1. Beta blockers
Introduction
Beta-blockers were first developed by Sir James black at the imperial chemical industries in
the United Kingdom in 1962. They are considered one of the most important contributions to
clinical medicine and pharmacology in the 20thcentury, and Sir James black was awarded the
Nobel prize in 1988 for advances in medicine.
Definition:
Beta blockers, also known as beta-adrenergic blocking agents, are medications that reduce
blood pressure. Beta blockers work by blocking the effects of the hormone epinephrine, also
known as adrenaline.
When take beta blockers, than heart beats more slowly and with less force, thereby reducing
blood pressure. Beta blockers also help blood vessels open up to improve blood flow.
What are beta blockers and how do they work?
Beta blockers, also known as beta-adrenergic blocking agents, are drugs that block
norepinephrine and epinephrine (adrenaline) from binding to beta receptors on nerves.
Norepinephrine and epinephrine are produced by nerves throughout the body as well as by
the adrenal gland. They serve as neurotransmitters (chemicals that nerves use to communicate
with one another) that may be active locally where they are produced, or elsewhere in the
body, when they are released into the blood. There are both alpha and beta receptors in the
body. There are three types of beta receptors and they control several different functions
based on their location in the body.
1. beta-1 (β1) receptors are located in the heart, eye, and kidneys.
2. beta (β2) receptors are found in the lungs, gastrointestinal tract, liver, uterus, blood
vessels, and skeletal muscle.
3. beta (β3) receptors are located in fat cells.
Beta blockers primarily block β1 and β2 receptors and thereby the effects of norepinephrine
and epinephrine. By blocking the effects of norepinephrine and epinephrine, beta blockers
reduce heart rate; reduce blood pressure by dilating blood vessels; and may constrict air
passages by stimulating the muscles that surround the air passages to contract considered an
adverse side effect).
2. Beta-blockers are medicines that work by temporarily stopping or reducing the body's
natural 'fight-or-flight' responses.
In turn, they reduce stress on certain parts of the body, such as the heart and the blood
vessels in the brain. They lower blood pressure, protect against heart attacks
Beta blockers work for heart protection:
Beta-blockers block the hormones adrenaline and nor-adrenaline in the sympathetic nervous
system.
The sympathetic nervous system is part of the autonomic nervous system. It activates the
'fight-or-flight' response.
Adrenaline: Adrenaline is a hormone released from the adrenal glands and its major action,
together with nor-adrenaline, is to prepare the body for 'fight or flight'.
{Adrenaline and nor-adrenaline are two separate but related hormones and neurotransmitters.
They are produced in the centre (medulla) of the adrenal glands and in some neurons of the
central nervous system. They are released into the bloodstream and serve as chemical
mediators, and also convey the nerve impulses to various organs. Adrenaline has many
different actions depending on the type of cells it is acting upon. However, the overall effect
of adrenaline is to prepare the body for the ‘fight or flight’ response in times of stress}
Adrenaline and nor-adrenaline prepare the muscles in the body for exertion. This is a
crucial part of responding to danger.
Overexposure to these hormones can be harmful. Too much adrenaline can lead to
rapid heartbeat, high blood pressure, excessive sweating, anxiety, and palpitations.
Blocking the release of these hormones blockers decreases the oxygen demands and
reduces stress on the heart.
This lowers the force of the contractions of the heart muscles, and of blood vessels in
the heart, the brain, and the rest of the body.
Beta-blockers also obstruct the production of angiotensin II, a hormone produced by
the kidneys.
Reducing the amount of angiotensin relaxes and widens the blood vessels, easing the
flow of blood through the vessels.
Indications of Beta-blockers
Angina, or chest pain
Heart failure
Hypertension, or high blood pressure
Atrial fibrillation, or irregular heartbeat
Myocardial infarction, or heart attack
3. Other uses: Less commonly, they may be used for migraines, glaucoma, overactive
thyroid, tremors, and anxiety.
Glaucoma: The high pressure within the eyeball is reduced using beta-blocker
eye drops. The medication lowers the production of fluid inside the eyeball.
Anxiety: Beta-blockers block the effects of stress hormones. As a result, they
can also reduce the physical symptoms of anxiety such as trembling and
sweating. A person experiencing persistent anxiety, however, may also need
additional treatment, such as counseling.
Hyperactive thyroid and tremor: Beta-blockers can reduce symptoms such
as tremor and slow the heart rate of patients with an overactive thyroid.
Side effects:
Beta blockers may cause:
Diarrhoea
Stomach cramps
Nausea
Vomiting
Other important side effects include:
Rash
Blurred vision
Disorientation
Insomnia
Hair loss
Weakness
Muscle cramps
Fatigue
As an extension of their beneficial effect, they slow heart rate and reduce blood pressure, but
they may cause adverse effects such as heart failure or heart block in patients with heart
problems.
