Learning objectives module 1 Flashcards
Definition of Disease
Any compromise to the normal function of the body and systems of which are compromised
- Unhealthy state caused by the effects of injury
- Impairment of health or condition of abnormal functioning
· A change from homeostasis
Pathology:
The study of changes in bodily structure and function that occur as a result of disease
Anatomical pathology:
The study of structural changes caused by disease
(Assessment of tissue specimens like a biopsy)
Clinical pathology:
The study of the functional aspects of disease by lab study of tissue, blood, urine, or other fluids
What kind of pathology do pharmacists look at?
Clinical pathology
Idiopathic:
Unknown etiology
Iatrogenic:
If the disease is a by product of diagnosis or treatment (it is physician caused)
Prevalence:
The number of persons who have the disease at any given moment (snapshot in a specific time frame)
Incidence:
The number of new cases of the disease per year
What is a sign?
A direct observation by the examiner
What is a symptom?
A complaint reported by the patient
What is a syndrome?
A collection of signs, symptoms along with data to support specific condition or disease (evidence based)
Definition of healthy
- Often the goal of treatment is to get the body back to or mimic homeostasis
- Healthy isn’t necessarily the absence of disease but the relationship between health and homeostasis is super important
Sick means…
the presence of disease
Healthy means…
The absence of disease
Normal and abnormal describe what?
Describe the results of measurements or observations used to determine weather a disease is present
How is normal range determined?
From a sample of people that do not have the disease
How is upper limit defined?
2 standard deviations above the mean
How is lower limit defined?
2 standard deviations below the mean
True negative:
The individual is healthy and gets a negative test result
False negative:
The individual is sick and gets a negative test result
True positive:
The individual is sick and gets a positive test result
False positive:
The individual is healthy and gets a positive test result
A negative test result means the patient is ___
Within normal limits (WNL)
Sensitivity:
The ability of a test to be positive in the presence of the disease or the true positive rate
Specificity:
The ability of a test to be negative in the absence of the disease of the true negative rate
Which kind of test would you start with? What kind after?
Sensitive test first, followed by a specific test
Hematopoiesis:
- When exposed to cytokines and surrounding stromal cells they differentiate into
Megakaryocytes - (platelates)
Erythrocytes (RBC)
Leukocytes (WBC) including lymphocytes, granulocytes, monocytes, macrophages, neutrophils, eosinophils
Innate immunity:
Refers to the host defense mechanisms that are immediately available on exposure to pathogens because they are always present
Includes epithelial barriers, mucous membranes
What are the types of granulocytes?
Neutrophils, eosinophiles, basophils, mast cells
Function of granulocytes?
- Are often the first cells to arrive at the site of injury
- They are characterized by granules in their cytoplasm and varying shapes pf nucleuses
- They engulf and kill pathogens with their cytoplasmic granules that contain substance that can kill the pathogen and enhance the inflammatory response
Not pathogen specific
Function of neutrophils?
Phagocytize microbial invaders
Function of eosinophils?
Phagocytize parasites, boost immune signal
Function of mast cells?
Histamine release, found in mucous membranes exposed to the environment
Function of basophils?
Like mast cell, boost immune signal
Function of mononuclear phagocytes?
(baby macrophages)
Monocytes circulate in the blood, then migrate to tissue and grow 5x into macrophages
- Macrophages have phagocytic and microbicidal activity
Engulf and eliminate pathogens, dead cells, and cellular debris
Function of natural killer cells?
- Cytotoxic lymphocytes that target tumor and virus infected cells (not a specific antigen)
- Selectively target damaged or infected host cells because they recognize abnormal expression of surface molecules on damaged cells but not healthy cells
Function of dendritic cells?
- Specialized cells that reside in tissues and stimulate the adaptive immune response
Immature dendritic cells
- Patrol peripheral tissues and capture pathogens via phagocytosis
Mature dendritic cells
- Migrate to the lymphoid organs to present the antigens they have discovered
Cells of the innate immune system?
Granulocytes, mononuclear phagocytes, natural killer cells, dendritic cells
Function of B-cells?
- A naïve B cell encounters a pathogen and binds to its through its immunoglobulin (B cell receptor)
- The B cell multiplies and its offspring differentiate into plasma cells and memory B cells
Plasma cell function?
Short lived and secrete antibodies
Memory B cells function?
