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PhArmacology 101 > Inflammation And Immune Function and Cardiovascular > Flashcards

Inflammation And Immune Function and Cardiovascular Flashcards

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1
Q

Innate Immunity

A
  1. Foot soldiers/ Artillery of Immune system
  2. Evolutionary, oldest, majority of response
  3. Self vs Non-self Fight with same strength, intensity and timing regardless of exposure
  4. Cells/Structures: Phagocytic/Scavenger Cells, Inflammation, Plasma Protein Complement System (attack and kill regardless of ID), structural/chemical barriers, microbiome
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2
Q

Adaptive

A
  1. Special Ops of Immune system (can use innate system)
  2. Evolved over a life time
  3. Exposure to pathogens leads to faster, stronger and more silent response
  4. Cells/Structures:B-Lymphocytes (antibody mediated immunity), T Lymphocytes (cell mediated immunity)
  5. Artificial: Vaccines
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3
Q

Pleuripotent Hematopoetic Stem Cell

A
  1. Found in bone marrow gives rise to all blood cells
  2. Differentiates into many different cells
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4
Q

Myeloid line

A

Scavenger cell, Macrophage, Neutrophil (myeloginous Leukemia)

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5
Q

Lymphoid Line

A

B and T Cells, Natural Killer cells (lymphogenous leukemia)

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6
Q

Phagocytic cells

A

Neutrophil Macrophage Mature dendritic cell

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7
Q

Steps triggering an Adaptive Immune response

A
    1. Antigen presenting cell (macrophage, dendritic or B-lymphocyte) finds antigen cell
    1. APC and antigen complex binds to specific CD4 cell
    1. CD4 activates response specific to antigen (B or T cells for antigen)
    1. CD4 releases cytokines that increase production of specific B or T cells 5. Effector (B or T) cells fight off current invader
    1. Memory (B or T) cells stored for next round
  6. ****CD4 (or Helper T) = General, regulates all adaptive response****
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8
Q

Interleukine 2

A
  1. Cytokine released by CD4 cell to activate T-Cell adaptive immunity.
  2. Important in organ rejection (suppression of IL2 can reduce organ rejection)
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9
Q

Interleukine 4, 5, 6

A

B-Cell activating cytokines. Facilitate antibody mediated response

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10
Q

Immunosuppressants

A
  1. Family/Class: large group
  2. MOA: Many - inhibit immune response
  3. Therapeutic Effect: Prevent organ rejection, treat autoimmunee
  4. Organisms: N/a
  5. ADVERSE: Increased risk of infection, increased risk of neoplasm (cancer)
  6. DVD/DVF: ?? Other Info: ??
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11
Q

Calcineurin Inhibitors

A
  1. Family/Class: Immunosuppressant
  2. MOA: Inhibit calcineurin = IL2 inhibitor = no T-cell proliferation
  3. Therapeutic Effect: Prevent organ rejection
  4. Other Info: Cyclosporine, tacrolimus, pimecrolimus
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12
Q

Cyclosporine

A
  1. Family/Class: Calcineurin Inhibitors
  2. Trade name: Sandimmune
  3. MOA: Inhibit IL2, interferon gamma and other cytokines
  4. Therapeutic Effect:
    1. Drug of choice to prevent organ rejection (kidney, liver, heart) of an allogenic transplant
    2. Some autoimmune diseases
  5. Contraindications: Some metabolize less = need smaller dose
  6. ADVERSE:
    1. Nephrotoxic,
    2. Hepatotoxic,
    3. Lymphoma,
    4. hypertension,
    5. tremor,
    6. hirsutism,
    7. Leukopenia,
    8. gingival hyperplasia,
    9. gynecosmastia,
    10. sinusitis,
    11. hyperkalemia,
    12. anaphylactic rxn
  7. DVD/DVF:
    1. Drugs that decrease:
      1. CYP3A4 inducers = phenytoin, Phenobarbital, carbamazepine, rifampin
    2. Drugs that Increase:
      1. CYP3A4 inhibitors = Azole antifungal, macrolide antibiotics, amphotericin B Nephrotoxic drugs, Grapefruit Juice, Repaglinide (cyclosporine increases - antidiabetic)
  8. Other Info: Developed first and used more than tacrolimus
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13
Q

Tacrolimus

A
  1. Family/Class: Calcineurin Inhibitors
  2. Trade: Prograf
  3. MOA: Inhibit calcineurin = IL2 inhibitor
  4. Use: Prophylaxis of organ rejection (kidney, liver, heart)
    1. Alt to cyclosporine - more effective but more toxic, Used with glucocorticoids
  5. ADVERSE:
    1. Nephrotoxicity,
    2. Neurotoxicity,
    3. GI,
    4. Hypertension,
    5. Hyperkalemia,
    6. Hyperglycemia,
    7. Hirsutism,
    8. Gum hyperplasia,
    9. Anaphylaxis with IV
  6. DVD/DVF:
    1. CYP3A inhibitors - build up,
    2. Grapefruit Juice,
    3. NSAIDs should be avoided (nephrotoxic)
  7. Other Info: Narrow therapeutic index
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14
Q

