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All inflammation is harmful and should be prevented. True or false?
false. inflammation is part of the normal healing process
What are some of the protective and healing effects of inflammation?
- increases blood supply to the affected area - dilute and immobilizes the cause of inflammation
- draws WBC's to the area - segs and macrophages (phagocytes) and lymphocytes (part of the immune system).
What are the 5 signs of inflammation?
- pain (dolor)
- heat (calor)
- redness (rubor)
- swelling (tumor)
- loss of function
When should inflammation be treated? What types of inflammatory conditions are commonly treated with anti-inflammatory drugs?
- when it is inappropriate or excessive, causes pain and tissue damage
- arthritis, allergies, autoimmune disease
In what ways can a fever be beneficial to a patient?
heat inactivation of invading microorganisms, can also speed up chemical reactions in the patient's body.
What is a "pyrogen"?
a substance that can cause a fever in a patient.
What do "exogenous" and "endogenous" mean?
- exogenus - from outside the patient's body
- endogenus - from inside the body
Are fevers usually controlled with NSAIDs or glucocorticoids?
How do anti-inflammatory drugs act?
block perception of pain and decrease tissue damage due to inflammation by blocking part of the inflammatory pathway.
What are the 2 main classes of anti-inflammatory drugs?
glucocorticoids and NSAIDs - non-steroidal anti-inflammatory drugs
In general, what do we mean by the "inflammatory pathway"?
when the patient's tissue is damaged in some way - trauma, burns, radiation, infection, etc - cell structures are exposed and acted on by enzymes, and broke down into compounds which cause inflammation
Be familiar with the arachidonic acid pathway.
- phospholipids cell membranes are disrupted by tissue damage, so that the phosopolipase enzymes can "get at" the phospholipids and break them down - one of the compounds formed is arachidonic acid.
- arachidonic acid can be either broken down or COX (cyclooxygenase) - to form prostaglandins and thromboxanes, or by LOX (lipoxygenase) to form leukotrienes
What do we call the inflammatory substances that are produced by the breakdown of arachidonic acid?
List 3 eicosanoids.
Are these 3 eicosanoids the only compounds produced in the body that can cause inflammation?
no - there are others, such as histamine
Different prostaglandins have different functions in different parts of the body. What do inflammatory prostaglandins do?
cause inflammation (musculo-skeletal system)
What do GI prostaglandins do?
are protective - cause increased fluid secretion into stomach, increased mucus production, decreased HCl production in stomach
What do reproductive prostaglandins do?
cause lysis of CL - corpus luteum
What do renal prostaglandins do?
renal COX 1 prostaglandins counteract vasoconstriction, allow vasodialtion of the renal blood supply - protective.
What do lung prostaglandins do?
beneficial - help to maintain bronchodilation
Cyclooxygenase comes in 2 forms (so far). In general, what do COX 1 and COX 2 do?
- COX 1 in the GI system forms "good" protective GI prostaglandins
- COX 2 forms "bad" inflammatory prostaglandins
How do glucocorticoids work?
by blocking phospholipase (and some depression of cyclooxygenase) to prevent or reduce the formation of eicosanoids - prostaglandins, thromboxanes, and leukotrienes
How do NSAIDs - non=steroidal anti-inflammatory drugs - work?
by blocking COX - cyclooxygenase to prevent or reduce the formation of prostaglandins and thromboxanes. some NSAIDs also block LOX - lipoxygenase and thuse prevent or reduce formation of leukotrienes also.
Do all "steroids" anti-inflammatory?
Are steroids water or lipid soluble?
What are "corticosteroids"?
steroid compounds formed in the adrenal cortex
List the 3 types of corticosteroids.
- gonadal steroids
Name 1 mineralocorticoid naturally formed in the body.
What disease is caused by lack of aldosterone?
Addison's disease - hypoadrenocorticism, high K, low Na.
What drug can be used to treat Addison's disease?
desoxycorticosterone - Percorten - V
Give 3 examples of gondal steroids.
- androgens (testosterone)
Briefly, what are "glucocorticoids"?
glucocorticoids are the "anti-inflammatory steroids" that happen to be named after their influence on glucose metabolism.
Briefly describe how the body regulates production of glucocorticoids.
- hypothalamus detects low blood levels of glucocorticoids.
