Term
What is the basic structure of a prostaglandin?
(Picture on back) |
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Definition
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Term
| What are the most important prostaglandins biologically? |
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Definition
Prostaglandins E and F
Prostacyclin (PGI)
Thromboxane (TXA) |
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Term
| Describe prostaglandin receptors |
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Definition
5 have been identified- EP, FP, IP, DP, and TP
They are coupled to G-protein |
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Term
| What is the major source for arachidonic acid? |
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Definition
| Cell membrane phospholipid esters |
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Term
| What is the role of phospholipase A2? |
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Definition
| To convert cholesterol esters into arachidonic acid |
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Term
| Describe the pathway for arachidonic acid to be transformed into leukotrienes |
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Definition
| Lipoxygenase changes arachidonic acid into HPETE, which goes on to form leukotrienes |
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Term
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Definition
Slow reactive substance for anaphylaxis
Made up of leukotrienes LTC4 and LTD4
Later discovered to be leukotrienes |
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Term
| Describe the pathway for arachidonic acid to be transformed into prostaglandins |
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Definition
| Cyclooxygenease changes arachidonic acid into PGG, which turns into PGH and then all other prostaglandins (as well as thromboxane) |
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Term
| What are the two classes of PG inhibitors? |
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Definition
| NSAIDs and Corticosteroids |
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Term
| Describe the mechanism of action of NSAIDs |
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Definition
Inhibit cyclooxygenase
Some focus on COX1, some COX2
(COX2 only inhibitors are thought to be better) |
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Term
| What are side effects of NSAIDs? |
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Definition
Inhibiting PG induces:
1. Loss of PG cytoprotective effect on GI
2. Increased bleeding due to inhibition of thromboxane synthesis |
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Term
| Describe the mechanism of action of corticosteroids |
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Definition
Protein synthesis of lipomodulin.
This inhibits phospholipase A2, which reduces free arachidonic acid, the source of prostaglandins |
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Term
| Which PG inhibitor class is more effective? |
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Definition
| Corticosteroids are more effective anti-inflammatories than NSAIDS because they inhibit the source of prostaglandins (arachidonic acid) |
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Term
| What type of cells are resistant to steroids? |
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Definition
Cells with an abundance of free arachidonic acid, or cells with no protein synthesis (that can't make lipomodulin)
eg, platelets |
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Term
| What is the effect of prostaglandins on the cardiovascular system? |
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Definition
Lowers BP short term by causing blood vessel dilation
Drop only lasts a few minutes due to reflex increase in CO and HR |
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Term
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Definition
| The vessel that shunts blood from mother's lungs to fetus heart |
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Term
| What is the effect of prostaglandins on the ductus arteriosis? |
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Definition
| PGEs and PG12 are involved in maintaining patency (openness) of the ductus arteriosis |
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Term
| What is the effect of prostaglandins on blood platelets |
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Definition
PG12 is an extremely potent inhibitor of platelet aggregation
TXA2 is a potent inducer of platelet aggregation |
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Term
| What is the effect of prostaglandins on broncheal smooth muscle? |
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Definition
PGEs and PGIs relax the broncheal SM
Leukotrienes constrict
(this is important for asthmatics) |
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Term
| What is the effect of prostaglandins on uterine smooth muscle? |
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Definition
PGFs contract and PGEs relax in non-pregnant uterus
In pregnancy, uterus is more sensitive to PG, and is contracted by PGs |
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Term
| What is the effect of prostaglandins on intestinal smooth muscle? |
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Definition
PGs contract the intestine
(This is the major side effect to therapeutic use of PG- leads to diarrhea, discomfort) |
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Term
| What is the effect of prostaglandins on gastric secretion? |
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Definition
PGs inhibit gastric acid and pepsin, but increase mucus secretion
This is a natural cytoprotective effect of PG |
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Term
| What is the effect of prostaglandins on peripheral nerves/pain? |
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Definition
| PGs cause long-lasting pain and irritation, sensitize nerve endings |
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Term
| What is the effect of prostaglandins on the immune response? |
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Definition
PGs are involved in inflammation
They potentiate the pain-producing effects of other autocoids |
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Term
| What is the effect of prostaglandins on reproduction |
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Definition
Unknown, but they are probably important since they are concentration in the male and female reproductive tract
Amniotic fluid PG elevated during labor |
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Term
Describe the use of PG for therapeutic abortion.
