PHAR 2005- P&P (TEST #1) PDF

Summary

This document is a test covering weeks 1-4 of the PHAR 2005 course. It includes questions on topics such as drug nomenclature, drug equivalency, drug approval, and drug scheduling. It also discusses prescription writing and dispensing responsibilities.

Full Transcript

SEM 3 PHAR 2005 - Pathophysiology & Pharmacology TEST #1 Content: Week 1, 2, 3, 4 WEEK 1: PHAR Part 1 What is Pathology? ○ The laboratory study of cell and tissue changes associated with disease ○ Study of disease What is Pharmacology?...

SEM 3 PHAR 2005 - Pathophysiology & Pharmacology TEST #1 Content: Week 1, 2, 3, 4 WEEK 1: PHAR Part 1 What is Pathology? ○ The laboratory study of cell and tissue changes associated with disease ○ Study of disease What is Pharmacology? ○ Study of drugs. ○ Their: Actions Dosage Therapeutic uses Adverse effect What are Drugs? ○ Chemical substances used to diagnose, prevent or treat disease ○ Various sources Drugs are mostly? ○ Mostly SYNTHETIC How are Drugs increasingly being used in medicine (pharmcare)? ○ Increase use of: Prescription drugs OTC drugs Herbal remedies What is the Dental Hygienist role in regards to Pharmcare/drugs? ○ Have a through understanding of a client’s drug use ○ Understand the implications of client drug use ○ Consult with client and other HCP about client’s drug use What are the Drug sources? ○ Plant ○ Animal ○ Microbial ○ Mineral or organic ○ Synthetic REMEMBER MOSTLY SYNTHETIC SEM 3 PHAR 2005 - Pathophysiology & Pharmacology TEST #1 Content: Week 1, 2, 3, 4 In the Drug names, all drugs have at least how many names? ○ All drugs have at least 2 NAMES; many have more DRUG NAMES Chemical Name Chemical structure Used when drug is being investigated Generic Name Single Official name of drug BEFORE it becomes marketed NOT CAPITALIZED - ALWAYS LOWER CASE Can be marketed by others after patent expired with other trade names NOTE: TRY TO ALWAYS USE IN CLINIC Trade Name If drug marketed commercially Registered with trademark and CAPITALIZED Protected for 20 years Used interchangeably with BRAND NAME ○ NAME OF COMPANY (Brand name) Give an example of Drug Nomenclature? ○ Chemical = 2-(4-Isobutylphenyl) propionic acid ○ Generic = ibuprofen ○ Trade = Advil, Motrin Generic drugs must enter the bloodstream at the same rate as? ○ Same rate as Trade name product DRUG EQUIVALENCY AND SUBSTITUTION Chemically Equivalent 2 drug formulation meet chemical and physical standard for the drug Biologically Equivalent 2 formulations produce similar concentration of the drug in blood and tissue Therapeutically 2 formulations have equal therapeutic effects in Equivalent clinical trials SEM 3 PHAR 2005 - Pathophysiology & Pharmacology TEST #1 Content: Week 1, 2, 3, 4 How are drugs approved in Canada? ○ Drugs approved in Canada through the HEALTH PRODUCTS AND FOOD BRANCH (HPFB) of Health Canada to asses drugs for: Safety Efficacy Quality What are the 2 Laws related to drug standards and controls in Canada? ○ The Food & Drug Act ○ The Controlled Drugs and Substances Act Who regulates Natural Health products? ○ By the Natural and Non-prescription Health Products Directorate (NNHPD) under the Natural Health Products Regulations (2004); within the Food and Drug Act Why do we need legislation and regulation? ○ Protect consumer from health hazards and fraud or deception in the sale and use of foods, drugs, cosmetics and medical devices ○ Monitor the potency, purity and safety of Canadian drug products ○ Includes provisions for: Conditions of drug sale Labeling and advertising of drugs Manufacturing standard Procedure of legalizing new drugs Inspection Importation What is a Drug Schedule? ○ Provides district drug categories defined by medical use & each specific drug’s potential for abuse and dependency ○ A method of classification that places drug in certain categories according to various characteristics When was drug scheduling made consistent across the country? ○ 1995 How many categories of drugs are in the Drug Schedule? ○ 4 categories of drugs 3 schedules 1 unschedule category SEM 3 PHAR 2005 - Pathophysiology & Pharmacology TEST #1 Content: Week 1, 2, 3, 4 What does Ontario utilize for reference as their model? ○ Ontario utilizes the National Drug Scheduling System schedule by reference as their model ○ “Off label” uses What model does Ontario adopt and who developed it? ○ Ontario adopts the National Drug Scheduling System model developed by the National Association of Pharmacy Regulatory Authorities (NAPRA) as the provincial model (scheduling by reference) DRUG SCHEDULES Schedule 1 Drugs Requires a PRESCRIPTION for sale Provided to the public BY A PHARMACIST following diagnosis & professional intervention ○ Potential for dependency Controlled in a regulated environment as defined by provincial pharmacy legislation ○ Minocycline hydrochloride (Arestin) ○ Doxycycline Hyclate gel (Atridox) ○ Antibiotics Schedule 2 Drugs Require professional intervention from a pharmacist at point of sale ○ Do not require a prescription: “Behind the Counter” Less strictly regulated than Schedule I drugs Stored where no public access or opportunity for patient self-selection ○ EX: Prevident toothpaste, codeine, methadone Schedule 3 Drugs Available without a prescription: “OTC” May be self-selection, but sold on store shelves UNDER SUPERVISION OF PHARMACIST ○ May pose some risk in some self-selection situations ○ EX: Fluorides containing 1mg or less of fluoride ion per dosage unit Unscheduled Sold WITHOUT PROFESSIONAL SUPERVISION Drugs ○ Sold from any retail outlet Labeled clearly, with instructions for use NOT INCLUDED IN SCHEDULES I,II, OR III ← FROM CDHO SEM 3 PHAR 2005 - Pathophysiology & Pharmacology TEST #1 Content: Week 1, 2, 3, 4 Where should unused and expired drugs be taken? ○ Unused and expired drugs should be taken to LOCAL PHARMACIST for proper disposal Some municipalities and police forces offer take back programs Why should expired drugs not be used? ○ No longer effective ○ May have dangerous interactions with other drugs ○ Can negatively affect the kidneys Why should Drugs not be flushed? ○ Can negatively affect water and environment What kind of Act is writing a drug prescription? ○ It a Controlled Act A prescription is a signed legal document; must include? ○ Must include: Patient’s name, address and age (If Significant) Prescriber’s name, address and identification Date Name and amount of the drug Permission for additional quantities if necessary (repeats) Is Electronic prescription now being permitted? ○ Yes When can Dental Hygienists only write prescriptions? ○ Dental hygienist can only write prescriptions after successfully passing the CDHO Drugs in Dental Hygiene Practice Examination (PDHPE) DH prescription writing responsibilities varies across Canada SEM 3 PHAR 2005 - Pathophysiology & Pharmacology TEST #1 Content: Week 1, 2, 3, 4 ○ What is Signatura? The instruction in the prescription ○ What is a Signature? Your signature What do all prescriptions require? ○ They all require a “Label” What does a Label should include? ○ Pharmacy information ○ Patient and prescriber’s name ○ Name, quantity and strength of medication ○ Directions for use ○ Warnings EX: Do not take with Alcohol ○ Use of generic and trade/ brand names When prescribing limited to Chlorhexidine Gluconate (CHG), most home fluoride treatments used in caries prevention do not require a Rx that contains? ○ Contain less than 1 mg of fluoride ion per dosage unit (schedule 2) Drugs purchased from a pharmacy for use in the DH practice should have what? ○ It should have “FOR IN OFFICE USE” clearly noted on prescription Where should accurate Rx composed be kept? ○ In client’s health record SEM 3 PHAR 2005 - Pathophysiology & Pharmacology TEST #1 Content: Week 1, 2, 3, 4 What should you provide during client education in regards to drugs? ○ Why drugs was prescribe ○ How it works ○ When to take it ○ Possible side effects What is Dispensing? ○ Similar criteria to prescribing ○ Must have valid Rx (DH or DDS) ○ Drugs not expired and not expected to expire within