Inflammation And Immune Function and Cardiovascular Flashcards
Innate Immunity
- Foot soldiers/ Artillery of Immune system
- Evolutionary, oldest, majority of response
- Self vs Non-self Fight with same strength, intensity and timing regardless of exposure
- Cells/Structures: Phagocytic/Scavenger Cells, Inflammation, Plasma Protein Complement System (attack and kill regardless of ID), structural/chemical barriers, microbiome
Adaptive
- Special Ops of Immune system (can use innate system)
- Evolved over a life time
- Exposure to pathogens leads to faster, stronger and more silent response
- Cells/Structures:B-Lymphocytes (antibody mediated immunity), T Lymphocytes (cell mediated immunity)
- Artificial: Vaccines
Pleuripotent Hematopoetic Stem Cell
- Found in bone marrow gives rise to all blood cells
- Differentiates into many different cells
Myeloid line
Scavenger cell, Macrophage, Neutrophil (myeloginous Leukemia)
Lymphoid Line
B and T Cells, Natural Killer cells (lymphogenous leukemia)
Phagocytic cells
Neutrophil Macrophage Mature dendritic cell
Steps triggering an Adaptive Immune response
- Antigen presenting cell (macrophage, dendritic or B-lymphocyte) finds antigen cell
- APC and antigen complex binds to specific CD4 cell
- CD4 activates response specific to antigen (B or T cells for antigen)
- CD4 releases cytokines that increase production of specific B or T cells 5. Effector (B or T) cells fight off current invader
- Memory (B or T) cells stored for next round
- ****CD4 (or Helper T) = General, regulates all adaptive response****
Interleukine 2
- Cytokine released by CD4 cell to activate T-Cell adaptive immunity.
- Important in organ rejection (suppression of IL2 can reduce organ rejection)
Interleukine 4, 5, 6
B-Cell activating cytokines. Facilitate antibody mediated response
Immunosuppressants
- Family/Class: large group
- MOA: Many - inhibit immune response
- Therapeutic Effect: Prevent organ rejection, treat autoimmunee
- Organisms: N/a
- ADVERSE: Increased risk of infection, increased risk of neoplasm (cancer)
- DVD/DVF: ?? Other Info: ??
Calcineurin Inhibitors
- Family/Class: Immunosuppressant
- MOA: Inhibit calcineurin = IL2 inhibitor = no T-cell proliferation
- Therapeutic Effect: Prevent organ rejection
- Other Info: Cyclosporine, tacrolimus, pimecrolimus
Cyclosporine
- Family/Class: Calcineurin Inhibitors
- Trade name: Sandimmune
- MOA: Inhibit IL2, interferon gamma and other cytokines
- Therapeutic Effect:
- Drug of choice to prevent organ rejection (kidney, liver, heart) of an allogenic transplant
- Some autoimmune diseases
- Contraindications: Some metabolize less = need smaller dose
- ADVERSE:
- Nephrotoxic,
- Hepatotoxic,
- Lymphoma,
- hypertension,
- tremor,
- hirsutism,
- Leukopenia,
- gingival hyperplasia,
- gynecosmastia,
- sinusitis,
- hyperkalemia,
- anaphylactic rxn
- DVD/DVF:
- Drugs that decrease:
- CYP3A4 inducers = phenytoin, Phenobarbital, carbamazepine, rifampin
