Hypertension &
ACE Inhibitors
By: Linda Hernandez
What is Hypertension?
• High Blood Pressure
http://www.nlm.nih.gov/medlineplus/ency/article/000468.htm
Two types of pressure
1. Systolic Blood Pressure
2. Diastolic Blood Pressure
http://www.nlm.nih.gov/medlineplus/ency/article/000468.htm
How is it diagnosed?
• Blood pressure testing
– Sphygmomanometer
– Stethoscope
http://www.nlm.nih.gov/medlineplus/ency/imagepages/19255.htm
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
Who is at risk?
http://www.cdc.gov/mmwr/preview/mmwrhtml/figures/m433qsf.gif
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
Untreated Hypertension
http://www.nlm.nih.gov/medlineplus/ency/imagepages/18166.htm
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
http://www.colorado.edu/kines/Class/IPHY3430-200/image/angiotensin.jpg
Pharmaceutical Treatment
• Diuretics
• Alpha-blockers
• Beta-blockers
• Calcium channel blockers
• Angiotensin receptor blockers
• ACE inhibitors
– Captopril
– Enalapril
– Benazepril
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
Drug Design
• Structure-based design
– Indirect
– Designed based on carboxypeptidase A
Carboxypeptidase ACE
http://www.bmb.leeds.ac.uk/illingworth/cardio/index.htm
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
Angiotensin I
Captopril
http://www.bmb.leeds.ac.uk/illingworth/cardio/index.htm
Drug Mechanism
• Sulfhydryl group of captopril provides a
high potency of ACE inhibition
• It produces an endothelium-dependent
vasorelaxation
http://en.wikipedia.org/wiki/Image:Captopril.png
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
Captopril Co$t
90 tablets 180 tablets 360 tablets
12.5mg $30 $60 $87
25mg $40 $67 $108
50mg $50 $75 $130
Side Effects
• Dry cough
• Rashes
• Abdominal pain
• Dizziness
• Loss of taste
• Loss of appetite
• Vomiting
• Angioedema
• Hyperkalemia
Pictures courtesy of google image search
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
Other ACE Inhibitors
http://www.pharmacy.umaryland.edu/courses/PHAR531/lectures_old/fig/enzymes_fig5.GIF
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
Check This Out!!!
• These videos will help you review today's
lecture:
– http://heart.health.ivillage.com/bloodpressure/
aceinhibitors.cfm?ivNPA=1&sky=ggl|hco|acei
nhibitors|ht|PPC4254|c
– http://www.youtube.com/watch?v=ZyKqwKEN
Xqo
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/S236.pdf
(5) http://hyper.ahajournals.org/cgi/reprint/17/4/589.pdf
(6)http://www.medicinenet.com/captopril/article.htm
(7)http://www.uic.edu/classes/pcol/pcol331/dentalhandouts2005/dentle
cture23.pdf
(8) http://www.medicinenet.com/hyperkalemia/page3.htm
(9) http://www.mayoclinic.com/health/hives-and-
angioedema/DS00313/DSECTION=8
(10) http://alternative-medicine-and
health.com/conditions/hypertension.htm
(11) http://www.freerepublic.com/focus/f-news/1562500/posts
Pictures courtesy of google image search