Week 3: Allergies and Immunology Flashcards
What is an allergic reaction?
What can cause allergic reactions?
An allergic reaction is caused by the body’s immune response to an allergen causing an inappropriately large response
They can be caused by food, chemical, environmental, insect stings or ocular.
Pathophysiology of an allergy
Antigen presenting cells (macrophages) first detects the allergen. They then migrate to the T cells (naive cells) that become TH2 cells (knowledge of antibody) which causes synthesis of IgE antibodies on B cell to the allergen
Next time the allergen is present the IgE antibodies attach themselves to mast cells on mucosal surface and basophils in the blood
The mast cells then release inflammatory mediators including prostaglandins, histamines, cytokines and leukotrienes
Local and Systemic symptoms of an allergic reaction
Local Symptoms - itching, swelling, nausea, vomiting, cramping, diarrhea
Systemic symptoms - airway swelling, hives, hypotension, arrhythmis
What is the effect of antihistamines on the body?
Antihistamines reduce the effects of histamines by binding to the histamine 1 (H1) receptor. This blocks the effect of histamine released in response to an allergen.
What are the effects of histamine during an immune response?
Histamine causes vasodilation, inflammation, increased vascular permeability and contraction of smooth muscle in lungs and heart
Antihistamine Drug Types
- Topical/Local
- Oral
Topical/Local - Intraocular - Intranasal Oral - Older (sedating - cross the BBB) - Newer (less sedating)
What is Dexchlorpheniramine (Polaramine)?
Dexchlorpheniramine (Polaramine) is an older oral antihistamine
What is Promethazine (phenergan)?
Promethazine (phenergan) is an older oral antihistamine
What is Certirizine (Zyrtec)?
Certirizine (Zyrtec) is a newer oral antihistamine (considered the most sedating of the newer antihistamines)
What is Loratadine (Aerius/Claratyne)?
Loratadine (Aerius/Claratyne) is a newer oral antihistamine
What is fexofenadine (Telfast)?
Fexofenadine (Telfast) is a newer oral antihistamine
What contraindications/cautions exist around older (sedating) antihistamines?
Elderly - avoid use or use in low dose due to increased risk of sedation, hypotension, falls and anticholinergic effects
Children - Do not use for children under 2 yrs due to risk of sedation or paradoxical reactions
Safe in pregnancy
Breast feeding - cay cause sedation but short term use likely safe
Avoid use in GI obstruction, bladder outlet obstruction, at risk of PACG
Caution with alcohol or driving
What contraindications/cautions exist around newer (less-sedating) antihistamines?
Elderly - better than older but still at risk of sedation
Hepatic impairment - Caution as it may increase liver enzymes therefore reduce dose
Children - safe to use from 6 month for fexofenadine, 1 year for others
Pregnancy - should be safe but more data on older antihistamines
Breastfeeding - safe
Renal impairment - reduce dose
Intranasal Antihistamines
Provide 2 examples of intranasal antihistamines
Faster onset of action than oral antihistamines and effects tend to be limited to local tissue
Well tolerated
Include - Azelastine (Azep) and Levocabastine (Livostin)
What contraindications/cautions exist around intranasal antihistamines?
Elderly, hepatic impairment, pregnancy, renal impairment have no cautions
Children - over 5 years for azelastin and over 6 for levocabastine
Additive effects with alcohol, caution driving if sedation
What is the mechanism of action of intranasal corticosteroids?
