Test 1 Flashcards
(24 cards)
What are the characteristics of glucocorticoids?
- Glucocoritocids are secreted from ADRENAL CORTEX, which is stim from ACTH from the hypophysis (HF), which is then stim from CRF from hypothalamus (HT)
- Gcc can go through membrane, to the glucocorticoid receptor in the cytoplasm.
- > Together they can enter the nucleus of the cell (to impact the genes)
Physiological effects of Glucocorticoids
- It’s a stress hormone - mobilizing hormone
- Inhibits the effect of insulin (antagonist of insulin)
- Stimulate gluconeogenesis (in liver) from proteins and fats
- Ketone bodies produced
- Decrease cellular glucose use -> muscle weakness
Pathological effect of Glucocorticoids
- Muscle weakness, atrophy
- Osteoporosis (bc decreased calcium absorption)
- Delayed wound healing (bc decreased collagen synthesis)
- Alpoecia and thinning of skin
- Decrease growth
- PU/PD
Pharmacological effect of Glucocorticoids
- Antiallergic
- Antiinflammatory
- Antishock
- Immunosuppressive
- Neuroprotective
Mechanism of action of Glucocorticoids
(Cellular damage - membrane phosphorlipids - (By phospholipase A2) - arachidonic acid - (by COX) - PG)
Gcc inhibits PLA2
Antiinflammatory and immunosupressive effects:
- Inhibit PLA2 (Membr. phosphorlipids converting to arachidonic acid, which convert to prostagladins etc)
- COX enzyme expression decreases (which prod. prostagladins)
- Inhib. expression of interleukins (IL-1, IL-2, 3, 4, 5, 6, 10, 12)
- TNF and IFN synth. decreased
- Apoptosis
- Neutrophilia
Antishock:
- Vasoconstiction
- Decrease membrane permeability (enhance microcirculation)
Neuroprotective:
- Trauma will lead to bleeding, which will lead to vasoconstriction
- Ischemia can lead to lipid peroxidation -> ROS released -> apoptosis and necrosis!
However, Gcc will inhibit lipid peroxidation and enhance microcirculation
Active substances (+ effect) of Glucocorticoids
- Cortisol (short)
- Prenisolone (medium)
- Methylprednisolone (medium)
- Betamethasone (long)
- Dexamethasone (Long)
Side effects of Glucocorticoids
- HT - HP - adrenal cortex axis inhibition
- Gastric ulcers (inhib. PG) - treat with omeprazol - gastroprotective)
- Hepatopathy (ALKP increase sign.) - treat with silimarine - hepatoprotective
- Pancreatitis
- Thinning of skin, delayed wound healing, alpoecia
- PU/PD
- Polyphagia
- Glaucoma/cataracta
- Muscle atrophy
- Immunosupression
Systemic usage and indications of Glucocorticoids
Systemic usage:
1) High dosage, once (e.g. omeprazole)
- short term, few side effects
2) ADT (alternate day therapy) (e.g. prednisolone, methylprednisolone)
- every other day (mornings for dogs and evenings for cats)
3) Long acting injections (depot)
- not recommended
- only if tablet can not be administered
Indications:
1) Local use (atropic dermatitis)
2) Single injectable dose
3) Inhalation usage (asthma, RAO)
4) Intraarticular
5) ADT
6) Depot injections
Indications of immunosupression
1) Autoimmune diseases
- lupus, IHA, KCS
2) Hypersensitivity diseases
- Atopic dermatitis, asthma, RAO, Inflammatory bowel disease
3) Transplantation
- Need to supress the immune system to accept new organs if transportation
Immunosupression drugs:
- Antimetabolites
- Purine-analogues:
azathioprine (for autoimmune diseases) - Pyrimidine- analouges:
Leflunomide (rheumatoid arthritis and psoriatic arthritis) - Folic acid antagonists:
Methotrexate (antineoplastic)
Immunosupression drugs:
- Alkylating agents
Cyclophospamide (antineoplastic and autoimmune disorder)
Immunosupression drugs:
- Glucocorticoids
- Cortisol
- Prednisolone
- Methylprednisolone
- Betamethasole
- Dexamathasole
Immunosupression drugs:
- Cytokine gene expression inhibitors
- Cyclosporin: Autoimmune diseases, atopic dermatitis, IBD
- Tacrolimus: more active than cyclosporin, but more toxic! For atopic dermatitis
- Pimecrolimus: more active than cyclosporin, but more toxic! Locally atopic dermatitis, KCS
COX enzymes; function, Location, Constitutive/ induced,
COX- enzymes helps the production of prostagladins and Thromboxane.
