Pharmacology Revision Cards PDF

Pharmacology – the study of the action of drugs ­ Helps predict and avoid drug interactions. ­ Manage effects of co morbidities ­ Helps decide most appropriate for the condition and form of drug. Helps us to understand the effects of ageing, pregnancy, hepatic and renal dysfunction on drugs and ou...

Pharmacology – the study of the action of drugs ­ Helps predict and avoid drug interactions. ­ Manage effects of co morbidities ­ Helps decide most appropriate for the condition and form of drug. Helps us to understand the effects of ageing, pregnancy, hepatic and renal dysfunction on drugs and our bodies Pharmacokinetics The way the body effects the drug with time. ­ Dose ­ Frequency ­ Dose adjustments. ­ Interactions ADME Half Life – Time at which a drug has lost half its max concentration Cmax – Highest concentration Cmin – Lowest concentration Tmax – Time in which the maximum concentration occurs. T1/2 – half-life – T1/2= 0.693 x Vd Cl (Clearence) Pharmacodynamics - Effect of the drug on the body over time (concentration + Effect) If a drug is going to have an effect on the body, it needs to be present: - In the right place ­ At the right concentration ­ At the right time Absorption The passage of the drug from its site of administration into the plasma Gut > Liver > Vein > Heart > Lungs > Heart > Artery. Different routes of administration can result in differing Cmax and Tmax despite the dose being the same. The half-life of the drug is not affected by eh route of administration as this is a property of the drug. Most drugs are absorbed in the gut by passive diffusion. Drugs move from one area of high concentration to low concentration until equilibrium is reached. Factor affecting absorption: Body Related- - GI function - Food - Disease Drug related- - Properties of the drug – lipid solubility, particle size and concentration Dosage for - Formulation How do drugs get into the body- - Enteral - Parental - Sub cut. - Intravenous - Intramuscular - Topical - Inhalation IV route is the most direct – 100% bioavailability and does not undergo 1st pass metabolism The rate of absorption depends on 3 factors: - The concentration gradient - The absorptive surface - The fat solubility of the drug Fat soluble molecules can pass directly through the phospholipid bilayer of the cell membrane. 1st Pass Metabolism - Takes place before the drug reaches systemic circulation. - Drugs absorbed from the digestive tract pass to the liver via the hepatic portal vein to be metabolised by the CYP450 enzymes before entering circulation. - The extent of 1st pass metabolism will determine the amount of the drug that is available in the circulation to perform its therapeutic task (bioavailability) Some drugs are almost completely metabolised by the liver during 1st Pass resulting in low bioavailability and ineffective therapeutic action. Pro Drugs – - Need to be metabolised by the liver before they become active. They are not inactivated by the liver. - Examples of pro drugs: Aspirin, Codeine, Morphine Help improve medicinal effectiveness Plasma Protein Binding - Drugs do not travel freely dissolved in the blood but are bound to plasma proteins- particularly albumin. - Drugs bind and unbind to proteins but on free drugs can exert its therapeutic effects and act on receptor sites. - Drugs with low protein binding -> 90% unbound 10% bound = therapeutic effect. - Drugs with high protein binding -> 5% unbound, 90% bound. - Changes in plasma protein binding are significant for drugs which are greater than 90% bound. Bioavailability- The fraction of administered drug that enters the circulation intact and available to exert its desired effect. Low volume of distribution – confined to plasma and body water – very little distributed to tissue. High volume of distribution – widely distributed to tissues. Lipid soluble drugs distribution Water soluble drugs distribution Distribution - Move from blood plasma stream to the tissues. - Poor blood supply means poor distribution. For a drug to move from the plasma to the tissues it must be ­ Free to move. ­ Free to act. ­ Unbound. Factors effecting protein binding: - Renal impairment - Low plasma albumin levels (Chronic liver disease, Malnutrition) Late pregnancy and increased albumin but diluted by increased blood volume Metabolism Phase 1- Rely on a group of enzymes in the liver called cytochrome P450 enzymes, they catalyse chemical reactions: - Oxidation - Reduction - Hydrolysis The activity of the CYP450 enzymes can be induced or inhibited by other drugs. Metabolism - The process is the same regardless of administration but occurs earlier for drugs taken orally and continues to occur in circulation. - The process in the liver can result in the creation or activation of an inactive drug (pro drugs) The aim of metabolism is to make drugs more water soluble, so they are more easily excreted by the kidneys. Factors affecting metabolism. - Liver disease - Genetics - Age - Nutritional status Enzyme inhibitors and inducers block or speed up the rate of metabolism by CYP450. Inhibition of CYP will slow down the metabolism and lead to increase in serum plasma concentration to potentially toxic levels. Induction of CYP450 will speed up metabolism causing a decrease in serum concentration and potential treatment failure. Excretion Mostly done via the kidneys Some vis the biliary system Rate elimination is important to determine the duration of response and time interval doses. Water solubility is a key factor for renal excretion, lipid soluble drugs are reabsorbed into the renal tubules. Volume of urine produced is related to the GFR rate Metabolism Phase 2 Involves addition of a further group of chemicals that increase the water solubility of the drug, this process is known as conjugation Concentration of drug plasma is related to the drug dose given. Can be affected by: - Drug reabsorption from nephrons – reduced concentration therefore clearance. Steady state is achieved after 5 half-lives and drug eliminated after 5 half-lives. First order kinetics Rate of elimination is proportionate to the current concentration. Higher concentration = faster excretion or more in plasma Half-life remains constant. The concentration the more is eliminated Rate of excretion does not increase with increased doses. Once the enzyme is no longer saturated the