- Examples
Intranasal corticosteroids cause local anti-inflammation, decreased capillary permeability, mucus production and causes nasal vasoconstriction
NOTE - does not immediately relieve symptoms (min 4 weeks)
Examples include
- Beclomethasone
- Fluticasone
Intranasal Corticosteriods contraindications/cautions
Safe in hepatic impairment, renal impairment, children from age of 2, pregnancy, breastfeeding
Contraindications in active severe nasal infection, bleeding disorders, recent nasal surgery
Decongestants
- MOA
- Examples of oral decongestants
- Examples of intranasal decongestants
MOA - activate alpha adrenoceptors on respiratory tract vascular smooth muscle
- Vasoconstriction of nasal mucosa
- Reduces tissue swelling
- Reduces nasal congestion
Oral Decongestants
- Phenylephrine (Sudafed PE)
- Pseudoephedrine (Sudafed) (limited use as can be made into methamphetamine)
Intranasal decongestants (not specific for respiratory tract)
- Oxymetazoline
- Xylometazoline
Oral Decongestant contraindications/cautions
Elderly are more likely to have CVD and ADRs - lower dose required
Pregnancy - avoid in 1st trimester
Breastfeeding - avoid
Renal and hepatic impairment - no cautions
Children - not used in under 6yrs and only used for 6-11 yrs under specialist advice
Contraindications within 14 days of MAOI, diabetes, prostatic, hypertrophy, hyperthyroidism, severe CVD, HT
Intranasal decongestants contraindications/cautions
Safe in elderly, pregnant, breastfeeding, hepatic impairment, renal impairment
Children - avoid in under 6 yrs
Theoretica contraindications within 14 days of MAOI
Montelukast
- Type of drug
- MOA
- When to use
- Example and ADR
Montelukast is a leukotriene antagonist
MOA - blocks the cysteinyl leukotriene receptor, stops smooth muscle contractions of airways, minimises inflammation from leukotrienes, reduces mucus secretions
Used as last line in allergies along with antihistamines/corticosteroids
Oral tablet - Singulair
- ADR - nightmares, hallucination, mood/behavior changes
Allergy - Rhinitis
- What it is
- Causes/associations
- Classifications
- Symptoms
Rhinitis = nasal involvement Most often due to environmental allergens (seasonal, occupational) Can also be drug induced Can be associated with other conditions - Asthma (30%) - Pregnancy (change in hormones) Classified by - Duration (intermittent or persistent) - Severity (impaired daily activity/sleep) Symptoms - Red, itchy, watery eyes - Sneezing, congestion, runny nose - Itchy or sore throat, post-nasal drip, couch
Seasonal allergies
- Symptoms
- How to treat
Symptoms of seasonal allergies include - Rhinitis - Itchy - Watery eyes - Itchy throat - Cough Treatment - Preferred is oral/intranasal antihistamines as they can be used for the duration of the season - Long term decongestants not indicated due to rebound congestion, abuse of oral therefore only used short term for blocked nose
Allergy - Anaphylaxis
- What is it
- What triggers it
Anaphylaxis is a severe, acute, potentially life threatening allergic response due to patient hypersensitivity to allergen Triggered by - Exercise - Current infections - Commodities - Drugs
Anaphylaxis pathophysiology
See lecture for diagram
Antigen triggers production of IgE antibodies which bind to surface of mast cell or basophil
Subsequent exposure to the same antigen which bridges the gap between two antibody molecules, de granulation of cell and release of histamines and other mediators which increase the permeability and distension of blood capillaries
Anaphylaxis signs and symptoms
- Swelling of the conjunctiva
- Runny nose
- Swelling of lips, tongue and/or throat
- Heart and vasculature (fast/slow heart rate and low BP)
- Skin (hives, itchiness, flushing)
- Pelvic pain
- CNS (lightheadedness, loss of consciousness, confusion, headache, anxiety)
- Respiration (Shortness of breath, wheezes or stridor, hoarseness, pain with swallowing, cough)
- Gastrointestinal (rampy abdominal pain, diarrhea, vomiting)
- Loss of bladder control
Anaphylaxis - Pharmacotherapy
