MIDTERM II - TOPIC 26-28 Flashcards

26: ANTIHISTAMINES: 27-28: PHARMACOLOGY OF THE RESPIRATORY TRACT:

1
Q

26: ANTIHISTAMINES:

  1. Used for? Efficacy?
  2. In severe histamine release, what reaction do we see?
    1. Example when we see this reaction
  3. Severity of the reaction?
  4. Treatment for this reaction?
  5. What happens during the reaction?
  6. Antihistamines combined whit?
A
  • These are the oldest drugs used as an anti-allergic however, their efficacy is not that high.
  • In severe histamine release where we can see anaphylactic reactions and anaphylactic shock for example in
    • vaccines,
    • penicillins,
    • insect bites or even
    • when we administer LOKIVETMAB to a cat or horse etc.
  • Anaphylactic reactions can be life-threatening and in these cases, antihistamines can be used as a treatment but they must be combined with other, more effective, drugs.
  • In anaphylactic reactions, vascular permeability increases i.e. epiglottis oedema can occur, leading to suffocation.
  • Angioedema (tumors and nodules on the head) can occur like in the picture below of the dog.
  • This can be followed by a vaccination reaction.
  • In extreme cases, severe vasodilation can lead to shock i.e. anaphylaxis can be life-threatening in which we treat it with antihistamines combined with
    • adrenaline,
    • glucocorticoids etc.
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2
Q

26: ANTIHISTAMINES:

  1. Other allergy mediated diseases?
  2. Antihistamines and efficacy, how many % active in the dog?
  3. Due to atopic dermatitis, it is mediated by histamine and?
  4. Safety and economic point of view
A
  • Allergy mediated diseases e.g.
    • atopic dermatitis,
    • cutaneous food adverse reactions (food allergy) or
    • flea allergy dermatitis (FAD),
      • antihistamines have a low efficacy where they are active in only 20% of the dog.
      • This is due to the fact that the majority of cases of atopic dermatitis are not only mediated by histamine but by other cytokines e.g. interleukins etc.
      • They are safe and cheap and this is why they are tried.
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3
Q

26: ANTIHISTAMINES:

  1. When can we use antihistamines prior to?
  2. Which substance?
  3. Before the administration of which drug (causes serious histamin release)
A
  1. Used before surgery as
  2. ACEPROMAZINE e.g.
  3. before morphine administration as we have learned that morphine causes a serious histamine release.
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4
Q

26: ANTIHISTAMINES:

Mechanism of action:

  1. ​Acts like which inhibitors?
    1. ​Not …..?
    2. Do not bind to which receptor to block histamine binding
    3. Known as??
  2. ​Histamine receptor has 2 stages?
  3. If histamin is present - Which reaction?
    1. ​Side effects
  4. ​In case of drug administration what will favor which reaction? What will happen due to it?
A

Mechanism of action:

  • These, like JAK inhibitors,
    • are not antagonists i.e.
    • they do not bind to the histamine receptor to block histamine binding.
    • Instead, they are known as inverse agonists.
  • The histamine receptor has an active state (GTP present) and an inactive state (GDP present) that are within a unique balance with each other.
  • If histamine is present e.g. in an anaphylactic reaction, the active state will be initiated and side effects of
    • vasodilation,
    • epiglottis oedema,
    • nodules etc. can be seen.
  • In the case of drug administration, these inverse agonists (antihistamines) will favor the left reaction and inactive the action and the side effects will be inhibited.
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5
Q

26: ANTIHISTAMINES:

Usage:

A

Usage:

  • These are used in allergic reactions of course.
  • In asthma or RAO,
    • their use is controversial where their activity is not high enough and they usually do not work.
  • They are used in anaphylactic reactions in combination with
    • adrenaline and
    • glucocorticoids (antihistamines will not be enough).
  • In the case of atopic dermatitis etc. the chance of success with antihistamines is approx. 20-25%.
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6
Q

26: ANTIHISTAMINES

Other classes of drugs used:

A
  • These drugs have a very unique place in the veterinary field.
  • They are put into two generations.
  1. Ist generation: These cross the blood-brain barrier very easily, this is why their side effects include
    1. sedation,
    2. uncoordinated movement,
    3. sleepiness,
    4. ataxia etc. i.e. CNS side effects
  2. 2nd generation: These drugs do NOT cross the blood-brain barrier as well and this is why they cause sedation much less frequently when administered. Most of the human drugs are 2nd generation
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7
Q

26: ANTIHISTAMINES

Other classes of drugs used:

Ist generation:

A
  • Ethylenediamines:
    • CHLOROPYRAMINE,
    • CHLORPHENIRAMINE
  • Ethanolamines:
    • DIPHENHYDRAMINE,
    • DIMENHYDRINATE.
      • These two drugs are frequently used for vaccine allergy i.e. if you expect vaccine allergy, which is primarily seen in small dogs >10 kg.
      • This can occur in cases when an owner tells you that when their dog was previously vaccinated, they suffered an allergic reaction.
      • They are given orally, half an hour before administering the vaccination.
  • Phenothiazines:
    • PROMETHAZINE,
    • ACEPROMAZINE
  • Piperazines:
    • HYDROXYZINE.
    • This drug has the best activity in atopic dermatitis.
    • This was used before we had LOKIVETMAB.
    • The drug worked however, the action is slower than lokivetmab.
    • It is very safe but its efficacy is not as high as lokivetmab.
  • Other:
    • DIMETINDEN,
    • CYPROHEPTADINE.
      • Used as an appetite stimulant
      • Feline asthma.
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8
Q

26: ANTIHISTAMINES

Other classes of drugs used:

Ist generation:

Ethylenediamines:

A

Ethylenediamines:

  1. CHLOROPYRAMINE,
  2. CHLORPHENIRAMINE
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9
Q

26: ANTIHISTAMINES

Other classes of drugs used:

Ist generation:

Ethanolamines:

A

Ethanolamines:

  1. DIPHENHYDRAMINE,
  2. DIMENHYDRINATE.
  • ​These two drugs are frequently used for vaccine allergy i.e.
    • if you expect vaccine allergy, which is primarily seen in small dogs >10 kg.
  • This can occur in cases when an owner tells you that when their dog was previously vaccinated, they suffered an allergic reaction.

They are given orally, half an hour before administering the vaccination.