Long lives and express the same immunoglobulin as the parent B cell
(responsible for a quick secondary response to the same pathogen)
What is an immunoglobulin?
An antigen that is in the cell membrane (transmembrane domain)
What is an antigen?
An antigen that is free to move around in the body
Function of a T-cell?
Express receptors that only recognize antigens that are expressed by the dendritic cells or any other antigen presenting cell
What are the types of T-cells and their function?
Cytotoxic T cells (Destroy host cells that are infected)
Helper T cells (Secrete cytokines that enhance the function of other cells to help in getting rid of the pathogen)
Memory T cells (Can persist for years and mount a quick response upon re-exposure)
What is the lymphatic system and what does it do?
- A network of lymphatic vessels connected to lymph nodes
- Collects plasma continuously leaking out from blood vessels into the interstitial spaces, and returns the fluid to the blood
- Lymph only travels upwards
B and T cells are in both blood and lymph
What are the primary lymphoid organs and what are they responsible for?
- Responsible for lymphocyte maturation and development
(Bone marrow, thymus)
B cells completely differentiate and mature in the bone marrow
T cells originate in the bone marrow but mature in the thymus
What are the secondary lymphoid organs and what are they responsible for?
- Where mature lymphocytes interact with antigen presenting cells
(spleen, lymph nodes, tonsils, appendix,
Spleen
- Has red pulp where old or damaged erythrocytes are recycled
- And white pulp, which consists of lymphocytes
Lymph nodes
Round specialized structures positioned along the lymphatic vessels
Lymphocyte recirculation (3 steps)
- B & T cells develop in the bone marrow and thymus then enter the blood
- When they reach a secondary lymphoid organ, they enter it
- If an antigen is detected it stays in the tissue and becomes activated
- If no antigen it exits in the lymph and goes back to the blood stream - Allows continuous monitoring of the secondary lymphoid organs for infection
Causes of bacterial disease:
- Bacteria grow rapidly and cause disease by sheer numbers
- Bacteria produce toxins that cause disease
Bactericidal:
Drugs that Kill/destroy the bacteria entirely by themselves
Bacteriostatic:
Drug that slows down the growth of the bacteria, allowing the body’s immune system to dispose of the bacteria
Only useful when the patients immune system is working (not immunosuppressed)
Broad spectrum antibiotics:
drugs that are effective against a wide variety of bacteria
- Prescribed empirically when we don’t know the specific pathogen
May not be the best prescription, but can be the most cost effective
Narrow spectrum antibiotics:
Drugs that are effective against a very specific microorganism
- Prescribed when the pathogen is clear from a test determining the specific pathogen
Function of penicillin (beta-lactam)
- Disrupt bacterial cell walls
- Bactericidal
Penicillin binding protein:
A protein only bacterial cell walls have that penicillin binds to (weakens the cell wall, allows for fluid to enter and destroys the cell)
- Penicillin’s contain a beta-lactam ring in its structure that is necessary for its activity
Penicillinase (beta-lactamase):
a natural defense to penicillin
- It breaks the beta lactam ring, leaving it ineffective (penicillin resistance)
Function of amoxicillin + clavulanic acid
Clavulanic acid inhibits beta-lactamase of some microorganisms to allow amoxicillin to be active against it
- This is a synergistic pharmacodynamic relationship
Function of cyclosporin
- A classic immuno-suppressant used for transplants
Inhibits the production and release of interleukin 2 and inhibits interleukin 2 induced activation of resting T-lymphocytes
- They are not specific and suppress the entire immune system
Function of methotrexate
- A folate antimetabolite that inhibits DNA synthesis, repair, and cellular replication
Actively proliferative tissues are more susceptible to the effects of methotrexate
- It slows cellular turn over
- Used to treat rheumatoid arthritis, psoriasis, crones disease
What are antihistamines used for?
