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By: Ala'a Fadhel Hassan
5th
stage, Pharmacy dept.
Hospital Training
Supervised by: Dr.Anas
2
Definition
Malignant hypertension isvery high bloodpressure thatcomes on suddenly
and quickly.The lower (diastolic)bloodpressure reading, which is normally around
80 mmHg, is often above130 mmHg (1)
It is a rare but very serious form of high bloodpressure. Officially, definedas severe
hypertension thatoccursalong with internalbleedingof the retinasin both eyes
and swelling of opticnervesbehindtheretinas (2)
Alternative Names
Acceleratedhypertension; arteriolarnephrosclerosis;Hypertension -malignant;
High bloodpressure – malignant (1)
Causes, incidence & risk factors
Malignant hypertension isnota single disease entity but rather, a
syndromein which thehypertension can beeitherprimary (essential)or secondary
to any oneof a number of different causes (3)
The disorderaffects about 1% of peoplewith high bloodpressure, including both
children andadults. It is more common in youngeradults,( which is the opposite
of the risk profile for essential hypertension),especially African-American men(1)
in which the underlyingcause is almost always essential hypertension thathas
entereda malignant phase (2)
Anyonewith a history of kidney failure or a renal artery stenosis (narrowingof
arteries in the kidney)has a greatly increasedrisk(3) .History of primary renal
parenchymaldisordersis The most common secondary causes of malignant
hypertension(Chronicglomerulonephritisisthought to be thecause of
malignant hypertension in upto 20% of cases)(2)
Pregnantwomen with gestationalhypertension,orwomen experiencingcertain
pregnancy relatedcomplications(toxemiaof pregnancy)appearto havean
increasedrisk(3)
It also occurs in people with Collagen vascular disorders(1)
Drug Related Malignant Hypertension(MAOInhibitors,ColdPreparations,
WithdrawalAntihypertensive Medicinesas" Clonidine,-Blockers"&“Street
drugs" Cocaine, PCP)(4)
3
Clinical presentation
Symptoms of Malignant Hypertension
Because malignant hypertension affectsorgan systems that are directly
sensitiveto bloodpressure (kidneys,eyes, brain,cardiovascular system), the
symptoms of the disease tendto bethose associate with problems in theseother
organ systems. For example, some symptomsinclude:
Blurry vision
Chest pain
Seizure
Decreasedurine output
Weakness orstrange tingling/numbnessin the arms, legs, or face
Headache
Shortnessof breath
These symptoms are notexclusive to malignant hypertension,butare
generally associated with a number of potentially serious medical conditionslike
heartattack, stroke, or kidney problems(2)
Physical Examinations and Tests
Malignant hypertension isa medicalemergency in which the physicalexam
commonlyshows:
Extremelyhigh bloodpressure
Swelling in the lowerlegs and feet
Abnormalheartsounds andfluid in the
lungs
Changes in thinking,sensation,muscle
ability,and reflexes
An eye examination will revealchanges that
indicatehigh bloodpressure, including:
Bleedingof theretina
Narrowing of thebloodvessels in
theeye area
Swelling of theopticnerve
Other problemswith the retina
4
Kidney failure, as well as othercomplications,may develop.(1)
Tests to determinedamageto the kidneysmay include:
Arterialbloodgas analysis
BUN
Creatinine
Urinalysis
A chestx-ray may show congestion in thelung and an enlargedheart.
This disease may also affect the results of the following tests:
Aldosterone level
Cardiac enzymes(markers of heart damage)
CT scan of the brain
Electrocardiogram(EKG)
Renin level
Urinary sediment(1)
Principles of Therapy
LowerB.P. overhours, Initial goal B.P.  160’s/90’s
Too rapidlowering may cause dire consequences(CVA, MI)
May take several days to get to reasonablelevels
Avoidmedicationsthatcannotbecontrolled(sublingual nifedipine)
For most patientsthegreatest risk of treating a hypertensive
emergency is the risk of accompanyinghypotension.
