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287 Cards in this Set
- Front
- Back
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Name the vasoactive peptides that are vasoconstrictors.
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angiotensins, endothelins
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Name the vasoactive peptides that are vasodilators.
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bradykinin, natriuretic peptide
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What is the first product formed from angiotensinogen?
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angiotensin I
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What reaction does renin stimulate?
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angiotensinogen to angiotesin I
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What is angiotensin I converted to? By what?
|
to Ang II
by ACE |
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What mechanisms control renin secretion?
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renal vascular receptor
macula densa chemoreceptor beta 1 adrenergic receptor angiotensin receptor |
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What is the function of the renal vascular receptor?
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senses changes in perfusion pressure in the afferent arteriole
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What is the function of the macula densa chemoreceptor?
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senses changes in NaCl delivery to the distal tubule
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What is the function of the beta 1 adrenergic receptor in the angiotensin pathway?
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mediates renal sympathetic nerve activity
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What is the function of the angiotensin receptor?
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inhibited by Ang II
short-lop negative feedback |
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Name some tissues in which ACE is found.
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blood vessels, kidney, brain
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Which angiotensins are biologically active?
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Ang II has the highest
Ang III Ang IV in CNS and periphery different from II |
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What receptors mediate most of the effects of Ang II? Result?
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AT1
activate phospholipase C, other phospholipases, and several kinases leads to protein phosphorylation |
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What are AT2 receptors?
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found in fetal and some adult tissues
modulate effects of Ang II during growth and development activates phosphotases which dephosphorylate regulatory cell proteins |
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Compare AT1 and AT2 receptors.
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opposite functions
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What is the effect of Ang II on blood vessels?
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vasoconstrictor, AT1 stimulates inc in intracell Ca2+
AT2 cause vasodilation to prevent reduced blood flow |
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Why don't the effects of Ang II on the heart cause reflex bradycardia?
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acts on the brain to reset baroreceptor control of R
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What are the effects of Ang II on blood vessel and heart cells?
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cell growth and proliferation by AT1, also inc EC matrix
inhibited by AT2 |
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What is the effect of Ang II on the adrenal cortex?
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inc sythesis and secretion of aldosterone
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What is the effect of aldosterone secretion?
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promotes sodium reabsorbtion (exchanged for potassium) in distal and collecting tubules
may also promote cardiac fibrosis |
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What is the effect of Ang II on the kidneys?
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constricts renal arterioles
contracts mesangial cells (filtration) promotes sodium reabs by Na/H exchange in prox tubule inhibits renin secretion |
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What is the effect of Ang II on the ANS?
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enhances catecholamine release from the adrenal medulla and peripheral nerve terminals
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What is the effect of Ang II on the CNS?
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inc sympathetic activity
stimulates thirst and drinking inc secretion of ADH, ACTH, and others |
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How can activation of the RAS be detrimental?
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hypertension
trophic actions accelerate heart failure LV hypertrophy & fibrosis renal hypertrophy atherosclerosis |
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Name the inhibitors of renin secretion.
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B1 antagonists
NSAIDs central alpha 2 agonists |
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What is aliskiren?
|
a direct inhibitor of renin activity
tx of primary hypertension |
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Describe the pharmokinetics of aliskiren.
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orally active
low bioavailibility long half-life (24 hr) |
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What is a contraindication for aliskiren?
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pregancy
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What is the MOA of ACE inhibitors?
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inhibit conversion of ang I to ang II by ACE BUT NOT by alternative pathways
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What are the side effects of ACE inhibition?
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plasma renin activity and Ang I levels inc (no feedback inhib)
decreased aldosterone |
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What is the result of decreased aldosterone?
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dec retention of sodium
inc retention of potassium |
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What is aldosterone escape?
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aldosterone levels increase over time despite ACE inhibition
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What are the benefits of ACE inhibition?
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dec BP by dec PVR
dec after load prevent and/or reverse vascular remodeling improve renal perfusion improve insulin sensitivity & glucose metabolism |
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Name the prototype ACE inhibitor.
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catopril
shortest half-life |
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Name the important ACE inhbitors.
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catopril
enalapril lisinopril |
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What type of drug is enalipril?
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pro-drug, converted to enalaprilat in liver
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When can enalaprilat be administered directly?
