International Journal of Pharmaceutical Sciences and Nanotechnology Volume 3 • Issue 1 • April – June 2010 Research Paper In vitro Passive and Iontophoretically Assisted Transport of Salbutamol sulphate through Hairless Mice Skin Abdul Faruk*, Gurpreet Singh and Mohan Paul Singh Ishar Department of Pharmaceutical Sciences, Guru Nanak Dev University,
and pHarmacological treatment
Cesare Gorruso, Hypertension: aetiology and pharmacological treatment Copyright 2013 Tangram Edizioni Scientifiche Gruppo Editoriale Tangram Srl – Via Verdi, 9/A – 38122 Trento www.edizioni-tangram.it – firstname.lastname@example.org Prima edizione: febbraio 2013, Printed in Italy In copertina: Blood Pressure Concept, backgroundstore – Fotolia.com Stampa su carta ecologica proveniente da zone in silvicoltura, totalmente priva di cloro. Non contiene sbiancanti ottici, è acid free con riserva alcalina.
and pHarmacological treatment
This abstract, dealing with heart and circulation, aims to provide clear information and practical advice on drugs and medicines that can be readily understood by a non-medical reader. It reflects current medical knowledge and standard medical practice and is intended to comple- ment and reinforce the advice to the doctor.
Heart and circulation
The blood transports oxygen, nutrients, and heat, carries chemical
messages in the form of hormones and drugs, and removes waste prod- ucts from cells for excretion, by the kidneys. It is pumped by the heart through the lungs, and then in a separate circuit to the rest of the body, including the brain, digestive organs, muscles, kidneys, and skin.
The heart is a pump with four chambers – two atria and two ventri- cles. The atrium and ventricle on the left side pump oxygenated blood to the body, while those on the right pump oxygenated blood to the lungs. Backflow of blood is stopped by one-way valves at the chamber exits. Arteries carry blood away from the heart. Their muscle walls are elastic, contracting and dilating in response to nerve signals. Veins carry blood back to the heart. Their walls are thinner and less elastic What can go wrong
The efficiency of the circulation may be impaired by weakening of the
heart’s pumping action (heart failure), too fast a heart rate (tachycardia), or irregularly of the heart rate (arrhythmia). In addition, the blood ves- sels may be narrowed and clogged by fatty deposits (atherosclerosis). This may reduce blood supply to the brain, the extremities (peripheral vascular disease), or the heart muscle (coronary heart disease and angina): these last disorders can be complicated by the formation of clots that may block a blood vessels. A clot in the arteries supplying the heart muscle is known as coronary thrombosis; a clot in an artery inside the brain (cerebral thrombosis) is the most frequent cause of stroke.
One common circulatory disorder is hypertension (abnormally high blood pressure), in which the pressure of circulating blood on the blood vessel walls is increased for reasons not yet fully understood; loss of elasticity of the vessels walls (arteriosclerosis) may be a factor. Several other conditions, such as migraine and Raynaud’s disease are caused by temporary alterations to blood vessel size.
Why drug are used
Because people with heart disease often have more than one problem,
several drugs may be prescribed at once. Many act directly on the heart to alter the heart rate and rhythm. These drugs are known as anti-ar- rhythmics; they include beta blockers and digoxin. Other drugs affect the diameter of the blood vessels by either dilating them (vasodilators) to improve the blood flow and reduce blood pressure, or by constrict- Drugs may also reduce blood volume an fat levels, and alter its clot- ting ability. Diuretics (used in the treatment of hypertension and heart failure) increase the body’s excretion of water. Lipid-lowering drugs re- duce the levels of cholesterol in the blood, thereby minimising the risk of atherosclerosis. Drugs to reduce blood clotting are administered if there is a risk of abnormal blood clots forming in the heart, veins, or arteries, drugs that increase clotting are given when the body’s natural Major drug grouPs
Digitalis is the collective terms for the naturally occurring substances (also called cardiac glycosides) found in the leaves of plants of the fox- glove family and used to treat certain heart disorders. The principal drugs in this group are digoxin and digitoxin. The former is more com- monly used because it is shorter acting and dosage is easier to adjust.
Why there are used
Digitalis drugs do not cure heart disease, but they improve the heart’s
pumping action and thereby relieve many of the symptoms that result from poor heart function. They are for treating conditions in which the heart beats irregularly or too rapidly, notably in atrial fibrillation, when it pumps too weakly (in congestive heart failure), or when the heart muscle is damaged and weakened following a heart attack.
Digitalis drugs can be used for a short period when the heart is working poorly but have to be taken indefinitely in many cases. Their effect do not diminish with time. In heart failure, these drugs are of- ten given together with a diuretic drug.
How they work
The normal heart beat results from electrical impulses generated in
nerve tissue within the heart. These impulses cause the heart muscle to contract and pump blood. By reducing the flow of electrical impulses in the heart, digitalis makes the heart beat more slowly.
The force with which the heart muscle contracts depends on chemi- cal changes in the heart muscle. By promoting these chemical chang- es, digitalis increases the force of muscle contraction each time the heart is stimulated. This compensates for the loss of power that occurs when some of the muscle is damaged following a heart attack. The stronger heart beats increases blood flow to the kidneys. This increases urine production and helps to remove the excess fluid that often ac- cumulates as a result of heart failure.
