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Lisinopril

The dangerous drug attorneys at the Law Offices of Gregory Krasovsky can provide legal advice and representation to individuals and families considering pursuing a Lisinopril lawsuit. In order for a plaintiff to secure a maximum settlement in litigation of a Lisinopril claim, regardless of whether in an individual lawsuit or in a class action lawsuit, it is crucial that the law firm representing you have a competent and experienced team of Lisinopril lawyers to guide you through all of the legal hurdles as well as sufficient funding (litigation funding or legal finance) to cover litigation costs. Contact a Lisinopril attorney today to schedule a free consultation and take your first step to obtaining compensation for losses caused by Lisinopril side effects.

 

Lisinopril is an ACE inhibitor, which is marketed under the names Prinivil and Zestril. Lisinopril is used to treat congestive heart failure, hypertension, and other conditions related to heart attacks. Lisinopril was introduced into the pharmaceutical market in the early 1990s. Lisinopril was developed by Merck & Co., but is is currently manufactured by AstraZeneca as well.

Unfrotunately, Lisinopril, like other ACE inhibitors has some very serious side effects. These Lisinopril adverse effects include, but are not limited to, the following:

  • Death or serious injury from Angioedema (swelling of the mucous membranes, such as lips, around eyes, tongue, mouth, breathing passages. See below)
  • Liver Damage

  • Liver Failure

  • Fatal Liver Damage

  • Fainting

  • Rash

  • Dry Cough

  • Jaundice

  • Syncope

  • Anaphylais

  • Difficulty swallowing

  • Difficulty Breathing

  • Abdominal Pain

  • Decreased Urination

  • Dark Urine

  • Nausea

  • Muscle Cramps

Of these side effects, the ones that cause the most lawsuit involve liver complications. The liver damage that lisinopril might be fatal. In the past, patients have had to get liver transplants as a result of Lisinopril side effects. Some of these users were people who had no previous liver problems and were not much advanced in age.

If you or a loved one has been injured as a result of takng Lisinopril, you might be entitled to compensation. In order to maximize the size of the damages, it is important to hire an attorney from a Lisinopril law firm.

Contact one of our unsafe drug attorneys today to schedule a free and condifidential consultation and take the first step to reclaiming justice and your life's normalcy.

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Please watch the following 4 videos to understand how we handle prospective Lisinopril and dangerous drug & medical device and medical malpractice claims:

1. The dangers of Lisinopril (brand Names Zestril, Prinivil)

     YouTube Video: https://youtu.be/bZZVxXOqDfY

2. Initial evaluation of potential dangerous drug, medical device and medical malpractice claims.

     YouTube Video: https://www.youtube.com/watch?v=-lCB4Foe-TE
 
3. Dangerous Drugs & Defective Medical Devices/Products - Part 1

     YouTube Video: https://www.youtube.com/watch?v=kV5R5U7q5vM
 
4. Dangerous Drugs & Defective Medical Devices/Products - Part 2

     YouTube Video: https://www.youtube.com/watch?v=v7csYaM1OO4  
 
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Lisinopril

pronounced as (lyse in' oh pril)

What special precautions should I follow?
 
Before taking lisinopril,

-    tell your doctor and pharmacist if you are allergic to lisinopril; other ACE inhibitors such as enalapril (Vasotec, in Vaseretic), benazepril (Lotensin, in Lotrel), captopril (Capoten), fosinopril (Monopril), moexipril (Univasc, in Uniretic), perindopril (Aceon), quinapril (Accupril, in Accuretic, in Quinaretic), ramipril (Altace), and trandolapril (Mavik, in Tarka); any other medications; or any ingredients in lisinopril tablets and solution. Ask your pharmacist for a list of the ingredients.


-    tell your doctor or pharmacist if you are taking valsartan and sacubitril (Entresto) or if you have stopped taking it within the last 36 hours. Your doctor will probably tell you not to take lisinopril, if you are also taking valsartan and sacubitril. Also, tell your doctor if you have diabetes and you are taking aliskiren (Tekturna, in Amturnide, Tekamlo, Tekturna HCT). Your doctor will probably tell you not to take lisinopril if you have diabetes and you are also taking aliskiren.