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IV in hypertensive emergencies
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What is Lisinopril?
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lysine derivative of enalaprilat
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What are the therapeutic uses of ACE inhibitors?
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hypertension
herat failure post-MI chronic renal failure |
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What precautions must be taken with ACE inhibitors?
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hypotension
hyperkalemia renal function impairment drug interactions |
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What is the effect of Ang II receptor blockers (ARBs)?
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selectively block AT1
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What is the prototype ARB?
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losartan
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Describe the pharmacokinetics of losartan.
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orally active
extensive first pass hepatic metabolism active metabolite w/ longer half-life uricosuric properties |
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Name the prodrug forms of losartan.
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cadesartan cilexetil
olmesartan medoxomil |
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What are the therapuetic uses of ARBs?
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hypertesion
heart failure diabetic nephropathy esp in pts intolerate of ACE inhibitors |
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What type of drug is enalipril?
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pro-drug, converted to enalaprilat in liver
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When can enalaprilat be administered directly?
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IV in hypertensive emergencies
|
|
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What is Lisinopril?
|
lysine derivative of enalaprilat
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What are the therapeutic uses of ACE inhibitors?
|
hypertension
herat failure post-MI chronic renal failure |
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What precautions must be taken with ACE inhibitors?
|
hypotension
hyperkalemia renal function impairment drug interactions |
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What is the effect of Ang II receptor blockers (ARBs)?
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selectively block AT1
|
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What is the prototype ARB?
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losartan
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Describe the pharmacokinetics of losartan.
|
orally active
extensive first pass hepatic metabolism active metabolite w/ longer half-life uricosuric properties |
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Name the prodrug forms of losartan.
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cadesartan cilexetil
olmesartan medoxomil |
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What are the therapuetic uses of ARBs?
|
hypertesion
heart failure diabetic nephropathy esp in pts intolerate of ACE inhibitors |
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What are the adverse effects of ARBs?
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dizziness
angioedema (rare) |
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From what are kinins produced and by what? What are the two major ones?
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kininogens by kallikreins
bradykinin and kallidin |
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What converts kinins to metabolites?
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kininases I & II
(II = ACE) |
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What are the kinin receptors?
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B1- induced by chronic inflammation
B2- contitutively, actue inflammation |
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What is the results of B1/ B2 activation?
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phospholipase activation
stimlate formatio and release of prostaglandins and NO |
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What are the adverse effects of ARBs?
|
dizziness
angioedema (rare) |
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From what are kinins produced and by what? What are the two major ones?
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kininogens by kallikreins
bradykinin and kallidin |
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What converts kinins to metabolites?
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kininases I & II
(II = ACE) |
|
|
What are the kinin receptors?
|
B1- induced by chronic inflammation
B2- contitutively, actue inflammation |
|
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What is the results of B1/ B2 activation?
|
phospholipase activation
stimlate formatio and release of prostaglandins and NO |
|
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What is the effect of kinins?
|
vasoD and inc permiability
contraction of nonvasc smooth muscle (reg GI motility) regulate urine vol and comp elicit pain (sub P) |
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How do ACE inhibitors affects the kinins?
|
potentiate actions of bradykinin by inhibiting degredation
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What produces endothelins? What are the active endothelins?
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ECEs
ET1, ET2, ET3 |
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Which is the predominant endothelin in the CVS?
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ET-1
secreted by vascular endothelial cells |
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How is ET-1 gene expression increased?
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growth factors
cytokines vasoCs mechanical stress |
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How are endothelins cleared from circulation?
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degraded by NEP and clearance by ETb receptors
rapid |
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What does activation of ETa and ETb receptors by endothelins cause?
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activation of phospholipases
|
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What is the effect of ET-1 on blood vessels?
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transient vasoD (ETb- endothelial cells) followed by prolonged vasoC (ETa- smooth musc)
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What is the effect of ET-1 on the heart?
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direct positive inotropic and chronotropic effects (ETa on myocardial cells)
in heart failure has neg effect on LV contraction |
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What is the effect of ET1 on nonvasc smooth muscle
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VasoC
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What are the potentially pathologic roles of ET1?
