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EFFECT OF ANTYHYPERTENSIVE DRUGS ON
BLOOD PRESSURE
TABLE
OF CONTENTS
TITLE
DECLARATION
DEDICATION
CONTENTS
ACKNOWLEDGEMENT
ABSTRACT
CHAPTER
ONE
1. INTRODUCTION AND LITERATURE REVIEW
DEFINITION OF
HYPERTENSION
FACTORS THAT AFFECT
HYPERTENSION
ETIOLOGICAL
CLASSIFICATION
CONSEQUENCES OF
HYPERTENSION
OBJECTIVES OF THE STUDY
CHAPTER
TWO
2. METHODOLOGY (MATERIALS AND METHODS)
MATERIALS
METHOD
SAMPLE COLLECTION
SMAPLE PREPARATION AND
ANALYSIS
CHAPTER
THREE
3. RESULTS
RESULTS
EFFECT OF ANTIHYPERTENSIVE
DRUGS ON THE MEAN ARTERIAL PRESSURE OF HYPERTENSIVE PATIENTS
EFFECTS OF
ANTIHYPERTENSIVE DRUGS ON MEAN ARTERIAL PRESSURE AND SODIUM ION CONCENTRATIONS
BLOOD AND URINE OF INPATIENTS
EFFECTS OF
ANTIHYPERTENSIVE DRUGS ON MEAN ARTEIRIAL PRESSURE AND SODIUM ION CONCENTRATIONS
IN BLOOD AND URIONE OF OUT PATIENTS
EFFECTS OF
ANTIHYPERTENSIVE DRUGS ON MEAN ARTERIAL PRESSURE AND POTASSIUM ION
CONCENTRATION IN BLOOD AND URINE OF INPATIENTS
EFFECTS OF
ANTIHYPERTENSIVE DRUGS ON MEAN ARTERIAL PRESSURE AND POTASSIUM ION
CONCENTRATIONS IN BLOOD AND URINE OF OUTPATIENTS
EFFECTS OF
ANTIHYPERTENSIVE DRUGS ON MEAN ARTERIAL PRESSURE AND CALCIUM ION
CONCENTRATIONS, IN BLOOD AND URINE OF INPATIENTS
EFFECTS OF
ANTIHYPERTENSIVE DRUGS ON MEAN ARTEIRAL PRESSURE AND CALCIUM ION CONCENTRATIONS
IN BLOOD AND URINE OF OUTPATIENTS
CHAPTER
FOUR
4. DISCUSSION
SUMMARY
REFERENCES
ABSTRACT
The
study was carried out on nineteen hypertensive patients from both inpatients
and outpatient’s wards, to determine the effects on antyjhypertensive drugs,
namely, alpha methyldopa, moduretic and hydralazine on the arterial blood
pressure and the levels of sodium, potassium and calcium ions in the blood and
urine. Blood pressure was measured by Ausculatatory method. Whereas sodium and
potassium ion concentrations were quantitated using the flame photometer,
calcium ion was measured colorimetrically. The inpatients were placed on the
drug – regimen administration for two weeks and the outpatients for three
weeks. Blood pressure, sodium ion, potassium ion and calcium ion concentrations
were measured every four days for inpatients and weekly for the outpatients. It
was found that the administration of alpha methyldopa and moduretic
consequently lowered the blood pressure in the patients. Greater effect was
achieved when hydralazine was added to this regimen. Alpha methydopa in
combination with moduretic increased the excretion of sodium ion and elevated
the blood level of potassium ion concentration. These effects correlated with
the lowering of blood pressure in these patients. Initially these drugs
decreased the level of calcium ions and later elevated the level of this action
in the blood and urine. There was no correlation on the effects of calcium with
the drug induced decrease in blood pressure. The effects on blood pressure,
alteration of sodium, potassium and calcium ions concentrations were greater in
inpatients than in outpatients. The data suggest that alteration of the
electrolytes, sodium and potassium, may be possible mechanism of the
antihypertensive effects of these drugs. Furthermore, lowering the sodium ion
concentration and elevation of potassium ion concentration may be important in
the lowering of blood pressure by moduretic and alpha methyldopa. Multiple drug
therapy consisting of drugs possessing different mechanisms of action may prove
advantageous in the management of hypertension. The study suggests that
treatment of hypertension. The study suggests that treatment of hypertensive
patients on outpatient basis requires proper education on the dangers of the
disease as this would encourage sticks compliance to the drug prescriptions.
CHAPTER
ONE
INTRODUCTION
AND LITERATURE REVIEW
In an average young adult of 70kg body
weight, the normal systolic and diastolic pressures are 120mmHg and 80mmHg
respectively, thus having a mena arterial pressure of 93 mmHg. (Guyton, 1980).
