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212 Cards in this Set
- Front
- Back
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which cells secrete gastric acid? what stimulates acid secretion?
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parietal cells
stimulation by: ACh: (M3 receptors) gastrin (CCK2-receptors) histamine (H2 receptors) |
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what is the source of protons for gastric acid secretion? what is the consequence of that?
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water (Carbonic anhydrase)
leads to alkaline tide (HCO3-) in blood |
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what are the 3 stimulates of gastric acid secretion, what are their intracellular mechanisms?
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ACh: M3 receptors (Ca dependent)
gastrin: CCK2 receptors (Ca dependent) Histamine: H2 receptors (cAMP dependent) |
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what is the source of histamine stimulating gastric acid secretion?
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Enterochromaffin cells (ECL)
release histamine in response to gastrin and ACh from vagus |
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what is the source of gastrin stimulating gastric acid secretion?
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G cells in stomach antrum release gastrin in response to vagal nerve activity
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prostaglandins: effect on stomach
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natural: PGE2 and PGI2
inhibit acid secretion by parietal cells, stimulate mucous and HCO3 secretion by gastric epithelial cells synthetic: misopostol (PG analog) |
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PPIs: pharmacokinetics and pharmacodynamics
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t1/2: two hours
absorbed in high pH SI reach parietal cells via bloodstream require ACID ACTIVATION! then covalently inhibit H/K ATPases on parietal cells effect of inhibition can last long beyond the 2 hours |
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how are PPIs eliminated?
drug interactions? |
by the liver (CYPs)
increase Warfarin concentration decrease clopidogrel activation |
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what is zollinger-ellison syndrome and how do you treat it?
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gastrin secreting tumor (ACID!)
treat with PPIs or H2-R-antagonist |
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what class of drugs is best for excessive nocturnal acid secretion?
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H2-R-antagonists
(cimetidine, famotidine, ranitidine) |
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what is the side effect associated with long term use of cimetidine?
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decreased androgen binding (dec. sperm count and gynecomastia in males, galactorrhea in females)
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what is the mechanism and use for sucralfate?
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it is acid activated and forms a neutral polymer over ulcers...especially good for duodenal ulcers
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what is the difference between Mg and Al antacids?
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Mg antacids are faster acting and stimulate gastric emptying
Al antacids are slower acting and inhibit gastric emptying |
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what is the major contraindication to any Mg antacid?
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renal disease (kidney stones!)
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what is the mechanism and use of metoclopramide?
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dopamine antagonist
stimulates GI motility antiemetic SE: parkinsonian symptoms |
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what is the mechanism of tegaserod and cisapride?
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they are serotonin (5-HT4) agonists that stimulate GI motility
serious cardiac arrhythmia SEs |
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what is motilin and what are the motilin agonists?
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Motilin is a natural pro-kinetic peptide
macrolides are agonists (erythromycin) |
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what is the average daily water load on the GI tract?
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2 L ingested
7 L secretions most re-absorbed by SI LI can reabsorb up to 5 L/day |
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how do you differentiate between stool hardness and actual constipation?
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constipation: < 3 stools/week
treat stool hardness with increased fiber in the diet |
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what is the difference between laxation and catharsis?
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laxation: increased solid stool evacuation
catharsis: synchronized contraction of the colon leading to shooting out of wet fecal matter |
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lactulose is an especially helpful laxative in patients with...
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hepatic failure
decreases colon luminal pH => traps NH4 decreases NH4 load on liver |
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what is the mechanism of docusate?
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they are lipid emulsifiers which do not increase frequency of stools just soften stool
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what are the 2 uses for glycerin?
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renal osmotic diuretic
anal suppository => laxative |
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what opioid antidiarrheal has potential for abuse?
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diphenoxylate-difenoxin can enter the CNS. packaed with atropine to discourage abuse
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what is the mechanism and uses for octreotide?
