From: Brian Symonds   <[log in to unmask]>
 
Generally speaking, low blood pressure is harder to treat than high blood
pressure.
Unlike high blood pressure, low blood pressure is not a disease process on
its own, but rather is usually due to some process, and the treatment of the
low blood pressure becomes the treatment of the process causing it. For
example, if you have an infection and it causes your blood pressure to be
low, the treatment is to treat the infection. If you are on a medication and
it causes your blood pressure to be low, then the treatment is to stop the
medication. There are some things that can be done to "support" a person's
blood pressure while you are waiting for treatment to become effective. For
example, getting extra fluid into the body (either by IV or mouth) will help
raise a person's blood pressure, and if the fluid is leaking out of the
person's arteries into the tissues, giving protein into the blood (such as
albumin) will help hold the fluid in the arteries. However, there also may be
adverse consequences to giving extra fluids and proteins (or other such
substances). PD patients may get undesirable leg and foot swelling with extra
fluids for example.
 
Also low blood pressure with some medications may be unpredictable, and not
preventable. For example, orthostatic hypotension (low blood pressure with
change in postion) with or without syncope (fainting) can occur with Clozaril
(clozapine) treatment and may represent a continuing risk in some patients.
Rarely (approximately 1 case per 3,000 patients), collapse can be profound
and be accompanied by respiratory and/or cardiac arrest. Orthostatic
hypotension is more likely to occur during initial titration in association
with rapid dose escalation  and may even occur on first dose. In one report,
initial doses as  low as 12.5 mg were associated with collapse and
respiratory arrest. Low blood pressure to the point of collapse is a rare
complication with Clozaril and other drugs, but can happen even with a first
dose, and is thus not predictable or currently preventable. Benefit must
always be balanced against risk.
 
There are drugs used to treat low blood pressure. The main group of
medications are called sympathomimetic agents.The sympathomimetic agents
(except isoproterenol) are indicated for the correction of hypotension,
unresponsive to adequate fluid volume replacement, as part of shock syndrome
caused by myocardial infarction, trauma, bacteremia, open-heart surgery,
renal failure, chronic cardiac decompensation, drug overdose, or other major
systemic illness. Vasopressors such as Dopamine, Dobutamine, Ephedrine,
Epinephrine or Adrenalin, Norepinephrine or Noradrenalin, Mephentermine,
Metaraminol, Methoxamine, and Phenylephrine are all used in some
circumstances to help raise blood pressure, but their usefulness is limited
by the fact that some of these can only be given intraveneously, by the fact
that they may constrict the arteries in the kidneys and decrease kidney
function, by the fact that they can increase the work that the heart has to
do, and the fact that they can cause the heart to beat irregularly. They are
thus difficult medications to use, and are generally only used for short
periods of time till the problem causing the low blood pressure is corrected.
 
What can be done in the situation where a person has low blood pressure due
to a disease or medication, and the disease can't be cured, or the medication
can't be stopped? The only medication that I am aware of that is currently in
use in this situation is Fludrocortisone, and following is information about
it. As always, do not be dismayed by the impressive list of potential adverse
effects. Used carefully, it is a fairly safe drug, but its potential benefit
and its potential harm must always be carefully weighed.
 
FLUDROCORTISONE ACETATE
Category/Indications
Category:  Corticosteroid (mineralocorticoid); antihypotensive (idiopathic
orthostatic); diagnostic aid (renal tubular acidosis).
 