Treatment course ○ Container marked appropriately What is Selling? ○ Reserved for special circumstances EX: Pharmacy cannot be accessed ○ Only actual cost of drug can be charged Selling drug for profit not permitted What are the reasons why there is a Non-compliance with medications? ○ Costs = cannot afford ○ Lack of understanding ○ Fear of medication side effects ○ Forgetfulness ○ Start to feel better WEEK 1: PHAR Part 2 What can Drugs modify? ○ Drugs can modify cellular function Produce either the same action or block the action of an endogenous agent DO NOT IMPART A NEW ACTION DRUG ACTION Log dose-response curve Relation between dose and response Potency Amount of a drug required to produce an effect Efficacy Maximum intensity of effect or response that can be produced Half life Amount of time that passes for concentration of drug to fall to half its original blood level How quickly drug is removed from the body ○ TAKES 4-5 HALF LIVES FOR DRUG TO BE ELIMINATED FROM THE BODY SEM 3 PHAR 2005 - Pathophysiology & Pharmacology TEST #1 Content: Week 1, 2, 3, 4 What is the Dose-Effect curve? ○ When a drug exerts an effect on biologic systems, it is possible to measure the response to the dose of the drug given What is the Therapeutic Index? ○ Ratio of the minimum toxic concentration to the median effective concentration ○ Helps determine the efficacy and safety of a drug ○ A ratio of the median lethal dose (LD50) to the median effective dose (ED50) ○ THE MARGIN OF SAFETY What is the use of Therapeutic index? ○ Used to find toxicity of a drug Because death is the end point when one is measuring the lethal dose, LD50 is the dose that causes death in how many test animals? ○ Causes death in 50% of test animals The ED50 ( effective dose) is the dose required for? ○ The dose required to produce the desired clinical effect in 50% of the test animals Therapeutic index: ○ TI = LD50/ED50 Toxic dose in 50% of population/ Effective dose in 50% of the population ○ REMEMBER: THE GREATER THE TX, THE SAFER THE DRUG SEM 3 PHAR 2005 - Pathophysiology & Pharmacology TEST #1 Content: Week 1, 2, 3, 4 The greater the TI, the safer the drug. BUT drugs with LOWER TI (close to zero) require what? ○ Drugs with lower TI(close to zero) require careful monitoring to avoid toxic reactions EX: a drug with a low TI is DIGOXIN = drug used to treat heart failure What must Drugs do to exert an effect? ○ Drugs must BIND with a receptor site on a cell to exert an effect Enhancement or Inhibition Where are receptor sites located? ○ Located on a cell membrane or within cell ○ Usually specific weak bonds Some drugs have higher affinity to same site Once bound, how does it alter the function of an organism? ○ AGONIST ANTAGONIST Binds to receptor + Binds to receptor and ENHANCES normal cell BLOCKS cell activity activity HAS NO EFFECT HAS EFFECT What is Pharmacodynamics? ○ Drug interaction with receptor ○ Produce change in cell function How does interaction happen? ○ Via chemical bonds with the receptor site ○ Receptor is unique 3 dimensional = selective ○ Drug act by forming a chemical with specific receptor site SIMILAR TO A LOCK AND KEY SEM 3 PHAR 2005 - Pathophysiology & Pharmacology TEST #1 Content: Week 1, 2, 3, 4 What is Pharmacokinetics? ○ Change in concentration of a drug as it moves through compartments of the body ○ Movement of drugs in the body What does Pharmacokinetics require? ○ Requires drug passing through various tissue membranes Simple diffusion Active transport Facilitated diffusion What are the 4 steps involved in the typical route of drugs? ○ 4 STEPS INVOLVED IN THE TYPICAL ROUTE OF DRUGS:ADME 1. Absorption What happens to the drug before it reaches systemic circulation Depends of route of administration “HOW WILL IT GET IN?” 2. Distribution Drug moves from vascular to extravascular space After drug gets into systemic circulation “WHERE IT WILL GO?” 3. Metabolism Irreversible transformation of parent compound into daughter compound Via enzymes in liver = how it breaks down “HOW IS IT BROKEN DOWN?” 4. Elimination Removal of substance from the body “HOW DOES IT LEAVE?” 1. ABSORPTION: how does it process? ○ Process where drug molecules are transferred from site of administration to systemic circulation Requires most drugs to pass through biological membranes 1. ABSORPTION: rate of absorption is influenced by? ○ By: Site of absorption = route of administration Physicochemical factors = ionization, lipid, solubility & molecular size + shape 1. ABSORPTION: What is Bioavailability? ○ Fraction of overall dose that reaches systemic circulation (IV= 100%) 2. DRUG DISTRIBUTION: how do drugs occur in blood? ○ Drug occur in 2 forms in blood: Bound or Unbound to plasma protein = reversible SEM 3 PHAR 2005 - Pathophysiology & Pharmacology TEST #1 Content: Week 1, 2, 3, 4 Free form = exerts a pharmacological effect Bound form = serves as storage (plasma proteins) 2. DRUG DISTRIBUTION: what is distribution? ○ The passage of drugs into various body fluid compartments such as plasma, intestinal fluids, and intercellular fluids to the site of action specific and nonspecific site of action EX: fat, muscle, intracellular, interstitial 2. DRUG DISTRIBUTION: how is Distribution determined? ○ Determined by: Size or organ Blood flow Drug solubility Plasma protein binding capacity Presence of barriers 2. DRUG DISTRIBUTION: What is Redistribution? ○ The movement of drug from site of action to non-specific site of action EX: Thiopental induces sleep quickly redistributed to other site causing no action on CNS 3. DRUG METABOLISM (BIOTRANSFORMATION): what is drug metabolism? ○ Irreversible transformation of parent drug compound to daughter drug compound Enzyme-mediated chemical reaction = usually in liver 2 sets of chemical reactions = two-phase system 3. DRUG METABOLISM (BIOTRANSFORMATION): what is the goal in this route? ○ Goal is to chemically change a drug to a more H2O soluble compound that is easier to eliminate via the kidneys Resulting metabolites usually more: more ionized Less lipid soluble More readily excreted Renal reabsorption will be reduced Less likely to bind plasma,tissue or stored in fat resulting in excretion SEM 3 PHAR 2005 - Pathophysiology & Pharmacology TEST #1 Content: Week 1, 2, 3, 4 ○ IF GI = absorbed + broken down by liver then goes to the blood IV to Mouth = higher dose ○ IF NOT GI = much faster Mouth to IV = lower dose 3. DRUG METABOLISM (BIOTRANSFORMATION): what is Phase 1? ○ Goal is to make drug more water soluble-elimination via kidneys ○ Liver enzymes (oxidases) chemically converts drug to more H2O soluble compound through oxidation process What is the largest family of enzymes? ○ Cytochrome p450 (CYP 450) = MAIN ENZYME 3. DRUG METABOLISM: What are Phase 1 reactions? ○ 3 possible results of phase 1 metabolism: Active to inactive = MOST COMMON Parent drug becomes completely inactive Inactive to active Original substance is not pharmacologically active BUT one of its metabolites “Prodrug” must be metabolized before it becomes activated (acyclovir) Active to (less) active First converted into 2nd less active form One or more of the metabolites are pharmacologically active BUT less so than the original drug (diazepam) 3. DRUG METABOLISM: What is Phase 2? ○ Reactions chemically change phase 1 metabolites, so they are soluble enough-easier to eliminate via kidneys Metabolites formed in phase 2 are HIGHLY H2O SOLUBLE to avoid reabsorption by kidney tubules SEM 3 PHAR 2005 - Pathophysiology & Pharmacology TEST #1 Content: Week 1, 2, 3, 4 3. DRUG METABOLISM: What is First - Pass Effect? ○ When drug is given orally or rectally, it passes through hepatic portal circulation and to liver first via portal vein, where it metabolized ○ Drugs are inactivated to varying degrees before going to systemic circulation ; has less systemic effect 3. DRUG METABOLISM: A drug with high first pass effect requires what when administered orally? ○ A drug with high first pass requires HIGHER DOSE when administered orally 4. DRUG EXCRETION: What is Excretion? ○ Elimination of an unbound drug or metabolite