Hypertension occurring during childhood and adolescence is being recognized more frequently today than in the past. Hypertension in the pediatric population differs from that in adults with respect to incidence, etiology, clinical presentation, and drug treatment. This article reviews both the pathophysiology and drug treatment of hypertension in pediatric patients. A plan for drug management is presented.
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References
1.
MitchellSCThe pediatrician and hypertension. Pediatrics1975; 56: 3–5.
2.
LondeS.Blood pressure in children as determined under office conditions. Clin Pediatr1966; 5: 71–8.
3.
MaslandRPHypertensive vascular disease in adolescence. N Engl J Med1956; 255: 894–7.
4.
KilcoyneMM.Adolescent hypertension. I. Detection and prevalence. Circulation1974; 50: 758–64.
5.
LoggieJ.Essential hypertension in adolescents. Postgrad Med1974; 56: 113–40.
6.
RanceCPPersistent systemic hypertension in infants and children. Pediatr Clin North Am1974; 21: 801–24.
7.
LoggieJMH.Hypertension in children and adolescents. I. Causes and diagnostic studies. J Pediatr1969; 74: 331–5.
8.
OoiBSCauses of hypertension in the young. Br Med J1970; 3: 744–6.
9.
SinghSPPageLB.Hypertension in early life. Am J Med Sci1967: 253: 255–62.
10.
LondeSHypertension in apparently normal children. J Pediatr1971; 78: 569–77.
11.
GillDGAnalysis of 100 children with severe and persistent hypertension. Arch Dis Child1976; 51: 951–6.
12.
MalekzadehMHHypertension after renal transplantation in children. J Pediatr1975; 86: 370–5.
13.
BlaufoxMD.Systemic arterial hypertension in pediatric practice. Pediatr Clin North Am1971; 18: 577–93.
14.
KilcoyneMM.Adolescent hypertension. Am J Med1975; 58: 735–9.
15.
ZinnerSHFamilial aggregation of blood pressure in childhood. N Engl J Med1971; 284: 401–4.
16.
JuliusS.Clinical and physiological significance of borderline hypertension at youth. Pediatr Clin North Am1978; 25: 35–45.
17.
VoorsAWEpidemiology of essential hypertension in youth — implications for clinical practice. Pediatr Clin North Am1978; 25: 15–27.
18.
LondeS.Causes of hypertension in the young. Pediatr Clin North Am1978; 25: 55–65.
19.
PereraGA.The course of primary hypertension in the young. Ann Intern Med1958; 49: 1348–50.
20.
ConwayJThe vascular effect of the thiazide diuretics. Arch Intern Med1963; 111: 203–7.
21.
TobianL.Why do thiazide diuretics lower blood pressure in essential hypertension? Ann Rev Pharmacol1967; 7: 399–408.
22.
ConwayJHemodynamic and hypotensive effects of long-term therapy with chlorothiazide. Circulation1960; 21: 22–7.
23.
LethA.Changes in plasma and extracellular fluid volume in patients with essential hypertension during long-term treatment with hydrochlorothiazide. Circulation1970; 12: 479–85.
24.
McLeodPJEffects of large and small doses of hydrochlorothiazide in hypertensive patients. Clin Pharmacol Ther1970; 11: 733–9.
25.
MurphyJThe effect of dosage regimen on the diuretic efficacy of chlorothiazide in human subjects. J Pharmacol Exp Ther1961; 134: 286–90.
26.
BeermanBAbsorption, metabolism and excretion of hydrochlorothiazide. Clin Pharmacol Ther1976; 19: 531–7.
27.
SinaikoAHydrochlorothiazide therapy in hypertensive and renal insufficient children: elimination kinetics and metabolic effects. Pediatr Res1977; 11: 418.
28.
WilliamsonHE.Furosemide and ethacrynic acid. J Clin Pharmacol1977; 17: 663–72.
29.
HomerML.Deafness after ethacrynic acid. N Engl J Med1971; 285: 1152.
30.
WertheimerLFurosemide in essential hypertension. Arch Intern Med1971; 127: 934–8.
31.
AndersonJA comparison of the effects of hydrochlorothiazide and of furosemide in the treatment of hypertensive patients. Q J Med1971; 40: 541–60.
32.
FinnertyFALong-term effects of furosemide and hydrochlorothiazide in patients with essential hypertension. Angiology1977; 28: 125–33.
33.
HuangCMPharmacokinetics of furosemide in advanced renal failure. Clin Pharmacol Ther1974; 16: 659–99.
34.
CutlerREPharmacokinetics of furosemide in normal subjects and functionally anephric patients. Clin Pharmacol Ther1974; 15: 588–96.
35.
PruittAWDiuretic effect of furosemide in acute glomerulonephritis. J Pediatr1976; 89: 306–9.
36.
