TEMA-18.

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Anónimo

Farmacología II

4º Grado en Farmacia

Facultad de Farmacia
Universitat de València

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PHARMACOLOGY OF VASCULAR INSUFFICIENCY, SHOCK AND HYPOTENSIVE STATES

PATHOPHYSIOLOGY - Defined as an inadequate blood flow

- Arterial insufficiency: arterial narrowing or obstruction, generally due to atheromatous
plaques, that reduces blood flow to the tissue, leading to hypoxia.
- Venous insufficiency: venous blood escapes from its normal antegrade path of flow and

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refluxes backward due to problems in the valves, causing congestion. It manifests with various
veins

TYPES AND CAUSES

- Both types of vascular insufficiencies lead to chronic non healing skin ulcerations, which
can be infected if they are not properly treated.

OBJECTIVES AND THERAPY Objectives:

- To prevent, suppress or return to normal the obstructions of vascular lumen.

- To improve reversible lesions originated at the corresponding organ.

Therapy:

- Patient education: exercise, proper diet, quit smoking and control of predisposing diseases
- Surgery

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 - Pharmacologic treatment:

- For the predisposing disease: antihypertensives, antihyperlipidemics, antidiabetics.

- Specifics: antiplatelets, anticoagulants, vasodilators, hemorheologic

DRUGS Arterial:

- ACE Inhibitors: RAMIPRIL (to treat predisposing disease)

- Calcium channel blockers: NIFEDIPINE, NIMODIPINE
- α-blockers: PRAZOSIN
- Stimulators of cellular aerobic metabolism: NAFTIDROFURYL
- Hemorheological: PENTOXIFYLLINE
- PDE III inhibitors: CILOSTAZOL
- Prostaglandins i.v.: ILOPROST
- Others

Venous insufficiency: venotonics.

DRUGS USEFUL FOR ARTERIAL INSUFFICIENCY

CALCIUM CHANNEL BLOCKERS (DHP) - They are used for acute problems of cerebral circulation (ischemia, spasms).
- NIFEDIPINE: treatment of Raynaud’s disease.
- NIMODIPINE: (prophylactic) treatment of migraine.

α-BLOCKERS - PRAZOSIN: it lowers neurogenic vasoconstriction in Raynaud’s disease. Its efficacy may
diminish after 2 months of treatment.

STIMULATORS OF CELLULAR AEROBIC - NAFTIDROFURYL is used for the treatment of cerebral and peripheral arterial insufficiency
METABOLISM (Raynaud’s and claudication), administered orally.
- Mechanism of action: increases the consumption and entry of glucose in the brain
through the stimulation of the enzyme succinate dehydrogenase, which participates in both the
Krebs cycle and the electron transport chain.
- Is a 5HT2 antagonist and a peripheral and cerebral vasodilator.

HEMORHEOLOGICAL - Refers to all active principles that favour blood circulation

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 PENTOXIFYLLINE does so by:

- Decreasing blood viscosity and increasing red cells deformability through an unknown
mechanism.
- Decreasing platelet aggregation by increasing cAMP in platelets.
- Favouring the formation of PGI2 in the vascular wall, which also decreases platelet
aggregation.
- Decreasing total systemic vascular resistance.
- It also enhances tissue oxygenation

PHOSPHODIESTERASE III INHIBITORS - CILOSTAZOL increases cAMP concentrations by inhibiting PDE III
- Inhibit platelet aggregation and induce vasodilation
- It is administered orally to treat intermittent claudication
- Contraindicated in HF.

PROSTAGLANDINS - ILOPROST is a PGI2 synthetic derivative

It is administered through i.v. infusion in severe cases, and it ameliorates the condition by:

- Strongly inhibits platelet aggregation.

- Shows certain fibrinolytic action.
- Induces intense arterial vasodilation.

OTHER MOLECULES: FROM PLANT ORIGIN - Smooth muscle relaxants: NICOTINIC ACID, PAPAVERINE, NITROGLYCERIN

Alkaloids with vasodilatory properties at cerebral level:

- VINCAMINE and DIHYDROERGOCRISTINE. Used for cerebral circulatory insufficiency in the

elderly.
- Ginkgo biloba extracts. Indicated for mild cerebral circulatory disorders (vertigos) and
extremities

DRUGS USEFUL FOR VENOUS INSUFFICIENCY

VENOTONICS AND CAPILLARY PROTECTORS - Flavonoids and other polyphenols: DIOSMINE, HYDROSMINE, TROXERUTIN, RUTOSIDE.

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 No se permite la explotación económica ni la transformación de esta obra. Queda permitida la impresión en su totalidad.
- Saponins: AESCIN, RUSCOGENIN.
- They promote venous return, thus they are used for the treatment of hemorrhoids and
varicose veins.

SULODEXIDE - Consists in a highly purified mixture of glycosaminoglycans

It improves hemodynamics through three main pharmacological mechanisms:

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- Antithrombotic: inhibits thrombin enzyme and factor Xa synthesis.
- Fibrinolytic: increases t-PA release and lowers PAI levels.
- Anti-varicose: decreases blood viscosity.

Indications:

- Intermittent claudication in peripheral arterial occlusive disease (stage II).

- Chronic venous insufficiency.
- Chronic venous ulcer.

TREATMENT OF SHOCK

CHARACTERISTICS - Is a syndrome of inadequate perfusion of vital organs

- Due to the lack of oxygen, organs switch to anaerobic metabolism, thus increasing lactate
levels and leading to a metabolic acidosis

Types:

- Hypovolemic
- Cardiogenic
- Endotoxic (septic)
- Neurogenic
- Traumatic
- Anaphylactic

TREATMENT - Ventilation, adequate posture.

- Restoration of volemia if the shock is hypovolemic, not in cardiogenic: electrolytic

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 solutions, blood or plasma, expanders of plasma
(dextrans).
- Improve cardiac output (+ inotropic): DIGOXIN,
DOBUTAMINE, DOPAMINE, ADRENALINE (only
in anaphylactic shock).
- Vasodilators (not used in hypovolemic):
α-blockers, β-agonists, nitrates and
MOLSIDOMINE (the latter two in cardiogenic
shock).
- Corticoids (in septic shock).

TREATMENT OF ORTHOSTATIC HYPOTENSION

CHARACTERISTICS - The causes must be determined: they can be hypovolemia, heart failure, endocrine
disorders or certain drugs.

General measures must be adopted:

- Avoid dehydration and lack of salt.

- Be seated some minutes before getting up from bed.
- Sleep with your head elevated

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 Pharmacological treatment:

- Fast acting: ETILEFRINE (α1-agonist) EFORTIL®. Anti-hypotensive sympathomimetic amine

used in asthenia and convalescences.
- Long term: FLUDROCORTISONE (mineralocorticoid) ASTONIN®.

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