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Pharmacology 2 > Inflammation > Flashcards

Inflammation Flashcards

1
Q

Glucocorticosteroids

  • anti-shock
A
  • capillary membrane permability decrease –> enhance microcirculation
  • high dosage: vasoconstriction
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2
Q

Immunosuppression

  • Cyclosporin and Tacrolimus
A

* Calcineurin inhibitors

Calcineurin:

  • Dephosphorylates NFAT (activation)
  • Translocation to the nucleus
  • IL-2 expression

Mechanism:

  • ONLY in T-cells
  • Calcineurin inhibition
  • Mastocyte inhibition, inhibition of degranulation
  • Decreased IL and TNF-a expressions

Cyclosporin:

  • Application: very common
  • Per os with food and locally
  • Indications: Autoimmune diseases, Atopic dermatitis, IBD
  • Side effects: GI: vomitting, diarrhea, Alopecia, Gingival hyperplasia

Tacrolimus, Dimecrolimus:

  • 500 times more active than cyclosporin
  • Increased toxicity
  • Topical application: 0.1 % ointment. –> Atopic dermatitis, Lupus

Pimecrolimus:

  • Locally atopic dermatitis, KCS
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3
Q

Antihistamines

  • side effects
A
  • 1st generation: CNS depression, Anticholinergic effect
  • 2nd generation: Prolonged QT interval
  • appetite depression (cyproheptadine)
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4
Q

Antihistamines

  • usage
A
  • individual differences
  • allergic diseases
  • asthma, RAO?
  • anaphylactic reactions?
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5
Q

Glucocorticoids (SAIDs)

  • Side effects
A
  • HT-hypophysis-adrenal cortex axis inhibition: approx 1-2 weeks –> cortex atrophy. Slow, continous ending
  • gastric ulcers
  • hepatopathy: ALKP significantly increase
  • pancreatitis
  • glucoma, cataracta
  • thinning of skin, delayed wound healing, alopecia
  • polyuria, polydypsia
  • polyphagia
  • muscle atrophy
  • immunosuppression
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6
Q

Immunosuppression

  • Cyclophosphamide
A

* Alkalytic agent

  • Nitrogen mustad, DNA alkalyticing: Proliferating cells
  • B-and T-cells equally effected
  • GI, BM side effects: <2 G/L, whiskers
  • Haemorrhagic cystitis (acrolein, Fe rare) –> Furosemide
  • Mostly per. os–> Antineoplastic, Autoimmune disorders
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7
Q

Glucocorticosteroids

  • neuroprotective effects
A
  • Trauma –> bleeding –> local vasoconstriction
  • Ischaemia –> lipid peroxidation –> ROS –> Apotosis, necrosis

Glucocorticoids conteract lipidperoxidation and enhance microcirculation

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8
Q

Antihistamines

  • mechanism of action and classes
A

Mechanism of action:

  • Antihistamines: inverse agonists, NOT antagonists

Classes:

1st generation:

  • Ethylenediamines: Chloropyramine, chloropheniramine
  • Ethanolamines: diphenhydramine, Dimenhydrinate
  • Phenothiazines: promethiazines
  • Piperazines: Hydroxyzine
  • Other: dimetinden, cyproheptadine

2nd generation:

  • Loratadine, Cetrizine, Levocetrizine
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9
Q

NSAIDs

  • Pharmacokinetics
A

Absorption:

  • usually weak acids
  • feed (ketoprofen, carprofen/meloxicam, mavacoxib)

Distribution:

  • extensive albumin binding
  • hypoalbuminaemia

Metabolism:

  • mostly glucoronic acid conjugation –> Feline sensitivity!

Excretion:

  • urine active + inactive
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10
Q

Glucocorticosteroids

  • antiinflammatory and immunosuppressive effects
A
  • PLA2 (see drawing)
  • COX enzyme expression decrease
  • Interleukin expression (IL-1, IL-2, 3, 4, 5, 6, 10, 12) decrease
  • TNF and IFN synthesis decrease
  • Apoptosis in lymphocytes –> lymphocytopenia
  • Neutrophilia (demargination)
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11
Q

JAK inhibitors

  • indications, inhibits, pharmacological effect:
A

Veterinary: Olacitinib, Apoquel

Pharmacological effect:

  • antiinflammatory, antiallergic, antipruritus

Indications:

  • atopic dermatitis

Inhibits:

  • Primary JAK 1
  • IL-2, IL-4, IL-6, IL-13: Allergy, inflammation
  • IL-31: Pruritus
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12
Q

Immunosuppression

  • Drugs
A

* Usually in combination of 2 or 3

Antimetabolites:

  • purine-analouges: Azathioprin, Mycophenolate-mofetil
  • pyrimidine-analouges: Leflunomide
  • folic acid antagonists: Methotrexate

Alkalytic agents:

  • Cyclophosphamide

Glucocorticoids

Cytokine gene expression inhibitors:

  • calcineurin-inhibitors: Cyclosporine, Tacrolimus, Pimecrolimus
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13
Q

Antihistamines:

  • severe histamine release –> anaphylaxis
A
  • vaccines, penicillins, insect bites etc
  • vascular permeability –> epiglottis oedema, angiedema
  • vasodilation –> shock

Other allergy mediated diseases: atopic dermatitis, cutaneous food adverse reactions, FAD

Other allergy mediated problems during surgery (eg morphine): premedication –> Acepromazine

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14
Q

Glucocorticoids (SAIDs)

  • Pharmacological effects
A
  • antiinflammatory
  • antiallergic
  • immunosuppresive
  • antishock
  • neuroprotective –> Glucocorticoids counteract lipidperoxidation and enhance microcirculation
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15
Q

Glucocorticosteroids

  • systemic use
A
  1. High dosage, once
    - I.V: eg shock, spinal trauma, allergy
  2. ADT (Alternate day therapy)
    - Prednisolone, methylprednisolone
    - every other day
    - Mornings (dog), evenings (cat)
  3. Long acting injections (depot)
    - only if ADT is not possible
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16
Q

Antihistamines

  • pharmacokinetics
A

Absorption:

  • good oral absorption: Cmax 2-3 hours

Distribution:

  • CNS 1st generation
  • 2nd generation –> ionized form + extensively albumin bound

Metabolism:

  • Liver –> CYP450 inducers!
17
Q

Immunosuppression

  • Indications
A

Autoimmune diseases:

  • lupus, pemphigus omplex
  • IHA: immune haemolytic anemia
  • KCS

Hypersensitivity disease:

  • atopic dermatitis
  • asthma
  • IBD: inflammatory bowel disease

Transplantation

18
Q

JAK inhibitors

  • Pharmacokinetics
A
  • excellent per os absorption: 90%
  • Give with food
  • Tmax: 1 hour
  • Metabolism: Liver, CYP450 NOT influenced
19
Q

NSAIDs

  • Active substances - Non-acidic substanves
A

Anilin derivatives: Paracetamol (Acetaminophen) (Pandol, soridon, NeoCitran)

  • COX-3 inhibition –> minor analgesic, antipyretic
  • Never in cats –> methaemogloniaemia

Metamizole sodium (Alyopyrin A.U.V)

  • COX-3, but not specific
  • Never in cats
20
Q

Glucocorticoids (SAIDs)

  • active substances
A

Esters, salts:

Na phosphate, Na succinate

Diprionate, phenylpropionate, acetate –> Acetonide

Dexadreson

  • Cortisol: Potency 1. Short effect
  • Prednisolone: Potency 4. Medium effect
  • Methylprednisolone: Potency 5-7. Medium effect
  • Triamicinolone: Potency 5-10. Medium effect
  • Betamethazone: Potency 25-30. Long effect
  • Dexamethasone: Potency 25-30. Long effect
  • Beclomethasone. potency 300-400. Local
  • Fluticason: Potency 400-500. Oral
  • Budesonide: Oral
21
Q

NSAIDs

  • side effects
A
  • GI ulcerations –> local irritation (ion trapping) that leads to decreased PGE = Ulceration
  • kidney damage –> dehydration, anaesthesia. Preexisting renal disease
  • Hepatotoxicity –> Rarely (Paracetamol, carprofen)
  • Platelet aggregation inhibition –> Aspirin, flunixin, tolfenamic acid, ketoprofen
  • Allergic reactions
  • Methaemoglobinaemia –> Paracetamol (Cat!)
  • Proteoglycan synthesis inhibition (cartilage damage) –> Aspirin, ketoprofen, ibuprofen, naproxen
  • Fetal damage (teratogenicity)
  • Placenta retention (48-36 hours)
  • Cardiotoxicity (Coxibs)
22
Q

NSAIDs

  • Active substances - Acidic substances:
A

Salicylates:

  • Acetylsalicylic acid (Aspirin): Dog, farm animals
  • Na salicylate
  • Sulfasalozine, mesalazine: Chronic colitis

Arilpropionic acids:

  • Ketoprofen (Ketofen A.U.V): Platelets! Cat: short term safity
  • Vedaprofen: Horse
  • Carprofen (Rimadyl A.U.V): Hepatopathy in retrivers). Carefull in combination with phenobarb. Cattle: long action.