-    tell your doctor and pharmacist what prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking. Be sure to mention any of the following: aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) such as diuretics ('water pills'); everolimus (Zortress); gold compounds; indomethacin (Indocin, Tivorbex); insulin or other medications to treat diabetes; lithium (Lithobid); potassium supplements; sirolimus (Rapamune); and temsirolimus (Torisel). Your doctor may need to change the doses of your medications or monitor you carefully for side effects.-

-    tell your doctor if you have or have had certain types of angioedema (a condition that causes difficulty swallowing or breathing and painful swelling of the face, throat, tongue, lips, eyes, hands, feet, ankles, or lower legs). Your doctor will probably tell you not to take lisinopril.

-    tell your doctor if you have or have ever had heart or kidney disease or diabetes.

-    tell your doctor if you are breastfeeding.

-   if you are having surgery, including dental surgery, tell the doctor or dentist that you are taking lisinopril.

-    you should know that diarrhea, vomiting, not drinking enough fluids, and sweating a lot can cause a drop in blood pressure, which may cause lightheadedness and fainting.
 
What side effects can this medication cause?

Lisinopril may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:

    cough
    dizziness
    headache
    excessive tiredness
    nausea
    diarrhea
    weakness
    sneezing
    runny nose
    decrease in sexual ability
    rash

Some side effects can be serious. If you experience any of these symptoms, call your doctor immediately:

    swelling of the face, throat, tongue, lips, eyes, hands, feet, ankles, or lower legs
    hoarseness
    difficulty breathing or swallowing
    fever, sore throat, chills, and other signs of infection
    yellowing of the skin or eyes
    lightheadedness
    fainting
    chest pain

Lisinopril may cause other side effects. Call your doctor if you have any unusual problems while taking this medication.

If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration's (FDA) MedWatch Adverse Event Reporting program online (http://www.fda.gov/Safety/MedWatch) or by phone (1-800-332-1088).

https://medlineplus.gov/druginfo/meds/a692051.html
 
***

Lisinopril

Side Effects by Likelihood and Severity

If experienced, these tend to have a Less Severe expression:

headache
cough

INFREQUENT side effects

If experienced, these tend to have a Severe expression:

high levels of potassium in the blood

If experienced, these tend to have a Less Severe expression:

dry mouth
constipation
the inability to have an erection
fainting
low energy
taste impairment
gas
diarrhea
generalized weakness
RARE side effects

If experienced, these tend to have a Severe expression:

diabetes
a disorder with excess antidiuretic hormone called syndrome of inappropriate antidiuretic hormone
a type of joint disorder due to excess uric acid in the blood called gout
low amount of sodium in the blood
a type of blood disorder where the red blood cells burst called hemolytic anemia
decreased function of bone marrow
decreased blood platelets
low levels of white blood cells
low levels of a type of white blood cell called neutrophils
increased eosinophils in the blood
high levels of white blood cells
orthostatic hypotension, a form of low blood pressure
vocal cord swelling
acute liver failure
inflammation of the liver called hepatitis
a blockage of the bile duct that resulting in high bilirubin levels
acute inflammation of the pancreas
acute kidney failure
a skin disorder with blistering and peeling skin called toxic epidermal necrolysis
a skin disorder with blistering and peeling skin called Stevens-Johnson syndrome
hives
abnormal liver function tests
a significant type of allergic reaction called anaphylaxis
a type of allergic reaction called angioedema
a type of allergic reaction involving the intestines called intestinal angioedema
a type of allergic reaction involving the head and neck called head and neck angioedema

If experienced, these tend to have a Less Severe expression:

confusion
mood changes
visual sensitivity to light
double vision
blurred vision
a change in vision
ringing in the ears
increased sensitivity of the skin to the sun
psoriasis
itching
hair loss
hallucinations
sensation of spinning or whirling
a distorted sense of smell called parosmia
temporary redness of face and neck
a non-cancerous skin reaction called a cutaneous pseudolymphoma

https://www.webmd.com/drugs/2/drug-6873-9371/lisinopril-oral/lisinopril-oral/details/list-sideeffects

***

Lisinopril (Oral Route)

Description and Brand Names

Drug information provided by: IBM Micromedex

US Brand Name
    Prinivil
    Zestril
 
Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

    Angioedema (swelling of the face, lips, tongue, throat, arms, or legs) with other ACE inhibitors, history of—May increase risk of this condition occurring again.

    Collagen vascular disease (an autoimmune disease) together with kidney disease—Increased risk of blood problems.

    Diabetes or
    Kidney problems—Increased risk of potassium levels in the body becoming too high.