How they affect you
Digitalis relieves the symptoms of heart failure – fatigue, breathlessness,
and swelling of the legs – and increases your capacity for exercise. The frequency with which you need to pass urine is also increased initially.
risks and special precautions
Digitalis drugs can be toxic: if blood levels rise too high, symptoms
of digitalis poisoning (including nausea, appetite loss, vomiting, diar- rhoea, confusion, and visual disturbance) may occur. It is important to report any such symptoms to you doctor promptly. Digoxin is nor- mally removed from the body by the kidneys; if the kidney function is impaired, the drug is more likely to accumulate in the body and cause toxic effects. Digitoxin, which is broken down in the liver, is sometimes preferred in such cases. If liver function is severely impaired, digitoxin can accumulate after repeated dosage. Both digoxin and Digitoxin are more toxic when blood potassium levels are low. Potassium deficiency is commonly due to diuretics; the effects of both drugs and the blood potassium levels of people taking diuretics with digitalis drugs require careful monitoring. Potassium supplements may be required.
Beta blockers are drugs that interrupt the transmission of stimuli thor- ough receptors called beta receptors. The function that they block originate in the adrenal glands (and elsewhere), so the drugs are also sometime called beta adrenergic blocking agents. There are two types of beta receptors in the body: beta 1 and beta 2. beta 1 receptors are located mainly in the heart muscle; beta 2 receptors in the airways and blood vessels. Cardioselective drugs act mainly on beta 1 recep- tors; non-cardioselective drugs on both types. Used mainly in heart disorders, these drugs are occasionally prescribed for other conditions.
Why they are used
Beta blockers are used for treating angina, hypertension and irregular
heart rhythm. They are usually given after a heart attack to reduce the likelihood of abnormal heart rhythms or further damage to the heart muscle. Beta blockers are also prescribed to improve heart function in heart muscle disorders (which are called cardiomyopathies).
Beta blockers may also be given to prevent migraine headaches and they are sometimes prescribed to reduce the physical symptoms of anxi- ety. These drugs may be given to control symptoms of an overactive thy- roid gland. A beta blocker is sometimes given in the form of eye drops to lower the excessive fluid pressure inside the eye that occurs in glaucoma.
How to work
By occupying the beta receptors in different parts of the body, beta blockers nullify the stimulating action of norepinephrine (noradrena- line), the main “fight or flight” hormone. Blocking the transmission of signals through beta receptors produces a wide variety of benefits and side effects depending on the disease being treated.
Heart – Slowing of tile heart rate and reduction of the force of the heart beat reduces the workload of the heart, helping to prevent an- gina and abnormal heart rhythms. This action may worsen heart fail- Lungs – Constriction of the airways may provoke breathlessness in asthmatic people or those with chronic bronchitis.
Brain – Dilation of the blood vessels that surround the brain is inhib- Blood vessels – Constriction of the blood vessels may cause coldness of Blood pressure – The pressure is lowered due to reduction in the rate and force at which the heart pumps blood around the body.
Eye – Beta blocker eye drops reduce fluid production, lowering pres- Muscles – Muscle tremor caused by anxiety or overactivity of the thy- How they affect you
Beta blockers are taken to treat angina. They reduce the frequency and
severity of attacks. As part of the treatment for hypertension, they help to lower the blood pressure and thus reduce the risks that are associated with this condition. Beta blockers help to prevent severe attacks of ar- rhythmia, in which the heart beat is wild and uncontrolled.
Because beta blockers affect many parts of the body, they often pro- duce minor side effects. By reducing the heart rate and air flow to the lungs, they may reduce the capacity for strenuous exercise. This is unlikely to lie noticed by somebody whose physical activity was previously limited by heart problems, however. Many people taking these drugs experience cold hands and feet as a result of a reduction in the blood supply to the limbs. Reduced circulation can, rarely, lead to temporary impotence during treatment.
risks and special precautions
The main risk of beta blockers is that they may provoke breathing dif-
ficulties due to their blocking effect on beta receptors in the lungs. Cardioselective beta blockers act mainly on the heart and are thought to be less likely than non-cardioselective ones to cause such problems. But all beta blockers are prescribed with caution to people with asthma, bronchitis, or other forms of respiratory disease.
Beta blockers are not commonly prescribed to people with poor circu- lation in the limbs because they reduce blood flow and may aggravate such conditions. Large doses are not normally given to people subject to heart failure because they may further reduce the force of the heart beat, although small doses are helpful. Diabetics should be aware that they may notice a change in the warning signs of low blood sugar; in particular, they may find that symptoms such as palpitations and Beta blockers should not be stopped suddenly after prolonged use; this may provoke a sudden and severe recurrence of symptoms of the origi- nal disorder, or even a heart attack. The blood pressure may also rise markedly. When treatment with beta blockers needs to be stopped, the drugs should be withdrawn gradually under medical supervision.
Cardioselective – Atenolol, Betaxolol, Bisoprolol, Celiprolol, Esmolol,
Non-cardioselective – Acebutolol, Carvedilol, Labetalol, Nadolol, Ox- prenolol, Pindolol, Propranolol, Sotalol, Timolol.
Final Draft of the original manuscript: Jung, F.; Franke, R.-P.: Extreme reduction of the capillary lumen in segments of the venular legs of human cutaneous capillaries In: Microvascular Research (2009) Elsevier DOI: 10.1016/j.mvr.2009.02.010 Extreme reduction of the capillary lumen in segments of the venular legs of human cutaneous capillaries F. Jung1*, R.P. Franke1 1 GK