Elderly and Diuretics

Luis V. Limchiu, Jr. MD
USE OF DIURETICS IN
THE ELDERLY
L O L A L A N D
NAVIGATING THE CHALLENGES OF ELDERLY CARE1

L O L A L A N D
NAVIGATING THE CHALLENGES OF ELDERLY CARE
• Review diuretic definition, indications, mechanism of actions,
kinetics, common side effects
• Diuretic resistance mechanism and management
• Why is it important to know about diuretic use in the elderly?
• Who are the elderly?
• Extend of diuretic use in the elderly
• Indications for diuretic use in the following elderly?
• Special concern of diuretic use in the elderly
• Literature review
• Conclusion and summary
Topics

L O L A L A N D
• Diuretics- drugs use to increase salt
(sodium) and secondarily water losses thru
the kidney and are thus, basically a
natriuretics
• Aquaretics- increases essentially pure water
loss thru the kidneys - Tolvaptan
• glucoretics - increase glucose loss thru the
kidneys - SGLT2 inhibitors (gliflozin)
Diuretics

L O L A L A N D
• Relieve pulmonary congestion
• Help control peripheral edema and ascites
• as an antihypertensive
• miscellaneous uses- hyponatremia,
hypercalcemia, calcium stone prevention,
hyperkalemia, hypokalemia
PURPOSE OF DIURETICS

L O L A L A N D
• ECF volume is intimately related to total body sodium ( but not
serum sodium)- high total body sodium- increase ECF, low total
body sodium- Low ECF.
• Control of total body sodium (therefore ECF volume) is primarily
by the kidney filtration and reabsorption
• Diuretics used to Decrease ECF volume by Inhibiting
reabsorption of filtered sodium at various sites of the nephron,
• This secondarily decreasing capillary hydrostatic pressures
allowing the interstitial fluid to refill the space maintaining
effective arterial blood volume thus help maintain BP.
General Mechanism of
Diuretics

L O L A L A N D
• Almost all diuretics act thru the tubular lumen. Tubular drug
level is more important than drug blood level for desired drug
effect. Blood levels is important for side effects. - exceptions
are - tolvaptan, spironolactone.
• Most diuretics are secreted by the proximal tubular cells to
the lumen via specific transport system
• Most diuretic block a specific sodium reabsorption
transporter at various specific sites of the nephron
• Maximum effect of drug is dependent on site of action
Generalities of
Diuretics

L O L A L A N D
Sodium Reabsorption
in the Nephron

L O L A L A N D
Threshold and Ceiling

L O L A L A N D
9
CONCEPT OF CEILING DOSE
EFFECT
< No effect
Ceiling Effect
Ceiling Effect
ACTUAL DOSE
< threshold
Ceiling Dose
> Ceiling Dose

L O L A L A N D
10
DETERMINANTS OF CEILING EFFECT
VARIABLE
Ceiling Effect Depends on:
•Diuretic
•Disease
Diuretic Loop > Thiazide > K-Sparing
CEILING EFFECT
Disease
Diminished Nephron Response
in Nephrotic Syndrome, Cirrhosis,
& Heart Failure.

L O L A L A N D
Dose Response Curve to Loop Diuretics
in Different Clinical Situations

L O L A L A N D
Loop diuretics transport to the
nephron tubular lumen

L O L A L A N D
CEILING DOSES FOR I.V. LOOP DIURETICS
(in mgs)
CIRRHOSIS HEART FAILURE
40 to 80
1 to 2
10 to 20
NEPHROTIC
SYNDROME
AFR/CRF
Moderate
AFR/CRF
Severe
160 to 200
8 to 10
50 to 100
80 to 160
4 to 8
20 to 50
80 to 120
2 to 3
20 to 50
40 to 80
1 to 2
10 to 20
Furosemide
Bumetanide
Torsemide
Protein Binding
Increases Ceiling
Dose
Impaired Delivery
Increases Ceiling
Dose

L O L A L A N D
14
MECHANISMS OF DIURETIC
RESISTANCE
Proxima
l
Dista
lN
a
N
a
Proxima
l
Dista
lN
a Proxima
l
Dista
l
N
a
N
a
N
a
Proxima
l
Dista
l
N
a
N
a
Acute
Loop
Chronic
Loop
Chronic
Loop +
Thiazide

Nephron sites distal to the inhibited portion exhibit adaptation
could underlie the inappropriate renal Na+ retention that can
persist for up to 2 weeks after abrupt cessation of diuretic
therapy
L O L A L A N D
Do not abruptly stop Loop
Diuretics