Pimecrolimus

A
  1. Family/Class: Calcineurin Inhibitors
  2. MOA: Inhibit calcineurin = IL2 inhibitor
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15
Q

Neoral or Gengraf

A
  1. Family/Class: Cyclosporin Immunosuppressant
  2. Trade: Gengraf
  3. Therapeutic Effect: Rheumatoid Arthritis, Psoriasis
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16
Q

mTOR Inhibitor

A
  1. Family/Class: Mammalian Target of Rapamycin
  2. Trade: n/a
  3. MOA:Inhibits p.kinase that regs cell growth = suppresses B and T cell proliferation
  4. Other Info: Structure similar to tacrolimus. (No calcineurin inhibition)
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17
Q

Rapamycin

A
  1. Protein Kinase that helps regulate cell growth, proliferation and survival (MTOR target)
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18
Q

Sirolimus (Rapamune)

A
  1. Family/Class: mTOR inhibitor **prototypic
  2. Trade: Rapamune
  3. MOA: see mTOR
  4. Therapeutic Effect: RENAL TRANSPLANT rejection prevention ONLY - use with cyclosporine and glucocorticoids
  5. ADVERSE:
    1. Risk for infection,
    2. Raises cholesterol and triglycerides,
    3. Risk of renal injury,
    4. BAD severe cx in liver and lung transplants,
    5. Rash,
    6. anemia,
    7. thrombocytopenia,
    8. joint pain,
    9. D,
    10. HYPOKALEMIA
  6. DVD/DVF:
    1. Inhibit or Induce cyp3A4 will impact,
    2. High fat foods can INCREASE ABSORBTION by 35% (imp. High toxicity),
    3. Grapefruit inhibits metabolism
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19
Q

Everolimus (Zortress)

A
  1. Family/Class: mTOR inhibitor
  2. Trade: Zortress
  3. MOA: see mTOR
  4. Therapeutic Effect: prevent LIVER OR KIDNEY transplant rejection in 18+ pts
  5. Contraindications: not in Pregnancy
  6. ADVERSE:
    1. Peripheral edema,
    2. N/C,
    3. Hypertension,
    4. Anemia,
    5. UTI,
    6. Hyperlipidemia,
    7. Teratogenic AND enters breast milk
  7. DVD/DVF:
    1. Inhibit OR induce CYP3A4 enzymes,
    2. High-fat foods,
    3. Grapefruit juice
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20
Q

Glucocorticoids

A
  1. MOA: Suppress immune response via Phospholipase inhibitor
  2. Therapeutic Effect:
    1. Anti inflammatory, Suppress phospholipid to arachodonic acid
    2. (immune) Suppress allograft rejection, tx asthma, r. Arthritis, systemic lupus erytheematosus (SLE),
  3. MS Type: Cortisol, Cortizone, Corticosterone
  4. ADVERSE:
    1. Risk of infection,
    2. thin skin,
    3. bone dissolution with fracture,
    4. impaired growth in -18,
    5. suppression of hypothalamic pituitary-adrenal axis,
    6. Kushings Syndrome (moon face, chipmunk cheeks, buffalo hump, center body weight gain) Women esp.
  5. Other Info: LARGE doses used in organ transplant, Elevate blood glucose, synthesized in adrenal cortex
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21
Q

