Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
92 Cards in this Set
- Front
- Back
Explain the Renin-Angiotensin system
|
1. Angiotensinogen is synthesized in the Liver
2. Angiotensinogen is converted to Anngiotensin I by Renin (secreted from Kidneys) 3. ACE converts Angiotensin I (decapeptide) ➡ Angiotensin II (octapeptide) |
|
Cells that secrete Renin
Cells that regulate Renin secretion |
Juxtaglomerular cells
Macula densa |
|
List the 3 mechanisms in which Renin secretion can be inhibited
|
1. increased NaCl flux thru chemoreceptors in Macula Densa
2. Elevated BP thru baroreceptors in Afferent Arteriole wall 3. Beta-adrenergic blockade by inhibiting symathetic stimulation via B1-adrenergic receptors |
|
What are the 2 major effects of Angiotensin II?
|
1. Increases Peripheral Resistance = increases Afterload
2. Increases Aldosterone secretion = Increases Fluid retention = increased Preload |
|
What 2 actions do ACE inhibitors cause?
|
Decrease in Preload and Afterload
*Afterload = via vasodilation from loss of AT-II *Preload = via loss of Aldosterone |
|
What do ACE inhibitors protect against after Myocardial Infarcts?
|
Subsequent failure by slowing the remodeling
|
|
What common ending do all ACE inhibitors share?
|
-PRIL
**i.e. Benza-pril, Capto-pril |
|
This is the only intrinsically active ACE inhibitor
|
Capto-pril
|
|
Other than Capto-pril, what must all ACE Inhibitors be converted to to be active?
|
Di-acids
|
|
T or F: All ACE Inhibitors are equally effective in blocking conversion of Antiotensin I to Angiotensin II, have the same clinical uses and adverse effects, and there is no compelling reason to favor one over another
|
True
|
|
What is the mechanism of action of ACE inhibitors?
|
Inhibit ACE = reduce formation of Angiotensin II = Lower BP
|
|
List the 3 mechanisms in which ACE inhibitors lower Blood Pressure
|
1. reduced Angiotensin II Vasoconstriction = vasodilation lowers BP by reducing peripheral vascular resistance
2. Reduced Angiotensin II will decrease Aldosterone release from Adrenal Medulla = decreases fluid volume = decreases Cardiac Output 3. Reduced destruction of Bradykinin = increases Bradykinin Levels = Vasodilation to enhance BP lowering |
|
When administering ACE Inhibitors,what explains the Blood Pressure lowering in hypertensives whose Renin levels are low or normal?
|
Elevated Bradykinin levels
**the BP lowering is not due to reduced Angiotensin II formation |
|
What causes the side effects of Coughing and Angioneurotic edema when administering ACE inhibitors?
|
Elevated Bradykinin levels
|
|
What plasma product may increase when administering ACE Inhibitors?
|
Renin
|
|
Unlike other vasodilators, what do ACE inhibitors not elicit? Why?
|
Reflex tachycardia
Concurrent baroreceptor resetting or parasympathetic activation |
|
ACE inhibitors lower BP without compromising blood supply to these 3 organs
|
Heart
Brain Kidneys |
|
ACE inhibitors are most effective in what type of Hypertensives?
|
those with elevated plasma Renin levels
**BUT will still lower BP even when renin levels are not high (via Bradykinin) |
|
What is the advantage of ACE Inhibitors over other Antihypertensive drugs like Diuretics or B-adrenergic blockers?
|
have milder and fewer side-effects without chaning blood lipids or glucose
|
|
ACE Inhibitor
1. administration 2. lower BP in what % of patients with mild-moderate HTN |
1. Oral for monotherapy
2. 50% |
|
What groups of patients are ACE inhibitors most effective? Less Effective?
|
Young to Middle-age Caucasians
Elderly Blacks |
|
ACE Inhibitors are the 1st choice Antihypertensive drugs for treatment of Hypertensives with these 3 conditions
|
1. Diabetes
2. Chronic Renal Disease 3. LVH |
|
How do ACE Inhibitors enhance the antihypertensive efficacy of Diuretic drugs?
|
attenuate (diminish) Aldosterone secretion = natriuresis induced by the diuretic is unopposed
|
|
What are the common adverse effects of ACE Inhibitors? (3)
|
1. Dry, hacking, non-productive cough (5-20%)
2. Angioedema and anaphylaxis (due to Bradykinin) 3. Hyperkalemia (due to inhibited Aldosterone secretion, especially in patients with renal insufficiency) |
|
When are ACE Inhibitors contraindicated?
|
During last 2 trimesters of Pregnancy due to fetal risks of:
-Hypotension -Renal Failure -Malformations -Death |
|
What is the common ending for Angiotensin II Antagonists?
|
-SARTAN
|
|
Which Angiotensin receptors predominate in vascular smooth muscle and cause most of the known actions of Angiotensin II?
|
AT1 receptors
**AT2 receptors exist in Fetal Tissues |
|
Where do AT2 receptors mainly occur?
