Term
| Definition of HTN and 2 stages |
|
Definition
SBP > 140 and/or DBP > 90
Must be measured on multiple occasions
Stage 1: 140-159/90-99
Stage 2: 160+/100+ |
|
|
Term
| In who does Isolated Systolic Hypertension most often occur? |
|
Definition
|
|
Term
| What is hypertensive crisis? |
|
Definition
aka malignant hypertension
DBP > 110
accompanied by acute organ injury: stroke, HF, MI, aneurysm |
|
|
Term
| What are some symptoms of hypertension? |
|
Definition
| mood changes, dizziness, HA, decreased overall well-being |
|
|
Term
| Factors that can attribute to essential (primary) HTN |
|
Definition
Genetic:
Dyslipidemia
Diabetes/elevated fasting glucose (>110)
Obesity
Age >55 (men) and 65 (women)
Family Hx of premature CV disease (<55 [M] and <65 [W])
Low GFR (<60 ml/min) or elevated urinary protein
Environmental:
Stress
Smoking
Inactivity
Obstructive sleep apnea
Diet: high Na
Excessive EtOH consumption |
|
|
Term
| What percentage of people with HTN are uncontrolled? |
|
Definition
50%
30% of US population has HTN and 25% of those don't even know it |
|
|
Term
| What ethnicity has the highest proportion of HTN? |
|
Definition
Blacks
they also progress faster once diagnosed |
|
|
Term
| Is HTN more prevalent in men or women? |
|
Definition
|
|
Term
| What are 3 types of primary HTN? |
|
Definition
Moderate/High renin: Most common; treat with RAS drugs and diuretics
Low renin: more common in blacks and elderly; treat with diuretics, CCB, beta-blockers
Resistant: requires 3+ drugs |
|
|
Term
| Effects of HTN (what it can lead to) |
|
Definition
Stroke
CHF
CAD, angina, MI
Renal failure
PAD
Aneurysm
Retinopathy
Erectile dysfunction |
|
|
Term
| Classification of pre-hypertension |
|
Definition
|
|
Term
|
Definition
1. Renal/vascular:
renovascular stenosis
renal parenchymal disease (renal disease activates the RAS since translated as insufficient BP)
aortic coarction (narrowing of aorta)
2. Endocrine:
primary aldosteronism (Conn's disease) [MOST COMMON]
hyperadrenalism (Cushing's)/pheochromocytoma (glucocorticoid secreting tumor)
Hyperthyroidism
Pregnancy (self-limiting)
3. Medications:
OC - esp if overweight, smoker, black (HRT not a problem)
Corticosteroids
Amphetamines/appetite suppressants
MOAIs
Anti-depressants (venlafaxine)
Licorice (candy doesnt have true licorice in it) |
|
|
Term
| What physiological factors determine blood pressure? |
|
Definition
1. CO
2. TPR
BP = CO x TPR
NOTE: CO = SV x HR |
|
|
Term
| What is the major physiological determinant of DBP? |
|
Definition
| TPR - sum of all vascular resistance of each organ |
|
|
Term
| In hypertension what physiological factor/contributor typically increases? |
|
Definition
TPR is increased (while CO usually remains constant)
NOTE: in developing HTN, CO and HR are usually elevated, but over time CO becomes normal and TPR increases |
|
|
Term
| What are three BP control mechanisms? |
|
Definition
1. Rapid: nervous system mediated (baroreceptor reflex)
2. Intermediate acting: circulating vasoactive agents (angiotensin)
3. Long acting: changes in blood volume (renal function) |
|
|
Term
| Which receptors in the kidney, when stimulated, trigger release of renin |
|
Definition
beta (1) receptors
(why you can use a beta-blocker to control HTN) |
|
|
Term
|
Definition
beta receptor stimulation trigger the release of RENIN (from granular cells of JGA)
RENIN converts circulating ANGIOTENSINOGEN (from liver) to ANGIOTENSIN I
ANG I is converted to ANG II via ACE (in vasculature - thought to primarily occur in lungs)
ANG II controls BP and causes release of ALDOSTERONE
ALDOSTERONE is the ultimate regulator |
|
|
Term
|
Definition
1. potent vasoconstrictor
2. stimulates release of aldosterone (for adrenal gland) |
|
|
Term
| Renal mechanism of blood pressure control |
|
Definition
controls ECF and blood volume
Decrease in BP or BV decrease GFR
-triggers kidney to retain Na and water to restore BV, GFR, renal perfusion pressure, and BP
-renin is released -->RAS mech -->ADH release, vasoconstriction, thirst, and ALDOSTERONE RELEASE (promotes Na retention) |
|
|
Term
| Release of ADH can be triggered by what? |
|
Definition
1. Osmolarity of blood (osmoreceptors in hypothalamus)
2. Decreased blood volume (measured in kidney) [RAS system] |
|
|
Term
| Release of aldosterone is triggered by what? |
|
Definition
1. Ang II
2. Hyponatremia
3. Hyperkalemia
From zona glomerulosa of adrenal contex (outermost) |
|
|
Term
|
Definition
| Retention of Na -->promotes water reabsorption (increase volume) |
|
|
Term
| What plays the most important role in controlling Na excretion and fluid volume |
|
Definition
|
|
Term
| T or F: all essential HTN can be viewed as reno-vascular dysfunction |
|
Definition
T: for HTN to persist, kidneys must fail to compensate for the elevated BP or volume expansion
NOTE: effective therapy requires renal function to be addressed |
|
|
Term
| What is first line treatment for HTN |
|
Definition
|
|
Term
| T or F: Chronic Kidney Disease (CKD) is prevalent in pre-HTN |
|
Definition
T: direct relationship between CKD and increasing HTN
GFR < 60 ml/min or urinary albumin:creatine >30 mg/g (macroalbuminuria) |
|
|
Term
| T or F: HTN is the result of neurological and renal mechanisms |
|
Definition
|
|
Term
| What is the genetic polymorphism associated with HTN |
|
Definition
variants of STK39 (serine/threonine kinase)
Phosphorylates Na/K/2Cl (loop) and Na/Cl (thiazides) pumps
3.3 mmHg if heterozygous and 6.6 mmHg increase if homozygous |
|
|
Term
| Non-pharmacologic therapy for HTN |
|
Definition
1. Weight reduction (upto 20 mmHg for 10 kg)
2. DASH diet (upto 14 mmHg)
3. K+ supplementation
4. Vit D supplementation: 800 IU + Ca
5. Magnesium supplementation: >270 mg/d (3-4 mmHg)
6. Aerobic exercise (up to 10 mmHg)
7. Na restriction: about 1/2 hypertensives are salt-sensitive (esp blacks) - recommended <4g/d, <3g/d if over 70 [Na increases vasoconstriction (SNS) NOT volume expansion]
8. EtOH restriction: moderation |
|
|
Term
| Common drugs for the treatment of HTN |
|
Definition
Diuretics: first line (thiazides first)
CCB: more effective than beta-blockers and RAS drugs in LOW RENIN HTN (elderly/blacks)
RAS: becoming more popular (dont use with beta-blockers); preferred in diabetics
beta-blockers: vasodilating beta-blockers becoming preferred; preferred over diuretics in post-MI patients (but can increase chance of DM) |
|
|
Term
| Drugs not recommended for routine use |
|
Definition
| 1. Vasodilators: hydralazine, minoxidil (use when diuretics, BB, ACEIs ineffective) 2. alpha-1-antagonists: doxazosin (ADRs big issue - orthostatic hypotension, fluid retention 3. Central sympatholytics/alpha-2-agonists: clonidine, guanfacine (CNS ADRs: sedation, depression, sexual dysfunction; best with a diuretic, can sub for beta-blockers) 4. Minor sympatholytics: guanadrel, reserpine (minor orthostatic hypotension, sexual dysfunction, volume expansion; Reserpine = sledgehammer ADRs) |
|
|
Term
| What makes up the ultra-fitration barrier of the glomerulus? |
|
Definition
Basement membrane and vascular endothelial
prevents passage of blood cells and proteins |
|
|
Term
