Week 2 - Hypertension Flashcards
What is normal blood pressure?
when correctly measured is < 120/80 mmHg (<115 mmHg systolic is probably truly healthy)
A truly healthy, normal BP is a systolic < 115 mmHg but it is controversial at what point pharmacotherapy should be initiated to lower a BP (until > 150 mmHg which everyone agrees is too high at any age)
Define HTN
sustained (repeated measures) blood pressure >140/90 mmHg
Stage 1, 2, and 3 HTN
Stage 1: systolic BP from 140 - 159 and diastolic BP in the 90’s
Stage 2: systolic BP from 160 – 179 and diastolic BP in the 100 - 109 range
Stage 3: systolic BP ≥180 and diastolic BP≥110 (stage 3 may also be referred to as malignant hypertension)
Atherosclerotic: myocardial infarction and stroke and HTN
elevated blood pressure accelerates atherosclerosis in all arteries (happens in the arterial wall)
Cardiac Outcomes of HTN
higher pressures increases the workload on the heart which results in heart failure
- can cause both systolic heart failure (impaired contraction and pumping) and diastolic heart failure (impaired relaxation and filling)
Renal Outcomes of HTN
The kidneys are uniquely susceptible to elevated arterial pressures since they use them to filter blood and make urine.
- sustained, elevated blood pressure leads to chronically damaged kidneys and can eventually lead to the need for dialysis
What are the known complications of an untreated, sustained elevation in BP?
atherosclerosis (MI and stroke)
heart failure
kidney damage
BP and Genetics
a bell curve distribution in a healthy population dictated largely by genetics: other factors just modulate
Most all of the genetic contribution to hypertension involves sodium handling
Other factors that affect BP
Na+ intake, stress, obesity, kidney disease, atherosclerosis (high cholesterol, smoking)
Non-pharmacologic Txs of HTN
sodium restriction, sodium restriction, sodium restriction
and then weight loss, smoking cessation and stress management
Goal of diuretics
get rid of sodium
B - blockers
reduce cardiac output
dampen cardiac contractility
Ace and ARBs
reduce Angiotensin 2 to give vasodilation
Calcium Channel Blockers (CCBs)
forces arterial relaxation
What are diuretics?
substance that promotes the excretion of urine:
caffeine, yerba mate, nettles, cranberry juice, alcohol
What are Natriuretics?
substance that promotes the renal excretion of Na+
This is what we really need.
LOOP diuretics are more potent
because they are working upstream in the loop of Henle
Furosemide (prototype)
Bumetanide
Torsemide
Ethacrynic acid
*Pt should NOTICE the effect of these drugs - if not, not the right dose (go to restroom within an hour after taking)
** Only used in pts with markedly advanced kidney disease, when thiazides no longer work
Thiazide Diuretics
active in distal convoluted tubule. Some commonly used:
Chlorothiazide (prototype)
Hydrochlorothiazide
Chlorthalidone
Metolazone
MOA of Thiazides
inhibit Na+ and Cl- transporter in distal convoluted tubules
increased Na+ and Cl- excretion
Natriuretic effect on Na+ reduces circulating blood volume and relaxes vascular smooth muscle in the wall of arteries
- increased K+/Mg2+ excretion
- decrease Ca2+ excretion
beware of hypokalemia
Side Effects of Thiazides
- hypokalemia
- hyponatremia
Hyperglycemia (very mild effect and rare at the low doses which are used for hypertension) - diminished insulin secretion, elevated plasma lipids (minor)
Hyperuricemia (may be a factor in patients with gout)
Hypercalcemia (reduced Ca++ excretion in kidney can be helpful in patients with history of kidney stones)
*TEST WITHIN 6 MONTHS
Pharmacokinetics of thiazides:
- orally administered, generally fairly poorly absorbed
- onset of action in ~ 1-2 hours but BP effects takes several days for full effect after initiation initiated
- wide range of t1/2 (half life) amongst different thiazides, generally considerably longer than loop diuretics and can all be dosed once daily
- free drug enters tubules by filtration and by organic acid secretion
- Working in the kidney
MOA of Loop Diuretics
enter proximal tubule via organic acid transporter
inhibits apical Na-K-2Cl transporter in thick ascending loop of henle (these drugs really make you pee)
competes with Cl- binding site
enhances passive Mg2+ and Ca2+ excretion
increased K+ and H+ excretion in CCD
inhibits reabsorption of ~25% of glomerular filtrate
Pharmacokinetics of Loop Diuretics
orally administered, rapid absorption. (preferred over thiazides in patients with moderate-severe chronic kidney disease)
rapid onset of action for both diuresis and BP effect. Preferred over thiazide agents when patients have reduced kidney function (eGFR< 30)
increase toxicity lithium (causes retention of lithium)
may have additive toxicity with other ototoxic drugs but only at high doses of intravenous formulations
inhibitors of organic acid ion transport decrease potency (NSAID’s like ibuprofen, naproxen) - of unclear clinical implication
Side Effects of Loop Diuretics
* hypokalemia hyperuricemia (bad for gout patients) metabolic alkalosis (at higher doses) * hyponatremia ototoxicity (with higher doses of intravenous formulations) Mg2+ depletion *REPEAT LEVEL TESTING WITHIN 1 MONTH
Renin-Angiotensin Inhibitors for Hypertension: ACE-I and ARBs
*RAS inhibitors are among the best tolerated of the antihypertensive drugs.
ARBs are even better tolerated (less cough and risk for angioedema).
The direct renin inhibitor (DRI) aliskiren is one of the newest BP drugs, but there are no completed or ongoing RCTs of aliskiren monotherapy.
Why is “Dual RAS blockade” CI’d?
“Dual RAS blockade” either with an ACEI plus an ARB or with aliskiren plus an ACEI or ARB—is now contraindicated.
1-More hypotension,
2-Accelerate the decline in renal function,
3-Cause more hyperkalemia
ARB
blocks the receptors in BVs from receiving Angiotensin 2
ACE
block production of angiotensin 2
Which is better, ARB or ACE?
Clinically they are equally effective
Common ACEs
Lisinopril, Enalapril, Captopril, Ramipril
Common ARBs
Losartan, Irbesartan, Valsartan, Candesartan
Side Effects of ACEs/ARBs
All RAS inhibitors are contraindicated in pregnancy (can cause birth defects)
MC:
- ACEIs is a dry cough, which is more common in black patients and more common still in Asian patients.
If a cough develops in a patient taking an ACEI who needs RAS blockade, an ARB should be substituted.
- Angioedema (swelling of soft tissue, commonly around face/throat which can be life threatening) is much more common with ACE-I than ARB and more common in African Americans
- ACE-Is and ARBs have an equal incidence of hyperkalemia which is dose dependent
Because of unique effects in the vasculature of the kidney, ACE-Is and ARBs can cause small reductions in kidney function which are usually transient.
** Paradoxically, they are the drugs of choice for patients with hypertension and chronic kidney disease