KellyMRPharmacokinetics of orally administered furosemide. Clin Pharmacol Ther1974; 15: 178–86.
37.
CoopermanLBToxicity of ethacrynic acid and furosemide. Am Heart J1973; 85: 831–4.
38.
LoggieJMHRenal function and diuretic therapy in infants and children. Part II. J Pediatr1975; 86: 657–69.
39.
VaughanADVolume factor in low and normal renin essential hypertension: treatment with either spironolactone or chlorthalidone. Am J Cardiol1973; 32: 523–32.
40.
CareyRThe syndrome of essential hypertension and suppressed plasma renin. Arch Intern Med1972; 130: 849–54.
41.
AdlinEVSpironolactone and hydrochlorothiazide in essential hypertension. Arch Intern Med1972; 130: 855–8.
42.
FergusonRKSpironolactone and hydrochlorothiazide in normal renin and low renin essential hypertension. Clin Pharmacol Ther1977; 21: 62–9.
43.
BrooksCSDiuretic therapies in low renin and normal renin essential hypertension. Clin Pharmacol Ther1977; 22: 14–20.
44.
GreenblattDJ.Gynecomastia and impotence complications of spironolactone treatment. JAMA1973; 223: 82.
45.
LoubeSDBreast cancer associated with administration of spironolactone. Lancet1975; 1: 1428–9.
46.
HollandOBPropranolol in the treatment of hypertension. N Engl J Med1976; 294: 930–6.
47.
FrohlichEDThe paradox of beta-adrenergic blockade in hypertension. Circulation1968; 37: 417–23.
48.
HanssonLHemodynamic effects of acute and prolonged β-adrenergic blockade in essential hypertension. Acta Med Scand1974; 196: 27–34.
49.
BuhlerFRPropranolol inhibition of renin secretion. N Engl J Med1972; 287: 1209–14.
50.
WoodsJWRenin profiling in hypertension and its use in treatment with propranolol and chlorthalidone. N Engl J Med1976; 294: 1137–43.
51.
MookherjeeS.Hemodynamic and plasma renin effects of propranolol in essential hypertension. Arch Intern Med1977; 137: 290–5.
52.
PotterDETreatment of high-renin hypertension with propranolol in children after renal transplantation. J Pediatr1977; 90: 307–11.
53.
GriswoldWRPropranolol as an antihypertensive agent in children. Arch Dis Child1978; 53: 594–5.
54.
EslerMPathophysiologic and pharmacokinetic determinants of the antihypertensive response to propranolol, Clin Pharmacol Ther1977; 22: 299–308.
55.
DolleryCTCentral hypotensive effect of propranolol, Postgrad Med J1976; 52 (Suppl 4): 116–20.
56.
WitsonMThe effect of blood pressure of β-adrenoceptor blocking drugs administered once daily and their duration of action when therapy is ceased. Br J Clin Pharmacol1976; 3: 857–61.
57.
BerglundGPropranolol given twice daily in hypertension. Acta Med Scand1973; 194: 513–5.
58.
BrogdenRNMetoprolol: A review of its pharmacological properties and therapeutic efficacy in hypertension and angina pectoris. Drugs1977; 14: 321–48.
EvansGHDisposition of propranolol v. drug accumulation and steady-state concentrations during chronic oral administration in man. Clin Pharmacol Ther1973; 14: 487–93.
61.
LowenthalDTPharmacokinetics of oral propranolol in chronic renal disease. Clin Pharmacol Ther1974; 16: 761–9.
62.
DayMDSome observations on the pharmacology of alpha-methyldopa. Br J Pharmacol1964; 22: 72–86.
63.
TrinkerFR.The significance of the relative potencies of noradrenaline and alpha methylnoradrenaline for the mode of action of alpha-methyldopa. J Pharm Pharmacol1971; 23: 306–8.
64.
FrankelRJRole of central and peripheral mechanisms in the action of alpha-methyldopa on blood pressure and renin secretion. J Pharmacol Exp Ther1977; 201: 400–5.
65.
DayMDThe mechanism of the antihypertensive action of alpha-methyldopa in hypertensive rats. Eur J Pharmacol1973; 21: 271–80.
66.
FrosythRPHemodynamic effects of systemic and central administration of alpha-methyldopa. J Pharmacol Exp Ther1978; 205: 675–82.
67.
KwanKCPharmacokinetics of methyldopa in man. J Pharmacol Exp Ther1976; 198: 264–77.
68.
BuhsRPThe metabolism of methyldopa in hypertensive human subjects. J Pharmacol Exp Ther1964; 143: 205–14.
69.
WrightJMAntihypertensive efficacy of a single bedtime dose of methyldopa. Clin Pharmacol Ther1976; 20: 733–7.
70.
