DSM
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| Hypertension is.... | the "silent killer", characterized by elevated peripheral resistance
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| Hypertension targets what organs? | blood vessels, heart, kidney, brain, eyes
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| Why do we give antihypertensives? | Control symptoms, try to prevent organ damage
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| What factors do we consider when selecting drug therapy? | Compliance, side effects, economics
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| What was JNC VII? | guidelines to increase awareness, prevention, and treatment of hypertension based on large clinical trials '97-'03
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| List the various lifestyle modifications and their effect on SBP | Weight reduction (5-10mmHg/Kg), DASH dies (8-14 mmHg), dietary sodium reductuion (2-8mmHg), physical actvity (4-9 mmHg), moderate alcohol consumption (2-4mmHg)
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| How long should a patient try lifestyle modifications before being put on medication? | 3 months-6 months
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| Normal blood pressure is... | Below 120/80
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| Pre-hypertension is... | 120-139/80-89
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| Stage 1 hypertension is... | 140-159/90-99
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| Stage 2 hypertension is... | over 160/over 100
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| Name some non-pharmacological therapies | sodium restriction, weight reduction, exercise, stress reduction, eliminating risk factors (cholesterol,tobacco, alcohol)
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| When would drugs be used for pre-hypertension? | Drugs for compelling indications only (no compelling indication, no drugs)
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| What is a compelling indication? | Other co-morbidities to consider
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| What drug therapy would be used for stage 1 hypertension (w/o compelling indications)? | THIAZIDE-type diuretics for most, may consider ACEI,ARB,CCB,BB or some combo of these
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| What drug therapy would be used for stage 1 hypertension (w/compelling indications)? | THIAZIDE-type diuretics for most, may consider ACEI,ARB,CCB,BB or some combo of these ? Plus drugs for co-morbidities
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| What drug therapy would be used for stage 2 hypertension (w/o compelling indications)? | 2 drug combo (THIAZIDE + ACEI,ARB,BB OR CCB)
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| What drug therapy would be used for stage 2 hypertension (w/compelling indications)? | Other hypertensive drugs (CCB,ACEI, ARB,BB) as needed
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| List the 6 comorbid conditions to consider when selecting therapy | CHF, post MI, High coronary disease risk, diabetes mellitus, chronic kidney disease, recurrent stroke prevention
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| What was the ALLHAT study? | Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial, evaluated whether occurrence of fatal CHD or nonfatal MI is lower for high risk pts w/ hypertension treated w/ and ACEI or CCB vs. a diuretic
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| What drugs did the ALLHAT study compare? | amlodipine, lisinopril, and chlorthalidone
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| What did the ALLHAT study find in reference to diuretics? | Thiazide diuretics should be considered in nearly all pts includ. (untreated, inadequately controlled not on diuretics, and those controlled on non-diuretics unless there's a compelling indication for an alt. drug)
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| What was ALLHAT'S conclusion in regards to second-line agents? | Most hypertensives req additional drugs for bp control, but since no direct comparison of 2nd line agents was made with ALLHAT the optimal add-on agent is unknown
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| Why should diuretics be 1st line therapy for everyone, including pts w. diabetes and asymptomatic LVH? | Diuretics=least expensive & most effective
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| List the classes of antihypertensive agents | diuretics, ACEI, ARB, BB,CCB, alpha antagonists, K sparing diurteics, vasodilators, CNS agents, sympatholytics
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| What drugs does JNC VII recommend for heart failure and why? | ACEI (#1), DIURETICS(for edema-mainly loop), BB (reduce mortality but monitor volume-dose lower than pt w/o CHF), ARB(if can't take ACEI), ALDOSTERNONE ANTAG (spironolactone-add to pts w/NYHA II or IV failure or post-MI pts w/ new left ventricular issues
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| What drugs did JNC VII recommend for MI and why? | BB(#1 b/c decr. subsequent MI and sudden cardiac death), ACEI (improves cardiac remodeling & function & reduces later cardiac events), ARB (if pt can't take ACEI), ALDOSTERONE ANTAG (decr. mobidity & mortality if added in 14 days post MI in pts w/ EF<30%
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| What drugs did JNC VII recommend for coronary artery disease? | BB (1st line if stable chronic angina to avoid ISA),CCB (if pts can't do BB-long acting)
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| What drugs did JNC VII recommend for diabetics? | ACEI,ARB (1st-reduce CV risk& nephroprotective), BB (reduce CV risk), CCB (lower BP more, add-on therapy, same CV risk protection as ACEI or ARB)
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| Why did the JNC VII recommend those certain drugs for diabetics? | Diabetes is considered equivalent to coronary artery disease
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| What drugs did JNC VII recommend for chronic kidney disease? | ACEI/ARB-reduce BP &intrarenal pressure, also ACEI+ARB may be more effective than monotherapy
