Aneurysms

Pharmacology II (UPHA 306)

Dr. Gregg Ward
October 14th, 2014

Collaborators:
Archaleck McDonald:

Causes and Drugs Used in Treatment

Antoine Russell:

Pathophysiology of Aneurysms

Marquel Wallace:

Introduction, and Table

Introduction
An aneurysm is a confined abnormal dilation of a blood vessel or the heart (Kumar,
Fausta, & Mitchell, 2007). Although it is confined or localized it often indicates the presentation
of more widespread arterial disease (Reid & Roberts, 2005). An artery is a type of blood vessel
that transports oxygenated blood from the heart to the peripheral body system. The main problem
that exists with an aneurysm is that if it becomes too large it can burst which leads to internal
bleeding, and become fatal. Aneurysms may be congenital or acquired.
There are different types of aneurysms, which are divided into two main classes. The first
type is Fusiform aneurysm of the abdominal aorta. This type usually occurs due to atheroma.
This often occurs below renal arteries and may also affect iliac arteries, especially in elderly
males. Several complications arises from fusiform aneurysm. They include:

Local pressure effects

Fatal retroperitoneal/ Intraperitoneal hemorrhage
Thrombosis with embolism to legs

The other type of aneurysm is saccular aneurysm. This type of aneurysm arises from the aorta
and is now usually due to atheroma, but in the past was due to syphilis. Complications of
saccular aneurysm include:

Pressure effects
o On nerves (e.g. recurrent laryngeal nerve paralysis
o On bones (e.g. vertebral, sterral, or rib erosion)
o On neighboring viscera (e.g. oesophagus heart, lungs)
Fatal hemorrhage

Apart from the two main types of aneurysms, other varieties of aneurysm exist, such as
dissecting aneurysm, berry aneurysm and microaneurysm. Dissecting aneurysm begin in the arch

of the aorta. Berry aneurysm occurs in the medium-sized vessels in the brain base. For example
on Circle of Willis (Kumar, Fausta, & Mitchell, 2007). This type of aneurysm is associated with
congenital deficiency of arterial media. Subarachnoid hemorrhage arises due to this rupture.
Microaneurysm is associated with hypertension and affects smaller arteries and arterioles,
especially in the brain. Here, this rupture causes inter-cerebral hemorrhage.
Generally aneurysms are classified according to shape and size. Saccular aneurysms
involve only a portion of the vessel wall. They are spherical outpouchings. These aneurysms
vary from 5-20 cm (in diameter), and contain thrombus (Reid & Roberts, 2005). Whereas,
fusiform aneurysms involve diffuse, circumferential dilation of a long vascular segment. They
can go up to 20cm in diameter and vary in length.
Pathophysiology
As stated earlier there are different types of aneurysms that can occur in the body and are
classified depending on the location of the aneurysm. In this part of the paper, we will be looking
into the pathophysiology of the different type of aneurysms and also the different factors that
contribute to aneurysms being formed with in the body.
Intracranial Aneurysms
Intracranial aneurysms can be classified into three different categories which are saccular,
fusiform and dissecting which saccular being 90 percent of all cranial aneurysms and also
responsible for most of the morbidity and mortality caused by subarachnoid hemorrhaging
(Vega, Kwoon & Lavine 2002). Saccular aneurysms are developed by defects in the muscular
layer of arteries. In the internal elastic membrane, alternations are thought to weaken the blood
vessels within the intracranial and prove them to be less resistance to changes in different