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a synthetic somatostatin analogue
quiets GI tract in pancreatitis, gallstones, post-surgical dumping, chemo-induced diarrhea |
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where are emetic toxins sensed?
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at the chemoreceptor trigger zone. samples both CSF and blood toxins
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where is the emetic center?
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in the medulla
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what are the uses for the 5-HT3 receptor antagonists?
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most commonly used for chemotherapy induced emesis
act at the Chemoreceptor Trigger Zone (CTZ) and Solitary Tract Nucleus (STN) the -setrons |
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what are the side effects of the -setron antiemetics?
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ondasetron, palonosetron, granisetron, and dolasetron
constipation, because serotonin normally induces GI motility |
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where do the dopamine antagonists work to fx as anti-emetics?
specifically, which dopamine agonists work for which types of emesis? |
in the CTZ and the STN
metoclopramide works for chemo induced emesis prochloperazine and chlorpromazine work well for motion sickness |
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anticholinergics and antimuscarinics are anti-emetic by their actions at...
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the STN and the inner-ear/cerebellum
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what is the difference between ulcerative colitis and crohn's diase?
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both autoimmune
ulcerative colitis: ulcers limited to colon crohn's: lesions throughout the GI tract focused at ileocecal valve. has transmural lesions and fistulas |
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what does the role of inflammatory cell balance play in ulcerative colitis and Crohn's disease?
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Crohn's Disease: way more Th1 cells than Th2
Ulcerative colitis: way more Th2 than Th1 |
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what are the 5-ASA drugs and what is their mechanism/use?
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mesalazine, sulfasalazine and olsalazine
anti-TNF-alpha mechanism for Ulcerative colitis and Crohn's |
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what are the anti-TNF-alpha antibodies and how are they different?
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infliximab: a mouse antibody (more effective)
adalimumab: a human antibody (less effective) |
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what is Irritable Bowel Syndrome and how do you treat it?
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NOT IBDisorder
alternating constipation/diarrhea symptomatic laxative or anti-diarrheal therapy if diarrhea prominent: can give alosetron (5-HT3 antagonist) if constipation dominant: can give tegaserod or cisapride (5-HT4 agonist) |
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how does dysfx in platelets manifest itself different than dysfx of humoral factors?
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platelets: arterial bleeding
factors: venous bleeding |
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what coagulation factors are synthesized in the liver? which are Vit K dependent?
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2, 5, 7, 9, and 10
only 5 is NOT K-dependent |
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how is heparin administered?
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must be given IV (not oral) in "units" because only a part of unfractionated heparin has activity, so you can't give it by mass
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how does heparin work?
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binds antithrombin III to inhibit factors:
IIa (thrombin) IXa Xa |
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what are the 3 SEs of heparin?
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bleeding, thrombocytopenia and osteoporosis
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why is LMWH safer than unfractionated heparin?
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high molecular weight heparin can bind PLATELETs, then Abs can bind the heparin and activate the platelets leading to CLOTTING!
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the active form of heparin is...
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a pentasaccharide
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when is an important time to use direct thrombin inhibitors?
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when you have heparin induced thrombocytopenia
they act independent of ATIII |
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what is the mechanism of warfarin?
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it prevents the reduction of Vit K so you can't get vit K dependent carboxylation of factors II, VII, IX, and X
also anti-coagulant proteins C and S are inhibited |
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how do you begin dosing with warfarin?
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you begin on heparin because protein C has the shortest half life and can lead to a transietn HYPERcoagulable state before warfarin acts as an anticoagulant
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when should you not give a patient warfarin?
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if they have liver failure
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what are the mechanisms of warfarin's many drug interactions?
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increased metabolic clearance of agents metabolized in the liver
nutritional Vit K antagonism drugs bind the same albumin site |
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you can treat (heparin or warfarin) toxicity with fresh frozen plasma?
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warfarin (because it depletes quantity of clotting factors)
heparin inhibits the clotting factors themselves |
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(heparin or warfarin) is teratogenic?
