Introduction to PD PDF

+-----------------------------------+-----------------------------------+ | **TOPIC** | EXPLAIN | +===================================+===================================+ | **Pathway of drug delivery and | - The pathway of drug delivery | | it...

+-----------------------------------+-----------------------------------+ | **TOPIC** | EXPLAIN | +===================================+===================================+ | **Pathway of drug delivery and | - The pathway of drug delivery | | its effect** | and its effect involves | | | several steps, including | | | ingestion, absorption, | | | distribution, metabolism, and | | | clearance. | | | | | | - The drug is first ingested | | | into the stomach, where it is | | | absorbed into the | | | bloodstream. | | | | | | - The drug is then distributed | | | throughout the body via the | | | circulatory system. | | | | | | - The liver plays a crucial | | | role in metabolising the | | | drug, breaking it down into | | | its active form. | | | | | | - The kidneys are responsible | | | for clearing the drug from | | | the body. | | | | | | - The brain is the target organ | | | for the drug, where it binds | | | to receptors and produces its | | | effects. | +-----------------------------------+-----------------------------------+ | **Pharmacokinetics** | - Pharmacokinetics is the study | | | of the absorption, | | | distribution, metabolism, and | | | clearance of drugs. | | | | | | - It involves understanding how | | | the drug is absorbed, | | | distributed, metabolised, and | | | cleared from the body. | +-----------------------------------+-----------------------------------+ | **Pharmacodynamics** | - Pharmacodynamics is the study | | | of the effects of drugs on | | | the body. | | | | | | - It involves understanding how | | | the drug produces its | | | effects, including its | | | mechanism of action and its | | | interactions with receptors. | +-----------------------------------+-----------------------------------+ | **The stages of alcohol | - The stages of alcohol | | intoxication** | intoxication are based on | | | blood alcohol content (BAC) | | | and range from sobriety to | | | death. | | | | | | - The stages are: | | | | | | - Sobriety (BAC: -.05) | | | | | | - Euphoria (BAC:.03 -.12) | | | | | | - Excitement (BAC:.09 -.25) | | | | | | - Confusion (BAC:.18 -.30) | | | | | | - Stupor (BAC:.25 -.4) | | | | | | - Coma (BAC:.35 -.45) | | | | | | - Death (BAC:.45+) | | | | | | Blood Alcohol Content (BAC) | | | | | | - BAC is a measure of the | | | amount of alcohol in the | | | blood. | | | | | | - BAC is typically measured in | | | percentages, with higher | | | percentages indicating higher | | | levels of intoxication. | | | | | | Effects of Alcohol Intoxication | | | | | | - The effects of alcohol | | | intoxication vary depending | | | on the stage of intoxication. | | | | | | - The stages of intoxication | | | are characterized by | | | different physical and | | | behavioural symptoms, ranging | | | from mild impairment to | | | life-threatening conditions. | +-----------------------------------+-----------------------------------+ | **Ethanol concentration and its | - Ethanol concentration is | | effects** | measured in millimolar (mM) | | | and milligrams per deciliter | | | (mg/dL). | | | | | | - The effects of ethanol on the | | | human body vary depending on | | | the concentration vs level. | | | | | | Concentration Levels and Effects | | | | | | - 6 mM / 28 mg/dL: Euphoria, | | | Perception of drunkenness | | | | | | - 13 mM / 60 mg/dL: Relaxation, | | | well-being, Anxiolytic | | | effect, Minor motor | | | impairment, Memory, judgment | | | and self-control impairment | | | | | | - 20 mM / 92 mg/dL: Sedation, | | | Motor incoordination, High | | | memory, judgment and | | | self-control impairment | | | | | | - 27 mM / 124 mg/dL: High motor | | | impairment, Loss of good | | | judgment, Slurred speech | | | | | | - 33 mM / 152 mg/dL: Lack of | | | physical control, Dysphoria | | | starts to appear | | | | | | - 44 mM / 203 mg/dL: Dysphoria, | | | Nausea | | | | | | - 54 mM / 249 mg/dL: Mental | | | confusion, Nausea and | | | vomiting | | | | | | - 90 mM / 415 mg/dL: Loss of | | | consciousness, Onset of coma, | | | Death risk | | | | | | Molecular Targets | | | | | | - Ethanol affects various | | | neurotransmitter receptors | | | and ion channels, including | | | NMDA, GABA, glycine, and | | | calcium channels. | +-----------------------------------+-----------------------------------+ | **How medicines do what they do** | How Medicines Do What They Do | | | | | | - Medicines interact with the | | | body\'s natural chemicals and | | | cellular receptors to either | | | stimulate or inhibit cellular | | | activity. | | | | | | - There are two main types of | | | medicines: stimulatory and | | | inhibitory. | | | | | | Stimulatory Medicine | | | | | | - Stimulatory medicines enhance | | | cellular activity by | | | interacting with receptor | | | sites on the cell membrane. | | | | | | - They work by mimicking the | | | body\'s natural chemicals and | | | binding to receptor sites, | | | leading to an increase in | | | cellular activity. | | | | | | Inhibitory Medicine | | | | | | - Inhibitory medicines block | | | cellular activity by | | | interacting with receptor | | | sites on the cell membrane. | | | | | | - They work by binding to | | | receptor sites and preventing | | | the body\'s natural chemicals | | | from binding, leading to a | | | decrease in cellular | | | activity. | | | | | | Normal Cellular Activity | | | | | | - Normal cellular activity | | | occurs when the body\'s | | | natural chemicals interact | | | with receptor sites on the | | | cell membrane. | | | | | | - This leads to a normal level | | | of cellular activity, which | | | is necessary for the body\'s | | | functions. | +-----------------------------------+-----------------------------------+ | **Mechanism of action** | Mechanisms of Action | | | | | | - Mechanisms of action refer to | | | the ways in which medicines | | | interact with the body to | | | produce their effects. | | | | | | - There are several types of | | | mechanisms of action, | | | including agonists, | | | antagonists, modifiers, and | | | modulators. | | | | | | Actions | | | | | | - Agonists: bind to a receptor | | | and activate it, leading to a | | | response. | | | | | | - Antagonists: bind to a | | | receptor and block its | | | activation, leading to a | | | decrease in response. | | | | | | - Modifiers: alter the activity | | | of a protein or enzyme, | | | leading to a change in | | | response. | | | | | | - Modulators: regulate the | | | activity of a protein or | | | enzyme, leading to a change | | | in response. | | | | | | Molecular Targets | | | | | | - Molecular targets are the | | | specific proteins or | | | molecules that medicines | | | interact with to produce | | | their effects. | | | | | | - Examples of molecular targets | | | include: | | | | | | - Receptors: proteins on the | | | surface of cells that receive | | | signals from hormones or | | | neurotransmitters. | | | | | | - Enzymes: proteins that | | | catalyze chemical reactions | | | in the body. | | | | | | - Transporters: proteins that | | | move molecules across cell | | | membranes. | | | | | | - Ion channels: proteins that | | | regulate the flow of ions | | | across cell membranes. | | | | | | Typical Effects of Medicines | | | | | | - Medicines typically alter or | | | modulate a physiological or | | | biochemical process in the | | | body. | | | | | | - This can lead to a range of | | | effects, including changes in | | | cellular activity, hormone | | | levels, or enzyme activity. | +-----------------------------------+-----------------------------------+ | **Opioid drugs and their | Opioid Drugs and Their Effects | | effects** | | | | - Opioid drugs interact with | | | opioid receptors in the body | | | to produce their effects. | | | | | | - There are three main types of | | | opioid receptors: Mu, Kappa, | | | and Delta. | | | | | | - Opioid drugs can act as | | | agonists, antagonists, or | | | partial agonists at these | | | receptors. | | | | | | Opioid Drugs Listed | | | | | | - The table lists 11 different | | | opioid drugs, including: | | | | | | - Morphine | | | | | | - Meperidine | | | | | | - Fentanyl | | | | | | - Sufentanil | | | | | | - Alfentanil | | | | | | - Remifentanil | | | | | | - Butorphanol | | | | | | - Nalbuphine | | | | | | - Naloxone | | | | | | - Naltrexone | | | | | | - Nalmefene | | | | | | Effects on Opioid Receptors | | | | | | - The table indicates the | | | effect of each opioid drug on | | | Mu, Kappa, and Delta | | | receptors as either | | | \"Agonist\", \"Antagonist\", | | | or \"Partial agonist\". | | | | | | - Agonists activate the | | | receptor, leading to a | | | response. | | | | | | - Antagonists block the | | | receptor, leading to a | | | decrease in response. | | | | | | - Partial agonists activate the | | | receptor, but to a lesser | | | extent than full agonists. | | | | | | Chemical Structures | | | | | | - The image includes chemical | | | structure diagrams for | | | several of the listed | | | opioids, including: | | | | | | - Morphine | | | | | | - Meperidine | | | | | | - Fentanyl | | | | | | - Sufentanil | | | | | | - Alfentanil | | | | | | - Naloxone | | | | | | - Nalbuphine | | | | | | - Each chemical structure is | | | labeled with the | | | corresponding drug name and | | | shows the molecular | | | arrangement of atoms. | +-----------------------------------+-----------------------------------+ | **Understanding the quote** | - The quote by Paracelsus, a | | | 16th-century physician and | | | alchemist, highlights the | | | concept that all substances | | | can be toxic or beneficial | | | depending on the dose. This | | | idea is crucial in | | | understanding the principles | | | of toxicology and | | | pharmacology. | | | | | | Key Points: | | | | | | - Dose-response relationship: | | | The quote emphasizes that the | | | effect of a substance on an | | | organism depends on the dose. | | | A small dose might be | | | harmless or even beneficial, | | | while a larger dose can be | | | toxic or lethal. | | | | | | - Toxicity vs. therapeutic | | | effect: Paracelsus\' | | | statement suggests that the | | | same substance can have both | | | toxic and therapeutic | | | effects, depending on the | | | dose. This is a fundamental | | | concept in pharmacology, | | | where drugs are designed to | | | have a therapeutic effect at | | | a specific dose, while | | | minimizing toxic side | | | effects. | | | | | | - Contextualizing toxicity: The | | | quote implies that toxicity | | | is not an inherent property | | | of a substance, but rather a | | | function of the dose and the | | | context in which it is used. | | | This perspective is essential | | | in understanding the | | | complexities of toxicology | | | and the importance of careful | | | dosing in medical treatment. | +-----------------------------------+-----------------------------------+ | **Concentration effect | - Description: A graph | | relationship** | illustrating the relationship | | | between drug concentration | | | and its effects, including | | | benefit and harm. | | | | | | Benefit Curve: | | | | | | - Starts at the bottom left | | | corner | | | | | | - Rises in a sigmoid (S-shaped) | | | curve | | | | | | - Levels off at the top right, | | | suggesting a plateau effect | | | | | | Harm Curve: | | | | | | - Begins to rise later than the | | | benefit curve | | | | | | - Also follows a sigmoid shape | | | but is shifted to the right | | | | | | - Continues to rise at the | | | right edge of the graph, | | | suggesting potential for | | | increased harm at higher | | | concentrations | | | | | | - Therapeutic Window: | | | | | | - The goal is to achieve a drug | | | concentration that maximizes | | | benefits while minimising | | | harmful effects | | | | | | - The benefit curve plateaus, | | | while the harm curve | | | continues to rise | | | | | | Insights: | | | | | | - The graph effectively | | | illustrates the concept of a | | | therapeutic window or index | | | | | | - The relationship between the | | | benefit and harm curves | | | demonstrates the importance | | | of finding an optimal drug | | | concentration to maximise | | | benefits while minimising | | | harm | +-----------------------------------+-----------------------------------+ | **Adverse drug reactions** | Description: Unwanted or harmful | | | effects that occur when a drug is | | | taken. | | | | | | Key Points: | | | | | | - Definition: Adverse drug | | | reactions (ADRs) are | | | unintended and harmful | | | effects of a drug. | | | | | | Types: | | | | | | - Type A: Dose-dependent, | | | predictable, and related to | | | the drug\'s pharmacological | | | action. | | | | | | - Type B: Dose-independent, | | | unpredictable, and not | | | related to the drug\'s | | | pharmacological action. | | | | | | Causes: | | | | | | - Pharmacological: Due to the | | | drug\'s mechanism of action. | | | | | | - Pharmacokinetic: Due to the | | | drug\'s absorption, | | | distribution, metabolism, and | | | excretion. | | | | | | - Pharmacodynamic: Due to the | | | drug\'s interaction with the | | | body. | | | | | | Risk Factors: | | | | | | - Age: Older adults are more | | | susceptible to ADRs. | | | | | | - Polypharmacy: Taking multiple | | | medications increases the | | | risk of ADRs. | | | | | | - Genetic