What is the drug for this? |
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Definition
Not consistently effective
Becomes more effective later in pregnancy, but this is undesirable
PGE2 Dinoprostrone (Prostin E2, Cervidil) |
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Term
| Describe the therapeutic use of prostaglandin for labor induction |
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Definition
| PGE2 causes cervical ripening (softening) and can stimulate uterine contractions |
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Term
| Describe the therapeutic applications of prostaglandin for dysmenorrhea |
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Definition
| NSAIDs are used to inhibit PG that causes dysmenorrhea |
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Term
| Describe the therapeutic application of prostaglandin on male impotence |
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Definition
| PGE Alprostadil (Caverject) vasodilates the cavernosa, enhancing erectile function |
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Term
| Describe the therapeutic application of prostaglandin on platelet aggregation |
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Definition
PGE (Alprostadil) is used to prevent aggregation and to harvest platelets for transfusion
Aspirin is used to inhibit thromboxane synthesis to prevent aggregation |
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Term
| What is Epoprostenol (Flolan) used for? |
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Definition
| It is a prostacyclin used via continuous iv for smooth muscle relaxation to treat pulmonary hypertension |
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Term
| What is Alprostadil used for? |
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Definition
To maintain open (patent) ductus arteriosis in congenital heart defect prior to surgery
Also, to prevent aggregation and to harvest platelets for transfusion |
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Term
| Define Misoprostol (Cytotec) |
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Definition
A synthetic analog of PGE that reduces acid secretion without the side effect of GI stimulation
Used as a cytoprotective agent in patients on long-term NSAID therapy |
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Term
| Define Latanoprost (Xalatan) |
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Definition
| PGF2 derivative eyedrops that increase outflow of aqueous humor- lowers intraocular pressure in glaucoma |
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Term
| Describe the pathway that leads to cortisol production |
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Definition
1. Hypothalamus releases CRF
2. Anterior pituitary releases ACTH
3. Fasiculate reticularis releases cortisol |
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Term
| What is the effect of aldosterone? |
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Definition
| Water retention (increases kidney juxtaglomerular cell uptake of Na and water) |
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Term
| What is the effect of renin? |
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Definition
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Term
| What is the effect of angiotensin? |
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Definition
| Vasiconstriction and induces aldosterone |
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Term
| Describe the cellular mechanism of action of steroids |
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Definition
| Steroids cleaves heat shock proteins off their stable binder, then forms steroid-receptor dimers that act as transcription factors |
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Term
| What are the three classes of adrenal steroids? |
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Definition
1. Glucocorticoids
2. Mineral corticoids
3. Gonadal steroids |
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Term
| List physiological actions of glucocorticoids |
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Definition
1. Increases carb/protein/lipid metabolism (gluconeogesis, catabolic)
2. Increases calcium metabolism (osteoperosis)
3. Anti-inflammatory, immunosuppresive
4. Suppression of ACTH
5. Psychosis |
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Term
| List physiological actions of glucocorticoids |
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Definition
1. electrolyte metabolism:
Na and H20 retention
K+ and H+ loss |
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Term
| How are corticosteroids classified? |
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Definition
By glucocorticoid (anti-inflammatory) potency and mineralocorticoid (Na-retaining) activity
Ideal corticosteroids have high glucocorticoid and low mineralcorticoid activity
ex. dexamethasone |
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Term
| Describe the absorption and distribution of corticosteroids |
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Definition
Well absorbed from GI, good oral activity
endogenous corticoids 95% bound to Corticosteroid Binding Protein, but synthetic steroids have less affinity (and higher potency) |
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Term
| How common are side effects of adrenal cortical steroids? |
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Definition
| Nearly 100% in long term therapy |
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Term
| What are the two categories of adrenal cortical steroid side effects? |
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Definition
1. Adrenal insuffiency during withdrawl (lower ACTH secretion leads to adrenal atrophy)
2. Drug induced Cushing syndrome |
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Term
| What are the two types of adrenal insufficiency? |
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Definition
1. Primary: decreased glucocorticoid AND mineralocorticoid secretion
2. Secondary: cortisol secretion decreased, aldosterone secretion normal |
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Term
| Define congenital adrenal hyperplasia |
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Definition
| Excessive testosterone produced, usually due to lack of 21 Beta-hydroxylase and deficiencies in glucocorticoids and mineralocorticoids |
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Term
| What is the most common therapeutic use of corticoids? |
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Definition
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Term
| What is the main difference between rheumatoid arthritis and osteoarthritis? |
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Definition
| Osteoarthritis only affects a single joint (therefore injection is best ROA for it) |
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Term
| Other than arthritis, what disorders can be treated with corticoids? |
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Definition
Allergic reactions, ocular inflammation,
Nephrotic syndrome, ulcerative colitis, certain lymphatic and
neoplastic diseases, cerebral edema. |
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Term
| List contraindications of adrenal steroids |
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Definition
1. Agitated psychotic state.
2. Active peptic ulcer - causes acid secretions.
3. Diabetes.
4. Osteoporosis.
5. Hypertension.
6. Infection - will mask signs of infection. |
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Term
| Define and describe Aminoglutethimide (Cytadren) |
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Definition
A glucocorticoid synthesis inhibitor
Inhibits enzymes involved in all steroid biosynthesis
Used to treat Cushings and to produce "medical adrenalectomy" in patients with advanced breast/prostate cancer |
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Term
| Define and describe Spironolactone (Aldactone) |
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Definition
-Mineralocorticoid receptor antagonist
-Antagonist of aldosterone and testosterone
-K+ sparing diuretic
-Used to treat hirsuitism in women |
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