    Diabetes patients who are also taking aliskiren (Tekturna®) or
    Hereditary or idiopathic angioedema or
    Patients who have kidney problems and are also taking aliskiren (Tekturna®)—Should not be used in patients with these conditions.

    Electrolyte imbalance (eg, low sodium in the blood) or
    Fluid imbalances (caused by dehydration, vomiting, or diarrhea) or
    Heart or blood vessel problems (eg, aortic stenosis, hypertrophic cardiomyopathy) or
    Liver disease—Use with caution. May make these conditions worse.

Side Effects

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:
More common

    Blurred vision
    cloudy urine
    confusion
    decrease in urine output or decrease in urine-concentrating ability
    dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
    sweating
    unusual tiredness or weakness

Less common

    Abdominal or stomach pain
    body aches or pain
    chest pain
    chills
    common cold
    cough
    diarrhea
    difficulty breathing
    ear congestion
    fever
    headache
    loss of voice
    nasal congestion
    nausea
    runny nose
    sneezing
    sore throat
    vomiting

Rare

    Arm, back, or jaw pain
    chest discomfort, tightness, or heaviness
    fast or irregular heartbeat
    general feeling of discomfort or illness
    joint pain
    loss of appetite
    muscle aches and pains
    shivering
    trouble sleeping

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:
Less common

    Decreased interest in sexual intercourse
    inability to have or keep an erection
    lack or loss of strength
    loss in sexual ability, desire, drive, or performance
    rash

Rare

    Acid or sour stomach
    belching
    burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings
    feeling of constant movement of self or surroundings
    heartburn
    indigestion
    muscle cramps
    sensation of spinning
    stomach discomfort or upset
    swelling

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

https://www.mayoclinic.org/drugs-supplements/lisinopril-oral-route/side-effects/drg-20069129?p=1

***

Lisinopril
From Wikipedia, the free encyclopedia

Lisinopril is a medication of the angiotensin-converting enzyme (ACE) inhibitor and is used to treat high blood pressure, heart failure, and after heart attacks.[7] For high blood pressure it is usually a first-line treatment. It is also used to prevent kidney problems in people with diabetes mellitus.[7] Lisinopril is taken by mouth.[7] Full effect may take up to four weeks to occur.[7]

Common side effects include headache, dizziness, feeling tired, cough, nausea, and rash.[7] Serious side effects may include low blood pressure, liver problems, high blood potassium, and angioedema.[7] Use is not recommended during the entire duration of pregnancy as it may harm the baby.[7] Lisinopril works by inhibiting the renin–angiotensin–aldosterone system.[7]

Lisinopril was patented in 1978 and approved for medical use in the United States in 1987.[7][9] It is available as a generic medication.[7] In 2019, it was the third most commonly prescribed medication in the United States, with more than 91 million prescriptions.[10][11] In July 2016, an oral solution formulation of lisinopril was approved for use in the United States.[7][12]

Contraindications

Lisinopril is contraindicated in people who have a history of angioedema (hereditary or idiopathic) or who have diabetes and are taking aliskiren.[1]
Adverse effects

The incidence of adverse effects varies according to which disease state the patient is being treated for.[1]

People taking lisinopril for the treatment of hypertension may experience the following side effects:[1][failed verification]

Headache (3.8%)
Dizziness (3.5%)
Cough (2.5%) Persons with the ACE I/D genetic polymorphism may be at higher risk for ACE inhibitor-associated cough.[16]
Difficulty swallowing or breathing (signs of angioedema), allergic reaction (anaphylaxis)
Hyperkalemia (2.2% in adult clinical trials)
Fatigue (1% or more)
Diarrhea (1% or more)


Some severe skin reactions have been reported rarely, including toxic epidermal necrolysis and Stevens–Johnson syndrome; causal relationship has not been established.

People taking lisinopril for the treatment of myocardial infarction may experience the following side effects:[1][failed verification]

Hypotension (5.3%)
Kidney dysfunction (1.3%)

People taking lisinopril for the treatment of heart failure may experience the following side effects:[1][failed verification]

Hypotension (3.8%)
Dizziness (12% at low dose – 19% at high dose)
Chest pain (2.1%)
Fainting (5–7%)
Hyperkalemia (3.5% at low dose – 6.4% at high dose)
Difficulty swallowing or breathing (signs of angioedema), allergic reaction (anaphylaxis)
Fatigue (1% or more)
Diarrhea (1% or more)


Some severe skin reactions have been reported rarely, including toxic epidermal necrolysis and Stevens–Johnson syndrome; a causal relationship has not been established.
Agranulocytosis

https://en.wikipedia.org/wiki/Lisinopril

***


Fatal angioedema associated with lisinopril

J L Ulmer  1 , M J Garvey
Affiliations

Case Reports
Ann Pharmacother

1992 Oct; 26(10):1245-6.
 
PMID: 1330096
DOI: 10.1177/106002809202601012


Abstract

Objective: To report a case of fatal angioedema associated with the use of lisinopril, a long-acting angiotensin-converting enzyme (ACE) inhibitor.