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elevated in CHF, acute MI, pulmonary HTN, cerebral vasospasm, and renal failure
may contribute to fibrosis and hypertorphy (ETa) |
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Name the ET receptor antagonists?
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bosentan
ambrisentan |
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What is bosentan?
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nonselctive orally active ETa/ ETb blocker
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Whtat is ambrisentan?
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selective ETa blocker
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What are the therapuetic uses of ET blockers?
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tx of pulmonary arterial HTN
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What are the contraindications of ET blockers?
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pregnancy
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Procainamide
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class I antiarrhythmic
sodium channel blocker intermediate kinetics |
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Lidocaine
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class Ib antiarrhythmic sodium channel blocker
weak, rapid recovery |
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Flecainide
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class Ic antiarrhythmic sodium channel blocker
strong, slow recovery |
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Propanolol
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class II antiarrhythmic non-selective beta-blocker
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Amiodarone
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class III antiarrhythmic potassium channel blocker
beta blocking activity |
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Dofetilide
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class III antiarrhythmic potassium channel blocker
no beta blocking |
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Verapamil
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class IV antiarrhythmic
calcium channel blocker supraventricular tach |
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Adenosine
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reduces diastolic depl
slows conduction and inc refractory period (AV) terminate reentrant arrhyth. AV |
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Magnesium
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correct hypomagnesemia
refractory ventricular arrhythmias, some digitalis-induced arrhythmias, and drug-induced torsades |
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Potassium
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correct hypokalemia
suppress ectopic pacemaker |
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In cardiac muscle cells, how many phases are in the action potential?
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five
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In cardiac muscle cells, what causes phase 0?
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inward sodium curren
upstroke depolarizes membrane |
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In cardiac muscle cells, what causes phase 1?
|
aka rapid early repol
inactivated Na channels transient outward K+ |
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In cardiac muscle cells, what causes phase 2?
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aka plateau
inward Ca2+ thru L-type chan |
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In cardiac muscle cells, what causes phase 3?
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aka late rapid repol
inactivation of Ca2+ act/inac of outward K+ |
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In cardiac muscle cells, what causes phase 4?
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aka diastole
no net current flow |
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In cardiac pacemaker cells, how many phases are present in the AP?
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three (0, 3, 4)
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In cardiac pacemaker cells, what causes phase 0?
|
inward Ca2+, L-type channels
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In cardiac pacemaker cells, what causes phase 3?
|
outward K+
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In cardiac pacemaker cells, what causes phase 4?
|
diastole
gradually becomes less neg d/t inward sodium current |
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What three factors determine the rate of fire of a cardiac pacemaker cell?
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maximum diastolic potential (MDP)
slope of diastolic depol (phase 4) threshold potential |
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On an ECG, what does the heart rate represent?
|
SA node automaticity
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On an ECG, what does the P wave represent?
|
atrial depolarization
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On an ECG, what does the PR interval represent?
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time required for conduction of the AP thru the artia and AV node
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On an ECG, what does the QRS complex represent?
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ventricular depolarization
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On an ECG, what does the T wave represent?
|
ventricular repolarization
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On an ECG, what does the QT interval represent?
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ventricular AP duration
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What may cause an arrhythmia?
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disturbance in impulse generation, impulse conduction, or both
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What are the two causes of changes in automaticity?
|
altered normal pacemaker activity
abnormal pacemaker activity |
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What are after-depolarizations?
|
transient depols that interupt repol during phase 3 OR
arise after repol during phase 4 |
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What is triggered automaticity?
|
when after-depolarizations initiate extra systoles, following a normal AP
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What are the two types of abnormal impulse conduction?
|
block
reentry |
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What are the goals of antiarrhytmic therapy?
|
-reduce automatcity and slow rate of spont. impulse gen
-inhibit triggered activity -slow conduction velocity -prolong ERP |
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What are the four classes of antiarrhythmics?
|
class I: sodium channel blockers
class II: beta blockers class III: postassium channel blockers IV: calcium channel blockers |
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What are the three subclasses of class I antiarrhythmics?
|
calss Ia: intermediate
class Ib: weak, rapid recovery class Ic: strong, slow recovery |
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Give an example of each class of antiarrhythmic.
