Pharmacology And Toxicology I PDF

PHARMACOLOGY AND TOXICOLOGY PRINCIPLES OF PHARMACOLOGY I WO N G C H U N K E U N G 2 SEP 2024 1 PHARMACOLOGY Pharmacology - Scientific study of the effects of drugs and chemicals on living organisms Drug - Natural or synthetic chemical substance that affect a biolo...

PHARMACOLOGY AND TOXICOLOGY PRINCIPLES OF PHARMACOLOGY I WO N G C H U N K E U N G 2 SEP 2024 1 PHARMACOLOGY Pharmacology - Scientific study of the effects of drugs and chemicals on living organisms Drug - Natural or synthetic chemical substance that affect a biological system https://www.sharinginhealth.ca/sih/modules/pharmacology.html 2 IMPORTANCE OF PHARMACOLOGY Understand the biochemical and physiologic aspects of drug effects Determine the effectiveness and safety of drugs Help in the diagnosis, prevention and treatment of diseases. https://elifesciences.org/articles/70148 3 TOXICOLOGY Toxicology - The field of science that studies the harmful and adverse effects of chemicals, substances, physical agents or situations, that have on living organisms, and the environment https://www.slideserve.com/chance/toxicology 4  DRUG–RECEPTOR INTERACTIONS Concern with the ability of a drug to affect a given receptor Probability or strength of the drug to occupy a receptor at any given time - Drug's affinity inhibit on Degree to which a drug or ligand activates the receptors S and resulting in the cellular offert response - Intrinsic efficacy dungs https://www.youtube.com/watch?v=X9TkD8DbomY 6  affect effect drugs on Ractors EFFECT OF A DRUG DEPENDS ON: Disease states: – Chronic kidney diseases affects dramatically the drug pharmacology y i t to – Pharmacokinetics studies how body does to the drug Number of Receptors: – Differentially expressing of receptors mediate biological responses of different levels Drug dosage: – Increase in drug amount increase drug effect until saturation of receptor Drug potency/affinity: – More potent drug – Faster binding to receptor and slower releasing from receptor Drug efficacy – Ability of drug to block or activate the receptor 10 DOSE-RESPONSE RELATIONSHIP The most important concept in pharmacodynamics is the dose-response relationship which describes the dependence of the effect of a drug from its concentration at its receptor Pharmacodynamics describes the course of action of drugs leading to the physiological effect at a specific site in the body 16 FOUR MAIN PHARMACOKINETIC PROCESSES e Four main components of pharmacokinetics include: Absorption, distribution, metabolism and excretion (ADME) They are used for explaining the various characteristics of different drugs in the body The pharmacokinetic processes may be influenced by: – Patient factors such as the sex, age, genetics, and diseases – The properties of drugs such as protein binding, molecule size, and chemical characteristics 21 MECHANISMS OF ABSORPTION OF DRUGS FROM THE GASTROINTESTINAL (GI) TRACT Passive diffusion: Vast majority of drugs absorbed by this mechanism Driving force: Concentration gradient across a membrane separating two body compartments Moving of drug: From an area of high concentration to one of lower concentration Passive diffusion does not involve a carrier https://www.nonstopneuron.com/post/factors-affecting-drug-absorption-route- specific-factors Whalen, K. (2023). Lippincott Illustrated Reviews: Pharmacology (Lippincott Illustrated Reviews Series) (8th ed.). LWW. 30 MECHANISMS OF ABSORPTION OF DRUGS FROM THE GASTROINTESTINAL (GI) TRACT Facilitated diffusion Specialized transmembrane carrier proteins allowing passage of drugs into interior of cells Does not require energy It facilitates the passage of large molecules Can be inhibited by compounds competing for the carriers https://nayturr.com/types-of-diffusion/ Whalen, K. (2023). Lippincott Illustrated Reviews: Pharmacology (Lippincott Illustrated Reviews Series) (8th ed.). LWW. 31  BIOAVAILABILITY It is the rate and extent that an administered drug reaches the systemic circulation Determining the bioavailability is important – Especially for calculating the drug dosages for the nonintravenous routes of administration Example: 100 mg of a given drug is administered orally by patient  60 mg is absorbed unchanged, What is the bioavailability? Whalen, K. (2023). Lippincott Illustrated Reviews: Pharmacology (Lippincott Illustrated Reviews Series) (8th ed.). LWW. 38  BIOAVAILABILITY Example: 100 mg of a given drug is administered orally by patient  60 mg is absorbed unchanged, What is the bioavailability? Answer: The bioavailability is 0.6 or 60% Whalen, K. (2023). Lippincott Illustrated Reviews: Pharmacology (Lippincott Illustrated Reviews Series) (8th ed.). LWW. 39  DRUG DISTRIBUTION - VOLUME OF DISTRIBUTION Features of Drugs affecting the Volume of Distribution Acid-Base Characteristics ⑪ Drugs may have a propensity to- bind proteins throughout the body Reach a point of equilibrium between a bound & unbound phase I Basic (alkaline) molecules - I pH high Strong interactions with negatively charged phospholipid head groups located on phospholipid membranes Will leave the systemic circulation leading to higher Vd as compared to acidic molecules Acidic molecules 2 9 capillary · blood. es Higher affinity for albumin molecules at lower lipophilicity than neutral or basic molecules More likely to bind albumin and remain in the plasma Leading to lower mine Vd as compared to more basic molecules 49 DRUG DISTRIBUTION - VOLUME OF DISTRIBUTION Features of Drugs affecting the Volume of Distribution Lipophilicity IU lipid -> leave bloodstream -> ↑(d) Lipophilic molecules More likely to pass through lipid bilayers More likely to leave the bloodstream and distribute to areas with high lipid density such as adipose tissue ->Pat (Guarcoler 504) Have a higher Vd -> Nrd) Hydrophilic molecules IX lipid -> stay bloodstream Less likely to pass through lipid bilayers More likely to remain in the bloodstream Have a lower Vd 50 PHARMACOLOGY AND TOXICOLOGY PRINCIPLES OF PHARMACOLOGY- II WO N G C H U N K E U N G 9 SEP 2024 1 DIFFERENT ROUTES OF DRUG ADMINISTRATION Enteral Route of Medication A Rectal route of medication – Rapid and effective absorption of medications ii – Absorption via highly vascularized rectal mucosa – Medications undergo passive diffusion – Partially bypass the first-pass metabolism Parenteral Route of Medication Intravenous injection * AK 3II – Most common parental route of medication administration, bypass liver’s first-pass metabolism – Provide easy access to the circulatory system https://www.pharmacyteach.com/2022/09/different-routes-of-drug- B administration.html – Upper extremity is commonly the preferred site for https://www.ncbi.nlm.nih.gov/books/NBK568677/ intravenous medication EAK- – Lower incidence of thrombophlebitis and thrombosis than the lower limbs 8 DIFFERENT ROUTES OF DRUG ADMINISTRATION Parenteral Route of Medication Intramuscular injection – Administered in different body muscles patpat – The buttock's upper outer quadrant is chosen traditionally for intramuscular injections Subcutaneous injection – Administered to the layer of skin just below the dermis and epidermis layers – Subcutaneous tissue has few blood vessels https://www.pharmacyteach.com/2022/09/different-routes-of-drug- administration.html – Absorption at a slow, sustained rate https://www.ncbi.nlm.nih.gov/books/NBK568677/ – Administered to various sites, including the upper arm's outer area and abdomen A 9 DRUG CALCULATIONS Three primary methods for calculation of medication dosages Ratio and Proportion Method Desired Over Have or Formula Method Dimensional Analysis Method