L O L A L A N D
Diuretic Braking and post
diuretic salt retention

L O L A L A N D
MECHANISMS OF DIURETIC RESISTANCE
(Continued)
MECHANISM SOLUTION
Bed Rest
More Frequent Dosing or Continuous Infusion
Combination Therapy
(Sequential Blockade)
Changes in “Volume Hormones”
(SNS, RAS, ADH & ANF)
Compensation by Distal Nephron
Diminished Nephron Response
(CHF, Cirrhosis, Nephrotic Syndrome)

L O L A L A N D

L O L A L A N D
RATIONALE FOR MORE FREQUENT
DOSING
OR CONTINUOUS I.V. INFUSION
[Diuretic]TL Ceilin
g
[Diuretic]TL
[Diuretic]TL
Ceilin
g
Ceilin
g

L O L A L A N D
Effects of metolazone in man:
Comparison with chiorothiazide
Kidney International, Vol. 1 (1972), P. 169—181

L O L A L A N D
Elderly
• Age of retirement
• Non functional individual of age or non contributory to societal needs
• Most common n definition is chronological age above 65
• Early Elderly 65 to 75 yo
• Late Elderly above 75 year old
• Frail elderly person age above 65 who have functional impairments

L O L A L A N D
• Four out of five people aged over 75 years take at least one medicine.36 per cent of this age group
take four medicines or more. Increase risk for drug interaction like use of NSAID and diuretics. With
multiple medicines, there is an increased chance of side effects ACEI and spirolactone
• The ageing body can be more susceptible to the side effects of medicines. Elderly are more sensitive
to some side effects of drugs. Hyponatremia secondary to thiazides which can increase their risk for
fall and fracture with their risk for osteoporosis.
• problems taking them correctly can lead to under dosing with no diuretic effect or over dosing with
volume depletion.
• The physical effects of ageing, such as arthritis and failing eyesight and memory, can also cause issues
in taking medicines the way your doctor intended.
ELDERLY PEOPLE CAN BE AT INCREASED RISK FROM
MEDICINES FOR VARIOUS REASONS.
Netdoctor Hearst publication 2017

L O L A L A N D
• Declining liver and kidney function.
• The brain and nervous system become more sensitive to certain
medicines as we get older. Hyponatremia is more common in elderly
female with because of lost of estrogen effect.
• Arthritis is a common problem affecting elderly people, Taking ASAIDs
with diuretics can increase risk for AKI, as it limits the capacity of the
kidney to respond to volume loss.
• Elderly are more commonly taking cardiac medicines like ACEI and
Angiotensin inhibitors which increase the risk for AKI if at same time they
are taking loop diuretics. For acute decompensation I usually start with
diuretics wait a few days then add the ACEI.
ELDERLY PEOPLE CAN BE AT INCREASED RISK FROM
MEDICINES FOR VARIOUS REASONS.
Netdoctor Hearst publication 2017

L O L A L A N D
TRENDS IN ANTIHYPERTENSIVE DRUG PRESCRIPTIONS
IN US ADULTS
American Journal of Hypertension 29(10) October 2016

L O L A L A N D
THE LATEST GUIDELINES AND
THIAZIDE-TYPE DIURETICS
American Journal of Hypertension 29(10) October 2016

L O L A L A N D
• Antihypertensive therapy has been shown to reduce morbidity and mortality in older
patients with elevated systolic or diastolic blood pressures. This benefit appears to
persist in patients older than 80 years, but less than one third of older patients have
adequate blood pressure control.
• Low-dose thiazide diuretics remain first-line therapy for older patients.
Thiazides in Elderly
Dickerson L. American Academy of Family Physician's 2005

L O L A L A N D
• Diuretics are effective in producing diuresis and relieving symptoms
in acute CHF in the short term.
• Decrease LV filling pressure
• Disadvantage include:
• Decrease venous return
• Increase peripheral resistance
• Activate RAS and sympathetic nervous system which will produce the
tachycardia and arterial vast construction
• Elderly with their limited functional reserves and compensatory
capacity are particularly prone to the development of these side
effects and also have decrease tolerance to these side effects
THE ELDERLY, DIURETICS AND CHF

L O L A L A N D
• Although thiazide diuretics have been reported to affect serum
glucose and lipid levels adversely, there is a decreased incidence of
metabolic abnormalities and associated clinical outcomes with low-
dose therapy.
• Patients taking digoxin (Lanoxin) and a thiazide diuretic may be at
increased risk of digoxin toxicity because of diuretic-induced
electrolyte disturbances.
• Nonsteroidal anti-inflammatory drugs(NSAIDs) may reduce diuretic
and antihypertensive effects of thiazides
• When adding an ACE inhibitor or ARB to existing diuretic therapy,
there is a possibility of first-dose hypotension and the risk of acute
renal insufficiency.
THIAZIDES AND THE ELDERLY

