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Eicosanoids
Subatances produced by the tissues that produce the signs of inflammation and start the healing process.
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Dosage Form
- -Tablets
- -Solutions
- -Capsules
- -Liniment
- -Caplets
- -Creams
- -Etc.
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Dosage
- The amount any patient should be given over time
- ex. 5ml/kg, PO, b.i.d.
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Analgesics
Drugs that reduce the perception of pain without significant loss of other sensations.
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Dose
- The amount of a drug administered at one time.
- ex. 2 tablets, 1.5 mls, 2 Tbl
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Arachidonic Acid Pathway
- The domino effect caused when tissue is traumatized.
- Trauma occurs
- The Phospholipids of the cell membrane are converted into Arachidonic Acid by the enzyme Phospholipase.
- AA is then acted on by either cyclooxygenase (COX) to make prostaglandins and thromboxanes (which are eicosanoids), or lipoxygenase (LOX) to make leukotrienes.
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Corticosteroids
- Thchnically adrenocorticosteroids
- Produced by cortex of the Adrenal gland
- mineralocorticoids and glucocorticoids
- Inhibits Phospholipase/stabilizes phospholipid membranes
-
Addison's Dz
- Hypoadrenocorticism
- Low functioning adrenal gland cortex which leads to Hyperkalemia (too much K in blood stream) and hyponatremia (too little Na in blood stream) due to lack of aldosterone production.
- Tx w/ mineralocorticoids.
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Glucocorticoid production
- Hypothalamus releases corticotropin releasing factor (CRF)
- Anterior pituitary gland releases adrenocorticotropic hormone (ACTH)
- Adrenal glands release glucocorticoids
- Glucocorticoids block Phospholipase, stabilize Phospholipid membranes, and block COX
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Hydrocortisone
- A glucocorticoid a.k.a. cortisol
- Provides needed systemic effect on body
- Provides negative feedback to Hypothalamus and anterior pituitary gland
-
Cortisone
- A glucocorticoid
- Provides needed systemic effect on body
- Provides negative feedback to Hypothalamus and anterior pituitary gland
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Exogenous glucocorticoids
- Administered drugs used to reduce inflammation and have the same negative-feedback effect on the hypothalamus and pituitary gland as endogenous cortisol
- The negative feedback to the pituitary gland can result in side effects.
- Ex. prednisone, prednisolone, methylprednisolone
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Short-acting glucocorticoid
- Exerts an antiinflammitory effect for less than 12 hrs.
- ex. Hydrocortisone common in topical
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Intermediate-acting glucocordicoids
- exert their boilogic activity for 12-36 hrs.
- Includes the "preds" (prednisone, prednisolone, methylprednisolone, and isoflupredone) and triamcinolone.
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Signs of inflammation
- Redness
- Heat
- Edema
- Pain
- Loss of function
-
-
Inflammation
- Increases blood flow to injured area
- Increases Leukocyte migration
- Increases phagocytosis activity
- acute vs. cronic
-
2 classes of antiinflammitories
- steroidal (corticosteroids)
- nonsteroidal (NSAIDs)
-
NSAIDs
- Block COX (Cyclooxygenase) and (LOX) Lipooxygenase
- reducing production of Prostaglandins, thromboxane, and leukotrienes
-
Corticosteroids and NSAIDs also decrease production of several other compounds...
- Histamine
- Kinins
- Substance P
- Superoxide Radicals
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Mineralocorticoids
- Affect minerals in the body (Na, K, & other electrolytes)
- Involved in water and electrolyte balance in body
- little-no antiinflammitory effect
- Aldosterone - promotes Na reabsorption (K excretion)
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Glucocorticoids
- Antiinflammitory effect-inhibits Phospholipsae (COX)
- Decreasing production of Prostaglandins, and leukotrienes involved w/ inflammation
- Inhibit production of mediators involved in toxic & immune-mediated cellular damage (preventing allergic reactions)
- Reduce production of cell factors that cause increased vascular permiability of capillaries (reduce swelling)
- Increases blood-glucose level (enhanses deposition of glycogen in liver)
- On negitive feedback loop w/ Hypothalamus and Pituitary gland (CRF & ACTH)
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-
NSAIDs Ex.
- Aspirin
- Rimadyl
- Deramaxx
- Metacam
-
Cortisone
must be converted by the liver to hydrocortisone
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Prednisone
Must be converted by the liver to prednisolone
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Long-acting glucocorticoids
- Exert activity for more than 48 hrs.
- dexamethasone
- betamethasone
- flumethasone
-
Aqueos solution glucocorticoids
- Made water soluable by combining with salt
- Can be given in Lg doses IV w/ less risk of adverse reactions than alcohol solutions or suspensions.