from the body Renal excretion is most common Drugs can be excreted in original form as metabolites 4. DRUG EXCRETION: What are the 3 steps of excretion? ○ Filtration ○ Reabsorption ○ Secretion 4. DRUG EXCRETION: What are the 3 Renal Routes? ○ Glomerular filtration Most common Filtered by glomerulus and concentrates in renal tubular fluid ○ Active tubular secretion Transports drug form systemic blood across renal tubular epithelium into renal tubular fluid ○ Passive tubular diffusion Reabsorption of un-ionized, lipid soluble compounds ○ OTHER(EXTRA-RENAL) ROUTES OF DRUG EXCRETION: Bowels (via bile) Respiration Saliva Gingival crevicular fluid Perspiration and breast milk SEM 3 PHAR 2005 - Pathophysiology & Pharmacology TEST #1 Content: Week 1, 2, 3, 4 What are Factors influencing drug action? ○ Age Infants and children need lower dosage due to lower body weight + immature hepatic system Elderly Have increased risk of accumulating drugs in tissues Liver is less efficient at breaking down drugs and kidneys are less efficient at excreting them ○ Body weight Increased body weight takes more time for drug action Increase dosage required Lower body weight require lower dosage ○ Pregnancy Drugs can potentially cross the placenta and cause genetic abnormalities During lactation drugs excreted into milk ○ Genetic variation Responsible for most IDIOSYNCRATIC RESPONSE Role in drug allergies What is Idiosyncratic Response? ○ Weird response = when you just do not know why you are getting that reaction What are more factors influencing drug action? ○ Physiological factors/emotional state Placebo effect EX: m&m’s as medicine ○ Pathological state Patients with disease may respond differently to drugs ○ Time of administration Especially with regards to timing with eating meals ○ Route of administration Some routes take longer than others EX: IV vs. Orally ○ Drug Dosage Increase dose increases the drug response Desired and adverse effects ○ Drug Formulation Liquid vs Pill form Enteric covering present ○ Client compliance Adherence to prescribed drug Drug action will be compromised if the drug is not taken or is not taken at the recommended intervals SEM 3 PHAR 2005 - Pathophysiology & Pharmacology TEST #1 Content: Week 1, 2, 3, 4 ○ Tolerance Need for increasing dose to obtain same effects ○ Environmental factors Can effect drug Ex: Chemicals, drug, diet ○ Drug interactions Some drugs should not be take together Reaction can cause inhibitory or excitatory action What does Desired Effect mean? ○ Exerts the effect expected by stimulating/inhibiting cell function What does Adverse Effect mean? ○ An unwanted or undesirable effect of a drug on the body even at recommended doses ○ Can be dangerous Can cause tissue damage or be life threatening EX: side effect, toxic effect How are the routes of “drug administration various ways of drug can be administered” classified as? ○ Classified as: Enteral (oral route) In to Gastro-intestinal tract via oral or rectal Oral is safest, least expensive, most convenient GI = PILL + WATER Parenteral Bypasses GI Primarily refers to various injection routes but also includes inhalation and topical Fastest onset and more predictable Useful for emergencies, unconscious, uncooperative and nausea Requires asepsis, more painful, more irreversible, more pronounced adverse effects, not easily administred, $$ and more dangerous THINK IV + NO GI = NEEDLE + SYRINGE Topical Includes: ○ Epicutaneous ○ Transdermal ○ Inhalation ○ Mucous membrane ○ Subgingival SEM 3 PHAR 2005 - Pathophysiology & Pharmacology TEST #1 Content: Week 1, 2, 3, 4 What are the 2 routes in Enteral? ○ Oral (PO) ○ Rectal (PR) What is the most common route of drug administration in NA? ○ Enteral (PO) Most simple way to deliver a drug to the body Includes: tablets, capsules and liquids Small intestine provides a large area of absorption Slow onset = less predictable drug blood level What can result in Enteral(PO)? ○ Stomach and intestinal irritation and upset ○ Nausea and vomiting In Enteral(PO), some drugs are inactivated by? ○ GI tract acidity or enzymes In Enteral (PO) what does it require from patients? ○ Patient cooperation In Enteral (PO), what is the average onset drug action? ○ 30 - 60 minutes average onset drug action In Enteral (PR), how is it given? ○ Given as suppositories, creams or enemas In Enteral (PR), who is it suitable for? ○ Suitable for vomiting or unconscious patients In Eternal (PR), what kind of effect is it for? ○ For local or systemic effect In Enteral (PR), what are the disadvantages? ○ Poor and irregular absorption ○ Poor patient acceptance What is the Parenteral Route? ○ Not involving the GI System What does Parenteral mean? ○ “By injection” SEM 3 PHAR 2005 - Pathophysiology & Pharmacology TEST #1 Content: Week 1, 2, 3, 4 What are the 3 most frequently used parenteral routes? ○ Intramuscular (IM) ○ Subcutaneous (SQ) ○ Intravenous (IV) ○ PARENTERAL ROUTES Intravenous (IV) Direct injection into blood No absorption phase MOST RAPID drug response Almost immediate onset action Phlebitis may occur: due to local irritation and allergy Intramuscular (IM) High blood flow of skeletal muscle permits drug absorption Suitable for more irritating drugs Usually deltoid and gluteal mass Subcutaneous (SQ) Solutions or suspensions into subcutaneous areolar tissue Gain access to systemic circulation Avoids liver inactivation for some drugs Can result in sterile abscesses OTHERS Intradermal route = injected into dermis of skin providing L.A. Intrathecal route = injection of solution into Spinal Subarachnoid space = EPIDURALS Intraperitoneal route = placing fluid into peritoneal cavity where exchange of substances occur What are the Topical routes? ○ Epicutaneous route ○ Transdermal route ○ Inhalation route ○ Sublingual route SEM 3 PHAR 2005 - Pathophysiology & Pharmacology TEST #1 Content: Week 1, 2, 3, 4 What is the Epicutanous route? ○ Direct application to the skin for a LOCALIZED effect ○ Administration gels & liquids Antifungal creams, estrogen creams What are the advantages and disadvantages of Epicutaneous Route (topical route)? ○ Advantages: Some are OTC Overdose is rare ○ Disadvantages: May be difficult to regulate dosage What is a Transdermal Route? ○ Provides continuous, controlled systemic absorption of medication through a semipermeable membrane by application of medication to intact skin ○ Reduces need for repeated dosing ○ May cause local irritation ○ EX: Birth control patch (estrogen) Nicotine patch What is Inhalation route? ○ Includes oral and nasal ○ Used for both local and systemic effects ○ Drug is deposited bronchial epithelium Can produce dilation or reduces inflammation ○ Administration of gaseous, microcrystalline, liquid powder form drugs What are the advantages and disadvantages of Inhalation route? ○ Advantages: Very rapid onset of action No drug destruction ○ Disadvantages: May be difficult to regulate dosage Irritation to mucosa Popular abuse of drugs What is the Sublingual route? ○ Includes application to mucous membranes In the sublingual route, how many minutes is the immediate onset? ○ Immediate onset is 1 -3 mins ○ Goes directly into the blood with little loss of the drug (nitroglycerine) SEM 3 PHAR 2005 - Pathophysiology & Pharmacology TEST #1 Content: Week 1, 2, 3, 4 What does the Sublingual route avoid? ○ GI acid ○ Enzymes ○ First Pass effect What are the Dental Anesthesia Routes of administration? ○ Infiltration Injection of local anesthetic solution into tissues in peripheral area of small terminal nerve endings ○ Nerve Block Injection of local anesthetic solution into tissues close to main nerve trunk to anesthetize a group of nerves What is the Topical Route for dental? ○ Subgingival strips and gels ○ Dental specific topical application ○ Placement of drug-impregnated strips or gels subgingivally ○ Uses small doses and minimizes systemic effects What is NILA? ○ Non Injectable Local Anesthetic ○ EX: Oraqix LIST ACCORDING TO THEIR ONSET OF ACTION FROM FASTEST TO SLOWEST 1 IV/ Inhalation 2 Sublingual 3 Intramuscular 4 Subcutaneous 5 