https://clipart-library.com/calculator-cliparts.html 17  RATIO AND PROPORTION METHOD Example One: A consultant orders 4 mg intravenous (IV) of a drug On hand, a clinician has 2 mg/mL vials How many milliliters are required to carry out the ordered dose? 19  DESIRED OVER HAVE OR FORMULA METHOD Example Three: A SMO orders lorazepam 4 mg IV for a patient in severe alcohol withdrawal On hand, a Medical Officer has 2 mg/mL vials How many milliliters should they draw up in a syringe to deliver the desired dose? 24 WHAT IS LORAZEPAM? - Used to relieve anxiety, and to treat insomnia caused by anxiety In a class of medications called benzodiazepines Commonly used to treat alcoholism and alcohol withdrawal symptoms In a tablet form as well as in liquid form for injection Help to decrease withdrawal symptoms https://family-intervention.com/wp-content/uploads/2016/05/Alcohol- Addiction-Treatment.jpg and reduce any cravings to drink 25 DIMENSIONAL ANALYSIS METHOD Uses a series of conversion factors of equivalency No need memorizing specific formulas Start with unit of measure Build the equation with available information – Place information with the same unit of measure as the preceding denominator in the numerator – So that unwanted labels will cancel out – Repeat until all units of measure not needed in the answer are cancelled out – Determine the numeric answer with correctly unit of measure 30  DIMENSIONAL ANALYSIS METHOD Example Five: A Resident Specialist need to administer digoxin 0.5 mg IV daily for a patient with heart failure  Drug concentration available from the pharmacy is digoxin 0.25 mg/mL How many milliliters will she need to administer to deliver the desired dose? https://www.nursingcenter.com/ncblog/august-2021/dimensional-analysis 31  DIMENSIONAL ANALYSIS METHOD Answer to Example Five Step 1: Place the unit of measure needed on the left side of the equation Step 2: On the right side, place the information given with mL in the numerator. In this example, the drug concentration available is 0.25 mg/mL. Place mL in the numerator and 0.25 mg in the denominator https://www.nursingcenter.com/ncblog/august-2021/dimensional-analysis 32  DIMENSIONAL ANALYSIS METHOD Answer to Example Five Step 3: The desired dose is 0.5 mg. Place information to the equation in the numerator to cancel out the unwanted labels Step 4: Multiply numbers across the numerator, and similarly across the denominator. Divide the numerator by the denominator for the final answer Answer: Administer 2 mL of digoxin daily https://www.nursingcenter.com/ncblog/august-2021/dimensional-analysis 33 COMMON PHARMACY ABBREVIATIONS https://images.squarespace-cdn.com/content/v1/5e48489da899cd09424943db/1628797586063- 68JF1Y1T4G1UTY6RBSQS/medical+abbreviation+list+acronyms+terms+common+nursing+cna+pharmacy 35 STEP 3: CLINICAL RESEARCH (CLINICAL RESEARCH PHASE STUDIES - PHASE 3) Study Participants: 300 to 3,000 volunteers who have the disease/condition Purpose: Efficacy and monitoring of adverse reactions Length of Study: 1 to 4 years (Approximately 25-30% of drugs move to the next phase) Demonstrate whether or not the drugs offer a treatment benefit to a specific population Involve 300 to 3,000 participants Provide most of the safety data While in previous studies less common side effects may be undetected Larger and longer studies can show long-term or rare side effects https://www.fda.gov/patients/learn-about-drug-and-device-approvals/drug-development-process 48 STEP 3: CLINICAL RESEARCH (CLINICAL RESEARCH PHASE STUDIES - PHASE 4) Study Participants: Several thousand volunteers who have the disease/condition Purpose: Safety and efficacy https://www.fda.gov/patients/learn-about-drug-and-device-approvals/drug-development-process 49 STEP 3: CLINICAL RESEARCH (CLINICAL RESEARCH PHASE STUDIES DETAILS) FDA IND Review Team Consists of a group of specialists in difference areas: Project Manager: Coordinates the team’s activities Medical Officer: Reviews all clinical study information and data before, during, and after the trial Pharmacologist: Reviews the preclinical studies Pharmakineticist: Focuses on the drug’s absorption, distribution, metabolism and excretion processes. Interprets the blood-level data Chemist: Evaluates a drug’s chemical compounds, how it is made, its stability, quality control and the presence of impurities Microbiologist: Reviews the data if the product is an antimicrobial product Statistician: Interprets clinical trial designs and data, evaluate protocols, safety and efficacy data https://www.fda.gov/patients/learn-about-drug-and-device-approvals/drug-development-process 52 PHARMACOLOGY AND TOXICOLOGY PRINCIPLES OF NEUROPHARMACOLOGY WO N G C H U N K E U N G 16 SEP 2024 1 DRUGS THAT ALTER AXONAL CONDUCTION - LOCAL ANESTHETICS 1 P B TFF I Local anesthetics stop the nerves in part of body sending signals to brain Unable to feel pain after application of local anaesthetic May still feel some pressure or movement Work by decreasing axonal conduction Nonselective inhibition of axonal conduction Suppress transmission in any nerve get reach of Local anesthetics are valuable but with limited indications https://basicmedicalkey.com/basic-principles-of-neuropharmacology/ https://decisionsindentistry.com/article/trends-in-local-anesthesia-delivery/ 8 DRUGS USED AS LOCAL ANESTHETIC Amino amides –Commonly used includes bupivacaine, etidocaine, lidocaine, mepivacaine, prilocaine, and https://en.wikipedia.org/wiki/Amide ropivacaine, etc. Amino esters –Commonly used includes benzocaine, chloroprocaine, https://en.wikipedia.org/wiki/Ester cocaine, procaine, and tetracaine 9 MONOAMINES NEUROTRANSMITTERS What is monamines? – Monoamines is a compound containing a single amine group in its molecule. One example is the neurotransmitter (e.g. serotonin, noradrenaline). Serotonin – Calming chemical: Regulate mood, anxiety, sleep patterns, appetite, sexuality and pain – Serotonin imbalance: Depression, anxiety, depression and chronic pain – Medications: Increase the levels of Serotonin by inhibiting the reuptake after their functioning at the postsynaptic receptor sites – Facilitating memory and assists in decision- making behavior https://study.com/academy/lesson/amine-definition-structure-reactions-formula.html 20 MONOAMINES NEUROTRANSMITTERS (CONTINUE) Dopamine #zE A Act as “pleasure chemical” - Released when receiving a reward in response to some behavior; such as reward relating to food and drugs Involves feelings of pleasure, focus of attention, mood, sleep, concentration, memory and motivation Diseases relating dysfunctions of the dopamine system - Parkinson’s disease, etc Some highly addictive drugs (cocaine, amphetamines, etc) - Act on brain's dopamine circuits 21 WHAT IS ADHD? Attention-deficit/hyperactivity disorder (ADHD) One of the most common mental disorders among children Symptoms include: Inattention - Unable to keep focus Impulsivity - Rash acts occurring with moment without thought Hyperactivity - Excess movement which is unfit to the setting https://foto.wuestenigel.com/doctor-holding-clipboard-with-medical-report-text/ 24 CENTRAL NERVOUS SYSTEM PHARMACOLOGY Sub-classifications Sigma (σ) receptors able to bind, with high affinity, a variety of pharmacologically active Narcotic analgesics: drugs, named σ ligands – Act on the sigma and mu The mu (μ) receptors involve in receptors in the body neuromodulating different physiological – Reduce the patient’s perception functions. Primarily affecting nociception of pain but also memory, mood, motivation, stress, temperature, respiration, endocrine and Non-narcotic agents: gastrointestinal activity – Decrease the level of