L O L A L A N D
• This study examine the antihypertensive effects and all cause mortality or 1
CVE, that is, myocardial infarction, new diagnosis of coronary heart disease,
stroke, or congestive heart failure

L O L A L A N D
Chlorthalidone

L O L A L A N D
• CTDN is superior to HCTZ in preventing cardiovascular events. This cannot be attributed entirely
to the lesser effect of HCTZ on office systolic blood pressure but may be attributed to the
pleomorphic effects of alternative medications(Hypertension. or to the short duration of action
of HCTZ

L O L A L A N D
• prospective, randomized, open-label design, with blinded as-
sessments of end points.
• screening, blood pressure was measured by trained study nurses
using a mercury sphygmomanometer in all eligible subjects 65 to 84
years of age.
• subjects who were taking antihypertensive drugs, medication was
discontinued under medical supervision. Subjects were required to
be free of antihypertensive drugs for at least one week before the
study entry visit

L O L A L A N D
• Criteria for exclusion included any life-threatening illness,
contraindication to an ACE inhibitor or diuretic, a plasma creatinine
concentration of more than 2.5mg per deciliter (221 µmol per liter),
malignant hypertension, or dementia.
• end points
• The primary end point was all cardiovascular events or death from
any cause. Both initial and subsequent fatal and nonfatal
cardiovascular events were included
EXCLUSION CRITERIA

L O L A L A N D
Results

L O L A L A N D
ADVISE TO THE ELDERLY ON
DUIRETICS
• All medications should be cleared with your doctors
• Provide medication guides
• If taking duiretics. Easy access to the comfort room (avoid fall) and most of dose taken in the Morning.
• Make them aware of the possible side effects. Like postural dizziness or light headedness with volume loss in diuretics
• Start low and go slow. Start with the lower dose and gradual in dosage increase.

L O L A L A N D
• Check electrolyte closely. Avoid hypokalemia. addition of a
potassium-sparing diuretic like spironolactone (Aldactone), or the use
of a combination product such as
triamterene/hydrochlorothiazide(Dyazide, Maxzide). This is
important because in the SHEP trial, older patients with potassium
levels less than 3.5 mg per dL (0.9 mmol per L) lost the cardiovascular
protective benefit from the thiazide.
• Older patients are more prone to thiazide-induced dehydration and
orthostatic changes, so physicians should check for orthostatic
hypotension and suggest measures for preventing falls.
• Although poorly studied, their efficacy may be decreased in patients
with chronic kidney disease. Uric acid and thiazides compete for
excretion at the level of the renal tubule, so caution is necessary in
patients with a history of gout
THIAZIDES AND THE ELDERLY

L O L A L A N D
• Patients with mild to moderate renal impairment with falls on diuretics generally had a
higher overall BUN/Cr ratio than patients without falls on diuretics. In patients with stages 1
and 2 CKD, patients with falls on diuretics had aBUN/Cr ratio of 28.5 ± 1.2 (n = 78) versus
22.0 ± 0.9 (n = 71) in patients without falls on diuretics.
• In stage 3 CKD, the results were similar, with patients with falls on diuretics having a
BUN/Cr ratio of 23.5 ± 1.1 (n = 46) versus 19.2 ± 1 (n = 59) in patients without falls on
diuretics.
• In stages 4 and 5 CKD, the BUN/Cr ratio did not differ between the groups.
DEHYDRATION SECONDARY TO DIURETICS MAY
CONTRIBUTE TO FALLS IN THE ELDERLY

L O L A L A N D
Conclusion
• diuretics are commonly used among the Elderly
• Among it numerous function Diuretics mainly act to decrease total body sodium
to decrease ECF volume
• Diuretics have been threshold dose and a ceiling dose with therapeutic
consequences.
• Diuretic braking and diuretics resistance are commonly seen with diuretic use.
Maneuvers than can be use include not stopping diuretics abruptly, more
frequent dosing or using longer acting drugs, or diuretics combination
• Elderly are at risk for the side effects and drug interaction with diuretic used
• To avoid this it is best to start low and go slow in the Elderly, educate them about
complication, monitor electrolytes and affective arterial blood volume closely.

L O L A L A N D
Thank you next time APO

Elderly and Diuretics

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