DIRECT-ACTING ADRENERGIC
AGONISTS
1)Phenylephrine
2)Midodrine
BY:
BHARGAVI CHIDAMBARAM
GROUP:1
PHENYLEPHRINE
Phenylephrine is
a medication primarily used as
a decongestant,
• to dilate the pupil,
• to increase blood pressure
• to relieve hemorrhoids.
Route of administration:
By mouth, in the nose, on
the eye, intravenous,
intramuscular
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PHARMACOKINETIC data:
Bioavailability
38% through GI tract
Protein binding
95%
Metabolism
Liver (oxidative deamination)
Onset of action
Very rapid (IV); within 20 min (by mouth)
Elimination half-life
2.1–3.4 h
Duration of action
Up to 20 min (IV); 4 hrs (by mouth)
[2]
Pharmacodynamics:
Phenylephrine is a sympathomimetic drug, which means that it mimics the actions of
epinephrine (commonly known as adrenaline) or norepinephrine. Phenylephrine selectively
binds to alpha-1 receptors which cause blood vessels to constrict.
Whereas pseudoephedrine causes both
• vasoconstriction and
• increase of mucociliary clearance
through its nonspecific adrenergic activity.
Phenylephrine's selective α-adrenergic agonism causes vasoconstriction alone, creating
a difference in their methods of action.
Medical uses
• Decongestant:Phenylephrine is used as a decongestant sold as an oral medicine or as
a nasal spray.
• Hemorrhoids:Hemorrhoids are caused by swollen veins in the rectal area. Phenylephrine
can be used topically to prevent symptoms of hemorrhoids.
• Pupil dilation:Phenylephrine is used as an eye drop to dilate the pupil to facilitate
visualization of the retina. Phenylephrine eye drops are applied to the eye after a topical
anesthetic is applied.
• Intraocular bleeding:Phenylephrine has been used as an intracameral injection into the
anterior chamber of the eye to arrest intraocular bleeding occurring during cataract and
glaucoma surgery.
• Vasopressor:Phenylephrine is commonly used as a vasopressor to increase the blood
pressure in unstable patients with hypotension, especially resulting from septic shock. Such
use is common in anesthesia or critical-care practices
• Priapism:Phenylephrine is used to treat priapism. It is diluted with normal saline and
injected directly into the corpora cavernosa. The mechanism of action is to cause
constriction of the blood vessels entering into the penis, thus causing decreased blood flow
and relieving the priapism.
SIDE EFFECTS:
Common side effects when taken by mouth or injected
include
 nausea,
 vomiting,
 headache and
 anxiety.
Use on hemorrhoids is generally well tolerated.
Severe side effects may include
 slow heart rate,
 intestinal ischemia,
 chest pain,
 kidney failure, and
 tissue death at the site of injection.
It is unclear if use during pregnancy or breastfeeding is safe.
MIDODRINE
Midodrine is used to treat low blood
pressure (hypotension). It works by
stimulating nerve endings in blood vessels,
causing the blood vessels to tighten. As a
result, blood pressure is increased.
a vasopressor/antihypotensive agent (it raises the
blood pressure). Midodrine was approved in the
United States by the Food and Drug
Administration (FDA) in 1996 for the treatment
of dysautonomia and orthostatic hypotension.
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PHARMACOKINETIC data:
The plasma levels of the prodrug peak after about half an hour, and decline with a
half-life of approximately 25 minutes, while the metabolite reaches peak blood
concentrations about 1 to 2 hours after a dose of midodrine and has a half-life of about
3 to 4 hours.
Bioavailability
93%
Protein binding
less than 30%
Metabolism
By the liver into an active metabolite, desglymidodrine
Route of transmission
mouth
Pharmacodynamics:
Midodrine is an orally active adrenergic agonist useful
in the treatment of hypotension.
Mechanism of Action:
Midodrine is a prodrug which forms an active metabolite, desglymidodrine, which is
an α1-receptor agonist and exerts its actions via activation of the alpha-adrenergic
receptors of the arteriolar and venous vasculature, producing an increase in vascular
tone and elevation of blood pressure. Desglymidodrine does not stimulate
cardiac beta-adrenergic receptors. Desglymidodrine diffuses poorly across the blood–
brain barrier, and is therefore not associated with effects on the central nervous
system.
MEDICAL USES:
•
It can reduce dizziness and faints by about a third, but can be limited by troublesome goose
bumps, skin itch, gastrointestinal discomfort, chills, elevated blood pressure while lying down,
and urinary retention.
•
A meta-analysis of clinical trials of midodrine or droxidopa in patients with low blood pressure
when standing found that midodrine increased standing blood pressure more
than droxidopa but that midodrine but not droxidopa increased the risk of high blood pressure
when lying down.
•
Small studies have also shown that midodrine can be used to prevent excessive drops in
blood pressure in people requiring dialysis.
• Midodrine has been used in the complications of cirrhosis. It is also used
with octreotide for hepatorenal syndrome; the proposed mechanism is constriction of
splanchnic vessels and dilation of renal vasculature. Studies have not been sufficiently well
conducted to show a clear place for midodrine.
SIDE EFFECTS:
• Headache
• feeling of pressure/fullness in
the head
• scalp tingling
• confusion/thinking abnormality
• dry mouth
• nervousness/anxiety
• rash
• vasodilation/flushing face
THANK YOU!!