Prostaglandins are hormone-like substances prostaglandin synthesis affecting several bodily functions, including Reduce the inflammatory inflammation, pain and uterine contractions response 31 CENTRAL NERVOUS SYSTEM PHARMACOLOGY Sub-classifications (Continue) Acetylcholine is an amino acid and acts as a neurotransmitter sending messages from one The cholinergic agents: neuron to another – Pharmaceutical agents either increase Acetylcholinesterase is a cholinergic enzyme or decrease the amounts of available found at postsynaptic neuromuscular junctions. acetylcholine or acetylcholinesterase It breaks down or hydrolyzes acetylcholine Adrenergic agents: Sympathetic nervous system helps the body – Affect the sympathetic nervous activate its “fight-or-flight” response on alert. Parasympathetic have opposite but system complementary roles that carries signals for – Adrenergic agents are site specific returning those systems to their standard activity levels CNS stimulants: Norepinephrine (noradrenaline) is a – Increase the available amount of the neurotransmitter of the brain that roles in neurotransmitter norepinephrine regulation of arousal, attention, cognitive – Increase cellular impulse transmission function, and stress reactions 32 CENTRAL NERVOUS SYSTEM PHARMACOLOGY Sub-classifications (Continue) GABA - It slows down the brain and producing a Anti-convulsants: calming effect. It works by blocking specific signals in central nervous system – Either increasing Na+ evacuation or preventing its entry into the cell, elevating Thalamus and cortex -Thalamus is the body's gamma aminobutyric acid (GABA) levels information relay station. All the information – or decreasing acetylcholine levels from body's senses (except smell) must be Sedatives and hypnotics: processed through the thalamus before being – Reduce the activity in the thalamus and the sent to the cerebral cortex of the brain for cortex. Hypnotics induce sleep while the interpretation. Besides, the thalamus also plays sedatives induce calmness in the recipient a role in consciousness, wakefulness, sleep, learning and memory Anti-depressants, either: – Either increase the norepinephrine and Serotonin, also known as 5-hydroxytryptamine serotonin levels in the brain or (5-HT), is a monoamine neurotransmitter. It is – Inhibit the production of monoamine called as the “happy” chemical because it oxidase (MAO) which breaks down the contributes to happiness and well-being. neurotransmitter Serotonin appears to affect mood, emotions, digestion as well as appetite 33 CENTRAL NERVOUS SYSTEM PHARMACOLOGY Sub-classifications (Continue) Dopamine receptors - a class of G protein- coupled receptors that are prominent in the Antipsychotics: vertebrate central nervous system (CNS). It acts like an inbox for messages in form of – Block the dopamine receptor sugars, lipids, peptides and proteins sites in the brain or The limbic system - part of the brain – Decrease the responsiveness involved in emotional and behavioural responses, especially for survival such as of the medulla feeding, reproduction and caring for our young, and fight or flight responses Anxiolytics: – Alter the responses in the limbic center or – They increase GABA levels 34 CENTRAL NERVOUS SYSTEM PHARMACOLOGY ANALGESICS NON-OPIOID ANALGESICS Mechanism: Three major classes, salicylates (aspirin), para-aminophenal (Tylenol), and Non-steroidal anti-inflammatory drugs (NSAIDS, e.g., Ibuprofen). All inhibit prostaglandin synthesis which may A increase the body’s response to pain. They exhibit an anti- pyretic effect by either peripheral vasodilation or by acting on the thermoregulatory center Indication: Pain, Fever Side effects: GI problems, Headache, Dizziness Examples: Aspirin, Acetaminophen, Ibuprofen, Naproxen sodium https://www.adph.org/ems/assets/StudentManual_CentralNervousSystemAgents.pdf 39 CENTRAL NERVOUS SYSTEM PHARMACOLOGY Glaucoma A common eye condition Damage to optic nerve, which connects the eye to the brain Caused by fluid building up in front part of eye Increases pressure inside the eye May lead to loss of vision 43 CENTRAL NERVOUS SYSTEM PHARMACOLOGY adrenerge - acetylcholine Narcolepsy acetylcholiness evase A rare long-term brain condition May prevent the people from choosing when to sleep or wake The brain is unable to regulate sleeping and waking patterns May lead to excessive daytime sleepiness Drowsy throughout the day difficult to concentrate and stay awake Attention-deficit hyperactivity disorder Common for kids with hyperactive behaviors 55 CENTRAL NERVOUS SYSTEM PHARMACOLOGY ANTI-CONVULSANTS Depresses the discharge of abnormally fired neurons by a number of Mechanism: different mechanisms. These mechanisms range from promoting Na+ exit from the cell, inhibiting Na+ from entering the cell, increasing the inhibitory effect of gamma-amino butyric acid (GABA), prevention of release of glutamate and aspartate, and decreasing acetylcholine released by the nerve impulses Indication: Seizures Side effects: Nystagmus, Drowsiness, Hypotension, Respiratory depression Examples: Hydantoins (ethtoin, felbamate, phenytoin) Barbiturates (phenobarbital, mephobarbital, primidone) Benzodiazepines (clonazepam, clorazepate, diazepam) https://www.adph.org/ems/assets/StudentManual_CentralNervousSystemAgents.pdf 56 PHARMACOLOGY AND TOXICOLOGY PRINCIPLES OF CARDIOVASCULAR PHARMACOLOGY WO N G C H U N K E U N G 23 SEP 2024 1 PRINCIPLES OF CARDIOVASCULAR PHARMACOLOGY Types of heart medications Pharmacology of blood vessels Drugs for hyperlipidemia Anticoagulants and antiplatelet agents 5 COMMON SYMPTOM OF MYOCARDIAL ISCHEMIA - ANGINA E in Not a disease itself Instead, it is a symptom of the other underlying condition Patient feel like pressure, squeezing or pain in the chest Angina occurs when part of the heart not receiving enough oxygen https://vivircomoadultomayor.blogspot.com/2016/08/que-es-la-angina-de-pecho.html 8  ANTI-ISCHEMIC DRUG THERAPY Anti-ischaemic drugs decrease myocardial oxygen consumption 76 Lowering heart rate, blood pressure, myocardial contractility or ventricular preload Increase myocardial oxygen supply (by coronary vasodilatation) https://wtcs.pressbooks.pub/pharmacology/chapter/6-3-common-cardiac-disorders/ 9 ANTI-ISCHEMIC DRUG THERAPY >mostly elderly Nitroglycerin – A vasodilatory drug (drugs that open the blood vessels) – Provide relief from anginal chest pain (chest pain due to reduced blood flow to heart muscles) – Acute relief of an attack of angina pectoris (or simply angina) https://thuocdantoc.vn/thuoc/glyceryl-trinitrate 10 COMMON CALCIUM CHANNEL BLOCKERS Nimodipine Lipid soluble Penetrates the blood-brain barrier Suitable for vascular spasm after intracerebral bleeding Vascular spasm Narrowing of the arteries Persistent contraction of the blood vessels This vasoconstriction reduce blood flow https://s3.amazonaws.com/static.wd7.us/f/fd/Nimodipine_label_01.jpg 18 TWO MAIN TYPES OF CALCIUM CHANNEL BLOCKERS Dihydropyridines Nondihydropyridines Nimodipine Diltiazem Nicardipine Verapamil Nifedipine Dihydropyridines target blood vessels and cause them to relax Non-dihydropyridines. There are two calcium channel blockers approved in the U.S. that aren’t dihydropyridines. They target heart muscle as well as blood vessels, effective at treating heart rhythm problems 23 MOST COMMONLY PRESCRIBED DIURETICS Thiazides are the most commonly prescribed diuretics Not only decrease fluids, thiazides also cause the blood vessels to relax #1 Earn y Avoid diuretics if you: Have severe dehydration Have anuria (lack of urine production) Have an electrolyte abnormality Have a known hypersensitivity