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warfarin
heparin is NOT |
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what is the cause of coumadin induced skin necrosis?
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intiial warfarin dose causes hypercoagulability which leads to clots in small vessels
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how is streptokinase different than urokinase?
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streptokinase is harvested from strep so you need to give a very large dose to overcome antibodies, and you risk anaphylaxis
urokinase is from human cells...smaller dose, no risk of anaphylaxis |
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what is the mechanism of abciximab?
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binds glycoprotein IIb/IIIa receptors on platelets and irreversibly inhibits fibrinogen binding to platelets
=> no platelet aggregation |
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what is the mechanism of tirofiban
kinetics? |
binds glycoprotein IIb/IIIa receptors on platelets, binds reversibly and has a short half life
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how do you measure LMWH activity?
|
anti factor Xa assay (to see how much Xa inhibitor is present)
LMWH does NOT prolong PTT as you would expect |
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how is heparin cleared?
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by the reticular endothelial system
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what are the 4 main effects of Angiotensin II and III?
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vasoconstriction by AT1 receptors
increased NE release (inc SNA) increase vasopressin from SFO (subfornical organ) aldosterone secretion |
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what is the negative effects of Angiotensin II on the heart?
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increased afterload
cardiac remodeling leading to hypertrophy...BAD |
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what happens to renin levels when you are on an ARB?
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they increase
loss of feedback inhibition more Angiotensinogen activation, more Ang 1-7 beneficial! |
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what is the mechanism of lisinopril side effects?
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increased bradykinin leads to cough and angioedema
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what are the causes of central and nephrogenic diabetes insipidus?
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mutations in the AVP (ADH) gene (central) or the ADH-receptor gene (nephrogenic)
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what is the mechanism by which AVP increases blood pressure?
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V1 receptors increase PLC and Ca levels
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what is the mechanism by which AVP mediates its antidiuretic effects?
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V2 receptors increase cAMP, increasing aquaporin insertion
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how do you treat a hypervolemic but hyponatremic patient?
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give them a vaptan (AVP-R blocker)
increases water excretion while leaving Na excretion constant |
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which vaptans are selective for V1 vs. V2 receptors
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Tolvaptan: V2 selective
conivaptan: V1/V2 equal |
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what is the role of kinins in blood pressure regulation?
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they dampen hypertension but they have no role in normotensives
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what are the neuro-vascular effects of the kinins?
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vasodilation
increased Cap permeability stimulation of sympathetic ganglia pain |
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what are the neural effects of kinins?
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stimulate sympathetic ganglia
can direclty stimulate pain neurons |
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what is the main bradykinin receptor?
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B2
mediates the pain, vasodilation, and neural effects |
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ACE is also known as...
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kininase
degrades bradykinin and other kinins to inactive form |
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what two adrenal abnormalities can cause secondary HTN?
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adrenal cortex tumor: hyperaldosteronism
adrenal medulla tumor: pheochromocytoma |
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what are renin levels in people with essential HTN?
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only 15% have elevated renin levels yet most benefit from ACE inhibitors or ARBs
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what are the mechanisms of the endothelial derived vasodilators?
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release molecules active on VSM
PGI2=> increased cAMP NO=> increased cGMP both lead to relaxation |
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what are the mechanisms of endothelial derived vasoconstrictors?
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TXA2 and Endothelin both increase [Ca] in VSM
contraction |
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what is the mechanism of VSM dysfunction in CV disease?
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increased Rho-kinase=>
inactivation of Myosin Light Chain Phosphatase (MLC-P)=> more P-lated MLC more active contraction of VSM |
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what is the result of very low sodium concentrations?
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it can increase BP!
increased risk of CV disease |
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what pathologic effects does increased [Na] have besides increased blood volume?
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increased basal and responsive vasoconstriction
increased release of NE and Epi |
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what are the side effects of thiazides?
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decreased Ca excretion
effects reduced by NSAIDs hypokalemia sulfonamide cross-reactivity Gout |
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what are the 2 mechanisms of Beta-blocker antihypertension?