Indications: Accepted
Adrenocortical insufficiency, chronic primary (treatment); or
Adrenocortical insufficiency, chronic secondary (treatment) - Fludrocortisone
is indicated as partial replacement therapy in the treatment of
adrenocortical insufficiency.
Adrenogenital syndrome, congenital (treatment) - Fludrocortisone is indicated
in salt-losing forms of adrenogenital syndrome.
Hypotension, idiopathic orthostatic (treatment)(1) - Fludrocortisone is used
in conjunction with increased sodium intake in the treatment of idiopathic
orthostatic hypotension.
[Acidosis, in renal tubular disorders (diagnosis and treatment)](1) -
Fludrocortisone is used in the treatment of Type IV renal tubular acidosis
associated with hyporeninemic hypoaldosteronism. Fludrocortisone is also used
as an aid in diagnosing the cause of the condition. Effectiveness of
fludrocortisone therapy indicates that the condition is caused by
hyporeninemic hypoaldosteronism rather than by renal tubular transport
dysfunction.
(1)Not included in Canadian product labeling.
 
BRAND NAMES: Astonin*; Florinef
* Foreign brand name outside U.S.
 
FORMULARIES: Aetna; BC/BS; Medi-Cal; PCS; WHO
 
DESCRIPTION
Fludrocortisone Acetate Tablets USP contain fludrocortisone acetate, a
synthetic adrenocortical steroid possessing very potent mineralocorticoid
properties and high glucocorticoid activity; it is used only for its
mineralocorticoid effects. The chemical name for fludrocortisone acetate is
9-fluoro-11(beta),17,21-trihydroxypregn-4-ene-3,
20-dione 21-acetate.
 
Fludrocortisone Acetate is available for oral administration as scored
tablets providing 0.1 mg fludrocortisone acetate per tablet. Inactive
ingredients: calcium phosphate, color additive (D&C Red No. 27), corn starch,
lactose, magnesium stearate, sodium benzoate, and talc.
 
CLINICAL PHARMACOLOGY
The physiologic action of fludrocortisone acetate is similar to that of
hydrocortisone. However, the effects of fludrocortisone acetate, particularly
on electrolyte balance, but also on carbohydrate metabolism, are considerably
heightened and prolonged. Mineralocorticoids act on the distal tubules of the
kidney to enhance the reabsorption of sodium ions from the tubular fluid into
the plasma; they increase the urinary excretion of both potassium and
hydrogen ions. The consequence of these three primary effects together with
similar actions on cation transport in other tissues appear to account for
the entire spectrum of physiological activities that are characteristic of
mineralocorticoids. In small oral doses, fludrocortisone acetate produces
marked sodium retention and increased urinary potassium excretion. It also
causes a rise in blood pressure, apparently because of these effects on
electrolyte levels.
 
In larger doses , fludrocortisone acetate inhibits endogenous adrenal
cortical secretion, thymic activity, and pituitary corticotropin excretion;
promotes the deposition of liver glycogen; and, unless protein intake is
adequate, induces negative nitrogen balance.
 
The approximate plasma half-life of fludrocortisone (fluorohydrocortisone) is
3.5 hours or more and the biological half-life is 18 to 36 hours.
 
CONTRAINDICATIONS
Corticosteroids are contraindicated in patients with systemic fungal
infections and in those with a history of possible or known hypersensitivity
to these agents.
 
WARNINGS
BECAUSE OF ITS MARKED EFFECT ON SODIUM RETENTION, THE USE OF FLUDROCORTISONE
ACETATE IN THE TREATMENT OF CONDITIONS OTHER THAN THOSE INDICATED HEREIN IS
NOT ADVISED.
 
Corticosteroids may mask some signs of infection, and new infections may
appear during their use. There may be decreased resistance and inability to
localize infection when corticosteroids are used. If an infection occurs
during fludrocortisone acetate therapy, it should be promptly controlled by
suitable antimicrobial therapy.
 
Prolonged use of corticosteroids may produce posterior subcapsular cataracts,
glaucoma with possible damage to the optic nerves, and may enhance the
establishment of secondary ocular infections due to fungi or viruses.
 