|
class Ia: procainamide
class Ib: lidocaine class Ic: flecainide class II: propanolol class III: dofetilide class IV: verapamil |
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What are the principle pharmacologic effects of class Ia antiarrhythmics?
|
dec Vmax of phase 0
inc ERP mod dec conduction V dec fast inward Na+ inhib K+ repol current |
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What are the principle pharmacologic effects of class Ib antiarrhythmics?
|
min change in Vmax of ph 0
dec cardiac AP duration dec inward Na+ current in vent inc outward K+ current |
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What are the principle pharmacologic effects of class Ic antiarrhythmics?
|
markedly dec Vmax of phase 0
big dec in vent conduction big inhib of inward Na+ high potential for proarrhythmia |
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What are the principle pharmacologic effects of class II antiarrhythmics?
|
beta blocker & membrane stabilizer
indirect SA/AV node effects to dec rate of spon. diastolic depol, slow cond V, inc ERP |
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What are the principle pharmacologic effects of class III antiarrhythmics?
|
prolong vent AP
prolong ERP inhib K+ repol currents Torsades potential |
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What are the principle pharmacologic effects of class IV antiarrhythmics?
|
inhib slow inward Ca+ current
min effect on vent AP major effect on AV slowed conduction velocity inc ERP |
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What are the potential adverse effects of procainamide?
|
lupus-like syndrome
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For what rhythms is lidocaine ineffective?
|
most supraventricular arrhythmias
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For what condition is verapamil contraindicated?
|
wolff-parkinson-white syndrome
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Catopril
|
ACE inhibitor
prevents progression of HF |
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Losartan
|
ARB
prevents progression of HF |
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Carvediol
|
nonselective sympatolytic
blocks alpha 1, beta 1 & 2 prevents progression & promotes regression of HF |
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Metoprolol
|
selective beta 1 blocker
prevents progression & promotes regression of HF |
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Hydrochlorothiazide
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thiazide diuretic
reduces preload on heart |
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Furosemide
|
loop diuretic
reduces preload on heart |
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spironoloactone
|
reduces fluid retention and K+ loss
|
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eplerenone
|
prevents aldosterone induced CV disfunction & remodeling, platelet aggregation, and secretion of pro-inflammatories
prevents progression of HF |
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Hydralazine
|
arterial vasoD
|
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Isosorbide dinitrate
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venous vasoD
|
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Digoxin
|
cardiac glycoside
inhibits Na+/K+ ATPase stimulates vagus nerve inc contractility dec HR |
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Name the types of drugs used to prevent the progression of HF?
|
RAAS blockers (ACE, ARBs)
beta blockers |
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Name the types of drugs used to treat the symptoms of HF?
|
diuretics
vasoDs inotropic drugs (cardiac glycosides, sympathomimetics, PDE inhibitors) |
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What is the first choice treatment for CHF?
|
ACE inhibitors
|
|
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What is the MOA of ACE inhibitors?
|
- dilate arteries/ veins, reducing pre and afterload
- promote excretion of water & Na - inhibit cardiac remodeling |
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What are the contraindications to ACEIs?
|
pregnancy
|
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What is the major difference in side effects between ARBs and ACEIs?
|
ARB- no dry cough
|
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What is the MOA of ARBs?
|
block AT1 receptors
|
|
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What is result of beta blockers in HF?
|
reduce workload
promote regression and slow progression of HF |
|
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What additional effects does carvedilol have?
|
antioxidant and antiproliferative
|
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For what patients are beta blockers NOT recomended?
|
dsypnea at rest
unable to tolerate hemodynamically unstable |
|
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What are the contraindications for beta blockers?
|
non-selectives: asthma/ COPD
all: unstable HF, severe bradycardia, heart block |
|
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What do loop diuretics inhibit?
|
Na+-K+-2Cl- antiporter in epithial cells of ascending loop
very powerful |
|
|
What is the first choice drug for quick relief of congestion and edema in CHF?
|
loop diuretics (furosemide)
|
|
|
What are the side-effects of loop diuretics?
|
hypokalemia
metabolic alkalosis |
|
|
What is the MOA of thiazide diuretics?
|
inhibit Na+-Cl- cotransporter on epithelial cells in distal tubule
less effective |
|
|
For what patients are thiazide diuretic ineffective/ not used?