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decrease release of renin from sympathetic nerves
decreased cardiac output |
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what antidiuretics can lead to hyperkalemia?
|
the K sparing diuretics
and ACE inhibitors (decrease aldosterone secretion!) |
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calcium channel blockers are especially useful in what type of HTN?
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HTN with low renin levels (because ACE-I and ARBs will not be as effective)
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what is the main side effect of the alpha-1 antagonist antihypetensives?
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orthostatic hypotension
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metoprolol is associated with what unique side effect?
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sleep disorders
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what receptors to labetalol and carvedilol block?
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alpha 1, and beta-1/2
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what mixed alpha/beta antagonist has serendipidous side effects?
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carvedilol has antioxidant and antiproliferative effects
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what is the main limiting factor for using reserpine?
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depression
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what is the mechanism of hydralazine?
side effect? |
preferentially increases cGMP in arterioles (dilation)
causes reflex increase in SNA to heart...therefore often combined with Beta blocker |
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what is the mechanism of minoxidil (rogaine)
contraindication? |
it preferentially hyperpolarizes arterioles (dilation)
reflex increase in SNA to heart and SNA renin secretion, fluid retention...don't use in HF!! |
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what is the mechanism of epoprostenol?
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increases cAMP in VSM
direct antagonism of TXA2 |
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what are the agents used for pulmonary hypertension how do their effects differ from one another?
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epoprostenol (increases cAMP)
bosentan (ET-R blocker) ambrisentan (ETa-R blocker) epoprostenol has a very short half life, must be continuously IV infused bosentan and ambrisentan can be used chronically |
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what are the side effects of the endothelin receptor inhibitors
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bosentan and ambrisentan:
headache, edema, decreased spermatogenesis, URIs, decreased hematocrit |
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what are the 3 coronary conduit arteries and what do they supply anatomically?
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LAD: anterior, apex of LV
LCx: posterior LV RC: RV and part of inferior LV |
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what are the 3 main determinants of myocardial oxygen consumption (MVO2)
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wall tension
contractility heart rate |
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which part of the heart experiences the most wall-tension?
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the endocardium
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what stimulates endothelial cells to release their endothelial derived vasodilators?
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shear stress (i.e. during exercise)
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why do ROS decrease the vasodilatory effects of NO?
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Superoxide reacts with NO to make ONOO- (oroxynitrate)
failure to dilate |
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what is the physiologic change in step-wise growth of a coronary artery lesion?
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with no lesion: you can get 4x resting coronary blood flow during exercise
at 50% you're still pretty normal at 75% you begin to lose ability to increase coronary blood flow at 90% your resting coronary blood flow is below normal |
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what is the physiologic difference between chronic stable angina and unstable angina?
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unstable angina: >80% lesion with decreased coronary flow at rest
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what is the mechanism of vasodilation by nitrovasodilators?
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nitroprusside (NTP) releases NO nonenzymatically
nitroglycerin (GTN) releases NO non-enzymatically AND by mtALDH NO increases cGMP increases activity of MLC phosphatase=> less contraction |
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what is the difference between nitroglycerin and nitroprusside...why?
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nitroglycerin: dilates LARGE arteries and veins
nitroprusside: dilates all arteries non-preferentially and veins this is because large arteries have mtALDH which de-nitrates nitroglycerin (GTN) |
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what are the important notes about nitroglycerin dosing?
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lots of first past metabolism (sublingual)
dosing must be interrupted every 8-12 hours (overnight) or you get tolerance |
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what are the side effects and contraindications to nitroglycerin?
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SEs: headache (develop tolerance)
orthostatic hypotension reflex tachycardia (take with a B blocker!) contraindication: PDE5 inhibitors (viagra-verdafanil) |
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what is the mechanism of PDE5 inhibitors?
