Term
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Definition
| Affect tonicity control, acid base regulation, potassium balance, cation metab, renal perfusion, hormone action on kidney |
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Term
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Definition
Reabsorbs 50-55%filtered NaCl/60% filtered water/90% filtered HCO3/all glucose/amino acids/K/P/Ca/Mg/urea/uric acid
Major nephron site of ammonia production |
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Term
| Thick ascending Loop of Henle f'n |
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Definition
Reabs 35-40% NaCl/50% Mg/20-30% Ca
Active NaCl transport via Na-K-2Cl co transport |
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Term
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Definition
Reabs NaCl and concentrates urine;
Principle cells absorb Na/Cl, secrete K w/ partial aldosterone influence
Intercalated cells secrete H, reabs/secrete K, secrete HCO3
Reabs water/urea relative to ADH
secretes H/NH3, alters urine pH
Action via Na channels |
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Term
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Definition
Acts in PROXIMAL TUBULE via CARBONIC ANHYDRASE INHIBITION; must block 99% to bring on diuresis; causes HCO3 dumping, rapidly absorbed from the gut, 8-12 hours to excrete; continuous use=mild hyperchloremic acidosis, terminates diuretic action
Effects=good in edema w/ metab alkalosis (loss HCO3), urinary alkalinization, decrease aqueous humor, decrease CSF production and pH in acute mountain sickness
Contra=hepatic cirrhosis
Tox=hyperchloremic metab acidosis, renals stones, K loss, hypersensitivity rxn |
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Term
| Acetazolamide effects on urine |
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Definition
pH ++
Na +
K +
HCO3 ++
Cl -
PO4 + |
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Term
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Definition
water diuresis w/ some Na/K loss, doesn't permeate cells well, urine flow increased => Na/K/Cl/bicarb/Ca/Mg excretion; lowers resistance/increases total renal plasma flow
Effect=Inc urine volume, reduced ICP/IOP
Tox=Dehydration, hypernatremia (lose too much water), extracell volume expansion |
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Term
| Thick ascending Loop of Henle diuretics |
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Definition
FUROSEMIDE, BUMETANIDE, TORSEMIDE, ETHACRYNIC ACID
Most potent diuretics available, called high ceiling/loop diuretics;
INHIBIT ACTIVE CHLORIDE TRANSPORT, increase fractional excretion of sodium
Furo (and ~EA) affects proximal sodium reabs |
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Term
| Loop diuretic urine composition effect |
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Definition
pH+/-
Na +++
K ++
HCO# +/-
Cl +++
Ca +
Mg +
NA excretion max 20% |
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Term
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Definition
Works on luminal side of tubule, secreted into tubule to work
30-60 minutes after oral admin, peak in 1-2 hrs, last 4-8 hrs
5 minutes post IV, peak 15-45 mins, last 2-3 hrs
EA excreted by kidney and liver (2:1), Furo excrete by kidney and feces (2:1)
Furosemide generic not as good, volume of distro/half life increased in elderly |
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Term
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Definition
Reserved for pts w/ impaired renal f'n, refractory edema, acute pulm edema, hypertensive crisis
Not indicated as single agent;
Use in edema disorders, acute pulm edema, nephrotic edema, NA balance in acute/chronic renal fail, hypercalcemia, acute anion overdose |
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Term
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Definition
| Dehydration, hypokalemic metab alkalosis, azotemia, hyponatremia (loopF, unique), GI bleed (EA>F)
Interactions=aminoglycosides, allopurinol, cephaloridine, lithium, torsemide, warfarin (displaces drugs from plasma proteins; watch for sulfur allergy |
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Term
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Definition
DISTAL TUBULE
Chlorothiazide
Polythiazide
Methyclothiazide
Hydrochlorothiazide
Bendroflumethiazide |
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Term
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Definition
Works at both ends of acid/base balance; acts on Na/Cl co transporter by COMPETING FOR CHLORIDE SITE ON TRANSPORTER, INCREASE Ca REABS;
action additive to EA and Furo
Chlorthalidone/quinethazone/indapamide/metolazone not real thiazide but have similar diuretic properties |
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Term
| Thiazide urine composition effect |
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Definition
pH +
Na ++
K ++
HCO3 +
Cl ++
Uric +acid
Ca - |
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Term
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Definition
PReferred intial treat w/ normal renal f'n, ineffective w/ renal failure
Lower total periph resist, control mild essential HTN in 2/3
Adverse=K loss, insulin resist, lipid elevate
Used=HTN, CHF, edema, nephro diabetes insipidus |
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Term
|
Definition
HypoK, Hyperuricemia, Hyperglycemia, Hyperlipid, HyperCa (all dose related)
Acute pancreatitis, cholecystitis, hypoNa, drug interaction, decreased GFR, azotemia, sexual dysf'n |
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Term
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Definition
COLLECTING TUBULE ACTING
Class I=aldosterone antagonists (SPIRONOLACTONE, EPLERENONE)
Class II=NOT specific aldosterone inhib (TRIAMTERENE, AMILORIDE; inhibit sodium reabs)
Not potent alone, major use w/ loop/thiazide |
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Term
| Class 1 K-sparing diuretics |
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Definition
competitive inhib of aldosterone
Aldost=opens Na channels/ups number of channels
Spiro active at extra renal sites (seat glands, saliva, L intest), augments effects of ACEI in reducing proteinuria |
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Term
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Definition
reduce systolic/diastolic, lower incidence hypoK, dose related increase of hyperK;
gynecomastia, breast pain, menstrual irregularitites, impotence, decreased libido |
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Term
| Class 2 K-sparing diuretics |
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Definition
Blocks Na channel, no need for aldosterone site; prevents development of lumen-negative transepithelial voltage that drives K secretion;
Triam=effective from peritubular side, IRREVERSIBLY inhibits transbasolateral potential difference in collecting duct
Amilo=luminal side of tubule cell, REVERSIBLY inhib development of transluminal potential difference |
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Term
| K-sparing diuretic toxicity |
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Definition
Class 1=hyperK, gynecomastia, impotence, menstrual irreg, hypertriglyceride
Triam=hyper K, azotemia, glucose intolerance in diabetics, crystalluria, cast formation, triam stones, acute renal failure
Amilo=hyperK (highly selective, few side effects) |
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Term
Diuretic side effects
for thiazide/loop/k-sparing |
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Definition
Effect Thiazide Loop K-sparing
HypoK/hypoCl + + 0
alka
HyperK 0 0 +
Azotemia + + +
HypoNa + rare 0
Hyperglycemia + + 0/rare
Hyperuricemia + + rare
HyperCa + 0 0 |
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Term
| Adverse interactions of diuretics on potassium |
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Definition
1) K wasters with steroids/amphotericin/cation exchange resins result in hypokalemia; laxatives lower K; result in V-tach, torsade
2)with K-sparing, ACEI, ARB, transfusion, low salt milk, K-meds, and salt substitutes makes hyperK |
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Term
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Definition
| use of NSAIDs w/ diuretics inhibt prostaglandin synth=>unopposed pressor activity=>BP incr. |
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Term
| Diuretics and ototoxicity |
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Definition
| aminoglycoside IV or oral neomycin with loop diuretic; greater with preexisting renal insuff, old age, dehydration, or other similar drugs |
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Term
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Definition
| increase paralyzing effect of non-depolarizing muscle relaxants(atracurium) |
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Term
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Definition
| Increased hypotension and/or CNS depression w/ anxiolytics, sedatives, hypnotics, antidepressants, antipsychotics, narcotic analgesia, alcohol, muscle relaxants |
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Term
| Diuretics and acute phosphate nephropathy |
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Definition
| caused by use of oral sodium phosphates and diuretics, ACEI, ARB, NSAIDs from large phosphate load, fluid shifts and decreased intravascular volume |
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Term
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Definition
common, decreased effectiveness of Carbonic anhydrase inhibitors with development of metab acidosis
Acute=due to marked increase in proximal tubule sodium reabs (diminsh loop action)
Rebound sodium retention when loops wear off
Chronic therapy with loops increases sodium to distal sites=>hypertrophy of distal nephrons nad increase in distal resorptive capabilities=> lower sodium loss |
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Term
| Vasodilators through autonomic nervous system |
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Definition
Block alpha-1 (PRAZOSIN), non-selective alpha (PHENTOLAMINE)
Beta-1/2 block (ATENOLOL, PROPANOLOL, SOTALOL)
Block alpha-1/betas (LABETALOL, CARVEDILOL)
Deplete norepi (guanadrel) or prevent uptake (reserpine)
Activate alpha-2A to reduce central symp activity (CLONIDINE)
Activate D1 dopamine receptor (FENOLDOPAM) |
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Term
| Vasodilators through renin-angiotensin-aldosterone system |
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Definition
ACE inhibitor (CAPTOPRIL)
AT1 receptor blockers (LOSARTAN)
Aldosterone receptor antag (SPIRONOLACTONE, EPLERENONE)
Renin inhibitors (ALISKIREN) |
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Term
| Vasodilators through vascular smooth muscle and/or adjacent vascular endothelium |
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Definition
HYDRALAZINE (unknown mech)
MINOXIDIL (K channel opener)
SODIUM NITROPRUSSIDE, organic nitrates (NO donor) |
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Term
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Definition
NIFEDIPINE (dihydropyridine, voltage gated L-type antagonist)
VERAPAMIL (non-dihydropyridine, voltage gated L-type antagonist) |
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Term
| Phosphodiesterase inhibitors |
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Definition
| Theophylline (non-specific PDE inhibitor) |
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Term
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Definition
Exogenous false neurotransmitter stored/released like NE; active transport into the neuron, replaces NE, inhibits peripheral postganglionic adrenergic neurons
By IV, initially releases NE to increase BP at first, not noticeable with oral route
CONTRA=pheochromocytoma
During blockade, cells become supersensitive to NE |
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Term
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Definition
Binds tightly to storage vesicles in central/periph adrenergic neurons for long time
Inhibits vesicular catecholamine transporter that facilitates storage; nerve endings lose capacity to concentrate/store NE/dopamine=>pharma sympathectomy
Recovery requires synth of new storage vesicles |
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Term
Clonidine
Guanabenz
Guanfacine |
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Definition
Centrally acting sympatholytic agents
Stimulate alpha-2A adrenergic receptors in the brainstem, reduce CNS symp outflow; can activate alpha-2B receptors on vascular smooth mm at high doses |
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Term
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Definition
Oral ARTERIOLAR vasodilator, direct arteriolar smooth mm relaxation; decr resistance (afterload), BP; reflex incr HR, contractility, renin, fluid retention
May act thru memb hyperpol, K channel activation, IP3-induced Ca release in smooth mm sarcoplasmic retic.
Prevents nitrate tolerance (maybe by inhib vascular superoxide prod)
Supplemental to other major vasodilators, used in pregnant hypertensive emergencies
Adverse=reflex HR increase, contractility (bad in CAD) |
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Term
Minoxidil
(~Cromakalim, Pinacidil, Nicorandil as well) |
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Definition
K channel opener, direct vasodilation; metab to active minoxidil sulfate=>activates ATP modulated K channel in ARTERIOLAR smooth mm.