- Drugs that Increase:
- CYP3A4 inhibitors = Azole antifungal, macrolide antibiotics, amphotericin B Nephrotoxic drugs, Grapefruit Juice, Repaglinide (cyclosporine increases - antidiabetic)
- Drugs that decrease:
- Other Info: Developed first and used more than tacrolimus
Tacrolimus
- Family/Class: Calcineurin Inhibitors
- Trade: Prograf
- MOA: Inhibit calcineurin = IL2 inhibitor
- Use: Prophylaxis of organ rejection (kidney, liver, heart)
- Alt to cyclosporine - more effective but more toxic, Used with glucocorticoids
- ADVERSE:
- Nephrotoxicity,
- Neurotoxicity,
- GI,
- Hypertension,
- Hyperkalemia,
- Hyperglycemia,
- Hirsutism,
- Gum hyperplasia,
- Anaphylaxis with IV
- DVD/DVF:
- CYP3A inhibitors - build up,
- Grapefruit Juice,
- NSAIDs should be avoided (nephrotoxic)
- Other Info: Narrow therapeutic index
Pimecrolimus
- Family/Class: Calcineurin Inhibitors
- MOA: Inhibit calcineurin = IL2 inhibitor
Neoral or Gengraf
- Family/Class: Cyclosporin Immunosuppressant
- Trade: Gengraf
- Therapeutic Effect: Rheumatoid Arthritis, Psoriasis
mTOR Inhibitor
- Family/Class: Mammalian Target of Rapamycin
- Trade: n/a
- MOA:Inhibits p.kinase that regs cell growth = suppresses B and T cell proliferation
- Other Info: Structure similar to tacrolimus. (No calcineurin inhibition)
Rapamycin
- Protein Kinase that helps regulate cell growth, proliferation and survival (MTOR target)
Sirolimus (Rapamune)
- Family/Class: mTOR inhibitor **prototypic
- Trade: Rapamune
- MOA: see mTOR
- Therapeutic Effect: RENAL TRANSPLANT rejection prevention ONLY - use with cyclosporine and glucocorticoids
- ADVERSE:
- Risk for infection,
- Raises cholesterol and triglycerides,
- Risk of renal injury,
- BAD severe cx in liver and lung transplants,
- Rash,
- anemia,
- thrombocytopenia,
- joint pain,
- D,
- HYPOKALEMIA
- DVD/DVF:
- Inhibit or Induce cyp3A4 will impact,
- High fat foods can INCREASE ABSORBTION by 35% (imp. High toxicity),
- Grapefruit inhibits metabolism
Everolimus (Zortress)
- Family/Class: mTOR inhibitor
- Trade: Zortress
- MOA: see mTOR
- Therapeutic Effect: prevent LIVER OR KIDNEY transplant rejection in 18+ pts
- Contraindications: not in Pregnancy
- ADVERSE:
- Peripheral edema,
- N/C,
- Hypertension,
- Anemia,
- UTI,
- Hyperlipidemia,
- Teratogenic AND enters breast milk
- DVD/DVF:
- Inhibit OR induce CYP3A4 enzymes,
- High-fat foods,
- Grapefruit juice
Glucocorticoids
- MOA: Suppress immune response via Phospholipase inhibitor
- Therapeutic Effect:
- Anti inflammatory, Suppress phospholipid to arachodonic acid
- (immune) Suppress allograft rejection, tx asthma, r. Arthritis, systemic lupus erytheematosus (SLE),
- MS Type: Cortisol, Cortizone, Corticosterone
- ADVERSE:
- Risk of infection,
- thin skin,
- bone dissolution with fracture,
- impaired growth in -18,
- suppression of hypothalamic pituitary-adrenal axis,
- Kushings Syndrome (moon face, chipmunk cheeks, buffalo hump, center body weight gain) Women esp.