Used to stop histamine release from mast cells to stop the symptoms from occuring by blocking the histamine receptors
Histamine:
- A bioactive amine packaged in dense intracellular granules
- When released they bind to histamine receptors (H1,H2,H3)
H1:
smooth muscle of vascular system, bronchial tree, digestive tract, nasal glands
Antagonizing these receptors helps with allergic rhinitis symptoms
1st generation antihistamines:
- Block H1 receptors
- Shorter acting, cause more drowsiness, and work faster than 2nd generation
Diphenhydramine (Benadryl) & chlorpheniramine are the most common
Last 4-6 hours
2nd generation antihistamines:
- Block H1 receptors
- Longer acting, less sedating, take longer to start working (longer onset then 1st gen)
Can take hours to start working but is safe to use for years
H2 receptor:
Lining of the stomach, produce gastric acid
Antagonizing theses receptors reduces the acidity of gastric contents
H3 receptor:
found in the central nervous system, involved in releasing neurotransmitters like dopamine, GABA, etc
Inflammation:
A physiologic response to tissue injury and infection
- Can be acute or chronic
- Inflammation is present in almost all diseases or conditions
Inflammation does not equal infection
What is the purpose of acute inflammatory response?
Provides protection following tissue injury and or infection by:
- Restricting damage to the localized site (clotting)
- Recruiting immune cells to eliminate invading pathogens
- Initiate wound repair
Clotting:
produces fibrin strands that accumulate to stop the spread of possible infection and bleeding to outside
Kinin:
produces bradykinin which induces vasodilation and increased permeability
- Increased permeability allows for immune cells to move form the blood into tissues to find pathogens
Diapedesis: (4 steps)
The movement of leukocytes out of the blood into the site of infection or tissue damage
Occurs in 4 steps
- Chemoattraction (by various inflammatory mediators released earlier) (mast cells)
- Rolling adhesion (By carbohydrate chains on the surface of the neutrophil)
- Tight adhesion (By multiple cytokine and integrin receptors)
- Transmigration (leukocyte squeezes between the cells of the blood vessel into the tissue)
Can a drug transmigrate?
No
What are the mediators released by leukocytes after they phagocytize the pathogen?
- Cytokines
- Histamine
- Prostaglandins
- Leukotrienes
What is chronic inflammatory response?
- Continues after the acute response (cleans up debris and facilitates the healing process)
Characterized by accumulation and activation of macrophages and lymphocytes, as well as fibroblasts that replace the original damaged tissue
Fibrosis:
An extensive deposition of fibrous connective tissue that interferes with normal tissue function (scarring)
Cytokines:
- Soluble factors secreted by activated immune cells
- Organized according to their major activities:
1. Promote inflammation & mediate natural immunity
2. Support allergic inflammation
3. Immunoregulatory activity (slow it all down)
Act as hematopoietic growth factors
What kind of drugs effect cytokines:
Biologics
- Medications produced using biological processes in living organisms such as yeast and bacteria
- They are complex, large molecules derived from living sources
What are monoclonal antibodies?
use the ability of antibodies to target specific receptors or pathogens
- The antibody is the delivery system for a drug
- We can attach a drug to an antibody, which then only targets and affects those specific cells, making therapy more effective with fewer adverse effects
Histamines:
- A bioactive amine packaged in dense intracellular granules
- Mast cells are known for releasing histamine
- When released, binds to histamine receptors (H1,H2,H3)
Prostaglandins & leukotrienes:
- Newly generated mediators
Arachidonic acid is released from immune cell membranes and is metabolized in 2 different ways - Both work to intensify the inflammation process
Function of prostaglandins?
- Wide variety of functions around the entire body
- Cause constriction or dilation in vascular smooth muscle cells
- Cause aggregation or disaggregation of platelets
- Induce labour
- Released during menstruation
- Play an important role in mucosal production in GI tract
Act on thermoregulation center of hypothalamus to produce a fever
What enzyme converts arachidonic acid into prostaglandins?
cyclooxygenase (COX)
What drugs affect prostaglandins?
NSAIDs
Function of NSAIDs?
- Inhibit cyclo-oxygenase (COX), which reduces prostaglandin synthesis —-> inhibiting inflammation
- Has no effect on prostaglandins that are already present
- Have analgesic and antipyretic properties
- Used to treat mild to moderate inflammation, fever, platelet inhibition
Classic NSAID’s inhibit COX-1 and COX-2
COX-2 inhibitors are more specific for inflamed tissue
Adverse effects of NSAIDs?
: Nausea, dyspepsia, ulcer with long term use, potential anti-platelet action, hypertension, increased risk of cardiac event with long term use
- Take with food on an as needed basis
Leukotrienes:
- Particularly active in smooth muscle lining of the bronchioles
- Contribute significantly to the pathophysiology of asthma
- Airflow obstruction
- Increased secretion of mucous
Bronchoconstriction
Drugs that affect leukotrienes?