Hyperpol and relax in arteriolar smooth mm, little/no effect on venous/capacitance vessels
Adv=reflex incr HR, contractility, renin, fluid retention; increase O2 demand of heart=>ischemia in CAD/vent hypertrophy
Co-administer w/ sympatholytics (beta-blockers) to prevent adverse; GROWS HAIR (rogaine) |
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Term
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Definition
Releases NOthru spontaneous process, non-specific vessel relaxation (ARTERIES AND VEINS)
Decr pre/afterload, reflex incr in cardiac action but less than other vasodilators
Liberates NO and CYANIDE, leads to acid/base disturbance, arrhythmias, death; worse in renal failure=>diorientation, psychosis, muscle spasm, convulsion
IV in HTN emergencies/severe cardiac failure; rapid onset, short duration |
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Term
Ca channel Blockers
Nifedipine
verapamil |
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Definition
Ca influx thru L-type channels blocked, reducing Ca mediated activation of myosin light chain kinase, actin/myosin interaction, smooth mm contractility
Greatest effect on vascular smooth mm, arteriolar>venous
Decreases contractility, SA node rate, AV node conduction velocity in myocardium
Skeletal mm not effected by Ca blockers (relies on intracellular Ca, no influx needed)
Decr afterload, BP, cerebral vessels dilate, reflex HR/contractility incr (initial w/ nifed), decr HR/AV/contractility (eventually,w/ verap) |
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Term
| Ca channel blockers application |
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Definition
HTN, HTN emergency, angina, heart failure (nifed), arrhythmia (verap), prevent neuro deficit in cerebral artery spasm (nimodipine); great effects in low renin people, elderly, blacks
Adv=excessive vasodilate, AV block (verap), cardiac output drop, CHF precipitation (verap) |
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Term
Calcium channel blocker
overview of effects |
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Definition
Dihydro(nifed) Non-dihydro (verap)
Coronary dilate +++++ +++
Oeripheral dilate +++++ +++
HR + reflex -----
Contractility + reflex ----
AV conduction +/- -----
Ca channel recovery +/- --- |
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Term
Phosphodiesterase inhibitors
amrinone, milrinone |
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Definition
Prevent hydrolysis of cyclic nucleotides (cAMP, cGMP) to inactive forms; fairly selective to cardiac/vascular PDE3, result in incr cAMP=>positive inotropism, dilation of periph vessels
Use in short-term support of severe circulation fail, can get thrombocytopenia in 10%
Sildenafil=selective for cGMP PDE5 in erectile tissue, retina(small)
Adv=hypotension, MI, sudden death |
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Term
| Hypertensive emergency drugs |
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Definition
Sodium Nitroprusside=short acting arterial/venodilator in seconds; cyanide tox
Nicardipine/clevidipine=Ca channel block, 1-5 min/2-4 min respectively
Fenoldopam=D1 agonist, 4-5 min, maintain/incr renal perfusion
Nitro=arteriolar/venodilator, 2-5 min, good in cardiac ischemia/post-bypass
Phentolamine=non-selective alpha blocker, 1-2 min, for catecholamine related emergencies
Esmolol=Beta blocker, <5 min, for aortic dissection/post-op HTN
Labetalol=alpha/beta blocker, 5-10 min, safe in active coronary disease
Hydralazine=arteriolar dilation, 10-30 min, for eclamptic HTN emergency |
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Term
| Renin-Angiotensin-Aldosterone pathway |
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Definition
| Angioteninogen=>Angiotensin I (via Renin)=>Angiotensin II (via ACE, Chymase)=> AT1/2 |
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Term
| Rapid response of AT1 on AT1 receptor |
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Definition
Incr vasoconstriction, incr NE release, decr NE reuptake, incr catecholamine release in CNS/adrenal medulla
==>Increased resistance/afterload |
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Term
| Slow response of AT1 on AT1 receptor |
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Definition
Incr Na reabsorption (proximal), incr aldosterone (adrenal cortex), incr renal hemodynamics via direct constriction/catecholamine release/sympathetic tone)
==>Increased volume/preload |
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Term
| Non-hemodynamic response of AT1 on AT1 receptor |
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Definition
Incr proto-oncogenes, incr growth factors, incr synthesis of extracellular matrix proteins
==> Hypertrophy (w/ help from increased pre/afterload) |
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Term
|
Definition
Captopril, Enalapril; all similar acting end in -pril.
Prevent Angiotensin II formation, prevent bradykinin degradation (block kininase II)
Use=HTN, CHF, hypertrophic cardiomyopathy, MI, renal fail/fibrosis, diabetes, etc. |
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Term
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Definition
| useful in patients w/ LV hypertrophy and ischemic HD, less effective in blacks, superior to diuretic/beta blocker in diabetics |
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Term
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Definition
Relax vascular smooth mm, improve clinical/hemodynamic state of patient. No BP change
Arterial vasodilate=decrease resistance/afterload, outflow impedance to heart=> incr ejection fraction/stroke volume/cardiac output
Venous dilation=reduce preload, lowering left vent end diastolic press.
Great for diabetic HF, slow progression of nephropathy, decrease glomer cap pressure by decr BP and dilate renal arterioles |
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Term
| ACEI contra/adverse/interactions |
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Definition
Renal artery stenosis, hyperkalemia, symptomatic hypotension, pregnancy.
Adv=severe hypotension (more likely in hypovolemic), chronic nonproductive cough (block bradykinin degrade), altered taste, renal hemodynamic dysf'n (due to low renal perfusion), hyperkalemia (worse in renal insuff)
Intxn=ibuprophen (reduce antiHTN effect, renal tox), digoxin (reduced clearance), K supplements (hyperK), thiazide/loop diuretic (big hypotensive effect) |
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Term
|
Definition
LOSARTAN, similar end in -sartan
Nonpeptide receptor antagonism from binding angiotensin II, don't effect bradykinin degradation |
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Term
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Definition
| pts w/ high or normal renin, monotherapy if can't tolerate ACEI or in combination, less effective in blacks; NO COUGH, NO EDEMA |
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Term
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Definition
| Candesartan reduces CV mortality in LV dysf'n when substituted for ACEI or adding to ACEI, reduce CV events in high risk CAD, reduce mortality/morbid after MI, reduce mortality after stroke |
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Term
|
Definition
Renal artery stenosis, hyperkalemia, symptomatic hypotension, pregnancy.
Adv=severe hypotension (more likely in hypovolemic), altered taste, renal hemodynamic dysf'n (due to low renal perfusion), hyperkalemia (worse in renal insuff) |
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Term
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Definition
| Aldosterone receptor antag, K sparing diuretic, weak androgen receptor ANTAG/progesterone receptor AGONIST |
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Term
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Definition
| K sparing diuretic, selectivealdosterone receptor blocker w/ less affinity for androgen/progesterone/glucocorticoid receptors |
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Term
|
Definition
synth/secretion affected by angiotensin II, plasma K, ACTH
Receptors in kidney, brain, heart, vessels
Actions=stimulate Na retention by distal nephrons, K excretion, volume expansion, BP incr, stim myocardial fibrosis, reduce arterial elasticity, incr inflammation |
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Term
| Aldosterone receptor antag applications/contra/adv/interxn |
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Definition
HTN, CHF (low dose spirono, no large diuretic action)
Contra=hyperK, cirrhosis
Adv=Hyper K, progestational/antiandrogenic effects (only SPIRO; gynecomastia, impotence, menstrual irreg)
Interxn=DIGITALIS (lowers clearance) |
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Term
|
Definition
Stable, variant (Prinzmetal), unstable, acute MI
Acute coronary syndrome= Unstable, MI |
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Term
|
Definition
| deep, poorly localized chest/arm discomfort (not pain); caused by exertion/stress, fix in 5-15 minutes w/ rest/nitro; NO MYOCARDIAL NECROSIS; considered a chronic coronary artery disease |
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Term
| Variant/Prinzmetal angina |
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Definition
| almost exclusively at rest, not usually precip by exertion/stress; ST SEGMENT ELEVATIONS; caused by transient coronary vascular tone increase/vasospasm |
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Term
|
Definition
| At rest >20 minutes, described as new frank pain, crescendo quality over time |
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Term
|
Definition
| unstable angina w/o ST elev; 40-60% have myocardial necrosis, change in cardiac biomarkers; an acute coronary syndrome, artery not 100% occluded |
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Term
| General angina information |
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Definition
Caused by lack of O2 sufficient for the heart; coronary to LV only fills during diastole (in systole, interstitial tissue press is higher deeper); if tachycardic/elev LV diastolic press, flow is impaired.
Ca induces vascular contraction, NO induces relaxation |
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Term
|
Definition
Release NO: NITROGLYCERIN, ISOSORBIDE DINITRATE, ISOSORBIDE-5-MONONITRATE (all have 'nitr' in the name)
NO release, activates cyclase, incr cGMP, uncouples myosin/actin in smooth mm and dilates, BIG ACTION IN VENULES |
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Term
|
Definition
Decrease preload and pressure in ventricle during diastole=>incr coronary blood flow
Decrease O2 demand of heart by decreasing cardiac wall tension w/o directly changing contractility
Dilate large epicardial coronary vessels, preventing coronary steal (if all vessels expanded, those getting enough already steal blood from parts that need it); small vessels still controlled by local metabolites |
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Term
| Nitrate application/contra/adv/interx |
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Definition
Angina, CHF, MI
Contra=taking sildenafil, hypoTN, hypertrophic obstructive cardiomyopathy, diastolic HF
Adv=HypoTN, headache, dizziness, weakness, reflex tachycardia
Interx=all PDE5 inhibitors (sildenafil, vardenafil, tadalefil) |
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Term
| Nitrate tolerance/withdrawl, kinetics |
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Definition
Tolerance from continued/frequent exposure, needs interrupted for 8-12 hours daily (usually overnight)to restore effect
Withdrawl=angina intensified after discontinuing large doses of long acting nitrates and heightened sensitivity to constriction stimuli
Low bioavailability b/c of high first pass metab in liver (needs sublingual/IV/inhale); half life 2-8 minutes |
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Term
| Ca channel blocker classes |
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Definition
Phenylalkylamines=VERAPAMIL
Dihydropyridines=NIFEDIPINE, NIMODIPINE
Benzothiazepine=DILTIAZEM
Diarylaminopropylamine ether=bepridil
Diphenylpiperazine |
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Term
| Ca channel blocker action |
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Definition
Block both vascular smooth mm and myocardium, predominantly arteriolar dilators
T=low threshold; L,N,P/Q,R=high threshold Ca channels
L-type channel=critical in vascular/cardiac mm, blockers=VIRAPAMIL, DILTIAZEM, NIFEDIPINE
Inhibit Ca influx and evoke relaxation of arteriole but not venous smooth mm, decrease coronary resistance/incr coronary blood flow=>reduces angina
Ca block=>decr contractility of heart |
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Term
| Ca channel block mechanisms |
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Definition
Dilate arteriolar tension to reduce afterload/O2 demand;
Reduce contractility (decr O2 demand);
Decr HR (lower O2 demand);
Decr coronary resistance (incr coronary flow |
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Term
|
Definition
Variant angina, MI, stable/unstable angina
Nifedipine relaxes vascular at lower concentrations than takes to act on heart;
Verapamil=decr HR/contractility, rate of Ca channel recovery after opening (slows AV conduction)
Diltiazem=non-specific antag of symp NS, good for supraventricular reentry tachycardia, atrial tachycardia/flutter/fibrillation
Nimodipine=high affinity for cerebral vessels, may reduce vasospasm after sub-arachnoid hemorrhage |
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Term
|
Definition
cardiac depression/arrest, bradycardia, AV block, CHF
Contra=patients with HF |
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Term
|
Definition
Non-selective=PROPANOLOL, pindolol, SOTALOL
Beta-1 selective=ATENOLOL |
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Term
| Beta receptor distribution/action |
|
Definition
Beta 1=Myocardium, renal juxtaglomerular cells
Beta 2=Arteriolar vasculature of skeletal mm, venous vasculature, bronchioles, GI, bladder, uterus;
Reduces HR/contractility/arterial BP to decrease O@ consumption |
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Term
|
Definition
| Erectile dysf'n, CNS effects (depression/insomnia), CONTRA in asthma (bronchoconstriction). |
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Term
| Non-selective Beta blockers in vasospastic angina |
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Definition
May worsen condition;
Blockade of Beta 2 allows unopposed alpha 1 coronary vasoconstrict/systemic vascular resistance increase/increase preload in coronaries/variable response;
Tho beta blockers increase resistance initially, net effect is decr BP by negative inotrope/renin inhib/CNS actions |
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Term
| Hypertension prevalence/epid |
|
Definition
2x risk of CVD, 3-4x CVA;
Big in male, elderly, blacks
2 million new pts annually |
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Term
|
Definition
Output x peripheral resistance
HR x (preload/afterload) x contractility x resistance |
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Term
|
Definition
| HTN with low renin levels |
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Term
|
Definition
3 separate levels of elevated BP
140/90 or worse |
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Term
| Labs taken for HTN diagnosis |
|
Definition
| CBC, fasting CHEM-7, calcium, lipid panel, U/A, 12 lead EKG; urinary albumin/creatinine ratio in diabetics/renal insuffs |
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Term
| HTN cutoffs and treatments |
|
Definition
BP categ syst diast treat
Pre-HTN 120-139 80-89 lifestyle change
HTN stage 1 140-159 90-99 Thiazide, ACEI, ARB/BB/CCB
HTN stage 2 >160 >100 Two-drug combo |
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Term
|
Definition
| Diuretic, beta blocker, ACEI, ARB, aldosterone antag |
|
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Term
|
Definition
| Beta blocker, ACEI, aldosterone antag |
|
|
Term
| High coronary disease risk HTN drugs |
|
Definition
| Diuretic, beta blocker, ACEI, Ca channel blocker |
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Term
|
Definition
| Diuretic, beta blocker, ACEI, ARB, Ca channel blocker |
|
|
Term
| Chronic kidney disease HTN drugs |
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Definition
|
|
Term
| Recurrent stroke prevention HTN drugs |
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Definition
|
|
Term
| Behavioral treatment of HTN |
|
Definition
GET BELOW 140/90
Weight reduction, regular physical activity, reduced alcohol, reduced sodium, increased potassium |
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Term
|
Definition
Lifestyle change, monotherapy, second drug, third drug.