First line therapy is IM adrenaline (should be administered a first suspicion of anaphylaxis)
MOA - acts as alpha and beta adrenocepter agonist
Effects
- Restores BP and CO
- Lessens vasodilation and vascular permeability
- Allows bronchodilation to restore airway
Anaphylaxis - Contraindications and Cautions
Eldery - N/A
Hepatic impairment - N/A
Renal impairment - N/A
Pregnancy - Benefit outweighs risk (monitor)
Breastfeeding - safe
Children - Safe
Often it is life saving therefore the benefit generally outweighs the risk
Anaphylaxis - Further management
If IM adrenaline is not adequate to manage symptoms after repeat administration consider
- IV fluids to restore intravascular volume and restore BP
- Short acting beta2 agonists (inhaled or nebulised) to help relieve bronchospasm
- Glucagon restores BP for patients taking beta blockers
- Corticosteroids are an adjunct therapy to help reduce duration of reaction and prevent relapse (4-6hrs for effect to occur)
Antihistamines in Anaphylaxis
AMH - no evidence that H1 and H2 antagonists are effective in acute anaphylaxis
They are adjuncts that helpful for associated urticaria, angioedema and itch
- In severe anaphylaxis they may be carried as a part of an allergy management plan
Difference between bacterial cells and human cells
Bacterial cells have no nucleus or nuclear membrane
DNA structure is essentially same however, bacterial chromosomes are usually circular DNA
Bacterial ribosomes have 50S subunit and 30S subunit whereas human ribosomes have subunits 60S and 40S
Antibacterial targets (bacterial cells)
See slides for image
Cell wall synthesis inhibitors
- Only affects bacterial cells as human cells do not have a cell wall
Folate synthesis inhibitors
- Human get it from diet - don’t synthesis it
- Bacterial cells cannot get it through the cell wall therefore they make it
- Needed for development of DNA
Protein synthesis inhibitors
- Bacteria have different ribosome subunits than our cells
Drugs affecting DNA integrity
- Bacteria have circular DNA which is not contained in a nucleus
Antibiotic Classification
- Gram Positive
- Gram Negative
Gram Positive
- Stains purple
Gram Negative
- Does not stain as it has an extra outer membrane preventing stain from penetrating which also acts to keep out certain antibiotic classes
Antibiotic Classification
- Bactericidal
- Bacteriostatic
Bactericidal
- Kills bacteria for us
- Penicillins, Cephalosporins, Aminoglycosides, Quinolones
Bacteriostatic
- Inhibits growth of bacteria so own defenses can kill the bacteria
- Macrolides, Lincosamides, Tetracyclines, Sulfonamides, Trimethoprim
Antibiotic Classification
- Broad Spectrum
- Narrow Spectrum
- Extended Spectrum
Broad spectrum
- Active against wide variety of microbial species
- E.g. Tetracyclines, amoxycillin + clavulanic acid
- Cannot just use these due to resistance
Narrow Spectrum
- Only active against either a single or very limited amount of organism
- E.g. clindamycin, penicillin G (older penicillin)
Extended Spectrum
- Active against gram positive bacteria and many gram negative bacteria
- E.g. Cephalosporins, fluoroquinolones
Antimicrobial Creed
MIND ME
- Microbiology to guide therapy
- Indications should be evidence based
- Narrowest spectrum therapy required
- Dosage individualized, appropriate to site and type of infection
- Minimize duration of therapy
- Ensure oral therapy used whenever appropriate
Antibiotic resistance
- How it occurs
- How it spreads
How it occurs
- Lots of germs with a few resistant to drugs
- Antibiotics kill bacteria causing the illness as well as good bacteria protecting body from infection
- Drug resistant bacteria are now allowed to grow and take over
- Some bacteria give their drug resistance to other bacteria
How it spreads
- Animals develop resistance and human consumes animal
- Bacteria can remain on meat or in fertilizer or on water (containing animal feces) used on food crops
- Between people
Antibiotics: Cell wall inhibitors
- MOA
- Drug classes
MOA
- Inhibits the bacteria’s ability to build/maintain cell wall
