Blood Regulation

The following mechanisms help regulate blood pressure:

The cardiovascular center provides a rapid, neural mechanism for the regulation of blood pressure by managing cardiac output or by adjusting blood vessel diameter. Located in the medulla oblongata of the brain stem, it consists of three distinct regions:

The cardiac center stimulates cardiac output by increasing heart rate and contractility. These nerve impulses are transmitted over sympathetic cardiac nerves.

The cardiac center inhibits cardiac output by decreasing heart rate. These nerve impulses are transmitted over parasympathetic vagus nerves.

The vasomotor center regulates blood vessel diameter. Nerve impulses transmitted over sympathetic motor neurons called vasomotor nerves innervate smooth muscles in arterioles throughout the body to maintain vasomotor tone, a steady state of vasoconstriction appropriate to the region.

The cardiovascular center receives information about the state of the body through the following sources:

Baroreceptors are sensory neurons that monitor arterial blood pressure. Major baroreceptors are located in the carotid sinus (an enlarged area of the carotid artery just above its separation from the aorta), the aortic arch, and the right atrium.

Chemoreceptors are sensory neurons that monitor levels of CO   2  and O   2. These neurons alert the cardiovascular center when levels of O   2  drop or levels of CO   2  rise (which result in a drop in pH). Chemoreceptors are found in carotid bodies and aortic bodies located near the carotid sinus and aortic arch.

Higher brain regions, such as the cerebral cortex, hypothalamus, and limbic system, signal the cardiovascular center when conditions (stress, fight‐or‐flight response, hot or cold temperature) require adjustments to the blood pressure.

The kidneys provide a hormonal mechanism for the regulation of blood pressure by managing blood volume.

The renin ‐ angiotensin ‐ aldosterone system of the kidneys regulates blood volume. In response to rising blood pressure, the juxtaglomerular cells in the kidneys secrete renin into the blood. Renin converts the plasma protein angiotensinogen to angiotensin I, which in turn is converted to angiotensin II by enzymes from the lungs. Angiotensin II activates two mechanisms that raise blood pressure:

Angiotensin II constricts blood vessels throughout the body (raising blood pressure by increasing resistance to blood

flow). Constricted blood vessels reduce the amount of blood delivered to the kidneys, which decreases the kidneys' potential to excrete water (raising blood pressure by increasing blood volume).

Angiotensin II stimulates the adrenal cortex to secrete aldosterone, a hormone that reduces urine output by increasing retention of H   2O and Na   +   by the kidneys (raising blood pressure by increasing blood volume).

Various substances influence blood pressure. Some important examples follow:

Epinephrine and norepinephrine, hormones secreted by the adrenal medulla, raise blood pressure by increasing heart rate and the contractility of the heart muscles and by causing vasoconstriction of arteries and veins. These hormones are secreted as part of the fight ‐ or ‐ flight response .

Antidiuretic hormone (ADH), a hormone produced by the hypothalamus and released by the posterior pituitary, raises blood pressure by stimulating the kidneys to retain H   2O (raising blood pressure by increasing blood volume).

Atrial natriuretic peptide (ANP), a hormone secreted by the atria of the heart, lowers blood pressure by causing vasodilation and by stimulating the kidneys to excrete more water and Na +(lowering blood pressure by reducing blood volume).

Nitric oxide (NO), secreted by endothelial cells, causes vasodilation. Nicotine in tobacco raises blood pressure by stimulating sympathetic

neurons to increase vasoconstriction and by stimulating the adrenal medulla to increase secretion of epinephrine and norepinephrine.

Alcohol lowers blood pressure by inhibiting the vasomotor center (causing vasodilation) and by inhibiting the release of ADH (increasing H 2O output, which decreases blood volume).

CVS Physical Examination

Cardiovascular (CVS) ExaminationThis is essentially an examination of the patient’s heart; however it is a complex examination which also includes examination of other parts of the body including the hands, face and neck.  The CVS examination aims to pick up on any cardiovascular pathology that may be causing a patient’s symptoms e.g. chest pain, breathlessness, heart failure.  This examination is performed on every patient that is admitted to hospital and regularly in clinics and general practice.