predisposition: Some | | | individuals may be more prone | | | to ADRs due to genetic | | | factors. | | | | | | Consequences: | | | | | | - Morbidity: ADRs can lead to | | | illness, disability, or even | | | death. | | | | | | - Mortality: ADRs can be fatal | | | in some cases. | | | | | | Prevention: | | | | | | - Monitoring: Regular | | | monitoring of patients taking | | | medications. | | | | | | - Dose adjustment: Adjusting | | | the dose of the medication to | | | minimise the risk of ADRs. | | | | | | - Alternative medications: | | | Switching to alternative | | | medications with a lower risk | | | of ADRs. | +-----------------------------------+-----------------------------------+ | **Concentration effect | - Main Concept: The | | relationship in pharmacology** | relationship between drug | | | concentration and its effects | | | on the body, including both | | | beneficial and harmful | | | effects. | | | | | | Key Points: | | | | | | - Therapeutic Window: The range | | | of drug concentrations where | | | the beneficial effects are | | | achieved with minimal harmful | | | effects. | | | | | | - Benefit Curve: The blue solid | | | line representing the | | | therapeutic effect of the | | | drug, which rises steeply in | | | the middle and then levels | | | off at higher concentrations. | | | | | | - Harm Curve: The red dotted | | | line representing the | | | potential harmful effects of | | | the drug, which starts rising | | | later than the benefit curve | | | and represents the potential | | | harmful effects of the drug | | | at higher concentrations. | | | | | | - Safety Margin: The light blue | | | shaded area between the | | | benefit and harm curves, | | | representing the range of | | | drug concentrations where the | | | benefit is high but the harm | | | is still low. | | | | | | - | +-----------------------------------+-----------------------------------+ | **Concentration effect | - Main Concept: The | | relationship in | relationship between drug | | pharmacodynamics** | concentration and its effects | | | on the body, including both | | | beneficial and harmful | | | effects. | | | | | | Key Points: | | | | | | - Dose-Response Curve: The | | | curve that shows the | | | relationship between drug | | | concentration and its effect, | | | typically hyperbolic in | | | shape. | | | | | | - Logarithmic Scale: The use of | | | a logarithmic scale on the | | | x-axis to display a wider | | | range of concentrations, | | | resulting in a sigmoidal | | | (S-shaped) curve. | | | | | | - Concentration-Effect | | | Relationship: The concept | | | that the effect of a drug | | | changes with its | | | concentration, with the goal | | | of achieving a therapeutic | | | effect while minimising harm. | +-----------------------------------+-----------------------------------+ | **Concentration effect | - Main Concept: The | | relationship in | relationship between drug | | pharmacodynamics** | concentration and its effects | | | on the body, including both | | | beneficial and harmful | | | effects. | | | | | | Key Points: | | | | | | - Emax: The maximal | | | pharmacological response, | | | representing the maximum | | | effect of a drug. | | | | | | - EC50: The concentration of a | | | drug that produces 50% of the | | | maximal effect, representing | | | the drug\'s potency. | | | | | | - Sigmoidal Curve: A graph that | | | shows the relationship | | | between drug concentration | | | and its effect, typically | | | S-shaped. | | | | | | - Logarithmic Scale: The use of | | | a logarithmic scale on the | | | x-axis to display a wider | | | range of concentrations. | +-----------------------------------+-----------------------------------+ | **Concentration effect | - Drug Potency: Drug A is more | | relationship in | potent than Drug B as it | | pharmacodynamics** | achieves the same effect at | | | lower concentrations. | | | | | | - EC50: The concentration at | | | which a drug achieves 50% of | | | its maximum effect. Drug A\'s | | | EC50 is lower than Drug B\'s, | | | indicating it is more potent. | | | | | | - Emax: The maximum effect | | | level, represented by a | | | horizontal dotted line at the | | | top of the graph. | | | | | | - Emax/2: Half of the maximum | | | effect, represented by | | | another horizontal dotted | | | line midway up the y-axis. | | | | | | - Sigmoid-Shaped Curves: Both | | | Drug A and Drug B\'s curves | | | are sigmoid-shaped, | | | indicating a typical | | | dose-response