Drugs for peripheral vascular

diseases (CV-Ph-005)

Learning Objectives
Outline the pharmacological concepts of drugs used in
peripheral vascular diseases
Peripheral vascular diseases
Occlusive (Buerger’s disease with intermittent claudication
of legs),
mainly vasospastic (Raynaud’s phenomenon with episodic
blanching ± cyanosis of fingers followed by hyperaemia),
Both as in arteriosclerotic/diabetic vascular insufficiency,
• Clinical presentation --- ischaemic leg ulcers, frost bite,
gangrene, cerebrovascular inadequacy, etc.
• Increased cardiovascular risk is associated with all PVDs.
• When atheroma involves peripheral arteries, the first symptom is
usually pain in the calves on walking (claudication), followed by pain
at rest, and in severe cases gangrene of the feet or legs. Other
vascular beds (e.g. coronary, cerebral and renal) are often also
affected by atheromatous disease in patients with peripheral vascular
disease. Treatment is mainly surgical, combined with drugs that
reduce the risk of ischaemic heart disease and strokes. Drug
treatment includes antiplatelet drugs (e.g. aspirin, clopidogrel), a
statin (e.g. simvastatin) and an ACEI
Measures to be taken in peripheral vascular diseases
Risk factor management Drugs
• Smoking cessation, • Antiplatelet drugs
• BP normalization, • Vasodilators
• diabetes control, • CCBs, α blockers

• weight management, • Cilostazol, Pentoxiphylline

• exercise training • Statins
Drugs to be avoided/contraindicated
• Drugs to be avoided in peripheral vascular disease --- β blockers
• Drugs contraindicated in peripheral vascular diseases --- ergot
alkaloids, Tryptans
Drugs that worsen the peripheral vascular
diseases
• β blockers
• Cold hands and feet, worsening of peripheral vascular disease are
noticed due to blockade of vasodilator β2 receptors.
• Nonselective β blockers can induce peripheral vasoconstriction.
Clinical symptoms can range from a sensation of cold extremities in
individuals with otherwise normal circulation, to worsening of
claudication in patients with peripheral vascular disease.
• Beta1-selective blockers are generally better tolerated and can be
used with caution.
Drugs contraindicated in peripheral vascular
diseases
• The ergot derivatives are best avoided in patients with peripheral
vascular disease.
• Ergotamine and dihydroergotamine are contraindicated in patients with
angina and peripheral vascular disease because they are significant
vasoconstrictors.
• Triptans
• Tobacco is particularly harmful in hypertensive patients. Many
patients with peripheral vascular disease experience an exacerbation
of symptoms with smoking.
Alpha-receptor–blocking drugs
• Alpha-receptor–blocking drugs do not seem to be effective in
the treatment of peripheral vascular occlusive disease
characterized by morphologic changes that limit flow in the
vessels.
• Occasionally, individuals with Raynaud phenomenon and
other conditions involving excessive reversible vasospasm in
the peripheral circulation do benefit from prazosin or
phenoxybenzamine, although calcium channel blockers may
be preferable for most patients.
• Alpha-receptor–blocking drugs
• Buerger’s disease --- occlusive disease characterized by
morphologic changes that limit flow in the vessels ------ No
role
• Raynaud’s phenomenon and other conditions involving
excessive reversible vasospasm in the peripheral
circulation do benefit from alpha blockers
• CCBs
• Preferred
Anti platelet drugs
• Clopidogrel --- oclusive peripheral vascular disease, the dosage is 75
mg/d.
• Aspirin/clopidogrel may produce some improvement in intermittent
claudication and reduce the incidence of thromboembolism.
 Cilostazol is used to treat intermittent
claudication
•Phosphodiesterase inhibitor that
promote vasodilation and inhibition of
platelet aggregation
Fibrinolytic drugs
• Fibrinolytic drugs by the intravenous route --- intra-arterially,
especially for peripheral vascular disease
• Pentoxiphylline is mainly used in intermittent claudication (calf pain on
walking) due to occlusive vascular disease (Buerger’s disease); walking
distance is increased

• Cilostazole is indicated for intermittent claudication in patients with no rest

pain or heart failure.