- Other Info: LARGE doses used in organ transplant, Elevate blood glucose, synthesized in adrenal cortex
Cortisol
Family/Class: Glucocorticoids
Cortizone
Family/Class: Glucocorticoid
Corticosterone
Family/Class: Glucocorticoid
Metabolic pathway of inflammation through phospholipids
- All cell membranes have phospholipids
- Phospholipidase converts to ARACHIDONIC ACID
- 3a. Cyclooxygenase (COX) converts Arach.Acid to PROSTOGLANDIN
- 3b. 5-Lipoxygenase converts Arach.Acid to Leukotrienes (eventually)
Cytotoxic Drugs
- MOA: Suppress immune by killing B and T lymphocytes during proliferation
- Therapeutic Effect: non-specific destruction of proliferating cells
- ADVERSE:
- Bone marrow suppression = Neutropenia, thrombocytopenia,
- GI distrubances (reduces absorptive surface),
- Reduced fertility (blocks ovulation b/c no miosis),
- Alopecia (hair is from stem cells)
Azathioprine
- Family/Class: cytotoxic
- Trade: Imuran
- MOA: Suppresses cell mediated and humoral immune response
- Therapeutic Effect: Additive treatment with transplants
- ADVERSE:
- Blood dyscrasias,
- N/V,
- mutagenic and teratogenic,
- Neoplasms (cancer)(longterm),
- Pancreatitis
- Other Info: HIGHER mutagenic and teratogenic than other B and T Cell blockers
Cyclophosphamide
- Family/Class: Cytotoxic
- Therapeutic Effect: Anticancer
Methotrexate
- Family/Class: Cytotoxic
- Trade: Rheumatrex, Trexall
- Therapeutic Effect:
- R. Arthritis,
- Psoriasis,
- Suppression of B and T lymphocytes by messing with folate metabolism
Mitoxantrone
- Family/Class: Cytotoxic
- Trade: Novatrone
- Therapeutic Effect: Anticancer, Reduce neurologic disability and relapse for MS patients
- Other Info: HAZARDOUS - only for people who can’t use safer drugs
Mycophenolate mofetil
- Family/Class: Cytotoxic
- MOA: Acts on B and T lymphocytes = inhibit inosine monophosphate dehydrogenase
- Therapeutic Effect: prophylaxis of organ rejection
- Other Info: selective inhibition of B and T lymphocyte proliferation
Histamine
- Type: Endogenous ligand
- Location: Found in specialized cells, in all tissues. ESP skin, lungs, GI. Low in plasma
- Synthesis: Mast cells and basophils, Cells in GI tract, Neuronal cells of CNS (post. Hypothal. W/frontal lobe and temporal areas)
- Role:
- Allergic Rxn - Rxn requires prior exposure to the allergen, Rxn will not occur during initial exposure - (Major role in MINOR rxn, minor role in anaphylaxis - Leukotrienes are dom)
- Regulation of gastric acid secretion
- Nonallergic = radiactive dyes, plasma expanders, any cell damage
Basiliximab
- Family/Class: Monoclonal manufactured antibody
- Trade: n/a
- MOA: Blocks T Cell by binding to IL2
- Therapeutic Effect: Prophylaxis of organ rejection RENAL transplant
- ADVERSE:
- Does not increase infection risk,
- no cancers reported after 1 year of tx
- Other Info: Reminder - IL1 released by CD4 or Helper T - then Cytotoxic T Cell proliferate?
Antithymocyte, Lymphocyte immune globulin
- Family/Class: manufactured antibody
- Trade: [Atgam]
- MOA: Decrease T-lymphoctes
- Therapeutic Effect: Prevent RENAL transplant rejection, Aplastic Anemia
- ADVERSE: Hypersensitivity, anaphylaxis
- Other Info: Made from equine serum inoculated with human T-lymphocytes
H1 Receptor
- Type: Histamine receptor
- Role:
- Allergic Rxn - Vasodialation (Skin, face, upper body), Can cause hypotension, Up cap. Perm. = edema (lets albumin and H2O into tissue), Bronchoconstriction,
- CNS effects - plays a role in sleep/wake, cognition, memory (CNS has own supply, doesn’t cross B/B barrier but antihistimines can), Itching, pain, mucus secretion
H2 Receptor
- Histamine Receptor (ECL) Role: Secretion of Gastric Acid,
- Act directly on parietal cells to increase acid release,
- Major role in acid release
Dyphenhydramine
- Family/Class: 1st Gen H1 Antagonist
- Trade: Benadryl
- MOA: Block histamine at H1 receptor, some bind to muscarinic receptors
- Therapeutic Effect:
- Reduce localized flushing,
- Reduce itching and pain
- Use:
- Mild allergy,
- Severe allergy (additive),
- Insomnia,
- Common cold (reduce rhinorrhea b/c anti-cholinergic)
- ADVERSE:
- HIGHLY Sedating - CNS depression,
- Dizzy, fatigue, coordination issues, confusion,
- GI - N/V/C (give with food), loss of app.,
- Anti-cholinergic - weak atropine effects???