Hypertension or high blood pressure can
be defined as an elevation of the arterial blood pressure above the normal.
(Guyton, 1980). However, it has been established that blood pressure increases
with age in individuals. (Mull and Lavell, 1967), thus, blood pressure is higher
in older people than it is in the young.
Epidemiological studies have revealed
that apart from age that some other factors such as, emotion and physical,
seasonal changes and race, influence individual blood pressures. (Akinkugbe,
1972).
There has been an evidence that the
arterial pressure in Negro populations in the United States and in the West
Indies is higher than in white populations. In West Africa, the systolic and
diastolic pressures of indigenous rural and urban populations differ in no important
respects from those of Negro populations. (Shaper, 1962). However, in Nigeria
about 35% of the total population suffer from hypertension (Akinkugbe, 1972).
80% of these hypertensive cases, have been attributed to environmental factors
such as dietary babits, patterns of infections and body bulk. (Akinkungbe,
1972).
Based on aetiology, hypertension is
either primary or secondary. (Guyton et al, 1981). It is said to be primary
when tis cause is unknown, and secondary when it is of a known cause. About 90%
of hypertensive subjects suffer from essential hypertension (Guyton et al,
1980). Secondary hypertension, may be classified into renal parenchymal,
renovascular, Adrenal, Neurogenic, coarctation, Toxemia of pregnancy,
Hypercoalcemia and Myxedema. (Kwan, 1973)..
Many untreated cases of hypertension have
been associated with, heart failure, uremia, charcot-Bochard aneurysms, and
fibrinoid necrosis. Others are congestive cardiac failure, cardiac hypertrophy,
left ventricular failure, arteriosclerosis (atheroma), cerebral infarction,
coronary artery disease and retinopathy (Hunt, 1977). Because of these diseased
states that can be brought about by hypertension, prevention or control of high
blood pressure has important. Drug therapy is one of the many ways in which
hypertension can be controlled. Drugs used in the treatment of hypertension
include alpha-methyl dopa, moduretic (75% hydro-chlorothiazide + 25%
amiloride), hydralazine and others.
ALPHA-METHYL
DOP (ALDOMET
The major antihypertensive action of methl
dopa is on the central nervous system. Alpha-methyl dopa is known to enter the
central nervous system, where it is decarbohydrated, and B-hydroxlated to
alpha-methylnorepinephrine in central adrenergic neurons. When released,
alpha-methyl norepinephrine potently stimulate central alpha-adrenergic
receptors and this inhibits sympathetic out flow resulting in decrease of total
peripheral resistance and blood pressure. Important evidence for this was that
decartboxylase inhibitors that penetrated the central nervous system abolished
the hypotensive response to alpha-methyl dopa, but thiose that act only
peripherally were ineffective (Henning, 1969, Kersting, et al, 1977). There was
a slight decrease in renin secretion following the administration of alpha-methyl
dopa. This decrease was attributed to its antihypertensive effect, although,
not its dominant mode of actions. (Halushka and Keiser, 1974, Lowder and
Liddle, 1975).
The extent of absorption of unchaged
alpha-methyl dopa has been found to be only approximately 25%. (Kwan et al,
1976). Differnces in metabolites that are found after oral and intravenous
administration suggested the possibility of first pass interstinal metabolism.
(Saavera et al, 1975).
Alpha-methl dopa given orally or
paraenterally. Is regularly associated with sedation. (Elkington et al, 1969).
However, a persistent lassitude and drowness, particularly disturbing to
individuals doing mental work, represent the overall most important side
effects. Other unwanted side effects referable to the central nervous system
(CNS), include, vertigo, extrapyramidal signs, night mores and psychic
depression. Dry mouth and nasal stuffiness may also be central in origin. Other
side effects include, retention of salt and water, sexual dysfunction, primary
importance occurs in some males and drug fever which may be severe and minic
sepsis, with shaking chills and high spiking temperatures. (Glontz and saslaw,
1968). Fever sometimes has been associated with changes in metabolism of
alpha-methyl dopa. (Valnes et al, 1978), or hepatic disfunction reflected by
elevation of hepatic enzymes in plasma and occasionally by appearance of
jaundice. (Elkington et al, 1969).
MODURETIC
(combination
of diuretics, hydrochlorothiazide, = 150mg amd a potassium sparing diuretic,
amiloride = 50mg in a tablet of moduretic of 200mg).
HYDROCHLOROTHIAZIDE
The
dominant action of hydrochlorothiazide is found to be the increase in the renal
excretion of sodium and chloride and an accompanying volume of water. This
effect is virtually independent of acid-base balance. (Crawford and Kennedy,
1959). Hydrochlorothiazide also increases potassium excretion. It inhibited the
reabsorption of sodium nad chloride in the distal segment of the renal tubules.