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they inhibit the breakdown of cGMP to GMP
stimulates cGMP-dependent-protein-kinase VSM relaxation |
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what are the side effects of PDE5 inhibitors?
|
sudden hearing loss
blurred vision, loss of color discimination orthostatic hypotension when combined with nitrovasodilators rhinitis, headache, flushing |
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what is the effects of Beta-2 blockade at the pancreas?
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impaired glycogenolysis
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which beta-blockers have intrinsic sympathomimetic activity
what is their use? |
PINDOLOL, acetbutolol
they are like partial agonists more useful in chronic use for people with too much bradycardia, not as useful for MI or angina trx |
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what are the contraindications to beta blocker use?
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SEVERE HF
severe asthma marked bradycardia advanced AV blockade severe peripheral vascular disease type II diabetes |
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what is the concern when you d/c beta blockers?
|
severe rebound HTN
gradually taper |
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what is the difference in effect between diltiazem and verapamil?
|
diltiazem: decreases HR
verapamil: decreases HR AND decreases contractility |
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which calcium channel blocker is used exclusively in subarachnoid hemorrhage?
|
nimodipine
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which calcium channel blocker can actually worsen outcomes after an MI?
|
nifedipine
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which is better for long term outcomes after an MI, Ca channel blockers or B blockers?
|
B blockers
calcium channel blockers have shown no effect or to be harmful (nifedipine) |
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what are the uses for cardioselective Ca channel blockers?
|
supraventricular arrhythmias
acute coronary syndrome hypertension |
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what are the side effects of nifedipine?
|
worsened MI outcomes
gingival inflammation and hyperplasia |
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what are the side effects of the calcium channel blockers
|
dizziness, HA
prolonged QT interval arrhythmias |
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what are the preferred Ca channel blockers in heart failure and why?
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amlodipine, felodipine
they have a smaller negative inotropic effect |
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what is the mechanism of Ranolazine?
|
it inhibits late Na influx, prevents exchange of Na for Ca, preventing Ca overload
shift energy utilization to glycolysis no effect on BP, HR, contractility improved exercise toolerance |
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what is the use for ranolazine?
|
chronic angina patients refractory to traditional therapy (nitrovasodilators, beta blockers, Ca channel blockers)
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what is the mechanism of the thienopyridines?
|
prasugrel and clopidogrel are both ADP antagonists that must be activated in the liver
prevent ADP mediated thrombogenesis |
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which is better, prasugrel or clopidogrel?
|
prasugrel!
hepatically actived faster less inactive metabolite longer duration of action |
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which lipoproteins contain TG?
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IDL, VLDL, chylomicrons
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which lipoproteins contain only cholesterol esters?
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HDL and LDL
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what is the difference between the endogenous and exogenous cholesterol pathway?
|
exogenous: ingested cholesterol and bile acids, including chylomicrons in circulation from GI tract to Liver
endogenous: produced in the Liver, circulating to tissues as VLDL, IDL, LDL, and HDL |
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what is the function of lecithin:cholesterol acyl transferase?
|
it esterifies cholesterol to a fatty acid in HDL for transport back to the liver
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when do you treat people with hypercholesterolemia?
|
if borderline high: only diet
if high with CHD or 2 risk factors: diet and drug if very high: drug and diet even without CHD or risk factors |
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what is the effect of cholestyramine and colestipol on liver cholesterol balance?
|
the liver produces MORE VLDL to compensate and blood TGs increase
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what is the mechanism of nicotinic acid?
|
prevents liver production of LDL
decreasese TGs way more than cholesterol |
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what are the two main SE concerns of the statins?
|
hepatotoxicity
rhapdomyolysis if taken with cyclosporin, clofibrate, niacin, or erythromycin) |
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what is the mechanism of the fibric acids?
|
clofibrate and gemfibrozil
stimulate lipoprotein lipase to decrease VLDL, increase HDL |
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what is the mechanism of probucol?
|
increased LDL catabolism
decreased LDL oxidation |
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what are the side effects of probucol?