Start on 2 drugs if begin at stage 2 HTN |
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Term
|
Definition
| Decrease peripheral resistance, produce no reflex tachycardia/hypoTN/fluid retention, regresses LVH, protects heart/kidney/vasculature, enhances compliance, low cost |
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Term
|
Definition
Decrease PVR, good with young athletes/mild renal failure/diabetes/CHF;
5-20% cough, tendency hyperkalemia, precip acute renal failure if used in HTN secondary to renal artery stenosis |
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Term
|
Definition
Low side effects, no potentiation of bradykinin system, indication/contra similar to ACEI
Help in CHF, DM, renal disease, synergistic w/ diuretics |
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Term
| Beta blocker characteristics |
|
Definition
Decrease HR/cardiac output, cardioprotective post MI, help in migraine/angina
May aggravate asthma/CHF (except carvedilol), cause impotence/depression.
PROVEN IMPACT ON MORBIDITY AND MORTALITY IN HTN |
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Term
| Ca channel blocker characteristics |
|
Definition
Decrease PVR, lower HR/contractility; useful in elderly, pts w/ angina/dyslipidemia.
Adv=constipation, AV block, flushing, edema. 60% increase in MI w/ short acting dihydropyridine, LONG ACTING SAFER TO USE |
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Term
| Diuretics characteristics |
|
Definition
Work well in black/elderly, best reduced morbid/mortal;
thiazides may adversely effect dyslipidemia, hyperglycemia, gout; cause hypokalemia, impotence |
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|
Term
| Renin inhibitor characteristics |
|
Definition
| Reduced production of aldosterone, reduced mean albumin/creatinine ratio; similar adverse/contra as ACEI/ARB |
|
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Term
|
Definition
| Useful in prostatic hypertrophy and dyslipidemia and HTN |
|
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Term
|
Definition
| Not first line, may have other advantages (clonidine patch 1x week) |
|
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Term
|
Definition
| carvedilol may be used in CHF with decreased mortality |
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|
Term
| HTN in diabetics first choice |
|
Definition
|
|
Term
| Favorable effects on Co-morbid conditions in HTN |
|
Definition
Angina Beta block, Ca channel
A-tach/Afib Beta block, Ca channel
Cyclosporine induced Ca channel
Diabetes w/ proteinuria ACEI, Ca channel
Type 2 diabetes Low dose diuretic
dyslipidemia alpha-blocker
Essential tremor Beta blocker
Hyperthyroid Beta blocker
Migraine Beta blocker, Ca antagonist
Osteoporosis Thiazide diuretic
Preop HTN Beta blocker
Prostatic hypertrophy Alpha-blocker
renal insuff ACEI |
|
|
Term
| UN-favorable effects on Co morbid condition in HTN |
|
Definition
Bronchospastic disease Beta blocker
Depression Beta blocker,
central alpha agonist,
reserpine
Diabetes Beta block, high dose diuretic
Dyslipidemia Beta block, high dose diuretic
Gout Diuretic
2nd/3rd degree heart block Beta block, Ca channel
Heart Failure Beta block, Ca channel
Liver disease Labetolol, methyldopa
Periph vascular disease Beta block
Pregnancy ACEI, angiotensin 2 block
Renal insuff K-sparing
Renovascular disease ACEI, angiotensin 2 block |
|
|
Term
| Monotherapy failure predictors |
|
Definition
| Previous CV complications of HTN, cardiomegaly, LVH |
|
|
Term
|
Definition
Initial follow-up 1-2 months, then 3-6 if well controlled
Step down drugs if well controlled after 1 year |
|
|
Term
|
Definition
65-75% of elderly HTN, BP >140/<90;
Goal of <160 initially, <140 in the end |
|
|
Term
|
Definition
CVA, LV failure w/ pulm edema, eclampsia, acute MI; treatment involves IV nitroprusside/nicardipine/enaliprilat/nitro/hydralazine/labetalol/fenoldapam/esmolol/labetalol phentolamine/diazoxide
Nitro=acute MI, Esmolol=aortic dissection, hydralazine=eclampsia; goal=reduce MAP by 20-25% w/in minutes |
|
|
Term
|
Definition
| Needs reduction w/in 24 hrs; use clonidine, labetalol, beta blocker, loop diuretic, ACEI |
|
|
Term
|
Definition
Treat w/ methyldopa, hydralazine;
Atenolol, metoprolol, labetalol can be used in late pregnancy
ACEI CAUSE FETAL ABNORMALITIES |
|
|
Term
| Secondary HTN inducing agents |
|
Definition
| Cocaine, amphetamines, decongestants, hormones, cyclosporine, erythropoeitin, NSAIDs, ergotamine, MAOI, licorice, chewing tobacco |
|
|
Term
|
Definition
| Inability to lower BP despite maaximal triple therapy; usually due to non-compliance/sub-optimal therapy |
|
|
Term
| 4 stages of CHF treatment |
|
Definition
Prevention of heart failure
Prolong life
Reduce symptoms
End-stage consideration |
|
|
Term
| Left Ventricle CHF function |
|
Definition
Ineffective pumping
Decreased cardiac output="forward failure", DECREASED EXERCISE TOLERANCE, decr renal perfusion w/ azotemia, cachexia, hypoTN
Venous congestion="backward failure", neurohumoral responsecauses Na/fluid retention; Manifests as atrial enlargement (A-fib), thromboembolism (stasis), edema, hypoxemia, dyspnea |
|
|
Term
| Preload consideratinos in CHF |
|
Definition
Excess preload=> venous congestion in almost all CHF; DIURETICS, NITRATES, MORPHINE (vasodilate), Na RESTRICTION, WATER RESTRICTION, FUROSEMIDE (loop) for therapy
Add SPIRONOLACTONE, decr mortality 27%
ACEI, DIGOXIN improve forward flow, reduce preload |
|
|
Term
| Afterload consideration in CHF |
|
Definition
Decr cardiac output causes a compensatory increase in resistance=> incr afterload;
ACEI, ARB reduce response and lower afterload |
|
|
Term
| Systolic Dysfunction/contractility in CHF |
|
Definition
Ejection fraction <45%, commonly MI/dilated cardiomyopathy;
DIGOXIN/beta agonist (dopamine, dobutamine, epinephrine)/PDE inhibitors/vesnarinone improve systolic fxn
Therapy centers on afterload reduction
BETA BLOCKERS reduce contractility short term, chronic INCREASE in ejection fraction
Ca CHANNEL BLOCKERS (except amlodipine) REDUCE CONTRACTILITY, LEAD TO INCREASED MORTALITY |
|
|
Term
| Diastolic dysfunction/contractility in CHF |
|
Definition
Normal Ejection Fraction but still has HF
Contract INCREASED via ventricular hypertrophy/hypertrophic cardiomyopathy
Stroke volume reduced from small chamber volume=>depressed cardiac output despite high ejection fraction;
Beta block/verapamil recommended
Excessive afterload reduction is dangerous, leads to cavity obliteration (ventricle completely empties in systole, causes syncope from reflex bradycardia [BEZOLD-JARISCH RESPONSE] or pulm edema from tachycardia) |
|
|
Term
| Systolic vs Diastolic dysfunction |
|
Definition
Physiology Syst dysfxn Diast dysfxn
dPdT ---- +
Ejection fraction ---- ++
Chamber volumes ++ --
LV diastolic press + -
Etiology Ischemia, HTN, toxin, HTN, HOCM
infxn, tachycardia
ACEI +++ (1st line) +
Ca channel CONTRAINDICATE ++
Beta block ++ +++
Diuretics + (spironolactone) +/-
Digoxin ++ CONTRA |
|
|
Term
| Heart rate and rhythm in CHF |
|
Definition
Chronic bradycardia lowers output; PACEMAKER is treatment; acute episodes may use atropine/beta agonists
Chronic tachycardia limits diastolic filling, can cause severe systolic dysf'n
A-fib in 10-15% mild/moderate CHF
AMIODARONE=maintain sinus rhythm
DIGOXIN controls ventricular rate; so can beta block or combo of both |
|
|
Term
| Neurohumoral response to reduced cardiac output |
|
Definition
Increased sympathetic tone thru renin-angiotensin system=>incr PVR, CO, Na/water retention; long term=increased cardiac work load/progressive HF
ACEI and Beta block=reduce this response
ARB (valsartan) similar when ACEI can't be tolerated
Excess inhibition of symp NS is undesirable |
|
|
Term
| New York Heart Assoc heart failure classes |
|
Definition
1=No symptoms
2=sympt w/ ordinary activity
3=sympt w/ less than ordinary activity
4=sympt at rest |
|
|
Term
|
Definition
Improves exercise capacity in pts w/ systolic failure w/o increasing mortality;
when added to ACEI, reduces fluid retention drastically
CONTRA in diastolic dysf'n (makes squeeze harder, but it's already squeezing too hard) |
|
|
Term
| Reduced risk of sudden death in CHF |
|
Definition
| BETA BLOCKERS, ACEI, spironolactone |
|
|
Term
| Reduced likelihood of progressive pump failure |
|
Definition
| ACEI, beta blocker, maybe ARB |
|
|
Term
| Standard of care in screening for LV dysfunction |
|
Definition
Determine if systolic/diastolic
Do echocardiogram, nucleotide study, or angiogram |
|
|
Term
| Systolic dysfunction therapy |
|
Definition
| ACEI (afterload reduction) is essential, AVOID UNNECESSARY NSAIDs |
|
|
Term
| Therapy, goals and toxicities for 4 classes of CHF |
|
Definition
Therapy Goal Tox
Class 1 ACEI decr BP, suppress RAS cough, allergy
Class 2 ACEI, ARB Treat ischemia
Na restrict
BETA BLOCK select/non-select BRADYCARDIA
digoxin reduced symp tone? Arrhythm, hypoK
Class 3 ACEI, ARB
BETA BLOCKER TITRATE UP CAN WORSEN
SYSTOLIC
DYSF'N AT FIRST
DIGOXIN
Na restrict
Diuretics SPIRONOLACTONE Watch serum K
1ST LINE
Class 4 ACEI, ARB Treat ischemia
BETA BLOCK CONSIDER TRANSPLANT
DIGOXIN
|
|
|
Term
|
Definition
Most common=inducing bradycardia w/ excessive beta blockade
HypoK caused by excessive diuresis
HyperK by combo K-sparing and ACEI
Induce acute renal fail by combo NSAID and ACEI |
|
|
Term
|
Definition
Steroid/steroid glycoside, exerts POSITIVE INOTROPIC/ELECTROPHYSIOLOGIC effects on the heart
Enhance output during CHF, no change in normal patients
Treat SUPRAVENTRICULAR CARDIAC ARRHYTHMIAS, but OD may cause arrhythmia |
|
|
Term
|
Definition
Oral bioavailability
tablet 70%
capsule >80%
Onset of action
Oral 1.5-6hr
IV 15-30 min
Peak effect
Oral 4-6 hr
IV 1.5-4 hr
T1/2 36 hr
Route of elim Renal, some GI
Protein bound in plasma 23%
Therapeutic concent 0.8-1.6
Toxic concent >2.4
|
|
|
Term
|
Definition
| Retarded by food/antacids, delayed gastric emptying, malabsorption syndromes, antibiotics (neomycin, sulfasalazine), steroid binding resins |
|
|
Term
|
Definition
Most body tissues including RBCs, skeletal muscle, heart
Heart concentration 15-30x plasma at equilib |
|
|
Term
|
Definition
| 1.5 days, dependent on renal function; old/renal dysfunction=dosage must be reduced |
|
|
Term
|
Definition
| Without loading dose, max effect in 7 days; REQUIRES LOADING DOSE |
|
|
Term
|
Definition
Cholestyramine, antacids, kaopectate and bran diminish absorption
Antibiotics increase plasma digoxin levels (eradicate gut flora=>more absorption)
Antiarrhythmics (quinidine, verapamil, amiodarone) increase digoxin level (decrease clearance/volume of distribution) |
|
|
Term
|
Definition
Direct action, no direct effect on contractile proteins/chemical energy for contraction
INHIBIT MEMBRANE BOUND Na-K-ATPase!