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10
Q

26: ANTIHISTAMINES

Other classes of drugs used:

Ist generation:

Phenothiazines:

A

Phenothiazines:

  1. PROMETHAZINE,
  2. ACEPROMAZINE
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11
Q

26: ANTIHISTAMINES

Other classes of drugs used:

Ist generation:

Piperazines:

A

Piperazines:

  • HYDROXYZINE.
    • This drug has the best activity in atopic dermatitis.
    • This was used before we had LOKIVETMAB.
    • The drug worked however, the action is slower than lokivetmab.
    • It is very safe but its efficacy is not as high as lokivetmab.

.

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12
Q

26: ANTIHISTAMINES

Other classes of drugs used:

Ist generation:

Other:

A

Other:

  1. DIMETINDEN,
  2. CYPROHEPTADINE.
    1. Cyproheptadine is also used as an appetite stimulant
    2. Used in cases of feline asthma
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13
Q

26: ANTIHISTAMINES

Other classes of drugs used:

2nd generation:

A
  • Most of the human drugs are 2nd generation e.g.
    • LORATADINE,
    • CETIRIZINE,
    • LEVOCETIRIZINE,
    • CLARITINE.
  • These are primarily used in humans however, they can also be used in dogs as trial and error drugs.
  • Some can react well while others may not react at all.
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14
Q

26: ANTIHISTAMINES

Pharmacokinetics:

  1. Absorbtion
  2. Dirstribution
  3. Blood brain barrier
  4. Metablolized
  5. CYP-450
A

Pharmacokinetics:

  • These drugs have good oral absorption however, it can be
  • Slow with the maximum plasma concentration (Cmax)
    • being 2-3 hours.
  • There is a difference in distribution between the 1st and 2nd generation drugs as they do not cross the blood-brain barrier with the same efficiency.
  • This is because the 2nd generation is in an ionized form in the blood which
    • hinders its transport through the membranes.
    • They are also extensively albumin-bound.
  • These two factors reduce the blood-brain barrier penetration.
  • Metabolized in the liver and they are cytochrome (CYP-450) inducers i.e.
    • they affect (mainly reduce) other drug’s activity as they
    • increase cytochrome enzymes
    • which will help their metabolism.
      • This is one reason why they are not used.
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15
Q

26: ANTIHISTAMINES

Side effects:

A

Side effects:

  • They are very safe drugs.
  • They can cause CNS depression (sedation)
  • Cardiac toxicity
    • Primarily associated with 1st generation drugs and in humans
      • resulting in a prolonged QT interval in the ECG
    • Fortunately, this is not so frequent in animals.
  • These drugs can be appetite suppressants (primarily in 1st generation drugs and in humans)
  • Exception of CYPROHEPTADINE = Appetite stimulant.
  • These are very safe but have low efficacy.

All in all, the best drugs to use would be

  1. OCLACITINIB,
  2. LOKIVETMAB or
  3. CYCLOSPORIN.
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16
Q

26: ANTIHISTAMINES

PHARMACOLOGY OF IMMUNOSUPPRESSION:

A
  • When we apply glucocorticoids in higher doses,
    • Immunosuppressive effect.
  • Other immunosuppressant agents include
    • antimetabolites,
    • alkylating agents
    • cytokine gene expression inhibitors.
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17
Q

26: ANTIHISTAMINES

Immunosuppression indications:

A

Immunosuppression indications:

  1. Autoimmune diseases:
  2. H**ypersensitivity diseases:
  3. Transplantation:
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18
Q

26: ANTIHISTAMINES

Immunosuppression indications:

Autoimmune diseases:

A

Autoimmune diseases:

  • These affect the mucous membrane and the skin.
  • LUPUS, pemphigus complex
    • Reaction against keratinocytes i.e.
      • Breakdown of intracellular desmosomal bridges
      • Release of rounded keratinocytes
  • IHA (immune haemolytic anaemia)
  • KCS (keratoconjunctivitis sicca) - dry eye disease
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19
Q

26: ANTIHISTAMINES

Immunosuppression indications:

Hypersensitivity diseases:

A

Hypersensitivity diseases:

  • Atopic dermatitis
  • Asthma
  • IBD (inflammatory bowel diseases)
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20
Q

26: ANTIHISTAMINES

Immunosuppression indications:

Transplantation:

A

Transplantation:

In order to avoid transplantation, immunosuppressant agents should be applied.

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21
Q

26: ANTIHISTAMINES

Immunosuppression indications:

  1. What does the picture show
  2. What to do, 1st step?
  3. If not enough fluid?
  4. What should you apply?
  5. Name the drug(s)?
A
  • KCS with damage to the cornea.
  • An ulcer can form in the cornea
  • First stage = Perform the Schirmer test
    • Tell you whether or not there is enough tear fluid on the eye.
  • If there is not enough, we would suspect the presence of KCS.
  • You can apply cholinergic parasympathomimetics to the eye such as
  1. PILOCARPINE but this is only symptomatic treatment. For better results, you can use
  2. CYCLOSPORINE or
  3. PIMECROLIMUS.

Immunosuppression can alleviate KCS.

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22
Q

26: ANTIHISTAMINES

Drugs:

In general + antimetabolites

A

Drugs:

We can sometimes combine these drugs e.g.

  1. CYCLOSPORINE can be combined with PREDNISOLONE which is a glucocorticoid.
    * This combination can have a beneficial effect if you would like to treat auto-immune disorders.

Antimetabolites:

  • These block enzymes irreversibly
  • Inhibit or cause damage to DNA.
  • This means that they can be used to treat cancer as well as an antineoplastic agent.
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23
Q

26: ANTIHISTAMINES

Drugs:

A
  1. Purine-analogues:
  2. Pyrimidine-analogues: LEFLUNOMIDE.
  3. Folic acid antagonists: METHOTREXATE.
  4. Alkylating agents:
  5. Glucocorticoids:
  6. Cytokine gene expression inhibitors:
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24
Q

26: ANTIHISTAMINES

Drugs:

1. Purine-analogues:

  1. AZATHIOPRINE
  2. Integrates into? What will it do?
  3. Used to treat?
  4. Its antineoplastic has a significant effect on? Causing?
  5. Sideeffects?
  6. Prodrug?
  7. Sensitivity and species?
  8. Release?
  9. Administration
  10. Appication for which disease
  11. How often administered
  12. Contraindications
A