• CCBs like nifedipine and α blockers like prazosin, phenoxybenzamine have

been used in PVDs. ---------------------------------- However, no vasodilator can
overcome organic obstruction. They obviously are more useful when
vasospasm is involved, e.g. in Raynaud’s phenomenon.
R&D
• When atheroma involves peripheral arteries, the first symptom is usually pain in the calves on walking (clau­
dication), followed by pain at rest, and in severe cases gangrene of the feet or legs. Other vascular beds
(e.g. coronary, cerebral and renal) are often also affected by atheromatous disease in patients with
peripheral vascular disease. Treatment is mainly surgical, combined with drugs that reduce the risk of
ischaemic heart disease and strokes. Drug treatment includes antiplatelet drugs (e.g. aspirin, clopidogrel;
see Ch. 24), a statin (e.g. simvastatin; see Ch. 23) and an ACEI (e.g. ramipril; see p. 274-275).
• RAYNAUD’S DISEASE
• Inappropriate vasoconstriction of small arteries and arte­rioles gives rise to Raynaud’s phenomenon
(blanching of the fingers during vasoconstriction, followed by blue­ness owing to deoxygenation of the static
blood and redness from reactive hyperaemia following return of blood flow). This can be mild, but if severe
causes ulcera­tion and gangrene of the fingers. It can occur in isolation (Raynaud’s disease) or in association
with a number of other diseases, including several so-called connective tissue diseases (e.g. systemic
sclerosis, systemic lupus erythematosus). Treatment of Raynaud’s phenomenon hinges on stopping
smoking (crucially) and on avoiding the cold; β-adrenoceptor antagonists are contraindicated. Vasodilators
(e.g. nifedipine; see Ch. 21) are of some benefit in severe cases, and evidence from several small studies
suggests that other vasodilators (e.g. PGI2, CGRP) can have surprisingly prolonged effects, but are difficult
to administer.
• Peripheral Vascular Disease
• A number of studies have investigated the use of PGE1 and PGI2 compounds in Raynaud phenomenon and
peripheral arterial disease. However, these
• studies are mostly small and uncontrolled. Currently, these therapies do not have an established place in the
treatment of peripheral vascular disease.
• Administration of fibrinolytic drugs --- These drugs are also given intra-arterially, especially for peripheral
vascular disease

• Clopidogrel 75 mg in pvd

• Dietary measures are initiated first—unless the patient has evident coronary or peripheral vascular disease—
Page 601 tripathy
• Dietary measures are initiated first—unless the patient has evident coronary or peripheral vascular disease—
• KD Tripathy
• Phenoxybenzamine is used primarily in phcochromocytoma, occasionally m peripheral vascular disease.
• Cold hands and feet may be noticed during winter due to blockade of vasodilator p2 receptors. Peripheral
vascular disease is worsened.
• Peripheral vascular disease Aspirin/ c lopidogrel may produce some improvement in interm itte nt c la ud
icatio n and reduce the incidence of thromboembolism.
• the benefits may exceed the risks, eg, in patients with myocardial
• infarction. Beta1-selective antagonists may be preferable in patients with diabetes or peripheral vascular
disease when therapy with a β blocker is required

• In general, β1-selective antagonists are preferred in patients with asthma, COPD, diabetes mellitus, or
peripheral vascular disease
Limitations of Non-selective β-Blockers
• By causing vasoconstriction (β2 is vasodilatory), these drugs can
worsen peripheral vascular disease (contraindicated in Raynaud’s
disease).
Cardioselective (Selective β1 ) β-Blockers
• These agents are preferred in patients with diabetes mellitus,
bronchial asthma, peripheral vascular disease or hyperlipidemia.
• All of the following are therapeutic uses of prazosin, except: (Recent
NEET Pattern Question) (a) Peripheral vascular disease (b)
Pheochromocytoma (c) Lupus erythematosus (d) Scorpion sting

• Ans. (c) Lupus erythematosus (Ref: KDT 8th/e p156-157) Prazosin is a

selective a1 blocker and can be used for treatment of
pheochromocytoma, peripheral vascular disease, benign hyperplasia
of prostate and hypertension. It is the drug of choice for scorpion
sting.
• After taking some drug for acute attack of migraine, a patient developed
nausea and vomiting. He also developed tingling and numbness in the
tip of the finger that also turned blue. Which of the following is the
most likely drug implicated in causing the above findings? (AI 2012) (a)
Dihydroergotamine (b) Sumatriptan (c) Aspirin (d) Butorphanol
• Ans. (a) Dihydroergotamine (Katzung 11th/e p289) This is a classical sign
of ergot induced vasoconstriction. Dihydroergotamine can be used for
acute attack of migraine and can result in these symptoms. Due to their
vasoconstricing potential, ergot alkaloids are contra-indicated in a
patient with peripheral vascular disease. These may also lead to
development of gangrene
• CCBs are especially suitable for elderly patients, patients with low renin
hypertension, patients with diseases like asthma, migraine or
peripheral vascular disease and in cases of isolated systolic
hypertension. DHPs are safe in pregnancy