Binds external portion, inhibits the enzyme (K binds too, enhanced in hypoK)
Intracellular Ca increases=>increased availability of Ca to myocardium |
|
|
Term
|
Definition
Results in increased cardiac output=>improves renal perfusion/ejection fraction=>decrease filling pressure
Decr venous pressure/LV end diastolic press=>heart returns to smaller size/relieves edema |
|
|
Term
| Patient w/o HF using digitalis |
|
Definition
| Causes DIRECT VASOCONSTRICTION; w/o CHF, afterload increases; w/ CHF, peripheral resistance already very high, no additional constriction, just inotropic action |
|
|
Term
|
Definition
Treat CHF from LV systolic dysf'n (dilated cardiomyopathy), usually from MI, myocarditis, toxins, or chronic mechanical overload
Improve symptoms, exercise capacity, decrease hospitalization, treat LVSD and A-fib
Used only for SYMPTOMATIC CHF, A-FIB |
|
|
Term
| Digoxin as antiarrhythmic |
|
Definition
Enhances vagal tone due to sensitized arterial baroreceptors, increased excitability efferent vagal fibers, increased sensitivity of heart to ACh;
Slows AV NODAL CONDUCTIONS and sinus rate
Won't bring out of A-Fib, but will slow the rate
Manages supraventricular arrhythmias (A-FIB, A-flutter, paroxysmal supraventricular tachycardia); MOST USED IN A-FIB |
|
|
Term
| Digitalis toxicity predisposing factors |
|
Definition
Ionic imbalance (DECREASED K, Mg; inc Ca)
Heart disease, renal/hepatic dysf'n, hypothyroid, drug interactions |
|
|
Term
|
Definition
Cardiac arrhythmias and conduction disturb
Anorexia, nausea, vomit (stimulate trigger zone)
Distortion of color vision, appearance of halos on dark objects
Headache, fatigue, insomnia, confusion, depression |
|
|
Term
| Arrhythmias caused by digoxin |
|
Definition
| Premature ventricular systoles, ventricular tachycardia, V-fib, junctional tachycardia, supraventricular tachyarrhythmias, A-V block |
|
|
Term
| Arrhythmia mechanisms in digoxin |
|
Definition
Neural: toxic doses activate both symp/parasymp nerves to the heart
Direct: Inhibit Na-K-ATPase, alter myocardium Ca/K/Na fluxes
Net effect can be A-V dissociation, premature ventricular beats, V-tach, V-fib |
|
|
Term
|
Definition
Stop drug, ECG monitor, correct electrolytes (high K=fatal)
Bradyarrhythmias from increased vagal tone (atropine OK to treat)
V-tach often lethal
TREAT WITH DIGIBIND
Don't shock, can cause unfixable arrhythmia problems and kill them |
|
|
Term
|
Definition
Inamrinone, milrinone=inhibit cyclic nucleotide PDE3 enzyme (cardiac specific cAMP PDE), leads to elevated intracellular Ca, act as vasodilators too.
Short term use in advanced HF;
Inamrinone tox=reversible thrombocytopenia
MILRINONE=Short term IV for severe CHF, post surgery/await transplant, bypasses Beta blockers, AGENT OF CHOICE |
|
|
Term
|
Definition
| Abnormal left ventricular function and neurohumoral regulation |
|
|
Term
|
Definition
| Most commonly A-fib; treat with beta blocker, digoxin, amiodarone |
|
|
Term
|
Definition
| Ibuprophen leads to lower renal f'n=>glomerular starving; major problem in little old ladies |
|
|
Term
|
Definition
| Change frequency of heart beats |
|
|
Term
|
Definition
| Change contraction strength of heart |
|
|
Term
|
Definition
| Change the speed of heart contraction |
|
|
Term
|
Definition
Biggest signal of contractility to heart
High NE, strong contraction |
|
|
Term
|
Definition
Low output from bad pump, use IV positive inotrope to treat
Systolic <100, output <2.2L/min/m2 with a high preload |
|
|
Term
|
Definition
Dopamine, dobutamine
Release NE from synapses=> increased cAMP=> incr Ca in cell=> stronger squeeze |
|
|
Term
| Beta agonism and arrhythmia |
|
Definition
| Higher rate of agonism, the higher chance of creating an arrhythmia |
|
|
Term
|
Definition
Wolff-Parkinson-White, cardiac amyloidosis, hypertrophic/restrictive cardiomyopathy
Relative contra=renal insuff, hypokalemia, hyperthyroid, acute coronary symptoms |
|
|
Term
| Supraventricular tachycardia |
|
Definition
| Many common forms are not considered life-threatening |
|
|
Term
|
Definition
All possess some automaticity
Ca dependent SLOW RESPONSE cells |
|
|
Term
|
Definition
His bundles, bundle branches, Purkinje fibers;
Na dependent FAST RESPONSE cells |
|
|
Term
|
Definition
Na inward current in slow-response cells;
Forms phase 4 (spontaneous depol)of action potential
Beta blockers decrease rate of Na current by inhibitin cAMP production and Protein Kinase A activation=>reduction of automaticity or HR |
|
|
Term
|
Definition
| Voltage gated Ca (inward current) in slow response cells, forms phase 0 (upstroke depol) |
|
|
Term
| I-Ca channel and beta blockers |
|
Definition
| Beta blockers decrease rate of Ca current by inhibiting PKA phosphorylation and activation of I-Ca channels=>reduction of automaticity/conduction velocity in AV node; decreases HR |
|
|
Term
| I-Ca channel and Ca channel blockers |
|
Definition
Slow the rise of action potential upstroke (phase 0) in slow response cells of SA/AV nodes, prolong AV node repolarization
Slowed conduction velocity thru AV node, increases effective refractory period of AV node
Verapamil/diltiazem=antiarrhythmic |
|
|
Term
|
Definition
| Outward K current channel open at rest, determines the membrane potential of the fast-response cells; plays key role in myocardial excitation and contraction |
|
|
Term
|
Definition
Voltage gated, phase 0 upstroke of rapid depolarization of fast response cells
Major determinant of velocity of impulse conduction thru ventricle
Na blockers=Class 1, bind both active/inactive state channels, increases threshold voltage for Na activation and increases refractory period |
|
|
Term
|
Definition
Phase 2 (plateau) of action potential, finely tuned balance between inward Ca and outward K current
T=transient, inactivate w/ time, insensitive to block by nifedipine
L=long lasting, dominant Ca current in virtually all cardiac cells, sensitive to Ca blockers |
|
|
Term
| Ca channel blocker action in I-Ca channels |
|
Definition
Accelerate the ventricular response by decreasing Ca influx, decreasing phase 2 period from continued outflow of K
REDUCES MYOCYTE CONTRACTILITY, SHORTENS REFRACTORY PERIOD and REPOLARIZATION IN FAST RESPONSE CELLS
Anti-arrhythmic properties of Ca channel blockers=action on slow-response cells in A-flutter/fib |
|
|
Term
|
Definition
| extrude 3Na for 2 K inflow; inhibited by digitalis |
|
|
Term
|
Definition
| Move Ca back into storage sarcoplasmic retic; blocked by Beta Blockers thru inhib of PKA-mediated phosphorylation of phospholamban |
|
|
Term
|
Definition
|
|
Term
|
Definition
Fast response cells=determined by voltage dependent recovery of Na channels
Slow response cells=time-dependent recovery of Ca channels |
|
|
Term
| Defects in Impulse formation |
|
Definition
Altered SA automaticity/ectopic automaticity (sinus tach, V-tach)
Early afterdepol (Torsades de pointes)
Drugs that prolong QT interval (amiodarone, procainamide, ibutilide) trigger EAD
Delayed afterdepol (MI, adrenergic stress, digitalis intox under intracellular Ca overload) |
|
|
Term
| Defects of Impulse conduction |
|
Definition
Re-entry (paroxysmal supraventricular tach)
Conduction block (MI, pharm agents pamiodarone, procainamide]) |
|
|
Term
| Defects in impulse formation AND conduction |
|
Definition
| A-fib w/ various degree of AV block |
|
|
Term
| Antiarrhythmic drugs act by altering... |
|
Definition
| Max diastolic potential in pacemaker and/or resting membrane potential in ventricular cells; phase 4 depol; threshold potential; action potential duration (thru phase 2,3 depol); refractory period |
|
|
Term
|
Definition
Fast Na channel blockers, bind in active state; PROCAINAMIDE, Quinidine, disopyramide
Moderate Na block w/ repol prolongation (decr phase 0 upstroke velocity); also block K channels;
Prolong SA node/vent myocyte repol
INCREASES QT INTERVAL, decreases reentry |
|
|
Term
| Class 1b Na channel blockers |
|
Definition
Bind channel in active/inactive, dissociate very fast
LIDOCAINE; mild Na block, little effect/decrease repol period in vent potential
NO QT INCREASE |
|
|
Term
| Class 1c Na channel block |
|
Definition
| FLECAINIDE; strong Na block, no effect on repolarization, NO QT INCREASE |
|
|
Term
|
Definition
Beta blocker
Non-selective=PROPANOLOL (1st gen)
Beta 1=ATENOLOL (2nd gen)
Beta 1 w/ vasodilation=CARVEDILOL (also block alpha receptor) |
|
|
Term
|
Definition
K channel blockers
Determine duration of plateau phase; larger hyperpol, shorter plateau
Increases refractory period=>decreased re-entry (increases time for Na to recover, facilitating EAD)
PROLONG QT INTERVAL, increased chance of EAD, Torsade |
|
|
Term
|
Definition
| Class 1/2/4, alters lipid membrane where channels live for A-fib |
|
|
Term
|
Definition
| Class 2, nonselective Beta antag, treats SEVERE VENTRICULAR ARRHYTHMIAS, prevent recurrent atrial flutter/fib |
|
|
Term
|
Definition
| Class 3, enhance slow inward Na current=>prolongs repol; TERMINATE A-FIB/FLUTTER, INCREASE QT INTERVAL, SERIOUS TORSADE RISK |
|
|
Term
|
Definition
Class 3 and anti-HTN, concentrated in terminals of sympathetics causing NE release and then inhibiting further release ("chemical sympathectomy")
Increases action potential duration in normal/diseased cardiac cells
Major action in Purkinje, second in vent myocytes; no effect on atrial tissue
USE ONLY IN PTS W/ RECURRENT V-TACH/FIB AFTER LIDOCAINE/DEFIB HAS FAILED |
|
|
Term
|
Definition
| Ca channel blockers; VERAPAMIL, DILTIAZEM; preferential to SA/AV nodal tissue |
|
|
Term
|
Definition
Bind specific P1 purinergic GPCRs, activates ACh sensitive K current in atrium/sinus/AV nodes=> shortening of action potential duration,hyperpol,slow normal automaticity
Reduces Ca currents, increases AV refractoriness and inhibiting DADs elicited by symp stimulation
TERMINATE PSVT |
|
|
Term
|
Definition
| Directly inhibit Na-K ATPase activity used in heart failure pts w/ re-entrant tachycardia |
|
|
Term
| A-fib w/ atrioventricular conduction via accessory pathway |
|
Definition
| PROCAINAMIDE, DC cardioversion |
|
|
Term
|
Definition
| AMIODARONE, LIDOCAINE, PROCAINAMIDE |
|
|
Term
| Ventricular premature beats |
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
Class Mech Drugs
I Na Block
Ia ++repol duration Procainamide, Quinidine, disopyramide
Ib -phase 0 in abnormal tissue Lidocaine
Ic ----conduction velocity Flecainide
II Beta blocker Propanolol, Atenolol
III ++ repol duration Amiodarone, Bretylium,
Sotalol, Ibutilide
IV Ca channel blocker Verapamil, Diltiazem
|
|
|
Term
| Specific arrhythmia therapies |
|
Definition
Arrhythmia Therapy
Atrial fibrillation Control vent response/restore sinus rhythm
Atrial flutter Same as a-fib
PSVT IV adenosine, verapamil, digitalis, procainamide
V-tach IV amiodarone, lidocaine, procainamide,sotalol
V-fib Lidocaine, amiodarone, procainamide, bretylium
Torsade Isoproterenol
Digitalis tox Stop drug, add digibind/Mg
|
|
|
Term
| Arrhythmia contraindications |
|
Definition
Condition Exclude/caution
Heart failure Flecainide
SA/AV dysf'n Digitalis, verapamil, Beta block, amiodarone
Wolff-Park-White Digitalis, verapamil
SA/AV conduction disease Lidocaine, amiodarone
Aortic/subaortic stenosis Bretylium
Hx of MI Flecainide
Long QT Amiodarone, quinidine, procainamide, sotalol, dofetilide
Heart Transplant Adenosine
Diarrhea Quinidine
Prostatism, glaucoma Disopyramide
Arthritis Chronic procainamide
Lung disease Amiodarone
Tremor Mexiletine, tocainide
Constipation Verapamil
Asthma, PVD, hypoglycemia Beta block, propafenone
|
|
|
Term
| Anti-arrhythmic Side effects |
|
Definition
Procainamide=Long QT, hypoTN, torsade, lupus-like syndrome
Lidocaine=confusion, dizziness, seizures; half life ~20min
B-block=B2-block effects, exaggerated B1 effects, insomnia, depression
Amiodarone=Long QT, hypoTN, reduced contractility, hyper/hypothyroid, elevated liver enzyme activity, periph neuropathy, headache, corneal microdeposits, testicular dysf'n, skin discoloration (mimic thyroid hormone, concentrate in many tissues, slow elim)
Adenosine=headache, flushing, chest pain, bronchoconstriction in asthma, half life <10 sec IV
Verapamil=neg. inotropic effect, chest fullness, dyspnea, hypoTN
Digoxin=arrhythmias, nausea, vomit, cognitive disturbance, blurred/yellow vision |
|
|
Term
| Anti-arrhythmic interactions |
|
Definition
Lidocaine=de-ethylated in liver; B-block/cimetidine reduce clearance (liver inhib); Barbiturate/phenytoin/rifampin induce enzymes