(Fendleton et al, 1968). Bioelectricical of sodium itself. (Pendleton et al,
1968). Bioelectrical studies had suggested a direct action on the movement of
sodium itself. (Pendleton et al, 1968). It increased the excretion of potassium
by increasing secretion of the cation at the distal portion of the renal tubule
(Giebisch, 1976). Hydrochlorothiazide may decrease the excretion of uric acid
in man, thus increasing its concentration in plasma. The hyper uricemic effects
primarily from inhibition of tubular secretion of urate. It was found to decrease
the renal excretion of calcium ions (Edwards et al, 1973).
Tydrochlorothiazide is rapidly absorbed
from the gastrointestinal tract. Hydrochlorothiazide is distributed throughtout
the extracellular space and has been found not to accumulate in tissues other
than the kidney. It is rapidly excreted within 3 – 6 hours.
Depression of the central nervours system
function, hypersensitivity reactions, (for example, purpura, dermatitis with
photiosensitivity and neorotizing vascultis), hypokalemia and elevation of uric
acid level have been associated with the use drug. (Christensson et al, 1977).
Hydrochlorothiazide might induce hyperglycemmia and aggravate prexisting
diabotos mellitus. (Dollery, 1973).
AMILORIDE
Amiloride increases the renal excretion of
sodium and chloride without a significant change in the glomerular filtration
rate Amiloride also inhibits the secretion of potassium. (Gatzy, 1971).
After oral administration, 15 – 26% of
the drug is absorbed from the gastrointestinal tract. When given parenterally,
amiloride is almost completely excreted in the urine. The peak effect was
observed 6 hours after oral administration, which ceased after 24 hours.
(Goodman and Gilman, 1980).
Toxic effects include, hyperkalaemia,
muscle weakness, abdominal pain, stiffness, paraesthesia and cardiac arrest.
(Eaer et al, 1967).
HYDRALIAZINE
The major action of hydralazine is direct
relaxation of vascular smooth muscle. The effect on arterioles was greater than
veins. (Ablad, 1963).
Major effects of hydralazine were on the
cardio vascular system. In both laboratory animals and man, adequate doses
decreased arterial blood pressure, diastolic often more than systolic and
peripheral vascular resistance. The drug increased heart rate, stroke volume
and cardiac output. The preferential dilatation of arterioles, as compared to
veins, minimised postural hypotension and promoted the increase in cardiac
output, splanchnic, coronary, cerebral and renal blood flows increased, unless
the fall in the blood pressure was very marked (Gillman and Goodman, 1980).
Hydralazine increased remin activity in plasma, presumably as a result of
increased secretion of renin by the renal juxtaglomerular cells in response to
reflex sympathetic discharge. Vascular resistance in the cutaneous beds
decreased. (Freis et al, 1953), blad, 1963). Hydralazine also caused sodium and
water retention. (Ablad, 1963).
Due to extensive first pass metabolism in
the liver the bioavailability of hydralazine is relatively low after oral
administration. ( Reindberg et al, 1973). It has been demonstrated that the
drug is metabolised by multiple pathways, but acetylation seems to be the major
route (Reidenberg et al, 1972-3). The simultaneous ingestion of food and
hydralazine has been found to increase the bioavailability of the drug.
(Melander et al, 1977).
Headache, palpitation, anorexia, nausea,
dizziness and sweating are known side effects of hydralazine. (Faskin, 1965).
Others include, nasal congestion, flushing. Lacrimation, conjunctivitis,
paraesthesia, skin rash, polyneuritis, gastro intestinal haemorrhage, anemia
and pancytopenia and peripheral neupathies which have been corrected by giving
pyridoxine. (Raskin and fishman, 1965).
OBJECTIVE
As indicated above, the antihypertensive
agents under discussion have been reported to alter the concentration of
important electrolytes, namely, sodium, potassium and calcium ions. (Freser et
al, 1981). Furthermore, it has been demonstrated that patients placed on food
enriched with potassium were devoid of hypertension induced disease states.
(Skrabal et al, 1981)
in a study carried out by Lever et
al, relating sodium and potassium with essential hypertension, it was found
that:
(1)
The exchangeable sodium correlated
positively with arterial pressure in the patients with essential hypertension
but not in the normal subjects;
(2)
Total body sodium also correlated
positively with arterial pressure in patients
(3)
Values of exchangeable sodium were
subnormal in young patients;
(4)
The correlations of potassium with blood
pressure were closest in young patients.
Therefore,
the present study was carried out in order to evaluate the relationship between
the concentrations of the aforementioned electrolytes and changes induced in
blood pressure of patients consequent upon anti-hypertensive therapy. It is
hoped that the knowledge gained from this study would help in giving a further
insight into the management and treatment of hypertension.
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