- OD: CNS stimulation, convulsions, dilated pupils, flush, hyperpyrexia, tachy, dry mouth
- WATCH OUT young children more sensitive
- DVD/DVF:
- CNS depressants,
- Avoid during pregnancy
- Contraindications:
- 3rd trimester,
- Nursing, newborns.
- CAUTION: young, old, condition worse from muscarinic blockade (anti-cholinergic effects)
- Other Info: Tx for OD = no antidote, remove drug (activated charcoal), IV benzodiazepiens (lorazepam, midazolam) for convulsions, tx fever with physical cooling
Promethazine
- Family/Class: 1st Generation H1 Antagonist Antihistamine
- Therapeutic Effect: Use in Motion sickness
Dimenhydrinate
- Family/Class: 1st Generation H1 Antagonist Antihistamine
- Therapeutic Effect: Use in Motion sickness
Fexofenadine
- Family/Class: 2nd Gen H1 Antagonist
- Trade: Allegra
- MOA: Block histamine at H1 receptor
- Therapeutic Effect: Seasonal allergy, CHRONIC IDIOPATHIC URTICARIA
- Contraindications: CAUTION patients with RENAL impairment
- ADVERSE: MOST SAFE of 2nd Generation Antihistamines
- DVD/DVF: NO FRUIT JUICE
- Other Info: low affinity for CNS H1
Cetirizine
- Family/Class: 2nd Gen H1 Antagonist
- Trade: Zyrtec
- MOA: Block histamine at H1 receptor
- Therapeutic Effect: Seasonal allergy, CHRONIC IDIOPATHIC URTICARIA
- ADVERSE: MOST SEDATION of 2nd Generation Antihistamines
- DVD/DVF: Food delays absorbtion
- Other Info: low affinity for CNS H1
Levocetirizine
- Family/Class: 2nd Gen H1
- Antagonist Trade: Xyzal
- MOA: Block histamine at H1 receptor
- Therapeutic Effect: Seasonal allergy, CHRONIC IDIOPATHIC URTICARIA
- ADVERSE:
- MORE SEDATING of 2nd Generation Antihistamines,
- Drowsiness,
- fatigue,
- muscle weakness,
- dry mouth
- DVD/DVF:
- Avoid ETOH,
- Avoid CNS depressants
- Other Info: low affinity for CNS H1
Loratidine
- Family/Class: 2nd Gen H1 Antagonist
- Trade: Claritin
- MOA: Block histamine at H1 receptor
- Therapeutic Effect: Seasonal allergy
- Contraindications: CAUTION patients with RENAL OR HEPATIC impairment
- ADVERSE: Well tolerated
- DVD/DVF: Food delays absorbtion
- Other Info: low affinity for CNS H1
Desloratadine
- Family/Class: 2nd Gen H1 Antagonist
- Trade: Clarinex
- MOA: Block histamine at H1 receptor
- Therapeutic Effect: Seasonal allergy, perennial allergy, chronic idiopathic urticaria
Cycloooxygenase Inhibitors
- Use: suppress inflam, relieve pain, reduce fever
- MOA: Inhibit cyclooxygenase (COX) enzyme
- Adverse:
- Gastric ulceration,
- bleeding, RENAL impairment
- Reminder: Phospholipid +(Phospholipidase) —> Arachidonic Acid + (Cyclooxygenase) —> Prostonoids = Prostoglandins —> INFLAMMATION
COX 1
Good Cox Inhibiting: GI Ulceration, Bleeding, RENAL impairment, PROTECT against MI and Stroke
COX 2
Bad Cox Inhibition: Suppress Inflammation, Pain relief, Reduce fever, PROTECT against COLON cancer