Drug classes
- Beta-Lactams (Penicillin, Cephalosporins, Carbapenems and Meropenems)
- Glycoprptides (Vancomycin)
Beta Lactams - Penicillin
- MOA
- Class
- Drugs
- Resistance
- Penicillin was the first mass produced antibiotic
- MOA to inhibit cell wall synthesis
- Bactericidal
- Drugs include (Amoxicillin, Penicillin G/V, Flucloxacillin
- Anaphylaxis/intolerances to this class is common
- Antibiotic resistance is a big problem
Penicillin Resistance
- Beta-lactamases
- Clavulanic acid
Many bacteria have enzymes called beta-lactamases which attack beta-lactam drugs and render penicillin useless thus limiting their spectrum
Clavulanic acid is a beta-lactamase inhibitor thus stops the bacteria’s enzymes from breaking down the penicillin therefore extending penicillin’s spectrum
- E.g. Amoxycillin + Clavulanic acid = Augmentin Duo
Beta- Lactams - Cephalosporins
- MOA
- Class
- Drugs
- MOA to inhibit cell wall synthesis
- Bactericidal
- Drugs include (Cephalexin, Cefaclor, Ceftriaxone)
- Closely related to penicillins therefore if someone is anaphylactic to penicillin DON’T generally try cephalosporins
Glycopeptides
- MOA
- Class
- Drugs
- Use
- MOA to inhibit cell wall synthesis
- Bactericidal
- Drugs include (Vancomycin)
- Used in serious infection via IV (Endocarditis, meningitis, MRSA, C. dificile
Antibiotics: Non cell wall inhibitors (Aminoglycosides)
- MOA
- Class
- Drug
- Use
Aminoglycosides
- MOA is to inhibit bacterial protein synthesis by attaching to specific ribosome subunit
- Bactericidal (high concentration)
- Drugs include (Gentamicin)
- Use for serious, usually hospital acquired infections (Nephrotoxic and Ototoxic)
Antibiotics: Non cell wall inhibitors (Macrolides)
- MOA
- Class
- Drug
- Use
Macrolides
- MOA to inhibit protein synthesis and also have anti-inflammatory and immuno-modifying effects
- Bacteriostatic
- Drugs include (Azithromycin, Clarithromycin, Erythromycin)
- Used for a wide variety of infections
Antibiotics: Non cell wall inhibitors (Tetracyclines)
- MOA
- Class
- Drug
- Use
Tetracyclines
- MOA is to inhibit bacterial protein synthesis
- Bacteriostatic
- Drugs include (Doxycycline, Tetracycline)
- Used for many types of skin infections (including acne) and a wide variety of other infections
Antibiotics: Non cell wall inhibitors (Quinolones)
- MOA
- Class
- Drug
- Use
Quinolones
- MOA to inhibit bacterial DNA synthesis
- Bactericidal
- Drugs include (Ciprofloxacin, Norfloxacin)
- Used in severe or complicated infections
Name all branches of the immune system
Immunity:
- Innate
- Adaptive
Adaptive immunity:
- Natural
- Artificial
Natural immunity:
- Passive (maternal)
- Active (infection)
Artificial immunity:
- Passive (antibody transfer)
- Active (immunization)
The innate immune system
First line of defense
- Skin (epithelial cells) - slightly acidic pH
- Enzymes
- Cytokines
- Phagocytic cells
- Natural killer cells
Passive vs Active immunity
Active immunity:
- Immune response with production of antibodies (mount against exposed type of pathogen) - can either be from an infection (natural) or vaccination (artificial)
Passive Immunity:
- Receive actual antibodies from the transfer of maternal antibodies across placenta (natural) OR administration of immunoglobulin (artificial) through injection
- Use for immediate and effective and transient effect with no immune response mounted by recipient
Adaptive Immune response
See slides for host response to infection
- Basis for immunological memory - more powerful defense and high targeted for pathogen
Two major types of response
- Humeral - B lymphocytes, once activated produce antibody to bind pathogen and neutralizes, some form of memory cells allowing response to subsequent exposure to be quicker and stronger
- Cellular - designed to defend against intracellular pathogens which are not accessible by innate immune response, T lymphocytes which act via search and destroy missions on infected cells with intracellular pathogens, some also form memory T cells
What is immunization and how it works?
