OFF- LABEL USES

OF
CARDIOVASCULA
R DRUGS
Off-Label uses:

■ It’s mean unapproved indication

■ Population
■ Or unapproved dosage form
■ Dosage
■ Un usual uses of common drugs given flexibility to deal with drugs in research reang
To wards a new ways to the effect of medication
Diltiazem

■ is a calcium channel blocker medication used to treat high blood pressure, angina, and

certain heart arrhythmias
■ The synthesis of diltiazem can be obtained by oxidizing N-(N,N-dimethylethanamine)-
4-aminophenol and adding 3-mercaptopropionic acid via a Michael reaction.
■ Mechanism of Action

Primarily, diltiazem inhibits the inflow of calcium ions into the cardiac, smooth
muscle during depolarization. Reduced intracellular calcium concentrations
equate to increased smooth muscle relaxation resulting in arterial vasodilation
and, therefore, decreased blood pressure.
Off-Label uses

1. Anal fissures
■ Topical cream with or without lidocaine
By relaxes the smooth muscles around the rectum and promotes blood flow to help the
growth of new skin over the tear in the lining of rectum
And reduces anal pressure lead to decrease pain and spasm
■ Prepared by mix 600 mg of diltiazem in 30 g of petroleum jelly
2- migraine prophylaxis

■ By
1. Vasodilation effects
2. Antispasmodic effects
3. Action against the cellular consequences of brain hypoxia
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3_ myopathic
■ Cramps in lowe leg related to rest
■ Myopathic neurologic and metabolic most cases of leg cramps are idiopathic
4- pulmonary hypertension

As combinations therapy
Once daily doses of nifedipine 120 to 240 mg
Diltiazem 540to900 mg and amlodipine 2.5 mg to 40 mg

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5_ PROTEIN URIA
Associated with diabetic nephropathy
By vasodilation and increase reabsorption in kidney
Nifedipine

■ is a calcium channel blocker medication used to manage angina, high blood pressure

■ Nifedipine is a calcium channel blocker. Although nifedipine and other 
dihydropyridines are commonly regarded as specific to the L-type calcium channel,
they also possess nonspecific activity towards other 
voltage-dependent calcium channels.[22][23]
■ Nifedipine has additionally been found to act as an antagonist of the 
mineralocorticoid receptor, or as an antimineralocorticoid.
Off- label uses

■ 1 as tocolytic in premature labor

■ By prevent contraction it’s blocks the inter calcium into certain tissue relaxation the
uterine muscles
■ Intinal dose 20 mg orally if contraction persist after 30 minutes further 20 mg orally
■ And give further two dose maintenance 20 -40 mg four times daily for up 48 hour
■ Maximal dose is 160 mg per day
■ ( drug of choice)
2 – treatment of Raynaud disease

■ By makes blood vessels relax and widen to help blood flow to fingers and toes
■ Dose 10 - 30 mg 3 times daily orally
3 _ Achalasia
Achalasia is a rare disorder that makes it difficult for food and liquid to pass from
the swallowing tube connecting your mouth and stomach (esophagus) into your
stomach. Achalasia occurs when nerves in the esophagus become damaged.
■ Symptoms include trouble swallowing heart burn and chest pain
Sublingual administration of nifedipine in patients with achalasia is very useful way
of medical treatment in two respects, 1) nifedipine decreases LESP, and 2)
sublingual administration does not need to pass through the drug through
esophagogastric junction which pressure is abnormally high in achalasia patients
4- high altitude pulmonary edma

■ In high-altitude pulmonary edema (HAPE), it's theorized that vessels in the

lungs constrict, causing increased pressure. This causes fluid to leak from the
blood vessels to the lung tissues and eventually into the air sacs.
■ High-altitude pulmonary edema (HAPE) is a life-threatening form of non-
cardiogenic pulmonary edema that occurs in otherwise healthy people at altitudes
typically above 2,500 meters (8,200 ft).[2] However, cases have also been reported
between 1,500–2,500 metres or 4,900–8,200 feet in more vulnerable subjects.
■ Nifedipine act by reduced intracellular calcium reduces peripheral arterial vascular
resistance and dilation of coronary arteries leading to reduction in systemic blood
pressure and increased myocardial oxygen delivery
Distal ureteric calculus

■ Ureterolithiasis or ureteric calculi are stones that form in or travel down to the
ureters, which are the slender muscular tubes that connect the kidneys to the
urinary bladder.
■ Treatment During the procedure, the surgeon will insert the ureteroscope into
your urethra and through the urinary tract until the stone is located. Once the
surgeon can see your stone, he or she can use a tool to either grab the stone
and remove it or to break it into tiny pieces you will be able to pass when you
urinate.
■ Nifedipine uses for treatment renal colic type abdominal pain
By smooth relaxation in ureteral tract
Propranolol

