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EFFECT OF ANTYHYPERTENSIVE DRUGS ON BLOOD PRESSURE

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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

  1. METHODOLOGY (MATERIALS AND METHODS)

MATERIALS

METHOD

SAMPLE COLLECTION

SMAPLE PREPARATION AND ANALYSIS

CHAPTER THREE

  1. 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

  1. 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:

  • The exchangeable sodium correlated positively with arterial pressure in the patients with essential hypertension but not in the normal subjects;
  • Total body sodium also correlated positively with arterial pressure in patients
  • Values of exchangeable sodium were subnormal in young patients;
  • 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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