Average and large doses of hydrocortisone or cortisone can cause elevation of
blood pressure, salt and water retention, and increased excretion of
potassium. These effects are less likely to occur with the synthetic
derivatives except when used in large doses. However, since fludrocortisone
acetate is a potent mineralocorticoid, both the dosage and salt intake should
be carefully monitored in order to avoid the development of hypertension,
edema, or weight gain. Periodic checking of serum electrolyte levels is
advisable during prolonged therapy; dietary salt restriction and potassium
supplementation may be necessary. All corticosteroids increase calcium
excretion.
 
Patients should not be vaccinated against smallpox while on corticosteroid
therapy. Other immunization procedures should not be undertaken in patients
who are on corticosteroids, especially on high dose, because of possible
hazards of neurological complications and a lack of antibody response.
 
The use of Fludrocortisone Acetate Tablets in active tuberculosis should be
restricted to those cases of fulminating or disseminated tuberculosis in
which the corticosteroid is used for the management of the disease in
conjunction with an appropriate antituberculous regimen. If corticosteroids
are indicated in patients with latent tuberculosis or tuberculin reactivity,
close observation is necessary since reactivation of the disease may occur.
During prolonged corticosteroid therapy these patients should receive
chemoprophylaxis.
 
PRECAUTIONS
General
Adverse reactions to corticosteroids may be produced by too rapid withdrawal
or by continued use of large doses.
To avoid drug-induced adrenal insufficiency, supportive dosage may be
required in times of stress (such as trauma, surgery, or severe illness) both
during treatment with fludrocortisone acetate and for a year afterwards.
 
There is an enhanced corticosteroid effect in patients with hypothyroidism
and in those with cirrhosis.
 
Corticosteroids should be used cautiously in patients with ocular herpes
simplex because of possible corneal perforation.
 
The lowest possible dose of corticosteroid should be used to control the
condition being treated. A gradual reduction in dosage should be made when
possible.
 
Psychic derangements may appear when corticosteroids are used. These may
range from euphoria, insomnia, mood swings, personality changes, and severe
depression to frank psychotic manifestations. Existing emotional instability
or psychotic tendencies may also be aggravated by corticosteroids.
 
Aspirin should be used cautiously in conjunction with corticosteroids in
patients with hypoprothrombinemia.
 
Corticosteroids should be used with caution in patients with nonspecific
ulcerative colitis if there is a probability of impending perforation,
abscess or other pyrogenic infection. Corticosteroids should also be used
cautiously in patients with diverticulitis, fresh intestinal anastomoses,
active or latent peptic ulcer, renal insufficiency, hypertension,
osteoporosis, and myasthenia gravis.
 
Information for Patients
The physician should advise the patient to report any medical history of
heart disease, high blood pressure, or kidney or liver disease and to report
current use of any medicines to determine if these medicines might interact
adversely with fludrocortisone acetate (see DRUG INTERACTIONS).
 
Patients who are on immunosuppressant doses of corticosteroids should be
warned to avoid exposure to chicken pox or measles, and, if exposed, to
obtain medical advice.
 
The patient's understanding of his steroid-dependent status and increased
dosage requirement under widely variable conditions of stress is vital.
Advise the patient to carry medical identification indicating his dependence
on steroid medication and, if necessary, instruct him to carry an adequate
supply of medication for use in emergencies.
 
Stress to the patient the importance of regular follow-up visits to check his
progress and the need to promptly notify the physician of dizziness, severe
or continuing headaches, swelling of feet or lower legs, or unusual weight
gain.
 
Advise the patient to use the medicine only as directed, to take a missed
dose as soon as possible, unless it is almost time for the next dose, and not
to double the next dose.
 
Inform the patient to keep this medication and all drugs out of the reach of
children.
 
Laboratory Tests
Patients should be monitored regularly for blood pressure determinations and
serum electrolyte determinations (see WARNINGS).
 
Drug/Laboratory Test Interactions
Corticosteroids may affect the nitrobluetetrazolium test for bacterial
infection and produce false-negative results.
 
Carcinogenesis, Mutagenesis, Impairment of Fertility
Adequate studies have not been performed in animals to determine whether
fludrocortisone acetate has carcinogenic or mutagenic activity or whether it
affects fertility in males or females.
 