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| What is an early warning sign of Chronic Kidney Disease? | Microalbuminuria
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| What was JNC VII's drug recommendations for recurrent stroke? | Diuretic +ACEI b/c reduces incidence of stroke in pts w/ prior stroke or TIA
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| What is the major issue in regard to preventing secondary stroke? | Reduction of BP
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| What special factors should be considered in elderly pts? | Least BP control, isolated SBP common, more than 50% need combo therapy, sensitive to vol. depletion & inhibition of SNS, altered drug metabolism, cognitive impairment, polypharmacy and economics (fixed income) should be considered
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| What is the first line tx for the elderly and how does the dose differ from normal? | THIAZIDE but lower than normal dose
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| What special factors should be considered in female patients? | Prevalence of hypertension higher after age 50, also oral contraceptives can cause 2ndary hypertension so bp should be checked every 6 mo if on bc or hormone replacement
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| What special factors should be considered for african american patients? | They have a higher incidence of hypetension & organ damage, monotherapy w/ BB, ACEI, and ARBS not as effective; THIAZIDES & CCB more effective, high risk for angioedema and cough
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| What is the ISHB and what are their guidelines? | ISHB= International Society for Hypertension in Blacks; guidelines similar to JNC-lifestyle mods, THIAZIDES 1st, combo therapy if SBP
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| What drug therapies should be considered if the pt has dyslipidemia? | ALPHA BLOCKERS have favorable effects
THIAZIDES and BB may INCREASE lipids-BAD
ACEI, ARB, CCB-NEUTRAL
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| What drug therapies should be considered in pts w/ left ventricular hypertrophy? | ACEI and ARB (improved bp control improves LVH)
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| What should be considered in pts w/ erectile dysfunction? | Hypertension=risk factor for erectile dysfunction, diabetes is also a risk factor, major concerns are CNS acting agents, BB, sympatholytics
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| Which thiazide-type duiretics do we have to know? | It's easy-just the ones that end in thiazide
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| Name the 2 loops diuretics mentioned? | Furosemide (lasix) and ethacrynic acid (edecrin)
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| Name 3 K sparing diuretics | Amiloride (Midamor), Spironolactone (Aldactone), Triamterence (Dyrenium)
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| What is the MOA of diuretics? | Produce a moderate but persistent decr. in ECF and plasma vol, inital decr. BP due to reduced CO, long term decr.BP due to autoreg which decr. TPR
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| List some advantages of diuretics | effective in many pts, inexpensive, few SE, docs know about them
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| Name some disav. of diuretics | can cause electrolyte imbalances, can elevate serum lipids,can cause metabolic alkalosis, carb metabolism can be impaired, hyperuricemia can occur or incr.
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| When do we use diuretics? | 1st line tx in obese, elderly, or black but less effective in lean ppl, can minimize SE of other agents, decr. intracranial pressure, decr. intraoccular pressure, reduce edema, tx of CHF
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| Why do we use the lowest effective dose of diuretics? | Max decr. in BP occurs over a relatively small dosage & if dosage is pushed SE incr.
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| How are diuretics dosed? | Continue therapy for at least 2 weeks be changing dose or drug, dose pt qam to reduce nocturia
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| What is the most common problem with diuretics and what can this problem manifest as? | Problem=loss of electrolytes--causes dizziness, cramps, nausea, postural hypotension but effects diminish after a few days
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| What is a renal SE of thiazides? | May reduce GFR so don't use in pts with decr. renal function
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| Name 2 general side effects of diuretics | may precip gout by decr. secr. of uric acid &n use cautiously in diabetics-can produce hyperglycemia
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| List some characteristics of spironolactone | K sparing diuretic, aldosterone antagonist, weak progesterone, hyperkalemia can occur, gynecomastia can also occur
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| List some characteristics of direct-acting K sparing diuretics | Include trimterene and amiloride, DON'T antag. aldosterone so effective regardless of aldosterone status, more reliable than spironolactone, can cause hyperkalemia
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| List 3 characteristics of loop diuretics | urine vol is greater than w/ other agents, can cause hyperuricemia, misuse can be life-threatening
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| Name 4 CNS antihypertensive drugs | Methyldopa (Aldomet), Clonidine (Catapres),Guanabenz (Wytensin), Guanfacine (Tenex)
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| Many BB agents have what kind of activity? | CNS actions
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| What is methyldopa's MOA? | must be taken into the neuron, converted to methylNE and acts as false transmitter, stimulates central alpha-2 receptors to decr. SNS outflow