–.> P.O, S.C, I.V

—> No cartilage damage, rare side effects (Cox-2)

—> Also for exitoc animals

Heteroaryl acetic acids:

  • Diclofenac (Voltaren, Cataflam), Indomethacin. NO!
  • Etodolac. Safe!

Anthranilic acids:

  • Flonixin meglumin (Finadyne A.U.V): thrombocyte-aggregation inhibition, Antiendotoxic
  • Tolfenamic acid: safe short term, also in cats

Butyil pyrazolidines: Phenylbotazone

Oxicams:

  • Piroxicam, tenoxicam. NO!
  • Meloxicam (metacam). Safe!

–> COX-2 preferential. Antiendotoxin

23
Q

NSAIDs

  • Pharmacological effects
A
  • antinflammatory
  • antipyretic
  • analgesic
  • platelet aggregation inhibition
  • antiendotoxin
  • antineoplastic
  • spasmolytic
24
Q

Glucocorticosteroids

  • physiological and pathological effects –> catabolism
A
  • stress hormone –> mobilizing hormone
  • Diabetogenic (<–> insulin)
  • Gluconeogenesis increase (liver) –> hyperglycaemia

–> Proteins - amino acids - GNG

–> Fats - glycerine - GNG

  • Muscle atrophy, weakness
  • decreased calcium absorption, incorporation –> osteoporosis
  • decreased collagen synthesis –> delayed wound healing
  • skin thinning, alopecia (Ca <–> Fe)
  • Decreased growth
  • PU/PD (ADH inhibition and psychic)
25
Q

NSAIDs

  • Active substances
A

Acidic substances:

  • Salicylates, Arilpropionic acids, Heteroaryl acetic acids, Anthranilic acids, Butyl pyrazolidines, Oxicams.

Non- acidic substances:

  • Anilin derivatives, metamizole derivatives

Coxibs:

  • Deracoxib, Fibrocoxib, Rodenacoxib, Cimicoxib, Mevacoxib
26
Q

Lokivetmab

A

Cytopoint

  • IL-31: monoclonal antibody. Highly specific. S.C
27
Q

Immunosuppression

  • Mycophenolate mofetil
A

* Antimetabolites

  • Prodrug: plasma esterase –> mycofenolic adid (per os). Inosine Monophosphate Dehydrogenase inhibitor (GMP decrease)
  • Specific to T- and B-lymphocyes: De novo GTP synthesis. In other cells: Salvage pathway
  • Much safer than azathiopurine (GI, BM rare)
  • rarely used in vet.med
28
Q

NSAIDs

  • Active substances - Coxibs
A

COX-2 inhibitors

  • Deracoxib (Dermaxx A.U.V): -meloxicam. Dog
  • Fibrocoxib (Previcox A.U.V): Dog, horse. Highly selective COX-2 inhibitors
  • Robenacoxib (Onsior A.U.V): Dog and Cat. Injection + tablets.
  • Cimicoxib (Cimalgex A.U.V)
  • Mevacoxib (Trocoxil A.U.V): Dog. Long half-life. Empty vs full stomach. Albumin binding 98%.

NSAIDs vs COBIBS

  • Both: managing pain and inflammation (especially arthritis). Equivalent analgesic and antiinflammatory effect.
  • GI tract: COXIBS benefits over NSAIDs in reducing perforations, ulcers etc.
  • Kidney: equal
  • Cardiovascular system: NSAIDs benefits
29
Q

Immunosuppression

  • Methotrexate
A

* Antimetabolites

  • Folic acid antagonist
  • Dihydrofolate reductase inhibitors: PABA –> dihydrofolic acid –> tetrahydrofolic acid
  • Apoptosis of activated T-cells: No effect on cells in resting state
  • Antineoplastics
30
Q

NSAIDs

  • mechanism of action
A

COX1 isoenzyme

  • localization: stomach, kidney, platelets
  • Constitutive

COX2 isoenzyme

  • localization: macrophages, fibroblast
  • inductive
31
Q

Glucocorticoids (SAIDs)

  • indications, recommended order
A
  1. local use: atopic dermatitis, otitis externa, mastitis
  2. single injectable dose
  3. asthma, RAO: inhalation
  4. intra articular
  5. ADT
  6. Depot injections
32
Q

Immunosuppression

  • Azathioprine
A

* Antimetabloites

  • Prodrug: Mercaptopurine
  • Slow release - longer effect
  • I.V or Oral
  • Side effects: Feline
  • Application: Autoimmine disease

Pharmacology 2 (13 decks)

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