Transdermal SEM 3 PHAR 2005 - Pathophysiology & Pharmacology TEST #1 Content: Week 1, 2, 3, 4 Which is faster: Inhalation or Patch? ○ Inhalation LIST ACCORDING TO THEIR ONSET OF ACTION FROM FASTEST TO SLOWEST ENTERAL 1 Rectal 2 Nasogastric 3 Oral LIST ACCORDING TO THEIR ONSET OF ACTION FROM FASTEST TO SLOWEST PARENTERAL 1 Intravenous 2 Intramuscular 3 Subcutaneous 4 Intradermal LIST ACCORDING TO THEIR ONSET OF ACTION FROM FASTEST TO SLOWEST PERCUTANEOUS / MUCOSAL 1 Inhalation (lungs) 2 Sublingual (tongue) 3 Transdermal (through skin) 4 Topical (on skin) SEM 3 PHAR 2005 - Pathophysiology & Pharmacology TEST #1 Content: Week 1, 2, 3, 4 What is the Adverse response to drugs? ○ All drugs have multiple actions = drugs lack absolute specificity = can act on many different organs and tissues Therapeutic effect = clinically desirable action Adverse Effect = undesirable reactions ○ What are undesirable drug effects? Often unpredictable Maybe an exaggerated desired effect, allergic, unexpected Potentially harmful Sometimes unexplainable Occur at usual therapeutic doses ○ What should DH be aware of in regards to adverse response? DH should be aware of potential negative oral manifestation SEM 3 PHAR 2005 - Pathophysiology & Pharmacology TEST #1 Content: Week 1, 2, 3, 4 What are other Adverse Drug responses? ○ Teratogenic effect ○ Drug dependence What is the Teratogenic Effect? ○ Congenital abnormalities ○ Various pregnancy categories to delineate risk ○ FDA categories now include narrative information EX: Thalidomide for morning sickness for pregnant mothers = causes babies with no limbs What is Drug Dependence? ○ Characterized by physical or psychological symptoms when the drug is withdrawn Physical Dependence When drug is withdrawn there are intense physical disturbances Psychological Dependence(Habituation) State of emotional reliance on a drug Can occur with any drug When drug is withdrawn, manifestations range from cravings to severe psychological symptoms Inter-relationship between Tolerance, Dependence and Addiction (disease) What are Drug Interactions? ○ Potentiation Combining drugs together and observing a larger response than expected ○ Antagonism Combining 2 drugs together that nullify the effects of each other SEM 3 PHAR 2005 - Pathophysiology & Pharmacology TEST #1 Content: Week 1, 2, 3, 4 WEEK 2: Autonomic Nervous System NEW TERMINOLOGY 1. Tachycardia - How fast the heartbeat is 2. Palpitations - Heart beat 3. Arrhythmias - Irregular heart beat 4. Hypertension - High blood pressure 5. Cerebrovascular - Stroke Accident (CVA) 6. Bradycardia - Slow heartbeat 7. Tachypnea - Rapid breathing 8. Hypotension - Low blood pressure 9. Orthostatic or - Getting up too quickly = dizziness Postural Hypotension 10. Vertigo - Dizziness 11. Photophobia - Afraid of lights = some medications cause it 12. Hyperglycemia - High blood sugar 13. Myocardial - Heart attack Infarction 14. Mydriasis - Dilated pupils (eyes) = see if pupil retracts or not 15. Syncope - Fainting What is the Autonomic Nervous System? ○ Automatic modulating system for many bodily functions INVOLUNTARY What neurons in peripheral nervous system affecting target cells ○ Efferent neurons = almost all body tissues innervated by ANS What are the 2 neuron systems with 2 synapses? ○ PRE & POST Ganglionic neuron What are Neurotransmitters? ○ They travel across synapses to communicate between neurons or neuron and effector SEM 3 PHAR 2005 - Pathophysiology & Pharmacology TEST #1 Content: Week 1, 2, 3, 4 ○ They basically transfer signals What are the 2 divisions of ANS? ○ Sympathetic (SNS) Originates in CNS in middle of spinal cord Remember: SHORT axon - LONG axon FIGHT OR FLIGHT ○ Parasympathetic (PSNS) Originates in CNS in brain stem and bottom of spinal cord Remember: LONG axon - SHORT axon REST AND DIGEST & FEED AND BREED What do the Preganglionic neurons store? ○ Stores neurotransmitters in vesicles in axon terminals STEPS: Action potential reaches axon terminal Releases neurotransmitter at synaptic cleft Crosses cleft Binds to receptors in cell membrane of post ganglionic neuron Depolarized neuron Result = action potential Neurotransmitter is released and binds with? ○ With Effector receptor Excitation = heart beat faster Inhibition = relaxation What is the Similarity and difference of ANS? ○ Similarity Difference 2 neurons Reaction Release chemical reactions Length of nerves ○ ACh or NE SEM 3 PHAR 2005 - Pathophysiology & Pharmacology TEST #1 Content: Week 1, 2, 3, 4 What do neurotransmitters interact with? ○ Interact with receptors = specific bond with receptor How can Drugs modify ANS activity? ○ By altering neurotransmitter activity What are Cholinergic neurons and Adrenergic neurons? ○ CHOLINERGIC NEURONS ADRENERGIC NEURONS Store and produce Store and produce Acetylcholine (ACh) Norepinephrine (NE) Postganglionic neurons: Preganglionic neurons: ○ SNS ○ PSNS AND SNS WITH THE Postganglionic neurons: EXCEPTION ○ PSNS FOR SWEAT GLANDS AND SOME BLOOD VESSELS ARE CHOLINERGIC THINK CHILL = PSNS THINK ADRENALINE = SNS What are the specific receptor subtypes that organs and glands are dominated by? ○ Inhibition = EVEN #S ○ Excitation = ODD #S In Cholinergic receptors which is a receptor for ACh, what are the 2 subtypes? ○ Nicotinic (N2) All postganglionic neurons (in SNS) ○ Muscarinic (M) All PSNS effector cells (and some sweat glands) Subtypes: M1-M5 ○ REMEMBER: THE MOST IMPORTANT IN DENTISTRY IS M3 In Adrenergic receptors which are receptors for NE and EPI, they are all SNS effector cells, what are the 2 types? ○ α (alpha): α1 α2 ○ β (Beta) = EX: Beta 2 for most inhalers = makes lungs relax β1 SEM 3 PHAR 2005 - Pathophysiology & Pharmacology TEST #1 Content: Week 1, 2, 3, 4 β2 Β3 CHOLINERGIC RECEPTORS: What are Muscarinic receptor sites? ○ Named because of their affinity for muscarinic = found in mushroom ○ Located on effector target of PSNS: M1 - gastric glands, glands (excite:increase secretions) M2 - heart (decrease heart constriction, force) M3 - smooth muscle of viscera, glands, blood vessels (excite) AFFECTS SALIVARY GLANDS SO THIS IS IMPORTANT IN DENTISTRY CHOLINERGIC RECEPTORS: What are Nicotinic receptor sites? ○ Named because of affinity for nicotine ○ Located on: Postganglionic neurons of SNS and PSNS(N2) Adrenal medulla (NN) Neuromuscular junction (NM) = not part of ANS CNS Some organs and tissues are supplied with what type of receptor? ○ Some organs and tissues are supplied with ONLY ONE type of adrenergic receptor SOME tissues contain BOTH alpha and beta adrenergic receptors SEM 3 PHAR 2005 - Pathophysiology & Pharmacology TEST #1 Content: Week 1, 2, 3, 4 What are the α (alpha) and β (Beta) receptors? ○ α1 receptors ○ Salivary glands, heart vessels, smooth muscle α2 receptors ○ coronary , CNS, vessels , pancreas Β1 receptors ○ Heart Β2 receptors ○ Heart, lungs(bronchioles), vessels, kidney Β3 receptors ○ heart , fat SEM 3 PHAR 2005 - Pathophysiology & Pharmacology TEST #1 Content: Week 1, 2, 3, 4 How are neurotransmitters removed from the cleft? ○ Enzymes break them down, some gets reuse, some just disappear Explanation: ○ Adrenergic agonist (Sympathomimetics) Mime means similar Therefore it mimics SNS ○ Adrenergic antagonists (SNS blockers) Drugs that are against SNS Therefore they pretend to make PSNS ○ Cholinergic Agonists (Parasympathomimetics) Drugs that mimics PSNS ○ Cholinergic Antagonists (PSNS Blockers) Drugs that pretend to make SNS What are Autonomic Nervous System Drugs? ○ Mimic, intensify or block the effects of SNS or PSNS divisions of the ANS What are the 4 categories directly affecting ANS? ○ Adrenergic Agonists Mimic or enhance SNS Adrenergic Blockers Inhibit or diminish SNS Cholinergic Agonists Mimic or enhance PNS Cholinergic Blockers Inhibit or diminish PNS How are drugs classified? ○ By mechanism of action: Direct acting Indirect acting Mixed SEM 3 PHAR 2005 - Pathophysiology & Pharmacology TEST #1 Content: Week 1, 2, 3, 4 What is Direct acting? ○ Act on the receptor ○ Drug binds What is Indirect acting? ○ Act by inhibiting cholinesterase ○ ACh is not broken down ○ Build