Pharm 22 Objectives Flashcards
What are eicosanoids?
signaling molecules made up of 20-carbon fatty acids found in the cell membrane
How are eicosanoids produced?
Inflammation causes arachidonic acid to create eicosanoids
What are the three main types of eicosanoids?
Prostaglandins (COX)
Thromboxane (COX)
Leukotrienes (Lipoxygenase)
What are the steps inhibited by NSAIDs?
Drugs such as NSAIDs block the synthesis of prostaglandins and COX
Role of eicosanoids in: smooth muscle function
stimulates uterine contractions
and
Increases GI motility
Role of eicosanoids in: platelet function
Maintains bicarbonate gel layer lining of GI mucosa
Role of eicosanoids in: renal function
increase sodium and water excretion
Role of eicosanoids in: inflammation, pain, and fever
Actives specific prostanoid receptors in target tissue
released by physical trauma or chemical stimuli
promote tissue inflammation
affect smooth muscle and platelet aggregation
target tissues vary by PG, some PBs bind to sites better than others
Role of COX-2
mediate pain, fever, and inflammation
What is the main target of NSAIDs
COX-2
Role of COX-1
Support and protects GI mucosa
Increases mucosal blood flow, production of mucus, and bicarbonate
Stimulates epithelial cells that line GI tract
COX-1 catalyzes thromboxane A2 in platelets which results in
a trigger for platelet aggregation
Advantages of selective COX-2 inhibitors?
Less GI distress
Less incidence of GI Bleed
Clinical utilization of COX-2 selective NSAIDS
Osteoarthritis (100-200mg daily/100mg BID)
Rheumatoid arthritis (100-200mg BID)
Dysmenorrhea (400mg x 1/200mg BID)
Acute Pain (400mg x1/200mg BID)
Disadvantages of selective COX-2 inhibitors?
Cost
Increase risk for cardiac events
Prescription is needed
Advantages for nonselective COX inhibitors
minimal downiness
Anti-inflammatory action
No risk of abuse or diversion
OTC choices are available
Disadvantages for nonselective COX inhibitors
Only best for mild to moderate pain
Anti-inflammatory action is delayed about 3-5 days
GI tox and renal effects
Analgesic dose of aspirin?
300 - 600 mg q6 hrs
Cardiovascular dose of aspirin?
75 - 100 mg daily
What is the most commonly used salicylates for GI disorders?
Aminosalicylates
Aminosalicylates clinical uses?
Inflammatory bowel disease specifically Ulcerative colitis and Crohns disease
What are the available formations of aminosalicylates?
Sulfasalazine- PO tab
Mesalamine- rectal suppository or suspension and delayed-release tab.
Explain the MOA of Acetaminophen
Antipyretic action: direct action on hypothalamic heat regulating center
Almost as potent as ASA inhibiting prostaglandin synthesis in the CNS
What effect does acetaminophen have outside the CNS and inflammation?
Minimal effect outside the CNS
Little to no anti-inflammatory effect
Advantages of Acetaminophen?
- Inexpensive
- No risk of dependence, addiction or diversion
- Antipyretic as well as analgesic
- No effect on platelets
- Very low risk of GI bleeding
- Very low risk of renal dysfunction unless overdosed
- Little to no drowsiness
- use in chronic pain
Disadvantages of Acetaminophen?
- only useful in mild to moderate pain
- risk of overdose
- total daily dose is a limiting factor for combination products
- confusion about which products contain APAP.
If drinking and/or have liver disease what dose of Acetaminophen is safe?
NO APAP dose is safe due to lack of glutathione
If you are not drinking but have liver disease what dose of Acetaminophen is safe?
2.0 grams/day
Wher is acetaminophen metabolized?
Extensively metabolized by the liver
What occurs when pt OD with acetaminophen?
Overdoses use up glutathione then metabolites bind to liver cells.
What is the MAX dose limits of acetaminophen in healthy adults?
4.0 grams
What is the MAX dose limits of acetaminophen in elderly OR mild liver dysfunction?
3.1 grams
What is the MAX dose limits of acetaminophen in moderate liver dysfunction OR etoh use?
2.0 grams
S/S of acute acetaminophen poisoning?
N/V
Drowsiness
Liver tenderness
Chronic/acute hepatotoxicity
Acute renal failure
Describe the psychological process and pathway that regulate cortisol production and release.
- CRH stimulates release of ACTH from pituitary gland
- ACTH stimulates release of cortisol from adrenal cortex
- Adrenal cortex releases cortisol into the bloodstream and inhibitory feedback to they hypothalamus
Describe the effects of short term use of glucocorticoids
Stimulation/agitation (euphoria, psychosis, insomnia)
Hyperglycemia
Appetite changes (increase or decrease)
Describe the effects of long term use of glucocorticoids.
Cushingoid features (full face (moon face) and weight gain)
Thinning of bones (osteopenia, osteoporosis)
Impaired immune response
Thinning skin
How does systemic glucocorticoid administration at pharmacologic doses affect the HPA axis?
Doses can cause suppression of HPA axis
Give dose in AM to minimize suppression.
Alternate-day therapy, in which all or most of the dose is given on alternate days.
Duration of glucocorticoid that may cause withdrawal/rebound?
> 10 days of corticosteroid Tx = Watch out for rebound!
Between 7 – 10 days Tx MAY cause withdrawal/rebound
What is the clinical application of corticosteroids in tx of IBS?
Hydrocortisone rectal foam or enema 100mg/60ml (Cortenema®)
Systemic needed for more severe/less localized symptoms
Systemic oral (prednisone) helpful for achieving remission
Tx options for other GI disorders such as UC and crohns disease?
Hydrocortisone and other glucocorticoids have been extensively used for the treatment of both ulcerative colitis and Crohn’s disease.
Specific tx for mild UC?
Rectal corticosteroid
Specific tx for severe UC?
Orally or parenteral corticosteroids, specifically Budesonide
Tx for maintaining remission of UC?
Sulfasalazine, olsalazine, and their active metabolite mesalamine are used to induce and maintain the remission of ulcerative colitis
Describe how to administer glucocorticoids for acute disorders?
Give in large doses that are gradually tapered over several days until treatment is discontinued
Describe how to administer glucocorticoids for severe disorders?
Large doses of steroids must be given daily for several months until remission is achieved, then the dose is slowly tapered, and continued for 1 to 2 years or longer.
Why use depo glucocorticoid shot?
Depot preparations are useful in providing a sustained level of the drug for several week