intraluminal blood pressures within the cerebral hemispheres. This most often occurs in at the
sites of vessel bifurcation where the blood flow is more erratic and forces against the arterial wall
are at their greatest. Saccular aneurysm often occurs more frequently in the first and second order
arteries beginning from within the circle of Willis at the base of the brain. Within the intracranial
30 percent of patients often suffer from more than one type of aneurysm at a time (Vega, Kwoon
& Lavine, 2002).
Fusiform aneurysm another type of aneurysm that occurs within the brain is developed
from cerebral arteries that are ecstatic and also tortuous and can occur most often in the
vertebrobasilar system. Patients who suffer from this type on intracranial aneurysms often show
symptoms of cranial nerve or brainstem compression (Vega, Kwoon & Lavine, 2002).
Lastly, dissecting aneurysms that occur in the intracranial and can be the result of medial
necrosis or a traumatic tear of an artery. Just like with in other parts of the body dissecting
aneurysms are caused by false lumen when the true lumen has collapsed upon itself with in the
intracranial (Vega, Kwoon & Lavine, 2002).
Abdominal Aortic Aneurysms
Abdominal aortic aneurysms occur when major structural proteins of the aorta fail. The
reason to why these structural proteins fail is still unknown but it can be said that a genetic
predisposition does exist. Abdominal aortic aneurysms are dilation in the blood vessel walls but
they occur after the degeneration of the media of these walls. When this happens degeneration
occurs and caused widening of the vessel lumen and structural integrity is also compromised.
Also a research program, done by the US National Heart, Lung and Blood institute also
found and identified the mechanisms as important factors in the development of Abdominal

Aortic aneurysms which are Proteolytic degradation of the aortic wall, Inflammation and
immune responses, biomechanical wall stress and molecular genetics. When looking at surgical
specimens of abdominal aortic aneurysms different similarities are present as stated from the
mechanism that can cause it which is Inflammation with infiltration by lymphocytes and
macrophages, thinning of the media and lastly marked loss of elastin (Pearce, 2014).
Renal Artery Aneurysms
Just like other aneurysms, Renal artery aneurysms occur with a weakening then dilation
of the layers of the arterial wall but within the renal artery. Fibro muscular Dysplasia can occurs
or otherwise known as FMD weakening the wall of the can be cause of the aneurysm within the
renal aneurysms. Other conditions can also cause the formation of the aneurysms like the
autosomal dominant other known as Ehlers-Danlos which is a Type 3 Procallagen deficiency
which can lead to weakening and therefore dissections and aneurysms with thin the renal artery
(Gates, 2013).
Causes
Aneurysms may be due to: acquired diseases of vessel wall such as atheroma, arthritis,
syphilis, congenital weakness (berry aneurysm); hypertension; trauma. The blood pressure
pushing against the artery walls, along with damage to the walls can cause an aneurysm
(National Heart, Lung and Blood Institute, 2012). Many conditions and factors can damage and
weaken the walls of the aorta and cause aortic aneurysms. These include: aging, smoking, high
blood pressure, and atherosclerosis.
Rarely, bacterial (syphilis)/fungal infections cause mycotic aneurysms. In order for this
type of aortic aneurysm to occur the infection must be very deep and severe. Diseases that causes

inflammation of the blood vessels (vasculitis) also cause aortic aneurysms. Another cause of
aneurysms is family history. Certain aneurysms may be inherited. For example, Aortic
Abdominal Aneurysms are likely to run in families. Men in these affected families are at higher
risk for developing these aneurysms than women (MediResource, 2014).
Certain genetic factors also play a role in the development of thoracic aortic aneurysms.
Conditions such as, Marfan syndrome, Loeys-dietz syndrome, Enters-Danlos syndrome and
Turner syndrome, weaken the bodys connective tissues and damage the aorta. Persons afflicted
with these disease states, tend to develop aneurysms at an earlier age than other people, and are
at risk for higher rupture and dissection (MediResource, 2014). Trauma e.g. car accidents also
cause thoracic aortic aneurysms.
Two Drugs Used in the Treatment of Aortic Abdominal Aneurysm
Sodium Nitroprusside
Sodium Nitroprusside, as recently learned in Pharmacology II class, is a parenteral vasodilator.
Its mechanism of action involves the relaxation of vascular smooth muscle to reduce afterload
and preload by producing NO. This drug dilates both arteries and veins. It is also beneficial for
inhibiting platelet aggregation. This drug is not suitable for direct injection, and therefore it
requires dilution prior to infusion (Pearce & Baldwin, 2014). Side effects of this drug includes:
cyanide toxicity, arrythmiasis, excess hypotension and death (Ravindra & Campbell, 2014).
Morphine