• In hypertensive patients with peripheral vascular disease, calcium

channel blockers are recommended

• • In hypertensive patients with Raynaud’s phenomena and other

peripheral vascular diseases and migraine CCBs are especially suitable.
• Peripheral vasospasm is observed with which of the following
antiParkinsonian drugs? (AIIMS May 2014) (a) Ropinirole (b) Levodopa
(c) Bromocriptine (d) Entacapone

• Ans. (c) Bromocriptine (Ref: KDT 8/e p191; Goodman and Gilman
12th/1114) Ergot derivatives like bromocriptine can lead to worsening
of vasospasm especially in patients of peripheral vascular disease due
to their strong vasoconstrictor activity.
Principals of pharmacology page 483
• Peripheral vascular disease is another relative contraindication to -
antagonist therapy; the concern in this circumstance is the potential or
antagonism o the 2 -adrenergic receptors that mediate dilation o
peripheral vessels. In clinical practice, however, this concern is rarely
justified. Furthermore, patients with peripheral arterial disease have an
extremely high risk o concomitant CAD and are there ore likely to
benefit significantly from β-antagonist therapy

• Page 417 --- Clopidogrel is approved or secondary prevention in patients

with recent myocardial in arction, stroke, or peripheral vascular disease.
Brody’s human pharmacology page 812
• Serious but rare cardiac events, including coronary artery vasospasm,
transient myocardial ischemia, atrial and ventricular arrhythmias, and
myocardial infarction, have been reported with triptans. Triptans alter
vascular tone, which can cause arterial vasospasms and hypertension,
and are contraindicated in patients with ischemic, cardiac,
cerebrovascular or peripheral vascular disease, or uncontrolled
hypertension.
• Page 1000-1001 --- common clinical problems and related goals for
vasodilator pharmacotherapy.
• Peripheral vascular disease --- Increase blood flow to ischemic tissues
Bennet
• Uses of α – blockers
• Peripheral vascular disease

• Page 402 --- Vasodilators in peripheral vascular disease

• Page 493 ---
TREATMENT OF CLAUDICATION AND
PERIPHERAL VASCULAR DISEASE page 295-- G & G
• Most patients with peripheral artery disease also have coronary
artery disease and the therapeutic approaches overlap
• Reductions in cardiovascular morbidity and mortality in patients with
peripheral arterial disease have been documented with antiplatelet
therapy, ACE inhibitors, and treatment o hyperlipidemia
• Risk actor and life style modifications (physical exercise,
rehabilitation, and smoking cessation) remain cornerstones o
therapy or patients with claudication
• Pentoxifylline and cilostazol are drugs used specifically or lower
extremity claudication. »
• Pentoxifylline is a rheological modifier that increases the
deformability of red blood cells. »
• Cilostazol is PDE3 inhibitor that inhibits platelet aggregation and
vasodilation by increasing intracellular cyclic AMP in many cells,
including platelets
Board review page 142
• Adverse effects. Nicotine use contributes to cancer of the lungs, oral
cavity, bladder, and pancreas; obstructive lung disease; coronary
artery disease; and peripheral vascular disease.
• Page 162 ---Aspirin has significantly greater antithrombotic activity
than other NSAIDs and is useful in preventing or reducing the risk of
myocardial infarction in patients with a history of myocardial
infarction, angina, cardiac surgery, and cerebral or peripheral vascular
disease
Kaplan
• Hypertension (HTN) is a major risk factor for stroke, heart failure,
renal disease, peripheral vascular disease, and coronary artery
disease.
• Which one of the following is the most appropriate drug to use for
the patient described in parentheses? A. Captopril (60-year-old
woman with diabetic nephropathy) B. Nitroprusside (50-year-old man
with BP of 140/95) C. Losartan (29-year-old pregnant woman) D.
Propranolol (40-year-old patient with peripheral vascular disease) E.
Milrinone (57-year-old patient with chronic CHF)
• . Answer: A. ACEIs slow the progression of diabetic nephropathy and
are indicated for management of HTN in such patients. Nitroprusside
is used IV in severe HTN or hyper¬tensive crisis, not for management
of mild-tomoderate HTN. Losartan, which blocks AT-1 receptors, is
associated with teratogenic effects during fetal development, as are
the ACEIs. Nonselective beta blockers are not ideal for patients who
suffer from peripheral vascular disease, diabetes, or asthma.
Milrinone, like most inotropes, is not useful long-term in CHF patients.
The drug has been shown to increase mortality with chronic use, and
thus is indicated for acute CHF. Digoxin is currently the only inotrope
used chronically.
Measures to be taken in peripheral vascular
diseases
• Smoking cessation,
• BP normalization,
• Antiplatelet drugs,
• diabetes control,
• statins,
• weight management,
• exercise training
• In addition, vasodilators and some other drugs have been used.