COX- 1: physiologic! Located in stomach, kidney and platelets. Always present (constitutive) and is a good enzyme to maintain hemostasis.
Stomach: COX1 are physiologic, and prevents too much acid to be prod. If COX are inhibited too much acid will be produced.
Kidney: COX1 are physiologic, helps maintain normal flow to kidneys (vasodilation). If inhibited kidney will not remain normal flow and kidney will be damaged.
Platelets: COX1 physiologic. Produces thromboxane, so platelets can aggregate in case of trauma. If inhibited longer bleeding time. (So NSAIDs which inhib. COX can be good for thrombotic patients).
COX- 2: is only present during inflammation. Located at macrophages and fibroblasts. Induced during inflammation.
COX- 3: in brain (HT)
For sensation of fever and pain.
Inhib. by paracetamol (analgestic) and methamizole (antipyretic, analgestic) .
COX selectivity
We want drugs with higher affinity to COX-2, since that is the inflammatory enzyme. High COX2:COX1 ratio is good.
Firocoxib (Very selective: safest) Deracoxib Carprofen Meloxicam Ketoprofen Aspirin (Not selective)
Pharmacological effects of NSAIDs
- Antiinflammatory
- Antiendotoxin
- Antipyretic
- Antineoplastic
- Spasmolytic
- Platelet aggregation inhibition
- Analgestic
Phatmacokinetics (er dette viktig tho) of NSAIDs
Absorption: weak acids
Distribution: Extensive albumin binding (Hypoalbuminemia is a consequence)
- Interactions: Don’t combine with other drugs that bind to albumin
- WP: short or no wp in milk.
Metabolism: Mostly glucuronic acid conjugation -> feline sensitivity
Excretion: urine active + inactive
Side effects of NSAIDs:
- GI ulcers (treat with omeprazole)
- Kidney damage
- Platelet aggregation inhibition (aspirin and ketoprofen)
- Hepatotoxicity (Paracetamol and carprofen)
- Allergic reaction
- Methaemoglobinemia (paracetamol in cats)
- Fetal damage
- Placental retention
- Cardiotoxicity
- Cartilage damage (bc aspirin and ketoprofen)
NSAIDs drugs:
1) Aspirin (Dog and farm animals)
can cause:
- Platelet aggregation inhibition
- cartilage damage
2) Ketoprofen
can cause:
- Platelet aggregation inhibition
- cartilage damage
3) Carprofen
can cause:
- hepatotoxicity
4) Meloxicam - Safe in cats!!
- It’s antiendotoxin
5) Deracoxib (dog)
- COX2 selective
6) Firocoxib (dog and horse)
- COX2 selective
and
Etodolac: Safe
Flunixin
can cause:
- Platelet aggregation inhibition
- Antiendotoxic
Paracetamol: NEVER to cats
- COX-3 inhibitor: analgesic, antipyretic (minor analgesic)
can cause:
- Hepatotoxic
- Methaemoglobinaemia (cat)
JAK- inhibitors indications
1) Rheumatoid arthritis
2) Crohn disease
3) Leukemias
4) Alopecia
JAK- inhibitors action
Cytokine binds to cytokine receptors. There will be a phosphorylation of receptors, then STAT will bind to both sides of the receptors. The phosphorylated STAT will go through the nuclear membrane and bind to DNA
JAK- inhibitors drugs: 1
- Indication
- Inhibition
- Pharmacological effects
- Pharmacokinetics
- Side-effects
- Oclacitinib:
Indication: Itching and atopic dermatitis
Inhibits: mainly JAK-1,
IL-2, 4, 6, 13 (allergy and inflam.)
and IL 31 (pruritus)
Pharmacological effects: Antiinflammatory, antiallergic and antipruritus
Pharmacokinetics: Per Os, with food.
- Metabolism in liver
- Can be given with other drugs
Side-effects:
WBC decreased, Cholesterol increased, vomiting and diarrhoea
JAK- inhibitors drugs: 2
- Indication
- Inhibition
- Pharmacological effects
- Pharmacokinetics
- Side-effects
- Lokivetmab
Indication: itching
Inhibition: IL- 31
Pharmacological effects: Antiinflammatory, antiallergic and antipruritus???
Pharmacokinetics: Once a month, SC
Side-effects: Anaphylactic shock and allergic reaction
Classes of antihistamine:
1st generation: Prometazine Hydroxyzine Chloropyramin (mangler et par her tho)
2nd generation:
Lorataadine,
cetirizine,
levocetirizine