|
Definition
Afferent arterioles (from renal cortex)
Glomerulus (Bowman's capsule)
Efferent arteriole
Peritubular capillaries (surround loop of Henle and allow for reabsorption)
Renal venule |
|
|
Term
| What gets reabsorbed at the proximal tubule |
|
Definition
Active:
1. Glucose (100%)
2. AA (100%)
3. K, Ca, phosphate, bicarbonate, uric acid (>90%)
4. Na (>66%)
Passive reabsorption: Cl, water, urea |
|
|
Term
| What gets actively secreted at the proximal tubule and why is it significant to HTN? |
|
Definition
organic acids and bases (exchange H+ or Na+)
Diuretics get secreted here; this is crucial because they must be in the the tubule to illicit their action. |
|
|
Term
| What diuretics are active at the proximal tubule? |
|
Definition
1. carbonic anhydrase inhibitors
2. osmotic diuretics (active throughout the tubule) |
|
|
Term
| What are the osmotic diuretics? |
|
Definition
Mannitol
Glycerin
Isosorbide |
|
|
Term
| What are some carbonic anhydrase inhibitors |
|
Definition
acetazolamide (Diamox)
dichlorphenamide (Daranide)
methazolamide (Neptazane) |
|
|
Term
| How is sodium and water treated in the Loop of Henle? |
|
Definition
Descending: both flow readily in/out via passive diffusion (water flows out and Na flows in in accordance with concentration gradients)
(Thick) Ascending Loop:
-impermeable to water
Na/K/2Cl transporter = all pumped out of tubule (25% Na recovery) |
|
|
Term
| Examples of loop diuretics |
|
Definition
Furosemide
Ethacrynic acid (Edecrin)
Bumetanide (Bumex)
Toresemide (Demadex) |
|
|
Term
| What sodium transporter is unique to distal tubules/CD |
|
Definition
|
|
Term
| What can alter water movement in the distal tubules/CD |
|
Definition
| ADH - causes formation of aquaporins (facilitate water reabsorption) |
|
|
Term
| Diuretics that act on distal tubule |
|
Definition
Thiazides (Na/Cl transporter)
K+-Sparing Diuretics (work on CD too) |
|
|
Term
| Potassium sparing diuretics should always be used with another diuretic |
|
Definition
| True - very weak, but prevent potassium loss (dont need to be on potassium supp too) |
|
|
Term
| Examples of thiazide diuretics |
|
Definition
HCTZ (Hydrodiuril)
Chlortalidone (Hygroton)
Indapamide (Lozol) |
|
|
Term
| Examples of potassium-sparing diuretics |
|
Definition
Triamterene (Dyrenium)
Amiloride (Midamor)
Eplerenone (Inspra) |
|
|
Term
| What two diuretics directly antagonize aldosterone? |
|
Definition
Spironolactone (Aldactone)
Eplerenone (Inspra) |
|
|
Term
|
Definition
Promotes Na reabsorption in late distal tubule and collecting duct
HOW...
K is exchanged Na
Na retention promotes water reabsorption (causes increased BP/blood volume)
Promotes K+ Loss |
|
|
Term
| What is the primary regulator of aldosterone? |
|
Definition
|
|
Term
| What regulates aldosterone release |
|
Definition
ANG II
decreased blood pressure (which will also stim ANG II release)
Decreased Na
Increased K |
|
|
Term
| Diuretic response of osmotic diuretics |
|
Definition
BIG increase in urine flow with little increase in salt excretion = water diuresis
response proportional to dosage
Reduces ECF voluem (edema) and aqueous humor volume/pressure (glaucoma) |
|
|
Term
| When would you use an osmotic diuretic? |
|
Definition
NOT for HTN, emergency use
1. Shock: hypotension causes peripheral pooling of fluids and oliguria (will restore urine flow/decrease edema)
2. Brain edema/trauma
3. Rhabdomyolysis (crush injuries release myoglobin - clog glomerulus)
**Critical to maintain urine flow or kidneys will die** |
|
|
Term
|
Definition
Immediate EXPANSION of ECF and vascular volume - can further stress cardiac decompensation (risk for pulmonary edema especially if HF)
Mild hyperkalemia and/or hypernatremia (big loss in fluid without proportional loss of ions)
Common: HA, N/V |
|
|
Term
|
Definition
Distribute through ECF: water moves out of cells (diffusion) -->causes an immediate expansion of ECF -->increases renal blood flow
Na excretion is slightly increased due to increased fluid volume in tubule (pulls Na out of medullary interstitium)
-because decreased tonicity in peritubular capillaries, less water is pulled out of tubule (reabsorbed)
-increased excretion of all electrolytes b/c water cant be reabsorbed
Initially extracellular electrolyte content is NOT decreased (hypernatremia/hyperkalemia) |
|
|
Term
| Which osmotic diuretic is only given IV? |
|
Definition
| Mannitol - used in hospitals primarily |
|
|
Term
| Which osmotic diuretics are orally administered? |
|
Definition
|
|
Term
| Which osmotic diuretic can cause hyperglycemia? |
|
Definition
|
|
Term
| What are some uses for osmotic diuretics? |
|
Definition
NOT HYPERTENSION
1. Shock (hypotensive): fixes the peripheral pooling of fluids and oligouria (restores urine flow)
2. Brain edema from trauma
3. Rhabdomyolysis (from crush injuries) - helps maintain urine flow |
|
|
Term
| Which diuretic is self-limiting? |
|
Definition
Carbonic anhydrase inhibitors
Stimulate HCO3- secretion (pair with Na) by preventing CA from making water and CO2 from H2CO3
Once no more base, action is very limited. |
|
|
Term
| What are the carbonic anhydrase inhibitors (PO) |
|
Definition
acetazolamide (Diamox)
dichlorphenamide (Daranide)
methazolamide (Neptazane) |
|
|
Term
| Clinical uses of carbonic anhydrase inhibitors? |
|
Definition
1. Open-angle glaucoma
2. Altitude sickness (counteracts resportory alkalosis) - best if prophylaxis
3. Alkalinization of urine in OD (barbiturate, ASA, myoglobinuria)
4. Refractory CHF: when hospitalized patients develop "contraction alkalosis" from over diuresis (thiazides + loop) |
|
|
Term
| Actions and Adverse Effects of CA Inhibitors |
|
Definition
Excessive bicarbonate excretion: self limiting, acidosis
Increased excretion of Na, K, HCO3 (K+ loss can be significant)
CNS: paresthesias, drowsiness/fatigue, depression
Acetazolamide is shorter acting than methazolamide |
|
|
Term
| 3 people who CA inhibitors are CI? |
|
Definition
Pregnancy - teratogenic
Hepatic cirrosis - ammonia excretion is decreased
Severe COPD - will worsen respiratory acidosis |
|
|
Term
| T or F: all thiazides are therapeutically equivalent? |
|
Definition
|
|
Term
|
Definition
blocks Na/Cl transporter in early distal tubule
Modest diuretic effect - because 90% of Na is reabsorbed before reaching distal tubule
Increased Na in CD results in K exchange and concommitant loss of K |
|
|
Term
| Therapeutic uses of Thiazides |
|
Definition
1. First line for HTN
2. Edema: CHF, hepatic cirrhosis, renal (glomerulonephritis, chronic RF, nephrotic syndrome)
-most diuretics are ineffective with low GFR (<40 ml/min) because must get into urine to be effective
3. Diabetes insipidus
4. Kidney stones: because decrease Ca excretion by unknown MOA |
|
|
Term
| How many mmHg does a thiazide usually lower BP? |
|
Definition
|
|
Term
| thiazides in diabetes insipidus |
|
Definition
(ADH insensitivity)
causes hyponatremia -->increases Na and water reabsorption in proximal tubule and loop of Henle--> less water reaches distal tubule-->decreased urine volume (up to 50% decrease) |
|
|
Term
What are kidney stones usually composed of?