Cortisol

A

Family/Class: Glucocorticoids

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22
Q

Cortizone

A

Family/Class: Glucocorticoid

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23
Q

Corticosterone

A

Family/Class: Glucocorticoid

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24
Q

Metabolic pathway of inflammation through phospholipids

A
    1. All cell membranes have phospholipids
    1. Phospholipidase converts to ARACHIDONIC ACID
  3. 3a. Cyclooxygenase (COX) converts Arach.Acid to PROSTOGLANDIN
  4. 3b. 5-Lipoxygenase converts Arach.Acid to Leukotrienes (eventually)
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25
Cytotoxic Drugs
1. MOA: Suppress immune by killing B and T lymphocytes during proliferation 2. Therapeutic Effect: non-specific destruction of proliferating cells 3. ADVERSE: 1. Bone marrow suppression = Neutropenia, thrombocytopenia, 2. GI distrubances (reduces absorptive surface), 3. Reduced fertility (blocks ovulation b/c no miosis), 4. Alopecia (hair is from stem cells)
26
Azathioprine
1. Family/Class: cytotoxic 2. Trade: Imuran 3. MOA: Suppresses cell mediated and humoral immune response 4. Therapeutic Effect: Additive treatment with transplants 5. ADVERSE: 1. Blood dyscrasias, 2. N/V, 3. mutagenic and teratogenic, 4. Neoplasms (cancer)(longterm), 5. Pancreatitis 6. Other Info: HIGHER mutagenic and teratogenic than other B and T Cell blockers
27
Cyclophosphamide
1. Family/Class: Cytotoxic 2. Therapeutic Effect: Anticancer
28
Methotrexate
1. Family/Class: Cytotoxic 2. Trade: Rheumatrex, Trexall 3. Therapeutic Effect: 1. R. Arthritis, 2. Psoriasis, 3. Suppression of B and T lymphocytes by messing with folate metabolism
29
Mitoxantrone
1. Family/Class: Cytotoxic 2. Trade: Novatrone 3. Therapeutic Effect: Anticancer, Reduce neurologic disability and relapse for MS patients 4. Other Info: HAZARDOUS - only for people who can’t use safer drugs
30
Mycophenolate mofetil
1. Family/Class: Cytotoxic 2. MOA: Acts on B and T lymphocytes = inhibit inosine monophosphate dehydrogenase 3. Therapeutic Effect: prophylaxis of organ rejection 4. Other Info: selective inhibition of B and T lymphocyte proliferation
31
Histamine
1. Type: Endogenous ligand 2. Location: Found in specialized cells, in all tissues. ESP skin, lungs, GI. Low in plasma 3. Synthesis: Mast cells and basophils, Cells in GI tract, Neuronal cells of CNS (post. Hypothal. W/frontal lobe and temporal areas) 4. Role: 1. 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) 2. Regulation of gastric acid secretion 3. Nonallergic = radiactive dyes, plasma expanders, any cell damage
32
Basiliximab
1. Family/Class: Monoclonal manufactured antibody 2. Trade: n/a 3. MOA: Blocks T Cell by binding to IL2 4. Therapeutic Effect: Prophylaxis of organ rejection **RENAL** transplant 5. ADVERSE: 1. Does not increase infection risk, 2. no cancers reported after 1 year of tx 6. Other Info: Reminder - IL1 released by CD4 or Helper T - then Cytotoxic T Cell proliferate?
33
Antithymocyte, Lymphocyte immune globulin
1. Family/Class: manufactured antibody 2. Trade: [Atgam] 3. MOA: Decrease T-lymphoctes 4. Therapeutic Effect: Prevent **RENAL** transplant rejection, Aplastic Anemia 5. ADVERSE: Hypersensitivity, anaphylaxis 6. Other Info: Made from equine serum inoculated with human T-lymphocytes
34
H1 Receptor
1. Type: Histamine receptor 2. Role: 1. Allergic Rxn - Vasodialation (Skin, face, upper body), Can cause hypotension, Up cap. Perm. = edema (lets albumin and H2O into tissue), Bronchoconstriction, 2. 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
35
H2 Receptor
1. Histamine Receptor (ECL) Role: Secretion of Gastric Acid, 2. Act directly on parietal cells to increase acid release, 3. Major role in acid release
36
Dyphenhydramine
