Analgesia Flashcards
Hydrocortisone
Duration < 12 hr
Potency = 1
Uses: topical for pruritis and inflammation assoc. w/ allergy
Fludrocortisone
Duration < 12 hr
Potency = 10 (anti-inflam)
Mineralocorticoid potency: 125
Uses: systemically for cortisol and aldosterone replacement during adrenal insufficiency (hypoadrenocorticism/Addisons)
Prednisone
Duration 12-36 hrs
Potency = 4
Uses: systemically for long term management of allergy, chronic inflammation (arthritis) and immunosupression (autoimmune disease)
Pro-drug
Methylprednisolone
Duration 12-36 hrs
Potency = 5
Uses: systemically for long term management of allergy, chronic inflammation (arthritis) and immunosupression (autoimmune disease)
Used in situations of less prednisone to prednisolone conversion in the body: cats/horses and in hepatic failure
Dexamethasone
Duration 36-72 hrs
Potency = 25 (HIGH)
Uses: Systemically for immediate relief of hypersensitivity and septic shock, long term control of allergy and immunosuppression. Best for acute.
Nociceptors
Neurons that respond directly to noxious stimuli by starting APs that go directly to the CNS
(Heat cold, pain, chemical)
1st part of the perception of pain
A delta and C fibers
What are Transient Receptor Potential Channels?
Peripheral nociceptors activated by heat, pressure, cold, etc and inflammation, which increases pain.
What are some methods of central pain inhibition?
Glutamate (NDMA) antagonists -ketamine
Inhibitory interneuron
How do NSAIDs work?
Decrease prostaglandin synthesis and TPR activation through COX inhibition.
How do local anesthetics work?
Block action potentials, work anywhere along pain pathways.
What is an example of a glutamate antagonist?
Ketamine (NMDA)
How do alpha 2 agonists work to limit pain?
Work postsynaptically on nonadrenergic neurons
What are two classes of corticosteroids?
-Endogenous steroids produced in the adrenal cortex
Cortisol: glucocorticoid (zona fasciculata)
Aldosterone: mineralocorticoid (zona glomerulosa)
Do glucocorticoid drugs often possess mineralocorticoid activity?
Yes
Where does corticotrophin releasing hormone come from and what does it do?
The hypothalamus
CRH stimulates the anterior pituitary to release adrenocorticotropic hormone (ACTH)
Why is tapering steroids important?
High levels of glucocorticoids suppress the production of CRH and ACTH.
What are the two basic mechanisms of glucocorticoid signaling?
Genomic effects and non-genomic effects
Which is faster: genomic or non-genomic signaling?
Genomic: slow changes in gene expression that alter cellular function
Non-genomic: rapid changes in cellular function that do not involve changes in gene expression
How to glucocorticoids affect metabolism?
Increase gluconeogenesis leading to hyperglycemia
Increase insulin secretion and insulin resistance (diabetes mellitus)
Increase protein breakdown
Increase lypolysis and redistribution of lipids (weight gain)
How do glucocorticoids affect the heart?
Increase vasoconstriction and cardiac contraction
Increase adrenergic signaling
Increase angiotensin signaling
Assoc. w/ hypertension (dogs) and CHF (cats)
Mineralocorticoid effects (NaCl/H2O retention, incr. plasma vol)
How do glucocorticoids affect respiration?
Bronchodilation
Decrease retention of mast cells in lungs
Decrease histamine release
How do glucocorticoids affect skeletal muscle?
Muscle wasting (at pharmacological levels)
How do glucocorticoids affect the skin?
Epidermal and dermal thinning
Easy bruising and poor wound healing
Poor quality hair, alopecia
How do glucocorticoids affect the immune system?
too little or too much = decreased immune function and increased susceptibility to infection.
How do glucocorticoids affect water and electrolyte balance?
inhibit ADH release
PU/PD
How do glucocorticoids affect the GI?
Increased acid and pepsin production
Possible ulceration (esp w/ NSAIDs)
Are glucocorticoids anti-inflammatory?
At pharmacological/high doses
Do steroids help cure the disease?
No, steroids help treat the symptoms but do not address the underlying cause.
Do glucocorticoids affect cell mediated or humoral immunity?
Cell-mediated immunity is suppressed more than humoral.
How do glucocorticoids work in inflammation?
Suppressed production of inflammatory mediators.
White blood cell migration and function is suppressed
Cell mediated immunity
What is iatrogenic hypoadrenocorticism?
Induced Addisons from long term steroid administration that is stopped rapidly. Wash out period is important (1-2 weeks)
Additional GC supplementation may be necessary during periods of stress (surgery, anesthesia, illness)
Mitotane
Adrenal steroid inhibitor
Cytotoxic to zona fasciculata, reduces all adrenal steroids (except aldosterone)
Uses: HyPERadrenocorticism (Cushing’s), steroid-secreting adrenal tumors
Cushing’s Syndrome
Hyperadrenocorticism
Cats/dogs: hair loss, bald patches
Horses: heavy haircoat that does not shed
COX 1
Constitutive expression
-Involved in homeostatic processes
-Gastric mucosal protection, renal function, vascular function, and platelet function
Produces:
-PGE2 (prostaglandin E2) : vasodilation, sens of nociceptors, GI protection
-TxA2 (thromboxane A2): platelet aggregation and vasoconstriction > enhanced coagulation and clot formation
COX 2
inducible expresion
-expressed at site of injury and inflammation
Produces:
PGE2
PGI2 (prostacyclin): vasodilation, inhibits platelet aggregation
in the kidney these alter blood flow, stimulate renin, increase Na excretion, decr. Na absorption
What is the most common side effect of COX 1/2 inhibition?
GI related effects
What is an advantage of COX-2 selective drugs (COXIBs)?
Less GI effects