Amiodarone=Inhibit CYP3A4/2C9, slow warfarin, digoxin, flecainide, procainamide, quinidine metab
Verapamil=increase digoxin levels by competing for renal elim
Digoxin=Verapamil, amiodarone, cyclosporine, flecainide, spironolactone increases digoxin concent; hypoK potentiate arrhythmias (caused by diuretics, amphotericin B, corticosteroids) |
|
|
Term
|
Definition
| Activation, adhesion and aggregation of platelets making a WHITE THROMBUS; mainly in arteries, increased risk of ischemic injury |
|
|
Term
|
Definition
| Coagulation cascade, creating stable clot (RED THROMBUS); mainly in veins/deep tissues, increased risk of embolism |
|
|
Term
|
Definition
| PLASMIN breakdown of clot (insoluble fibrin) |
|
|
Term
|
Definition
| Main target for antiplatelet drugs; synthesizes thromboxane A2, a platelet derived vasoconstrictor/platelet activator-aggregator |
|
|
Term
| Major antiplatelet targets |
|
Definition
| COX1, TXA2, ADP receptor, GPIIb/IIIA surface antigens (bind fibrinogen, promote aggregation) |
|
|
Term
|
Definition
Acetylates COX, PERMANENT INACTIVATION; makes platelet incapable of TXA2 synthesis, can prevent recurrence of ischemic stroke; treat unstable angina, increases GI bleed/peptic ulcer, occasionally triggers allergy;
prevents benefits of fish oils (COX prevents TXA3 synth) |
|
|
Term
Clopidogrel
Prasugrel
Ticlopidine |
|
Definition
Thienopyridines; IRREVERSIBLE antag of ADP receptors P2Y1/P2Y12, prevents increase in IP3/cAMP respectively (stops surface expression of GP2b/2a fibrinogen receptor)
Treatment of choice for aspirin allergies
Prodrugs activated by P450, slow onset 3-5 days, peak 8-11 days |
|
|
Term
|
Definition
| P450 polymorphisms cause less drug metab; stomach disturb, PPIs help reduce the acid |
|
|
Term
|
Definition
| faster onset, more potent anti-platelet, less susceptible to patient P450 variations; side-effects greater; reduces thrombo CV events in pts w/ ACS w/ angioplasty |
|
|
Term
| Thienopyridine indications |
|
Definition
Take w/ aspirin following ACS, stent, or MI
Seldom prescribed for secondary prevent of cerebral vascular stroke (increased hemorrhage), primary prevent cardio disease
Adv=neutropenia, thrombocytopenia |
|
|
Term
|
Definition
Increases cAMP levels in platelets, acts similar to thienopyridines; INHIBIT cAMP PHOSPHODIESTERASE
ALSO A VASODILATOR
alone=post-op prophylaxis of thrombo w/ heart valves
Time release w/ aspirin=prevent stroke recur |
|
|
Term
|
Definition
Fab fragment of monoclonal Ab against GP2b/3a on platelets; blocks platelet interaction w/ vasculature/each other for up to a week;
IV during angioplasty for coronary thrombo/reduce restenosis
Risks=excessive bleeding |
|
|
Term
|
Definition
| Inhibits GP2b/3a; similar to abciximab, shorter duration of action, less immunogenic |
|
|
Term
|
Definition
| Reversible, non-peptide inhibitor GP2b/3a, similar to eptifibatide |
|
|
Term
| Major coagulation drug targets |
|
Definition
| antithrombin, thrombin, vitamin K epoxide reductase |
|
|
Term
|
Definition
| Most common hemophilia, Factor 8 deficiency; admin only after bleeding begins |
|
|
Term
|
Definition
Intrinsic coagulation
Tests 8, 9, 11, 12 |
|
|
Term
|
Definition
Intrinsic pathway
Tests factor 7 |
|
|
Term
|
Definition
UFH=secreted by mast cells, mix of negatively charged sulfated mucopolysaccharides
LMWH=enoxaparin, dalteparin, tinzaparin; cleared by kidney |
|
|
Term
|
Definition
Synthetic selective INHIBITOR of Factor 10a, smaller than LMWH;
prophylax DVT
Cleared via kidney; DOES NOT TRIGGER THROMBOCYTOPENIA |
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Term
|
Definition
BIND ANTITHROMBIN PROTEINS IN NORMAL BLOOD AND ENHANCE ACTIVITY
Acts as a catalytic surface to increase association b/w antithrombin and ACTIVE coag factors |
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Term
|
Definition
Binds thrombin with low affinity, heightened w/ heparin; inhibits activated factors 10,9,11,12,kallikrein, NOT FACTOR 7!!
AT3=suicide substrate (once complexes w/factor, both removed forever) |
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Term
|
Definition
UFH=can inhibit thrombin (requires all 3 components bind simultaneously, needs to be large to do so)
LMWH=INHIBIT FACTO 10a (doesn't need to be as big to hit factor) |
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Term
|
Definition
UFH=immediate by IV, half life increases w/ increasing dose, NOT cleared by kidneys (good w/ renal fail)
LMWH=greater bioavailability, longer plasma half-life, simpler kinetics, cleared by kidneys |
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Term
|
Definition
Treat venous thrombo
LMWH=FIRST LINE PREVENTION/TREAT, prevent recurrent angina/MI |
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Term
|
Definition
UFH=load 5-10k units IV, maintain 900-1600/hr; keep PTT 1.5-2.5x control
LMWH=subcutaneous 5k units 8-12 hrs, NEVER INTRAMUSCULAR (hematoma), don't monitor PTT |
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Term
|
Definition
Bleeding, heparin induced thrombocytopenia (<25% 7-14 days after start, may cause MI, stroke, artery occlusion; immune rxn, IgG-mediated platelet activation, less frequent w/ LMWH/synthetics)
DOES NOT CROSS PLACENTA, but still use caution in pregnant;
Less frequent adv=osteoporosis, spontaneous fracture, alopecia
CONTRA=hypersensitivity, active bleeders, thrombocytopenia, purpura, GI ulcers
NEVER GIVE IN BRAIN/CORD/EYE SURGERY (minor bleed=BIG complications) |
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Term
|
Definition
PROTAMINE SULFATE, tightly binds/neutralize heparin; also interacts w/ platelets/fibrinogen=>weak anticoag effect
NO EFFECT ON LMWH OVERDOSE |
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Term
|
Definition
Reversible, direct thrombin inhib
Inhibit clot bound/circulating thrombin, heparin alternative if get thrombocytopenia
Cleared by kidney, affects both PT/PTT |
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Term
|
Definition
| Small, reversible direct thrombin inhib, CLEARED BY P450 IN LIVER, monitor PTT, aim for 1.5-3x |
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Term
|
Definition
Oral anticoag
Inhibits reduction of vitamin K-epoxide back to active form, depleting co-factor needed for activating factor 2, 7, 9, 10
100% orally bioavailable, 99% plasma bound, long half life, inactivated in liver/kidney to urine, S-form 4x more potent than R-form |
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Term
|
Definition
Small daily doses, lowered to constant dose as indicated by PT, no loading dose;
NO EFFECT ON ALREADY SYNTHESIZED/CARBOXYLATED COAG FACTORS
Aim for PT 25% normal/INR 2.5-3.5 |
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Term
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Definition
| Prevent stroke/PE after MI, prevent stroke in high risk, A-fib (reduced stroke rate), prosthetic heart valves (reduced thrombo), treat/prophylax venous thrombo |
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Term
|
Definition
| Any agent that alters uptake/metab or drug/vitamin K, synth/f'n/clearance of factors, epithelial integrity |
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Term
| Warfarin increasing drugs |
|
Definition
Phenylbutazone, sulfinpyrazone=inhibit metab transformation of S-form and displaces from albumin
Metronidazole, fluconazole, trimethoprim-sulfametoxazole=inhibit S-form transformation
Amiodarone, disulfiram, cimetidine=inhib metab of both S/R forms
Aspirin=direct effect on platelet f'n
3rd gen cephalosporins=elim GI bacteria that make vitamin K |
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Term
| Warfarin decreasing drugs |
|
Definition
Barbiturates, rifampin=induce hepatic enzymes in metabolic clearance
Cholestyramine=reduces absorption of drug
Vitamin K rich food
Diuretics=concentrate clotting factors
Hereditary resistance to oral anticoag |
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Term
| Warfarin toxicity/reversal of overdose |
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Definition
Withhold at any sign of bleeding, increased fracture risk in elderly women
Vitamin K=antidote, may take 24 hrs; fresh frozen plasma/factor 11 concentrate in immediate emergency |
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Term
|
Definition
PREGNANCY!!! can cause birth defects/abortion
Unreliable patients (ineffective dosing)
EXTREME CAUTION w/ hepatic/renal disease, GI lesions
Stop days before major surgery |
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Term
|
Definition
| Promote conversion of plasminogen to plasmin |
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Term
|
Definition
| Thrombolytic, produced by kidney, direct plasminogen-plasmin conversion, RARELY USED |
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Term
|
Definition
Thrombolytic, forms stable complex w/ plasminogen facilitating conversion
Allergic response in 5% |
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Term
|
Definition
| Thrombolytic, complex of streptokinase and human plasminogen, made sensitive for spontaneous activation by cleavage, single IV injection |
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Term
| Tissue plasminogen activator |
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Definition
| Thrombolytic, activates plasminogen in PRESENCE OF FIBRIN, DOES NOT INDUCE SYSTEMIC PLASMIN ACTIVATION, only acts on the thrombus |
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Term
| Thrombolytic indications/contras |
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Definition
Multiple PE, central DVT, acute MI ONLY IN 1st timers (higher allergy in 2nd time)
CONTRA=Surgery, GI bleed, aneurysm, HTN, active bleed |
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Term
|
Definition
| Fat->chylomicrons->fatty acids + remnants->liver->VLDL->FFA + IDL->LDL via HDL->back to liver |
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Term
|
Definition
| LDL engulfed by macrophages w/in arterial walls to form foam cells; HDL removes cholesterol from foam cells |
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Term
|
Definition
Fish oil=> decr LDL, incr HDL, decr TG
Veggie oil=> decr LDL, decr HDL, incr TG |
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Term
| Major risk factors for coronary HD |
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Definition
DIABETES, FAMILY HISTORY OF CHD DEATH
Age, low HDL, high cholesterol, BP, smoking, obesity |
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Term
|
Definition
Cholestyramine, Colestipol, Colesevelam
Lower LDL chol by INCREASING ApoB100 ON HEPATOCYTES=>LDL REMOVAL |
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Term
|
Definition
| HETEROZYGOUS familial hypercholesterolemia, combined hyperlipid |
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Term
| Resin mechanism of action |
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Definition
| Nonspecific bile acid binding w/in intestine, inhibit acid reabsorption; cholesterol is acid precursor, inhibit reabs->incr channel of cholesterol to bile acids->decr intra-hepatic cholesterol->upreg of apoB/apoE->incr clearance |
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Term
|
Definition
stimulates secondary cholesterol production
Constipation, bloating, gallstones, steatorrhea
COLESEVELAM BETTER TOLERATED |
|
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Term
|
Definition
| Interferes w/ drug absorption (digitalis, thiazides, beta blockers, warfarin, fat soluble vitamins) |
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Term
| HMG-CoA Reductase inhibitors |
|
Definition
Lovastatin, Simvastatin, Atorvastatin, Rosuvastatin
Use in all forms FAMILIAL hypercholesterolemia/combined hyperlipidemia |
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Term
| Statin (HMG-CoA reductase) mechanism |
|
Definition
Competitively inhibit cholesterol synthesis enzyme
Reduced liver chol->upreg apoB/E->increased clearance
Increase HDL (especially simva/atorva), lower TG |
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Term
|
Definition
Mild hepatotox (high enzymes), myopathy (w/ cyclosporin/fibric acid coadmin, reverse by stopping drug), high doses=RHABDOMYOLYSIS w/ fibric acid derivatives
NEVER GIVE TO PREGNANT |