NickersonMAntihypertensive agents and the drug therapy of hypertension. In: GoodmanLSGilmanA eds. The pharmacological basis of therapeutics. 5th ed.New York: Macmillan, 1975: 709.
71.
DustanHPDependence of arterial pressure on intravascular volume in treated hypertensive patients. N Engl J Med1972; 286: 861–6.
72.
BonkowskyHLColitis and hepatitis caused by methyldopa. JAMA1976; 236: 1602–3.
FurhoffA.Adverse reactions with methyldopa — a decade's report. Acta Med Scand1978; 203: 425–8.
75.
GaffneyTEStudy of the relationship between the neurotransmitter store and adrenergic nerve block induced by reserpine and guanethidine. Circ Res1963; 12: 264–8.
76.
WoolamGLAntihypertensive drugs: clinical pharmacology and therapeutic use. Drugs1977; 14: 420–60.
77.
NickersonMDrugs inhibiting adrenergic nerves and structures innervated by them. In: GoodmanLSGilmanA eds. The pharmacological basis of therapeutics. 5th ed.New York: Macmillan, 1975: 557.
78.
ArmstrongBRauwolfia derivative and breast cancer in hypertensive women. Lancet1976; 2: 8–12.
79.
LaubieMPharmacological evidence for a central alpha-sympathoimetic mechanism controlling blood pressure and heart rate. Circ Res1976; 38 (Suppl II): 35–41.
80.
DaviesDSPharmacokinetics and concentration effect relationships of intravenous and oral clonidine. Clin Pharmacol Ther1977; 21: 593–601.
81.
DolleryCTClinical pharmacology and pharmacokinetics of clonidine. Clin Pharmacol Ther1976; 19: 11–7.
82.
MroczekWJProlonged treatment with clonidine: comparative antihypertensive effects alone and with a diuretic agent. Am J Cardiol1972; 30: 536–41.
83.
HanssonLBlood pressure crisis following withdrawal of clonidine, with special reference to arterial and catecholamine levels, and suggestions for acute management. Am Heart J1973; 85: 605–10.
84.
GoldberADThe over-shoot phenomenon on withdrawal of clonidine therapy. Postgrad Med J1976; 52 (Suppl VII): 128–34.
85.
WhitsettTLAbrupt cessation of clonidine administration: a prospective study. Am J Cardiol1978; 41: 1285–90.
86.
JainAKEfficacy and acceptability of different dosage schedules of clonidine. Clin Pharmacol Ther1977; 21: 382–7.
87.
ReidenbergMMHydralazine elimination in man. Clin Pharmacol Ther1973; 14: 970–7.
88.
TalsethT.Clinical pharmacokinetics of hydralazine. Clin Pharmacokinet1977; 2: 317–29.
89.
MelanderAEnhancement of hydralazine bioavailability by food. Clin Pharmacol Ther1977; 22: 104–7.
90.
LesserJMFate of hydralazine — C14 in man and dog. Clin Pharmacol Ther1973; 14: 140.
91.
ZaastRRelation of hydralazine plasma concentration to dosage and hypotensive action. Clin Pharmacol Ther1972; 420–5.
92.
TalsethT.Kinetics of hydralazine elimination. Clin Pharmacol Ther1977; 21: 715–20.
93.
O'MalleyKDuration of hydralazine action in hypertension. Clin Pharmacol Ther1975; 18: 581–6.
94.
ZinsGR.Alterations in renal function during vasodilator therapy. In: WessonLGFianelliGMJr eds. Recent advances in renal physiology and pharmacology. Baltimore: University Park Press, 1974: 165–86.
95.
IriasJJ.Hydralazine-induced lupus erythematosus-like syndrome. Am J Dis Child1975; 129: 862–4.
96.
OatesHFMechanism of the hypotensive action of prazosin. Arch Int Pharmocodyn1977; 227: 41–58.
97.
BrogdenRMPrazosin: a review of its pharmacologic properties and therapeutic efficacy in hypertension. Drugs1977; 14: 163–97.
98.
TurnerASPrazosin in hypertension. Part I: clinical experience in 100 patients. NZ Med J1977; 86: 282–5.
99.
BradleyWFComparison of prazosin and methyldopa in mild to moderate hypertension, a multicenter cooperative study. Curr Ther Res1977; 21: 28–35.
100.
HuaASPStudies with prazosin — a new effective hypotensive agent. II. Two double-blind cross-over studies comparing the effects of prazosin and hydralazine. Med J Aust1977; 2: 5–9.
101.
CollinsISPharmacokinetics of prazosin, a new antihypertensive compound. Clin Exp Pharmacol Physiol1975; 2: 445–6.
102.
WoodAJPrazosin in normal subjects; plasma levels, blood pressure and heart rate. Br J Clin Pharmacol1976; 3: 199–201.
103.