https://www.pharmacy180.com/article/sar-of- thiazide-diruretics-2268/ 26 ANGIOTENSIN RECEPTOR BLOCKERS (ARBS) Also known as angiotensin II receptor antagonists Used to treat high blood pressure and heart failure Also used in chronic kidney disease and prescribed following a heart attack 32 WHAT IS CHRONIC AND ACUTE HEART FAILURE? Chronic Heart Failure A condition that the heart has trouble pumping blood through the body The condition may develop over a long period of time Symptoms include shortness of breath, swelling of the ankles, feet and abdomen, problems exercising and fatigue Acute heart failure A sudden, life-threatening condition that the heart can no longer do its job 37 PHARMACOLOGY AND TOXICOLOGY PRINCIPLES OF ENDOCRINE PHARMACOLOGY WO N G C H U N K E U N G 30 SEP 2024 1 DIFFERENCE BETWEEN ENDOCRINE AND EXOCRINE GLANDS What is a gland? Examples of exocrine glands – Functional unit of cells working Sweat gland, salivary glands, mammary glands, together etc – Releasing a certain products into Examples of endocrine glands either a duct or to the bloodstream Adrenal gland, pituitary Exocrine gland gland, thyroid gland, etc – Secretes the products via a ductal system to an epithelial surface, Endocrine gland – Secrete products directly into the bloodstream https://www.medschoolcoach.com/endocrine-vs-exocrine-glands-mcat-biology/ 3  OVERACTIVE THYROID UNDERACTIVE THYROID (HYPERTHYROIDISM) (HYPOTHYROIDISM) The thyroid gland makes too The thyroid gland do not make many hormones. Side effects may enough hormones. Side effects include: may include: Weight loss Weight gain Nervousness Irregular pulse Depression Irritability Forgetfulness Sleep problems Fatigue Vision problems Dry skin Muscle weakness Feeling cold all the time Feeling hot all the time 5 MEDICATIONS FOR TREATING HYPERTHYROID Methimazole is the first line of treatment of hyperthyroidism –It works quickly and has few side effects Propylthiouracil is the first line of treatment in pregnant women –lower risk of birth defects Usually needs 1-2 months for noticing the change in symptoms after starting these medications 9 MEDICATIONS FOR TREATING HYPOTHYROID Hypothyroidism is commonly treated by replacing the missing thyroid hormones of patients with oral synthetic thyroid hormones such as levothyroxine, liothyronine, or liotrix. Regular blood tests are required clinically for ensuring that patients taking the suitable dose since the dosage vary among patients 12 PHARMACOLOGY OF BONE MINERAL HOMEOSTASIS Active metabolites of vitamin D – Increase absorption of calcium from both bone and gut – Stimulates both calcium and phosphate homeostasis – Provides adequate mineral for normal bone formation Parathyroid hormone – Increases calcium reabsorption from bone – Effects on bone, gut and kidney for maintaining serum calcium in tight range – With a reciprocal effect on phosphate metabolism Parathyroid hormone and Vitamin D metabolites both reduce urinary excretion of calcium 18 MEDICATION FOR HYPERPARATHYROIDISM Cinacalcet commonly used for: Treating hyperparathyroidism, particularly if the patient is not a surgery candidate Cinacalcet decreases the amount of parathyroid hormone of the parathyroid glands and lowers calcium levels in the blood https://www.wikidoc.org/index.php/Cinacalcet Treat high calcium levels in patients with primary hyperparathyroidism who cannot have surgery 25 PROGESTINS PRESCRIPTION Help other hormones work properly Regulate the menstrual cycle and treat unusual stopping of the menstrual periods (amenorrhea) Prevent anemia (low iron in blood) and too much menstrual blood loss and cancer of the uterus Progestins are also used as contraceptives, in combination with https://www.npwomenshealthcare.com/progestins-in-combination-oral- contraceptives/ estrogens 29 ESTROGEN RECEPTOR MODULATORS Used in treatment of osteoporosis, postmenopausal symptoms and breast cancer Hormone receptor-positive (or hormone-positive) breast cancer cells have either estrogen (ER) or progesterone (PR) receptors or both These breast cancers can be treated with hormone therapy drugs that block the estrogen receptors This induces an antiproliferative effect in estrogen receptor (ER) positive breast cancer Preventing the estrogen's growth stimulating effects https://www.pngall.com/breast-cancer-ribbon-png/ in the tumor 30 MEDICATION SPECIFICALLY FOR THE MALE REPRODUCTIVE SYSTEM Androgens Male sex hormone Testosterone is the predominant androgen in all genders Important for male sexual and reproductive function Crucial for development of secondary sexual characteristics in men – Such as facial and body hair growth and voice change Affect muscle and bone development as well as metabolism 34  DIABETES TYPE 1 AND TYPE 2 Type 1 diabetes –A lifelong condition –Immune system of body attacks and destroys the cells that produce insulin Type 2 diabetes –The body does not produce enough insulin, or –Body's cells do not react to insulin properly 46 MEDICINE FOR TYPE 1 DIABETES Insulin is the main medicine Insulin given either by – Injection or – Released by a small insulin pump attached to body https://healthjade.com/insulin-pump/ https://www.diabetes.co.uk/about-insulin.html 47 INSULIN PEN Introduced in the late 1980s as an alternative to vials and syringes Containing the hormone insulin for lowering levels of glucose in blood People with diabetes use it for administering insulin Providing a convenient, simple and accurate delivery For each application, simply: https://www.drugs.com/cg/insulin-pens.html – Add in a new needle, dial a dose, inject the insulin, and carefully put the used needle into a sharps container 48 STEPS FOR USING THE INSULIN PEN Remove a new pen from the refrigerator – Wait 30 minutes for bringing to room temperature before use Wash the hands – Use soap and water or alcohol-based hand rub Remove the cap from the pen and wipe the area with alcohol Attach a new needle to the pen – Do not remove the outer cap of the needle – Make sure the needle is straight Remove the needle caps Remove air from the pen – Gently tap the pen to move air bubbles Select the correct dose on the pen by turning the dial 49 BODY SITES FOR INJECTING INSULIN Inject insulin into the upper outer arms, abdomen, buttocks or upper outer thighs Insulin works fastest for injection into the abdomen Do not inject insulin into areas of a wound or a bruise May not get into body correctly Use different body area within the site each time for injection Injected into the same area may lead to swelling, lumps or thickened skin https://www.drugs.com/cg/insulin-pens.html 50 INJECTION OF INSULIN WITH A PEN Clean the skin of injecting the insulin with alcohol pad Grab a fold of the skin between the thumb and first finger Insert the needle straight into the skin Push the injection button to inject the insulin Pull the needle out Remove the needle from the pen and put into sharp box Replace the pen cap Store the pen as directed 51 INSULIN PUMP An alternative to insulin injections A wearable medical device Holds a given amount of insulin in a cartridge or reservoir Supplies a continuous flow of insulin underneath the skin Entering the bloodstream, then insulin allows cells of the body to absorb glucose and metabolize it as energy Easier and painless to take additional insulin https://www.bmj.com/content/365/bmj.l1226 as required, without need for injection 52 PHARMACOLOGY AND TOXICOLOGY PRINCIPLES OF PHARMACOLOGY FOR R E S P I R AT OR Y D I S O R D ER S WO N G C H U N K E U N G 7 OCT 2024 1 COUGH SUPPRESSANTS Suppress the coughing reflex Usually narcotics acting on medulla oblongata of brain to prevent coughing Codeine is found