What minerals/vitamins can decrease the incidence of kidney stones? |
|
Definition
oxalate (big issue) and calcium
intake of K, citrate, and Mg can reduce incidence |
|
|
Term
| Thiazides effects on aldosterone production |
|
Definition
The decreased ECF volume caused by thiazide stimulates aldosterone secretion. Aldosterone promotes synthesis of Na/K exchange transporter
This decrease in K is usually small and can be controlled by diet/supplementation |
|
|
Term
| What are the overall changes in ions normally excreted renally? |
|
Definition
Increased excretion of Na, K, Mg (unknown MOA)
Decreased excretion of Ca (indirectly due to decreased ECF volume), uric acid (competition for organic transporter in proximal tubule with actual drug) |
|
|
Term
| Examples of thiazides diuretics? |
|
Definition
Chlorthiazide (Diuril)
HCTZ (Hydrodiuril)
Hydroflumethiazide (Saluron)
Methychlorthiazide (Enduron)
Polythiazide (Renese)
Chlorthalidone (Hygroton)
Indapamide (Lozol)
Metolazone (Mykrox) |
|
|
Term
| When does hypokalemia with thiazide diuretics become an issue? |
|
Definition
patients with ventricular arrhythmias
-Quinidine (anti-arrhythmic) can cause torsades de points which is aggrevated by K depletion
-Mg deficiency increases risk
Liver cirrhosis, HF (patient on cardiac glycosides)
SHOULD GIVE WTIH K+ SUPP OR K+ SPARING DIURETICS |
|
|
Term
| Adverse effects of thiazides |
|
Definition
Hypokalemia
Hyperglycemia (possibly causes new onset DM)
Hyperlipidemia (modest increase)
Hyperuricemia (issue only if have gout) - gout attacks may occur more frequently
Hypomagnesia: more common in elderly
Contraindicated if have sulfonamide allergy |
|
|
Term
| Thiazides and New Onset Diabetes |
|
Definition
Controversial
-can cause hyperglycemia
-K+ depletion thought to play a role by decreasing insulin secretion and sensitivity (dr. should establish baseline K levels for patient) --- other studies oppose this
-Overall, no increase in incidence of CV disease (ultimate issue with DM) |
|
|
Term
| Comparison of thiazides (ADME) |
|
Definition
Different potencies - baseline is HCTZ (=1)
-Chlorothiazide is least potent (0.1)
-Others are 20-25x's the potency of HCTZ
HCTZ - short half-life [2.5 hr] (chlorthalidone has same potency, but much longer half-life)
More longer acting = more lipid soluble = bigger volumes of distribution
All renal clearance except newer agents (Indapamide, Methychlothiazide) |
|
|
Term
| Chlorthalidone versus HCTZ |
|
Definition
Chlortalidone has:
-Longer half-life: QD versus HCTZ which can be BID
-Better inhibitor of carbonic anhydrase: possible benefit in platelet aggregation, angiogenesis |
|
|
Term
| What other drugs can HCTZ be found in combo with? |
|
Definition
ACE inhibitors (ex: lisiinpril, benazepril) - good in very elderly
Potassium-sparing diuretics (ex: triamterene)
ARBs (losartan)
Tribenzor: HCTZ, ARB, CCB |
|
|
Term
| Examples of loop diuretics |
|
Definition
aka high ceiling diuretics
Furosemide (Lasix)
Ethacrynic Acid (Edecrin)
Bumetanide (Bumex)
Torsemide (Demadex) |
|
|
Term
|
Definition
1. Edema (cardiac, hepatic, renal)
2. Pulmonary edema: venodilation decreases left ventricular filling pressure
3. Hypercalcemia
4. HTN (if unresponsive to thiazides)
5. Renal failure: acute or chronic) - potent diuresis to maintain urine flow |
|
|
Term
|
Definition
block Na/K/2Cl uptake in thick ascending loop of Henle
overall increased excretion of Na (K, and Cl) and therefore water
~25% of Na is usually reabsorbed in Loop of Henle
Less Na in late distal tubule and CD means less K and Na exchange (where Na would normally be secreted into tubule and K would be saved from excretion) BUT less Na = decreased ECF volume -->aldosterone synthesis
Aldosterone causes increases in the K/Na exchanger is late tubule = more K is lost
Increased excretion of: Ca, Mg, H |
|
|
Term
| What is the overall ion loss with loop diuretics |
|
Definition
|
|
Term
| Why is H+ excretion increased with loop diuretics? |
|
Definition
| Distal tubule has an H/Na exchanger tries to save some of the Na from being excreted by exchanging with H --> can cause mild alkalosis -less likely with furosemide - has weak ability to inhibit carbonic anhydrase and promote HCO3- elimination |
|
|
Term
| Affect of loop diuretics on macula densa signaling |
|
Definition
Loop diuretics block Na uptake into macula densa
Effects: GFR is not reduced (even though sig loss of Na), Renin secretion is NOT suppressed (so aldosterone cant be suppressed this way)
-Appears to involve increased PGI/E2 synthesis |
|
|
Term
| T or F: uric acid excretion is increased with Loop Diuretics |
|
Definition
T, at first
increased acutely (because of contraction of ECF), but then decreased chronically because of competition at organic acid transporters
Rare instances can cause gout |
|
|
Term
| T or F: loop diuretics can cause venodilation and increased renal blood flow. |
|
Definition
T: via prostaglandin synthesis
(inhibited by NSAIDs)
can help with acute pulmonary edema (venodilation)
Increased renal blood flow also partially contributed to macula densa sensing being blocked |
|
|
Term
| Pregnancy and Loop diuretics |
|
Definition
| Teratogenic in first trimester |
|
|
Term
| Adverse effects of loop diuretics |
|
Definition
1. Electrolyte imbalances: decreased K, Na, Ca, H (alkalosis)
2. Ototoxicity: rare (esp with ethacrynic acid) deafness can be temporary or permanent; more likely to occur with concurrent use of other ototoxic drugs and renal insufficiency
3. GI: bleeding, diarrhea (esp with ethacrynic acid)
4. Sulfonamide sensitivity (low risk) - rashes, paresthesias, anemias, photosensitivity (common with furosemide)
5. CHO intolerance (because K depletion) can aggravate diabetes
6 Elevate uric acid (increase gout attacks)
7. HIGH fracture risk in post-menopausal women
5. |
|
|
Term
| T or F: there are loop and thiazide diuretic combinations |
|
Definition
| F - synergistic effect/too similar |
|
|
Term
| Which is the longest acting loop diuretic? |
|
Definition
|
|
Term
| T or F: loop diuretics are highly protein bound |
|
Definition
| T - be aware of potential competition with other meds for binding sites (ex: warfarin) |
|
|
Term
| What is the only loop diuretic to undergo significant metabolism (all others excreted renally unchanged)? |
|
Definition
|
|
Term
| What are the potassium sparing diuretics? |
|
Definition
Sprionolactone (Aldactone)
Eplerenone (Inspra)
Triamterene (Dyrenium)
Amiloride (Midamor) |
|
|
Term
| Uses of K+ Sparing Diuretics |
|
Definition
1. HTN
2. CHF
3. Ascities (cirrhosis) **Preferred diuretic in hepatic cirrhosis
4. Primary and secondary aldosteronism
5. Hypokalemia |
|
|
Term
| Which type of diuretic is preferred in patients with hepatic cirrhosis |
|
Definition
|
|
Term
MOA of triamterene?