Like most major examination stations this follows the usual procedure of inspect, palpate, auscultate (look, feel, listen).  It is an essential skill to master and is often examined in OSCE’s.

Subject steps1. Wash your hands, introduce yourself to the patient and clarify their identity.  Explain

what you would like to do and obtain consent.  A chaperone should be offered for this examination

Introduce yourself to the patient

2. For this examination the patient should be on the bed with their trunk at 45degrees, they should be exposed from the waist up.

3. Begin by observing the patient from the end of the bed.

You should note whether the patient looks comfortable.

Are they cyanosed or flushed?

Is their respiration rate normal?

Are there any clues around the bed such as PCA machines, GTN sprays or an oxygen mask?

Comments should be provided to the examiner on each of these areas.

Observe the patient from the end of the bed

4. Inspect the patient’s hands. Initially note how warm they feel as this gives an indication of how well perfused they are. Particular signs which you should be looking for are nail clubbing, splinter haemorrhages, palmar erythema, janeway lesions, osler’s nodes, and nicotine staining.

Inspect the patient's hands

5. Take the radial pulse. It is not a suitable pulse for describing the character of the pulsation, but can be used to assess the rate and rhythm. At this point you should also check for a collapsing pulse – a sign of aortic incompetence.

Remembering to check that the patient doesn’t have any problems with their shoulder, locate the radial pulse and place your palm over it, then raise the arm above the patient’s head. A collapsing pulse will present as a knocking on your palm.

* Please note in the picture below, the examiner has incorrectly placed the dorsum of her fingers rather than her palm on the patient’s wrist, when assessing for collapsing pulse.

Take the radial pulse

Check for a collapsing pulse

6. Examine the extensor aspect of the elbow for any evidence of xanthomata.

7. At this point you should say to the examiner that you would like to take the blood pressure. They will usually tell you not to and give you the value.

8. Move up to the face. Look in the eyes for any signs of jaundice (particularly in the sclera beneath the upper eyelid), anaemia (in the conjunctiva beneath the lower eyelid) and corneal arcus. You should also look around the eye for any xanthelasma.

Inspect the eyes

9. Whilst looking at the face, check for any malar facies; look in the mouth for any signs of anaemia such as glossitis; check the colour of the tongue for any cyanosis; and around the mouth for any angular stomatitis – another sign of anaemia.

Inspect the mouth and tongue

10. Move to the patient’s neck to assess their jugular venous pressure (JVP).

Ask them to turn their head to look away from you. Look across the neck between the two heads of sternocleidomastoid for a pulsation. If you do see a pulsation you need to determine whether it is the JVP – if it is then the pulsation is non-palpable, obliterable by compressing distal to it, and will be exaggerated by performing the hepatojugular reflex.

Having warned the patient that it may cause some discomfort, press down on the liver. This will cause the JVP to rise further. If you decide the pulsation is due to the JVP, note its vertical height above the sternal angle.

Assess the patients jugular venous pressure

11. Move the examination to the chest, or precordium*. Start by inspecting the area, particularly looking for any obvious pulsations, abnormalities or scars, remembering to check the axillae as well.

*In some courses, precordium is spelt “praecordium”.

12. Palpation of the precordium starts by trying to locate the apex beat. Start by doing this with your entire hand and gradually become more specific until it is felt under one finger and describe its location anatomically.

The normal location is in the 5th intercostal space in the mid-clavicular line. However, it is not uncommon to not feel the apex beat at all.

Locate the apex beat

13. Now palpate for any heaves or thrills. A thrill is a palpable murmur whereas a heave is a sign of left ventricular hypertrophy. A thrill feels like a vibration and a heave feels like an abnormally large beating of the heart. Feel for these all over the precordium.

Palpate for any heaves or thrill

14. Auscultation is now performed for all four valves of the heart in the following areas:

Mitral valve – where the apex beat was felt.

Tricuspid valve – on the left edge of the sternum in the 4th intercostal space.

Pulmonary valve – on the left edge of the sternum in the 2nd intercostal space.

Aortic valve – on the right edge of the sternum in the 2nd intercostal space.