-
Alcohol solution glucocorticoids
Don't need salt to dissolve
-
Suspension glucocorticoids
- Opaque
- Need resuspension (ex shaking) before use
- Terms: acetate, diacetate, pivalate, acetonide, valerate
- Longer release (Lg crystals- dissolve)
- SQ
- must be stored in temp. range
-
Negative effects of glucocorticoids
- Delays healing of wounds
- Greater opportunity for infection
- Muscle wasting/atrophy, thin skin, alopecia, osteoporosis, pot belly from weakening of abd. muscles due to catabolism
- Can induce abortion/parturition
- Hyperglycemia threat to diabetics
- Possibility of developing Cushings or Addisons
- Alters hemogram-stress leukogram
-
Glucocorticoid uses
- Non-infectious inflammation
- Allergies, allergic reactions
- Pruritis
- Immune-mediated disease
- Anaphylactic shock
- Adrenal insufficiency (Addison’s)
- Spinal cord trauma
- Neoplasia
- AFTER diagnosis is made!!
-
Glucocorticoid routs
- PO
- IV (SLOW)
- IM
- Topical
- Intra-articular
- Intralesional
- Subconjunctival
-
Glucocorticoid Contradictions
- Undiagnosed conditions
- Fungal infections
- Modified live virus vaccine
- Cornial ulcer
- Pregnant animals
- Horses-laminitis!
- Immature animal
- Liver Dz
-
Glucocorticoid effected leukogram
- Cause WBCs to move into tissues (Ex lungs, spleen) and out of systemic circulation
- Lower Lymphocytes, Monocytes, and Eosinophils. (-penia)
- Higher Neutrophils (neutrophilia) and platelets
- Like a stress leukogram
-
catabolism
- Breakdown of proteins for amino acids for gluconeogenisis
- Over time can cause muscle wasting, thinning of skin, alopecia, & decreased bone density.
- "Pot belly"
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Corneal Ulcer
Contradiction for use of glucocorticoids which may deepen the ulcer and slow its healing.
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Opthalmic corticosteroids - horses
normal fungus fought off by the cell-mediated immunity may cause infection with steroids and a scratch.
-
diabetes mellitus + glucocorticoids
may require an increase in insulin dose if given for an extended period
-
Hyperadrenocorticism or Cushing's
- Overuse of exogenous glucocorticoids (iatrogenic) or overproduction by the body.
- Alopetia
- Thin skin
- Muscle atrophy
- Pot belly
- Polyuria
- Polydipsia
- polyphagia
-
Hypoadrenocorticism or Addison's
- Can be caused by stopping steroid use "cold turkey" production of CRF and ACTH will resume but the adrenal gland is unable to respond
- Weakness
- Lethargy
- Vomiting
- Diarrhea
- Death in severe cases
-
Steroid potency low to high
- Cortisone
- Hydrocortisone
- Prednisone
- Methylprednisolone
- Dexamethasone
- Betamethasone
-
methylprednisolone sodium succinate
SoluMedrol ®
-
Rules of thumb for glucocorticoids
- Use NSAIDs instead if avalible without contradictions
- Avoid continuous use (adrenal atrophy)
- Use intermediate acting for systemic administration
- Aim for smallest effective dose then reduce (alternate day)
- When used over extended period reduce gradually
-
Hydrophilic glucocorticoids
- Very soluble
- Ok admin. IV
- released for only mins. after injection
- Succinate
- Phosphate
- May be given in Lg doses (shock, trauma)
- Ex.SoluMedrol ® (methylprednisolone sodium succinate
-
Moderately soluble glucocorticoids
- released days - weeks after
- Lg crystals Suspended in liquid (SHAKE)
- Do NOT give IV!!
- Acetate
- Pivalate
- Ex. DepoMedrol® (methylprednisolone acetate)
-
Poorly Soluble glucocorticoids
- Lipophilic
- Released for weeks
- Acetonide
- Topical preps
- Ex. Vetalog® (triamcinolone acetonide)
-
NSAIDs vs steroids
- block further down AA pathway, less effective
- Many same steroidal effects w/ less adverse effects
- not good for severe bone or intense pain
- Do NOT use NSAIDs & CCS together!!
-
COX 1
- Exists in stomach, Kidney, and other organs
- Produces prostiglandins for physiological regulation
- In stomach promotes protective mucus layer, good blood flow, decrease acidity
- In kidney counteracts vasoconstriction
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COX 2
Enzyme, produces prosteglandins associated w/ signs of inflammation
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NSAID side effects
- Diarrhea
- Anorexia
- Lethargy
- Melina
- GI Ulcers
- Hepatotoxic
- Increased bleeding tendency
- Affects renal prostiglandins: lower blood flow, low GFR, papillary necrosis (lack of O2
- Never w/ dehydrated or hypotensive shock!!