Which other drug has the same MOA |
|
Definition
Block Na+ channel in late distal tubule/CD (on luminal membrane)
Prevents the exchange of K and Na on blood side
Overall, the sodium in the tubule will stay in the tubule
Amiloride = same MOA |
|
|
Term
MOA of spironolactone.
What other drug has the same MOA |
|
Definition
Competitive aldosterone antagonist at the MR (mineralocorticoid) receptor
Prevents aldosterone from binding and thus increasing synthesis and activity of the luminal Na+ channel (which is directly blocked by the other K+ sparing diuretics)
Eplerenone (same MOA) |
|
|
Term
| T or F: All potassium sparing diuretics are ineffective in the absence of aldosterone |
|
Definition
| F - the aldosterone antagonists are (spironolactone, eplerenone) but the Na-channel blockers (triamterene, amiloride) have limited effectiveness |
|
|
Term
| K+ sparing diuretics are the drugs of choice with HTN due to what? |
|
Definition
| Primary or secondary aldosteronism (this way they are fixing the cause more than just adjusting the BP by another mechanism) |
|
|
Term
| Role of K+ sparing diuretics in the treatment of HTN |
|
Definition
Use as dual therapy always!
(much more effective with a drug (thiazide or loop) that will increase the Na in the late distal tubule/CD.
Use to prevent hypokalemia due to other drugs |
|
|
Term
Which is more specific, eplerenone or spironolactone?
What is the result of this? |
|
Definition
Eplerenone is more specific for the MR
Fewer sex hormone related ADRs (impotence, gynecomastia) |
|
|
Term
| Can eplerenone be used with RAS drugs? |
|
Definition
| Yes, even though aldosterone will decrease with RAS drugs, there are other sources of aldosterone and |
|
|
Term
| Which would be more effective in blacks, eplerenone or lostartan? |
|
Definition
|
|
Term
| Which is the most effective K+ sparing diuretic at lowering BP (alone) |
|
Definition
Eplerenone (~10 mmHg)
possibly because higher specificity for MR |
|
|
Term
| What is a common drug interaction to be aware of with eplerenone and how does it manifest? |
|
Definition
CYP3A4 inhibitors will block its metabolism
causes hyperkalemia |
|
|
Term
| T or F: Hyperkalemia cant occur with potassium sparing diuretics if a K wasting diuretic is coadministered |
|
Definition
|
|
Term
| When are K supplements contraindicated in HTN therapy? |
|
Definition
K+ Sparing Diuretics risk of hyperkalemia
RAS drugs can also cause hyperkalemia, use with caution in these patients |
|
|
Term
| T or F: it is okay to give triamterene and spironolactone concomitantly? |
|
Definition
| F - both are K+ sparing and work by different mechansisms - elevated risk of hyperkalemia |
|
|
Term
|
Definition
1. Sex hormone issues:
-Men: gynecomastia, decreased libido, impotence
-Women: hirsutism, menstrual irregularities, breast tenderness
2. GI: ulcers/bleeding, gastritis, diarrhea
3. hyperkalemia |
|
|
Term
|
Definition
N/V
Leg cramps
Dizziness
Photosensitivity
Patients with cirrhosis - risk for megaloblastic anemia
Kidney stones (containing drug and metabolites)
Hyperkalemia |
|
|
Term
|
Definition
N/V, diarrhea, HA
Hyperkalemia |
|
|
Term
| When starting spironolactone when should you expect to see an effect? |
|
Definition
| Can take up to 2-3 days to see maximal effect because principal metabolite is active and has a very long half-life |
|
|
Term
| What are signs of hyperkalemia and how should people on K+ sparing diuretics be monitored? |
|
Definition
Numbness, paresthesias
Confusion, SOB, fatigue
Biggest concern = heart issues
Monitor blood levels |
|
|
Term
| What is the number one sign for hypernatremia? |
|
Definition
Thirst
Otherwise, it can have a similar presentation to hyperkalemia) |
|
|
Term
| What 3 things does the JGA regulate? |
|
Definition
1. GFR
2. glomerular blood flow
3. Renin release |
|
|
Term
| The JGA is reacts to changes in ____ and ____ and reacts by ____ and _____. |
|
Definition
| The JGA is reacts to changes in NaCl IN DISTAL TUBULE (via macula densa PGI2/PGE2) and DECREASED BP and reacts by VASODILATING AFFERENT ARTERIOLE and RELEASING RENIN |
|
|
Term
| To increase GFR should the afferent and efferent arterioles be constricted or dilated? |
|
Definition
Afferent should be dilated
Efferent should be constricted |
|
|
Term
|
Definition
| in all vasculature, but thought to activate Angiotensin in lungs (all blood must flow through here) |
|
|
Term
Angiotensinogen
Where is it made?