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| List the side effects of Methyldopa | Sexual dysfunction, othostatic hypotension, adverse effects on lipis profiles, somnolence esp. in 1st weeks of therapy, depression can be unmasked or exacerbated
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| How does Clonidine work? | direct alpha 2 receptor agonist, can stim. alpha 1 receptors in the periphery and incr. BP
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| What was the first antihypertensive agent incorporated into a cutaneous patch? | Clonidine
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| List the side effects of Clonidine | Anti-SLUD, dizziness, sedation, orthostatic hypotension, sexual dysfunction, insomnia, depression, nervousness, agitation, restlessness, anxiety
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| What are two factors to consider if clonidine patches are being used? | SE lower incidence w/ the patch but skin rxn with the patch are more common in women and those w/ fair skin
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| How is Clonidine dosed? | qd or bid, split dosage can be taken at bedtime to prevent daytime sedation and limit daytime sedation
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| What is Guanfacine and how is it used? | similar to clonidine, longer doa, SE less than clonidine, unlabeled use for heroin withdrawal and migraine
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| What is withdrawal syndrome? | Occurs 18-36h after abrupt d/c of CNS acting antihypertensives, BP elevated(can exceed pre-tx levels), anxiety, tremors, tachycardia, excessive SNS effects, may involve a central opiodergic component
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| What is the last resort for sympatholytics? | Guanfacine
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| List the nonselective Beta blockers | Propanolol (Inderal), Nadolol (Corgard0, Timolol (Blocadren, Timoptic), Penbutolol (Levatol)
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| List the Beta 1 selective blockers | Atenolol (Tenormin), Acebutolol (Sectral),Metoprolol (Lopressor),Bisoprolol (Zebeta), Betaxolol (Kerlone)
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| Which 2 beta blocking drugs are non-selective and have intrinsic sympathomimetic activity? | Pindolol (Viskin) and Carteolol (Cartrol)
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| Name the vasodilatory beta blocking drug | Celiprolol (Selecor)
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| What is the MOA of Beta Blockers? | complex-Beta blockade decr. CO, adrenergic blocking action (taken up by presynaptic nueron, displaces NE, acts as false transmitter), acts in CNS to reduce SNS outflow, inhibits renin rls
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| Name some general considerations of BB therapy? | 1st gen nonselective, 2nd gen more selective, 1st and 2nd gen may decr. CO and incr.TPR (decr.exercise resistance b/c of airway resistance and metabolic actions),3rd gen have ancillary prop (ISA, Beta 2 agonists, direct vasdoilation),
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| Name some nonselective Beta blocking drugs | PROPANOLOL (prototype-highly protein bound, subject to 1st pass), Nadolol (long half life, not extensively protein bound), Timolol (for glaucoma)
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| When are Beta 1 selective blocking agents used and what is the prime example? | Used when beta 2 blockade must be avoided (B2 blockade worsens cardiac issues), selectivity is a functiion of dose, ATENOLOL (minimal 1st pass & qd dosing)
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| Why are Nonselective Beta Blockers used with ISA? | cardioselectivity as a result of partial Beta agonism, maintain HR and CO better than other ganes
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| When are vasodilatory Beta blocking drugs used and how do they work? | B/C of incr. TPR w/ traditional agents, vasodilation due to Beta 2 agonism or direct action, effective in pts w/ peripheral vascular disease or pulmonary probs
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| What are the side effects of Beta blocking drugs? | Excessive beta blockade (bradycardia, hypotension, heart failure, pulmonary dysfunction), CNS effects (depression, nightmares, insomnia), fatigue, withdrawal syndrome, may worsen pulmonary dysfunction, affects plasma lipids, mask hypoglycemia in diabetics
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| What are 2 ex of mixed blocking agents? | Labetolol (Normodyne, Tarnsdate) and Carvedilol (Coreg)
both combine alpha 1 and beta 1 blockade
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| How does carvedilol work, what are its specific problems, and what is the max dose? | Carvedilol has alpha 1 antagonism and nonselective Beta blockade, the nonselective Beta blockade is an issue, it is well tolerated up to 50 mg
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| What are the side effects of mixed blocking agents? | BP decr. due to HR and CO (Beta 1 blockade) and decreased TPR (alpha 1 blockade), bradycardia occurs but w/lower freq., orthostatic hypotension during intial therapy-worse w. warm temp
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| What are three examples of alpha antagonists? | Pazosin (Minpres),terazosin (Hytrin) and Doxazosin (Cardura)
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| How has the MOA of alpha antagonists changed? | now selective blockade of alpha 1 receptors but early agents were nonselective
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| Name 2 characteristics of prazosin | prototype agent, highly protein bound
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| Name 3 characteristics of terazosin | higher bioavail. than prazosin, lower DOA, lower incidence of postural hypotension
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| Name 3 characteristics of doxazosin | highly protein bound, longer half life than prazosin, 1st dose effest less