1. Purine-analogues:

  1. AZATHIOPRINE,
  2. MYCOPHENOLATE-MOFETIL.
  • Azathioprine is a purine-analog that, once integrated into DNA, will
    • interfere with transcription and
    • reduces proliferation of the cells i.e.
    • Used to treat
      • immune-mediated hemolytic anaemia,
      • inflammatory bowel disease,
      • lupus etc.
    • This antineoplastic will have a significant effect on
      • cell division (will block cell division)
      • Block enzymes irreversibly i.e.
        • Cause inhibition or DNA damage
      • Several side effects - especially
        • vomiting,
        • diarrhea (GI disturbances because it has a significant effect on proliferative cells)
        • vomero suppression
        • Reduction in lymphocyte numbers (lymphocytopenia),
        • Anaemia
        • Thrombocytopenia.
    • Due to this DNA inhibition, it is also used to treat cancer.
    • Its prodrug is MERCAPTOPURINE and
      • cats are very sensitive to it.
    • The release is slow i.e.
      • takes up to 2 weeks to start working
      • but the effect is prolonged.
    • It is applied i/v but orally is also possible.
    • The application is for auto-immune diseases.
    • It is administered once a day for one week or every second day.
    • Please do NOT administer to pregnant or breeding animals as it has irreversible damage to gonads.
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26: ANTIHISTAMINES Drugs: 1. Purine-analogues: **2. MYCOPHENOLATE-MOFETIL.** 1. Mycophenolate-mofetil vs azathioprine? 2. Side effects 3. Usage in cats 4. Mechanism of drug 5. Censequence 6. Onset of action 7. Usage in combinations 8. Effect on which organ 9. If applied orally 10. In which condition is it especially better to use mycophenolate-mofentil instead of azathioprine?
*_1. Purine-analogues:_* 1. AZATHIOPRINE, 2. **MYCOPHENOLATE-MOFETIL.** * The second purine-analog is **mycophenolate mofetil.** * **We prefer this drug** to azathioprine as the * side effects are much rarer. * **Liver toxicity,** * **vomero suppression** * **acute pancreatitis** is not as significant in comparison. * This drug is also **safe to use routinely in cats.** * The mechanism of this drug is that it will **inhibit inosine monophosphate dehydrogenase** which is necessary to have purine. * The consequence of this is that there will be a **reduction in T** and **B cell proliferation.** * **This is much safer.** * **Gastrointestinal side effects are also rare.** * This has a **faster onset of action** also. * It is regularly used **in combination** with **steroid** and **CYCLOSPORINE**. * This drug will have an effect on **bone marrow** as there is **de novo GTP synthesis** i.e. **salvage pathway.** * Because of this, only the **T** and **B-lymphocytes** will be affected. * **GI bone marrow** will not be affected by the **salvage pathways.** * If this drug is **applied orally**, it will be hydrolyzed and converted to **MYCOPHENOLIC ACID** through the activation of plasma esterase i.e. * If there is a **liver insufficiency**, this drug is better to use in comparison to azathioprine.
26
26: ANTIHISTAMINES Drugs: *_2. Pyrimidine-analogues:_*
*_2. Pyrimidine-analogues:_* ## Footnote **LEFLUNOMIDE.**
27
26: ANTIHISTAMINES Drugs: *_3. Folic acid antagonists:_* 1. Blocks? 2. Result if we do not have enough tetrahydrofolic acid? 3. Administration? 4. Stimulates 5. Cells in resting phase 6. Applied against? 7. Side effects
*_3. Folic acid antagonists:_* **METHOTREXATE.** * Methotrexate will block **dihydrofolate reductase.** * The final result of this is that we do **not have tetrahydrofolic acid** i.e. * **Nucleic acid and DNA synthesis will be blocked**. * It can be **applied i/v, orally and i/m.** * It will **stimulate the apoptosis of T-cells** i.e. * this specifically **influences T-cells**. * It has **no effect on the cells in the resting phase.** * It can also be **applied against LYMPHOMA in dogs and cats** (antineoplastic agent). * The side effects can be * **hepatotoxicity,** * **pulmonary toxicity,** * **gastrointestinal side effects** * **Kidney** side effects also i.e. * they are **not as safe** as mycophenolate mofetil. **GI upset can occur.**
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26: ANTIHISTAMINES Drugs: Best choice of drug in the case of autoimmune glomerulonephritis?
**Mycophenolate mofetil** is the **best choice of drug i**n the case of **autoimmune glomerulonephritis,** **accompanied by protein** (mainly **albumin**) **loss**. It is also important as it is the **main drug of these** that can be **applied orally.**
29
26: ANTIHISTAMINES Drugs: 1. *_Alkylating agents:_* 2. *_Influence which cells_* 3. *_Against which disease_* 4. *_Cause what to the DNA_* 5. *_Drugs_*
*_Alkylating agents:_* * These will **influence lymphocytes** i.e. * fight **against lymphoma**, which is a **specific type** of **cancer**. * These cause **cross-linking** of **DNA** and **break DNA strands** i.e. * I**nterfere with DNA replication and RNA transcription.** 1. **CYCLOPHOSPHAMIDE,** 2. **CHLORAMBUCIL.**
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26: ANTIHISTAMINES Drugs: *_Alkylating agents:_* 1. ​**CYCLOPHOSPHAMIDE and** 2. **CHLORAMBUCIL** **​1. CYCLOPHOSPHAMIDE** 1. **Type of substance** 2. **Acrylating properties** 3. **Used to treat** 4. **Administration** 5. **Types of effects** 6. **Causes** 7. **Cats** 8. Side effects 9. What to do if you observe ACROLEIN accumulation? Why? **​2. CHLORAMBUCIL**
**CYCLOPHOSPHAMIDE,** ​**CHLORAMBUCIL** * **Cyclophosphamide is nitrogen mustard** * **DNA alkylating properties** i.e. * it will act mainly on proliferating cells. * **They can be used to treat lymphoma i**.e. * also **antineoplastic agents.** * It is applied either **orally, i/v** in form of infusion. * They have **GI side effects and bone marrow side effects.** * They will cause **thrombocytopenia** and **lymphocytopenia** * and this is why you must check the number of white blood cells. * If it is **low, then you postpone the therapy.** * In the case of **cats**, if the white blood cell number is \<2 giga/liter, you cannot start therapy. * Other **side effects** include the **whiskers falling out.** * Another side effect includes **hemorrhagic cystitis** due to the fact that the **byproduct** of this drug is **ACROLEIN.** * **This will be eliminated by urin**e, cats are not as sensitive to this than the dogs. * If you observe the acrolein accumulation, you can **administer FUROSEMIDE** which is a diuretic i.e. * it will **dilute the urine.** * These agents are mainly used orally and not only as autoimmune disorders, but also as antineoplastics. * These are better to use in cats in comparison to dogs. 2. **CHLORAMBUCIL** will have the same mechanism of action and are **applied orally.**
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26: ANTIHISTAMINES Drugs: *_Glucocorticoids_* 1. *_Mechanism of action_* 2. *_Dose dependent or not_* 3. *_Name drug_* 4. *_From anti inflammatory drug to immunosuppressant?_* 5. *_Side effects_* 6. *_Interleikins_*