Treat with short acting,easily titratable, I.V. drug(4)
Drug Dosage Onset Duration
Adverse
Effects
Indication(I)
Contraindication(C)
Vasodilators
Nitropru-
sside
0.3-10
mcg/kg/mi
n
1-2
min
1-2 min
N/V, muscle
twitching,
cyanide,
I: CHF, aortic dissect,
Catechol.
5
IV
infusion
Thiocyanide
tox. &
intracranial
pressure
C: hepatic,renal
insufficiency
Nitrogly-
cerin (IV)
5-100
mcg/kg/
min
2-5
min
3-5 min
Head ache,
dizziness,
vomiting,
methemgl-
obin
&tolerance
I: coronary dis.,CHF
C: CVA, Intracranial
pressure
Diazoxide
( IV)
1-3
(mg/kg)
IV
bolus,
q5-15
/min;
repeat
every 4-
24 hr as
needed
2-4
min
3-12 hr
Nausea,
hypoten-
sion ,
flushing,
tachycardia
, hypergly-
cemia,
aggravat-
ion of
angina&
fluid
retention
C: Syndromesof
coronary insufficiency,
(unless used with beta-
blockingagent),
cerebrovascular
accident& hypersensi-
tivity to sulfonamides
Fenoldo-
pam
mesylate
0.1-1.7
mcg/kg/
min (IV
infusion)
5-15
min
1-4 hr
Headache,
dizziness,
flushing,
increased
intraocular
pressure,
Hypokal-
emia& dose
related
tachycardia
I: Severehyperten-
sion with renal
insufficiency
C: Glaucoma
Hydrala-
zineHCl
10-20
mg IV
or IM
bolus,
(maxim
um
dose,
40 mg)
10-20
min
3-8 hr Tachy-
cardia,
flushing,
headache
,vomiting
&
aggravat-
ion of
angina
I: CHF
C: Coronary
insufficiency,aortic
dissection,
cerebrovascular
accident(may
increaseintracranial
pressure)
Enalaprilat
(IV)
1.25-5
mg q6
15 min
6 hr Precipit-
ous drop
I: CHF
C: Use with caution in
patientswith severe
6
hr IV in blood
pressure
in high
renin st.
renal insufficiency (not
receivingdialysis)
Nicardi-
pine HCl
5-15
mg/hr
IV
infusion
5-20
min
1-2 hr Tachycar
dia,
headache
,flushing,
local
phlebitis
C: Greater than first-
degree heartblock,
CHF
AdrenergicInhibitors
Phentol-
amine
-
blocker
5-20 mg
IV,
repeat
as
necess-
ary
1-2
min
10-30 min
Tachycardia
, nausea,
flushing,
abdominal
pain&aggr-
avation of
angina
I: Catecholamine
excess
C: Syndromesof
coronary
insufficiency
Esmolol
HCl
200-500
mcg/kg/
min
over1-4
min,
then 50-
300
mcg/kg/
min IV
infusion
1-2
min
10-20
min
Hypoten-
sion,
nausea,
bradycar-
dia or
heart
block&
dizziness
I: Syndromesof
coronary
insufficiency
C: Greater than first-
degree heartblock,
CHF
Labetalol
HCl
- blocker
20-80
mg IV
bolus,
(maxim
um
dose,
300 mg
2-10
min
2-4 hr Hypoten-
sion,
nausea,
itching,
scalp
tingling&
dizziness
I: Syndromesof
coronary insuffi-
ciency,catechol-
amine excess
C: first-degree heart
block,CHF,
bronchialasthma
7
References:
(1) Medline Plus-A service of the U.S. national library of
medicine
Malignant hypertension, causes, symp . &…
http://www.nlm.nih.gov/medlineplus/druginformation.html
(2) A.D.A.M. Medical Encyclopedia.