|
decreased HDL
prolonged QT interval |
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what are the side effects of nicotinic acid
|
cutaneous vasodilation
glucose intolerance decreases secretion of fibrinogen |
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what are the 3 ways the liver can get cholesterol?
|
1. chloremnant receptor
2. LDL receptor 3. hepatic synthesis |
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what is the functional part of the HMG CoA reductase inhibitors?
|
a lactone ring
|
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which HMG CoA reductase inhibitors have closed rings (prodrugs) and closed rings (active form)
|
closed: simvistatin, lovastatin, mevastatin
open: fluvastatin, pravastatin |
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how do HMG CoA reductase inhibitors exert their effect?
|
decreased Cholesterol synthesis contributes a little
upregulation of LDL-R on hepatocytes and increased clearance is responsible for the majority of the effect |
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what is the sequence of the bezold jarisch reflex?
|
serotonin release by thrombus or enterochromaffin cell
bradycardia (5-HT3 receptor) vasoconstriction (5-HT2 receptor) vasodilation (5-HT1 receptor) |
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what is the mechanism of cyproheptadine?
side effect mechanism? |
it is a 5-HT1 and 5-HT2 receptor antagonist
decreases symptoms of a carcinoid serotonin releasing tumor (bezold jarisch reflex) also an H1 antagonist! |
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what are the 2 mechanisms of ketanserin?
|
it is a selective 5-HT2receptor antagonist
also an alpha1 antagonist |
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what is the use for ergonovine?
|
diagnostic of vaspspastic angina
control of pastpartum hemorrhage a partial 5-HT2 receptor agonist |
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LSD is similar to which drugs?
|
the partial 5-HT agonists ergotamine, methysergide, ergonovine
|
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what are the 2 uses for methysergide?
|
trx of carcinoid tumors and migraines
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what is the use for ergotamine?
|
migraines and postpartum bleeding
|
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what is the mechanism and use of the triptans?
|
sumatriptan zolmitriptan, rizatriptan
5-HT1b/d agonists prejunction inhibition of the trigeminovascular system preventing inflammatory vasodilation of cerebral vessels works very well for migraines |
|
|
which serotonin receptor is responsible for platelet aggregation and vasoconstriction?
|
5-HT2A receptor
inverse agonists being developed |
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what are the causes of HF with high cardiac output?
|
hyperthyroidism
beriberi AV shunt anemia |
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how is the starling relationship of the heart altered during HF?
|
for a given increase in filling pressure you have LESS INCREASE in stroke volume
|
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in a normal heart, what is the function of the Na/Ca exchanger?
|
while polarized: pumps Na(in) for Ca(out)
when depolarized: pumps Na(out) for Ca(in) |
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what channel is responsible for allowing Ca to enter CMC to stimulate RyR?
|
L-type calcium channel activated after Na depolarizes
|
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what mechanism does NOT contribute to HF?
|
energy storage or utilization
|
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what happens to baroreceptor function in heart failure?
|
resetting of baroreflex "normal"
at high pressures, the baroreflex fails to decrease sympathetic nerve activity |
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what are the 4 stages of Heart Failure
|
A: at risk with no signs/symptoms
B: structural damage with no signs/symptoms C: structural damage with past/current signs/symptoms D: Refractory HF requiring special intervention |
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what treatments do you use for stage A HF?
|
ACE inhibitors or ARBs (even though they are asymptomatic)
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what treatments can you use for stage B HF?
|
ACE inhibitors, ARBs, and Beta blockers
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what drugs can you use for stage C and D HF?
|
ACE inhibitors, diuretics, and Beta blockers
for select pts: k sparing agents, digitalis, vasodilators |
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when are postive Inotropes used in HF?
|
rarely, only in short term
never used alone. when the patient urgently needs extra heart activity digitali glycosides, adrenergic agonists, cAMP PDE inhibitors |
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what drugs should always be prescribed to patients with reduced LVEF
|
ACE-Is and Beta blockers
|
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which (ACE-Is or ARBs) allow for beneficial AT2 receptor activity?