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Term
| Statin kinetics/interactions |
|
Definition
Excreted by liver
Intx=Grapefruit juice, verapamil =incr concentrations lova/simva by inhibit CYP3A4
Pravastatin not affected |
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Term
|
Definition
| First one made, prodrug activated in GI tract, high first pass metab; 5% reaches active state in blood |
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Term
|
Definition
| prodrug into active in GI; better absorbed than lova, 2x potency |
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Term
|
Definition
| Active as given, readily absorbed, 2x potency, more effective in reducing LDL (50-60%) and TG (20-30%) |
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Term
|
Definition
| Similar to atorva, higher incidence of adverse (rhabdo, renal fail); watch levels, asians easy overdose |
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Term
|
Definition
| ALL STATINS CAN CAUSE RHABDO IN HIGH DOSES!!!!!!!!!!!!!! |
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Term
|
Definition
| Active drug, equal to lova, similar absorption |
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Term
| Estrogen replacement therapy |
|
Definition
| Incr HDL 15%, decr LDL 15%, don't know why; higher HD/breast cancer |
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|
Term
| Cholesterol absorption inhibitor |
|
Definition
Ezetimibe
Acts on brush border, prevent chol absorption; combined with statin=LDL lowered additional 25%
NO PREVENTION OF PLAQUE, CORONARY EVENTS, ISCHEMIC STROKES |
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Term
|
Definition
Lowers TG
Use in heterozygous familial hyperchol, mixed lipidemia, combined hyperlipo, familial dysbetalipo, Lp(a)hyperlipo |
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Term
|
Definition
Direct decr VLDL synthesis, lowering IDL/LDL levels
Increases HDL lots by decreasing Lp(a) levels |
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Term
|
Definition
Flushing, pruritis, rashes, reversible carb tolerance impairment, hyperuricemia, hepatotox
LAROPIPRANT-prostaglandin D2 antag, prevents flushing |
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|
Term
| Fibric Acid derivative uses |
|
Definition
Fenofibrate
Moderate/severe familial hyperTG, familial disbetalipo |
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|
Term
| Fibric acid deriv mechanism |
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Definition
| bind PPAR-alpha in liver/brown fat regulating genes=>increased lipase activity (VLDL breakdown), decreased VLDL synth/excretion, incr HDL |
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Term
| Fibric acid deriv adverse/intx |
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Definition
Well tolerated, rarely get skin rash, GI symptoms; myopathy, rhabdo w/ statin coadmin; anemia, gallstones in obese/native amer.
Intx=potentiates warfarin/indanedione anticoag by displacing from albumin |
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Term
|
Definition
Decr TG by VLDL synth suppression
Incr HDL
May have anti-platelet activity |
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Term
| Lipid drugs in combination |
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Definition
Neomycin + niacin=highly synergistic in lowering chol
Statin + resin=lower LDL-C
Niacin + resin=lower LDL-C |
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Term
|
Definition
Disorder Manifest Rx
Chylomicronemia Incr chylo, incr VLDL Niacin + Fibrate
Familial hyperTG Incr VLDL, incr chylo Niacin + Fibrate
Familial combined Incr VLDL, incr LDL Niacin + resin/statin
hyperlipo
Familial hyperchol Incr LDL heterozy Niacin, statin +/- resin
homozy Niacin + atorvastatin
Lp(a) hyperlipo Incr Lp(a) Niacin + neomycin
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Term
| Steroids vs second messengers |
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Definition
Steroids=NO IMMEDIATE secretion of hormones
Messengers=rapid hormone secretion, gradual change in protein synth rate/gene transcription |
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Term
|
Definition
| adrenal, sex, calciferols, other vitamins |
|
|
Term
| peptides and protein hormones |
|
Definition
| hypothalamic releasing factors, pituitary hormones, insulin, glucagon, calcitonin, oxytocin, vasopressin, relaxin, GI hormones, angiotensin |
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Term
|
Definition
| dopamine, epinephrine, thyroid hormones |
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Term
| Simple negative feedback control |
|
Definition
| As substrate increases, inhibits release of hormone (ex. glucose/glucagon regulatino, PTH/plasma calcium, insulin/glucose) |
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Term
| Complex endocrine control |
|
Definition
| Regulated by hypothalamic releasing factors and anterior pituitary hormones (ex. TRH/TSH/thyroxine, CRH/ACTH/glucocorticoids) |
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Term
| Growth hormone (somatotrophin) actions |
|
Definition
Results in positive nitrogen balance and enhanced protein synthesis; makes Na, K, P, Ca, Cl retained by body;
Anabolic hormone (w/ insulin)
Favors fat for energy
Stimulates synth/release somatomedin C (aka IGF-1) in growth plate cartilage/kiver, stimulate matrix formation
GH=sirectly stim fat metab/incr gluneo in liver |
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Term
| GH/somatomedin C level regulation |
|
Definition
GH=GH releasing hormone/somatostatin from hypothalamus into pituitary portal system
Alter release of GH by altering adenylyl cyclase/Ca influx
Incr GH=>Incr IGF-1=>stim chondrocytes in bone |
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Term
|
Definition
GHRH activates stimulatory membrane transducer (Gs)=>stims adenylyl cyclase (requires GTP)=>cAMP activates protein kinase
SST=works thru inhibitory transducer(Gi, requires GTP)
Go=activated by SST, inhibits Ca channels
GHRH=DOMINANT REGULATOR |
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Term
|
Definition
| Hypoglycemia, amino acid administration (arginine most potent), deep sleep, exercise, dopamine agonists |
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Term
|
Definition
| Fully active agonist of GHRH, treats hypopituitary dwarfism |
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Term
|
Definition
Hyperpituitary dwarfism
GH receptors defective, unable to stim IGF-1 production
Treat w/ MECASERMIN (recombinant IGF-1) |
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Term
|
Definition
| Hypersecretion of GH in adult, usually from pituitary adenoma |
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Term
|
Definition
DOPAMINE AGONIST, treat acromegaly
inhibit GH release 50%
Best response in tumors w/ both GH/prolactin secretion=>dopamine receptors |
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Term
|
Definition
synthetic SST analog, much longer half-life
Inhibit GH release in acromegaly
SST/Octreo=inhibit ACTH/TSH/insulin/glucagon/vasoactive intestinal peptide/GI hormone release
Treat pancreatic cholera (excess VIP secretion block), become resistant
adv=diarrhea, nausea, ab pain 50%, subside over time |
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Term
|
Definition
GH ANTAGONIST
Modified agonist to bind receptors and block GH binding=> decr IGF-1 prod; conjugated to reduce renal clearance/immunogenicity
Treat acromegaly
adv=injection site rxns, nausea, diarrhea, chest pain, flu syndrome |
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Term
| Prolactin physiologic action |
|
Definition
| Works w/ thyroxine/sex steroids/adrenal steroids=> initiate/maintain lactation |
|
|
Term
| Prolactin release control via DOPAMINE |
|
Definition
Dopamine=main regulator of anterior pituitary lactotrophs, released in median eminence of hypothalamus
D2 receptor=activates Gi transducer=>inhib cAMP prod/open K channel/close Ca channel |
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Term
| Prolactin release and TRH |
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Definition
Thyrotropin-releasing hormone, enhances prolactin release
Mobilizes intracellular Ca via IP3 formation
Minor role only, dopa=major player |
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Term
| Prolactin secretion factor: INCREASE |
|
Definition
Pregnancy
Suckling
Stress
Hypoglycemia
Estrogen
Blocked dopamine receptors (chlorpromazine, haloperidol
Dopamine depleting drugs (reserpine, alpha-methyldopa) |
|
|
Term
| Prolactin secretion inhibition |
|
Definition
| Dopamine agonists (l-dopa, BROMOCRIPTINE) |
|
|
Term
| Hyperprolactinemia treatment |
|
Definition
| BROMOCRIPTINE (dopa agonist); cause prolactin-secreting tumors to shrink, must be kept on it or tumor reappears |
|
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Term
|
Definition
| Needed for child mental dev, proper thermoreg/metab in adults |
|
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Term
|
Definition
Involves iodination/condensation of tyrosine
Tyrosine + iodine->Monoiodotyrosine + Iodine->Diiodotyrosine
MIT + DIT=T3; DIT + DIT=T4 |
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Term
|
Definition
| T3 more active, binds receptors at nuclear level; stimulates transcription/translation |
|
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Term
|
Definition
Stimulate O2 consumption in most cells
Regulate lipid/carb metab
Enhance cell growth/develop, promote nervous system development
Increase heat prod/HR/contractility
Increase carb/protein/lipid/cholest metab |
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Term
|
Definition
| Absolute required for skel maturation, brain dev, myelinogenesis, dendritic/axonal prolif, synaptogenesis, glial prolif |
|
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Term
|
Definition
From HYPOthyroidism
Cold sensation, dry skin, eyelid edema, puffiness (hand/feet/face), pallor, hair thinning/dryness/loss, lethargy, fatigue, slowed speech, poor memory, anxiety/nervous, decr reflexes, bradycardia, hoarseness, weight gain, constipation, menstrual abnorm
SLOW DOWN AND SWELL UP |
|
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Term
|
Definition
Spontaneous thyroid degeration
Chronic autoimmune thyroiditis (Hashimoto)
Radiation damage
Dietary iodide deficient
anti-thyroid agents |
|
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Term
|
Definition
| TSH deficiency; less common, maybe from postpartum infarction |
|
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Term
|
Definition
| TRH deficiency, problem in the brain |
|
|
Term
| Thyroid hormone preparations |
|
Definition
Thyroid USP (dessicated thyroid, potency varies)
Thyroglobulin (potency varies)
sodium LEVOTHYROXINE (DRUG OF CHOICE for myxedema)
sodium LIOTHYRONINE (short acting, rapid onset) |
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Term
|
Definition
| Heat intolerance, weight loss, sweating, palpitations, nervousness, insomnia, diarrhea, stare, tachycardia (beta receptor sensitivity), finger/tongue tremor, hot/moist skin, diffuse goiter |
|
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Term
|
Definition
Toxic nodular adenoma (benign, excess T4/T3 secretion, usually in older)
Graves (autoimmune, activates TSH receptors, symmetric goiter) |
|
|
Term
| Inhibition of thyroid peroxidase=>inhibit T4 prod |
|
Definition
METHIMAZOLE
PROPYLTHIOURACIL (CAUTION IN PREGNANT [placenta, milk cross])
LUGOL'S SOLUTION (KI/I2, high iodine interferes w/ f'n)
RADIOACTIVE IODINE (destroy adenoma, NEVER IN PREGNANT!) |
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Term
|
Definition
Parathyroid hormone
Calcitonin
1,25-dihydroxycholecalciferol |
|
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Term
|
Definition
| Increases Ca levels by: increasing osteoclast action, increasing 1,25(OH)2D3 synthesis in kidney, increase renal tubular reabs |
|
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Term
|
Definition
| Increases levels by: increasing Ca binding transport protein synth=> increased gut absorption, Increasing Ca from bone in high doses |
|
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Term
|
Definition
DECREASES levels by: decreased osteoclast action, decreased tubular reabs