Immunization is defined as rendering a person protected from an infectious agent (act of making immune) and it is achieved by introducing an antigen to a person to give protection without causing the disease
What is an antibody?
An antibody is produced in response to antigen exposure
- Y shaped glycoprotein
- Neutralizes the pathogen
- Often measured to gauge success of vaccination
What is a vaccine?
A vaccination is the use of vaccines to prevent a specific disease
It is the preparation of a weakened or killed pathogen, such as bacterium or virus, or of a portion of the pathogen’s structure
How vaccines work
See slides for diagram of cells involved
The goal of immunization is to produce memory of the vaccine antigen via a large population of memory cells, if the real pathogen enters the body in the future, memory cells will recognize it and the bodies response will be stronger and faster than if it had never encountered the pathogen
Herd immu nity
Occurs when large number in population are vaccinated
- Less chance of disease transmission
- Indirectly protects unimmunized
- Difficult for disease to maintain chain of infection
- Outbreaks can be limited
% of population required to be immunized varies according to disease (range from 40-90% for herd immunity to take place)
Types of vaccines
- Live Attenuated Vaccines (include viral and bacterial examples)
Live attenuated vaccine
- Virus or bacteria is alive but weakened and unable to cause disease
- Low virulent strains are selected from cultures for vaccines
- Single exposure may be sufficient for lifelong immunity
- Viral vaccines such as measles, mumps, rubella, yellow fever, varicella, rotavirus
- Bacterial vaccines such as tuberculosis or typhoid
- Do not use in immunocompromised patients
Types of vaccines
- Inactivated vaccines (include viral and bacterial examples)
Inactivated vaccines
- Multiple doses are required to establish immunity (need booster)
- No symptoms of disease as it is not living
- Safe in immunocompromised patients (but possible of poor immune response)
- Completed or parts of virus or bacteria that are inactivated with chemicals or heat
- Influenza vaccines are made by growing virus in chicken eggs along with chicken embryo
- Viral vaccines such as polio, influenza, hepatitis A
- Bacterial vaccines such as bordella pertussis (whooping cough) or vibrio cholerae
Types of vaccines
- Toxoid vaccines
Toxoid vaccines
- Consist of inactivated toxins - produced by some pathogens, inactivated with either heat or via chemical modification
- Action - stimulate production of antibodies against the bacterial toxins rather than the whole bacterial pathogen
- Examples include diphtheria, tetanus, botulism
Types of vaccines
- Subunit vaccines
Subunit vaccines
- Only include certain parts (proteins) of the virus
- Advantages include that it can be produced faster and safer than using eggs to make vaccines - viral proteins stored in saline
- Recombinant sub unit vaccines - insert some DNA of pathogen into another cell or organism then use as vaccine (e.g. recombinant hep B)
Issues with immunization
- Safety
- Benefits vs risks
- Practical issues
- Storage
Safety
- Vaccines must not induce illness or death
Risk vs benefits
- Must protect from illness induced by living pathogen
- Protection must last several years
Practical issues
- Cost, stability, invasiveness of administration
Storage
What can cause failure of immunization?
- Inadequate maintenance of cold chain (decreased vaccine potency)
- Expired
- Patients immune system is inadequate to mount an immune response
- Patient’s immunity has declined over time (boosters)
- Not 100% guaranteed effective
- Incorrect injection side
Antigenic shift (Mutation)
- Influenza
- Pandemic subtypes
Both influenza A and B viruses undergo frequent changes in surface antigens which involves step wise mutations of genes
- Results in changes in influenza antigens (antigenic shift)
- Responsible for annual outbreaks and epidemics of influenza
- Reason that composition of influenza vaccines require annual review
Pandemic subtypes
- Arise following antigenic shift (e.g. bird and swine flu)