- hypothalamus releases CRF - corticotrophin releasing factor - which causes the pituitary to release ACTH (adrenocorticotropic hormone) - ACTH travels to adrenal cortex, causes it to produce glucocorticoids (cortisol) - glucocoritcoid blood levels rise - hypothalamus detects this, stops releasing CRF
Can stress have any effect on glucocorticoid blood levels?
yes - stress can cause CRF release by the hypothalamus
List the effects of glucocorticoid in the patient's body.
- inhibit fibroblasts
- glucose metabolism
- Na and water retention
- polyphagia and weight gain
- induce parturition
- inhibits "good" GI prostaglandins
- stress leukogram
Is it possible for large doses of glucocorticoids to delay healing in the patient?
What effect can topical glucocorticoids have on a corneal scratch or ulcer?
may make it much worse by breaking down the protein exposed in the cornea. may cause perforation
Is glucocorticoid administration helpful or harmful to patient with pulmonary edema?
can be harmful - glucocorticoids cause the patient to retain sodium and water, which can make pulmonary edema worse
Glucocorticoids are used to treat what conditions?
- musculoskeletal inflammation
- Addison's disease
- autoimmune disease
- lymphocytic neoplasms
How can we cause iatrogenic Cushing's disease?
hyperadrenocorticism - by giving too much glucocorticoids for too long. usually overdoing "allergy shots"
How can we cause iatrogenic Addison's disease?
hypoadrenocorticism - by giving steriods long enough to trigger long-term negative feedback - the hypothalamus detects plenty of glucocoritcoids, stops sending out CRF, so the pituitary stops releasing ACTH, so the adrenal cortex is not stimulated to produce glucocorticoids, so the adrenal cortex atrophies. then, we abruptly stop giving glucocorticoids, the patient cannot make any, and he has an Addisonian crisis and may die
When we have had a patient on glucocorticoid therapy, is it best to stop the drug abruptly, or to wean the patient off of it gradually?
wean off gradually - to prevent the above scenario
What are the 3 classifications of glucocorticoids?
- short-acting (less than 12 hours)
- intermediate-acting (12-36 hours)
- long-acting (over 48 hours)
List 2 short-acting glucocorticoids. Which one is used the most, and why?
- hydrocortisone, cortisone.
- hydrocortisone is used the most - it is the active form
- cortisone is not active, and has to be converted by the liver to hydrocortisone to be active
List 5 intermediate-acting glucocorticoids.
- the 4 "preds"
Which has more activity - prednisone or prednisolone?
prednisolone (liver converts prenisone to prednisolone)
List 4 long-acting glucocorticoids.
- "the methasones"
- dexamethasone - Azium, Tresaderm
What injectable formulations are glucocorticoids available as?
- aqueous solution
- alcohol solutions
Are glucocorticoid solutions clear or opaque? Do they need to be shaken before administration? Can they be given IV?
What are the advantages of aqueous solutions of glucocorticoids?
can give IV - large amounts rapidly - for emergency purposes
What salts are glucocorticoids combined with to make the water soluble?
- sodium phosphate
- sodium succinate
Give 2 examples of aqueous glucocorticoids.
- dexamethasone Na phosphate - Azium
- prednisolone Na succinate - Solu-Delta-Cortef
Do we need to attach glucocorticoids to salts to make them dissolve in alcohol?
Are glucocorticoid suspensions clear or opaque? Do they need to be shaken before administration? Can they be given IV?
What forms do glucocorticoid suspensions come in?
Why are glucocoriticoid suspenstions long-acting (repository) forms?
the drug is in a crystal form, given IM, takes time for the crystal to dissolve and be absorbed
If methylprednisolone is an intermediate-acting glucocorticoid, why is methylprednisolone acetate (Depo-Medrol) a long-acting drug?
the actetate crystal suspension form is long-acting
What precautions do we need to take when storing glucocorticoid suspensions, and why?
avoid extreme temperatures - this causes larger crystals to be formed, which are more irritating when injected IM, and take longer to dissolve and be absorbed
Who tolerate glucocorticoid administration better - dogs or cats?
Why do we have to be careful when administering glucocorticoids?
prevent iatrogenic Cushing's disease
Describe safe use of glucocorticoids?
- avoid if possible
- use smallest dose possible
- reduce dose as patient improves
- use alternate-day dosing
- avoid frequent use of repository form
- wean patient off of glucocorticoids gradually