduces the bodies response, reducing background activity. has the opposite effects reduces same receptors baseline activity, supressing natural activity. Antagonist -- binds to a receptor but does not produce a response, prevents agonist binding so an activity cannot happen Synergists -- enhances the effect of another drug. Drug interactions may cause dramatic increase in the intended effect of the primary drug Competitive binding -- both agonist and antagonist compete over the same receptor site. Irreversible binding -- an antagonist will irreversibly bind to a receptor site, preventing an agonist from binding Allosteric binding -- an antagonist will bind to a different receptor site, preventing agonist binding Functional antagonist -- bind to a different receptor, initiates action to appose agonist. Enzyme inhibitors -- inhibit the enzymes responsible for the breakdown of neurotransmitters, therefor prolonging their action and effects Ion channel modulators -- allow ion channels to open of close, causes influx or efflux of ions which can be responsible for muscle contraction, nerve impulses, heart rhythms. Affinity -- the degree and strength to which a ligand will bind to a receptor Efficacy - the degree and strength to which a drug will create a response. Specificity -- how selectively the ligand will bind to a receptor Potency -- the maximum strength of a response that a drug can produce. The amount of drug needed to produce a response. Dose-response relationship -- the relationship between the dose of a drug given and the response produced Therapeutic dose -- the amount of drug required to produce a therapeutic effect The ceiling effect -- when even if the dose is increased there will no longer be an increase in effect Toxic dose -- the dose given when adverse and toxic effects become likely Therapeutic index -- describes how clow the therapeutic and toxic doses are, large gap makes a safe drug. Small gap gives less room for error and makes drug dangerous. Drug response times Onset of action -- how quickly a drug takes starts working after administration Peak effect -- is the time it takes to reach maximum therapeutic effect Duration of action -- how long the drug affects last. Side effects -- these are predictable, often mild, and usually life threatening. Are based on its pharmacological properties Adverse drug reactions -- unexpected, potentially harmful, more serious than side effects. May be potentially life threatening and require immediate intervention. Pharmacokinetics - How the body responds and interacts with any medication Absorption -- the process in which the drug is taken into the body and makes it way to the blood stream from site of administration Physiological factors - blood flow to the perfusion site will affect absorption, the more blood flow to a site of administration the quicker the absorption - Surface area of administration site, the more surface area the quicker absorption e.g. the intestines have a high surface area so drugs re absorbed quickly - Contact time with absorption site, if a drug is not in contact for long then not a lot of the drug will be absorbed, e.g. if a patient has diarrhoea Physio-chemical factors - Solubility of drug, solid drugs must be converted into a solution before they can be absorbed which takes longer - Ph of site, ph will affect the solubility and therefor the absorption of the drug Passive diffusion -- when it moves from an area of high concentration to area of low concentration Facilitated diffusion -- occurs with larger molecules that require carrier proteins or ion channels for substances to move from area of high conc to low conc. Active transport -- move from area of low to high concentrations, requires energy in the form of ATP Endocytosis -- when molecules are too large even for facilitated diffusion, the cell engulfes the molecule and pulls it into the cell Routes -- oral, sublingual, rectal, iv, im, subcut, inhilation Distribution - the process of which how the drug is transported from the bloodstream to the different tissues and organs around the body. Including how this affects the drugs effectiveness, mechanism of action and duration. Factors affecting distribution Patient considerations Patient condition -- if the patient is unconscious this will affect their absorption or rout chosen. Age -- children and elderly patients absorb drugs at different rates, so different doses should be considered Composition -- frail/small patients will require alternative doses to patients with higher BMIs that will not respond to the same doses. Metabolism - the way in which the body breaks down and coverts a drug so it can be eliminated easier. The liver -- is the main organ responsible for metabolism as it contains enzymes that modify the structure of drugs to make them easier to eliminate. The enzyme cytochrome p450 has a key role in the metabolism of drugs. Phase 1 (modification) -- the body chemically converts the drug through oxidation, reduction, or hydrolysis reactions. Making it more water soluble ready for phase 2 or elimination. Phase 2 (conjunction) -- the body further alters the structure of a drug by adding a substance to it, this makes it even more water soluble ready for elimination. Enables easier elimination, usually via urine or bile. First pass metabolism -- occurs when a drug is first taken into the body and is absorbed from the GI tract. When a drug is taken orally it will end up in the GI tract where it is absorbed into the hepatic vein and taken to the liver. The liver contains enzymes (cytochrome p450) which metabolises a portion of the drug before it reaches the systemic circulation. This means a portion of the drug is metabolised