1. Family/Class: 1st Gen H1 Antagonist 2. Trade: Benadryl 3. MOA: Block histamine at H1 receptor, some bind to muscarinic receptors 4. Therapeutic Effect: 1. Reduce localized flushing, 2. Reduce itching and pain 5. Use: 1. Mild allergy, 2. Severe allergy (additive), 3. Insomnia, 4. Common cold (reduce rhinorrhea b/c anti-cholinergic) 6. ADVERSE: 1. HIGHLY Sedating - CNS depression, 2. Dizzy, fatigue, coordination issues, confusion, 3. GI - N/V/C (give with food), loss of app., 4. Anti-cholinergic - weak atropine effects??? 5. OD: CNS stimulation, convulsions, dilated pupils, flush, hyperpyrexia, tachy, dry mouth 6. WATCH OUT young children more sensitive 7. DVD/DVF: 1. CNS depressants, 2. Avoid during pregnancy 8. Contraindications: 1. 3rd trimester, 2. Nursing, newborns. 3. CAUTION: young, old, condition worse from muscarinic blockade (anti-cholinergic effects) 9. Other Info: Tx for OD = no antidote, remove drug (activated charcoal), IV benzodiazepiens (lorazepam, midazolam) for convulsions, tx fever with physical cooling
37
Promethazine
1. Family/Class: 1st Generation H1 Antagonist Antihistamine 2. Therapeutic Effect: Use in Motion sickness
38
Dimenhydrinate
1. Family/Class: 1st Generation H1 Antagonist Antihistamine 2. Therapeutic Effect: Use in Motion sickness
39
Fexofenadine
1. Family/Class: 2nd Gen H1 Antagonist 2. Trade: Allegra 3. MOA: Block histamine at H1 receptor 4. Therapeutic Effect: Seasonal allergy, **CHRONIC IDIOPATHIC URTICARIA** 5. Contraindications: CAUTION patients with RENAL impairment 6. ADVERSE: **MOST SAFE** of 2nd Generation Antihistamines 7. DVD/DVF: **NO FRUIT JUICE** 8. Other Info: low affinity for CNS H1
40
Cetirizine
1. Family/Class: 2nd Gen H1 Antagonist 2. Trade: Zyrtec 3. MOA: Block histamine at H1 receptor 4. Therapeutic Effect: Seasonal allergy, CHRONIC IDIOPATHIC URTICARIA 5. ADVERSE: **MOST SEDATION** of 2nd Generation Antihistamines 6. DVD/DVF: Food delays absorbtion 7. Other Info: low affinity for CNS H1
41
Levocetirizine
1. Family/Class: 2nd Gen H1 2. Antagonist Trade: Xyzal 3. MOA: Block histamine at H1 receptor 4. Therapeutic Effect: Seasonal allergy, CHRONIC IDIOPATHIC URTICARIA 5. ADVERSE: 1. **MORE SEDATING** of 2nd Generation Antihistamines, 2. Drowsiness, 3. fatigue, 4. muscle weakness, 5. dry mouth 6. DVD/DVF: 1. Avoid ETOH, 2. Avoid CNS depressants 7. Other Info: low affinity for CNS H1
42
Loratidine
1. Family/Class: 2nd Gen H1 Antagonist 2. Trade: Claritin 3. MOA: Block histamine at H1 receptor 4. Therapeutic Effect: Seasonal allergy 5. Contraindications: **CAUTION patients with RENAL OR HEPATIC impairment** 6. ADVERSE: Well tolerated 7. DVD/DVF: Food delays absorbtion 8. Other Info: low affinity for CNS H1
43
Desloratadine
1. Family/Class: 2nd Gen H1 Antagonist 2. Trade: Clarinex 3. MOA: Block histamine at H1 receptor 4. Therapeutic Effect: Seasonal allergy, **perennial allergy,** chronic idiopathic urticaria
44
Cycloooxygenase Inhibitors
1. Use: suppress inflam, relieve pain, reduce fever 2. MOA: Inhibit cyclooxygenase (COX) enzyme 3. Adverse: 1. Gastric ulceration, 2. bleeding, **RENAL** impairment 3. Reminder: Phospholipid +(Phospholipidase) —\> Arachidonic Acid + (Cyclooxygenase) —\> Prostonoids = Prostoglandins —\> INFLAMMATION
45
COX 1
Good Cox Inhibiting: GI Ulceration, Bleeding, RENAL impairment, PROTECT against MI and Stroke
46
COX 2
Bad Cox Inhibition: Suppress Inflammation, Pain relief, Reduce fever, PROTECT against COLON cancer
47
NSAID
Non-steroidal Anti-inflammatory drug \*\*\*Not acetaminophen b/c no anti-inflam\*\*\*\*
48
Aspirin