What stimulates its release? |
|
Definition
Constantly being secreted from the liver
Plasma levels are increased by: glucocorticoids, estrogen, thyroid hormone, Ang II, inflammation, insulin, pregnancy |
|
|
Term
| Actions of Ang II, which is the most important? |
|
Definition
1. Increases aldosterone synthesis (MOST IMP)
2. Vasoconstrictor
3. ADH release
4. Na+ reabsorption in proximal tubule
5. Stimulates thirst center in hypothalamus |
|
|
Term
| How do NSAIDs affect the RAS system? |
|
Definition
Questioned about their role in the signaling of the macula densa to the JGA (mediated by PGI2/PGE2)
Block PG in the afferent arteriole, which normally cause it to be vasodilated - so NSAIDs cause vasoconstriction of afferent arteriole. |
|
|
Term
| What is the only renin inhibitor |
|
Definition
(Tekturna) Aliskiren
Decreases plasma renin ACTIVITY
lowers BP ~10-15 mmHg
NOTE: bonus - decreases B-type natriuretic peptide (BNP) [high levels associated with worsening HF] |
|
|
Term
| T or F: when discontinuing Aliskiren you can abruptly stop it without any concerns |
|
Definition
| F - aliskiren increases plasma renin (body trying to compensate for decrease in renin activity) so if d/c abruptly the will cause a spike in renin = spike in BP |
|
|
Term
| What is the only contraindication of aliskiren? |
|
Definition
| Do NOT use with ACEI or ARB in diabetic patients (probably shouldn't with anyone) -increased risk of renal impairment, hyperkalemia, hypotension |
|
|
Term
| Administration of aliskiren |
|
Definition
Avoid taking with high fat meals (already low bioavailability that decreases with fat)
QD
Max of 300 mg/day |
|
|
Term
|
Definition
fetal/neonatal morbidity
oligohydramnios (kidney injury)
Greatest risk in 2nd/3rd trimesters |
|
|
Term
| Common ADRs for all RAS drugs |
|
Definition
1. Dont use in preg
2. Head/neck angioedema
3. Hypotension
4. Slight suppression of hematopoiesis |
|
|
Term
|
Definition
Diarrhea
hyperkalemia (esp with combined with other RAS drugs or K-sparing diuretics)
slight suppression of hematopoiesis
fetal/neonatal morbidity assoc with use in pregnancy
head/neck angioedema
hypotension |
|
|
Term
|
Definition
1. Converts Ang I to Ang II
2. Degrades Bradykinin (vasodilator) |
|
|
Term
| What causes the cough associated with ACE inhibitors? |
|
Definition
| Bradykinin (cant be degraded) |
|
|
Term
| Degradation of Angiotensin II |
|
Definition
Plasma half-life only ~30 seconds
Degraded by angiotensinases (in blood cells and endothelium)
Breaksdown to Ang III (agonist) and Ang(1-7) (antagonist)
Ang III gets further broken down to Ang IV (antagoinst)
Agonist = AT1
Antagonist = AT2 |
|
|
Term
| T or F: All ACEI are therapeutically equivalent? |
|
Definition
T - but differ in potency
Even though there are three classes (most are dicarboxylates) |
|
|
Term
| What are three biological chemical levels that ACEI alter? |
|
Definition
1. Renin: increase levels (attempt to compensate)
2. Ang I: increase levels (attempt to compensate)
3. Bradykinin: increase levels (because cant breakdown) |
|
|
Term
| What type of enzyme is required for ACEI activation in the body? |
|
Definition
| Esterases - should use an ACEI that inst a prodrug if patient has hepatic disease |
|
|
Term
| Which ACEI are not prodrugs? |
|
Definition
Lisinopril
Captopril
Enalaprilat (IV only) |
|
|
Term
| How effective are ACEI at lowering BP? |
|
Definition
work in about 50% of patients with mild/moderate HTN
Lower SBP 6-9 mmHg (average)
Addition of a diuretic = effective therapy in 90% of patients |
|
|
Term
| Which maintains a fall in BP for a longer time, thiazides or ACEI? |
|
Definition
| ACEI, fall in BP maintained over long-course treatment without compensation |
|
|
Term
| T or F: ACEI prevent incidence of diabetes in people with HTN? |
|
Definition
| F - does not prevent diabetes, but are cardioprotective and renoprotective in people with diabetes |
|
|
Term
| What is the best agent to use for HTN in people with diabetes? |
|
Definition
| ACE inhibitors (Cardio and reno-protective) |
|
|
Term
|
Definition
1. Hypotension - titrate up and down
2. Cough - (20%) not dose related, more common in women, develops between 2 weeks and 6 months, ASA may reduce cough
3. Angioedema - usually with first dose (during first week), 2x greater in blacks and more common in women, resolves when d/c drug
4. Skin rash (esp captopril)
5. Dysgeusia (esp captopril)
6. Neutropenia (rare)
7. Hyperkalemia (rare, unless taking K supp or K sparing diuretics) |
|
|
Term
| Why does ACEI cause hyperkalemia? |
|
Definition
| Because aldosterone is being blocked which usually depletes K |
|
|
Term
| What can ACEI cause in patients with bilateral renal artery stenosis and severe CHF? |
|
Definition
| Acute renal failure because it decreases GFR in renally compromised patients |
|
|
Term
| T or F: Dose determines the duration of effect for ACE inhibitors |
|
Definition
T - too low of a dose will not maintain lowered BP throughout dosing interval
Exhibits a flat dosing curve (not true with ARBs) |
|
|
Term
| Which ACE inhibitors have a long duration of action? |
|
Definition
Lisinopril
Benzaepril
Enalapril
Ramipril
Citazapril
Fosinopril
Perindopril
Trandolapril
Zofenopril
QD |
|
|
Term
| T or F: all ACEI are cleared the same way |
|
Definition
NO!
Lisinopril, Captopril, and Enalapril are only cleared renally, the others are mix of hepatic and renal (varying degrees)
pay attention in renal/hepatic disease |
|
|
Term
| Which receptor dose ARBs block |
|
Definition
AT1 - block all the major effects of Angiotensin II (aldosterone, ADH release, thirst, vasoconstriction)
10,000x more selective for AT1 than AT2 |
|
|
Term
| What type of receptor is AT1? |
|
Definition
| Gq (in most cells) but can be Gi too |
|
|
Term
| Which ARB is the most selective for AT1? |
|
Definition
| Candesartan = Omesartan > Irbesartan = Eprosartan > Telmisartan = Valsartan > Losartan |
|
|
Term
| Are ARBs irreversible or reversible inhibitors? |
|
Definition
competitive and reversible, but have such affinity, they are essentially insurmountable
(receptor internalization may contribute) |
|
|
Term
| T or F: ARBs are not effective in low-renin HTN? |
|
Definition
|
|
Term
| T or F: ACEI and ARBs are therapeutically equivalent |
|
Definition
|
|
Term
| What is a big advantage (in terms of ADRs) that ARBs have over ACEIs? |
|
Definition
NO cough
They also block non-ACE pathways of Ang II, permit activation of AT2 (possibly more popular as they become generic) |
|
|
Term
| Irbesartan and losartan have a second unique indication, what is it? |
|
Definition
diabetic neuropathy in patients with HTN
DOC for renoprotection in diabetic patients |
|
|
Term
|
Definition
New drug (LCZ696)
MOA: inhibits neprilysin (neutral endopeptidase) to black atrial natriuretic peptide (ANP) degradation
-ANP is a potent vasodilator made by heart in response to high BP, hypernatremia, and ANGII
-ALSO an AT1 antagonist (AKA ARB) |
|
|
Term
| Which two types of patients are CCBs often used in? |
|
Definition
Elderly and Blacks
Low renin producers |
|
|
Term
| How do each class of CCB differ in mechanism? |
|
Definition
| They each bind to different sites in the alpha1-subunit of the L-type voltage gated Calcium Channel |
|
|
Term
| Which type of Calcium channel to CCBs act on? |
|
Definition
|
|
Term
|
Definition
Bind to L-type voltage-gated Ca channels on cell membrane