elimination will follow first order kinetics In zero order kinetics the relationship between dose and steady state becomes unpredictable Pharmacodynamics (mechanism of action) - Effect of drug on the body - Where drugs act - How drugs work - Does the dose affect the response? - Drug targets and site of action. - Therapeutic action & side effects Potency and effect on dosing and response Zero order kinetics (saturation kinetics) - How the body uses and breaks down some medicines - Drugs that work by zero order kinetics work at a predictable constant rate. - Metabolising enzyme is saturated - too much drug not enough enzyme to metabolise it. - Creates bottle neck and undergoes constant elimination regardless of plasma concentration. - Rate of excretion is independent of plasma concentration. - Half-life of a drug is no longer a constant value. These drugs are more easily overdosed. First order kinetics - Drug elimination is dependent on concentration (the higher the concentration the faster the clearance) - Water soluble drugs (hydrophilic) Low volume distribution - Fat (Lipid) soluble drugs (lipophilic) High volume of distribution. Drug effects on the cells: - Interaction with receptor (most drugs) - Block of action of specific enzymes (NSAIDs) - Inhibit cell transport mechanisms (Antidepressants) - Modify cells physical/chemical environment (Less common – oncology drugs) Act on invading organisms (Antibacterials, antifungals & antivirals) Receptors - Are specific proteins located on the cell surface - Agonists (Ligand) or voltage gated ion channels - G-Protein coupled receptors. - Nuclear receptors Kinase linked receptors Drug Targets - Receptors - Enzymes - Carrier molecules - Ion Channels RECI Downregulation - decreased density of receptors - decreased sensitivity. - Long term exposure to an agonist Increased exposure to an agonist decreases in number of receptors. Drug Targets RECI Specificity – most drugs will show a high degree of specificity of the substance or molecules that binds to and activates it and will ignore closely related molecules. The closer the fit of the drug to the receptor site the more likely it is to form a drug receptor complex and stimulate a response. Up regulation - increased density of receptors - increased sensitivity - Prolonged deprivation of an agonist - Long term administration/exposure to antagonist (Beta Blocker) Decreased exposure to an agonist increase in number of receptors Enzymes - Speed up chemical reactions. - Binds to a substrate and breaks down into new molecules. Inhibiting enzymes can affect biochemical pathways. Transporters - Neurotransmitters are released from neurons into the synaptic cleft. - Bind to receptors on the postsynaptic neurone. - Elicit a response – Activate/Inhibit Neurotransmitter is then transported back into the presynaptic neurone by a transporter. Agonists (Full) - Bind tightly to a receptor (High affinity) - Activates a response (High efficacy) Partial Does not activate thoroughly (Low efficacy) Antagonists - Block receptor from being activated. - Binds tightly. - High affinity - NO RESPONSE – No efficacy Competitive – Binds to the same site as agonist target so it cannot attach. Non-competitive – Near receptor target sites to stop agonist binding – distort the receptor. Agonists (Full) - High affinity - High efficacy Agonists (Partial) ­ High affinity ­ Low efficacy Inverse Agonists - A Ligand (molecule) that binds to the same receptor site as an agonist. - Antagonizes the effect of an agonist. Reduces max effect by inactivating the receptor to below its basal activity Ortho steric - The receptor binding site Allosteric An alternative receptor binding site which alters the shape of the receptor. Allosteric modulators - Indirectly influences (modulates) the effects of an agonist. - Binds to the Ortho steric agonist binding site. - Positive (enhancer) induces an amplification of the agonist effect. Negative (Inhibitor) inhibits binding of ligands (molecules) to the Ortho steric binding site – decreased activity. Dose – Response curve. - The more potent a drug the lower the dose required. - EC50 is used to measure potency of agonists. - If potency curve shifts right and EC50 . - If potency curve shifts to the left and EC50  A change in potency does not necessarily mean a change in efficacy. Classification of ADRs ­ Type A – Augmented (Predictable) ­ Type B – Bizarre (Unpredictable) ­ Type C – Continuing (Less common – Persistent) ­ Type D – Delayed ­ Type E – End of use (Withdrawal) ­ Type F – Failure of treatment Drug response. - Therapeutic level (sufficient level at a target tissue) - Onset of action (Time taken for drug to reach min effective level) Termination of action (when concentration falls below min effect to elimination). Therapeutic index (TI) - The range of doses at which a medication is effective without unacceptable adverse events. - Drugs with a narrow TI have a narrow window at which their effective doses and at which they produce adverse toxic effects. Drugs with wider TI are safer and have higher margin of error.  The Black Triangle - Medicine is subject to additional monitoring. - Report to the MHRA (Yellow card scheme) - Report any side effects. Pharmacovigilance - Collecting information about suspected ADRs through national reporting systems - Early warning system for unrecognised ADRs Can restrict use or withdraw medications that can potentially cause harm. Off Label - A medicine is licensed in the UK but is being used in a way that is different to that described in the product licence. Can prescribe as an IP but only if: - Evidence based practice is sufficient. - Patient/carer is informed. - Good documentation as to reasons for prescribing an off-label medicine. - Can do as SP and CMP Controlled drugs - Schedules 2,3 and 4 valid for 28 days - Limited quantity necessary for up to 30 days treatment. - Schedule 5 valid for 6 months from the appropriate date Not a legal requirement but is best practice Unlicensed Medicines - Outside the terms of their UK licence or that have no licence for use in the UK - Must not be prescribed as an IP. - Can prescribe as part of a CMP as a SP Legislation: The Medicines Act (1968) Human Medicines Regulations (2012) Misuse of drugs act (1971) Misuse of drugs regulations (2001) Medicines & Healthcare Products regulatory agency (MHRA) Human Rights act (1998)