Beta blockers should not be withdrawn suddenly because sudden withdrawal may worsen
angina (chest pain) and cause heart attacks, serious abnormal heart rhythms, or sudden death.
Central nervous system effects of beta blockers include:
o Headache
o Depression
o Confusion
o Dizziness
4. o Nightmares
o Hallucinations
Beta blockers that block β2 receptors may cause shortness of breath in asthmatics.
As with other drugs used for treating high blood pressure, sexual dysfunction may occur.
Beta blockers may cause low or high blood glucose and mask the symptoms of low blood
glucose (hypoglycemia) in people with diabetes.
Other serious side effects of beta-blockers include:
Toxic epidermal necrolysis
Raynaud's phenomenon
Lupus erythematosus
Bronchospasm
Serious allergic reactions
Erythema multiform
Steven Johnson Syndrome
Toxic epidermal necrolysis
Examples of beta blockers
Some beta blockers mainly affect your heart, while others affect both your heart and your
blood vessels. Which one is best for you depends on your health and the condition being
treated.
Examples of oral beta blockers include:
Acebutolol (Sectral)
Atenolol (Tenormin)
Bisoprolol (Zebeta)
Metoprolol (Lopressor, Toprol-XL)
Nadolol (Corgard)
Nebivolol (Bystolic)
Propranolol (Inderal LA, InnoPran XL)
Propranolol:
Propranolol was discovered in 1964. It is on the World Health Organization's List of
Essential Medicines, the most effective and safe medicines needed in a health system.
Propranolol is available as a generic medication
Propranolol, sold under the brand name Inderal is a medication of the beta blocker type. It is
used to treat high blood pressure, a number of types of irregular heart rate, thyrotoxicosis,
capillary hemangiomas, performance anxiety, and essential tremors. It is used to prevent
5. migraine headaches, and to prevent further heart problems in those with angina or previous
heart attacks. It can be taken by mouth or by injection into a vein
Propranolol is a type of drug called a beta-blocker. It works by acting on the nerve impulses
in specific areas of the body such as the heart. This causes the heart to beat slower and more
steadily.There are some side effects and complications to consider before taking propranolol,
however, as well as certain people who should avoid it altogether.
As well as slowing the heart down, propranolol also decreases the blood pressure. This makes
sure a safe amount of blood and oxygen is pumping through the heart to the rest of the body.
Brand names of propranolol include Inderal, Inderal LA, InnoPran XL, and Hemangeol. It is
a prescription drug, so it is only available from a doctor. Propranolol comes in the form of
tablets, capsules, an oral solution (Hemangeol) and a solution used for injection.
Indication:
Propranolol is typically used alone or combined with other medications to treat high blood
pressure.
High blood pressure makes the heart work too hard. If it is left unchecked, the heart and
arteries may begin to wear down over time. The heart controls the blood supply and if it is
not working properly it can cause damage to many areas of the body.
Propranolol is also used to treat or prevent severe headaches and migraines, chronic chest
pain, and to help treat or prevent heart attacks.
The medication is also used for many other specific conditions. Doctors may prescribe
propranolol for:
portal hypertension
pheochromocytoma, a tumor of the adrenal gland
essential tremor
supraventricular arrhythmia, an abnormal rhythm in the top chambers of the heart
panic disorders
aggressive behaviors
restlessness caused by antipsychotics
infantile hemangioma
Taking propranolol
The amount of propranolol a person should take varies. The correct dose for one person may
be too much or too little for another. It is very important to work directly with a doctor to
make sure that the level of propranolol is correct and will have the desired effect.
6. There are a few different ways to take propranolol, but it is mostly taken orally. Extended-
release capsules slowly release the drug into the bloodstream over the course of the day.
These are usually taken once a day, and the effects last for 24 hours.
There are also immediate-release pills that begin releasing the drug into the blood soon after
being taken. These are taken in multiple doses throughout the day. The number of pills taken
depends on the person's response to the medication.
Usual Adult Dose for Hypertension:
Initial dose:
Immediate-release: 40 mg orally 2 times a day
Sustained-release: 80 mg orally once a day
Maintenance dose:
Immediate-release: 120 to 240 mg orally per day
Sustained-release: 120 to 160 mg orally per day
Usual Adult Dose for Angina Pectoris:
Immediate-release: Total daily doses of 80 to 320 mg orally 2 to 4 times a day have been
shown to increase exercise tolerance and to reduce ischemic changes in the ECG.
Sustained-release: Initial dose: 80 mg orally once a day. Dosage should be gradually
increased at 3 to 7 day intervals. The average optimal dosage appears to be 160 mg once a
day.