Inhibit Ca entry into cells needed for contraction
-Vasodilation (periphery and coronary)
-Decreased heart contractility/conduction (bind to cardiac myocytes and SA/AV nodes) |
|
|
Term
| T or F: CCBs are therapeutically equivalent to ACEIs |
|
Definition
| T, they are also therapeutically equivalent to beta-blockers |
|
|
Term
| Which type of CCB are used most often |
|
Definition
|
|
Term
| Which CCB(s) is/are most vasodilating? |
|
Definition
dihydropyridines (nifedipine, nicardipine, nimodipine) >> verapamil > diltiazem
Associated with baroreceptor reflex causing tachycardia and increased CO |
|
|
Term
| Which CCB(s) cause the most cardiac contractility and conduction |
|
Definition
| Verapamil > diltiazem >> dihydropyridines |
|
|
Term
| What types of patients should CCBs be avoided? |
|
Definition
HF (including left ventricular hypertrophy)
post-MI
SA or AV node conduction defects |
|
|
Term
| What other drugs are CCBs usually combined with? |
|
Definition
| ACEIs, beta-blockers, methyldopa |
|
|
Term
| does diltiazem act more similarly to verapamil or nifedipine? |
|
Definition
|
|
Term
| Can you combine two CCBs with different mechanisms? |
|
Definition
No, even though they might have different predominant mechanisms, they still have same mech
Only dihyropyridine + diltiazem is okay in hard-to-control cases |
|
|
Term
| What are some longer acting CCBs |
|
Definition
amlodipine, isradipine, felodipine
QD |
|
|
Term
| What enzyme does verapamil inhibit? What might this effect? |
|
Definition
PGP transporter
decreased clearance of digoxin
also a CYP3A4 substrate |
|
|
Term
| When might doses of CCB might need to be adjusted? |
|
Definition
Impaired hepatic function (metabolism)
Elderly |
|
|
Term
| What is the biggest ADR concern with CCBs |
|
Definition
Hypotension (probably with just about any HTN med)
+EDEMA big complaint - why many stop these |
|
|
Term
|
Definition
1. Hypotension: dizzy, HA, flushing, nausea, PERIPHERAL EDEMA
-Myocardial ischemia related to hypotension/decreased coronary perfusion (most common with IR formulations)
2. GERD: relaxation of esophageal sphincter
3. Gingival hyperplasia
4. Occasional: Constipation, coughing, wheezing, pulmonary edema, rash
5. Rare elevations in liver function tests (verapamil/diltiazem)
6. Bradycardia (verapamil, esp IV) - potentiated with beta-blockers - bad if SA/AV defects |
|
|
Term
| CCB vs Diuretic as second line agent with ACEIs |
|
Definition
| equivalent effectiveness for BP, but with CCB reported CV events was lower |
|
|
Term
| What alpha-1 blockers are used in HTN |
|
Definition
prazosin (Minipress) BID-TID
terazosin (Hytrin) QD
doxazosin (Cardura) QD |
|
|
Term
|
Definition
antagonize post-synaptic alpha-1 receptor found in the periphery on vascular smooth muscle
prevent vasoconstriction: this will persist but initially there is also in increase in HR, CO, and renin (baroreceptor reflex) that goes away
(and may suppress sympathetic outflow from CNS) |
|
|
Term
| What is an additional benefit of alpha-1 blockers? |
|
Definition
| improve serum lipids (good if have atherosclerosis too) |
|
|
Term
| Administration of alpha-1 blockers |
|
Definition
QHS (prazosin = BID/TID)
taper up (if dont take for a few days then need to re-taper again)
Start at 1 mg, Do not exceed 20 mg (usually need 1-5 mg dose)
undergo hepatic metabolism (possibly require dose adjustment)
If BP doesnt stay down for the entire dosing interval then need to increase dose. |
|
|
Term
|
Definition
Postural Hypotension (take at night): dizziness, edema, fatigue
Nausea
Nasal Congestion
Palpitations
Rarely: anaphylaxis, priapism
Generally ADRs decrease with continued use
Preg Cat C (teratogenic in animals) |
|
|
Term
| How should alpha-1 blockers be used in the treatment of HTN? |
|
Definition
Not usually recommended as monotherapy with HF
Use in conjunction with diuretics, beta-blockers, RAS drugs
Appropriate for diabetics, gout, BPH
Beneficial in atherosclerosis (improves lipids) |
|
|
Term
| MOA of beta-blockers in HTN |
|
Definition
1. Blockade of RAS via beta-1 (MOST IMP)
-But antiHTN effect does not always correlate with plasma renin levels
2. Decrease cardiac contractility and HR to decrease CO |
|
|
Term
| T or F: all beta-blockers are equally effective in HTN? |
|
Definition
| T - doesnt matter if selective or non-selective |
|
|
Term
| T or F: Beta-blockers do NOT lower BP in normotensive patients? |
|
Definition
| T - because no sympathetic nervous system overactivation |
|
|
Term
| MOA of labetalol and carvedilol |
|
Definition
alpha-1 blocker: lowers TPR
beta-1 and -2 blocker with intrinsic activity (aka partial agonist): vasodilation and blocks RAS |
|
|
Term
| Which provides better glycemic control in diabetes, carvedilol or metoprolol? |
|
Definition
| Carvedilol because of addition of alpha blocker, can lower the required dose of beta-blocker |
|
|
Term
|
Definition
|
|
Term
|
Definition
high specificity of blocking beta-1
vasodilation by stimulating NO production |
|
|
Term
| How long will it take to see a full effect of a beta-blocker |
|
Definition
|
|
Term
| When are beta-blockers first line for the treatment of HTN |
|
Definition
after MI
HF
arrhythmias
angina
(because will be used anyways) |
|
|
Term
| Why are beta-blockers not generally recommended to be used with ACEIs and ARBs? |
|
Definition
| mechanism is too redundant - renin system |
|
|
Term
| Would beta blockers be a good choice of blacks and elderly? |
|
Definition
| Not generally, because they are low renin producers, which is the primary way beta-blockers elicit their anti-HTN effect |
|
|
Term
| T or F: a diuretic should always be added to beta-blocker anti-HTN therapy |
|
Definition
F - because beta-blockers do not cause water/Na retention, it is not needed HOWEVER, addition of a diuretic is common
Diuretic + minoxidil (vasodilator) + BB = effective in almost all patients |
|
|
Term
| What anti-hypertensive drug class should be avoided in patients with COPD? |
|
Definition
| beta-blockers (block b2 - studies are showing specific beta-blockers are generally safe) |
|
|
Term
| Who should avoid beta-blockers? |
|
Definition
1. Insulin dependent diabetics - mask symptoms of hypoglycemia
2. COPD - bronchoconstriction risk (starting to decrease)
3. Cardiac Conduction Issues - cause bradycardia, may not be able to tolerate initial drop in CO |
|
|
Term
| What HTN drugs should be used for people with cardiac conduction issues? |
|
Definition
| Diuretics or vasodilators |
|
|
Term
| What would you expect to see if someone abruptly discontinued a beta-blocker they were taking for HTN? |
|
Definition
rebound HTN
taper over 2 weeks |
|
|
Term
| ADRs associated with beta-blockers |
|
Definition
fatigue, dizziness, depression
bronchoconstriction
bradycardia |
|
|
Term
| T or F: even though beta-blockers decrease BP, morbidity/mortality has not shown to decrease with beta-blocker monotherapy |
|
Definition
| T - still at higher risk for complications than other anti-HTN drugs (ex: stroke, cause insulin resistance, increased risk of DM) |
|
|
Term
| Which beta-blocker has not been found to cause new onset diabetes? |
|
Definition
| Carvedilol (probably because alpha action) |
|
|
Term
| What are the centrally acting drugs used in HTN and what is their class |
|
Definition
alpha-2-agonists
Guanfacine
Clonidine
Guanbenz
Methyldopa |
|
|
Term
|
Definition