|
ARBs
ACE-Is deplete Ang II/III ARBs only block AT1 both ACE-Is and ARBs increase Ang (1-7) |
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in HF patients, what effects do diuretics have on cardiac output?
|
despite decrease in preload, they don't greatly decrease CO because these patients are on a very shallow starling curve
|
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which chronic HF trx has the fastest effect?
|
diuretics (days)
ACE-Is, beta blockers, digitalis all take weeks-months |
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|
what effects do Beta blockers have on heart function?
mechanisms of effects? |
decreased inotropy
INCREASED LVEF anti-arrhythmic: decreased SNA prevents cardiac remodeling improves Ca handling: prevents hyper-phosphorylation of RyR |
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|
what vasodilator directly antagonizes TXA2?
|
epoprostenol (increases VSM cAMP)
|
|
|
what is the mechanism of digoxin's effect on the heart?
|
inhibits Na/K ATpase
decreased intracellular Na NCX allows more Ca inside the cell during polarized state increased contractility! |
|
|
what is the effect of digoxin at the kidney?
|
increased renal perfusion
inhibition of Na/K ATPase at kidney diuresis |
|
|
what drug desensitizes baroreceptors?
|
digoxin
desensitizes baroreceptors back toward normal increase PSNA and decreased SNA |
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when is digoxin used?
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HF patients in A-Fib
HF patients with severe symptoms on ACE-Is, ARBs, and/or Beta blockers |
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what are the risks and benefits of digoxin?
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risks: long term use can lead to arrhytmias
benefits: only in short term. no long term mortality improvement |
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what are the clinical uses for spironolactone and epleronone?
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improved survival in class III or IV HF used only in combination with other diuretics (they have little diruetic effect, just prevent hypokalemia)
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what 2 vasodilators are often used in combination therapy?
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hydralazine (arteriolar dilation)
isosorbide dinitrate (venodilator) |
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what is the mechanistic difference of dopamine infusion in low dose vs. high dose
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low dose: Beta1 heart agonist (increased SV, HR, EF)
high dose: alpha1 agonist (vasoconstriction, increased BP) |
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when is high dose dopamine infusion indicated?
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circulatory collapse (NOT HF!!)
agonist at alpha1 to promote peripheral vasoconstriction and increased BP |
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what are the main effects of dobutamine?
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Beta1 agonist: inotrope
little chronotropic activity at higher doses some Beta2 agonist activity |
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what are the physiologic effects of the cAMP PDE inhibitors?
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balanced arteriolar and venous dilation
inotropic increased myocardial relaxation |
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what is the preferred cAMP PDE inhibitor?
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milrinone > inamrinone
shorter t1/2 fewer side effects more selective |
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what is the last part of the heart to depolarize?
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the epicardium at the base of the LV
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what is the basis for the hyperpolarization of CMCs?
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K leak allows -90mV potential
would be -30mV with only Na/K ATPase pump |
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what are the 2 mechanisms of cardiac sodium channel opening/closing?
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m gate: activation gate activated (opened) by depolarization
h gate: inactivation gate activated (closed) temporally after m gate opens |
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what is unique about nodal cells and their action potentials?
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NO Na channels
If channel responsible for slow depolarizing current => automaticity |
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why do APs propagate slower through nodal cells?
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because of the slow Ca upstroke.
voltage moves faster when there is a greater rate of voltage change and a greater net voltage change |
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the PR interval is an indication of
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the speed of conduction through the AV node
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the length of the QRS complex is an indication of...
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the speec of the His-Purkinje system
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the QT interval is an indication of...
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the duration of AP (L-type Ca mediated)
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what are the 2 AP refractory periods?
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Effective (absolute): from AP onset to point where you can get an AP if you provide strong stimulation
Relative: from end of effective refractory period until normal membrane potential |
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what is by far the most common cause of cardiac arrhythmias?