Pregnancy Category C.
Adequate animal reproduction studies have not been conducted with
fludrocortisone acetate. However, many corticosteroids have been shown to be
teratogenic in laboratory animals at low doses. Teratogenicity of these
agents in man has not been demonstrated. It is not known whether
fludrocortisone acetate can cause fetal harm when administered to a pregnant
woman or can affect reproduction capacity. Fludrocortisone acetate should be
given to a pregnant woman only if clearly needed.
 
Pregnancy. Nonteratogenic Effects.
Infants born of mothers who have received substantial doses of
fludrocortisone acetate during pregnancy should be carefully observed for
signs of hypoadrenalism.
 
Maternal treatment with corticosteroids should be carefully documented in the
infant's medical records to assist in follow up.
 
Nursing Mothers
Corticosteroids are found in the breast milk of lactating women receiving
systemic therapy with these agents. Caution should be exercised when
fludrocortisone acetate is administered to a nursing woman.
 
Pediatric Use
Safety and effectiveness in children have not been established.
 
Growth and development of infants and children on prolonged corticosteroid
therapy should be carefully observed.
 
DRUG INTERACTIONS
When administered concurrently, the following drugs may interact with adrenal
corticosteroids.
 
Amphotericin B or potassium-depleting diuretics (benzothiadiazines and
related drugs, ethacrynic acid and furosemide)--enhanced hypokalemia. Check
serum potassium levels at frequent intervals; use potassium supplements if
necessary (see WARNINGS).
 
Digitalis glycosides--enhanced possibility of arrhythmias of digitalis
toxicity associated with hypokalemia. Monitor serum potassium levels; use
potassium supplements if necessary.
 
Oral anticoagulants--decreased prothrombin time response. Monitor prothrombin
levels and adjust anticoagulant dosage accordingly.
 
Antidiabetic drugs (oral agents and insulin)--diminished antidiabetic effect.
Monitor for symptoms of hyperglycemia; adjust dosage of antidiabetic drug
upward if necessary.
 
Aspirin--increased ulcerogenic effect; decreased pharmacologic effect of
aspirin. Rarely salicylate toxicity may occur in patients who discontinue
steroids after concurrent high-dose aspirin therapy. Monitor salicylate
levels or the therapeutic effect for which aspirin is given; adjust
salicylate dosage accordingly if effect is altered (see PRECAUTIONS,
General).
 
Barbiturates, phenytoin, or rifampin--increased metabolic clearance of
fludrocortisone acetate because of the induction of hepatic enzymes. Observe
the patient for possible diminished effect of steroid and increase the
steroid dosage accordingly.
 
Anabolic steroids (particularly C-17 alkylated androgens such as
oxymetholone, methandrostenolone, norethandrolone, and similar
compounds)--enhanced tendency toward edema. Use caution when giving these
drugs together, especially in patients with hepatic or cardiac disease.
 
Vaccines--neurological complications and lack of antibody response (see
WARNINGS).
 
Estrogen--increased levels of corticosteroid-binding globulin, thereby
increasing the bound (inactive) fraction; this effect is at least balanced by
decreased metabolism of corticosteroids. When estrogen therapy is initiated,
a reduction in corticosteroid dosage may be required, and increased amounts
may be required when estrogen is terminated.
 
ADVERSE REACTIONS
Most adverse reactions are caused by the drug's mineralocorticoid activity
(retention of sodium and water) and include hypertension, edema, cardiac
enlargement, congestive heart failure, potassium loss, and hypokalemic
alkalosis.
When fludrocortisone is used in the small dosages recommended, the
glucocorticoid side effects often seen with cortisone and its derivatives are
not usually a problem; however the following untoward effects should be kept
in mind, particularly when fludrocortisone is used over a prolonged period of
time or in conjunction with cortisone or a similar glucocorticoid.
 