Malignant hypertension
http://www.ncbi.nlm.nih.gov/pubmedhealth/
(3) Hypertension& The Kidney
Chapter8 (Hypertensive Crises) byCharles R. Nolan
(4) HypertensionEmergencies & Urgencies
By StephenS. Levin, D.O.
8

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Treating Malignant Hypertension: Drug Dosages and Principles of Therapy

  • 1. 1 By: Ala'a Fadhel Hassan 5th stage, Pharmacy dept. Hospital Training Supervised by: Dr.Anas
  • 2. 2 Definition Malignant hypertension isvery high bloodpressure thatcomes on suddenly and quickly.The lower (diastolic)bloodpressure reading, which is normally around 80 mmHg, is often above130 mmHg (1) It is a rare but very serious form of high bloodpressure. Officially, definedas severe hypertension thatoccursalong with internalbleedingof the retinasin both eyes and swelling of opticnervesbehindtheretinas (2) Alternative Names Acceleratedhypertension; arteriolarnephrosclerosis;Hypertension -malignant; High bloodpressure – malignant (1) Causes, incidence & risk factors Malignant hypertension isnota single disease entity but rather, a syndromein which thehypertension can beeitherprimary (essential)or secondary to any oneof a number of different causes (3) The disorderaffects about 1% of peoplewith high bloodpressure, including both children andadults. It is more common in youngeradults,( which is the opposite of the risk profile for essential hypertension),especially African-American men(1) in which the underlyingcause is almost always essential hypertension thathas entereda malignant phase (2) Anyonewith a history of kidney failure or a renal artery stenosis (narrowingof arteries in the kidney)has a greatly increasedrisk(3) .History of primary renal parenchymaldisordersis The most common secondary causes of malignant hypertension(Chronicglomerulonephritisisthought to be thecause of malignant hypertension in upto 20% of cases)(2) Pregnantwomen with gestationalhypertension,orwomen experiencingcertain pregnancy relatedcomplications(toxemiaof pregnancy)appearto havean increasedrisk(3) It also occurs in people with Collagen vascular disorders(1) Drug Related Malignant Hypertension(MAOInhibitors,ColdPreparations, WithdrawalAntihypertensive Medicinesas" Clonidine,-Blockers"&“Street drugs" Cocaine, PCP)(4)
  • 3. 3 Clinical presentation Symptoms of Malignant Hypertension Because malignant hypertension affectsorgan systems that are directly sensitiveto bloodpressure (kidneys,eyes, brain,cardiovascular system), the symptoms of the disease tendto bethose associate with problems in theseother organ systems. For example, some symptomsinclude: Blurry vision Chest pain Seizure Decreasedurine output Weakness orstrange tingling/numbnessin the arms, legs, or face Headache Shortnessof breath These symptoms are notexclusive to malignant hypertension,butare generally associated with a number of potentially serious medical conditionslike heartattack, stroke, or kidney problems(2) Physical Examinations and Tests Malignant hypertension isa medicalemergency in which the physicalexam commonlyshows: Extremelyhigh bloodpressure Swelling in the lowerlegs and feet Abnormalheartsounds andfluid in the lungs Changes in thinking,sensation,muscle ability,and reflexes An eye examination will revealchanges that indicatehigh bloodpressure, including: Bleedingof theretina Narrowing of thebloodvessels in theeye area Swelling of theopticnerve Other problemswith the retina
  • 4. 4 Kidney failure, as well as othercomplications,may develop.(1) Tests to determinedamageto the kidneysmay include: Arterialbloodgas analysis BUN Creatinine Urinalysis A chestx-ray may show congestion in thelung and an enlargedheart. This disease may also affect the results of the following tests: Aldosterone level Cardiac enzymes(markers of heart damage) CT scan of the brain Electrocardiogram(EKG) Renin level Urinary sediment(1) Principles of Therapy LowerB.P. overhours, Initial goal B.P.  160’s/90’s Too rapidlowering may cause dire consequences(CVA, MI) May take several days to get to reasonablelevels Avoidmedicationsthatcannotbecontrolled(sublingual nifedipine) For most patientsthegreatest risk of treating a hypertensive emergency is the risk of accompanyinghypotension. Treat with short acting,easily titratable, I.V. drug(4) Drug Dosage Onset Duration Adverse Effects Indication(I) Contraindication(C) Vasodilators Nitropru- sside 0.3-10 mcg/kg/mi n 1-2 min 1-2 min N/V, muscle twitching, cyanide, I: CHF, aortic dissect, Catechol.