and never reaches the systemic circulation. First pass metabolism may affect bioavailability of drug. Some drugs may be completely wiped out by first pass metabolism (GTN) or stomach acid so alternative routes or increased doses must be considered, so therapeutic dose is still reached. Second pass metabolism -- occurs after a drug has circulated around the body and returned to the liver. The drug has been used and circulated around the body before being excreted into the GI tract as bile where it is reabsorbed by the hepatic vein and taken back to the liver. where it is metabolised again preparing it for excretion. The cycle prolongs the drug process and its effects on the body. If a patient has liver disease, they may not metabolise drugs as well, which may lead to accumulation and toxic affects Bio-availability -- this describes the portion of the drug that reaches systemic circulation. Excretion Kidney -- the main organ involved in excretion of water-soluble drugs. Drugs are absorbed from the blood to the urine. Removing drug metabolites from the blood stream. Impaired kidney function may lead to accumulation, slower elimination and prolonged drug effects. Biliary -- after metabolism in the liver, altered drugs can be released as bile into the GI tract where they are excreted as faeces. May undergo enterohepatic circulation. Allowing the drug to be reabsorbed into intestine, prolonging its effect. If there is liver impairment may lead to accumulation and less elimination. Lung -- excretion of gaseous and volatile drugs, occurs quickly after administration stops. Half-life -- the time taken for its concentration in the blood to reduce by half. Short means quicker excretions. Long means less frequent dosing. Salbutamol -- a beta 2 agonist, binds to beta 2 receptors and activates them, causing a physiological cascade that results in an increase in CAMP levels that increase sympathetic activity, result in dilation of smooth muscles and increased air flow. Ipratropium bromide -- muscarinic antagonist. Ipratropium binds to a muscarinic receptors, preventing acetylcholine effects, therefor relaxing the smooth muscle in the airway, improving air flow. Prednisolone, hydrocortisone, dexamethasone -- corticosteroids, increase activation of anti-inflammatory genes. Also inactivation of inflammatory genes. Preventing inflammation and oedema production. Adrenaline -- a non-selective androgenic agonist. Bind to alpha 1 receptors causing vasoconstriction, improving blood pressure and increasing perfiferal vascular resistance to improve blood flow to major organs. Also binds to alpha 2 receptors which causes bronchodilation to improve airflow. Aspiring -- an antiplatelet, irreversibly inactivates cyclooxygenase by irreversibly acetylating the active enzyme therefore preventing synthesis of thromboxane in platelets as well as synthesis of prostaglandin in epithelial cells. Both contributing to the prevention of platelet agregation. TXA -- an antifibrinolytic, Competitively and reversibly binds to lysine receptor sites on circulating prostaglandin. This prevents it from binding to fibrinogen and synthesising into fibrin. Meaning it will stop the breakdown of an already existing clot. GTN -- a potent vasodilator, converted to nitric oxide, causing dephosphorylation which relaxes smooth muscle of blood vessels, increasing blood flow to cardiac tissue and reducing preload. Furosemide -- a loop diuretic, acts on the ascending limb of the loop of henley. Inhibits potassium-sodium-2-chloride transporter. Stopping reabsorption of potassium, sodium and chloride into blood and therefore the passive reabsorption of water is also inhibited. Leading to increased ion and water output as urine. Amiodarone -- an anti-arrhythmic, blocks potassium channels in the cardiac tissue. Affecting the repolarization in phase 3 of the cardiac cycle. It increased duration of action potential, therefore increasing refractory period and slowing the heart rate. Atropine -- irreversibly binds to muscarinic acetylcholine, blocking vagal activity, increasing the heart rate. Diazepam -- a gaba enhancer, binds to chlorine receptors on the post synaptic neurone, increasing there affinity to GABA. This leads to influc of negative chloride ions into post synaptic neurone, causing it to become hyperpolarized, making it less excitable and the chances of an action potential passing through less likely Nitrous oxide -- binds to 5ht3 receptors which prevent neurotransmissions of pain getting through Naloxone -- competitively binds to opioid receptors, preventing the opioid present from exerting its effect on the body. Ondansetron -- bind to 5HT3 receptors on vagal afferent nerves and chemoreceptor trigger zones, therefor inhibiting stimulatory effect of serotonin. Morphine -- bind to kappa, delta and mu receptors. Also allow calcium channels to open on presynaptic neurone which decreases release of neurotransmitters. while closing potassium channels on post synaptic neurone causing them to become hyperpolarized. Paracetamol -- don't know Ibuprofen -- an NSAID, a non-selective cox-inhibitor, inhibits cyclooxygenase, leads to decreased production of prostaglandin and thromboxane, causing anti-inflammatory/anti-pyretic/analgesic affects. Chlorphenamine -- an inverse agonist that binds to H1 receptors on target tissue, preventing histamine from binding and producing an effect. It also brings the receptors back to their baseline level that causes a gradual reduction in allergenic symptoms. Can cross blood brain barrierscausing sedative effects Benzo penicillin -- a narrow spectrum antibiotic that binds to receptors in the cell membrane, breaking it down, killing the bacteria.