*_Glucocorticoids:_* * **These can have an** * **anti-inflammatory,** * **immunosuppressive,** * **anti-shock or** * neuroprotective action * which is dose-dependent. * As an anti-inflammatory, **PREDNISOLONE** can be used at 0.5-1 mg/kg but if you **double or table this dose**, it can be used a s an **immunosuppressant** also. * The side effects include * **delayed wound healing,** * **skin thinning,** * **alopecia,** * **polyurea,** * **polydipsia diuresis increase,** * **muscle atrophy (weakness),** * **gross retardation and** * **osteoporosis due to the fact that the calcium absorption is lowered.** * They also influence certain **interleukins** also and because they **act against lymphocytes,** in the case of **lymphoma**, their application is proven.
32
26: ANTIHISTAMINES Drugs: *_Cytokine gene expression inhibitors:_*
*_Cytokine gene expression inhibitors:_* These are calcineurin-inhibitors just like 1. **CYCLOSPORINE,** 2. **TACROLIMUS,** 3. **PIMECROLIMUS.** **Calcineurin** is responsible for the **dephosphorylation of NFAT** (nuclear factor of activated T-cells). This means that in the **nucleus**, there will be the **transcription of IL-2** which will produce these cells. If **calcineurin is blocked,** the **T-cell number** will be **reduced.**
33
26: ANTIHISTAMINES Drugs: Cytokine gene expression inhibitors: **CYCLOSPORINE**, 1. Interfere with 2. Inhibiting 3. Type of drug (tablet, suspension etc) 4. Bioavailability 5. Cat vs Dog dose 6. Therapeutic indications 7. Side effects 8. With or without food 9. In humans - side effect 10. Negligable side effect in dogs and cats 11. Side effect due to metabolic function 12. Cyclosporine is combined with?
Cyclosporine works primarily to: * Interfere with **T-lymphocyte activation** * **Proliferation** by **inhibiting** the **production** of * **IL-2.** * It is administered **orally**, * mainly **emulsion** and **microemulsion** because the **bioavailability is 0.3.** * If it is **not** administered as a **microemulsion**, there will be a **reduced bioavailability.** * In cats, we apply a higher dose (7 mg/kg) than in dogs (5 mg/kg). * Local application is also possible. * Therapeutic indication includes * Autoimmune diseases: * lupus, * pemphigus, * KCS (applied locally), * AIHA (autoimmune mediated hemolytic anaemia); * Atopic dermatitis * IBD (inflammatory bowel disease). * The **side effects** include: **vomiting** **emesis**. * It is better to apply with food but, the food will reduce the absorption of the drug i.e. * administer with a small amount of food only. * In humans, there is liver toxicity and kidney problem * however, hepatotoxicity is negligible in dogs and cats. * **Alopecia** can occur as well as **gingival hyperplasia** * due to the fact that the metabolic function of the gingival fibroblast will be influenced through IL-6 level change i.e. * immune response but it is still questionable. * Cyclosporine is frequently combined with **PREDNISOLONE** i.e. * glucocorticoid cyclosporine combination is very frequent.
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26: ANTIHISTAMINES Drugs: Cytokine gene expression inhibitors: TACROLIMUS 1. Tacrolimus vs Cyclosporine 2. Toxicity 3. Local application 4. Use it to treat 5. What happens if you apply it for approx 1 year 6. What is important when applied for topical use?
* Tacrolimus is **500 times more active t**han cyclosporine. * The **toxicity is increased** and **local application** is possible. * You can use it to treat: * **atopic dermatitis,** * **lupus** * **pemphigus.** * If this drug is applied for approx. one year, * **melanomas** can develop, i.e. for **humans**, * **Important** to **wear rubber gloves** when using this drug for **topical application.**
35
26: ANTIHISTAMINES Drugs: Cytokine gene expression inhibitors: **PIMECROLIMUS** 1. Used for 2. What to apply for KCS 3. Which is the best and why
* Pimecrolimus is used for: * **atopic dermatitis** * **KCS**. * You can apply for KCS: * **artificial tears,** * **parasympathomimetic** * **pimecrolimus/cyclosporine .** * The **best to use is pimecrolimus** as it is an **immunosuppressant** and **KCS is an autoimmune disease**
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***_27-28: PHARMACOLOGY OF THE RESPIRATORY TRACT:_*** These drugs will be able to treat what in which species?
These drugs will be able to treat * **Asthma** in cats, * **RAO** (recurrent airway obstruction) in **horses** * **Eosinophilic bronchitis** in dogs.
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***_27-28: PHARMACOLOGY OF THE RESPIRATORY TRACT:_*** *_Pathophysiology of asthma:_* 1. *_Asthma is characterized by_* 2. *_This leads to_* 3. *_And causes_* 4. *_2 types of bronchioconstrictions_* 5. *_Acute or chronic asthma_* 6. *_Asthma - type of disease_* 7. *_Aggregating factors regarding inflammatory aspect of asthma_* 8. *_RAO_* 9. *_COPD_* 10. *_COPD divided into 2 frequently ovrelaping diseases_*
* **Asthma** is a **complex disease** that is characterized by * **airway inflammation,** * which leads to airway **hyperresponsiveness** and in turn, * that **causes symptomatic bronchoconstriction.** * There is a **reversible part of bronchoconstriction** that characterizes * The **acute asthmatic reaction** * **Chronic inflammation** can **induce airway remodeling** * which causes it to become **irreversible**. * **Asthma** is both an * **obstructive lung disease** * **Inflammatory disease.** * The obstructive component is characterized by * **bronchoconstriction**. * In terms of the **inflammatory aspect of asthma**, it will be marked by **aggregating factors s**uch as * **airway oedema,** * **goblet-cell hyperplasia,** * **mucus secretion** * infiltration by a **wide variety** of **immune** and **inflammatory** **cells** that **release** a number of associated **cytokines.** * **RAO: recurrent airway obstruction.** * This is characterised as **asthma in horses.** * **COPD: Chronic obstructive pulmonary disease** * **​D**escribes a **spectrum of disorders** that r**esults in obstructive lung disease**. * **COPD** is caused by an **abnormal inflammatory** **response** to an **inhaled environmental insult**. * COPD is divided into **two frequently overlapping Diseases:** 1. **Pulmonary emphysema** 1. emphysema refers to **alveolar enlargement** caused by THE **destruction of alveolar walls** 2. **Chronic bronchitis.** , 1. Chronic bronchitis is a **clinical diagnosis** made on the **basis of a chronic cough.**