  • 5. 5 IV infusion Thiocyanide tox. & intracranial pressure C: hepatic,renal insufficiency Nitrogly- cerin (IV) 5-100 mcg/kg/ min 2-5 min 3-5 min Head ache, dizziness, vomiting, methemgl- obin &tolerance I: coronary dis.,CHF C: CVA, Intracranial pressure Diazoxide ( IV) 1-3 (mg/kg) IV bolus, q5-15 /min; repeat every 4- 24 hr as needed 2-4 min 3-12 hr Nausea, hypoten- sion , flushing, tachycardia , hypergly- cemia, aggravat- ion of angina& fluid retention C: Syndromesof coronary insufficiency, (unless used with beta- blockingagent), cerebrovascular accident& hypersensi- tivity to sulfonamides Fenoldo- pam mesylate 0.1-1.7 mcg/kg/ min (IV infusion) 5-15 min 1-4 hr Headache, dizziness, flushing, increased intraocular pressure, Hypokal- emia& dose related tachycardia I: Severehyperten- sion with renal insufficiency C: Glaucoma Hydrala- zineHCl 10-20 mg IV or IM bolus, (maxim um dose, 40 mg) 10-20 min 3-8 hr Tachy- cardia, flushing, headache ,vomiting & aggravat- ion of angina I: CHF C: Coronary insufficiency,aortic dissection, cerebrovascular accident(may increaseintracranial pressure) Enalaprilat (IV) 1.25-5 mg q6 15 min 6 hr Precipit- ous drop I: CHF C: Use with caution in patientswith severe
  • 6. 6 hr IV in blood pressure in high renin st. renal insufficiency (not receivingdialysis) Nicardi- pine HCl 5-15 mg/hr IV infusion 5-20 min 1-2 hr Tachycar dia, headache ,flushing, local phlebitis C: Greater than first- degree heartblock, CHF AdrenergicInhibitors Phentol- amine - blocker 5-20 mg IV, repeat as necess- ary 1-2 min 10-30 min Tachycardia , nausea, flushing, abdominal pain&aggr- avation of angina I: Catecholamine excess C: Syndromesof coronary insufficiency Esmolol HCl 200-500 mcg/kg/ min over1-4 min, then 50- 300 mcg/kg/ min IV infusion 1-2 min 10-20 min Hypoten- sion, nausea, bradycar- dia or heart block& dizziness I: Syndromesof coronary insufficiency C: Greater than first- degree heartblock, CHF Labetalol HCl - blocker 20-80 mg IV bolus, (maxim um dose, 300 mg 2-10 min 2-4 hr Hypoten- sion, nausea, itching, scalp tingling& dizziness I: Syndromesof coronary insuffi- ciency,catechol- amine excess C: first-degree heart block,CHF, bronchialasthma
  • 7. 7 References: (1) Medline Plus-A service of the U.S. national library of medicine Malignant hypertension, causes, symp . &… http://www.nlm.nih.gov/medlineplus/druginformation.html (2) A.D.A.M. Medical Encyclopedia. Malignant hypertension http://www.ncbi.nlm.nih.gov/pubmedhealth/ (3) Hypertension& The Kidney Chapter8 (Hypertensive Crises) byCharles R. Nolan (4) HypertensionEmergencies & Urgencies By StephenS. Levin, D.O.
  • 8. 8