1. Family/Class:1st Generation NSAID 2. Trade: Aspirin 3. MOA: Non selective inhibitor of COX 1 and COX 2 I**RREVERSIBLE** 4. Use: 1. Analgesic, 2. antipyretic, 3. anti-inflam., 4. Suppress platelet aggregations (lower clot risk), 5. Dysmenorrhea, 6. Cancer prevention, 7. Prevent alzheimer’s 5. Indications: 1. R. Arthritis, 2. O.arthritis, 3. bursitis 6. Contraindications: 1. Pregnancy - Anemia, PPH, prolonged labor, 2. Under 18 - Reye’s syndrome 7. ADVERSE: 1. GI, Bleeding, 2. **RENAL impair,** 3. Salicylism - too much salicylic acid = Tinnitus, sweating, headache, dizzy, 4. Hypersensitivity Rxn 8. DVD/DVF: 1. Anticoags (Warfarin and heparin), 2. Glucocorticoids (Gastric ulcers worse), 3. ETOH (gastric bleed), 4. Ibuprofen (negate cardio benefits of low dose), 5. ACE inhib. And ARB **(NEPHROTOXIC)**, 6. Poisoning, 7. THREAT: resp depression, hypertherm, dehdration
49
Ibuprofen
1. Family/Class:1st Generation NSAID 2. Trade: Advil, Motrin 3. MOA: Non selective inhibitor of COX 1 and COX 2 **REVERSIBLE** 4. Use: Analgesic, antipyretic, anti-inflam. I 5. ndications: R. Arthritis, O.arthritis 6. Contraindications: Pregnancy - Anemia, PPH, prolonged labor, Under 18 - Reye’s syndrome 7. ADVERSE: 1. NO PROTECTION against MI or stroke, 2. Fewer issues than aspirin, 3. GI Bleeding INCREASED 8. DVD/DVF: 1. Anticoags (Warfarin and heparin), 2. Glucocorticoids (Gastric ulcers worse), 3. ETOH (gastric bleed), 4. Ibuprofen (negate cardio benefits of low dose), 5. ACE inhib. And ARB (NEPHROTOXIC), 6. Poisoning, 7. THREAT: resp depression, hypertherm, dehdration
50
Celecoxib
1. Family/Class:2nd Generation NSAID 2. Trade: Celebrex - last choice 3. MOA: Non selective inhibitor of COX 1 and COX 2 REVERSIBLE 4. Use: Analgesic, antipyretic, anti-inflam. 5. Indications: R. Arthritis, O.arthritis, Pain, Dysmenorrhea 6. Contraindications: Pregnancy not in 3rd trimester, \<18 Reye’s 7. ADVERSE: 1. **INCREASED MI o**r stroke vasoconstriction and no platelet inhibition, 2. Dyspepsia, 3. Abdo pain, 4. GI bleed less, 5. RENAL fx impaired, 6. hypertension, 7. edema, 8. sulfonamide allergy 8. DVD/DVF: 1. Anticoags (Warfarin and heparin), 2. Furosemide (decrease diuretic effect), 3. ETOH (gastric bleed), 4. ACE inhib. (Decrease effect of ACE), 5. Lithium (increase li levels), 6. Fluconazole (increase levels)
51
Acetaminophen
1. Family/Class: ??? 2. Trade: Tylenol 3. MOA: Inhibits prostaglandin synthesis in 4. CNS Use: Analgesic, antipyretic, NOT ANTI INFLAM!! 5. Indications: Pain, Fever 6. Contraindications: **Liver disease** 7. ADVERSE: 1. Few at normal dose, 2. SJSyndrome, 3. AGEP acute generalized exanthematous pustulosis, 4. TEN toxic epiermal necrolysis, 5. HEPATOTOXICITY, 6. OD: Hepatic necrosis - coma, death, N/V/D, diaresis, abdo pain 7. Tx for OD: Acetylcysteine (Mucomyst), 8. NOT ASSOC. WITH REYE’s 8. DVD/DVF: Alcohol, 1. Warfarin (increase bleed risk), 2. VACCINES (can blunt immune responses to childhood vaccines)
52
Preferred drugs for stages of heart failure
1. Stage A (High risk) - 1. treat HTN, 2. Smoke cessation, 3. Lipid disorders, 4. Exercise, 5. No ETOH, 6. Control metabolic syndrome 7. Drugs: 1. ACE or ARB, 2. Statin 2. Stage B (Structural heart disease w/o symptoms) - 1. Stage A Goals 2. Drugs: 1. ACE or ARB, 2. Statin, 3. Beta-blockers 3. Intervention: 1. Implantable defibrillator 3. Stage C (Structural heart disease with prior or current symptoms) - 1. A and B 2. plus salt reduction 3. Drugs: 1. Diuretic, 2. ACE, 3. Betablockers, 4. Statin PLUS 5. (sometimes) Aldosterone antagonist, 6. ARB, 7. Digitalis, 8. Hydralazine/nitrates 4. Interventions: 1. Biventricular pacing, 2. Implantable defib 4. Stage D (Refractory heart failure - end stage) - 1. All under A, B, C 2. Drugs; 1. Digoxin 3. Intervention: 1. heart transplant, 2. permanent mechanical support, 3. experimental treatments
53
ACE Inhibitor (-pril)
1. Class: ACEI 2. MOA: 1. block conversion of AI to AII, 2. Increase bradykinin in lungs 3. Dosing: Oral EXCEPT enalipril 4. Therapeutic use: 1. Hypertension, 2. CHF, 3. MI, 4. Diabetic and nondiabetic nephropathy, 5. prevent MI in high risk pts 5. ADVERSE: 1. FIRST DOSE HYPOTENSION, 2. teratogenic, 3. dry cough, 4. ANGIOEDEMA (rxn - swelling in tongue, lips, eyes = EMERGENCY), 5. **HYPERkalemia,** 6. **Renal failure**, 7. neutropenia 6. DVD: 1. Positive: 1. Diuretic - careful for low H20, Use with HYPOkalemic diuretic 2. Negative: 1. HYPERkalemic drugs, 2. **LITHIUM toxicity,** 3. **NSAIDS - reduce efficacy** of ACEI 7. Special considerations: 1. Enalipril - IV, 2. captopril and moexipril = with food