TurnerASPrazosin in hypertension. Part II: effects of initial dose. NZ Med J1977; 86: 286–9.
104.
DuCharmeDWPharmacologic properties of minoxidil: a new hypotensive agent. J Pharmacol Exp Ther1973; 184: 662–70.
105.
PlussRGTissue distribution and hypotensive effects of minoxidil in normotensive rats. J Lab Clin Med1972; 79: 639–47.
106.
GottliebTCombined therapy with vasodilator drugs and beta-adrenergic blockade in hypertension. Circulation1972; 45: 571–82.
107.
SinaikoARManagement of severe childhood hypertension with minoxidil: a controlled clinical study. J Pediatr1977; 91: 138–42.
108.
PennisiAJMinoxidil therapy in children with severe hypertension. J Pediatr1977; 90: 813–9.
109.
MakkerSP.Minoxidil in refractory hypertension. J Pediatr1975; 86: 621–3.
110.
GottliebTBPharmacokinetic studies of minoxidil. Clin Pharmacol Ther1972; 13: 436–41.
111.
GilmoreETreatment of essential hypertension with a new vasodilator in combination with beta-adrenergic blockade. N Engl J Med1970; 282: 521–7.
112.
BalfeJWRecognition and management of hypertensive crises in childhood. Pediatr Clin North Am1978; 25: 159–74.
113.
BoerthRCDose-response relation of diazoxide in children with hypertension. Circulation1977; 56: 1062–6.
114.
MauerSMTreatment of hypertension in infancy with diazoxide: report of a case with arrhythmia as a complication of therapy. J Pediatr1972; 80: 657–9.
115.
McLainePMIntravenous diazoxide for severe hypertension in childhood. J Pediatr1971; 79: 829–32.
116.
MillerWEManagement of severe hypertension with intravenous injections of diazoxide. Am J Cardiol1969; 24: 870–5.
117.
RubinAAPharmacology of diazoxide, an antihypertensive, nondiuretic benzothiadiazine. J Pharmacol Exp Ther1962; 136: 344–52.
118.
WilsonWRThe acute hemodynamic effects of diazoxide in man. Circulation1963; 28: 89–93.
119.
NaylerWGSome effects of the hypotensive drug diazoxide on the cardiovascular system. Am Heart J1968; 75: 223–32.
120.
PowellWJAction of diazoxide on skeletal muscle vascular resistance. Circ Res1971; 28: 167–78.
121.
Koch-WeserJ.Diazoxide. N Engl J Med1976; 294: 1271–4.
122.
Koch-WeserJ.Myocardial inactivity of therapeutic concentrations of hydralazine and diazoxide. Experientia1974; 30: 170–1.
123.
Koch-WeserJ.Vasodilator drugs in the treatment of hypertension. Arch Intern Med1974; 133: 1017–27.
124.
KumarGKSide effects of diazoxide. JAMA1976; 235: 275–6.
125.
SellersEMProtein binding and vascular activity of diazoxide. N Engl J Med1969; 281: 1141–5.
126.
SellersEMInfluence of intravenous injection rate on protein binding and vascular activity of diazoxide. Ann NY Acad Sci1973; 226: 319–32.
127.
LoggieJMH.Hypertension in children and adolescents. II. Drug Therapy. J Pediatr1969; 74: 640–54.
128.
Gordillo-PaniaguaGSodium nitroprusside treatment of severe arterial hypertension in children, J Pediatr1975; 87: 799–802.
129.
LudererJRLong-term administration of sodium nitroprusside in childhood. J Pediatr1977; 91: 490–1.
130.
DaviesDWSodium nitroprusside in children: observations on metabolism during normal and abnormal responses. Can Anaesth Soc J1975; 22: 553–60.
131.
BennettNRThe use of sodium nitroprusside in children. Anaesthesia1977; 32: 456–63.
132.
LupatkinWLProlonged use of sodium nitroprusside. J Pediatr1978; 92: 1032–3.
133.
TaylorTHSodium nitroprusside as a hypotensive agent in general anaesthesia. Br J Anaesth1970; 42: 859–64.
134.
MoracaPPClinical evaluation of sodium nitroprusside as hypotensive agent. Anaesthesiology1962; 23: 193–9.
135.
JonesGOMSodium nitroprusside as a hypotensive agent. BrJ Anaesth1968; 40: 804–5.
136.
PageIHCardiovascular actions of sodium nitroprusside in animals and hypertensive patients. Circulation1955; 11: 188–98.
137.
NourokDSHypothyroidism following prolonged sodium nitroprusside therapy. Am J Med Sci1964; 248: 129–38.
138.
PalmerRFSodium nitroprusside. N Engl J Med1975; 292: 294–7.
139.
BowerPJMethemoglobinemia after sodium nitroprusside therapy. N Engl J Med1975; 293: 865.