relationship. | +-----------------------------------+-----------------------------------+ | **Concentration effect | - Drug Potency: Drug A is more | | relationship in | potent than Drug B as it | | pharmacodynamics** | achieves the same effect at | | | lower concentrations. | | | | | | - EC50: The concentration at | | | which a drug achieves 50% of | | | its maximum effect. Drug A\'s | | | EC50 is lower than Drug B\'s, | | | indicating it is more potent. | | | | | | - Emax: The maximum effect | | | level, represented by a | | | horizontal dotted line at the | | | top of the graph. | | | | | | - Emax/2: Half of the maximum | | | effect, represented by | | | another horizontal dotted | | | line midway up the y-axis. | | | | | | - Sigmoid-Shaped Curves: Both | | | Drug A and Drug B\'s curves | | | are sigmoid-shaped, | | | indicating a typical | | | dose-response relationship. | +-----------------------------------+-----------------------------------+ | **Comparing relative potency of | - IC50 Values: The graph shows | | antidepressants** | IC50 values (in nM) for five | | | antidepressants: Citalopram, | | | Fluvoxamine, Fluoxetine, | | | Paroxetine, and Sertraline. | | | | | | - Potency and Selectivity: The | | | graph highlights the | | | differences in potency and | | | selectivity among the | | | antidepressants, with some | | | drugs being more potent at | | | certain receptors or uptake | | | pumps. | | | | | | - Receptors and Uptake Pumps: | | | The legend explains the | | | different receptors and | | | uptake pumps represented on | | | the graph, including | | | serotonin, norepinephrine, | | | dopamine, histamine, and | | | acetylcholine. | | | | | | - Benefits and Harmful Effects: | | | The highlighted points at the | | | bottom of the slide emphasize | | | the benefits of inhibiting | | | serotonin reuptake and the | | | harmful effects of inhibiting | | | other receptors. | +-----------------------------------+-----------------------------------+ | **Action versus outcome** | - Pharmacological Effect: The | | | table lists the | | | pharmacological effects of | | | four drugs: Warfarin, | | | Simvastatin, Allopurinol, and | | | Metoprolol. | | | | | | - Clinical Outcome: The table | | | also lists the clinical | | | outcomes associated with each | | | drug\'s pharmacological | | | effect. | | | | | | - Relationship between Action | | | and Outcome: The table | | | highlights the relationship | | | between the pharmacological | | | effect of a drug and its | | | clinical outcome. | +-----------------------------------+-----------------------------------+ | **Risk of death associated with | - Warfarin: An anticoagulant | | INR** | that prevents clots. | | | | | | - INR (International Normalised | | | Ratio): A surrogate measure | | | that represents the ratio of | | | clotting times. | | | | | | - Outcome: Prevent stroke. | | | | | | - Graph: A U-shaped curve | | | showing the relationship | | | between INR and mortality | | | rates. | | | | | | - Optimal INR Range: Around | | | 2-3, where mortality risk is | | | minimised. | | | | | | - Risks: Ischemic stroke at low | | | INR values and excessive | | | bleeding at high INR values. | +-----------------------------------+-----------------------------------+ | **Pharmacokinetics and | - Pharmacokinetics: The study | | pharmacodynamics** | of how a drug is absorbed, | | | distributed, metabolised, and | | | excreted by the body. | | | | | | - Pharmacodynamics: The study | | | of the effects of a drug on | | | the body. | | | | | | - PK/PD: The relationship | | | between pharmacokinetics and | | | pharmacodynamics, showing how | | | the effect of a drug changes | | | over time. | +-----------------------------------+-----------------------------------+ | **PK-PD relationship of | - PK-PD Relationship: The | | pentazocine** | relationship between the | | | plasma concentration of a | | | drug and its therapeutic | | | effect over time. | | | | | | - Pentazocine: A drug used to | | | relieve pain. | | | | | | - Graph: The graph shows the | | | relationship between plasma | | | pentazocine concentration and | | | analgesia score over time. | | | | | | - Curves: Two curves are | | | plotted on the graph: plasma | | | concentration and analgesia | | | score. | +-----------------------------------+-----------------------------------+ | **Pharmacokinetic parameters** | - Pharmacokinetic Profile: The | | | graph shows a typical plasma | | | concentration-time profile | | | after oral administration of | | | a