- Caution in geriatrics
-
All NSAIDs are...
- Anti-inflammitory
- Antipyretics (fever reducer)
- Analgesics
-
Some NSAIDs
- Aspirin
- Phenylbutazone
- Flunixin meglimine
- Carprofen
- Meloxicam
- Etodolac
- Deracoxib
- Tepaxolin
-
Aspirin
- Salicylic Acid
- Nonselective NSAID
- Terminate use 1 wk prior to Sx
- Cats extremely sensitive
- Uses: arthritis, lower PLT aggrigation, decrease thromboembolism in HW Tx, decrease thrombi in cats w/ hypertrophic cardiomyopothy
- SE: Vom.,gastric bleeding, increased clotting time
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Phenylbutazone
- Bute
- Common use w/ horses
- Lots of interactions
- IV and PO
- Highly protein bound
- Uses: osteoarthritis, colic, lameness, mild-mod pain
- SE: GI bleeding, GI upset, GI ulcers, renal necrosis, bone marrow supression (rare)
- Tissue necrosis if injected perivascular!!!!!
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Flunixin meglumine
- Banamine®
- Horses & calves
- more potent than Bute good analgesic
- Anti-endotoxic effect
- IV, IM, PO
- Uses: Colic, shock, corneal ulcers, keratitis, uvelitis
- SE: GI upset, neprotoxicity
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Carprofen
- Rimadyl®
- Selective
- Less ulcerogenic potential
- Analgesia in Sx
- Dogs & cats
- Injectable & PO
- SID or BID
- Uses: DJD (degenerative joint Dz), post op pain
- SE: GI ulcers, bleeding
-
Etodolac
- EtoGesic®
- nonselective
- dogs
- Uses: osteoarthritis
- SE: anorexia, V/D, lethargy, liver, DRY EYE!!
-
Meloxicam
- Metacam®
- Selective
- Dogs
- Oral suspension SID
- SE: V/D
-
Deracoxib
- Deramaxx®
- Selective
- Dogs
- Uses: post-op pain & oseoarthritis
- SID chewable tab
-
Ketoprofen
- Ketofen®
- COX & LOX inhibition
- Dogs, horses, & cats
- Uses: pain w/ musculoskelital dz, post-op pain
- SE: GI bleeding, GI ulcers, renal dysfunction, generalized bleeding
- Naproxen, Aleve, Orudis KT Very toxic in dogs!!!
-
Tepoxalin
- Zubrin®
- COX & LOX inhibition
- Uses: osteoarthritis in dogs
- Rapidly dissolving tablet SID PO
-
Firocoxib
- Previcox®
- Selective
- Used for osteoarthritis in dogs
-
Hyaluronic acid
- Legend®, and others
- component of sinovial fluid, acts as lubricant
- Dogs & horses
- IV, intra-articular, IM in dogs
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Polysulfated glycoaminoglycans/ PSGAGS
- Adequan®
- Chondroprotective, anti-inflammitory
- Used for arthritis in horses (IA &IM) and dogs (IM)
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DIMETHYLSULFOXIDE (DMSO)
- Clear liquid solvent
- Scavenges free radicals
- Used as carried to deliver drugs through skin
- Approved use:Topically to decrease swelling in horses & dogs
- SE: garlic taste, skin irritation, teratogenic
- WEAR GLOVES!!!
-
Cosequin® (glucosamine, chondroitin sulfate, manganese sulfate)
- Neutroceutical
- Precursor of cartilage matrix
- Repairs damaged cartilage
-
Acetaminophen
- Tylenol TM
- Not NSAID
- Antipyretic, analgesic, not anti-inflammitory
- No GI upset, ulcers, or PLT clumping
- Not metabolized well in cats 500mg = death
-
Prosteglandin E
- Increases gut mucous layer
- Decreases HCL production
- Increases gut motility
- improves blood flow to gut
- Parasympathetic
-
Oxyntic (parietal) cells have receptors and are stimulated to produce HCl by:
- Histamine
- Gastrin
- Acetylcholine
-
Histamine is released by:
- Mast cells and Basophils in inflammitory response
- Mast cell toumors (Boxers)
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Emetics
- Induce Vomiting
- To reduce absorption of ingested toxin
- Must be relyable and work quickly
-
Vomiting reflex stimulated by:
- Direct stimulation of EC (emetic center)
- Vagus Nerve
- Chemoreceptor Triggor Zone (CRTZ)
- Inner ear nerves
- Higher brain centers
-
Neuron receptors for emisis
- Seratonin Rc.
- Alpha Rc.