up of ACh is synapse results in stimulation Fatimah explanation: take enzymes, blocks Achytycholinestrase (AChE) so ACh can keep moving SEM 3 PHAR 2005 - Pathophysiology & Pharmacology TEST #1 Content: Week 1, 2, 3, 4 SNS - ADRENERGIC AGONISTS EFFECTS AND USES CNS Stimulation ADHD Alzheimer’s disease ○ ACh helps with memory Ocular effects Pupil dilation (mydriasis) Decrease intraocular pressure Salivary glands Reduce flow ○ A person who cannot swallow = give med that mimic SNS Decongestion Rhinitis Conjunctivitis Vasoconstriction Local anesthetic Hemostasis ○ Epinephrine (adrenergic) Cardiac Increase heart rate: BP Bronchodilation Increases respiration Relaxes bronchial smooth muscle COPD Anaphylaxis Asthma Metabolic Increase glycogenolysis (Ex: diabetes) Increased metabolic rate What are Adrenergic Agonists ADVERSE EFFECT: ○ CNS excitation and anxiety Apprehension, restlessness, tremors, seizures, insomnia ○ CVS effects: Hypertension, tachycardia, cerebrovascular accident (CVA), Angina, Myocardial Infarction (MI) ○ Photophobia - ocular sensitivity to light ○ hyperventilation , tachypnea ○ Hyperglycemia ○ Xerostomia Increase in caries, gingivitis, periodontal disease, tooth mobility and loss, candidiasis= when mouth is dry SEM 3 PHAR 2005 - Pathophysiology & Pharmacology TEST #1 Content: Week 1, 2, 3, 4 SNS - SPECIFIC ADRENERGIC AGONISTS DRUG USES AS MEDICATION EMERGENCY USES CONSIDERATIONS Epinephrine (Adrenalin) Peripheral Bronchodilator Administer with caution: vasoconstrictor ○ Keep on dental ○ Cardiac disorders Used in conjunction w/ tray during appt ○ Hyperthyroidism local anesthetics Cardiac stimulant/ CPR ○ Diabetes Eye surgery stimulates heart ○ Prostatic hypertrophy ○ Keeps pupil ○ Increase BP ○ Asses salivary flow dilated Anaphylaxis (Epi-pen) ○ Stress reduction protocol relaxes airway muscle may be required ○ Airway spasm- ○ Consider semi supine 1st response chair position Salmeterol (Serevent) Beta 2 adrenergic agonist Monitor vital signs Long lasting Consider semi-supine bronchodilator used for Mid morning appointments for control of asthma stress reduction prophylaxis OTHER SPECIFIC ADRENERGIC AGONISTS Dopamine (Intropin) Turns on SNS Causes increased heart contraction force and BP High doses increase vasoconstriction Used in treatment of low BP and shock Levonordefrin (Neo-Cobefrin) Local anesthetic additive Vasoconstrictor ○ Local anesthetic additive ○ Peripheral vasoconstrictor Phenylephrine Nasal decongestant (Neo-Synephrine) Turns on SNS = affect both heart and lungs Pseudoephedrine (Sudafed) Nasal decongestant Turns on SNS = affect both heart and lungs Methylphenidate (Ritalin) Attention deficit hyperactivity disorder (ADHD) Dipivefrin (Propine) Sympathomimetic ophthalmic used to treat glaucoma SEM 3 PHAR 2005 - Pathophysiology & Pharmacology TEST #1 Content: Week 1, 2, 3, 4 How is Epinephrine used as a medication? ○ Synthetic epinephrine is used to treat: Cardiac arrest/cardiopulmonary resuscitation (CPR) Epinephrine stimulates your heart Eye surgery Helps keeps pupils dilated Septic shock Increase BP Asthma Opens airways and decrease airway spasm Anaphylaxis Relaxes airway muscle 1st response treatment for this severe life threatening allergic reaction ○ REMEMBER: SEMI SUPINE POSITION What are Adrenergic Antagonists? ○ Drugs that BLOCK adrenergic receptors ○ Can block all receptors or selectively block receptors or combination of receptors (alpha and beta receptors) What are α blockers? ○ Competitively inhibit vasoconstriction effects on blood vessels, results in decreased in peripheral resistance and blood pressure EX: Tolazoline Prazosin Terazosin Doxazosin ○ (ZOSIN) What are β blockers? ○ Competitively block Beta receptors ○ Produces bronchoconstriction ○ Depresses heart Bradycardia, antihypertensive ○ Hypoglycemia ○ EX: Propranolol Acebutolol Atenolol (OLOL) SEM 3 PHAR 2005 - Pathophysiology & Pharmacology TEST #1 Content: Week 1, 2, 3, 4 What are α and β blockers? ○ Treatment of hypertension ○ Ex: Labetalol (ALOL) SNS - ADRENERGIC ANTAGONISTS EFFECTS AND USES Ocular Miosis ○ Constrict pupils Salivary glands Decrease in secretions CNS CNS depressant Decreases anxiety CVS Peripheral vasodilation Decrease BP Decrease in heart rate/pulse Cardiac output Respiratory Bronchoconstriction Decrease in respiration rate Metabolism Decrease in blood sugar ○ CAREFUL: hypoglycemia What are the Adrenergic Antagonist ADVERSE EFFECT? ○ Ocular Miosis = decrease night vision ○ Salivary glands Xerostomia ○ CNS Vertigo, dizziness, syncope ○ CVS Hypotension, orthostatic hypotension ○ Respiratory Exacerbate asthma Bronchospasm ○ Metabolism Hypoglycemic reaction “Insulin shock” SEM 3 PHAR 2005 - Pathophysiology & Pharmacology TEST #1 Content: Week 1, 2, 3, 4 SNS - SPECIFIC ADRENERGIC ANTAGONIST DRUG USES AS MEDICATION EMERGENCY USES CONSIDERATIONS Atenolol (Tenormin) Beta adrenergic Dental: blocker ○ Monitor vital signs OTHERS: Antihypertensive ○ Sit upright for 2-3 - Bisoprolol Anti-anginal min after supine - metoprolol Mild to moderate position heart failure ○ Xerostomia anti-arrhythmic ○ Use vasoconstrictors with caution ○ Stress reduction techniques Phenoxybenzamine Antihypertensive (Dibenzyline) Prazosin (Minipres) Antihypertensive Only exert therapeutic effects on peripheral blood vessels Terazosin (Hytrin) Antihypertensive Benign prostatic hypertrophy agent Doxazosin (Cardura) Antihypertensive Benign prostatic hypertrophy agent Tolamine (Regitine) For Raynaud’s Syndrome Tamsulosin (Flomax) Alpha adrenergic blocker used to treat benign prostatic hyperplasia Relaxes smooth muscle and improves urinary flow What are PSNS - Cholinergic agents? ○ Various drugs that inhibit, enhance or mimic the action of Acetylcholine (ACh) What are Cholinergic Agonists? ○ Aka Parasympathomimetic agents ○ Mimic or enhance action of ACh Direct acting Drugs acts on receptor Indirect acting Act by inhibiting cholinesterase ACh is not broken down Build up of ACh results in stimulation SEM 3 PHAR 2005 - Pathophysiology & Pharmacology TEST #1 Content: Week 1, 2, 3, 4 What are Cholinergic Antagonists? ○ Act on target receptors and suppress action of PSNS What is an example of Cholinergic agonist agents being limited and very specific in use? ○ Examples: Glaucoma (eye drops) and urinary retention What are Cholinergic Agonists ADVERSE EFFECT? ○ SLUD: S = Salivation L = Lacrimation U = Urination D = Defecation THINK PNS = CHILL ○ Orthostatic Hypotension What are the Cholinergic Agonist CONTRAINDICATIONS? ○ Bronchospasms or precipitates asthmatic attack ○ GI tract or urinary tract obstruction ○ Exacerbate severe cardiac condition (Slows down the heart) ○ Exacerbate ulcers Give an example seen in the medication list of clients for Specific Cholinergic Agonists agents? ○ Pilocarpine (Isoptocarpine) Treatment of glaucoma (intraocular pressure) ○ Pilocarpine (Salagen) Treatment of xerostomia Increase salivation ○ Bethanechol (Urecholine) Treatment of urinary retention not due to urinary tract obstruction How does the Cholinergic Antagonist work? ○ They are blockers ○ Competitively block the action of ACh on cholinergic receptors Describe the effect of Cholinergic Antagonist? ○ Effect are not as strong as Sympathomimetics What are Cholinergic Antagonist ADVERSE EFFECT? ○ Xerostomia ○ Photophobia ○ Tachycardia SEM 3 PHAR 2005 - Pathophysiology & Pharmacology TEST #1 Content: Week 1, 2, 3, 4 ○ Tachypnea ○ hypertension , angina, MI, CVA PSNS - CHOLINERGIC ANTAGONISTS EFFECTS AND USES Ocular Ophthalmologic exam Mydriasis (Pupil dilation) Exocrine Glands Decrease secretions ○ Decrease salivation = xerostomia CNS Stimulation or depression Reduction of Parkinson-like movements Motion sickness CVS Increase HR Cardiac output BP Generalized vasodilation Smooth muscle Relaxes smooth muscle in respiratory and GI tracts (decrease motility) Bronchodilation (asthma) Increase rate of respiration What are specific examples of Cholinergic Antagonists? PSNS - SPECIFIC ADRENERGIC ANTAGONIST DRUG USES AS MEDICATION Atropine Used as preoperative or pre-anesthetic agent Xerostomic agent Mydriatic