|
ineffective if GFR < 30 mL/min
not with significant impairment of renal function |
|
|
What are the side effects of thiazide diuretics?
|
hypokalemia
metabolic alkalosis |
|
|
What are the negative effects of aldosterone on the heart?
|
interstitial fibrosis and HF
|
|
|
What are the effects of aldosterone on the kidney?
|
Na+/ fluid retention, K+ secretion
congestion, electrolyte imbalance |
|
|
What are the negative effects of aldosterone on the blood vessels?
|
endothelial dysfunction (NO)
vascular growth & remodeling |
|
|
What are some general effects of aldosterone?
|
platelet aggregation
secretion of inflammatory mediators |
|
|
What are the clinical uses of aldosterone blockers?
|
combined w/ diuretics to prevent hypokalemia
combined w/ ACEI & BB to class III and IV HF |
|
|
What are the side-effects of aldosterone blockers?
|
generally well-tolerated
gynecomastia hyperkalemia |
|
|
What are the contraindications for aldoserone blockers?
|
renal insufficiency
serum creatinine > 2.5 mg/dl creatinine clearance < 30 ml/min serum K+ > 5.0 Eq/L combining w/ K+ sparing duretics |
|
|
What is the MOA of cardiac glycosides?
|
inhibition of Na+/K+ ATPase
|
|
|
What are the inotropic effects of cardiac glycosides?
|
positive
inc intracellular Na+ alter Na+/Ca++ exchange inc intracell Ca2+ |
|
|
What causes the chronotropic effects of cardiac glycosides?
|
mix of direct (Na+/K+ ATPase inhibition) and indirect (autonomic reflexes)
|
|
|
What are the chronotropic effects are low to therapeutic levels of cardiac glycosides?
|
indirect effects
stimulate paraS and suppress S activity |
|
|
What are the chronotropic effects at high concentrations of cardiac glycosides?
|
direct
shorten AP and ERP by inc intracell Na+ conc initially delay afterdepols by inc intracell Ca2+ may trigger PVCs |
|
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What are the chronotropic effects of cardiac glycosides at toxic concentractions?
|
inc sympathetic outflow
|
|
|
What are the effects of digoxin on the kidneys?
|
inc perfusion
dec renin secretion |
|
|
What are the effects of digoxin on the vasculature?
|
vaso C (direct, normal heart)
vasoD (reduced SNS, HF) |
|
|
What are the effects of digoxin on the GI tract?
|
inc smooth muscle tone (vagal) and stimulation of chemoreceptor trigger zone
|
|
|
Thru what do sypathomimetics and PDE3 inhibitors both exert effects on the heart?
|
thru cAMP to inc Ca2+
inc HR, contractility and conduction velocity |
|
|
Name two beta agonists used to treat heart failure.
|
dopamine
dobutamine |
|
|
What is dopamine? What receptors does it act on?
|
norepinephrine precursor
beta 1- positive inotropic D1/D2- regional vasoD alpha 1 (high dose)- vasoC |
|
|
What is dobutamine? Effects?
|
selective beta 1 agonist
positive inotropic w/ little effect on HR and arterial pressure |
|
|
Name two PDE3 inhibitors.
|
(aka bipyridines)
inamrinone milrinone |
|
|
What are the effects of inamirone? Side-effects?
|
inc SV w/o changing HR
nausea, vomitting, arrhythmia, hepatoxicity, thrombocytopenia |
|
|
What are the effects/ side-effects of milrinone?
|
inc SV w/o changing HR
less toxic than inamirone arrhythmia, hypotension |
|
|
What are beta agonists and PDE3 inhibitors used to treat?
|
acute HF or if patients are intolerate to digoxin
IV infusion, short-term effects |
|
|
What is nesiritide? For what is it used?
|
recombinant human BNP
acute decompensated HF IV bolus then continuous infusion |
|
|
Abciximab
|
glycoprotein IIb/ IIIa inhibitor
blocks platelet aggregation |
|
|
Aspirin
|
COX-1 inhibitor
inhibits platelet aggregation |
|
|
Clopidogrel
|
ADP receptor inhibitor
inhibits platelet aggregation |
|
|
UFH
|
anticoagulation
indirect thrombin inhibitor binds to antithrombin III inhibits IIa and Xa |
|
|
Enoxaparin
|
aka LMWH
anticoagulation indirect thrombin inhibitor binds to antithrombin III inhibits Xa |
|
|
Lepirudin
|
direct thrombin inhibitor
anticoagulation |
|
|
Warfarin
|
anticoagulation
inhibits vitamin K dependent synthesis of II, VII, IX, X, protein C & S |
|
|
Alteplase
|
fibrinolytic
tissue plasminogen activator |
|
|
Name clotting factors of the intrinsic pathway.