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myocardial infarction, ischemia, myopathy
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how do early afterdepolarizations happen?
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prolonged APs: reactivation of Ca channels (very time dependent) so you get another depolarization during your relative refractory period
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what is "torsades de pointes"
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a run of EADs (early afterdepolarizations)
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what individuals are at risk for EADs/Torsades de pointes?
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hERG mutation in Ikr channel
slower K repolarization current long APs Long QT intervals at risk for EADs |
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how do delayed afterdepolarizations happen?
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abnormal Ca handling leads to spontaneous activation of RyR receptor
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what is the mechanism of digoxin toxicity leading to arrhythmia?
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Digoxin inhibits Na/K ATPase in CMC (increased [Na])
NCX pumps Na out and Ca in Ca activates RyR spontaneously leading to a DAD |
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what are the two pharmacologic strategies (3 drugs) of preventing a re-entry loop arrhythmia?
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prolong refractory period (Na channel blockers stabilizing inactivated state, K channel blockers delaying repolarization)
slow conduction so it stops when reversing |
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what is state and use dependent sodium channel blockade?
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sodium channel blockers bind best to activated and inactivated channels (not to resting) prolonging the refractory period
when you are in a tachycardic arrhytmia more Na blockers bind |
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what is common to all 3 types of Class I antiarrhythmic drugs?
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they all slow phase 0 upstroke of AP, slowing conduction through atria and ventricles
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what are the uses for 1A, 1B, and 1C antiarrhythmic drugs?
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1A: atrial and ventricular arrhythmias
1B: ventricular arrhythmias (lidocaine for acute, mexiletine for chronic) 1C: atrial arrhythmias |
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which anti-arrhytmic drug can cause lupus-like symptoms?
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procainamide
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which class of antiarrhythmic drugs have CNS toxicity?
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class 1B: lidocaine and mixiletine
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which antiarrhytmic agents cause negative inotrophy?
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disopyramide a 1A antiarrhythmic
also B blockers Cardioselective Ca channel blockers |
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what types of patients should you avoid 1C antiarrhythmics?
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in patients with any structural heart disease-increased mortality even though it decreases PVCs...only in "normal" hearts with A-fib
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what is the safest class III antiarrhythmic?
what SEs can it cause? |
amiodarone - not arrhythmogenic
if taken longer than 6 months it can cause hyper/hypothyroidism, liver, pulmonary toxicity |
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what is the major concern for the class III antiarrhythmics?
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prolonged QT leading to torsades des pointes
except for amiodarone |
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which class III antiarrhythmics have beta blocking activity?
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amiodarone and sotalol (L-isomer)
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what type of arrhythmia can be effectively treated with cardioselective Ca channel blockers?
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supraventricular tachycardia (SVT)
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what is the mechanism of adenosine as an antiarrhythmic?
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facilitates Ik and blocks Ica completely blocking the AV node
can break a reentrant loop OR used as a diagnostic tool to see only atrial activity for 5-10 seconds |
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which Class I drug can cause torsade de pointes?
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procainamide (1A) can cause torsades de pointes in fast acetylators
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which Class 3 antiarrhythmic drug has a half life of 2 weeks
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amiodarone
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what are the side effects of the Class IV antiarrhythmic drugs?
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decreased gastric motility, muscle weakness
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quinidine SE?
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diarrhea
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what are the effects of digoxin?
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inhibits Na/K ATPase (inotropic)
and slows AV node conduction |
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what agent can you use to prevent torsades de pointes?
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magnesium
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what drugs are well known as being arrhythmogenic?
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erythromycin, terfenadine, theophylline, and TCAs
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what are the side effects of disopyramide?
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negative inotrophy
anticholinergic (dry mouth, urinary retention, constipation) |
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what type of antihypertensive do you want to avoid in a diabetic patient?
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beta blockers, they can hide hyperglycemia
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what drug is 1st line therapy for a person in A-fib?
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digoxin
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