drug. | | | | | | - Cmax: The maximum | | | concentration of the drug in | | | the plasma. | | | | | | - tmax: The time to reach | | | maximum concentration. | | | | | | - Onset Time: The time at which | | | the drug starts to take | | | effect. | | | | | | - Duration of Action: The time | | | during which the drug is | | | effective. | | | | | | - AUC: The area under the | | | curve, representing the total | | | exposure to the drug. | | | | | | - MTC: The maximum tolerated | | | concentration, the highest | | | concentration that can be | | | tolerated without adverse | | | effects. | | | | | | - MEC: The minimum effective | | | concentration, the lowest | | | concentration that produces a | | | therapeutic effect. | | | | | | - Therapeutic Range: The range | | | of concentrations between MEC | | | and MTC, where the drug is | | | effective and safe. | +-----------------------------------+-----------------------------------+ | **Concentration effect | - Concentration-Effect | | relationship of theophylline** | Relationship: The graph shows | | | the relationship between | | | theophylline plasma | | | concentration and FEV-1 (% | | | normal). | | | | | | - Theophylline: A drug used to | | | treat respiratory diseases | | | such as asthma and COPD. | | | | | | - FEV-1: Forced Expiratory | | | Volume at 1 sec, a measure of | | | lung function. | | | | | | - MEC: Minimum Effective | | | Concentration, the lowest | | | concentration of theophylline | | | that produces a therapeutic | | | effect. | | | | | | - MSC: Maximum Safe | | | Concentration, the highest | | | concentration of theophylline | | | that can be tolerated without | | | adverse effects. | | | | | | - Concentration vs Time | | | Profile: The slide also | | | mentions a concentration vs | | | time profile for | | | theophylline, but it is not | | | elaborated on in the visible | | | part of the slide. | +-----------------------------------+-----------------------------------+ | **Concentration vs time profile | - Concentration vs. Time | | of theophylline** | Profile: The graph shows the | | | concentration of theophylline | | | over time after a bolus | | | infusion. | | | | | | - Theophylline: A drug used to | | | treat respiratory diseases | | | such as asthma and COPD. | | | | | | - Bolus Infusion: A single dose | | | of the drug administered at | | | time 0. | | | | | | - Peak Concentration: The | | | highest concentration of | | | theophylline reached after | | | the bolus infusion, around 15 | | | μg/mL at 4 hours. | | | | | | - Therapeutic Window: The range | | | of concentrations between the | | | minimum effective | | | concentration (MEC) and the | | | maximum safe concentration | | | (MSC), where the drug is | | | effective and safe. | | | | | | - MEC: Minimum effective | | | concentration, the lowest | | | concentration of theophylline | | | that produces a therapeutic | | | effect, around 5 μg/mL. | | | | | | - MSC: Maximum safe | | | concentration, the highest | | | concentration of theophylline | | | that can be tolerated without | | | adverse effects, around 20 | | | μg/mL. | +-----------------------------------+-----------------------------------+ | **Effect vs time profile of | - Effect vs. Time Profile: The | | theophylline** | graph shows the effect of | | | intravenous (IV) theophylline | | | administration on FEV-1 | | | (Forced Expiratory Volume in | | | 1 second) over time. | | | | | | - Theophylline: A drug used to | | | treat respiratory diseases | | | such as asthma and COPD. | | | | | | - FEV-1: Forced Expiratory | | | Volume in 1 second, a measure | | | of lung function. | | | | | | - IV Administration: | | | Theophylline is administered | | | intravenously, as indicated | | | by the \"Theophylline IV\" | | | label on the graph. | | | | | | - Peak Effect Time: The graph | | | shows a peak effect time of | | | around 4 hours after IV | | | administration. | | | | | | - Duration of Action: The graph | | | shows a duration of action of | | | around 16 hours, with a | | | gradual decline in effect | | | after the peak.w | +-----------------------------------+-----------------------------------+ | **Agonist and antagonist** | - Naloxone: A medication used | | | to reverse opioid overdose. | | | | | | - Pharmacodynamic Actions: | | | Naloxone\'s effects last for | | | a briefer period than most | | | short-acting opioids. | | | | | | - Elimination Half-Life: | | | Naloxone\'s elimination | | | half-life is similar to | | | morphine (60-90 minutes). | | | | | | - Renarcotisation: Patients may | | | become renarcotised and | | | suffer harm if they | | | self-discharge from medical | | | care early. | | | | | | - Clinical Considerations: | | | Clinicians are \"walking a | | | tightrope\" between | | | precipitating Acute | | | Withdrawal Syndrome (AWS) and | | | avoiding renarcotisation. | +-----------------------------------+-----------------------------------+ | **Opioid overdose action plan** | - Signs of Overdose: Not | | | responding, shallow or no | | | breathing, blue lips or | | | fingernails, snoring or | | | gurgling. | | | | | | - Check for Danger: Look out | | | for uncapped needles and | | | ensure the environment is | | | safe. | | | | | | - Check for Response: Call the | | | person\'s name, shake | | | shoulders, rub chest. | | | | | | - Call for Help: If no | | | response, call 000 for an | | | ambulance. | | | | | | - Clear Airway: Check for | | | breathing and clear the | | | person\'s airway. | | | | | | - Rescue Breaths: If not | | | breathing, perform rescue | | | breaths. | | | | | | - Administer Naloxone: If | | | available, administer | | | Naloxone. | | | | | | - Recovery Position: If | | | breathing normally, place the | | | person in the recovery | | | position. | | | | | | - CPR: If still no response, | | | perform CPR (30 compressions, | | | then 2 breaths; repeat). | +-----------------------------------+-----------------------------------+ | **Concentration effect | - Concentration-Effect | | relationship** | Relationship: The graph shows | | | the relationship between drug | | | concentration and its effect. | | | | | | - Emax: The maximum effect of | | | the drug, represented by the | | | top of the curve. | | | | | | - EC50: The concentration of | | | the drug required to achieve | | | 50% of the maximum effect, | | | represented by the dotted | | | line on the x-axis. | | | | | | - Sigmoidal Curve: The curve | | | shows a steep rise in effect | | | as concentration increases, | | | followed by a plateau at the | | | top. | | | | | | - | +-----------------------------------+-----------------------------------+ | **Midazolam clinical | - Lipophilic Benzodiazepine: | | pharmacology** | Midazolam is a lipophilic | | | benzodiazepine, which affects | | | its pharmacokinetics and | | | pharmacodynamics. | | | | | | - Rapid Onset: Midazolam has a | | | rapid onset of action, which | | | is important for its clinical | | | use. | | | | | | - Extensive Metabolism: | | | Midazolam is extensively | | | metabolised by CYP3A4, which | | | can affect its half-life and | | | efficacy. | | | | | | - Large Volume of Distribution: | | | Midazolam has a large volume | | | of distribution (1-3 L/kg), | | | which can affect its | | | pharmacokinetics and | | | pharmacodynamics. | | | | | | - Half-Life: Midazolam\'s | | | half-life is 1.5 to 5 hours, | | | but this can be significantly | | | altered by multiple factors. | +-----------------------------------+-----------------------------------+ | **Drug action and disposition** | - Drug Action: The diagram | | | illustrates the journey of a | | | drug through the body, from | | | administration to excretion. | | | | | | - Free Drug: The central | | | element of the diagram, | | | representing the drug in its | | | free form. | | | | | | - Bound Drug: The drug bound to | | | plasma proteins, shown in the | | | \"PLASMA\" section. | | | | | | - Metabolism: The process of | | | breaking down the drug into | | | metabolites, leading to | | | excretion. | | | | | | - Excretion: The final stage of | | | drug elimination, where the | | | metabolites are removed from | | | the body. | | | | | | - Tissue: The relationship | | | between free and bound drugs | | | in tissues, shown in a | | | separate box. | +-----------------------------------+-----------------------------------+ | **The effect of age on the | - Key Points: | | pharmacokinetics and | | | pharmacodynamics of midazolam** | - - Study Title: The effect | | | of age on the | | | pharmacokinetics and | | | pharmacodynamics of | | | midazolam. | | | | | | - Study Design: Controlled | | | PK/PD investigations. | | | | | | - Study Parameters: | | | | | | - \- Young participants: 24 to | | | 28 years, 66 to 89 kg. | | | | | | - \- Elderly participants: 67 | | | to 81 years, 71 to 90 kg. | | | | | | - \- All male volunteers (n=9). | | | | | | - \- No use of any medication | | | within the previous 7 days. | | | | | | - \- Elderly allowed minor | | | stable diseases (e.g., mild | | | hypertension