|
XII, XI, IX
|
|
|
Name clotting factors of the extrinsic pathway.
|
III, VII
|
|
|
Name clotting factors of the common pathway.
|
I, II, X, XIII
|
|
|
Name three drugs that inhibit platelet adherence/ aggregation.
|
aspirin
clopidogrel abciximab |
|
|
Name two drugs that inhibit coagulation.
|
heparin
warfarin |
|
|
Name three fibrinolytics.
|
streptokinase
urokinase t-PAs |
|
|
What factors bind to cause platelet aggregation?
|
GPIa/ IIa and GPIb (platelets) bind to collagen and vWF (vessel)
|
|
|
What do adhered platelets release?
|
ADP, serotonin, thromboxane A2
|
|
|
To what does ADP bind? Result?
|
receptors P2Y1 and P2Y12
activates GPIIb/ IIIa and COX-1 |
|
|
What is the result of COX-1?
|
TXA2 synthesis
platelet aggregation |
|
|
What is the action of TXA2?
|
promotes platelet aggregation, degranulation, and vasoC
|
|
|
What binds to fibrinogen to cause aggregation?
|
GPIIb/ IIIa
|
|
|
What are the clinical uses of aspirin and clopidogrel?
|
primary and secondary prevention of coronary disease
|
|
|
For what patients in aspirin reccomended?
|
acute coronary syndrome w/ and w/o ST elevation
long-term Tx after PCI |
|
|
For what patients is clopidogrel reccomended?
|
pts who can't tolerate aspirin or contraindicated
|
|
|
For what patients is a combination of aspirin and clopidogrel reccomended?
|
undergoing PCI w/ stent placement
|
|
|
What is abciximab? How is it administered?
|
monoclonal antibody to glycoprotein IIb/ IIIa
blocks binding to fibrinogen IV |
|
|
What are the clinical uses of abciximab?
|
prevent PCI-caused thrombosis with planned procedure w/in 24 hr
acute coronary syndrome |
|
|
What are the adverse affects of abciximab?
|
bleeding
thrombocytopenia |
|
|
What is the effect of indirect thrombin inhibitors?
|
accelerate inhibitor effect of antithrombin on factors IIa and Xa by inc rate of thrombin- antithrombin III interaction
|
|
|
What are the risks with UFH?
|
unpredictable action
close monitoring of aPTT and platelet count required |
|
|
What are the advantages of LMWH/ enoxaparin?
|
predictable actions
monitoring of aPTT and platelet count not required |
|
|
How are UFH and LMWH cleared?
|
UFH- reticuloendothelial system
LMWH- kidneys |
|
|
What are the uses of heparin?
|
DVT/ PE prophylaxis
Tx of DIC and acute PE (large dose) |
|
|
What is the first line therapy for acute PE?
|
large dose heparins
|
|
|
What are the non-hemorrhagic side-effects of UFH?
|
thrombocytopenia
osteoporosis |
|
|
What is the antidote to heparin?
|
discontinue
protamine sulfate if bleeding (binds and inactivates) |
|
|
What are the pharmacokinetics of direct thrombin inhibitors?
|
IV administration
clearance affected by renal (lepirudin) or liver (argatroban) function |
|
|
What are the clinical uses of direct thrombin inhibitors?
|
pts w/ thrombosis secondary to heparin-induced thrombocytopenia
|
|
|
How is warfarin metabolized?
|
hepatic (CYP2C)
|
|
|
Which warfarin enatiomer is more active?
|
S-warfarin (4x R-warfarin)
|
|
|
How does warfarin inhibit synthesis of coagulation factors?
|
reduces gamma-carboxylation of glutamate residues in prothrombin factors
|
|
|
What are the clinical uses of warfarin?