54
Benazepril
1. Class: ACEI 2. Disease/Stage: Stage A (Hypertension)
55
Captopril
1. Class: ACI 2. Disease/Stage: 1. Stage A (Hypertension and Diabetic nephropathy), 2. Stage B (Post MI), 3. Stage C (HF) Special considerations: Give with food
56
Enalipril
1. Class: ACI 2. Disease/Stage: 1. Stage A (HTN, Diabetic Neuropathy), 2. Stage B (Asymptomatic LVSD), 3. Stage C (HF) 3. Special considerations: Not given orally
57
Fosinopril
1. Class: ACEI 2. Disease/Stage: 1. Stage A (Hypertension), 2. ——-, 3. Stage C (HF)
58
Lisinopril
1. Class: ACEI 2. Disease/Stage: 1. Stage A (HTN, Diabetic nephropathy), S 2. tage B (Post MI), 3. Stage C (HF)
59
Moexipril
1. Class: ACEI 2. Disease/Stage: 1. Stage A (Hypertension) 3. Special considerations: give with food
60
Perindopril
1. Class: ACEI 2. Disease/Stage: 1. Stage A (HTN, Cardiovascular RISK)
61
Quinapril
1. Class: ACEI 2. Disease/Stage: 1. Stage A (HTN), 2. ———, 3. Stage C (HF)
62
Ramipril
1. Class: ACEI 2. Disease/Stage: 1. Stage A (HTN, Cardiovascular Risk), 2. Stage B (Post MI), 3. Stage C (post MI)
63
Trandolapril
1. Class: ACEI 2. Disease/Stage: 1. Stage A (HTN), 2. Stage B(Post MI), 3. Stage C (Post MI)
64
ARBs
1. Class: Angiotensin II Receptor Blockers 2. MOA: Block access of Angiotensin II receptors 3. Physiologic effect: 1. dialation of arterioles + veins, 2. no pathologic changes in cardiac structure, 3. reduce K excretion, 4. reduce aldosterone, 5. INCREASE excretion of NA and H2O, 6. Do not inhibit kinase II, 7. Do not increase bradykinin 4. Therapeutic use: 1. Hypertension, 2. HF, 3. MI, 4. Diabetic Nephropathy (only in severe?), 5. Prevent diabetic retinopathy 6. Indications: 1. Poor tolerance of ACEI 7. ADVERSE: 1. Angioedema, 2. teratogenic, 3. renal failure, 4. NO DRY COUGH
65
Candesartan
1. Class: ARB 2. Disease/Stage: 3. Stage A (HTN), 4. ——-, 5. Stage C (HF)
66
Eprosartan
1. Class: ARB 2. Disease/Stage: 1. Stage A (HTN)
67
Irbesartan
1. Class: ARB 2. Disease/Stage: 1. Stage A (HTN, Diabetic Neuropathy)
68
Losartan
1. Class: ARB 2. Disease/Stage: 1. Stage A ( HTN, Diabetic nephropathy), 2. Stage B (Cardiovascular Risk)
69
Olmesartan
1. Class: ARB 2. Disease/Stage: 1. Stage A (HTN)
70
Telmisartan
1. Class: ARB 2. Disease/Stage: 1. Stage A (HTN)
71
Valsartan
1. Class: ARB 2. Disease/Stage: 1. Stage A (HTN, Diabetic nephropathy), 2. Stage B (Post MI), 3. Stage C (Post MI, HF)
72
Eplerenone (Inspra)
1. Class: Aldosterone Antagonist 2. MOA: Blocks aldosterone receptors (hormone receptors) 3. Dosing: not affected by food 4. Therapeutic use: 1. Hypertension, 2. Heart failure 5. ADVERSE: 1. **Hyperkalemia** 6. **​**DVD: 1. CYP3A4 inhibitors = accumulation, 2. other HYPERkalemic drugs, 3. **LITHIUM CAUTION**
73
Spironolactone
1. Class: Aldosterone antagonist 2. MOA: 1. Blocks aldosterone receptors - promiscuous 3. Therapeutic use: 1. Hypertension, 2. HF 4. ADVERSE: 1. **HYPERkalemia**, 2. gynecomastia, 3. menstrual irregularities, 4. impotence, 5. hirsutism, 6. deepening of voice
74
Beta Blockers
1. Action: 1. Protect from excessive sympathetic stimulation, 2. Protect against dysrhythmias HR DOWN 2. Adverse: 1. fluid retention, 2. **worsening HF,** 3. Fatigue, 4. **Hypotension,** 5. Bradycardia or Heart Block
75
Acebutolol
1. Betablocker 2. Stage A (HTN)
76
Atenolol
1. Betablocker 2. Stage A (HTN) 3. Stage B (POST MI)
77
Betaxolol
1. Beta Blocker 2. STage A (HTN)
78
Bisoprolol
1. Betablocker 2. Stage A(HTN) 3. —— 4. Stage C (HF)
79
Carteolol
1. Beta blocker 2. Stage A (HTN)
80
Carvedilol
1. Beta blocker 2. Stage A (HTN) 3. Stage B (Post MI) 4. Stage C( HF, Post MI)
81
Labetalol
1. Betablocker 2. Stage A (HTN)
82