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27-28: PHARMACOLOGY OF THE RESPIRATORY TRACT: *_Physiology of airway smooth muscle contraction:_*: 1. What causes bronchodilation? 2. What causes bronchoconstriction? 3. Airway smooth muscle cells express which receptors? 4. The receptors are activated by? 5. In order to induce bronchodilation we administer? 6. In order to induce bronchoconstriction we administer?
* **In the airways,** * **sympathetic (adrenergic) tone causes** * **bronchodilation** and * **parasympathetic (cholinergic) tone causes** * **bronchoconstriction.** * **Airway smooth muscle cells** express * **β2-adrenergic receptors**. * β2-adrenergic receptors are **activated** by * **Adrenalin** (beta-2-receptor agonist), * which is **secreted by the adrenal medul**la and causes * **bronchodilation**. * **Airway smooth muscle cells** also express * **muscarinic receptors**, * especially the **excitatory M3 subtype** of **muscarinic receptors.** * Upon **stimulation via cholinergic drug**s, these receptors * **induce bronchoconstriction.** * All in all, * in order **induce bronchodilation**, we administer * **parasympatholytics** (**anticholinergics**). * **sympathomimetics** (beta-2-agonists) or * In order to **induce** **bronchoconstriction**, * we **administer parasympathomimetics (cholinergics).**
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27-28: PHARMACOLOGY OF THE RESPIRATORY TRACT: *_Mast cells and leukotrienes:_* 1. Mast cell degranulation produces ? 2. Histamine released from the mast cells promotes? 3. Leading to? 4. Mast cells also release? 5. Essential to the pathophysiology of ASTHMA? 6. Because? 7. How to alleviate asthma causing bronchodilator? 8. An alternative way to inhibit the histamine release from the mast cells? 9. This will prevent?
* **Acutely**, mast-cell degranulation produces * **bronchoconstriction** and * **airway inflammation.** * Histamine released by the mast cells promotes * capillary leakage, * leading to airway edema. * Mast cells also release * **leukotriene** **C4** (LTC4), which is * subsequently converted into **LTD4** and **LTE4**. * These 3 leukotrienes, = **cysteinyl leukotrienes**, are **central to the pathophysiology of asthma** because **they induce marked bronchoconstriction.** * If we administer **leukotriene antagonists,** we can cause * **bronchodilation** and **alleviating asthma.** * We can also **sterilize** the mast cell in order to inhibit the **histamine release** and this will **prevent** * **capillary leakage i.e. airway oedema.**
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27-28: PHARMACOLOGY OF THE RESPIRATORY TRACT: ***_Drugs acting on the respiratory system:_***
1. Bronchodilators 2. Sympathomimetics: 1. Long acting 2. Short acting 3. Parasympatholytics: 4. *_Methylxanthine derivatives:_* 5. Respiratory antiinflammatory drugs 6. Inhalation glucocorticoids 7. Chromanes: 8. Leukotriene antagonists: 9. Antitussives: 10. Mucolytics: 11. Expectorants:
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27-28: PHARMACOLOGY OF THE RESPIRATORY SYSTEM ***_Drugs acting on the respiratory system:_*** ***_1. Bronchodilators_*** 1. Indication include? 2. Drugs can be? 3. Mechanism of action include?
* Their indications include * **Anaphylaxis** * **Allergic bronchitis** (Ca) * **Asthma** (Fe) * **RAO** (horse) * **Pulmonary edema** * **Pneumonia** * **Pleural effusion** * Excess fluid around the lung * **Pneumothorax** * When air escapes and gathers around the lung and adds pressure i.e. * **collapsed lung.** * **Tracheal collapse** * **Weakened cartilage** in a string of trachea * **Hypoplasia**. These can be either: 1. **Sympathomimetic** (specific or non-specific), 2. **Anticholinergic** substances, or 3. **XYLAZINE** derivatives. * Their mechanism of action includes either * **Dilation** via **an elevation in cAMP** levels, or * **Block phosphodiesterase** i.e. * **indirectly** **block cAMP levels.** * We can also **block acetylcholine** which is **responsible** for **bronchoconstriction** i.e. * this **antagonism will cause bronchodilation.**
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27-28: PHARMACOLOGY OF THE RESPIRATORY SYSTEM Drugs acting on the respiratory system: **2. Sympathomimetics:**
**Sympathomimetics:** * These act mainly on the **beta-2-receptors** to **convert** **ATP** to **cAMP** via the **adenylate cyclase enzyme** which leads to **bronchodilation.** * The **adverse effects** brought on by **adrenergic agonists** are minimized by **inhalant delivery.** * They can be either **non-specific** or **specific**. * The **non-specific sympathomimetics include** 1. **ADRENALINE,** 2. **ISOPROTERENOL,** 3. **EPHEDRINE.** * These are **non-specific** as they act on **beta-1** and **alpha-1** receptors as well as **beta-2-receptors.**
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27-28: PHARMACOLOGY OF THE RESPIRATORY SYSTEM Drugs acting on the respiratory system: 2. Sympathomimetics: ADRENALINE At which receptor does express Bronchodilation? When is it used? Administration in cats? Used in combination with? To do what? Also used to ? in bleeding
Adrenaline: * **Bronchodilation at β2 receptors** (and other receptors). * They are **only used in life-threatening cases** (e.g. **anaphylaxis** - also treated with **antihistamines** and **glucocorticoids**). * Their dose is 0.1-0.5 mg/dog. * In the **cat** it is administered **i/v, i/m** or **intratracheal** and, in case of **cardiac stop, intracardially.** * It is also used in **combination** with **LIDOCAINE** to **prolong the action of this local anaesthetic** and to **avoid the systemic effects of lidocaine.** * It is also used to c**onstrict the blood vessels** i.e. * in **bleeding**.