|
prevention of
- DVT/ PE - thromboembolism in pts w/ afib, artificial heart valves, MI - DVT reoccurance |
|
|
What monitoring does warfarin therapy require?
|
prothrombin time
|
|
|
When is warfarin contraindicated?
|
pregnancy
- fetal hemorrhagic disorder - fetal abnormal bone formation |
|
|
What is streptokinase?
|
protein synthesized by streptococci
binds to plasminogen exposing active site & allowing cleavage to plasmin |
|
|
What is urokinase?
|
human enzyme
synthesized by kidney converts plasminogen to plasmin |
|
|
What is the MOA of t-PAs?
|
activate plasminogen bound to fibrin (formed clot)
avoids systemic function |
|
|
What are the clinical uses of fibrinolytics?
|
-acute MI if PCI not available
-severe multiple PE not hemodynamically stable -severe DVT -ascending thrombophlebitis of iliofemoral vein -stroke (w/in 3 hrs) |
|
|
Atorvastatin
|
HMG-CoA reductase inhibitor
active form, abs enhanced by food metab by CYP3A4 14 hr half-life |
|
|
Simvastatin
|
HMG-CoA reductase inhibitor
lactone prodrug, abs enhanced w/ food metab by CYP3A4 1-2 hr half-life |
|
|
Colestipol
|
bile-acid binding agent
inc bile acid secretion induce up-reg of LDL receptors |
|
|
Cholestyramine
|
bile-acid binding agent
inc bile acid secretion induce up-reg of LDL receptors |
|
|
Ezetimibe
|
inhibits intestinal absorption of cholesterol
|
|
|
Gemfibrozil
|
fibrate
PPAR agonist half-life 1.5 hr |
|
|
Fenofibrate
|
fibrate
PPAR agonist half-life 20 hr |
|
|
Niacin
|
treats hypercholesterolemia and hyertriglyceridemia
|
|
|
What is the major lipid, protein, and source of chylomicrons?
|
TG
B48, CII, E diet, sm. intestines |
|
|
What is the major lipid, protein, and source of VLDL?
|
TG
B100, CII, E endogenous, liver |
|
|
What is the major lipid, protein, and source of LDL?
|
cholesterol
B100 liver, diet, peripheral tissues; circulation |
|
|
What is the major lipid, protein, and source of HDL?
|
cholesterol
A1, CII, E peripheral tissue; liver, EC |
|
|
What is the major lipid, protein, and source of IDL?
|
cholesterol, VLDL
B100, E extrahepatic formation |
|
|
What lipoprotein is elevated in type IIa hyperlipidemia?
|
familial hypercholesterolemia
LDL, cholesterol |
|
|
What lipoprotein is elevated in type IIb hyperlipidemia?
|
comined hypercholesterolemia
LDL + VLDL (chol. and TG) |
|
|
What lipoprotein is elevated in type III hyperlipidemia?
|
aka dysbetalipoproteinemia
VLDL, chylomicron remnants (TG, chol.) |
|
|
What lipoprotein is elevated in type IV hyperlipidemia?
|
aka familial
VLDL (TG) |
|
|
What lipoprotein is elevated in type V hyperlipidemia?
|
aka mixed
VLDL and chylomicrons (TG, chol) |
|
|
What is the cause of type IIa hyperlipidemia?
|
LDL receptor or ApoB 100 deficiency
inc intake |
|
|
What is the cause of type IIb hyperlipidemia?
|
overproduction of VLDL
|
|
|
What is the cause of type III hyperlipidemia?
|
abnormal apo E
|
|
|
What is the cause of type IV hyperlipidemia?
|
overproduction or dec clearance of VLDL
|
|
|
What is the cause of type V hyperlipidemia?
|
deficiency of LPL
|
|
|
What are the two major sequelae of hyperlipidemia?
|
acute pacreatitis (TG)
CHD (chol) |
|
|
What is the MOA of statins/ HMG-CoA reductase inhibitors?
|
dec LDL-cholesterol
others |
|
|
What is the standard lipid lowering Tx immediately after coronary syndromes?
|
statins
|
|
|
Why are statins given at night?
|
cholesterol synthesis occurs predominately at night
|
|
|
What are the potential adverse effects of statins?
