Concerning hypertension, the majority of cases are considered primary. True or False?
true
HTN is a multifactorial phenomenon: Name 4 of these factors.
physiology
genetics
stress
diet
What percent is heredity estimated to account for essential HTN?
30%
What BP would be considered normal based on JNC 7 2003 guidelines?
SBP <120 DBP <80
What BP would be considered prehypertension based on JNC 7 2003 guidelines?
SBP 120-139 DBP 80-89
What BP would be considered stage I HTN based on JNC 7 2003 guidelines?
SBP 140-159 DBP 90-99
What BP would be considered stage II HTN based on JNC 7 2003 guidelines?
SBP >160 DBP >100
What is the main purpose for prescribing diuretics?
to increase urine volume
What is the difference between diuretic and natriuretic?
diuretic increases urine volume
natriuretic increases sodium excretion
What is the MOA carbonic anhydrase inhibitors?
blocks dehydrongenation of carbonic acid in the proximal convoluted tubule which increases sodium bicarbonate secretion leading to diuresis
Name 4 indications for CAI use.
urinary alkalinization
glaucoma
acute mountain sickness
metabolic alkalosis
Name 3 side effects of CAI use.
drowsiness
anorexia
paresthesias
Name 4 contraindications for CAI use.
calcium stones
acidosis
renal potassium wasting
cirrhosis
What is the MOA of loop diuretics?
blocks reabsorption of NaCl in the thick ascending limb by interfering with Na/K/Cl transporter
What percent of sodium reabsorption occurs in the thick ascending limb of the nephron?
25%
Loop diuretics interfere with potassium recycling. What affect does this have on Calcium and Magnesium?
it increases the excretion for both Ca and Mg
Name 4 clinical indications for loop diuretic use.
Edema
hypercalcemia
ARF
hyperkalemia
The onset and clearance of loop diuretics depends on ____________ method and _____________ function.
delivery
kidney
The absorption of loop diuretics is not affected by acidosis. True or False?
true
Name 4 contraindications/cautions for loop diuretic use.
hypersensitivity due to SULFA allergy
hyperuricemia
ototoxicity
hypomag/hypokalemic metabolic alkalosis
Name 3 side effects of loop diuretic use.
dizziness
hypotension
photosensitivity (lasix)
What is the MOA for thiazides?
block reabsorption of NaCl in the Distal convoluted tubule
enhance Ca+ reabsorption
compete with uric acid secretion in the PCT
Name 4 clinical indications for thiazides.
HTN
HF
Hypercalciuria
nephrogenic DI
Name 3 side effects for thiazide use.
hypotension
electrolyte disturbance
photosensitivity
Name 4 contraindications/cautions for thiazide use.
hypomag/hypokalemic metabolic alkalosis
SULFA allergy
hyperuricemia
hyperglycemia/hyperlipidemia
What is the MOA for the potassium sparing diuretics?
prevent K+ secretion by opposing aldosterone in DCT
What are 4 clinical indications for potassium sparing diuretics?
HTN
primary or secondary hyperaldosteronism
Edema
Name 3 side effects for the potassium sparing diuretics.
hyperkalemia
gynecomastia
sexual dysfunction
Name 3 contraindications for the potassium sparing diuretics.
concomitant use of beta blockers, ACE inhibitors
liver impairment
potassium supplementation
What diuretic might be appropriate for the CHF patient with metabolic alkalosis who still needs additional diuresis?
CAI. because of the volume contraction alkalosis, CAI would be used to correct the pH and add additional diuresis
How do CAI diuretics help with acute mtn sickness?
with acute mtn sickness the s&s are weakness, dizziness, HA that can lead to pulmonary or cerebral edema. CAIs decrease CSF formation and pH, thus causing increase ventilation and reduction in symptoms
Name 3 toxidromes caused by CAI diuretics.
hyperchloremic metabolic acidosis
renal stones
renal K+ wasting
The hyperchloremic metabolic acidosis seen with CAI toxicity results from chronic loss of which anion?
HCO3-
You have a patient with a toxic ingestion of halogenated substance such as bromide. Which diuretic is most appropriate?
Loop diuretic due to anion overdose. Substances such as fluoride, iodide, and bromide are reabsorbed in the TAL and loop diuretics can help flush them out.