agent Scopolamine (TransDerm V) Motion sickness Ipratropium (Atrovent) Bronchodilator Anti-asthmatic medication (prophylactically) ○ Used in combo with other med Benztropine mesylate (Cogentin) Anti-parkinson’s agent Dicyclomine (Bentyl) Treatment of irritable bowel syndrome Bromocriptine (Parlodel) Parkinson’s disease Propantheline (Pro-Banthine) anti-diarrhea SEM 3 PHAR 2005 - Pathophysiology & Pharmacology TEST #1 Content: Week 1, 2, 3, 4 WEEK 3: Inflammatory Damage What are the 3 Body’s Lines of Defence? ○ 1st line of defense: Non-specific MECHANICAL BARRIER = blocks entry Includes: Skin and Mucous Membranes EX: The hair inside our nose Associated secretions ○ 2nd line of defense: Non-specific INFLAMMATION + PHAGOCYTOSIS Innate immunity (born with) Will act the same way no matter what the injury it ○ 3rd life of defense: SPECIFIC Protection Acquired / Adaptive immunity What is an Injury? ○ An alteration in the environment causing tissue damage Physical, Chemical, Infections, Nutritional What is the Precursor to inflammation? ○ Tissue damage What is the 1st line of defense against injury? ○ Intact skin ○ Mucosa What is Acute inflammation? ○ A nonspecific response to injury occurring in the SAME MANNER regardless of the nature of the injury SEM 3 PHAR 2005 - Pathophysiology & Pharmacology TEST #1 Content: Week 1, 2, 3, 4 During Acute inflammation, this can cause harm to normal tissue with inflammation becoming the dominant feature if response is? ○ Very strong ○ Prolonged ○ Inappropriate What are the 5 steps during inflammation? ○ 1st Injury ○ 2nd Local pro-inflammatory mediators released This is when certain chemical released to go to the next step ○ 3rd Vascular response ○ 4th Cellular phase ○ 5th Removal This is responsible for cleaning the mass, but not only cleaning the bacteria but also the white blood cells that is released SEM 3 PHAR 2005 - Pathophysiology & Pharmacology TEST #1 Content: Week 1, 2, 3, 4 What are the Functions of blood? ○ 3 general functions: Transportation Oxygen + carbon dioxide Nutrients, heat and wastes Hormones + enzymes Regulation pH Body temperature Water content / Electrolytes Protection Prevents blood loss through clotting Against foreign microbes + toxins ○ Explanation: In our body weight , 8% is whole blood and other fluids+tissues is 92% In the 8% whole blood, there is 55% Blood Plasma The other half is 45% Formed elements, that is your Platelets, WBC, RBC SEM 3 PHAR 2005 - Pathophysiology & Pharmacology TEST #1 Content: Week 1, 2, 3, 4 What are the CAUSES of Inflammation? ○ Associated with various types of injury Physical damage: Cuts Sprains Chemical damage: Acids Ischemia Infarction Allergic reactions Foreign bodies: Glass Splinter Infection Can cause inflammatory reactions What are the CARDINAL SIGNS of inflammation? Heat Vascular changes via chemical mediators (HISTAMINE) Redness Swelling Pain Bradykinin + Prostaglandins Add: loss of function - EX: Splinter = site get hot and swell so you can’t use that finger IN LATIN : Calor Rubor Tumor Dolor Loss of function SEM 3 PHAR 2005 - Pathophysiology & Pharmacology TEST #1 Content: Week 1, 2, 3, 4 What are the 2 main components of Acute inflammation? + Part of the 2nd line defense ○ 2 components that work in tandem: Vascular section = 2 steps Dilation Permeability Cellular response = 3 steps Adhesion Transmigration Chemotaxis ○ Localized to the site of injury ○ Normally circulating in the blood INFLAMMATORY PROCESS BRINGS THESE CELL TO THE INFECTION/INJURY SITE How is inflammatory response triggered? ○ Triggered by INJURY or INFECTION How does Vascular response? ○ Local cells release pro-inflammatory mediators called CHEMOKINES= chemical movers What does Chemokines initiate? ○ Initiate vascular changes ○ Key in bringing about inflammatory response What are the 2 things that Chemokines/Mediators produce? ○ “Plasma Derived” Inactivate whole circulating LIVER is a major source of chemokines Factory XII (Kinin)= complement, coagulation Mediator for: ○ Dilation ○ Permeability ○ Pain ○ “ Cell Derived” Produced by endogenous leukocytes (neutrophils, macrophages, etc) + mast cells Pre-formed + newly made in cell granules SEM 3 PHAR 2005 - Pathophysiology & Pharmacology TEST #1 Content: Week 1, 2, 3, 4 ○ Explanation: In Histamine = causes Allergies: runny nose, water eyes Basically, Histamine + Prostaglandins + Leukocytes They are just fancy names for chemical messenger GOULD PG 67; STEPS OF INFLAMMATION: ○ Steps of inflammation An injury to capillaries + tissue cells will result in the following reactions 1. BRADYKININ is released from the injured cells 2. Bradykinin activates pain receptors 3. Sensation of pain stimulates mast cells + Basophils to release HISTAMINE 4. Bradykinin + Histamine cause capillary DILATION - Result: increase of blood + increase capillary permeability 5. Break in skin allows bacteria to enter the tissue - Result: migration of neutrophils + monocytes to the site of injury 6. Neutrophils phagocytize bacteria 7. Macrophages leave the bloodstream + phagocytose microbes SEM 3 PHAR 2005 - Pathophysiology & Pharmacology TEST #1 Content: Week 1, 2, 3, 4 In Acute Inflammation: Vascular Response, what is the local immediate effect? ○ damaged/destroy cells, sentinel cells and local cells activated Released pro-inflammatory mediators locally into interstitial fluid What are Sentinel cells? ○ Waiting for invader and looking for cells that do not belong Think of Timon from Lion king! Steps of Acute inflammation: Vascular response: ○ Vasoconstriction ○ Vasodilation ○ Permeability In Acute Inflammation, what is the 1st thing to happen (Vascular Response)? ○ Transient Vasoconstriction Immediate + a temporary measure Smooth muscle CONTRACTS + causes narrowing of blood vessels BLANCHING Again, What is one of the 1st responses by tissue to a sudden physical injury? ○ Transient vasoconstriction Designed to REDUCE BLOOD LOSS at the site of injury In Acute inflammation: Vascular response, what immediately follows vasoconstriction? ○ Vasodilation Immediately following vasoconstriction there is migration of CYTOKINES (chemical messenger) What are Cytokines? ○ They migrate to endothelial cells = initiate vasodilation SEM 3 PHAR 2005 - Pathophysiology & Pharmacology TEST #1 Content: Week 1, 2, 3, 4 What are the main ones for Cytokines? ○ Bradykinin ○ Histamine Causes smooth muscle cell relaxation + capillaries to dilate Allows increased blood flow + engorging of capillary beds Hyperemia (redness; heat) What does Dilation cause? ○ Causes blood flow to decrease allowing WBC to slow down + migrate to the endothelial lining of vessels while the RBC remain in the middle After Vasodilation, what is next? ○ Permeability Cytokines act on endothelial receptors + stimulate cellular contraction = create species (gaps) between cells PLASMA STARTS TO LEAD OUT (EDEMA) What happens to the blood flow during permeability? ○ Blood flow increases to area causing movement of fluid (Transudate) from capillaries to tissue What does increased permeability allow? ○ Allows PLASMA PROTEINS to leak out of capillary ○ Transudation followed by Exudative leakage How is accumulation of fluid in tissues termed? ○ Edema TRANSUDATE OR EXUDATE NOTE: plasma proteins (ex:kinins) in injury site become activated; sensitize nerves + prostaglandins (PG) + swelling = pain During Permeability, what moves into the extravascular tissue? ○ Fluid and ion move into extravascular tissue ○ List which one are Granulocytes and Agranulocytes? SEM 3 PHAR 2005 - Pathophysiology & Pharmacology TEST #1 Content: Week 1, 2, 3, 4 ○ Granulocytes Agranulocytes Neutrophils Monocytes Basophils Lymphocytes Describe Granulocytes: NEUTROPHILS? ○ Most common (60%) ○ 1st RESPONDER What do Neutrophils do? ○ Capture + destroy invading organisms ○ Help start repair process ○ Help regulate immune system + inflammation in body Describe Granulocytes: BASOPHILS? ○ Least common ○ Present in greater number during allergic reactions + infection What do Basophils do? ○ Destroy foreign organisms by phagocytosis ○ Secrete HISTAMINE + HEPARIN Describe