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27-28: PHARMACOLOGY OF THE RESPIRATORY SYSTEM Drugs acting on the respiratory system: 2. Sympathomimetics: ISOPROTENOL
Isoproterenol: * **Similar to adrenaline** but it acts on the * **beta-1** and * **beta-2-**receptors only. * It is **applied in infusion.**
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27-28: PHARMACOLOGY OF THE RESPIRATORY SYSTEM Drugs acting on the respiratory system: 2. Sympathomimetics: EPHEDRINE
Ephedrine (Bronchopect A.U.V.): * **Directly** and **indirectly**, acting **sympathomimetic.** * **It has several mild side effects.** * It is a **bronchodilator** (also has other indications). * It causes **tachyphylaxis**. * Its dose is 1-2 mg/kg orally BID-TID. * This dose must be **increased within days** in order to have the same biological effect. * It acts on the * **beta-1,** * **beta-2** and * **alpha-1** receptors **at the same time.**
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27-28: PHARMACOLOGY OF THE RESPIRATORY SYSTEM Drugs acting on the respiratory system: Drug/receptor interaction Adrenalin Ephedrine Isoproterenol
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27-28: PHARMACOLOGY OF THE RESPIRATORY SYSTEM Drugs acting on the respiratory system: 1. Sympathomimetics 2. Specific sympathomimetic 3. Receptor 4. Selectiveness 5. Side effects 6. Contra indication 7. Broken up into?
* The specific sympathomimetics are: * beta-2 agonists. * Bronchodilators at the β2 * Receptors (and have a variable β1 receptorial effect). * These are **not selective** i.e. * they will have an effect on **beta-1-receptors** also which has a **positive inotropic** and **chronotropic** **effect** on the **heart** i.e. the side effects include * **tachycardia,** * **restlessness,** * **tremors** * **Decreased uterine contraction.** * Its **contraindications** include * **congestive heart failure,** * **arrhythmia** and * **decreased mast cell degranulation.** * They can be broken up into * **short**- (1-4 hours) and * **long-acting** (6-12 hours).
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27-28: PHARMACOLOGY OF THE RESPIRATORY SYSTEM Drugs acting on the respiratory system: 1. The short-acting specific sympathomimetics include 2. Ratio receptor 3. Safety 4. Side effects 5. Oral administration 6. Inhaled administration 7. How to alleviate the broncho construction in asthma atacs
The short-acting specific sympathomimetics include 1. **SALBUTAMOL** * This drug has a **β2:β1** ratio of approx. * **650:1** meaning it is **extremely safe to use** but you cannot **exclude its action on beta-1-receptors** also i.e. * side effects include * **tachycardia,** * **tremors,** * **palpation,** * **excitation** * When administered **orally**, it takes up to **30 mins** to work and when it is * **Inhaled**, it shows effects in **5 minutes.** * These **effects last for 1-4 hours.** * Its dosage, when inhaled, is 100-200 μg/cat and 400-800 μg/horse. * When it is given orally, its dose is 20-60 μg/kg dog, cat and 8 μg/kg horse. * **This is usually the first choice to alleviate bronchoconstriction in an asthamatic attack.**
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27-28: PHARMACOLOGY OF THE RESPIRATORY SYSTEM Drugs acting on the respiratory system: 1. Long-acting specific sympathomimetics include 2. Isoprotrenol and ephedrine can cause 3. Beta-2-adrenoreceptor agonist cause 4. Alpha-adreboreceptor activity causes 5. Adrenergic agonist can all cause
1. **TERBUTALINE,** 2. **CLENBUTEROL,** 3. **SALMETEROL.** * **Isoproterenol and Ephedrine** (beta-1-receptor activity) can cause * **cardiac effects** including * **tachycardia** and * **arrhythmias**. * **Beta-2-adrenoreceptor agonists** cause * **skeletal muscle tremors.** * **Alpha-adrenoreceptor activity** causes * **vasoconstriction** and * **hypertension**. * **Adrenergic agonists** can all cause * **tachycardia**. * Again, these effects are **minimized by inhalant delivery**
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27-28: PHARMACOLOGY OF THE RESPIRATORY SYSTEM Drugs acting on the respiratory system: TERBUTALINE 1. Specificity 2. Duration of action 3. Dose 4. Administration 5. Used for 6. Type of animals 7. Pulse above 200/min indicates
*_Terbutaline (Bricanyl®)_* * **Less specific** * Acts for **6-8 hours.** * Its dose is 0.312-0.625 mg/cat and 0.625-5 mg/dog **orally** **TID**. * It is administered **subcutaneously**, **i/v** or **inhaled**. * It is used for **feline asthma**, **organophosphate toxicosis**: * 5-7 puffs (auscultation! → 240/min) i.e. * do not apply again so easily. * It is usually used in small animals e.g. cats. * If the pulse is above **200/min,** then it is an indication that **you applied a higher dose than necessary.**
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27-28: PHARMACOLOGY OF THE RESPIRATORY SYSTEM Drugs acting on the respiratory system: **CLENBUTEROL** **Specoficity** **duration of action** **Less effective in** **Probibited = in case of**
* **Less specific** * **Action of** 6-8 hours. * It is **less effective in companion animal**s but is **frequently used in horses** (1-3 μg/kg orally). * Its **beta-2:beta-1** receptor ratio is * **4:1.** * It is **less effective in companion animals.** * It is **prohibited to administer in food-producing animal**s * because they cause the **meat to have less fat content** (this is forbidden), and racehorses because this is a doping agent.
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27-28: PHARMACOLOGY OF THE RESPIRATORY SYSTEM Drugs acting on the respiratory system: **SALMETEROL** * **specificity** * **duration** * **economics**
*_Salmeterol (Serevent®)_* * is the **most specific (50000:1**) * and also has the l**ongest duration** (10 mins-12 hours). * Unfortunately, it is also the **most expensive.** * Its dosage is 200 μg/horse.
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27-28: PHARMACOLOGY OF THE RESPIRATORY SYSTEM Drugs acting on the respiratory system: *_Parasympatholytics:_*
*_Parasympatholytics:_* * These are **acetylcholine antagonists (M3-receptors).** * They cause * **bronchodilation** and * **decreased mucus secretion.** * Their **side effects** include * **tachycardia** (because of anticholinergic effect), * **mydriasis**, * **decreased mucociliary clearance** (helps the body to remove irritants and contaminants) and * **paralytic ileus** (Eq). * Their indications are * **asthma** (Fe), * **horse** RAO an**d** * **organophosphate toxicosis**. * These include 1. **ATROPINE,** 2. **GLYCOPYRROLATE,** 3. **IPRATROPIUM.** *