Data sources: Case reports, review articles, short reports, and pertinent information from the patient's medical record.

Data extraction: Data was collected from contemporary medical journals and reviewed by both authors.

Data synthesis: Angioedema associated with ACE inhibitors (captopril and enalapril) is well documented in the literature. With increased prescribing of newer, longer-acting agents, this potentially lethal adverse reaction is of even greater concern. Because angioedema associated with ACE inhibitors is a class-related event, the number of reported cases would be expected to increase with increasing numbers of prescriptions written for these drugs. This report, describing a patient who developed angioedema following therapy with lisinopril, illustrates the severity of this adverse reaction.

Patient: A 66-year-old man presented to the emergency room complaining of increased swelling of the back of his throat and difficulty breathing. Despite treatment with epinephrine, antihistamines, and corticosteroids, the patient's condition progressed from that of severe laryngeal edema to total laryngospasm and complete airway obstruction. Emergency measures to intubate the patient were complicated by severe swelling of his neck and oropharynx, forcing the physician to perform a grossly traumatic tracheotomy. The difficulty encountered during intubation deprived the patient of oxygen for a significant amount of time, precipitating cardiopulmonary arrest. The anoxic episode resulted in hypoxic, ischemic encephalopathy and, ultimately, death.

Conclusions: Angioedema is a serious, potentially life-threatening adverse effect associated with the use of ACE inhibitors. Clinicians need to be aware of this effect when prescribing ACE inhibitors to treat hypertension and congestive heart failure, and when assessing patients presenting to the emergency room with complaints of tongue or pharyngeal swelling. Patients should be instructed to report immediately to an emergency room for medical attention if they experience any unexplained shortness of breath or swelling of the throat or tongue.

https://pubmed.ncbi.nlm.nih.gov/1330096/

***

Angioedema associated with lisinopril
Brief report
 
Authors
Richard S. Rees MD abcd
Jeffrey Bergman MD abcd
Rina Ramirez-Alexander MD abcd

a    Department of Medicine, New York, NY USA.

b    Department of Ambulatory Care, New York, NY USA.

c    the Department of Veterans Affairs Medical Center, New York, NY USA.

d    the NYU School of Medicine, New York, NY USA.

Received 7 November 1991, Accepted 25 November 1991, Available online 9 April 2004.

Abstract

Angioedema has been reported to occur in association with all angiotensin-converting enzyme inhibitors used in the United States.

We reviewed nine cases of angioedema associated with lisinopril use seen in the emergency department at our hospital among 1,970 patients that had been prescribed lisinopril from March 1989 to May 1990.

Cases were considered as probably (six cases) or possibly (three cases) drug related, depending on the temporal relationship of the initiation of therapy and the onset of angioedema.

All of the cases had edema of the lips, buccal mucosa, and or face.

None presented with laryngeal edema or stridor.

The angioedema resolved within 1 to 2 days with diphenhydramine treatment and discontinuation of lisinopril.

Our data suggest that the incidence of angioedema associated with lisinopril is greater than that associated with captopril or enalapril.

https://www.sciencedirect.com/science/article/abs/pii/073567579290010U

***
 
Angioedema
 
JAMA ( IF 157.335 ) Pub Date: 2018-05-15, DOI:10.1001/jama.2018.4860

James A. Tarbox , Arpana Bansal , Alan N. Peiris

Angioedema is swelling caused by fluid leakage from blood vessels into the surrounding skin and tissue.

Angioedema can involve any part of the body but is usually more pronounced around the eyes, lips, mouth, tongue, extremities, and genitalia.

The swelling may be accompanied by hives, which are more superficial, while angioedema affects the deeper layers of skin.

There are multiple causes of angioedema.

Allergic angioedema is the most common type and includes reactions to foods such as peanuts and shellfish, medications including antibiotics, insect bites and stings, and latex.