Agranulocytes: MONOCYTE? ○ Live 1-3 dyas in blood, then move out into tissues ○ Called MACROPHAGES once in the tissue to become phagocytes What do Monocytes do? ○ Produce DENDRITIC CELLS ○ 3 Main Functions are: Phagocytosis Cytokine production for Chemotaxis = “Hey Blood cells follow me!” Antigen presenting Describe Agranulocytes: LYMPHOCYTES? ○ T cells & B cells ○ T cells B cells - Attack viruses, fungi, - Destroy bacteria + inactivate transplanted cells, cancer cells their toxins - Involved immunity - Become antibodies SEM 3 PHAR 2005 - Pathophysiology & Pharmacology TEST #1 Content: Week 1, 2, 3, 4 During Acute inflammation-cellular response, what happens during the 1st 6 - 24 hours? ○ NEUTROPHIL STAGE (60 - 70% OF CELLS IN BLOOD) 1. Migration Increased of circulating neutrophils + monocytes on periphery of vessels Contact endothelial lining RBC accumulate in middle ○ NEUTROPHILS ACTION IS TO CAPTURE + DESTROY 2. Rolling & Adhesion WBC slowly roll along endothelial lining Interacts with activated P selectin ○ Protein on endothelial lining that promotes adhesion Is a cell adhesion molecule (aka P-CAM) -ADHESION P-CAM found on surface of: Platelets Monocytes Neutrophils 3. Extravasation Transmigration / passing/ leakage of neutrophils + monocytes through endothelial lining to site of injury or inflammatory (DIAPEDESIS) 4. Chemotaxis Chemotactic agents bind with WBC + attract to injury site via chemical gradient to injury site: (Positive chemotaxis) ○ Begin phagocytosis: 1st 6 - 24 hours neutrophils are PREDOMINANT Role is phagocytize debris (dead and injurious cells) During Acute inflammation - cellular response, what happens during Late: Macrophage phase (former monocytes) - next 24-48 hours? ○ Next 24 - 48 hours: similar function to neutrophils (Phagocytosis) Macrophages begin removal of injurious cells Secrete other chemokines IL1/TNFa IL8 ○ Promotes further WBC chemotaxis to bring more WBC to site of injury SEM 3 PHAR 2005 - Pathophysiology & Pharmacology TEST #1 Content: Week 1, 2, 3, 4 What do macrophages and neutrophils develop? ○ They develop PSEUDOPODS to pull foreign body toward, around and in = PHAGOCYTOSIS Macrophage Neutrophil - All foreign substances - Antigen pushed out degraded EXCEPT (EXOCYTOSIS) and “ANTIGENS” DIRECTED TO LYMPH - Act as antigen presenting - Help move garbage cells in lymph out + if the lymph is large its a sign What are Complement Proteins? ○ A type of plasma protein Liver constantly synthesizing Complement (C ) proteins which go into circulation When C proteins become stimulated, what do they release? ○ Release cytokines that amplify the cascade + increase phagocytosis + activate the macrophages (lysis of pathogen) ○ They help to identify the pathogen so macrophages can eliminate them = “eat them up” What is the Typical reaction in Lymphatic Response? ○ Increased lymph flow helps drain EDEMA from extravascular space Leukocytes, macrophages, and cell debris What happens when lymph nodes may become inflamed (Lymphadenitis) and enlarged (lymphadenopathy)? ○ Increased phagocytic cells in lymph nodes ○ Increased lymphocytes ○ Hyperplasia lymphoid tissue SEM 3 PHAR 2005 - Pathophysiology & Pharmacology TEST #1 Content: Week 1, 2, 3, 4 Are normal cells affected during the inflammatory response? ○ Defective leukocyte functions can cause injury to normal cells & tissues ○ 3 types: Bystander tissues are injured = occurs within normal attempt to clear damaged + dead tissues A normal defense reaction against infection Part of inflammatory response is inappropriately directed against host tissues Autoimmune disease Host reacts excessively against non-toxic environmental substance Allergy What is the systemic manifestation of inflammation? ○ Leukocytosis Increase in WBC count = typically when larger infection present Anything more than 10 000 cell/mm3 ○ Pyrexia FEVER BMR (Basal Metabolic rate) increase due to stimulation of the sympathetic nervous system via IL1/TNFa to hypothalamus ○ lymphadenopathy/Lymphadenitis Enlarged lymph ○ Loss of appetite, malaise(general feeling unwell), fatigue, headache as body attempts to fight infection ○ Increased Heart rate, BP and blood sugar due to stress on body Recall F&F SEM 3 PHAR 2005 - Pathophysiology & Pharmacology TEST #1 Content: Week 1, 2, 3, 4 In Acute inflammation, what are the outcomes? ○ 1. Resolution Neutralization or degradation of chemical mediators Normalization of vascular permeability Cessation of leukocyte migration + apoptosis of neutrophils followed by production of mediators inhibiting inflammation Vasoconstriction again ○ 2. Progression to chronic inflammation Whatever cause the injury has not been removed or the body thinks it has not been removed ○ 3. Scarring or Fibrosis When does Chronic inflammation develop? ○ Develops when: Cause of acute inflammation is not eliminated = irritation persist Inflammation stays active even after the initial threat eliminated Does Chronic Inflammation have a similar cellular response as acute inflammation? ○ Yes = increase morphs into a lingering state During Chronic inflammation, what does the immune system prompt? ○ Immune system prompts inflammatory cells to continue response ○ Nearby health tissue and organs become involved SEM 3 PHAR 2005 - Pathophysiology & Pharmacology TEST #1 Content: Week 1, 2, 3, 4 Give an example of where the Chronic Inflammatory process plays a central role in many diseases? ○ Periodontal disease ○ Rheumatoid arthritis ○ Cancer ○ Heart disease ○ Diabetes ○ Asthma ○ Alzheimer’s What are the Characteristics of Chronic inflammation relative to acute inflammation? ○ Less swelling + exudate ○ More lymphocytes, macrophages and fibroblasts ○ More tissue destruction ○ More collagen production = can have more fibrous scar tissue with development of granuloma What are the types of healing? ○ Resolution Recovery of damaged tissue cells Short term Minimal tissue damage ○ Regeneration Regeneration & wound healing ar complex processes that allow organs and tissues to regain their integrity and functionality after injury Those cells capable of MITOSIS form the replace injured tissue with exact same tissue + cells that are functional ○ Replacement With cells incapable of mitosis or in areas of extensive damage there is substitution of original tissue with fibrous/scar tissue Leads to loss of function SEM 3 PHAR 2005 - Pathophysiology & Pharmacology TEST #1 Content: Week 1, 2, 3, 4 Explain the healing process? ○ Injured cells activate coagulation + haemostasis = clot formation ○ Inflammatory process begins immediately followed by clotting ○ Result = fibrin clot ○ Gap Tissue fills with granulation tissue (from CT; highly vascular) + epithelial cells (mitosis) from outside margins-in ○ Fibroblasts and CT cells Produce collagen for strength + scaffolding (scarring) for wound ○ Growth factor Produce + stimulate further epithelial cell growth + ANGIOGENESIS Angiogenesis = formation of new blood cell in the area ○ Tightening + strengthening of scar Decrease capillaries ○ Scar Abnormal Non-functional tissue Lacks specialized structure What happens in the Healing Process - Healing by First intention? ○ Basically, everything goes well ○ Edges closely approximated ○ MINIMAL scarring + granulation tissue ○ Haemostasis , close proximity allows for clot formation and scab ○ Inflammation removes debris , fights infection In Healing by First intention, what is proliferation? ○ Cytokines released by inflammatory response cause Proliferation of fibroblast and formation of granulation tissue ○ Angiogenesis with maturation of granulation tissue get >O2, etc In healing by First Intention, what do you end up with? ○ End uo with complete return to function + minimal scarring What happens in the Healing Process - Healing by Second Intention? ○ Basically, this is where you get keloid ○ Wound margins TOO FAR APART, hemostasis causes large clot and scab to form Causing granulation tissue + large fibrin mesh to fill wound In Healing process - Second Intention, inflammation removes debris, fights infection but what is the reaction? ○ Reaction is