| Reduce sympathetic outflow by decreasing CNS NT release |
|
|
Term
| Role of alpha-2 agonists in the treatment of HTN |
|
Definition
Not usually first line (b/c ADR)
Appropriate in drug resistance and pregnancy
Used in combination (with diuretics or vasodilators[can replace beta-blocker]) |
|
|
Term
| Methyldopa is an analog of what? How does it work |
|
Definition
DOPA
gets converted to methylNE (replaces NE) in neurons of brainstem (central site of action)
Because MNE is not broken down by MAO (like NE is) it will accumulate and overcome NE ->why it works
Also: acts as dopa decarboxylase inhibitor -decreases peripheral NT synthesis ->more hypotension (probably contributes to ADRs in brain) |
|
|
Term
| Effect of methyldopa on TPR, CO, and HR |
|
Definition
Decreases TRP
Little effect on CO or HR except in elderly |
|
|
Term
| Is orthostatic hypotension an issue with methyldopa? |
|
Definition
| No, only a modest problem (because turning the SNS down, not off) |
|
|
Term
| Effect of methyldopa on renal blood flow and function |
|
Definition
Not affected
but plasma renin levels do decrease (b/c decrease SNS) |
|
|
Term
| When would you expect to see an effect from methyldopa? |
|
Definition
Peak effect is 6-8 hours and lasts 24 hours (b/c must be metabolized then packaged into vesicles)
QD dosing |
|
|
Term
|
Definition
CNS: sedation, inattentiveness, depression, dry mouth, parkinsonian signs, loss of libido, hyperprolactinemia, severe bradycardia
Hepatotoxicty (uncommon, usually reversible)
Na retention (with longterm therapy)
Hemolytic anemia/blood disorders - 20% develop autoantibodies to Rh on RBC - leads to anemia (d/c drug fixes anemia) |
|
|
Term
| With which drug class is the CV response to exercise impaired? |
|
Definition
|
|
Term
| Normally, clonidine activates the alpha-2a receptor but if dosed to high it can activate the alpha-2b receptor in the vasculature, what is the effect of this? |
|
Definition
| Causes vasoconstriction (counterintuitive) |
|
|
Term
| What is the effect on the alpha-2a agonists on CO and TPR |
|
Definition
decreases both
CO dominates in supine position
Vasodilation dominates in upright position |
|
|
Term
| T or F: Na retention can occur with all alpha-2 agonists? |
|
Definition
| T - advise giving a diuretic too less with guanabenz |
|
|
Term
| Renin levels decrease with all sympatholytics used in HTN except which class? |
|
Definition
| Alpha-blockers (ex: doxazosin) |
|
|
Term
| Which is the most selective alpha-2 agonist? |
|
Definition
guanfacine
no better activity, but fewer ADRs |
|
|
Term
|
Definition
Guanfacine Extended Release
Used in ADHD |
|
|
Term
| Which alpha 2 agonist is available as a patch |
|
Definition
| Clonidine - lasts for 1 week |
|
|
Term
| What is the preferred antihypertensive in pregnancy? |
|
Definition
|
|
Term
|
Definition
| CNS: sedation, dry mouth, vivid dreams/nightmares, depression, severe bradycardia, sexual dysfunction |
|
|
Term
| Overdosage of an alpha-2 agonist resembles what other common OD? |
|
Definition
opioid
disorientation, HTN followed by hypotension, bradycardia, respiratory depression, miosis |
|
|
Term
| T or F: you can get withdrawal from clonidine? |
|
Definition
T with any alpha-2 agonist
Sx: HA, apprehension, tremors, sweating, tachycardia, rebound HTN (greater than was before starting drug)
more likely with higher doses |
|
|
Term
| What are the two minor sympatholytics? |
|
Definition
Reserpine
Guanadrel (Hylorel) |
|
|
Term
|
Definition
targets postganglionic adrenergic neurons
taken up by PREsynaptic terminal by NE transporter- replaces NE - released as inactive NT
HAS NO AGONIST activity, just depletes NE (different than methyldopa)
Causes vasodilation |
|
|
Term
| What types of drugs would inhibit/blunt the effects of guanadrel? |
|
Definition
TCAs, cocaine, chlorpromazine, strattera
Anything that will block the uptake of NE |
|
|
Term
|
Definition
orthostatic hypotension
volume expansion (Na retention)
weakness, sexual dysfunction, diarrhea
Contraindicated in CHF b/c block sympathetic stimulation |
|
|
Term
| Administration of Guanadrel, what should be monitored |
|
Definition
PO BID
delayed effect because MOA requires uptake
use if other drugs fail/are insufficient
don't use as monotherapy (b/c postural hypotension)
Monitor renal and hepatic clearance |
|
|
Term
|
Definition
binds to NT storage vesicles and impairs transport of storage vesicles (in CNS and PNS)
Decrease TPR, renin, CO/HR (Na retention counteracts hypotensive effect, so orthostatic hypotension not a concern) |
|
|
Term
| Is the pharmacologic half-life of reserpine long or short |
|
Definition
| Very long - half-life is on the order of weeks and has a slow onset |
|
|
Term
| What NTs does reserpine inhibit? |
|
Definition
| adrenergic, dopamine, and serotonin |
|
|
Term
|
Definition
Sedation
Inattention
Nasal congestion
Sexual dysfunction
Depression with suicidal thoughts/psychosis - screen patients |
|
|
Term
| What are some vasodilators used for HTN? |
|
Definition
Hydralazine (Apresoline)
Minoxidil (Loniten/Rogaine)
Sodium nitroprusside (Nipride)
Diazoxide (Hyperstat) |
|
|
Term
| Is orthostatic hypotension a concern for patients on vasodilators? |
|
Definition
NO!
Because they directly relax arteriolar smooth muscle, they:
1. dont require innervation
2. dont rely on receptor activation
3. Dont affect SNS (SO NOT ortho hypotn)
AND dont cause VENOdilation |
|
|
Term
| When you give a vasodilator the body tries to compensate for the changes, how? |
|
Definition
Increase SNS activity (vasoconstriction, CO/HR, renin release)
Decreased blood flow to kidney also stimulates increased renin release
Because of this attempt to compensate must be used with other anti-HTN drugs |
|
|
Term
| What other anti-HTN drugs must vasodilators be used in combination with? |
|
Definition
1. beta-blocker (alpha-2 agonists can be substituted): prevents increased SNS activity (wont cause increased CO/HR/TPR/renin)
2. Diuretic: prevents Na loss so kidney wont trigger release of renin -->RAS |
|
|
Term
| MOA of sodium nitroprusside |
|
Definition
| requires activation by blood vessels to NO (which relaxes vascular smooth muscle) |
|
|
Term
| Which vasodilator also relaxes veins? |
|
Definition
nitroprusside
its also the only one that doesnt cause a compensatory increase in CO (but may increase HR) |
|
|
Term
| What is the mechanism of Minoxidil and Diazoxide? |
|
Definition
| activate the ATP-dependent K+ channel which hyperpolarizes and relaxes arteriolar smooth muscle cells |
|
|
Term
| Which vasodilator can elicit the greatest drop in BP |
|
Definition
|
|
Term
| T or F: Vasodilators elicit their effect on all smooth muscle. |
|
Definition
| F - other smooth muscle is not affected (ex: GI) |
|
|
Term
| Which vasodilators are administered orally? |
|
Definition
| Hydralazine and minoxidil |
|
|
Term
| Which vasodilators are administered IV? |
|
Definition
| nitroprusside and diazoxide |
|
|
Term
| For PO vasodilators, why is their therapeutic half-life longer than their plasma half-life? |
|
Definition
may accumulate in artery walls
minoxidil active metabolite may have longer half-life than parent drug |
|
|
Term
| Which PO vasodilator has a longer half-life and is used in more severe HTN |
|
Definition
|
|
Term
| When are diazoxide and nitroprusside used? |
|
Definition
| Hypertensive emergencies/crisis |
|
|
Term