Metoprolol succinate
1. Beta blocker 2. Stage A (HTN) 3. —— 4. Stage C (HF)
83
Metoprolol tartrate
1. Beta blocker 2. Stage A (HTN) 3. Stage B (Post MI
84
Nadolol
1. Beta blocker 2. stage A (HTN)
85
Penbutolol
1. Beta blocker 2. Stage A (HTN)
86
Pindolol
1. Beta blocker 2. Stage A (HTN)
87
Propranolol
1. Beta blocker 2. Stage A (HTN) 3. Stage B (post MI)
88
Timolol
1. Betablocker 2. Stage A (HTN) 3. Stage B (Post MI)
89
Digoxin (Lanoxin)
1. Class: positive inotrope 2. Disease/Stage: Endstage CHF 3. MOA: 1. increases force of vent. Contraction 2. myocardial contractility 4. Physiologic effects - 1. decreased symp. Tone, 2. increased urine production, 3. decreased renin release, 4. increase cardiac baroreceptor activity, 5. increases vagal firing, 6. increase SA node response to acetylcholine 5. Therapeutic use: 1. end stage heart failure, 2. NOT IN pregnant, 3. careful with renal insuff, 4. 1.5 day 1/2 life!!! 6. ADVERSE: 1. SMALL therapeutic index, 2. Change in K has HUGE effect, 3. CAUSE DYSRHYTHMIA, 4. N/V/A, 5. fatigue 7. DVD: 1. Positive - 1. Diuretics - often together with AceI or ARB- careful of 2 hypokalemics), 2. Negative: 1. Sympathomemetrics = counterproduct stim of symp., 2. Quinodine and Verapamil - increase dysrhythmia risk
90
Furosemide (Lasix)
1. Class: Loop Diuretic 2. MOA: Blocks reabsorption at loop of Henle 3. Dosing: PO 60 min, IV 5 min 4. Therapeutic use: 1. Pulmonary edema, 2. edematous states, 3. HTN 5. ADVERSE: 1. **HYPOnatremia-cholremia-hydration,** 2. HYPOtension (loss of volume, relaxation of venous smooth muscle), 3. **HYPOkalemia,** 4. **OTOTOXIC**, 5. **HYPERglycemia-uricemia**, 6. teratogenic - pre-eclampsia, 7. Increase Lipid, 8. Decrease Ca and Mg 6. DVD: 1. Digoxin - toxicity increase with change in K - **WATCH OUT FOR K,** 2. Ototoxic drugs, 3. **USE K SPARING diuretic**, 4. **LITHIUM - WATCH OUT,** 5. other Antihypertensive - **BP BOTTOM OUT,** 6. **NSAIDS** reduce furosemide 7. Special considerations: most frequently prescribed
91
Ethacrynic acid (Edecrin)
High Ceiling Loop Diuretic
92
Bumetanide (Bumex)
High Ceiling loop Diuretic
93
Torsemide (Demadex)
High Ceiling Loop Diuretics
94
Hydrochlorothiazide (HydroDIURIL)
1. Class: Thiazide diuretic 2. MOA: 1. DCT, 2. Increase renal excretion of Na, Cl, K and H20. 3. Dosing: 1. Peaks in 4-6 hours 4. Therapeutic use: 1. Essential Hypertension, 2. Edema, 3. Diabetes insipidus 5. ADVERSE: 1. **HYPO-natremia-chloremia-hydration-kalemia,** 2. **HYPERglycemia-uricemia**, 3. Impact CA, 4. Lipid, 5. MG 6. DVD: 1. **Digoxin**, 2. **LITHIUM,** 3. not as much ototoxicity, 4. NSAIDS blunt effect 7. Special considerations: Popular, **LESS EFFICACIOUS than Loop**
95
K-Sparing Diuretics
1. Therapeutic effect: 1. modest increase in urine, 2. **HYPER-K - DECREASE in potassium excretion** 3. ADJUNCTIVE 4. Aldosterone Antagonist: SPIRONOLACTONE IS ONE!!!!!! 5. Non-aldo antag: Triamterene and Amiloride
96
Triamteren
1. Non aldo antag = K sparing diuretics 2. MOA: 1. DCT na/K exchange, 2. inhibits exchange mech, 3. DECREASE sodium reuptake, 4. inhibits ion transport 3. Therapeutic use: 1. HTN, 2. Edema 4. ADVERSE: 1. HYPERkalemia, 2. Leg cramps, 3. N/V, 4. dizziness, 5. blood dyscrasia
97
Amiloride
1. non aldo antag - K sparing diuretics 2. MOA: Block Na/K DCT 3. Therapeutic use: Counteracts K loss by more powerful diuretics 4. ADVERSE: **HYPERkalemia** 5. DVD: Avoid with ACE and ARB, other hyperkalemia
98
Spironolactone as K sparing Diuretic
1. MOA: blocks aldo. In DCT, Retains K, Increase Na excretion 2. Therapeutic use: 1. HTN, 2. edema, 3. HF, 4. Primary hyperaldosteronism, 5. PMS, 6. PCOS, 7. Acne in young women 3. ADVERSE: 1. HYPERkalemia, 2. benign and malignant tumors, 3. endocrine (promiscuous) 4. DVD: 1. Thiazide and loop diuretics -good. 2. NO- other hyper K drugs
99
Mannitol (Osmitrol)