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27-28: PHARMACOLOGY OF THE RESPIRATORY SYSTEM Drugs acting on the respiratory system: Parasympatholytics: **ATROPINE** 1. **Type of drug** 2. **Administration** 3. **Dose** 4. **Side effects**
*_Atropine_*: * This is a **tertiary amine** i.e. * **crosses the BBB.** * It is mainly administered **sc** or **i/v.** * Its dose is * 0.02-0.04 mg/kg when used for **bronchodilation** (not usually our first choice for this) and * 0.2-2 mg/kg in **organophosphate toxicosis.** * Its **side effects,** as well as what is mentioned above * I**ncludes CNS signs in cats.** *
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27-28: PHARMACOLOGY OF THE RESPIRATORY SYSTEM Drugs acting on the respiratory system: Parasympatholytics: **GLYCOPYROLATE** 1. Duration of action? 2. safety? 3. does it cross BBB? 4. Used in cats?
*_Glycopyrrolate_*: * This drug has a longer action * and is much safer. * It cannot cross the BBB and * can be used in cats.
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27-28: PHARMACOLOGY OF THE RESPIRATORY SYSTEM Drugs acting on the respiratory system: Parasympatholytics: **IPRATROPONIUM** 1. Type of drug 2. route of administration 3. Does it cross BBB 4. Usefull in 5. Onset of action 6. Combination? 1. ​Causes?
Ipratropium (Atrovent®): * This drug is a **quaternary amine.** * For administration, **only inhalation is safe.** * It does **not cross BBB.** * It is **useful for mucociliary clearance.** * This drug's **onset of action is slower** (15-30 mins) * but it can **last for up to 6 hours** * Can be administered in **combination with Salbutamol**, * this can cause a **quick onset** and a **prolonged effect at the same time.**
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27-28: PHARMACOLOGY OF THE RESPIRATORY SYSTEM Drugs acting on the respiratory system: Parasympatholytics: ***_Methylxanthine derivatives:_***
*_Methylxanthine derivatives:_* 1. **CAFFEINE,** 2. **_THEOPHYLLINE,_** 3. **THEOBROMINE.**
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27-28: PHARMACOLOGY OF THE RESPIRATORY SYSTEM Drugs acting on the respiratory system: Parasympatholytics: **Methylxanthine derivatives:**
Methylxanthine derivatives: 1. CAFFEINE, 2. THEOPHYLLINE, 3. THEOBROMINE. **Their mechanism of action** is that they are **phosphodiesterase inhibitors** i.e * **cAMP level increases** * **leading to bronchodilation**. * They have various **pharmacological effects.** * Their **pharmacokinetics** include * **good absorption,** * **enterohepatic** circulation (→ activated carbon). * Their **side effects** are due to their * **small therapeutic index**, * Leading to **cardiovascular** and * **Gastrointestinal diuresis**. * Their **indications** are * **Bronchitis**, * **Pneumonia** etc. * They are **administered i/v** or **orally** as **retard tablets.**
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27-28: PHARMACOLOGY OF THE RESPIRATORY SYSTEM Drugs acting on the respiratory system: Parasympatholytics: Methylxanthine derivatives: **Derivatives of theophylline** 1. **Include** 2. **Therapeutic use** 3. **Adverse effect include**
* Derivatives of theophylline **include** 1. **AMINOPHYLLINE,** 2. **PROPEMTOPHYLLINE,** 3. **PENTOXIFYLLINE.** * Their **therapeutic uses** are to treat * **Acute** or **chronic** **asthma** that is **unresponsive to β-adrenoceptor agonists;** * they can be a**dministered prophylactically.** * These agents are also used to treat **chronic obstructive lung disease (COPD)** and **emphysema**. Their adverse effects include * **arrhythmias,** * **nervousness,** * **vomiting** * **gastrointestinal bleeding.**
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27-28: PHARMACOLOGY OF THE RESPIRATORY SYSTEM Drugs acting on the respiratory system: Parasympatholytics: ***_2. Respiratory antiinflammatory drugs:_*** 1. Indication 2. Drugs can be either
* Their indications include * **Asthma and** * **RAO.** * They can be either * **inhalation glucocorticoids** * **chromanes** * **leukotriene antagonists**
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27-28: PHARMACOLOGY OF THE RESPIRATORY SYSTEM Drugs acting on the respiratory system: Parasympatholytics: ***_Inhalation glucocorticoids:_* ​** 1. Function 2. Cause inhibition of ? Leading to? 3. IL-4 and IL-5 cause ? 4. Is systemic application possible 5. Side effects 6. Inhalation? 7. Drugs?
*_Inhalation glucocorticoids:_* * These are the **most effective anti-inflammatories.** * They **cause inhibition** of the **expression of several genes** * which leads to the **decrease of cytokine production** of * **IL-4 and IL-5.** * They cause **eosinophil apoptosis** * Due to **decreased mucus production** and * An **increasing diameter.** * **Systemic application is possible** * **​**but this has **several side effects** **including** in the * **HT-HP axis,** * **stomach,** * **liver etc.** * Because of this, they are mainly **inhaled** for **less frequent side effects.** * **When inhaled**, they affect * **15-20% airways a**nd * **80-85% pharynx** (due to the first pass effect). ​ 1. ​**BECLOMETHASONE,** 2. **FLUTICASONE.** * ***_Beclomethasone:_*** (14x dexamethasone) 500-1500 g/**horse BID** * *_**Fluticasone**:_* (23x dexamethasone) 100-200 g/**cat BID,** 2000 g/**horse BID**
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27-28: PHARMACOLOGY OF THE RESPIRATORY SYSTEM Drugs acting on the respiratory system: Parasympatholytics: ***_Chromanes_***: 1. Cause inhibition of? Therefor they are? 2. Administration route 3. Used in 4. Drugs 5. Administered?
*_Chromanes_*: * These cause the **inhibition of mast cell degranulation** i.e. * they are **mast cell stabilizers.** * They can be administered **orally** or **inhaled**. * They are **used rarely in cases of asthma.** 1. **Na-CHROMOGLYCATE,** 2. **NEDOCROMIL**. * They are administered * **orally,** * **inhanled** * used as an **eye drop** (externally).
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27-28: PHARMACOLOGY OF THE RESPIRATORY SYSTEM Drugs acting on the respiratory system: Parasympatholytics: *_Leukotriene antagonists:_* 1. What are they? 2. What are they? 3. They convert ? into ? 4. They can cause ? 5. Leukotriene synthesis include? 6. Administration? 7. Leukotriene antagonist include 8. Administration route in case of feline asthma 9. 3 strategies 10. Montelukast, Zafirlukast and Pranlukast are?