■ Mechanism of actionEdit
■ Propranolol is a non-selective beta receptor antagonist. [55] This means that it does not have
preference to Beta-1 or Beta-2 receptors. It competes with sympathomimetic
neurotransmitters for binding to receptors, which inhibits sympathetic stimulation of the
heart. Blockage of neurotransmitter binding to beta 1 receptors on cardiac myocytes
inhibits activation of adenylate cyclase, which in turn inhibits cAMP synthesis leading to
reduced PKA(Protein Kinase A) activation. This results in less calcium influx to cardiac
myocytes through voltage gated L-type calcium channels meaning there is a decreased
sympathetic effect on cardiac cells, resulting in antihypertensive effects including reduced
heart rate and lower arterial blood pressure. [63] Blockage of neurotransmitter binding to B2
receptors on smooth muscle cells will increase contraction, which will increase
hypertension.
■ Pharmacokinetics
■ Propranolol is rapidly and completely absorbed, with peak plasma levels achieved about
1–3 hours after ingestion. More than 90% of the drug is found bound to plasma protein
in the blood.[63] Coadministration with food appears to enhance bioavailability.[64]
 Despite complete absorption, propranolol has a variable bioavailability due to
extensive first-pass metabolism. Hepatic impairment therefore increases its
bioavailability. 
Usual uses

■ Atrial fibrillation and coronary artery disease

■ Improve Mortality and morbidity in those with hypertension complicated with heart
failure angina
Off-Label uses

■ Performance anxiety
Performance anxiety is exactly what it sounds like — a form of anxiety that develops before and during public
performances If you’re prone to performance anxiety, you may feel apprehensive and fearful before you speak in front of a
crowd, perform using a musical instrument, present something in front of a judge or simply perform any type of task in
public.
--‐------/

■ propranolol prevents the effects of stress hormones such as epinephrine and norepinephrine (also called noradrenaline)
from stimulating your heart and other organs.
■ Stress hormones are responsible for many of the physical effects of anxiety. For example, high levels of norepinephrine
are associated with elevated blood pressure, a rapid heart rate and an increase in physical activity.
■ While medications like alprazolam act as a “calm” button for your entire body, propranolol works more like a “stop”
button for the physical symptoms of performance anxiety. 
■ Propranolol works quickly. Propranolol can be taken one hour before it’s required,
such as before a speech, presentation or other performance. There’s no need to use
propranolol for several weeks in order to access its anti-anxiety effects.
■ Propranolol has minimal impact on cognitive function. Unlike other anti-anxiety
medications, which can temporarily affect your thinking, propranolol does not reduce
your mental alertness or cognitive function
anxiety – 40mg taken once a day which can be increased to 40mg taken 3 times a day
2- Thyroid storm

■ Dose
■ 10mg to 40mg, taken 3 or 4 times a day
■ Because it’s lipophlic so it can inter brain to reduce of anxiety and it’s act on heart
prevent palpitations and it’s help converted T4 to T3
Migraine prophylaxis

■ The way the drug helps to prevent migraine headaches is still not well-known. It is
believed that propranolol helps stabilize the blood vessels in the brain, preventing their
dilation.
■ In addition, the drug may reduce the excitability of the brain as well as improve patients'
anxiety, helping decrease the frequency of the migraines. Beta blockers also stabilize
serotonin levels (fluctuating serotonin levels are associated with migraine
■ Dose 80 mg divided 6- 8 hour and may be incresed to 20 – 40 mg daily Not exced 240
mg
Portal hypertension

■ Its non selective B blockers has been shown to be effective for the prevention of varices
bleeding is widely used as pharmacotherapy in patients with cirrhosis
----///__
Neuroleptic induced akathisia
Restless leg syndrome
Restless legs syndrome (RLS) is a condition that causes an uncontrollable urge to
move your legs, usually because of an uncomfortable sensation. It typically
happens in the evening or nighttime hours when you're sitting or lying down.
Moving eases the unpleasant feeling temporarily.
■ Both clonidine and propranolol have been reported as being useful in treating
RLS symptoms.
PLMD

■ Wich is distinctive rhythmic pattern of increased leg activity ( clonidine and

propranolol)
■ ---'--’----
■ Infantile hemangioma
Propranolol oral solution is used to treat proliferation infantile hemangioma benign non
cancerous growths or tumors appearing on or under the skin shortly after birth in infants
5week to 5 months of age
It works by narrowing the blood vessels already formed and by preventing new ones from
growing
■ Oral solution is usually taken twice daily during or immediately after meal

■ PRAZOSIN
■ Non selective a blocker
■ Treatment hypertension alone or combinations
 It is a less preferred treatment of high blood pressure because hypotension occurs
Off-Label uses

1. Benign prostatic hypertrophy

2. Raynaud phenomenon
3. Pheochromocytoma
4. Post traumatic stress disorder PTSD associated nightmare
5. Poisoning due to scorpion venom
Spironolactone

■ is a medication that is primarily used to treat fluid build-up due to heart failure, 

liver scarring, or kidney disease.[4] It is also used in the treatment of high blood pressure
, low blood potassium that does not improve with supplementation, Spironolactone is
used primarily to treat heart failure, edematous conditions such as nephrotic syndrome
 or ascites in people with liver disease, essential hypertension, 
low blood levels of potassium, secondary hyperaldosteronism (such as occurs with 
liver cirrhosis), and Conn's syndrome (primary hyperaldosteronism)
Off-Label uses

1. Treatment acne in women is aldosterone antagonists with anti androgenic prop6 the
mechanism of action includes competition for the androgen receptor suppression of
cytochrome p450 and inhibitor of sterolidogenesis as well as reduction in 5 a reductase
activity Also decrease sebumproduction
2. Androgen excess syndrome hirsutism
3. Polycystic ovary syndrome
4. Female pattern hair loss (androgenic alopecia)