Drug

Onset

Duration

Time to Peak
Serum
Concentratio
n

Average
Bioavailab
ility

Volume
of
Distribut
ion

Nitroprusside

< 2 mins

1-10
mins

Almost
Immediate

Low
Bioavailabi
lty

0.25 L/kg

PO: < 60 mins

PR: 20-60mins
SC: 50-90mins
IM: 30-60mins
IV: 20mins

PO:20IV:
40%
1PR:
36- 4.7L/kg
71%
IV/M100%

Brand
Name:
Nitropress
Morphine

PO:
4 hrs
Brand
15-30 mins (Immedia
Names:
IV: <5mins te
MS Contin
release)
Avinza
Depodur
Duramorph
Inumorph
Astramorph
Kadian

Half-Life Fraction
Excreted
Unchang
ed in the
Urine
Parent
N/A
Drug:
half-life
takes 2
mins
Immediat
e
Release:
(2-4hrs)
Avinza
(24hrs)
Kadian
(1113hrs)

Morphine is an analgesic of opiate receptors. It is classifies as a narcotic agonist. Opioids cause

hyperpolarization of nerve cells, inhibition of nerve firing and presynaptic inhibition of
transmitter release (e.g. Acetylcholine, Norepinephrine, Serotonin, and Glutamate) (Ravindra &
Campbell, 2014). It inhibits the ascending pathway which leads to change in response to pain.
This means that it works in the brain to change how the body responds to pain. This drug
produces analgesia, respiratory depression and sedation. It also suppresses cough by acting
centrally in the medulla. Morphine is clinically used to help relieve ongoing pain (moderatesevere). The use of this drug can be dangerous if not taken as prescribed. Morphine (opoid) has a
high risk of addiction, abuse, and misuse, which leads overdose and death (Pearce & Baldwin,
2014). Side effects of this drug includes: behavioral restlessness, respiratory depression, nausea

2-12%

and vomiting, increased intracranial pressure, postural hypotension, constipation, urinary

retention, and itching around the nose.
References
Gates, L. (October 3, 2013). Renal Artery Aneurysm. Retrieved October 11, 2014, Retrieved
from: http://e.medicine.medscape.com/article/463015-overview#a0104
Isselbacher, E.M. (2005). Thoracic and Abdominal Aortic Aneurysms. Contemporary Reviews
in Cardiovascular Medicine, 111. Retrieved from:
< http://aje.oxfordjournals.org/content/154/3/236.full>
Kumar, V., Abbas, A.K., Fausto, N. & Mitchell, R.N (2007). Robbins Basic Pathology.
Aneurysms and Dissection. Philadelphia: Saunders Elsevier Inc.
MediResource (2014). Aneurysm: Brian aneurysm, Aortic Aneurysm. Retrieved October
12, 2014, from:
<https://www.google.bs/url?
sa=t&rct=j&q=&esrc=s&source=web&cd=10&ved=0CHYQFjAJ&url=http%3A%2F
%2Fchealth.canoe.ca%2Fchannel_condition_info_details.asp%3Fdisease_id
%3D237%26channel_id%3D2111%26relation_id
%3D84973&ei=C645VJuSENOQgwTbtoGwAQ&usg=AFQjCNEjs3zfQ_I3cq6Op4mMvmIJDk74Q>
National Heart, Lung and Blood Institute. (2012). Aneurysms. Retrieved on October 12, 2014.

Retrieved from:
<http://www.nhlbi.nih.gov/health/health-topics/topics/arm/printall-index.html>
Ravindra, S. & Campbell, S. (2014) UTECH: Pharmacology II Manual. Jamaica: University of
Technology
Reid R., & Roberts, F., (2005). Pathology Illustrated. Cardiovascular Diseases-Aneurysms. Great
Britain: Elsevier Inc.
Pearce, W.H, & Baldwin, C. (August 5, 2014). Abdominal Aortic Aneurysm Medication.
Retrieved October 9, 2014, from:
< http://emedicine.medscape.com/article/1979501-medication#2>
Singh, K., Bonaa, K.H., Jacobsen, B.K., & Solberg, S. (January 17, 2001). Prevalence of and
Risk Factors for Abdominal Aortic Aneurysms in a Population Based Study. American
Journal of Epidemiology. 154 (3). Retrieved from:
< http://circ.ahajournals.org/content/111/6/816.full>
Vega, C., Kwoon, J.V. & Lavine S. D. (August 15, 2002). Intracranial Aneurysms: Current
Evidence and Clinical Practice. American Family Physician. 66(4). Retrieved from:
<http://www.aafp.org/afp/2002/0815/p601.html>

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