*_Leukotriene antagonists:_* * **Leukotriene synthesis inhibitors.** * These are the **final products of the lipoxygenase pathway.** * They **convert arachidonic acid** to **cysteinyl leukotrienes** (LTC4, LTD4, LTE4) * They can cause * **Bronchoconstriction,** * **Mucous production** * **Oedema**. * Leukotriene synthesis inhibitors include 1. **ZILEUTON,** 2. **FENLEUTON** * **Administered orally.** * Leukotriene antagonists include 1. **ZAFIRLUKAST,** 2. **MONTELUKAST.** * These are also given **orally** in cases of feline asthma: 0.5-1 mg/kg SID, BID. * **Inhibition of 5-lipoxygenase** by the drug zileuton **reduces the biosynthesis of leukotrienes.** * **A second strategy** involves **inhibition of the cysteinyl leukotriene receptor CysLT1.** * Montelukast, zafirlukast, and pranlukast are **CysLT1** **receptor antagonists.** * **A third strategy** involving **inhibition of the protein that activates 5-lipoxygenase** (5-lipoxygenase-activating protein or FLAP) is being actively explored.
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27-28: PHARMACOLOGY OF THE RESPIRATORY SYSTEM Drugs acting on the respiratory system: Parasympatholytics: ***_3. Antitussives:_*** 1. What is it 2. What to observe 3. What to administer for a dry cough 4. Which senter do we block 5. What to apply for a wet cough and why? 6. The pathway of a cough? 7. Peripheral antitussives include 8. Central antitussives include
*_3. Antitussives:_* * Any medicine used to **suppress** or **relieve** **coughing**. * With coughing, you must observe whether the cough is * Wet * Dry. * If it is a **dry cough**, we administer **antitussives**. * This means that we can **block/suppress** the **activity** of the **respiratory center.** * We can either apply * **Mucolytics** * **Expectorants** * if the **cough is wet** * Which will **help to decrease the viscosity** and make it **easier for the animal to cough up**. * Coughing causes an **impulse from the trachea or bronchi** (irritation, inflammation, mechanical, ACE inhibitors etc.) * Which **reaches the afferent sensory neurons** * Which then **reaches the cough center** (medulla oblongata). * **Peripheral antitussives** include: * **mucolytics** * **expectorants** * **bronchodilators** * **coating substances** * **local anesthetics.** * **Central antitussives include morphine derivatives.**
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27-28: PHARMACOLOGY OF THE RESPIRATORY SYSTEM Drugs acting on the respiratory system: Parasympatholytics: **3. Antitussives:** Central antitussives include morphine derivatives.
1. *_**Codeine vs morphine**:_* 1. These have a **better bioavailability orally**. They have 10 times lower analgesic potency and are similar to antitussives. 2. **They rarely have side effects** but in the **cat,** they can cause 1. **excitation**, 2. **convulsions**, 3. **sedation** and 4. **constipation**. 3. Their **dose** is 1-2 mg/kg BID-QID. 2. ***_Dihydrocodeine:_*** 1. *_​_*This is **more effective** but **cannot be administered to cats.** 3. ***_Hydrocodone_*** 4. *_**Butorphanol**:_* 1. This is the **most effective** but **can cause sedation.** 2. It is an **oral product.** 5. ***_Tramadol:_*** Used in **dogs** at 5mg/kg every 6 hours. 6. *_**Dextromethorphan**:_* 1. This is a **δ-receptor,** 2. **non addictive,** 3. **non analgesic.** 4. It is also **safe in cats.** 5. Its **dose** is 1-2 mg/kg orally TID-QID.
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27-28: PHARMACOLOGY OF THE RESPIRATORY SYSTEM Drugs acting on the respiratory system: Parasympatholytics: *_4. **Mucolytics**:_* *_Indication_* *_Mechanism of action_* Drugs
*_4. Mucolytics:_* * The **indications** for these drugs include * **bronchitis,** * **bronchopneumonia,** * **tracheitis,** * **rhinitis,** * **sinusitis and for** * **RAO as adjunctive therapy.** * Their **mechanism of action** is the * **dissolution of the dense, sticky mucus inside the respiratory tract** * which leads to **productive coughing.** * The clinical signs can be more pronounced ( antitussives).
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27-28: PHARMACOLOGY OF THE RESPIRATORY SYSTEM Drugs acting on the respiratory system: Parasympatholytics: **Mucolytic drugs**
1. **N-ACETYLCYSTEINE: (ACC®, Fluimucil®)** * This drug causes the **breaking up disulfide** bonds in **mucoproteins** * which leads to the **dissolution of viscous mucus.** * This leaves a **bad taste and odour.** * ​​​They are administered **orally or inhaled.** * They cause **AB penetration** * Their **dose** is 50 mg/kg **orally** BID, TID. * They are also an **antidote of paracetamol** when **administered i/v.** **CARBOCYSTEINE** These have a similar action, their **oral absorption is better.**
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27-28: PHARMACOLOGY OF THE RESPIRATORY SYSTEM Drugs acting on the respiratory system: Parasympatholytics: **5. Expectorants:**
*_5. Expectorants:_* * These act * **Directly on the mucous membrane of airways** (volatile oils e.g. eucalyptus, thymus, turpentine) or * **Indirectly by stimulating gastric mucous membrane** via **salts** (pl. NH4Cl, NaI) * Ipecacuanha, * Guaifenesin. 1. *_**Bromhexin**:_* 2. *_**Ambroxol**:_* metabolite of bromhexine 3. *_**Dembrexine**:_* horse, longer half-life (iv. → po.) 4. *_**Guaifenesin**:_* This drug does not change the amount of mucous secretion. It enhances ciliary movement (MC ). It can be combined with antitussives.
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27-28: PHARMACOLOGY OF THE RESPIRATORY SYSTEM Drugs acting on the respiratory system: Parasympatholytics: 5. **Expectorants** **BROMHEXIN**
*_**Bromhexin**:_* (Bisolvon A.U.V., Ventipulmin A.U.V.). * This drug has 3 actions. 1. The **first** is the **breaking up of mucopolysaccharides,** **dissolving mucus.** 2. The **second** is **increase the secretion of the serous glands** 3. The **third** is **enhancing ciliary movement.** * These cause **enhancing permeation** of * **Ig-s** * **ABs** * **IgA, IgG levels are increased.** * Their **indications** include * **rhinitis**, * **sinusitis** and * **tracheobronchitis** (but lead to purulent discharge). * Its **dose** is 2 mg/kg **orally** or **subcutaneously** **BID**.