Hypertension

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Hypertension ACE Inhibitors

• By Linda Hernandez

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What is Hypertension?

• High Blood Pressure

http//www.nlm.nih.gov/medlineplus/ency/article/00
0468.htm
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Two types of pressure

• Systolic Blood Pressure
• Diastolic Blood Pressure

http//www.nlm.nih.gov/medlineplus/ency/article/00
0468.htm
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How is it diagnosed?

• Blood pressure testing
• Sphygmomanometer
• Stethoscope

http//www.nlm.nih.gov/medlineplus/ency/imagepages
/19255.htm
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What causes it?

• Essential Hypertension
• Genetics
• Environmental factors
• Diet
• Secondary Hypertension
• Size condition of the arteries
• Volume of water in the body
• Salt content of the body
• Levels of various hormones
• Kidney nervous system disorders
• Some medications

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Who is at risk?
http//www.cdc.gov/mmwr/preview/mmwrhtml/figures/m
433qsf.gif
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What are the symptoms?

• There are usually no symptoms
• silent killer
• Mild headache
• Fatigue
• Confusion
• Visual Changes
• Nausea vomiting
• Anxiety
• Pale or red skin
• Chest pain

Pictures courtesy of google image search
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Untreated Hypertension
http//www.nlm.nih.gov/medlineplus/ency/imagepages
/18166.htm
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Renin-Angiotensin-Aldosterone Pathway

• Short term mechanism
• Used by body when there is a decrease in blood
  volume
• It increases blood pressure
• However
• its overactivity results in hypertension

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http//www.colorado.edu/kines/Class/IPHY3430-200/i
mage/angiotensin.jpg
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Pharmaceutical Treatment

• Diuretics
• Alpha-blockers
• Beta-blockers
• Calcium channel blockers
• Angiotensin receptor blockers
• ACE inhibitors
• Captopril
• Enalapril
• Benazepril

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Drug Discovery

• 1960s
• Vane Ferreira discover a peptide in Brazilian
  viper venom
• 1975
• Drug company Squibb develops first ACE inhibitor
  ? Captopril
• 1977
• Captopril was patented
• 1980s
• FDA approval

Picture courtesy of google image search
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Drug Design

• Structure-based design
• Indirect
• Designed based on carboxypeptidase A

Carboxypeptidase
ACE
http//www.bmb.leeds.ac.uk/illingworth/cardio/inde
x.htm
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Drug Mechanism

• Captopril is a competitive inhibitor of ACE
• It mimics angiotensin I
• It directly blocks the formation of angiotensin
  II
• Net results
• Reduced vasoconstriction
• Reduced sodium and water retention
• Increase vasodilation

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Angiotensin I
Captopril
http//www.bmb.leeds.ac.uk/illingworth/cardio/inde
x.htm
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Drug Mechanism

• Sulfhydryl group of captopril provides a high
  potency of ACE inhibition
• It produces an endothelium-dependent
  vasorelaxation

http//en.wikipedia.org/wiki/ImageCaptopril.png
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Drug Information

• Prescription required
• Orally administered
• Active form of drug
• Captopril dosage is individualized
• Duration of treatment depends on severity
• Captopril does NOT cure hypertension

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Captopril Cot
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Side Effects

• Dry cough
• Rashes
• Abdominal pain
• Dizziness
• Loss of taste
• Loss of appetite
• Vomiting
• Angioedema
• Hyperkalemia

Pictures courtesy of google image search
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Captopril Withdrawal

• Withdrawal results in a sudden increase of blood
  pressure
• Captopril is not additive by itself
• But drug combination leads to addiction

Pictures courtesy of google image search
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Other ACE Inhibitors
http//www.pharmacy.umaryland.edu/courses/PHAR531/
lectures_old/fig/enzymes_fig5.GIF
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Non-pharmaceutical Treatment

• Stop smoking
• Reduce body weight
• Aerobic physical exercise
• Eat more fruits, vegetables
• Increase potassium intake
• Decrease sodium intake
• Decrease alcohol intake
• Reduce stress
• Drink cocoa
• Garlic

Pictures courtesy of google image search
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Check This Out!!!

• These videos will help you review today's
  lecture
• http//heart.health.ivillage.com/bloodpressure/ace
  inhibitors.cfm?ivNPA1skygglhcoaceinhibitorsh
  tPPC4254c
• http//www.youtube.com/watch?vZyKqwKENXqo

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References

• (1)http//www.nlm.nih.gov/medlineplus/ency/article
  /000468.htm
• (2)http//www.fasebj.org/cgi/content/full/17/8/788
  
• (3) http//www.uahsj.ualberta.ca/files/Issues/1-1/
  html/7.htm
• (4)http//advan.physiology.org/cgi/reprint/275/6/S
  236.pdf
• (5) http//hyper.ahajournals.org/cgi/reprint/17/4/
  589.pdf
• (6)http//www.medicinenet.com/captopril/article.ht
  m
• (7)http//www.uic.edu/classes/pcol/pcol331/dentalh
  andouts2005/dentlecture23.pdf
• (8) http//www.medicinenet.com/hyperkalemia/page3.
  htm
• (9) http//www.mayoclinic.com/health/hives-and-ang
  ioedema/DS00313/DSECTION8
• (10) http//alternative-medicine-and
  health.com/conditions/hypertension.htm
• (11) http//www.freerepublic.com/focus/f-news/1562
  500/posts

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Pictures courtesy of google image search