|
Fetal tissues, with fxn being uncertain
|
|
T or F: All the currently available Angiotensin II antagonists act by blocking both AT1 and AT2 receptors
|
False = they selectively block AT1
|
|
What side-effect may the Angiotensin II Antagonists cause, especially in patients with Renal Insufficiency?
|
Hyperkalemia
*potentially fatal arrhythmias |
|
What is the major difference between Angiotensin II Antagonists and ACE Inhibitors?
|
Angiotensin II Antagonists are more specific in blocking Angiotensin effects b/c they do not affect Bradykinin metabolism = no coughing or angioedema
|
|
What are the 2 main uses of A-II Antagonists?
|
1. Lower BP in HTN patients
2. Slow morphologic changes (remodeling) after myocardial infarction and thus protect against subsequent development of heart failure |
|
Kinins are potent __1__ formed by enzymes called __2__ acting on protein substrates called __3__
|
1. Arteriodilators
2. Kallikreins 3. Kininogens = Kallikreins convert Kininogens to Kinins |
|
Where are Kallikreins present?
Where are Kininogens present? |
Plasma and many tissues (kidneys, pancreas, intestine, sweat and salivary glands)
Plasma, lymph, interstitial fluid |
|
There are 2 kinin receptors, which one is widely distributed and causes the biologic effects?
|
B2 receptors
|
|
When Kininogens are released in inflammation, what do they cause?
|
Redness, pain, swelling, heat
|
|
What are B2 receptor Antagonists used for?
|
Experimentally to evaluate kinin involvement in pain, hyperalgesia, and inflammtion
**none are available yet for clinical use |
|
What may B2 receptor agonists (Bradykinin) be useful for treating? Why?
|
HTN & CHF
b/c they produce vasodilation = decrease peripheral vascular resistance |
|
What catalyzes Kinin degradation? How is this knowledge used clinically?
|
ACE
ACE inhibitors reduce Bradykinin destruction -> Vasodilation = contribute to anti-HTN effect of ACE inhibitors |
|
Alternate name for Vasopressin-1
|
Antidiuretic hormone (ADH)
|
|
Vasopressin-1 (ADH) is synthesized in the __1__ together with __2__ and then secreted or released from the __3__
|
1. Hypothalamus
2. Oxytocin 3. Posterior Pituitary |
|
What 3 receptors does Vasopressin-1 act on? What are the effects?
|
1. V(1a) receptors in vascular smooth muscle -> Vasoconstriction
2. V(1b) receptors -> potentiate release of ACTH by anterior pituitary corticotropes 3. V2 receptors in Renal Cells produce Antidiuresis by increasing water permeability and reabsorption in Collecting Tubules |
|
Long-acting analog of Vasopressin with minimal V1 activity
|
Desmopressin = Vasopressin-2
|
|
What is the major function of Desmopressin?
|
Antidiuretic = fluid retention in the kidney
|
|
What is the antidiuretic-to-pressor ratio of Desmopressin compared to Vasopressin-1?
|
4000 times = much more potent at Antidiuresis than Vasoconstriction
|
|
What does ADH deficiency result in ?
|
Diabetes Insipidus = secretion of large amounts of severely diluted urine
|
|
What 2 drugs are used to treat Diabetes Insipidus?
|
Vasopressin & Desompressin
|
|
Which would you give to a patient with Coronary Artery Disease when trying to treat Diabetes Insipidus, Vasopressin or Desmopressin? Why?
|
Desmopressin
b/c Vasopressin may constrict Coronary blood vessels |
|
Describe the derivation of the word "Eicosanoid"
|
Eicosa = 20 = all Eicosanoids are synthesized from Fatty Acids that are 20 Carbon atoms in length
|
|
Eicosanoids refers to a large family of __1__ products of __2__ widely distributed in many plants and animal tissues
|
1. Oxygenation
2. Polyunsaturated long chain fatty acids |
|
If Eicosanoids cause a release of cAMP, what will happen?
If Eicosanoids cause release of IP3, what will happen? |
cAMP -> Vasodilation
IP3 -> Vasoconstriction by increasing intracellular Ca++ |
|
What is the most abundant and important precursor of Eicosanoids?
|
Arachidonic acid
**mobilized from the cell membrane phospholipids by PLA2 |
|
What Eicosanoids do COX enzymes produce?
|
Prostaglandins
Prostacyclin Thromboxane |
|
What Eicosanoids do Lipoxygenases lead to?
|
Leukotrienes
Lipoxins |
|
What do the P450 Epoxygenases lead to the formation of?
|
Epoxides
|
|
Which COX is constitutively expressed, widely distributed, and has "housekeeping functions"?
|
COX-1
|
|
Which COX is inducible and is an immediate early response gene product whose expression is stimulated by Growth Factors, Tumor promoters, and Cytokines?
|
COX-2
|
|
2 NSAIDs that are equipotent on COX-1 and COX-2
|
Meclo-fena-mate
Ibuprofen |
|
NSAIDs that preferentially inhibit COX-2
|
Celecoxib
Rofecoxib |
|
Eicosanoids have Smooth Muscle effects in what 4 places?
|
1. Vascular
2. GI 3. Airway 4. Reproductive sites |
|
What effects does Thromboxane have on Smooth Muscle?