Nonallergic, drug-induced angioedema is caused by certain medicines including a commonly prescribed blood pressure drug class, angiotensin-converting enzyme inhibitors (such as lisinopril).

This type occurs without an allergic component and is not associated with itching or hives.

The relatively rare hereditary angioedema is caused by lack of or dysfunction in an enzyme in the complement pathway, which is part of the immune system.

Acquired angioedema is related to infections, autoimmune diseases, and, rarely, malignancies such as lymphoma. Idiopathic angioedema means there is no clear cause.

https://en.x-mol.com/paper/article/669751

***


ACE inhibitors

ACE inhibitors are commonly used to treat heart failure and high blood pressure and are often prescribed to people following a heart attack.

Doireann Maddock puts some common questions to Dr Terry McCormack.

What are ACE inhibitors and how do they work?

ACE inhibitors can reduce the activity of an enzyme called angiotensin-converting enzyme, or ACE for short.

The enzyme is responsible for hormones that help control your blood pressure.

It has a powerful narrowing effect on your blood vessels, which increases your blood pressure.

ACE inhibitors inhibit or limit this enzyme, making your blood vessels relax and widen.

This, in turn, lowers your blood pressure and improves blood flow to your heart muscle.

A quarter of the blood pumped out in each heartbeat flows through the kidneys, so if your heart becomes less efficient, your kidneys also suffer.

Therefore, ACE inhibitors improve kidney, as well as heart, function.

https://www.bhf.org.uk/informationsupport/heart-matters-magazine/medical/drug-cabinet/ace-inhibitors

***

How do ACE inhibitors work?
Oct 2, 2018

British Heart Foundation

ACE inhibitors are a type of medication commonly used to treat heart failure and high blood pressure and are often prescribed to people following a heart attack.


Our animation shows how they work inside your body.

For more information on ACE inhibitors visit - https://www.bhf.org.uk/aceinhibitors

***

Poisonous Brazilian pit viper and Lisinopril:

Lisinopril = Angiotensin-Converting Enzyme (ACE) inhibitor used to treat high blood pressure 

Lisinopril is the lysine-analog of enalapril.

Angiotensin-Converting Enzyme (ACE) was identified as the enzyme responsible for the conversion of angiotensin I to the vasoconstrictor substance, angiotensin II, in the mid 1950s.

Bothrops jararaca = Poisonous Brazilian pit viper

In 1968, studies carried out in the Royal College of Surgeons laboratories of Nobel prize winner, John Vane, showed that peptides from the Brazilian viper’s venom inhibited the activity of ACE from dog lung.2

Captopril, the first ACE inhibitor, is a functional and structural analog of a peptide derived from the venom of the Jararaca, a Brazilian pit viper,

Captopril's effects on blood pressure mechanisms mimicked those of the Jararaca snake’s venom.

Prinivil® (Lisinopril), Captopril® (Enalapril), Integrilin® (Eptifibatide) and Aggrastat® (Tirofiban) are drugs based on snake venoms, which have been approved by the FDA.

***

The bite that cures: how we’re turning venom into medicine
By Kath Nightingale

Published: 05th July, 2019 at 14:05

Workers on banana plantations who’ve been bitten by snakes often pass out due to severe drops in blood pressure.

This led researchers to a peptide in the venom of the pit viper Bothrops jararaca.

The drug based on it – blood pressure medication captopril – works by stopping the molecules that would ordinarily prevent blood vessel dilation, allowing them to widen and lower blood pressure.

It was the first venom-based drug and continues to be one of the most popular medications on the market.

https://www.sciencefocus.com/nature/the-bite-that-cures-how-were-turning-venom-into-medicine/

 

***

Using venom to heal?

Medicines derived from modified toxins are already in use.

If you know anyone taking blood pressure medication, chances are it’s in the class of drugs known as ACE inhibitors, which contain modified snake toxins.

Researchers in the 1970s observed that plantation workers bitten by the Brazilian pit viper collapsed with crashing blood pressure.

They separated out this pressure-lowering component in the venom, modified it, and released a synthetic version in the mid-1970s.

The ACE inhibitor class of drugs has gone on to become one of the top 20 bestselling drugs of all time, with multibillion dollar sales. And many lives saved.

https://www.science.org.au/curious/people-medicine/using-venom-heal
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Snake Venoms in Drug Discovery: Valuable Therapeutic Tools for Life Saving

Snake venoms have also been used as medical tools for thousands of years especially in tradition Chinese medicine.