Maximum dose: 320 mg per day
Usual Adult Dose for Arrhythmias:
Immediate-release: 10 to 30 mg orally 3 to 4 times a day, before meals and at bedtime
IV: 1 to 3 mg at a rate not exceeding 1 mg/min. Sufficient time should be allowed for the
drug to reach the site of action even when a slow circulation is present. A second dose may
be given after 2 minutes. Thereafter, additional drug should not be given in less than 4 hours.
Usual Adult Dose for Myocardial Infarction:
Immediate-release:
Initial dose: 40 mg orally 3 times a day for 1 month, then increase to 60 to 80 mg orally 3
times a day as tolerated.
Maintenance dose: 180 mg to 240 mg orally per day in divided doses (2 to 4 times daily)
Maximum dose: 240 mg orally per day
Usual Adult Dose for Migraine Prophylaxis:
Immediate-release:
Initial dose: 80 mg orally per day in divided doses
7. Maintenance dose: 160 to 240 mg orally per day in divided doses
Sustained-release:
Initial dose: 80 mg orally once a day
Maintenance dose: 160 to 240 mg once a day
Usual Adult Dose for Benign Essential Tremor:
Immediate-release:
Initial dose: 40 mg orally 2 times a day
Maintenance dose: 120 to 320 mg orally per day
Usual Adult Dose for Aortic Stenosis:
Immediate-release: 20 to 40 mg orally 3 to 4 times a day, before meals and at bedtime
Sustained-release: 80 to 160 mg orally once a day
Side effects and complications
A number of side effect of propranolol have been highlighted. The most common side effects
include:
dry eyes
nausea
drowsiness
diarrhea
wheezing or symptoms of bronchitis
fatigue, feeling weak
hair loss
slower heart rate
changes in sex drive
changes in sexual performance
Some symptoms are mild and tend to go away within a few weeks as the body adjusts to the
medication. Any severe symptoms or symptoms that don't go away should be discussed with
a doctor. It may be that the person is taking too much of the drug or their body may not be
responding well to it.
There are also some less common, yet more severe symptoms associated with propranolol. A
person who experiences any of these symptoms should call their doctor right away.
breathing problems or bronchospasms
slow heart rate
allergic reactions, such as itching, rashes and hives, or swelling in the face or tongue
sudden weight gain
swelling of legs, ankles, or feet
8. circulation problems such as cold hands and feet
sudden changes in blood sugar
trouble sleeping or nightmares
hallucinations
Because of specific side effects, there are a few things that doctors will look out for to decide
if a patient is able to take propranolol.
People with breathing disorders, such as asthma, bronchitis, or emphysema, should not take
propranolol. Likewise, people with slow heartbeats or a low blood pressure should avoid the
drug.
Doctors will also need to know if the patient has a history of:
liver or kidney disease
blood sugar problems or diabetes
circulation problems
thyroid disorders
congestive heart failure
allergies
muscular disorders
symptoms of depression
Nursing women should also avoid taking the drug as it can pass into breast milk and harm a
nursing baby. Babies under 4.5 pounds should not be given propranolol.
Acebutolol (Sectral):
Acebutolol is a cardioselective beta blocker with ISA (intrinsic sympathomimetic activity; It
is therefore more suitable than non cardioselective beta blockers, if a patient with asthma or
chronic obstructive pulmonary disease (COPD) needs treatment with a beta blocker. In doses
lower than 800mg daily its constricting effects on the bronchial system and smooth muscle
vessels are only 10% to 30% of those observed under propranolol treatment, but there is
experimental evidence that the cardioselective properties diminish at doses of 800mg/day or
more.
The drug has lipophilic properties, and therefore crosses the blood–brain barrier. Acebutolol
has no negative impact on serum lipids (cholesterol and triglycerides). No HDL decrease has
been observed. In this regard, it is unlike many other beta blockers which have this
unfavourable property.
The drug works in hypertensive patients with high, normal, or low renin plasma
concentrations, although acebutolol may be more efficient in patients with high or normal
renin plasma concentrations. In clinically relevant concentrations, a membrane-stabilizing
effect does not appear to play an important role.
9. Pharmacokinetics:
Acebutolol is well absorbed from the GI tract, but undergoes substantial first-pass-
metabolization, leading to a bioavailability of only 35% to 50%. Peak plasma levels of
acebutolol are reached within 2 to 2.5 hours after oral dosing. Peak levels of the main active
metabolite, diacetolol, are reached after 4 hours. Acebutolol has a half-life of 3 to 4 hours,
and diacetolol a half-life of 8 to 13 hours.
Indications:
hypertension
ventricular and atrial cardiac arrhythmia
acute myocardial infarction in high-risk patients
Smith-Magenis syndrome
Contraindications:
Stable or Unstable Angina (due to its partial agonist or ISA activity)
Contraindications and Precautions:
Acebutolol may not be suitable in patients with Asthma bronchiale or COPD due to its
bronchoconstricting (β2 antagonistic) effects.