- Block these to control emisis
- Cats especially sensitive to the stimulation of these
-
CRTZ stimulant side effects
Toxins associated in renal failure
Excessive ketones in diabetes mellitus
Bacterial or metabolic toxins
-
Dopaminergic antagonists or antidopaminergic
drugs
- Decreases vomiting
- Have little effect on cats
- Work well on dogs, have many D2 receptors in CRTZ
-
Xylazine
- Powerful emetic on cats (Alpha2 agonist)
- Sedative, anesthetic
-
Do not induce vomiting if animal is...
- comatose
- debilitated
- extremely depressed
- unconscious
- lacking gag reflex
- chicken bones
- gasoline
-
Centraly acting emitics (nervous system)
- apomorphine (dogs, conjunctival sac)
- xylazine (cats a2 receptors, can be reversed)
-
Locally acting emetics (stomach)
- Giver PO 1 dose, do not repeat
- Syrup of Ipecac - Do NOT use!!
- Hydrogen peroxide - not always relyable
- Warm concentrated salt water, Na toxisity
- Solution of powdered mustard and water ?
-
Antiemetics
- Prevent or decrease vomiting
- Should only be used when vomiting is no longer beneficial
- May mask clinical signs, keep bod substance in GI longer
-
Chlorpromazine (Compazine, DarbazineTM)
- Phenothiazine Tranquilizer
- Used for motion sickness
- acute gastroenteritis
-
TYPES OF ANTIEMETICS
- Phenothiazine
- Tranquilizers
- Procainamide
- Derivative (metoclopramide)
- Cisapride
- Antihistamines
- Anticholinergics
- Maropitant
-
Phenothiazine Tranquilizers should not be used in
Dehydrated or sesure prone pt.
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METOCLOPRAMIDE (REGLANTM)
- Blocks dopamine and Seratonin Rc
- Increase stomach motility
- Don’t use with atropine or narcotic analgesics (negate)
- Cats & horses can become frenzied
- prokinetic
-
CISAPRIDE (PROPULSIDTM)
- $$$
- does not cross BBB
- For use in gastric stasis vomiting, prokinetic agent
- Dogs w/ megaesophogus
- Cats w/ megacolon
-
Antihistamines
- Motion sickness, middle ear infection
- Dogs: BenadrylTM (diphenhydramine) DramamineTM (dimenhydrinate)
- First generation H1 antagonists
-
Anticholinergic drugs a.k.a. Parasympatholytic
- Blocks parasympathetic NS
- Do not completely block emisis
- may increase emisis w/ decreased gastric motility or gastric atoney
- Not usualy for antiemetic unless IBD
-
CereniaTM
- Substance P induces vomiting via NK1 receptors in the G.I. tract and brain
- NK1 Rc antagonist
- injectable and tablet
-
Narcotic Antidiarrheals
- diphenoxylate (Lomotil®),
- paregoric (tincture of opium)
- loperamide (Imodium and Imodium A-D OTC)
- Sevear dry mouth if abused
- C-V or C-III
- increased intracranial pressure w/ head trauma
- analgesic makes dz motering hard
- “Morphine mania” in cats
- prolonged contact time with mucosa and pathogenic bacteria
-
Antidiarrheal Anticholonergic/ Parasympatholytic drugs
- Decrease effect of Ach neurotransmitter on GI tract
- Used as antispasmodics, decrease spastic colonic contractions
- Not as effective against small bowel dz
-
Antidiarrheals that block hypersecretion
- Block liquid contact with mucosa
- Bismuth subsalicylate (Pepto-BismolTM and Kaopectate TM)
- Flunixin meglumine (BanamineTM) for horses & cattle
- Sulfasalizine (Asulfidine)
-
-
Non-systemic antacids
- May cause electrolyte imbalance w/ prolonged use
- Ca, Mg, Al
- Gastric acid rebound syndrom
- Constipation
- Diarrhea
-
Systemic antacids
- decrease production of stomach acid
- Cimetidine (Tagamet®)
- ranitidine (Zantac®)
- famotidine (Pepcid®)Alternate w/ cardiac & other drugs
-
Omeprazole (Prilosec)
- binds to luminal surface of parietal cells and inhibits the
- hydrogen pump that transports hydrogen ions into stomach lumen
-
Sucralfate (Carafate)
- Needs ulcer to bind with
- "gastric band-aid"
- needs acidic environment
- Stimulates PGE production
-
Misoprostol (Cytotec)
- $$$ the good stuff
- Use for Dx ulcer
- Wear gloves if pregnant
-
Ruminatorics
- Increases Parasympathetic NS
- Increases motility
-
Neostigmine (Stiglyn®)
- combines with acetylcholineseterase
- prevents breakdown of acetylcholine
- Do not use with GI obstruction, asthma, bradycardia or with organophosphates or any other drug that increases parasympathetic tone
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