| How long does it take to see an effect from nitroprusside (diazoxide)? How does this play into their therapy? |
|
Definition
30 seconds (3-5 minutes) when given IV
Good, because used for HTN-ive crisis
Nitroprusside: within 2-3 minutes of d/c infusion, vasodilation will end
(D: action lasts 4-12 hr) |
|
|
Term
| Why does diazoxide need to be administered as a rapid injection? |
|
Definition
| to prevent binding to plasma proteins |
|
|
Term
| Which vasodilator requires activation by the liver? |
|
Definition
|
|
Term
| In order to prevent cyanide toxicity with nitroprusside, how long is an infusion of it limited to? |
|
Definition
|
|
Term
| If a patient has renal failure, which vasodilator is ideal to use? |
|
Definition
Minoxidil: only hepatic activation and biliary excretion
Hydralazine: renally eliminated
Diazoxide: renal + hepatic elimination
Nitroprusside: CN can be toxic in renal failure |
|
|
Term
| When is nitroprusside used? |
|
Definition
| hypertensive crisis associated with MI and ventricular failure |
|
|
Term
| What are some ADRs (in general) associated with vasodilators used in HTN? |
|
Definition
1. Vasodilation: HA, flushing, congestion, vertigo, N/V
2. Cardiac stimulation: tachycardia, palpitations (prevent with beta-blocker)
3. Fluid retention: lead to CHF, pulmonary HTN (give diuretic) |
|
|
Term
| What specific issue might hydralazine cause that is unique |
|
Definition
Autoimmune reactions
Lupus syndrome (arthritis, arthralgia, fever) - long-term, dose-dependent, more common in WOMEN and WHITES, resolves when d/c |
|
|
Term
| What specific ADR is associated with minoxidil? |
|
Definition
Hypertrichosis
remember, topical minoxidil (Rogaine) used for male pattern baldness |
|
|
Term
| What two unique ADRs does diazoxide cause |
|
Definition
1. Hyperglycemia: esp in non-insulin-dependent diabetics (but not used for long so not usually a problem) b/c inhibits insulin secretion (via K channel stimulation)
2. Can stop labor by relaxing uterine smooth muscle |
|
|
Term
| What patient population should nitroprusside be used with caution in because it can worsen hypoxemia? |
|
Definition
|
|
Term
| Is pulmonary arterial hypertension more common in men or women? |
|
Definition
|
|
Term
| What are the three forms of pulmonary arterial hypertension? |
|
Definition
1. Idiopathic (~40%)
2. Familial (few)
3. Associated (with certain diseases) |
|
|
Term
| What diseases can pulmonary arterial hypertension be associated with? |
|
Definition
Connective tissue diseases
Congenital heart disease
Portal hypertension (hepatic disease)
HIV
COPD
Schistosomiasis
Sickle Cell
Anorexic Drugs: FenFen, amphetamines, some chemo |
|
|
Term
| Presentation of pulmonary arterial hypertension |
|
Definition
Exertional dyspnea, fatigue
Edema
heart murmurs |
|
|
Term
| Who is pulmonary arterial hypertension confirmed |
|
Definition
Right heart catheterization: mean pulmonary arterial pressure >25 mmHg; pulmonary wedge pressure <15 mmHg
6 minute walking test for disease severity |
|
|
Term
| T or F: people with pulmonary arterial hypertension will have very high blood pressures |
|
Definition
| F - wont know - it is not evident with a cuff |
|
|
Term
What changes in endothelial function/factors occur with pulmonary arterial hypertension
PATHOPHYSIOLOGY |
|
Definition
Decreased: prostacyclin (PGI2), Nitric oxide synthase
Increased: thromboxane, endothelin-1 (vasoconstrictor)
Pro-coagulant state (incresaed von Willebrand factor)
Vascular inflammation: autoantibodies, proinflam. cytokines
FIBROSIS- leads to right ventricular hypertrophy and eventual failure |
|
|
Term
| What is the general pharmacologic treatment of pulmonary arterial hypertension? |
|
Definition
1. Oral anticoagulants: TE common
2. Diuretics: in right side failure/edema
3. Oxygen: apnea, dyspnea
4. Digoxin: use in heart failure
+Other agents to help with the HTN specifically (CCBs, PDE inhibitors, prostacyclin analogs, endothelin antagonists) |
|
|
Term
| T or F: everyone with pulmonary arterial hypertension should be on an CCB |
|
Definition
F - only effective in under 15% of patients with pulmonary arterial hypertension
-to know who should take a CCB test at same time catheterized for confirm diagonsis |
|
|
Term
| If chose to use a CCB in pulmonary arterial hypertension, which class is usually preferred? |
|
Definition
| dihydropyridines = peripheral vasodilators (less effect on heart) |
|
|
Term
| Name some phosphodiesterase inhibitors |
|
Definition
sildenafil
tadalafil
vardenafil |
|
|
Term
| Why are PDE inhibitors used in pulmonary arterial hypertension |
|
Definition
Increase nitric oxide = vasodilation
decrease pulmonary arterial pressure
decrease plasma endothelin-1 levels
improved exercise tolerance |
|
|
Term
| What should be avoided if on a PDE inhibitor |
|
Definition
|
|
Term
|
Definition
| blue vision, HA, diarrhea |
|
|
Term
| administration of PDE inhibitors in pulmonary arterial hypertension |
|
Definition
|
|
Term
|
Definition
vasodilator (G-protein coupled to cause K+ hyperpolarization--> smooth muscle relaxation)
platelet inhibitor
antiproliferative |
|
|
Term
| What are some major limitations to using prostacyclin to treat pulmonary arterial hypertension? |
|
Definition
VERY SHORT HALF-LIFE (3-5 min)
Must be kept on ice
Dose is limited by ADRs (cough, flushing, HA, jaw pain, diarrhea)
Sepsis is greatest risk |
|
|
Term
|
Definition
first inhaled prostacyclin analog used to treat pulmonary arterial hypertension.
given 6-9 times daily or Q2H |
|
|
Term
|
Definition
stable prostacyclin analog give SQ or IV and now inhaled (PREFERRED)
can be used in combination with Bosentan and sildenafil |
|
|
Term
| What are two prostacyclin analogs? |
|
Definition
|
|
Term
| Actions of ET-1 (endothelin-1) |
|
Definition
VASOCONSTRICTION
stimulates vascular smooth muscle proliferation
promotes aldosterone synthesis |
|
|
Term
| Two receptors that ET-1 can bind to? What are their effects? |
|
Definition
ETa: contraction vascular smooth muscle
ETb: contraction of vascular smooth muscle AND nitric oxide release (mix of vasodilation and contraction)
Want to block ETa |
|
|
Term
| What are the primary benefits seen with endothelin antagonists? |
|
Definition
improve exercise capacity
hemodynamics
slow disease progression |
|
|
Term
| Name two approved endothelin antagonists (and one still being studied) |
|
Definition
1. Bosentan (Tracleer)
2. Ambrisentan (letaris)
(3. Darusentan (Dorado)) |
|
|
Term
|
Definition
Blocks both ETa and ETb receptors
-dosed based on body weight
-elevates hepatic enzymes - monitor monthly
-metabolized by CYP2C9, 3A4, and 2C19 and induces them
-Cat X for pregnancy - monthly pregnancy tests required and 2 forms of birth control
-REMS because of hepatotoxicity (and preg) |
|
|
Term
| Administration of Bosentan |
|
Definition
orally active BID
dosed based on body weight |
|
|
Term
| Which endothelin antagonist is selective for ETa? |
|
Definition
|
|
Term
|
Definition
|
|
Term
| ADRs/Issues with ambrisentan |
|
Definition
Cat X for pregnancy (REMS)
NO hepatotoxicity -no testing
metabolized by CYP 3A4, 2C19
ADRs: edema, congestion, flushing, palpitations (prob will be on beta-blocker and diuretic anyway to help) |
|
|
Term
| Can endothelin antagonists be used in normal HTN? |
|
Definition
| No evidence yet. Darusentan trials tried, at first just peripheral edema, but second trial failed |
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