May play a role in maintaining bone mass |
|
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Term
|
Definition
| Activated by low plasma Ca; Stimulates cAMP increase in tissues=>incr synth of 1,25DHOCC in kidney, osteoclast activation, incr Ca reabs in tubules |
|
|
Term
| 1,25-DHOCC mechanism (CALCITRIOL) |
|
Definition
7 dehydrocholesterol=>Vitamin D3 in skin via UV rays=>25(OH)D3 in liver=>1,25-DHOCC in kidney;
PTH stims 1-alpha-hydroxylase=last step to DHOCC synth |
|
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Term
|
Definition
| Vitamin D2, derived from yeast/fungus, can be hydroxylated at 1,25 ot make 1,25-(OH)2D2=>supplement/replace DHOCC |
|
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Term
|
Definition
| Diffuses into target cells in intestine/bone/kidney, induces mRNA transcription=make proteins required for Ca transport (Ca binding transport protein CaBP) |
|
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Term
|
Definition
HypoCa/hyperP (PTH=P excretion)
Tx=Dietary Ca/calcitriol, IV PTH/Ca gluconate after parathyroidectomy to prevent tetany |
|
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Term
|
Definition
PTH levels normal/elevated w/ low Ca
End organs insensitive to PTH from Gs abnormality (transducer b/w PTH receptor-adenylyl cyclase)
Tx=Calcitriol to correct hypocalcemia, won't help bone disease always |
|
|
Term
|
Definition
Inadequate mineralization of bone matrix from lack of sun exposure=>impaired vit D3 synth
Tx=vitamin D2/D3 supplement |
|
|
Term
| Vitamin D dependent rickets |
|
Definition
Autosomal recessive, won't respond to exogenous vit D=> renal hydroxylase defect
Tx=Calcitriol (last step broken, need to give end product) |
|
|
Term
|
Definition
Anticonvulsants, phenytoin, phenobarbital, corticosteroids
Suppress Ca absorb in gut=>secondary hyperPTH; high dose steroids=inhib osteoblast differentiation/collagen synth=>decr bone mass
Tx= 25(OH)D3, D2, D3 improve sympt |
|
|
Term
|
Definition
Overactive osteoclasts=>demineralization of bone=>compression fractures
Tx=Calcitonin (not orally effective), Sodium etidronate (bisphoshphonate, SLOWS RATE OF DEMINERAL) |
|
|
Term
Alendronate
Risedronate
Ibandronate
Zoledronic acid |
|
Definition
Bisphosphonates, treat Paget's
Iban=1/month
Zol=IV 1/year |
|
|
Term
| Postmenopause osteoporosis |
|
Definition
Abnormal/rapid bone loss
Tx=Estrogen replacement (Incr HD, breast/uterine cancer)
Bisphosphonates (adv=heartburn, esoph irritation orally; fever/flu/headache/myalgia/A-Fib/osteonecrosis of jaw IV) |
|
|
Term
|
Definition
Human PTH, stimulates osteoblasts, injects SC daily;
Treats menopause osteoporosis |
|
|
Term
|
Definition
HyperCa=>Ca deposition in soft tissues (kidney)
Tx=Stop vitamin D!
Give PREDNISONE (glucocorticoids) to block intestinal absorption |
|
|
Term
| Primary hyperparathyroidism |
|
Definition
Adenoma of a parathyroid=>severe hyperCa, hypoP, prominent bone resorp, soft tissue calcification, elevated calcitriol, nephrolithiasis
Tx=surgical removal of adenoma |
|
|
Term
|
Definition
| Synthesis of catecholamines, adrenocortical steroids |
|
|
Term
|
Definition
| Homeostatic process control: Carb/lipid/protein metab, capillary perm/vasomotor response, most anything else in the body for homeostasis |
|
|
Term
|
Definition
| Maintain electrolyte balance: Na retention, direct effect on vascular tone |
|
|
Term
Weak androgens
DEHYDROEPIANDROSTERONE
ANDROSTENEDIONE |
|
Definition
| Main source of female androgens, metab to estrogens in male; no help in building muscle mass, increases estrogen, lowers HDL |
|
|
Term
| Adrenal steroid synthesis |
|
Definition
All derived from cholesterol
Cortisol (gluco, from zona fasciculata/reticularis)/aldosterone (mineral, from glomerulosa)=from pregnenolone |
|
|
Term
| Adrenal regulation/release |
|
Definition
Gluco=positive control of ACTH thru melanocortin MC2R receptor
ACTH=controlled by negative feedback/corticotropin releasing factor (CRF)
Aldost=Primary angiotensin 2 control |
|
|
Term
|
Definition
Steroid binds GR-alpha receptor=>bind promoter/interacts w/ other transcription factors=>altered rate of transcription
GR-beta=dominant negative inhibitor of GR-alpha action |
|
|
Term
|
Definition
| Anti-inflam, allergy, asthma, antiemesis, immunosuppress, acute mountain sickness, pneumocystis carinii pneumonia |
|
|
Term
| 11 beta-hydroxysteroid dehydrogenase |
|
Definition
| Inactivates cortisol, , minimizees glucocorticoid action in tissues; unable to prevent unwanted side effects |
|
|
Term
| Synthetic cortisol analogues vs. cortisol |
|
Definition
| Many don't bind corticosteroid binding globulin, have different half-lives/availability; excluded from CNS by P-glycoprotein |
|
|
Term
|
Definition
| Rapidly metab in the lung more than other gluco's, fewer side effects when inhaled |
|
|
Term
|
Definition
| extensive first-pass metab, fewer side effects systemically after inhalation |
|
|
Term
| Adrenal steroid toxicities |
|
Definition
| Pituitary-adrenal suppression, HypoK alkalosis, edema, Hyperglycemia, Infxn suscept, inhib wound healing, myopathy, Cushingoid, peptic ulcer, cataracts, growth arrest, osteoporosis |
|
|
Term
|
Definition
|
|
Term
| Apparent Mineralocorticoid Excess |
|
Definition
| Inherited form of HTN, mutation in HSD11B2 gene, decreased conversion of cortisol to cortisone |
|
|
Term
| Congenital adrenal hyperplasia |
|
Definition
| enzymatic defect, decreased levels of cortisol/aldost, increased androgens |
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
| Hereditary primary cortisol resistance |
|
Definition
| mutation in glucocorticoid receptor, no response |
|
|
Term
| Adrenal dosing regimens for replacement therapy |
|
Definition
Morning=Addison's, adrenalectomy, inhibited synth
Small AM/PM=keep ACTH low, repress adrenals for congenital adrenal hyperplasia
High daily=suppress |
|
|
Term
|
Definition
| POTENT anti-glucocorticoid, induce abortions (antiprogestational activity), treat Cushing's |
|
|
Term
|
Definition
| Competitive inhib of aldosterone binding to mineralo receptor; treat HTN/severe CHF |
|
|
Term
|
Definition
| Selective mineralo receptor antag (fewer side effects); treat HTN, HF, MI |
|
|
Term
|
Definition
| Glucocort, feedback inhibit ACTH/endogenous cortico prod |
|
|
Term
|
Definition
| Inhib 11-beta-hydroxylation rxn; Suppress glucocorticois, inhib aldosterone synth; compensated somewhat by deoxycorticosterone |
|
|
Term
|
Definition
| Inhib first committed step in adrenal synth (chol->pregnenolone), also inhib aromatase |
|
|
Term
| Adrenal Androgen synthesis |
|
Definition
| Made in cortex (zona reticularis), major androgen source in women, controlled by pituitary ACTH from cholesterol; makes mainly DHEA, minor prod androstenedione, androstenediol, testosterone |
|
|
Term
|
Definition
| Hypothalamic GnRH=>pituitary LH controls Leydig cell prod of testosterone, DHT, DHEA (minor), androstenedione |
|
|
Term
|
Definition
| Albumin (60%), Test-Estro binding protein (30%) |
|
|
Term
|
Definition
| Pass thru membrane, move to nucleus; converted to DHT by 5-alpha-reductase (type 1-2); convert to estrogen by aromatase |
|
|
Term
|
Definition
| External genitals during gestation/maturation, prostatic disease as adult; increased hair growth in puberty, baldness/facial hair in adult |
|
|
Term
| Testosterone in development |
|
Definition
| Wolffian duct develop in gestation, increase muscle mass/strength in puberty, deepens voice, erythropoeisis |
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Term
|
Definition
| From testosterone via Aromatase; EPIPHYSEAL CLOSURE |
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Term
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Definition
| Transdermal androgen, used in hypogonad (oral too weak, liver damage for long term) |
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Term
| Congenital adrenal hyperplasia |
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Definition
| 21 hydroxylase most common deficiency, increased ACTH/progesterone metabolites in urine/DHEA in blood, precocious puberty, post-puberty virilization in femalse |
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Term
Testoderm
Androderm
Androgel |
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Definition
| Testosterone replacements trans-dermally for andropause (1-2% decrease/year after 30), can increase strength, libido, well-being |
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Term
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Definition
| Treat Hereditary Angioedema, orally active, stimulate hepatic synth of C1-esterase inhibitor=>slow down overactive complement cascade (lowers vessel permeability) |
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Term
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Definition
| Stimulates erythropoeisis for hemolytic/thrombocytopenic purpura |
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Term
Testosterone propionate
Testosterone enanthate |
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Definition
17-beta modification=>prolong absorption, used as anabolic steroids
adv=decr libido, impotence, teste atrophy, gynecomastia, toxicity (can't be removed by liver) |
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Term
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Definition
| Extended release GnRH antag, reduces test secretion from decr LH secretion; Tx prostate cancer |
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Term
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Definition
| Androgen receptor antag, limited effect (increase in LH secretion=>rise in test secretion); combine w/ GnRH analogue to treat metastatic prostate cancer |
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Term
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Definition
| Weak antag at androgen receptor; Tx hirsuitism |
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Term
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Definition
Block type 2 (prostate-specific) 5-alpha-reductase, prevents conversion of T=>DHT; treat BPH, treat baldness (propecia);
Duta=blocks both type 1-2, works in all tissues |
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Term
| 5-alpha-reductase deficiency |
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Definition
| male pseudohermaphrodism; auto recessive, sex linked inability to convert T->DHT |
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Term
| Androgen insensitivity syndrome |
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Definition
| Testicular feminization; aromatase in mammary tissue produces estrogens, leads to breast dev in males |
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Term
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Definition
| Androgen receptor mutation=> androgen resistance (gynecomastia, progressive motor neuron atrophy) |
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Term
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Definition
| main estrogen produced by the ovary |
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Term
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Definition
Aromatization of testosterone/androstenedione by CYP19 found mainly in ovarian granulose cells/testicular Sertoli/Leydig/adipose stroma/bone/brain
Estriol/estrone=made in liver by type 2 hydroxysteroid dehydrogenase |
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Term
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Definition
| Stimulates vagina/uterus/fallopian development, breast/endometrial dev, long bone dev/closure, influence mineral deposition, lipid metab, carb/protein metab |
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Term
| 17-alpha ethinyl estradiol |
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Definition
|
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Term
|
Definition
| Equine estrogen, conjugated to SO4, removed in lower intestine to avoid 1st pass metab |
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Term
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Definition
| combined hormone replacement therapy w/ ethinyl stradiol; halted in 2002 ( high MI/stroke/clot/breast cancer risk, lowered colon cancer/fracture) |
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Term
| Selective Estrogen Receptor Modulators |