|
common: myopathy
rare: rhabdomylosysis hepatic toxicity |
|
|
What are the contraindications of statins?
|
pregnancy or breast-feeding
serious illness, trauma, surgery liver disease |
|
|
What is the MOA of ezetimibe?
|
binds to key mediator of cholesterol abs (NPC1L1) on GI epithelium and hepatocytes
reduce absorption inc expression of hepatic LDL receptors |
|
|
What is the MOA of bile acid-binding agetns?
|
inc bile acid secretion, causing increased conversion fo cholesterol to bile acid by 7alpha-hydroxylation (RL)
induce up-reg of LDL receptors |
|
|
What are the therapeutic uses of bile-acid binding agents?
|
hypercholesterolemia
digitalis toxicity (binds to and inactivates) |
|
|
How should resins/ bile-acid binding agents be taken?
|
with food (inc effectiveness)
other meds either 1 hr before or 2 hr after |
|
|
What are the contraindications to resins?
|
diverticulitis
elevated VLDL |
|
|
What are the drugs of choice of tx of hypertrigylceridemia?
|
fibrates/ PPAR agonists
|
|
|
What is the MOA of fibrates?
|
dec VLDL by
- inc LPL expresion - dec VLDL secretion inc HDL |
|
|
How do fibrates dec VLDL?
|
inc LPL expression by activating PPAR-alpha leading to inc lipolysis of VLDL TG
dec VLDL secretion by liver |
|
|
When does the risk of fibrate myopathy increase?
|
if given w/ statins
|
|
|
In what patients are fibrates contraindicated?
|
hepatic or renal dysfunction
biliary tract disease (caution- inc gall stones) |
|
|
What is niacin used to treat?
|
both hypercholesterolemia and hypertriglyceridemia
|
|
|
What is the MOA of niacin?
|
(unclear)
-inhibit VLDL secertion -inc VLDL clearance by LPL -dec catabolic rate of HDL -reduce Lpa -reduce fibrinogen levels |
|
|
Hydrochlorothiazide
|
thiazide diuretic
|
|
|
Nifedipine
|
dihydropyridine calcium channel blocker
peripheral vasoD |
|
|
Hydralazine
|
arterial vasoD
|
|
|
Propranolol
|
nonselective beta blocker
|
|
|
Prazosin
|
selective postsynaptic alpha-1 blockade, reducing NE vasoC
|
|
|
Captopril
|
ACE inhibitor
|
|
|
Minoxidil
|
arterial vaso D
severe or refractory HTN marked fluid retention |
|
|
Metoprolol
|
cardioselective beta-1 blocker
|
|
|
Clonidine
|
central-acting alpha-2 agonist
HTN urgencies |
|
|
Enalapril
|
ACE inhibitor
IV to quickly reduce BP in pt's w/ renin-dependent HTN or acute LV failure |
|
|
Nitroprusside
|
IV for HTN emergencies
arterial and venous vasoD reduces pre and afterload |
|
|
Labetalol
|
non-selective beta-blocker
also blocks alpha 1 orally or IV for HTN emergency |
|
|
Verapamil
|
calcium channel blocker
agina and supraventricular arrhythmia |
|
|
Losartan
|
ARB
only ARB w/ uricosuric effect |
|
|
Fenolodopam
|
arterial vasoD via DA1 recep
inc renal blood flow HTN emergencies |
|
|
What is the difference in initial versus long term effects of diuretic therapy?
|
intial- volume dec and dec CO
long- dec PVR w/ normal CO |
|
|
What are the potential side-effects of thiazide diuretics?
|
hypokalemia, hypomagnesemia, hyperuricemia, and hyperglycemia
|
|
|
What is the adverse effect of thiazide and loop diuretics?
|
inc plasma cholesterol and TG
|
|
|
What is the MOA of beta-blockers in HTN reduction?
|
dec HR and contractility -> dec CO (B1)
dec renin secretion (B1) dec NE release (prejun B2) reduced SNS outflow may stiumulate NO |
|
|
Why are cardioselective beta blockers preferred in diabetic patients w/ HTN?
|
nonselectives can-
interfer w/ insulin control in DM1 mask symptoms of hypoglycemia d/t epi release prolong recovery by inhibiting B2 glycogenolysis |