in many preparations, including tablets and syrups BRONCHODILATORS Breathing difficulty in certain airway disorders Constriction of muscles surrounding the airways Bronchodilators relax the muscles and relieve the constriction 4 ANTIBIOTICS Prescribed when there is a true bacterial infection When infection worsens existing airway disease Antibiotic treatment may or may not be necessary for treating inflammatory airway diseases ANTI-INFLAMMATORY DRUGS Corticosteroids such as glucocorticoids prevent release of inflammatory chemicals Control inflammation of the airways Suppress the immune system 6 TRIGGERS OF ASTHMA Allergic asthma is very common Though not all asthma caused by allergies Other types of asthma with different kinds of triggers exist Asthma may be triggered by: – Stress – Cold air – Exercise e – Gastroesophageal reflux disease Some people have more than one kind of trigger for asthma 8 TRIGGERS OF ASTHMA (CONTINUE) Some more triggers of asthma: Pollution Smoking Bacteria and viruses Genetic Pets Household chemicals Dust https://www.allergyclinical.com/asthma-care/ 9 DRUGS FOR TREATING ASTHMA What is an asthma inhaler: A device containing a medicine Take by inhaling (breathing in) Main used for treatment of asthma Control asthma symptoms Medicine of inhaler goes straightly into the airways Require much smaller dose medicine taken as liquid or tablet or by mouth https://www.wikidoc.org/index.php/Asthma_medical_therapy 12  DRUGS FOR TREATING ASTHMA What medicine is present inside the asthma inhalers? Medicine inside inhalers mainly divided into: Relievers (short-acting bronchodilators) Preventers (steroid inhalers) Long-acting bronchodilators https://www.wikidoc.org/index.php/Asthma_medical_therapy 14  DRUGS FOR TREATING ASTHMA Preventers (Steroid inhalers) Steroid preventer medications suggested for patients regularly using reliever inhalers Steroids reduce the inflammation in the airways, prevent them from becoming narrow Commonly to be taken twice per day and sometimes more frequently Needs 7-14 days to build up its effect and may not immediately relief the symptoms Common steroid preventer medications include Beclometasone, Budesonide, Ciclesonide, Fluticasone and Mometasone, etc https://www.wikidoc.org/index.php/Asthma_medical_therapy 16  AAT-> made by liver + protect lung di ban e CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) – RISK FACTORS 21  For patients experience symptoms of breathless STEROID INHALERS even when using a long-acting inhaler FOR COPD Or develop frequent flare-ups (exacerbations): Worsening of a disease or an increase in its symptoms Including a steroid inhaler as part of treatment Exacerbations commonly caused by a bacterial or viral lung infection May also be triggered by agents that make it difficult for breathing, such as air pollution or smoking Inhalers contain corticosteroid help to reduce the inflammation in the airways Commonly prescribed in combination with long- https://smw.ch/index.php/smw/article/view/3479 acting medicine 26 STEROID TABLETS FOR COPD Patients particularly bad flare-ups (exacerbations) - Worsening of a disease or an increase in its symptoms Prescribed a short course of steroid tablets – Normally a 5-day course of treatment is recommended – Reduce the inflammation of airways Troublesome side effects for long-term use of steroid tablets: – Weight gain – Mood swings – Weakened bones (osteoporosis) 29 ANTIBIOTICS Antibiotics for adults aged 18 years and over First choice: Doxycycline - 200 mg on the first day, then 100 mg once a day for 4 days (5-day course in total) Alternative first choices: Amoxicillin - 500 mg three times a day for 5 days OR Clarithromycin - 250 mg to 500 mg twice a day for 5 days OR Erythromycin - 250 mg to 500 mg four times a day or 500 mg to 1,000 mg twice a day for 5 days 33  HOW TO TEST FOR THEOPHYLLINE? The theophylline test Used to monitor the amount of theophylline in the blood It is usually requested as a trough level Measured just before the next dose When the blood concentration is expected to be at its lowest level 44 METHOD OF ANALYSIS OF THEOPHYLLINE? High performance liquid chromatography (HPLC) method with ultraviolet detection (272 nm) Simple, sensitive and selective laboratory method of testing Developed by scientist for the https://pharmasciences.in/principle-of-hplc/#google_vignette quantification of theophylline in plasma 45 PHARMACOLOGY AND TOXICOLOGY PRINCIPLES OF GASTROINTESTINAL PHARMACOLOGY WO N G C H U N K E U N G 14 OCT 2024 1 MOTILITY OF GASTROINTESTINAL (GI) TRACT For digestion and elimination of food Muscular structures between inner and outer part of the gut Circular muscle can narrow or restrict the lumen Longitudinal muscle can shorten the intestine Circular and longitudinal muscle produce the peristaltic waves – Progression of food from mouth to anus https://en.wikibooks.org/wiki/Medical_Physiology/Gastrointestinal_Physiol ogy/Motility 4  PATHOLOGIES OF THE GASTROINTESTINAL (GI) TRACT Impairment of one or more of these simple functions: – Absorption, secretion and motility Divided into functional and organic GI disorders: – Functional types, for example: Dyspepsia Irritable bowel syndrome (IBS) – Organic, for example: Peptic ulcer Gastroesophageal reflux disease (GERD) Inflammatory bowel disease (IBD) https://openoregon.pressbooks.pub/nutritionscience/chapter/3d-disorders-of-gi-tract/ 5 DIFFERENCE BETWEEN ORGANIC AND FUNCTIONAL GI DISORDERS Functional – Changes in function or with abnormal symptoms – But with no measurable changes in tissues Organic – A measurable change to tissues, organs, or body systems https://www.pngall.com/stomach-ache-png/ 6 COMMON CAUSES OF PEPTIC ULCER DISEASE Infection with Helicobacter pylori Non-steroidal anti-inflammatory drugs (NSAIDs) Less common causes include: – Tobacco smoking – Stress due to other health conditions 9 FACTORS INCREASING THE RISK OF DEVELOPING PEPTIC ULCERS Alcohol consumption Smoking Uncontrolled stress Undesirable eating habits https://missstewartteaches.blogspot.com/2015/10/alcohol-and-tobacco.html 10 DRUGS FOR GASTROINTESTINAL DISEASE - NONPRESCRIPTION MEDICINES Antacids that neutralize stomach acid Antacids containing calcium carbonate – Such as Mylanta Provide quick relief of symptoms Antacids alone do not heal an inflamed esophagus damaged by stomach acid Overuse of antacids – May cause side effects including diarrhea as well as kidney complications Mylanta Maximum Strength - Three active ingredients: Two antacids (aluminum hydroxide and magnesium hydroxide) and A gas medication (simethicone) Relieve the symptoms of heartburn, acid reflux, and gas 12  DRUGS FOR GASTROINTESTINAL DISEASE - NONPRESCRIPTION MEDICINES * Medicines that block acid production and heal the esophagus Proton pump inhibitors Stronger acid blockers than H-2 blockers Allow time for damaged esophageal tissue to heal Such as lansoprazole, omeprazole and esomeprazole https://vimed.org/thuoc-chua-dau-da-day-2979.html 14  GENERAL SIDE EFFECTS OF H-2 BLOCKERS H-2 Blockers are typically considered safe Pregnant people considering taking the H2 blocker should consult the doctor – All common H2 blockers pass into breast milk Certain H-2 Blocker may alter the effectiveness of some pain relief medications Certain H-2 Blocker may also reduce the body’s metabolism of warfarin, which is a blood thinner It may affect the body’s ability to absorb vitamin D, vitamin B12, folate, and some other nutrients https://www.youtube.com/watch?v=4vwUdxjXca8 16 HOW DO ANTIEMETIC MEDICATIONS WORK? Work by blocking some signals in the brain responsible for feeling nauseated Nausea and vomiting – Brain-related problem more than stomach-related problem – Actually brain that triggers the uncomfortable symptoms – Chemical messengers affect the “vomiting center” of the brain – Examples of the chemical messengers include: Histamine, dopamine, serotonin, neurokinins (NKs) etc 18 HOW DO ANTIEMETIC MEDICATIONS WORK? Work by blocking one or more of the chemical messengers Stop the chemicals from attaching to their target locations Locations called receptors (chemical binding sites) Receptors vary depending on what’s causing the nausea 19 DIFFERENT ANTIEMETIC DRUGS ⑳ - W ⑧ Antagonists of the serotonin, dopamine, histamine and neurokinin, etc Some antiemetic may be more effective for some specific indications Serotonin and neurokinin antagonists – More effective in treating chemotherapy- induced vomiting and nausea Antihistamines – First-line choice for nausea and vomiting in pregnancy https://cdn.shopify.com/s/files/1/0030/1871/9295/products/7159b234b0879037e328 82f0033fe86700520aaf190d50f72f430756f6afad77_1200x1200.png?v=1625503188 20 ADSORBENTS USED IN TREATMENT OF DIARRHEA Bind and inactivate bacterial toxins or other substances that cause diarrhea Action is non-specific May also adsorb digestive enzymes, nutrients or drugs May be ineffective at controlling fluid loss Unable to prevent dehydration Commonly used adsorbents include kaolin, pectin, activated charcoal, etc https://www.ecrater.com/p/35676060/norit-200mg-activated-charcoal-treatment-of 28  GAS WITH LOOSE STOOLS May be due to condition such as diverticulitis - Inflammation of irregular bulging pouches in the wall of the large intestine Or due to increase or change in bacteria of the small intestine Related to low-fiber diet, lack of physical activity and obesity, etc 30 Which types on the stool chart indicate constipation ? https://www.wikidoc.org/index.php/Constipation_(patient_information) 36 HOW DO DIFFERENT LAXATIVES WORK? Bulk-forming laxatives – Work by increase the "bulk" or weight of stool – It in turn stimulates the bowel Emollient stool softeners – Moisten and lubricate the stool – Makes it easier to pass Osmotic laxatives – Draw fluid into the bowel and soften stools Stimulant laxatives – Promote contraction of the intestines – Thus facilitates the movement of stools through the bowel 39  HOW ABOUT MINERAL OIL ENEMA FOR CONSTIPATION? Coats the fecal contents with mineral oil Prevent water from being absorbed from the stool Lubricates and softens the stool producing a bowel movement Good option if stools are difficult to pass or very hard Suitable for patients suffer from i r hemorrhoids, recovering from childbirth or surgery, etc https://www.personallydelivered.com/301-fleet-mineral-oil-enema PHARMACOLOGY AND TOXICOLOGY ANTIMICROBIAL PHARMACOLOGY WO N G C H U N K E U N G 21 OCT 2024 1 WHAT IS THE DIFFERENCE BETWEEN ANTIBIOTICS AND ANTIMICROBIAL DRUGS? Antimicrobials – A group of agents aim of reducing the possibility of infection and sepsis Antibiotics – Derived from moulds – Or are made synthetically – A group of agents aim of killing bacteria (bactericidal) or preventing their multiplication (bacteriostatic) https://www.tasnimnews.com/en/news/2018/01/31/1643315/for-children-with-respiratory- infections-antibiotics-with-narrower-targets-are-better 3 BASIS OF ANTIBIOTICS ACTION Various antibiotics act by interfering with: – Cell wall synthesis – Plasma membrane integrity – Nucleic acid synthesis – Ribosomal function and – Metabolic pathways of bacteria, such as folate synthesis 6 β-LACTAM ANTIBIOTICS Examples are the penicillin, cephalosporin, and carbapenem, etc Antibiotics all contain a β- lactam ring Work by inhibiting the last step in bacterial cell-wall peptidoglycan synthesis https://en.wikipedia.org/wiki/Beta-lactam_antibiotics 9 MODE OF ACTION FOR BACITRACIN Bacitracin is a complex polypeptide produced by Bacillus subtilis (Gram-positive bacilli, catalase-positive, normally present in the environment, considered non-pathogenic for humans) It inhibits peptidoglycan synthesis in a step of bacterial cell wall synthesis Peptidoglycan is an envelope surrounds the cytoplasmic membrane of most bacterial species 16 Short question ANTIBIOTICS ACT BY INTERFERING WITH FUNCTION OF PLASMA MEMBRANE Polymyxins - Such as Polymyxin B and colistin (Polymyxin E) – Disrupts the outer cell membrane – Binds and neutralizes lipopolysaccharide – Inhibits respiration of Gram-negative bacterial cells Lipopeptide (Such as Daptomycin) – Bind to bacterial membranes – Leading to a rapid depolarization of the membrane potential. – Loss of membrane potential causing the inhibition of DNA, RNA and protein synthesis – Daptomycin treats infections caused by Gram- positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin- https://onlinelibrary.wiley.com/doi/full/10.1002/jppr.1435 resistant Enterococci (VRE). 19 ANTIBIOTICS ACT BY INTERFERING WITH FUNCTION OF RIBOSOMES https://open.oregonstate.education/microbiology/chapter/14-2mechanisms-of-antibacterial-drugs/ 23 ANTIBIOTICS ACT BY AFFECTING THE DNA AND RNA OF BACTERIA DNA Synthesis (Fluoroquinolones) Ciprofloxacin Levofloxacin Moxifloxacin RNA Synthesis Rifamycin 31 WHAT IS RIFAMYCIN? Antibiotics act by affecting the RNA Synthesis of bacteria Particularly effective against mycobacteria Treat tuberculosis, leprosy, and mycobacterium avium complex (MAC) infections Common side effects of rifamycin may include: Constipation and headache 38 WHAT IS RIFAMYCIN? Synthesized either artificially or naturally by the bacterium Amycolatopsis rifamycinica Includes the "classic" rifamycin drugs as well as the Rifamycin derivatives rifampicin (or rifampin), rifaximin, rifabutin, rifapentine and rifalazil 39 ANTIBIOTICS ACT BY INTERFERING WITH METABOLIC PATHWAYS OF BACTERIA Folic acid synthesis Sulfonamides Sulfones Trimethoprim Mycolic acid synthesis Isoniazid 40 SIDE EFFECTS OF TOPICAL ANTIFUNGAL AGENTS The following side effects may occur: Burning Stinging Swelling Irritation Redness 47 & Short ROUTES OF ADMINISTRATION FOR ANTIVIRALS Most antivirals are oral drugs Other common routes of administration for antiviral medications includes: – Topical (skin) creams – Eye drops – Small-particle aerosol https://foto.wuestenigel.com/wp-content/uploads/api/herpes-on-the-lower-lip-of-a-man.jpeg – IV into a vein, etc DRUGS FOR COMMON VIRAL SKIN INFECTION https://open.oregonstate.education/app/uploads/sites/8/2019/06/Fig.-16.21.png 54 AGENDA Cancer basics Traditional chemotherapy Hormonal Therapy Targeted Therapy Immunotherapy Cell Therapy Clinical Application SCI 2006SEF Pharmacology And Toxicology Toxicology of Chinese medicinal herbs LEE YUEN CHI 18/11/2024 SCI 2006SEF LEEYC 18/11/2024 1  TCM Drugs Different parts of plants such as the leaves, roots, stems, flowers and seeds can be used Herbs are often combined in formulas and given as teas, capsules, liquid extracts, granules or powders SCI 2006SEF LEEYC 18/11/2024 24  Preparation of TCM 1. Reduce or eliminate toxic and side effects to ensure medication safety 2. Enhance drug efficacy and improve curative effect 3. Change performance or efficacy 4. Change properties to facilitate storage and preparation 5. Pure medicinal materials, modified and flavored SCI 2006SEF LEEYC 18/11/2024 26  Side Effects and Risks of Herbs - Reports of products being contaminated with drugs , toxins, or heavy metals or not containing listed ingredients - In general, Chinese medicines should be administered at least 1-2 hours before or after the western medicines. However, this can only avoid the potential drug-drug interactions occurred due to direct contact in the stomach, and cannot avoid any potential interactions