Leukotriene receptor antagonist (LTRA)
- Montelukast
- Reduce inflammation by blocking leukotriene receptors
- May be used in seasonal allergies
- Not as effective as corticosteroids
Must be taken daily
Cortisol:
- A hormone released in response to stress
Job is to bring body back to homeostasis
Cortisol has receptors all over the body
Muscle, fat, bones, arteries, liver, kidney, parathyroid gland, pancreas, pituitary, and in fetal development
Corticosteroids:
Drugs designed to mimic our endogenous cortisol
What are the 5 factors of complexity in understanding drug classification?
- Large volume of drugs
- There are over 10,000 agents currently available
- Nomenclature can confuse communications between professional and countries
2. Each individual drug within the class has its own distinct characteristics - Therapeutic usefulness, interactions, side effects, mechanisms
3. Each drug often has more than one indication and mechanism - You cannot diagnose a patient by their medication list
4. Drugs elicit different responses depending on individual factors - Age, sex, body mass, health status, organ function, genetics
5. Lack of consistency
- Could be classification systems, resources, professions
Chemical name:
A direct description of the chemical structure
Gives info on chemical makeup (NaCl, CaCO3)
Generic name:
The unique name given to a chemical structure that somewhat describes its structure
Remains the same across languages
Brand/trade name:
The marketed name given to a drug
What is the best way to reduce errors around drug names?
To use the generic name
Therapeutic drug classification:
Classification organizing drugs according to their therapeutic usefulness in treating a particular disease
Ex. Anti-inflammatories, anti-convulsant, immunosuppressants
They describe what they do
Pharmacological drug classification:
Classification that organizes drugs according to the way a drug works at a molecular level, tissue, and body system level
Ex. Calcium channel blocker, alpha agonist, proton pump inhibitor
Address the drugs mechanism of action
Family drug classification:
Classification that organizes drugs according to its chemical structure in some way
Ex. Tricyclic antidepressants (TCAs) - 3 ring structure
Penicillin’s - beta lactam ring structure
What are the 3 important documents in government drug classification?
- Narcotic control regulations
- Controlled drugs and substances act
- Food and drugs act and regulations
- Controlled drugs and substances act
What drugs do the federal government control?
Controlled substances and narcotics
What drugs do the provincial government control?
All other drugs, Rx, OTC, NHPs, schedule 1,2,3, unscheduled
Controlled substance:
any drug in whose manufacture, possession, or use is regulated by the government
What are the 6 drug classes?
Stimulants, depressants, opioids, NSAIDs, corticosteroids, anabolic steroids
Stimulants:
Classification - therapeutic
Common trait - Stimulate the CNS
Pathophysiology - The body needs a fight of flight response
Pharmacology - Stimulate adrenergic (Epinephrine) or cholinergic (Acetylcholine) receptors
Clinical result - Various presentation of fight or flight response depending upon specificity of the drug
Depressants:
Classification - Therapeutic
Common trait - Slow down the CNS
Pathophysiology - The nervous system is in need of rest
Pharmacology - Various ways - stimulate inhibitory pathways or block stimulation
Clinical result - Slowing down of processes specifically targeted
Opioids:
Classification - Family
Common trait - All stimulate opioid receptors
Pathophysiology - Pain
Pharmacology - Opioid stimulation provides altered perception of pain and provides sedation, constipation, nausea, euphoria
Clinical result - Can still feel pain but do not care
Non-steroidal anti-inflammatories:
Classification - Family
Common trait - Reduce inflammation while not being a steroid (specific structure)
Pathophysiology - Mild to moderate inflammation has occurred
Pharmacology - Inhibit cyclooxygenase which reduces prostaglandin synthesis
Clinical result - reduction in inflammation
Corticosteroids:
Classification - Family
Common trait - Steroid structure (17 carbon atoms arranged in 4 rings)
Pathophysiology - Moderate to severe inflammation or immune response
Pharmacology - …
Clinical result - Rapid reduction of inflammatory and/or immune response
Anabolic steroids:
Classification - Family
Common trait - Possess the steroid structure and stimulate androgen receptors
Pathophysiology - Delay puberty, andropause, low testosterone levels, transitioning
Pharmacology - Stimulate androgen receptors
Clinical result - masculine appearance and features