Musculoskeletal--muscle weakness, steroid myopathy, loss of muscle mass,
osteoporosis, vertebral compression fractures, aseptic necrosis of femoral
and humeral heads, pathologic fracture of long bones, and spontaneous
fractures.
 
Gastrointestinal--peptic ulcer with possible perforation and hemorrhage,
pancreatitis, abdominal distention, and ulcerative esophagitis.
 
Dermatologic--impaired wound healing, thin fragile skin, bruising, petechiae
and ecchymoses, facial erythema, increased sweating, subcutaneous fat
atrophy, purpura, striae, hyperpigmentation of the skin and nails, hirsutism,
acneiform eruptions, and hives and/or allergic skin rash; reactions to skin
tests may be suppressed.
 
Neurological--convulsions, increased intracranial pressure with papilledema
(pseudotumor cerebri) usually after treatment, vertigo, headache, and severe
mental disturbances.
 
Endocrine--menstrual irregularities; development of the cushingoid state;
suppression of growth in children; secondary adrenocortical and pituitary
unresponsiveness, particularly in times of stress (e.g., trauma, surgery, or
illness); decreased carbohydrate tolerance; manifestations of latent diabetes
mellitus; and increased requirements for insulin or oral hypoglycemic agents
in diabetics.
 
Ophthalmic--posterior subcapsular cataracts, increased intraocular pressure,
glaucoma, and exophthalmos.
 
Metabolic--hyperglycemia, glycosuria, and negative nitrogen balance due to
protein catabolism.
 
Other adverse reactions that may occur following the administration of a
corticosteroid are necrotizing angitis, thrombophlebitis, aggravation or
masking of infections, insomnia, syncopal episodes, and anaphylactoid
reactions.
 
OVERDOSAGE
Development of hypertension, edema, hypokalemia, excessive increase in
weight, and increase in heart size are signs of overdosage of fludrocortisone
acetate. When these are noted, administration of the drug should be
discontinued, after which the symptoms will usually subside within several
days; subsequent treatment with fludrocortisone acetate should be with a
reduced dose. Muscular weakness may develop due to excessive potassium loss
and can be treated by administering a potassium supplement. Regular
monitoring of blood pressure and serum electrolytes can help to prevent
overdosage (see WARNINGS).
 
DOSAGE AND ADMINISTRATION
Dosage depends on the severity of the disease and the response of the
patient. Patients should be continually monitored for signs that indicate
dosage adjustment is necessary, such as remissions or exacerbations of the
disease and stress (surgery, infection, trauma)(see WARNINGS and PRECAUTIONS,
General).
 
Addison's Disease
In Addison's disease, the combination of Fludrocortisone Acetate tablets with
a glucocorticoid such as hydrocortisone or cortisone provides substitution
therapy approximating normal adrenal activity with minimal risks of unwanted
effects.
 
The usual dose is 0.1 mg of Fludrocortisone Acetate daily, although dosage
ranging from 0.1 mg three times a week to 0.2 mg. daily has been employed. In
the event transient hypertension develops as a consequence of therapy, the
dose should be reduced to 0.05 mg. daily. Fludrocortisone Acetate is
preferably administered in conjunction with cortisone (10 mg. to 37.5 mg.
daily in divided doses) or hydrocortisone (10 mg. to 30 mg. daily in divided
doses).
 
Salt-Losing Adrenogenital Syndrome
The recommended dosage for treating the salt-losing adrenogenital syndrome is
0.1 mg. to 0.2 mg. of Fludrocortisone Acetate daily.
 
Storage
Store at room temperature; avoid excessive heat.
 
(E.R. Squibb & Sons, 11/91, J3-566C)
(91/11)
 
HOW SUPPLIED - EQUIVALENTS NOT AVAILABLE
Tablet, Uncoated - Oral - 0.1 mg
100's  $44.86  FLORINEF ACETATE, Bristol-Myers Squibb  00003-0429-50*