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| Explain the side effects of alpha antagonists | most due to excessive vasodilation, postural hypotension (b/c of dose size, fasting state, posture, low Na diet, BB,unexpanded plasma vol), 1st dose effect (sudden dizziness, palps b/c of decr. venous return & vasodilation), headache, drowsiness, fatigue
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| How are alpha antagonists dosed and why? | low initial dose and incr. over 2 weeks (avoid 1st dose effect), divide dose unequally w/ higher dose at bedtime
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| Other than hypertension, what other disease state are alpha antagonists used for? | BPH
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| Name 4 sympatholytics | Rauwolfia (Raudixin), Reserpine (Serpasil, Serapase, Sandril), Guanethidine (Ismelin), Guanadrel (Hylorel)
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| How does Reserpine work? | Depletes NE from neuron(prevent storage of NE in granules), inhibits amine transport sys of granules--hypotensive develops over 2-3 weeks
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| List some side effects of Reserpine | sedation, depression, nightmare, n/v, diarrhea, fluid retention, impotence, bradycardia, orthostatic hypotension, nasal congestion
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| What are some contraindications of reserpine? | d/c @ first sign of depression, don't use w/ MAOI or tricyclic antidepressants
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| Besides hypertension, what other disease state is Reserpine use for? | Relief of agitated psychotic states like schizophrenia
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| How does Guanethidine work? | Adrenergic neuronal blockade b/c of inhibition of action potential induced rls of NE, inhibition of NE uptake, displacement of NE--may take 1 week to work
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| When is Guanethidine used? | severe or refractory hypertension-last resort
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| List some side effects of guanethidine | impaired reflexes, fluid retention, sexual dysfunction
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| List 2 vasodilators | Hydralazine (apresoline) and minoxidil (loniten)
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| when are vasodilator used? | hypertension, hypertensive crisis, and hypotensive surgery, NEVER A MONOTHERAPY
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| What are some side effects of hydralazine? | tachycardia, fluid retenion, headaches, flushing, hypotension, Lupus (@ doses >400mg/day)
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| True or false: hydralazine is orally effective | True
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| True or false: Minoxidil is orally effective | True but reserved for severe or refractory hypertension
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| List some side effects of minoxidil | fluid and H20 retention, activation of reflexes, hypertrichosis
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| Besides hypertension, minoxidil is used to treat what other disease? | male pattern baldness
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| List some Angiotensin Converting Enzyme Inhibitors | Captopril(Capotrn), Enalapril (Vasotec), Enalaprilat, Lisinopril(Prinivil, Zestril), Quinapril (Accupril), Benazepril (Lotensin), Ramipril (Altace), Fosinopril (Monopril), Moexipril (Univasc)
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| How do ACEI work? | percent conversion of angiotenin 1 to angiotensin 2, competitiively inhibit converting enzyme, lower BP w/ minimaln effects on CO and HR
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| List the side effects of ACEI | Hypotension (worse w/ diurteic, low salt intake, high renin levels), cough, angioedema, taste issues
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| ACEI should not be prescribed to pts taking what other drug? | K sparing diuretics b/c can cause hyperkalemia
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| Explain how Alpha 2 antagonists like Losartan (Cozaar) work | direct blockade of alpha 2 receptor, had an active metabolite
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| List some SE of alpha 2 antagonists | diarrhea, dyspepsia, myalgia
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| Name 5 possible drug combination therapies for hypertension | diuretic +BB, diuretic + CNS acting drug, diuretic +ACEI, diuretic +BB+ vasodilator, diuretic +BB + vasodilator + CNS acting agent
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| List some Calcium antagonists | Verapamil (Calan, Isoptin), Nifedipine (Procardia, Adalat), Diltiazem (cardizem), Nimodipine (Nimotop), Nicardipine (cardene), Isradipine (Dynacirc, Lomir, Prescal),Amlodipine (norvasc), felodipine (plendil), Nisoldipine, Nitrendipine, Nepridil (vascor)
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| How do calcium antagonists work? | inhibit voltage gated calcium channels, reduce calcium mediate signalling leading to vasodilation, high doses cause alpha blockade
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| Which calcium antagonist has the greatest effect on cardiac conduction (dromotropic effect) | Verapamil
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| Which calcium antagonist has minimal side effects? | diltiazem
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| For which diseases are calcium antagonists used? | angina, hypertension, arrhythmias (verapamil), raynaud's, hypertrophic cardiomyopathy
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| List some side effects of calcium antagonists | cardiodepression, hypotension, peripheral edema (unresponsive to diuretics), constipation, dyspepsia, nausea, headache, facial flush, tingling, burning
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| List 4 characteristics of calcium antagonists | do not change blood lipids, maintain or incr. GFR, DON'T interfere w/ exercise, may induce slight natriuresis
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