|
Mitogenic
Vasoconstrictor |
|
What effects do PGE2 and PGI2 have on Smooth Muscle
|
Vasodilation by decreasing intracellular Ca++
|
|
What are the GI effects of Eicosanoids? Which ones cause it?
|
Longitudinal muscles contract & Circular muscles relax
PGE2 & PGF2-alpha cause Colicky cramps ** "F"eelings of "E"mesis |
|
What Eicosanoids cause Bronchial Smooth Muscle to be relaxed?
|
PGD2
PGE1 PGE2 PGI2 DIE-2, E1 |
|
What Eicosanoids cause Bronchial Smooth Muscle contraction?
|
Thromboxane (TXA2)
PGF2-alpha |
|
What is the major source of the Prostaglandins found in semen?
|
Seminal Vesicle
**different from the original thought that they came from the Prostate |
|
Explain the difference of prostaglandin concentration in fertile and infertile men
|
High PG in Fertile
Low PG in Infertile |
|
Prostaglandin production in human semen is enhanced by __1__ and reduced by __2__
|
Testerone
Aspirin |
|
What Eicosanoid relaxes Smooth Muscles in the Corpus Cavernosum to enhance Penile erection?
|
PGE1 = Alprostadil
*E1 = erection *"Al-the-PRO-STUD = gets the ladies with his erection |
|
What 2 Eicosanoids have potent Oxytocic actions and will end pregnancy by promoting Uterine Contractions?
|
PGE2 & PGF2-alpha
**End Fetus = E2 & F2a |
|
Oral PGE1 analog used for 1st and 2nd Trimester abortions
|
Misoprostol
|
|
Other than actually causing abortion, what are PGE2 and PGF2-alpha used for?
|
Priming or ripening the Cervix before abortion; softens the cervix by increasing Proteoglycan content & chaning biophysical properties of Collagen
|
|
What are the common adverse effects of PGE2 and PGF2-alpha when using them for abortion?
|
NVD
Fever Bronchoconstriction Hypo- or Hypertension Syncope Flushing |
|
Eicosanoid that is given vaginally for abortion
|
PGE2 = Dino-pro-stone
**Dino-saur abortion |
|
Platelet aggregation is enhanced by __1__ and inhibited by __2__ & __3__
|
1. TXA2
2. PGE1 3. PGI2 |
|
What cells in the blood have high Prostaglandin synthesis capacity?
|
Monocytes
Eosinophils |
|
What parts of the kidney can synthesize Prostaglandins?
|
Cortex = PGE2 & PGI2
Medulla |
|
What 3 PG's increase GFR by causing vasodilation?
|
PGE1
PGE2 PGI2 |
|
What drugs stimulate COX activity to increase PG synthesis in the kidney? Why is this important?
|
Loop Diuretics
Concurrent administration of COX inhibitors may diminish loop diuretic effects = don't take Aspirin when taking Loop Diuretics |
|
Prostaglandins that are effective at initiating and stimulating labor
|
PGE2 and PGF2-alpha
|
|
Facilitation of labor:
-__1__ is one-tenth as potent, but has more GI toxicity than __2__ |
1. PGF2-alpha
2. PGE2 |
|
Prostaglandins that are both as effective as Oxytocin for inducing labor, but with more GI side effects of NVD
|
PGE2
PGF2-alpha |
|
Dysmenorrhea may result from increased Endometrial synthesis of these 2 PG's
What would be the treatment? |
PGE2 & PGF2-alpha
NSAIDs = inhibit PG formation -Aspirin is also effective |
|
Orally effective PGE1 synthetic analog that increases production and secretion of gastric mucosa barrier
|
Misoprostol
|
|
Drug apporved for prevention of NSAID-induced peptic ulcers
What is it an analog of? |
Misoprostol
PGE1 |
|
Current drug of choice for inducing labor
|
Oxytocin
|
|
Oxytocin is synthesized in the __1__ together with __2__ and secreted from the __3__
|
1. Hypothalamus
2. Vasopressin 3. Posterior Pituitary |
|
Explain the mechanism of Oxytocin in inducing labor
|
1. binds to Oxytocin receptors in Uterine Smooth Muscle
2. alters transmembrane ionic currents to activate voltage-sensitive Ca++ channels 3. sustained uterine contractions |
|
Why does Uterine sensitivity to Oxytocin increase during pregnancy?
|
b/c the # of Oxytocin receptors increases markedly in late gestation
|
|
Aside from Inducing labor, what is Oxytocin's other effect?
|
Causes Milk ejection by contracting myoepithelium in mammary alveoli
Normal lactation cannot occur w/out Oxytocin-induced contraction |
|
What are the 4 clinical uses of Oxytocin?
|
1. Induce labor in uterine inertia, incomplete abortion, or conditions requiring early vaginal delivery (maternal diabetes)
2. control Postpartum hemorrhage 3. induce Milk ejection 4. Diagnose placental circulatory reserve |
|
Although adverse rxns to Oxytocin are rare, what are the possible ones?
|
1. Maternal death due to:
-HTN -Uterine rupture -water intoxication 2. Fetal death |