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Definition
| Beneficial in bone/brain/liver, antag in breast/endometrium by recruitment of co-repressor/co-activators of estrogen receptors |
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Term
|
Definition
SERM; Antag in breast, agonist in endometrium/bone; protects osteoporosis, incr thrombosis riskreduces recurrence of breast cancer
Trans=anti-estrogen (marketed type), cis=estrogenic |
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Term
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Definition
| Partial agonist at bone, antag at breast/endometrium; protects osteoporosis, no endometrial stimulation; reduces postmenopause bone resorption, reduces breast cancer recurrence |
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Term
|
Definition
|
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Term
|
Definition
| Aromatase inhib, treat breast cancer (block total estrogen prod); no incr risk of uterinecancer/thrombo, no hot flashes |
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Term
| Levonorgestrel-releasing IUD |
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Definition
5 year protection, makes sterile inflammation and sperm destruction, inhib ovulation; progestin decreases mentstrual bleed; NO MILK INHIB
+=no systemic hormone exposure, lactation okay, lower blood loss, lower endometrial cancer
-=acne, changes in flow, risk of uterine perforation, risk of pelvic infxn |
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Term
|
Definition
Six rods w/ levonorgestrel, 5 year protection, suppress ovulation, thicken cervical mucus, thins endometrium
+=lactation okay, decr anemia/PID/ectopic/endometrial cancer
-=irregular bleed, weight gain, headaache, acne, mood change, breast pain, minor surgery involved |
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Term
|
Definition
Injection of depot-medroxyprogesterone acetate x 3 months; inhibit ovulation, thicken cervical mucus, thins endometrium, less myalgia
+=milk okay, decr anemia/PID/ectopic/endometrial cancer
-=irregular bleed, amenorrhea (50% after 1 yr, 80% by 3), difficult to determine pregnancy after, weight gain, acne, mood change, headache, bone loss in adolescent |
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Term
Oral contraceptive
Norethindrome, norethynodrel, norgestrel, norgestimate, desogestrel, ethynodiol diacetate, gestodene |
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Definition
Inhibit LH surge (inhib ovulation), thicken mucus, altered uterine/tubal motility, decr glycogen prod by endometrium;
progestin-only not consistent inhib of ovulation
Increases fibrinogen/factor 5/7/10 production, increased thrombo risk
Increase angiotensinogen prod in liver, slight BP incr
Nausea, breast pain, fluid retention, depression, decrease sebum prod, decr risk endometrial/ovarian cancer
Progestin=increased glucose/insulin |
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Term
|
Definition
| Higher estrogen in the pill=>higher DVT chance |
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|
Term
| Oral contraceptive benefits |
|
Definition
| Reduced ectopic/benign breast disease/PID, controlled bleeding, decr dysmenorrhea/PMS/acne/blood loss/rheumatoid arthritis/osteoporosis/salpingitis, fewer ovarian cysts, reduced endometrial/ovarian/breast cancer |
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Term
| Oral contraceptive problems |
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Definition
| Increased risk of cervical dysplasia/cancer, increased thrombo, breast tenderness, nausea, fluid retention |
|
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Term
| Vaginal ring benefits/problems |
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Definition
Similar to the pill, preferred to patch
Prob=vaginal discharge/vaginitis, occasional irregular spotting, nausea, breast tenderness, unknown risk of cervical dysplasia/thrombo |
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Term
|
Definition
1 pill x2, 12 hrs apart;
Levonorgestrel only |
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|
Term
| Preven oral contraception |
|
Definition
2 pills x2, 12 hrs apart
low Levonorgestrel + ethinyl estradiol |
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Term
|
Definition
Ethinyl estradiol + Norgestrel
4 tabs split by 12 hrs |
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Term
|
Definition
15% of couples
40% male prob
50% female ability/tubal/peritoneal |
|
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Term
|
Definition
Hysterosalpingography (fallopian tubes
Serum progesterone test (ovulation)
Semen analysis |
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Term
|
Definition
Selective estrogen receptor modulator (SERM)
Similar to estrogen replacement DES; racemic mix 38% zu isomer (active), 62% en isomer
Potentially teratogen
TREAT INFERTILITY |
|
|
Term
| Clomiphene citrate mech/adv |
|
Definition
Uptake/binding of hypothalamic intra-nuclear estrogen receptors=>retard receptor replenishment=>decr negative estrogen feedback on GnRH release=>FAVORS FSH RELEASE OVER LH
Adv=flushing, blurred vision, scotomata, headache; Ensure no insulin resist/21 hydroxylase defic/hypothyroid/hyperprolactin |
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Term
| Exogenous gonadotropin mech |
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Definition
LH receptors on theca cells (has P450 C17=androgens)
FSH receptors on granulosa cells (has aromatase=>estrogen)
Need them to mature/release oocyte |
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Term
| Exogenous gonadotropin indications |
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Definition
Induce ovulation in clomiphene failure pts/hypothalamic anovulation pts
Controlled ovarian hyperstimulation in cases of unexplained infertility, agents of choice in ART (assisted reprod tech) when large #s of eggs need to be made
RESCUES oocytes that would otherwise die off |
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Term
| Ovulation induction in hypothalamic anovulatories |
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Definition
| LH/FSH a must for them; give hCG largely to surrogate the LH surge to cause ovulation |
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Term
| Ovulation induction in euestrogenic |
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Definition
| LH may not be necessary; goal of 2-3 follicles sought w/ hCG stim |
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Term
|
Definition
Altered cleavage sites increase half-life greatly
Initial flare at inject/inhale, lasts 7-10 days, then down regulation of receptors=>desensitization=>REDUCED PITUITARY GONADOTROPIN SECRETION |
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Term
|
Definition
ART=harness flare early in stim cycle=>fewer gonadotropin replacements needed
Prevents premature ovulation, reduces sympt/growth of uterine myomas, decreased myoma size, stabilize hematocrit prior to surgery
Adv=hypogonadal state, potential probs w/hypoestrogenemia=>low bone density, adverse lipid profile |
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Term
|
Definition
| Made in beta cells of pancreas; proteolytic cleavage removes C-peptide from proinsulin; stored in granules w/ Zn2+ |
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Term
|
Definition
Stim=glucose, amino acids, glucagon, acetylcholine, secretin, pancreozynin, GIP, GLP-1, beta-2 receptors
Inhib=alpha 2 receptors, somatostatin receptor |
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Term
| Glucose regulation via insulin |
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Definition
| Taken up by beta cells->phosphorylation/glycolysis->metabolism makes ATP->inhibs K channels->depol of beta cell->increased Ca influx->insulin release |
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Term
|
Definition
Secreted by alpha cells of pancreas
Amino acids stim release (insulin release, too) |
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Term
|
Definition
Enhances glucose uptake EXCEPT CNS, VESSELS, RENAL MEDULLA, HEPATOCYTES
stimulates anabolism in liver/muscle/adipose |
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Term
|
Definition
| 2 insulin molecules bind receptor->activated tyrosine kinase->phospho insulin receptor substrate->active enzymes for glycogen/prot/lipo synth-> makes glucose transporters relocate to cell memb to enhance uptake of sugar |
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Term
|
Definition
Hyperglycemia w/ screwey insulin secretion, thickening basement memb of capillaries
Sx=polyuria, polydipsia, weight loss (type I), fasting hyperglycemia/glycosuria |
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Term
|
Definition
Before age 30, 10% of all cases
Lean, ketoacidosis prone, labile plasma glucise; HLA associated, INSULIN REQUIRED |
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Term
|
Definition
After 30 years, 90% of all cases
Obese, ketoacidosis resistant, stable glucose; non-HLA linked; Insulin usually not required, just adjust diet/exercise/oral glycemic drugs |
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Term
|
Definition
| Zinc reacted w/ basic protein of insulin; long acting, released slowly from injection site |
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Term
|
Definition
| Ultra long lasting insulin, no peak concentration like other insulins |
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Term
|
Definition
| Newest peak-less long acting insulin 2x day for smooth insulin background |
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Term
|
Definition
| synthetic insulin analog, absorbed rapidly->inject just prior to eating |
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|
Term
|
Definition
| 20-28 hr duration of insulin |
|
|
Term
|
Definition
| 36 hr insulin preparation, peak at 8-14 hrs |
|
|
Term
|
Definition
Rimonabant=CB1 receptor antag to suppress appetite
Metformin=hyperglycemic drug
Glyburide=orally active hypoglycemic drug |
|
|
Term
| Sulfonylureas (tolbutamide |
|
Definition
| Oldest oral hypoglycemic drugs; direct stim insulin release from beta cells; bind K channels on beta cells=>inhib K efflux=>depol=>Ca entry=>insulin release |
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|
Term
|
Definition
| 2nd gen sulfonylurea 200x more potent=>insulin release |
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|
Term
|
Definition
| Oral hypoglycemic same as sulfonyl; faster acting/shorter duration of action |
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Term
|
Definition
Treat type II; INHIB GLUNEO IN LIVER!!
Reduces hypergly, almost never causes hypogly; can cause lactic acidosis |
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Term
|
Definition
Type II diabetes treat; alpha-glucosidase inhib, slows carb breakdown in intestine; INHIB SUCROSE BREAKDOWN TO GLUCOSE
Can cause gas/bloat/diarrhea |
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Term
|
Definition
Decreases insulin resistance, reduce MI/stroke, activate nuclear receptor PPAR-gamma (activates insulin responsive genes that regulate carb/lipid metab)
INCREASE GLUCOSE TRANSPORTER SYNTH/TRANSLOCATION, INHIB GLUNEO, INCREASE INSULIN SENSITIVITY |
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Term
|
Definition
| Stimulates insulin release, inhib glucagon release |
|
|
Term
|
Definition
Orally active inhib of enzyme DPP-4 (breaks down endogenous GLP-1);
ELEVATION OF GLP-1=>STIM INSULIN RELEASE/INHIB GLUCAGON RELEASE |
|
|
Term
|
Definition
Retinopathy, glomerulonephritis, neuropathy
Prone to complicated pregnancy, mycotic infxn, CAD, periph vascular disease (gangrene, amputations) |
|
|
Term
| Diabetic complication mech |
|
Definition
| Lens/retina/nerves/kidney/vessels freely permeable to ambient glucose, no insulin required; Hyperglycemia=influx to tissues=>osmotic inflow=>swelling/damage |
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|
Term
|
Definition
| ACE inhib, reduces kidney fail in 50% type I, increases insulin sensitivity->increase hypoglycemia risk |
|
|
Term
|
Definition
| anti-cancer drugs, prevent/reverse type I diabetes in mice via tyrosine kinase inhibition assoc w/ PDGF receptor |
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