1. Class: Osmotic Diuretic 2. MOA: diuresis by creating osmotic force within lumen of nephron 3. Dosing: PARENTERAL 4. Therapeutic use: 1. Prophylaxis of renal failure, 2. REDUCE ICP, 3. REDUCE Intraocular pressure 5. ADVERSE: 1. Edema, 2. Headache, 3. N/V, 4. fluid electrolyte
100
Hypertension
1. I - ideopathic, chronic, progressive 1. Pop: Older, AA, Post Menopausal 2. Essential Hypertension 2. II - id primary cause, 1. treat cause directly, 2. some can be cured
101
Consequences of HTN
1. Heart disease - 2. MI, 3. HF, 4. Angina pectoris 5. Kidney disease 6. Stroke
102
HTN Lifestyle modifications
1. NA restriction 2. DASH 3. ETOH restriction 4. Aerobic exercise 5. Smoking cessation 6. K and Ca intake
103
Types of Drugs to treat HTN
1. Diuretics (Thiazide, Loop, K-sparing) 2. Sympatholytics (antiandrenergic drugs) - 1. beta-adrenergic blockers, 2. Alpha 1 blocker, 3. Alpha/beta blockers (CARVEDILOL and LABETALOL), 4. Alpha 1 agonists, 5. Adrenergic neuron blockers, 3. Direct-acting vasodilators (HYDRALAZINE and MINOXIDIL), 4. Ca Channel blockers, 5. Drugs that suppress RAAS (ACE, ARB, Aldo antag, Renin inhib)
104
HTN for Renal disease
?
105
HTN for diabetes
?
106
HTN for AA
Drugs to lower fluid tend to work immediately and better
107
HTN for \<18
?
108
HTN for older
Lower dose b/c elimination is slower
109
Drugs for HTN emergencies
1. Sodium Nitroprisside - direct vasodiallator (plus a beta blocker) (Avoid reflex tachycardia, keep HR low) 2. Fenodlopam 3. Labetalol 4. Diazoxide 5. Clevidipe - Ca channel blocker
110
HMG-CoA Reductase Inhibitors (STATINS)
1. MOA: blocks liver synthesis of cholesterol - reduce LDL, 2. Dosing: Admin at night (cholesterol synthesis increases at night) 3. Therapeutic use: 1. Most effective for lowering LDL, 2. elevates HDL, 3. reduce triglyceride 4. ADDITIONALLY - 1. promote plaque stability, 2. reduce cardiovascular events, 3. increased bone formation, 4. Post MI, 5. Diabetes 4. ADVERSE: 1. HEADACHE, 2. rash, 3. GI, 4. RARE: 1. rhabdomyolysis, 2. Hepatotoxicity, 3. new-onsent diabetes, 4. cataracts 5. DVD: 1. combo with other lipid lowering EVEN other bile acid sequestrants, 2. NEGATIVE: 1. CYB3A4 inhibitors - increase blood plasma levels, 2. teratogenic
111
Nicotinic Acid (Niacin)
1. MOA: prevents recycling of bile 2. Therapeutic use: 1. Reduce LDL and TG levels, 2. increase HDL more than any other 3. ADVERSE: 1. Skin (flushing, itching) - treat with aspirin (decreased with SR), 2. GI, 3. **HEPATOTOXIC,** 4. HYPERglycemic, 5. Gouty arthritis, 6. raise blood levels of uric acid
112
Bile acid sequestrants
1. Adjuncts to statins 2. Better tolerated 3. Does not decrease uptake of fat soluble vitamins (like other ones) 4. Does not reduce absorption of statins, warfarin, digoxin or other drugs
113
Colesevelam
1. Class: Bile acid sequestrant 2. MOA: Increases LDL receptors on hepatocytes, prevents reabsorption of bile 3. Therapeutic use: 1. Reduces LDL, 2. Increases 3. VLDL 4. ADVERSE: constipation
114
Ezetimibe
1. class: cholesterol reducer 2. Therapeutic use: 1. Reduces total cholesterol, 2. LDL cholesterol and 3. apolipoprotein B, 4. monotherapy and combo with STATIN 3. ADVERSE: 1. Myopathy, 2. Rhabdomyolysis, 3. Hepatitis, 4. Pancreatitis, 5. Thrombocytopenia 4. DVD: 1. GOOD: Statins, Fibrates, Bile Acid sequestrates, 2. BAD: Cyclosporine - decrease absorption
115
Fibric Acid Derivative
1. **Most effective for lowering TG levels** 2. Can raise HDL 3. NO EFFECT ON LDL 4. Increase bleed in warfarin 5. Increase risk for rhabdomyolysis in statin takers
116
Gemfibrozil
1. Class: Fibric Acid Derivative (Fibrates) 2. MOA: Interacts with PPAR receptors T. 3. Use: Decrease VLDL if diet hasn’t worked, less effective than statin 4. ADVERSE: 1. **gallstones,** 2. **Hepatotoxic**, 3. rashes, 4. myopathy 5. DVD: 1. displaces warfarin = increase blood plasma levels, 2. Measure INR often

PhArmacology 101 (4 decks)

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