or arthritis). | +-----------------------------------+-----------------------------------+ | **The effect of age on the | - Study Title: The effect of | | pharmacokinetics and | age on the pharmacokinetics | | pharmacodynamics of midazolam** | and pharmacodynamics of | | | midazolam. | | | | | | - Table I: Total doses of | | | midazolam and duration of the | | | two infusion cycles in young | | | and elderly subjects. | | | | | | - Key Findings: | | | | | | - \- Young subjects: 41 ± 7 mg | | | (Cycle I), 30 ± 6 mg | | | (Cycle II) | | | | | | - \- Elderly subjects: 19 ± 4\* | | | mg (Cycle I), 17 ± 3\* mg | | | (Cycle II) | | | | | | - Conclusion: Older people need | | | about half the midazolam dose | | | to achieve the same effect. | +-----------------------------------+-----------------------------------+ | **Midazolam PK/PD in young and | - Study Title: Midazolam PK/PD | | elderly** | in young and elderly. | | | | | | - Parameters Compared: CL | | | (ml/min), Vss (L), t1/2 | | | (min), Emax (Hz), and EC50 | | | (ng/mL). | | | | | | - Key Findings: | | | | | | - \- CL: Similar values for | | | both age groups. | | | | | | - \- Vss: Slightly higher in | | | the older group. | | | | | | - \- t1/2: Higher in the older | | | group. | | | | | | - \- Emax: Very low values for | | | both groups. | | | | | | - \- EC50: Significantly higher | | | in the young group compared | | | to the older group. | | | | | | - Conclusion: The study | | | suggests that there are | | | age-related differences in | | | Midazolam\'s pharmacokinetics | | | and pharmacodynamics. | +-----------------------------------+-----------------------------------+ | **Concnetration effect | - Concentration-Effect | | relationship** | Relationship: The graph shows | | | the relationship between drug | | | concentration and effect. | | | | | | - Young vs. Older: The graph | | | compares the | | | concentration-effect | | | relationship between young | | | and older individuals. | | | | | | - EC50: The drug concentration | | | required to produce 50% of | | | the maximum effect. | | | | | | - Emax: The maximum effect of | | | the drug. | | | | | | - Sigmoidal Curve: The graph | | | shows a sigmoidal curve, | | | typical of dose-response | | | relationships in | | | pharmacology. | | | | | | - | +-----------------------------------+-----------------------------------+ | **Statin effects on LDL | - Statin Comparison: The graph | | cholesterol** | compares the effectiveness of | | | five different statin | | | medications in reducing LDL | | | cholesterol. | | | | | | - Dosage and Effectiveness: The | | | graph shows the percent | | | reduction in LDL cholesterol | | | for different dosages of each | | | statin. | | | | | | Key Findings: | | | | | | - Atorvastatin appears to be | | | the most effective, with the | | | highest bar showing | | | reductions up to about 55% at | | | 80mg dose. | | | | | | - Rosuvastatin also shows high | | | effectiveness, especially at | | | lower doses. | | | | | | - The other statins | | | (fluvastatin, pravastatin, | | | simvastatin) show lower | | | overall reductions in LDL | | | cholesterol. | | | | | | Important Notes: | | | | | | - Statins lower LDL cholesterol | | | and risk of heart disease. | | | | | | - If a person is not responding | | | adequately, increasing the | | | dose may not help. | +-----------------------------------+-----------------------------------+ | **Factors affecting drug response | - Pharmacokinetics: The study | | variability** | of how a drug is absorbed, | | | distributed, metabolised, and | | | excreted by the body. | | | | | | - Pharmacodynamics: The study | | | of the effects of a drug on | | | the body. | | | | | | - Influencing Factors: Various | | | factors that affect both | | | pharmacokinetics and | | | pharmacodynamics, including: | | | | | | - Renal disease | | | | | | - Hepatic disease | | | | | | - Pregnancy | | | | | | - Drug interactions | | | | | | - Obesity | | | | | | - Environmental factors | | | | | | - Age | | | | | | - Genetic differences | | | | | | - Other diseases | | | | | | - Variability in Drug Response: | | | The central concept, | | | influenced by the above | | | factors. | | | | | | - Adherence: A factor that | | | directly affects variability | | | in drug response. | | | | | | - Methods to Address | | | Variability: Therapeutic drug | | | monitoring, dose | | | individualisation, and | | | pharmacodynamic monitoring. | +-----------------------------------+-----------------------------------+