occurred after the drugs are absorbed into the body. - Some of the herbs can interact with drugs, can have serious sides effects, or may be unsafe for people with certain medical conditions. For example Ephedra (Ma Huang) has been linked to serious health complications, including heart attack and stroke SCI 2006SEF LEEYC 18/11/2024 28  Herb-Drug Interaction Two main approach : 1. Pharmacokinetic interaction - Processes that interfere with how the body deals with the drug, including absorption, distribution, metabolism and eliminiation 2. Pharmacodynamic interaction - Affect the action of the drug on the body, resulting in a change in the relationship between drug concentration and resultant drug action. SCI 2006SEF LEEYC 18/11/2024 29 PHARMACOLOGY AND TOXICOLOGY PRINCIPLES OF INFL AMMATION AND IMMUNE PHARMACOLOGY WO N G C H U N K E U N G 0 4 N OV 2 0 2 4 1 WHAT IS THE IMMUNE SYSTEM? Network of cells, tissues, organs, and the substances made by them Fight against infections and other diseases The immune system includes – White blood cells – Organs and tissues of the lymph system Bone marrow, spleen, thymus, If tonsils, lymph nodes, lymph vessels, etc https://philschatz.com/anatomy-book/contents/m46563.html 3 THE IMMUNE SYSTEM Two mechanisms to destroy pathogens The innate immune response and the adaptive immune response The innate immune response is rapid and nonspecific. Not always effective in its action The adaptive immune response develops slowly, such as in an initial infection with pathogen, but is effective and highly specific for attacking a wide variety of pathogens https://philschatz.com/anatomy-book/contents/m46571.html 4 BARRIER DEFENSES IN OUR BODY Oral Cavity – Salivary glands: Lysozyme Stomach – Low pH Mucosal surfaces – Mucosal epithelium: Nonkeratinized epithelial cells Normal flora (nonpathogenic bacteria) – Prevent pathogens from growing on mucosal surfaces Skin – Epidermal surface: Keratinized cells of surface, Langerhans cells Skin (sweat/secretions) – Sweat glands, sebaceous glands: Low pH, washing action https://philschatz.com/anatomy-book/contents/m46571.html https://freepngimg.com/png/82558-product-shield-photography-metal-sword-stock 5 WHAT IS INFLAMMATION? The hallmark of innate immune response is inflammation Inflammation is the response of immune system to harmful stimuli Such as toxic compounds, irradiation, pathogens and damaged cells, etc A defense mechanism which is important to health Acts by removing the injurious stimuli and initiating a healing process https://www.wikidoc.org/index.php/Inflammation 12 ANTIRHEUMATOID DRUGS eldely Antirheumatoid drugs - Agents used in the therapy of inflammatory arthritis, predominantly rheumatoid arthritis Inflammatory arthritis - Joint inflammation due to an overactive immune system, usually affects many joints at the same time Rheumatoid arthritis - An autoimmune and inflammatory disease, in which the immune system attacks healthy cells, causing inflammation (painful swelling) in affected parts of the body 15 DIAGNOSIS OF RHEUMATOID ARTHRITIS Medical history, signs and symptoms Physical examination – Joints examination Blood tests - White blood cell count, C-reactive Protein and Rheumatoid Factor, etc X-ray - To assess the severity of joint destruction Ultrasound - Detecting active inflammation, fluid buildup and erosion of bone MRI Scan - Better viewing the joints and determining for swelling 22 DRUGS FOR TREATMENT OF RHEUMATOID ARTHRITIS NSAIDs - Nonsteroidal anti-inflammatory drugs for pain relieving and reducing inflammation. Naproxen is low risk and is suitable for patients with both rheumatoid arthritis and a cardiovascular disease Steroids - Corticosteroid medications reduce inflammation, pain and slow joint damage Conventional DMARDs – Methotrexate, etc Other drugs as advised by the doctor 23 SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) Long-lasting (chronic) autoimmune disease Immune system attacks own tissues of our body Causes inflammation and may sometimes cause permanent tissue damage Affect many parts of the body May affects the joints, skin, lung, heart, kidneys and brain, etc Anyone can get Systemic Lupus Erythematosus (SLE) Women having the disease nearly nine times more often than men Most often SLE happens to people with ages https://cme.platform-med.org/wp- content/uploads/2020/06/received_856169788122828.png between 15 and 45 years 24 DRUGS FOR TREATMENT OF SLE NSAIDs - Nonsteroidal anti-inflammatory drugs for pain relieving and reducing inflammation Antimalarial drugs - Commonly used to treat malaria, such as hydroxychloroquine, can affect the immune system and can help decrease the risk of lupus suddenly worsen Steroids - Corticosteroid medications reduce inflammation Immunosuppressants - Suppress the immune system for serious cases of SLE Other drugs as advised by the doctor Conventional DMARDs – Methotrexate may caused abortion in women, there is a need to consult the doctors before using 26 MULTIPLE SCLEROSIS Chronic (Long-lasting) disease Autoimmune disorder – Body attacks itself by mistake – Mainly affects the central nervous system Unpredictable disease – Some have mild symptoms – Some may lose ability to walk, write, speak or see clearly – Affects people differently https://newsmedia.tasnimnews.com/Tasnim/Uploaded/Image/1394/01/2 2/139401221134357005077134.jpg 27  WHAT HAPPENS IN MULTIPLE SCLEROSIS Damage of myelin, the protective coating on nerve fibers, in central nervous system Myelin – Protein and fatty substance surrounding and protecting the nerve fibers In multiple sclerosis – Myelin is attacked by the immune system – Myelin is destroyed in different areas – Sclerosis is formed: Scar tissue formed by losing of myelin – The areas called lesions or plaques – Do not conduct electrical impulses normally to and from the brain https://en.wikipedia.org/wiki/Multiple_sclerosis 28  WHAT CAUSES MULTIPLE SCLEROSIS? Many possible causes of MS, including: Autoimmune disorders Environmental factors Infectious agents, such as viruses Genetic factors It is not commonly considered to be a hereditary disease Some genetic variations may increase the risk 29 PHARMACOLOGY AND TOXICOLOGY PRINCIPLES OF TOXICOLOGY I&II 11&25 NOV 2024 WO N G C H U N K E U N G 1 EXAMPLE OF DRUG SYNERGISM Aspirin and caffeine Good example of synergism With combination – giving greater efficacy and pain relief for patients with pain Without combination – Efficacy and pain relief not as high https://images.freshop.com/00310158109501/8078a2998a50df17d0df8d9fc55641d9_large.png 16 DRUG-FOOD INTERACTION The reaction between drug and food or beverage When food affects medications in the body – Food may affect the medicine in its proper working – May also affect the medicinal side effects Becoming better or worse Causing new side effects https://pharmafactz.com/wp-content/uploads/2016/02/important-food-drug-interaction.jpg On the other hand, the drug may change the way that the body uses food 18 COCA-COLA AND NSAID A significant increase in plasma concentration of ibuprofen when taken with Coca-Cola Showing an increased extent of absorption of ibuprofen Daily dosage and frequency of https://caogam.vn/sites/default/files/styles/anh_detail/public/2021-08/thuoc- nsaid_0.jpg?itok=8c90OOCo NSAID’s like ibuprofen should be well observed when Non-steroidal anti-inflammatory drugs (NSAIDs) are medicines used for administered with Coca-Cola relieving pain, reducing inflammation, and bringing down a high temperature of the body 19 GREEN VEGETABLES AND WARFARIN ↑ vita K -> Hotty Spinach is rich in vitamin K Vitamin K is important for the production of clotting factors