Consequently, snake venoms can be considered as mini-drug libraries in which each drug is pharmacologically active. However, less than 0.01% of these toxins have been identified and characterized.

For instance, Captopril® (Enalapril), Integrilin® (Eptifibatide) and Aggrastat® (Tirofiban) are drugs based on snake venoms, which have been approved by the FDA.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6832721/

***

10 heart drugs with weird origins

1. ACE Inhibitors

Brazilian viper Jararaca

ACE inhibitors are a frequently used class of drugs in heart medicine, used to treat high blood pressure and heart failure, and often prescribed following a heart attack. One common example is ramipril.

But did you know that the active ingredient in the first ACE inhibitor, captopril, was originally derived from snake venom? Launched in 1981, captopril was based on an ingredient of the venom of the poisonous Brazilian Viper (Bothrops Jararaca).

Nobel Prize winner John Vane initially tested peptides from the venom on dog lungs, finding that they were able to block the activity of angiotensin converting enzyme, from here Vane tentatively proposed an ACE inhibitor research programme to what is now Bristol Myers Squibb. Many revisions, tests and trials later, in 1975 captopril was born.

Captopril is rarely prescribed today but is still licensed for use in high blood pressure, heart failure and even kidney disease caused by diabetes. It was the first effective oral ACE inhibitor and its legacy of subsequent developments in this drug group has helped to manage the blood pressures of millions of people.

https://www.bhf.org.uk/informationsupport/heart-matters-magazine/medical/drug-cabinet/heart-drugs-with-weird-origins

***

***

From snake venom to ACE inhibitor — the discovery and rise of captopril

In this article on landmark drugs, Jenny Bryan looks at the discovery of captopril and how it changed cardiovascular treatment.

Landmark drugs

17 April 2009
By Jenny Bryan

In the early 1980s, hypertension conferences were routinely enlivened by the poisonous Brazilian viper, Bothrops jararaca.

With its striking zig-zag markings and aggressively protruding tongue, images of the snake were a welcome break from graphs and tables in presentations about captopril — the first of the angiotensin-converting enzyme (ACE) inhibitors, whose effects on blood pressure mechanisms mimicked those of the snake’s venom.

When the cardiovascular juggernaut alighted in Sao Paulo, Brazil, for a major congress in 1984, there was even an opportunity for delegates to visit a snake farm and see the beast in all its glory.

“The discovery of the ACE inhibitors and the creation of captopril was one of the really great advances in cardiovascular medicine, alongside beta blockers, calcium channel blockers and statins.

When captopril arrived, there was a lot of excitement and a feeling that acting on the renin-angiotensin system was going to be a very important step forward,” recalls Philip Poole-Wilson, emeritus professor of cardiology at the National Heart and Lung Institute, Imperial College, London.

ACE was identified as the enzyme responsible for the conversion of angiotensin I to the vasoconstrictor substance, angiotensin II, in the mid 1950s.1

In 1968, studies carried out in the Royal College of Surgeons laboratories of Nobel prize winner, John Vane, showed that peptides from the Brazilian viper’s venom inhibited the activity of ACE from dog lung.2

When Vane proposed an ACE inhibitor research programme to US pharmaceutical company, ER Squibb and Sons (now part of Bristol Myers Squibb), clinical advisers were wary because, at that time, the renin-angiotensin system was thought to play a role only in the most serious “malignant” hypertension.3,4

However, it was decided that there was enough clinical interest to proceed with trying to develop synthetic ACE inhibitors that were orally active.3,4
...
As it became clear that ACE inhibitors saved lives, there was renewed effort to find a way of administering them safely to heart failure patients.

Admitting every patient to hospital for a test dose was impractical and expensive. On the basis of a comparison of large fixed doses of captopril and enalapril, which showed that the longer acting drug produced more prolonged hypotensive effects,11 a system was introduced for administering a small test dose of the short-acting captopril and, if all went well, increasing the dose or switching to enalapril.

“It was all a nonsense because we now take the opposite view, that the longer acting ACE inhibitors, such as lisinopril and perindopril, which we use today, have a slower onset of action and are therefore less likely to cause problems than a fast onset, shorter acting drug.

What really mattered was the dose, and the need to start on a reasonable dose and move up gradually rather than starting high and reducing the dose, as tended to happen in the US,” says Professor Poole-Wilson.

https://pharmaceutical-journal.com/article/news/from-snake-venom-to-ace-inhibitor-the-discovery-and-rise-of-captopril

***

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