greater intense as wound is larger and takes longer SEM 3 PHAR 2005 - Pathophysiology & Pharmacology TEST #1 Content: Week 1, 2, 3, 4 In the Healing process - Second Intention, where does the granulation tissue form? ○ Granulation tissue forms at bottom of wound ○ This is Nb as epithelia can only proliferate and regenerate once granulation tissue fills wound, to level of original epithelia for epithelial to cover wound In the Healing process - Second Intention, what happens when Myofibroblast (mast cells) deposit? ○ Increase collagen for scar formation Complication are keloid scars due to excessive collagen production What is Scar Formation? ○ Loss of function due to loss of normal cells and any specialized structures Hair follicles, nerves, receptors During Scar formation, dysfunction in the wound healing process can be caused? ○ Hypertrophic scar tissue Overgrowth of fibrous tissue Leads to hard ridges of scar tissue or keloid formation (>>collagen) Can lead to contractures Contractures: ○ Shrinkage + lack of elasticity ○ Restricts movement ○ May result in fixation and deformity ○ Adhesion Bands of scar tissue joining 2 surfaces normally separated Especially in joint areas EX: frozen shoulder ○ Ulceration Blood supply may be impaired around scar Results in further tissue breakdown and ulceration at future time SEM 3 PHAR 2005 - Pathophysiology & Pharmacology TEST #1 Content: Week 1, 2, 3, 4 WEEK 4: Inflammatory Damage What is Pain? ○ Unpleasant sensation or discomfort caused by stimulation of pain receptors (nociceptors) ○ A BODY DEFENSE MECHANISM warning us of a problem ○ Series of COMPLEX MECHANISM What are the causes of pain? ○ Inflammation Chemokines, etc) ○ Infections ○ Ischemia + tissue necrosis ○ Muscle spasm Stretching of tissue Stretching of tendons, ligaments, joint capsule ○ Chemicals ○ Burns SEM 3 PHAR 2005 - Pathophysiology & Pharmacology TEST #1 Content: Week 1, 2, 3, 4 What are the types of pain? ○ TYPES OF PAIN Somatic pain From skin (cutaneous), bone muscle ○ Conducted by sensory fibers Visceral pain Originates in organs, conducted by sympathetic fibers ○ May be acute or chronic Pain Threshold vs Pain Tolerance Pain Threshold Pain Tolerance Level of stimulation required to elicit a pain Ability to cope with pain response Culturally related Usually does not vary among individuals Varies among individuals How much stimulation need for the body to feel pain What are Pain Pathways? ○ Nociceptors (pain receptors) are free sensory nerve endings ○ May be stimulated by: Temperature Thermal means in extremes of temperature Chemicals Acids or chemicals produced by body ○ Ex: bradykinin, histamine, prostaglandin Physical means Pressure, touch PAIN PATHWAYS #1: What is Dermatome? ○ Area of skin innervated by a specific spinal nerve ○ Somatosensory cortex = “mapped” Corresponds to source of pain stimuli SEM 3 PHAR 2005 - Pathophysiology & Pharmacology TEST #1 Content: Week 1, 2, 3, 4 PAIN PATHWAYS #1: What are reflex responses(Efferent response)? ○ Involuntary muscle contraction away from pain source ○ Involuntary muscle contraction to guard against movement What are the 2 fibers in the Spinothalamic bundle? ○ Both AFFERENT: Fast bundle - myelinated (A DELTA) Slow bundle - unmyelinated (C PAIN) SEM 3 PHAR 2005 - Pathophysiology & Pharmacology TEST #1 Content: Week 1, 2, 3, 4 Again, What are the Pain fibers? ○ Afferent fibers ○ Myelinated A delta fibers - FAST Unmyelinated C fibers - SLOW Transmit impulses very rapidly Transmit impulses slowly aka aka FAST A SLOW C Found in the Found in the NEOSPINOTHALAMIC PALEOSPINOTHALAMIC TRACT TRACT Acute pain Chronic pain ○ Sudden ○ Dull ○ Sharp ○ Diffuse ○ localized ○ Burning ○ Aching sensation ○ How do we make meaning of pain? ○ Somatic sensory area in the cerebral cortex located in the parietal lobe Perception + localization of sensation ○ HYPOTHALAMUS + LIMBIC SYSTEM Emotional factors ○ Communication with other regions of the brain to integrate responses What is the key role in pain perception + modulation? ○ Reticular activating system (RAS) Reticular formation in the pons and medulla Awareness of incoming brain stimuli This is at the brain stem SEM 3 PHAR 2005 - Pathophysiology & Pharmacology TEST #1 Content: Week 1, 2, 3, 4 What is the Gate Control theory? ○ Control systems, “gates” built into normal pain pathways ○ Can modify pain stimuli conduction + transmission in the spinal cord + brain What happens when gates open? ○ Pain impulses transmitted from periphery to brain ○ + when a positive ion is released= gates open= will feel pain What happens when gate closed? ○ Reduce or modifies the passage of pain impulses SEM 3 PHAR 2005 - Pathophysiology & Pharmacology TEST #1 Content: Week 1, 2, 3, 4 What are the characteristics of pain - Signs and Symptoms? ○ Characteristics of Pain - Signs and Symptoms Location of pain Descriptive terms ○ Aching, burning, sharp throbbing, widespread, cramping, constant, periodic, unbearable, moderate Timing of pain Association with an activity “hurts when i move my arm” Physical evidence of pain Pallor, sweating, high blood pressure, tachycardia Nausea & Vomiting, Fainting, May occur with acute pain Vertigo Anxiety and Fear Frequently evident in people with chest pain or trauma Clenched fists or Rigid faces Restlessness or Constant motion Guarding area to prevent stimulation of receptors= try to confuse brain ○ How does YOUNG CHILDREN react to pain? ○ Infants respond physiologically Ex: tachycardia, increased blood pressure, facial expressions ○ Great variation in different development stages Different coping mechanism Range of behavior Often have difficulty describing the pain Withdrawal and lack of communication in older children SEM 3 PHAR 2005 - Pathophysiology & Pharmacology TEST #1 Content: Week 1, 2, 3, 4 What is a Referred pain? ○ Source may be difficult to determine ○ Pain may be perceived at site distant from source Characteristics of visceral damage in the abdominal organs Heart attack or ischemia in the heart ○ What is Phantom Pain? ○ Phenomenon not fully understood ○ Usually in adults ○ More common if chronic pain has occurred ○ CAN FOLLOW AN AMPUTATION Pain, itching, tingling ○ Usually does not respond to common pain therapies ○ May resolve within weeks to months How does Pain perception and response occur? ○ PAIN PERCEPTION AND RESPONSE Pain tolerance Degree of pain, intensity or duration May be increased by endorphin release May be reduced because of fatigue or stress Varies among people in different situations Pain perception Subjective but can be compared from day to day in same person Response to pain Influenced by personality, emotions and cultural norms SEM 3 PHAR 2005 - Pathophysiology & Pharmacology TEST #1 Content: Week 1, 2, 3, 4 What is Acute pain? ○ Usually SUDDEN + SEVERE + SHORT TERM ○ Indicates tissue damage ○ May be LOCALIZED OR GENERALIZED ○ Initiates physiologic stress response Increase BP + heart rate, cool, pale, moist skin, increase respiratory rate, increase skeletal muscle tension ○ Vomiting may occur ○ Strong emotional response may occur What is Chronic Pain? ○ Occurs over extended time; may be recurrent ○ Usually more difficult to treat than acute pain ○ Often perceived to be generalized. ○ Individuals may be fatigued, irritable, depressed. ○ Sleep disturbances common ○ Specific causes may be less apparent. ○ Appetite may be affected. Can lead to weight gain or loss. ○ Frequently affects daily activities. ○ Accommodation and pacing of activities may be required. ○ Periods of acute pain may accompany chronic pain conditions. ○ Usually reduces tolerance to additional pain. SEM 3 PHAR 2005 - Pathophysiology & Pharmacology TEST #1 Content: Week 1, 2, 3, 4 What is Pain Management? ○ Pain control is important in dental care 2 components: Perception ○ PHYSIOLOGIC component; message carried through nerves to cerebral cortex (in consistent) Reaction ○ PSYCHOLOGICAL component; patient’s emotional response to pain (varies) Pain threshold may be increased by reassurance, sleep, activity,

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