that help prevent bleeding On the other hand, anticoagulants such as warfarin effects by inhibiting vitamin K Warfarin is clinically used for decreasing the tendency for thrombosis An increased intake of spinach thus may https://img.cndoct.com/upload/202112/17/202112171735256977.png prevent the warfarin from working 20 MILK AND TETRACYCLINES calcium->bioavailability -> antibiotics Milk, being the main component of dairy products, is rich in calcium Calcium can interact with certain antibiotics such as tetracyclines Tetracyclines may bind with calcium and forming insoluble substances The bioavailability of tetracyclines can be influenced Bioavailability refers to the extent a drug becomes completely available to its intended https://pngimg.com/uploads/milk/milk_PNG12726.png biological destination(s) 21 MATURED CHEESE AND PHENELZINE Mature cheese is the cheese product undergone with e umature/aged -> yum ripening process for a specific amount of time managed with temperature and humidity Aging cheese is important for changing the cheese's flavor and texture. As cheese ages, it loses moisture and concentrating its flavors Matured cheese contains the amino acid tyramine Tyramine interactions with phenelzine that is used for treating depressive disorders Eating mature cheese while taking phenelzine can raise the blood pressure to dangerous levels, causing life- threatening side effects Complications may included cardiac arrhythmias, https://www.pngmart.com/image/260742 cardiac failure, pulmonary edema, and death 22 GRAPEFRUIT AND STATINS Avoid eating grapefruit or drinking grapefruit juice while taking cholesterol lowering agents Such as statins: e.g. atorvastatin, lovastatin Grapefruit contain furanocoumarin chemicals causing an increase in statins potency Raising the level of the drug in bloodstream Increase the risk of side effects, such as leg pain and muscular weakness https://www.goodrx.com/classes/statins/why-cant-i-have-grapefruit- with-my-statin 23  MECHANISMS OF DRUG TOXICITY Major drug toxicities commonly grouped into five categories on the basis of their underlying mechanism: On-target Hypersensitivity and immunological Off-target Biological activation Idiosyncratic 25 CLASSIFICATIONS IN THE CONTEXTS OF DRUG TOXICITY Type Example On-target Statins (chlorosterols Hypersensitivity and immunological Penicillins Off-target Terfenadine Biological activation Acetaminophen Idiosyncratic Halothane https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4707670/ 26 MITOCHONDRIAL TOXICITY Inhibition of Protein Complexes Five protein complexes (Complexes I, II, III, IV and V) are located within the inner mitochondrial membrane and involved in ATP production Certain drugs, such as some antidiabetic and cancer drugs, etc are able to inhibit the protein complex Impair the mitochondrial ATP synthesis https://sitn.hms.harvard.edu/art/2018/mothers-mitochondria/ https://www.evotec.com/uploads/download-files/Downloadable_Publications/Cyprotex-Guides/Cyprotex- Mechanisms-of-Drug-Induced-Toxicity-Guide.pdf 35 MITOCHONDRIAL TOXICITY Inhibition of Mitochondrial Membrane Transporters Inhibition of transporters - such as the adenine nucleotide translocator The proteins that exchange mitochondrial ATP for cytosolic ADP https://ohiostate.pressbooks.pub/app/uploads/sites/36/2017/07/Mitochondrion-structure-1536x783.jpg Cause substrate depletion and https://www.evotec.com/uploads/download-files/Downloadable_Publications/Cyprotex- Guides/Cyprotex-Mechanisms-of-Drug-Induced-Toxicity-Guide.pdf reduced ATP production 36 MITOCHONDRIAL TOXICITY Inhibition of Krebs Cycle Enzymes and Fatty Acid Metabolism Inhibition of enzymes involved in the Krebs cycle (e.g., fluoroacetate) or Inhibition of enzymes involved in the fatty acid β-oxidation (e.g., tetracyclins) https://ohiostate.pressbooks.pub/app/uploads/sites/36/2017/07/Mitochondrion-structure-1536x783.jpg https://www.evotec.com/uploads/download-files/Downloadable_Publications/Cyprotex- Guides/Cyprotex-Mechanisms-of-Drug-Induced-Toxicity-Guide.pdf Cause substrate depletion and reduced ATP production 37 MITOCHONDRIAL TOXICITY Inhibition of mitochondrial DNA (mtDNA) replication and mtDNA-encoded protein synthesis Some drugs (e.g., nucleoside reverse transcriptase inhibitors) able to – inhibit mtDNA replication or mtDNA-encoded protein https://ohiostate.pressbooks.pub/app/uploads/sites/36/2017/07/Mitochondrion-structure-1536x783.jpg https://www.evotec.com/uploads/download-files/Downloadable_Publications/Cyprotex- synthesis Guides/Cyprotex-Mechanisms-of-Drug-Induced-Toxicity-Guide.pdf 38 MITOCHONDRIAL TOXICITY Oxidative Stress An imbalance of free radicals and antioxidants in the body can leads to cell damage For example, depletion of reactive oxygen species (e.g., acetaminophen) Lead to activation of cell death https://ohiostate.pressbooks.pub/app/uploads/sites/36/2017/07/Mitochondrion-structure-1536x783.jpg signaling and apoptosis (a series https://www.evotec.com/uploads/download-files/Downloadable_Publications/Cyprotex- Guides/Cyprotex-Mechanisms-of-Drug-Induced-Toxicity-Guide.pdf of molecular steps in a cell lead to its death) 39  MITOCHONDRIAL TOXICITY Mitochondrial Permeability Transition Pore Some drugs (such as some anticancer drugs) may induce irreversible opening of the pore Leading to influx of water and osmotic swelling Resulting in drug induced https://ohiostate.pressbooks.pub/app/uploads/sites/36/2017/07/Mitochondrion-structure-1536x783.jpg mitochondrial toxicity https://www.evotec.com/uploads/download-files/Downloadable_Publications/Cyprotex- Guides/Cyprotex-Mechanisms-of-Drug-Induced-Toxicity-Guide.pdf 40  TARGETS OF OXIDATIVE STRESS Lipid membranes Damage to cellular membranes DNA Modification of DNA bases Damage to deoxyribose sugar Proteins Damage to specific amino acid residues Changes in structure Degradation and fragmentation resulting in loss of enzyme activity https://www.evotec.com/uploads/download-files/Downloadable_Publications/Cyprotex-Guides/Cyprotex-Mechanisms-of-Drug-Induced-Toxicity-Guide.pdf 43  CELL CYCLE MEDIATED TOXICITY There are 4 main sequential phases of the cell cycle: G1 Phase (first growth phase) S Phase (synthesis phase) G2 Phase (second growth phase) M Phase (mitosis phase) https://www.evotec.com/uploads/download-files/Downloadable_Publications/Cyprotex-Guides/Cyprotex-Mechanisms-of-Drug-Induced-Toxicity-Guide.pdf 51  APOPTOSIS Mitochondrial Mediated (Intrinsic Pathway): Mitochondria play a key role in apoptosis In response to cell stress, mitochondria initiate or enhance cell death signalling An induction of mitochondrial outer membrane permeabilisation – Allowing water and other molecules to enter the mitochondria – Swelling and rupture of the membranes and release of mitochondrial pro-apoptotic factors – The pro-apoptotic factors being released and cross the outer membrane – Induce apoptosis by caspase activation and DNA fragmentation https://www.evotec.com/uploads/download-files/Downloadable_Publications/Cyprotex-Guides/Cyprotex-Mechanisms-of-Drug-Induced-Toxicity-Guide.pdf 61 ORGAN AND TISSUE TOXICITY https://image1.slideserve.com/2159450/drug-toxicity-in-various-organ-systems-l.jpg 67  WHAT DRUGS ARE RENAL TOXIC? Antimicrobials such as: Aminoglycosides Antifungals (such as amphotericin B) Beta-lactams (such as cephalosporins, penicillins) Quinolones (such as ciprofloxacin) Rifampin (such as Rifadin) Vancomycin (such as Vancocin) Can lead to drug-induced acute renal failure 77  SYMPTOMS OF NEUROTOXICITY Dysfunction relating to the nervous system such as: Confusion Poor concentration Memory loss Personality changes Loss of sensation Muscle weakness 82