Your patient is on gentamycin for the treatment of a nasty gram negative bacterial infection. He needs a diuretic to help mobilize extra fluid. Would a loop diuretic be appropriate?
most likely not. there is a dose-related ototoxicity that is worsened with othe agents such as aminoglycosides that cause hearing loss
All of the loop diuretics are sulfonamides. True or false?
false. ethacrynic acid is not
Name 3 toxidromes associated with thiazide diuretic use.
hypokalemic metabolic alkalosis & hyperuricemia
hyperlipidemia
hemolytic anemia (rare)
Your patient reports that their blood sugars have been elevated for some unknown reason. The only new finding is the addition of HCTZ to their medication listing. Is this new medication a potential cause?
yes, HCTZ is a thiazide and they can cause impaired pancreatic release of insulin and diminished tissue utilization of glucose leading to impaired CHO tolerance
This type of diuretic is most useful in mineralcorticoid excess from conditions such as Conn's, CHF, or nephrotic syndrome.
Potassium sparing
Name 2 centrally acting sympathoplegic drugs.
methyldopa & clonidine
Name 3 side effects for centrally acting sympathoplegic drugs such as clonidine.
postural hypotension
mild sedation
dry mouth
What is the purpose of centrally acting sympathoplegic medicatons such as clonidine?
to block vasoconstriction
Describe the MOA of clonidine.
lower BP by reduction of CO due to decrease HR, relaxation of capacitance vessels and decreased PVR. This happens by direct stimulation of alpha 2 adrenoreceptors that reduces release of NE in the brain
What is the most common undesirable effect of centrally acting sympathoplegics?
pronounced sedation
Name 3 negative side effects seen with long term use of either clonidine or methyldopa.
imparied concentration
lactation in men & women
+ Coombs (makes cross-matching blood difficult)
Name 2 ganglionic blocking agents and describe their MOA.
guanadrel & reserpine
block nicotinic Ach channels on sympathetic and parasympathetic ganglia to block vasoconstriction
Name 3 side effects seen with ganglionic blockers.
profound orthostatic hypotension
sexual dysfunction
parkinsonian EPS effects
List the 4 properties that characterize Guanethidine's mode of action on the presynaptic sympathetic terminal.
1. enters the presynaptic nerve terminal via Uptake 1 receptor
2. causes increased release of NE into the synaptic cleft
3. it binds to the synaptic vesicles to cause the release of catecholamines that are then degraded by MAO
4. causes adrenergic neuronal blockade by uncoupling the AP from NT release
Does guanethidine cross the blood brain barrier?
no
Which nervous system does guanethidine act exclusively on?
the peripheral nervouse system, because it does not cross the BBB
Name 2 sympathetic and 3 parasympathetic adverse effects of ganglionic blockers.
Sympathetic: orthostatic hypotension & sexual dysfunction
Describe the pharmacokinetics/dynamics of beta adrenoceptor antagonists. Specifically
beta-blockers are able to reduce sympathetic influences that normally stimulate chronotropy (heart rate), inotropy (contractility), dromotropy (electrical conduction) and lusitropy (relaxation). Therefore, beta-blockers cause decreases in heart rate, contractility, conduction velocity, and relaxation rate.
Discuss the machanism of action or alpha blockers
Alpha-blockers dilate both arteries and veins because both vessel types are innervated by sympathetic adrenergic nerves; however, the vasodilator effect is more pronounced in the arterial resistance vessels.
Specifically describe the mechanism of action of prazosin
It works by selectively blocking alpha 1 receptors in arterioles and venules. Alpha-1 receptor selectivity allow NE to exert unopposed negative feedback (mediated by presynaptic alpha-2 receptors) on its own release.
How do hydralazine and Nipride differ in terms of their MOA?
hydralazine dilates arterioles only, whereas Nipride dilates both venous and arterial vessels to reduce PVR
What medication activates guanylyl cyclase by nitric oxide release and direct enzymatic stimulation and increases cGMP which leads to relaxation of vascular smooth muscle?
sodium nitroprusside
What toxicty results from high doses or long treatment of Nipride?
cyanide
How are diltiazem and local anesthetic medications similar in terms of their MOA?
they both act from the inner side of the membrane and bind more effectively to open and inactivated channels
drug binding reduces the frequency of opening in response to depolarization
results in marked decrease transmembrane calcium current and long-lasting smooth muscle relaxation, decreased contractility, and SA & AV nodal conduction velocity
What characteristic of ACE inhibitors makes them superior to other agents in patients needing blood pressure reduction and diagnosed coronary artery disease?
they do not stimulate reflex tachycardia
What is the MOA of ACE inhibitors?
block conversion of angiotensin I to angiotensin II, this blocks vasoconstriction
Describe the pharmacologic management of hypertensive emergencies.