Usual Adult Dose for Hypertension
Initial dose: 400 mg orally per day in 1 to 2 divided doses
Maintenance dose: 400 to 800 mg orally per day
Usual Adult Dose for Ventricular Arrhythmia
Initial dose: 200 mg orally twice a day
Maintenance dose: 600 to 1200 mg orally per day
Side effects:
The development of anti-nuclear antibodies (ANA) has been found in 10 to 30% of
patients under treatment with acebutolol. A systemic disease with arthralgic pain and
myalgias has been observed in 1%. A lupus erythematosus-like syndrome with skin rash and
multiforme organ involvement is even less frequent. The incidence of both ANA and
symptomatic disease under acebutolol is higher than under Propranolol. Female patients are
more likely to develop these symptoms than male patients. Some few cases of hepatotoxicity
with increased liver enzymes (ALT, AST) have been seen. Altogether, 5 to 6% of all patients
treated have to discontinue acebutolol due to intolerable side effects. When possible, the
treatment should be discontinued gradually in order to avoid a withdrawal syndrome with
increased frequency of angina and even precipitation of myocardial infarction.
10. Nursing Responsibilities of Administering Beta Blockers:
Before administering beta-blockers:
Check for allergies
Know what other drugs the patient is receiving including over the counter (OTC) and
herbs. Do any of them have the same “effect” as the beta-blocker?
Know why the patient is receiving the drug
Obtain current BP and apical pulse rate; if below 90 systolic or 60 beats per
minute(BPM) hold the drug and notify the health care provider (HCP). Check your
institution’s policy, some say hold below 50 BPM
After administering beta-blockers:
Observe for intended effect
Monitor for side effects, especially orthostatic hypotension
Monitor older pts for mental confusion or changes in LOC which may indicate an
overdose
Diabetics are not usually given beta-blockers because they can effect the blood
glucose level and because the drugs will mask the cardiovascular effects of
hypoglycemia such as tachycardia, mild tremors and diaphoresis. If your pt is a
diabetic and on a beta-blocker monitor closely for signs of hypoglycemia unique to
the pt and monitor blood glucose frequently
Patients with COPD (including asthma) should be monitored closely for respiratory
issues such as wheezing and difficulty breathing (remember what beta blockers block
– bronchodilation) they should not be given non-selective beta-blockers.
Health Education:
Safety measures to prevent orthostatic hypotension such as changing positions slowly,
hold onto railings when using stairs
To check pulse rate and when to call HCP
Common side effects as well as potential long term effects such as sexual dysfunction
and depression. If any issues arise, discuss with HCP.
Do not stop taking drug suddenly. Doing so may cause tachycardia, dysrythmias,
elevated BP, angina and MI.
Always inform HCP before surgery or dental work they are on a beta-blocker
Any chest pain experienced during activity should be discussed with the HCP so that
safe activity levels can be discussed. (If they exercise regularly, their target heart rate
may need to be lowered)
Extended release forms of the drug should never be crushed and taken.
11. Abstract
BACKGROUND:
The benefit from a blood pressure lowering therapy with beta blockers may not outweigh its
risks, especially in older populations. The aim of this study was to look for evidence on risks
and benefits of beta blockers in older adults and to use this evidence to develop
recommendations for the electronic decision support tool of the PRIMA-eDS project.
METHODS:
Systematic review of the literature using a stage approach with searches for systematic
reviews and meta-analyses first, and individual studies only if the previous searches are
inconclusive. The target population were older adults (≥65 years old) with hypertension. We
included studies reporting on the effectiveness and/or safety of beta blockers on clinically
relevant endpoints (e.g. mortality, cardiovascular events, and stroke) in the management of
hypertension. The recommendations were developed according to the GRADE methodology.
RESULTS:
Fifteen studies were included, comprising one meta-analysis, four randomized controlled
trials, six secondary analyses of randomized controlled trials and four observational studies.
Seven studies involved only older adults and eight studies reported subgroup analyses by age.
With regard to a composite endpoint (death, stroke or myocardial infarction) beta blockers
were associated with a higher risk of events then were other antihypertensive agents. Further,
beta blockers showed no benefit compared to other antihypertensive agents or placebo
regarding mortality. They appear to be less effective than other antihypertensive agents in
reducing cardiovascular events. Contradictory results were found regarding the effect of beta
blockers on stroke. None of the studies explored the effect on quality of life, hospitalisation,
functional impairment/status, safety endpoints or renal failure.
CONCLUSION:
The quality of current evidence to interpret the benefits of beta blockers in hypertension is
rather weak. It cannot be recommended to use beta blockers in older adults as first line agent
for hypertension