You should listen initially with the diaphragm noting how many heart sounds you can hear:

Are there any extra to the two normal sounds?

Are there any murmurs?

Are the heart sounds normal in character?

Can you hear any rub?

If you hear any abnormal sounds you should describe them by when they occur and the type of sound they are producing. Feeling the radial pulse at the same time can give a good indication as to when the sound occurs as the pulse occurs at systole. Furthermore, if you suspect a murmur, check if it radiates. Mitral murmurs typically radiate to the left axilla whereas aortic murmurs often radiate to the left carotid artery. You should therefore listen over here for any carotid bruits

You may also wish to listen with the bell of your stethoscope for any low pitched murmurs.

Mitral valve location

Tricuspid valve location

Pulmonary valve location

Aortic valve location

15. To further check for mitral stenosis you can lay the patient on their left side, ask them to breathe in, then out and hold it out and listen over the apex and axilla with the bell of the stethoscope.

Further check for Mitral Stenosis

16. Aortic incompetence can be assessed in a similar way but ask the patient to sit forward, repeat the breathe in, out and hold exercise and listen over the aortic area with the diaphragm.

Assess for Aortic incompetence

17. Finally you should assess for any oedema. Whilst the patient is sat forward, feel the sacrum for oedema and also assess the ankles for the same.

Feel the sacrum for oedema

Assess the ankles for oedema

18. Thank the patient and allow them to dress. Wash your hands and report your findings to the examiner.  If you do find any abnormalities you should indicate that you would like to arrange an ECG and an echocardiogram.

- See more at: http://www.osceskills.com/e-learning/subjects/cardiovascular-examination/#sthash.NAmNFd1q.dpuf

Procedure for Blood Pressure measurement

Procedureso To begin blood pressure measurement, use a properly sized blood pressure

cuff. The length of the cuff's bladder should be at least equal to 80% of the circumference of the upper arm.

o Wrap the cuff around the upper arm with the cuff's lower edge one inch above the antecubital fossa.

o Lightly press the stethoscope's bell over the brachial artery just below the cuff's edge. Some health care workers have difficulty using the bell in the antecubital fossa, so we suggest using the bell or the diaphragm to measure the blood pressure.

o Rapidly inflate the cuff to 180mmHg. Release air from the cuff at a moderate rate (3mm/sec).

o Listen with the stethoscope and simultaneously observe the sphygmomanometer. The first knocking sound (Korotkoff) is the subject's systolic pressure. When the knocking sound disappears, that is the diastolic pressure (such as 120/80).

o Record the pressure in both arms and note the difference; also record the subject's position (supine), which arm was used, and the cuff size (small, standard or large adult cuff).

o If the subject's pressure is elevated, measure blood pressure two additional times, waiting a few minutes between measurements.

Character of abnormal pulse

Character

This refers to an impression of the pulse waveform derived during palpation. Again, like volume, it needs to be examined at one of the large arteries.

Some abnormalities of pulse are described below.

Anacrotic pulse

This is seen in aortic stenosis, and refers to a pulse wave that is slow rising and generally flat volume associated with a low cardiac output and prolonged left ventricular ejection time. It suggests more severe aortic stenosis.

Bisferiens Pulse

This is a more difficult pattern to recognize and is best palpated over the carotid arteries. It is characterized by two systolic peaks and is seen in aortic regurgitation with or without aortic stenosis, and in some patients with hypertrophic cardiomyopathy.

Diacrotic pulse

This is also a pulse with two peaks- one in systole and the other in early diastole. It may be seen after the administration of nitrates in otherwise normal subjects, in febrile patients or in cardiac tamponade, congestive cardiac failure or shock, where a ventricular contraction delivers a small volume of blood into a non rigid arterial circulation.

Plateau pulse

A slow rising pulse with a flattened peak. This is seen in severe aortic stenosis

Collapsing pulse

This is a sign of aortic regurgitation, although it is sometimes also seen in patients with a hyperdynamic circulation and with a rigid arterial system. A stiff arterial system leads to an accentuated systolic peak in the peripheral pulses. The pulse has an early peak and then quickly falls away, giving it a tapping quality. The preferred method is to palpate the brachial pulse with the whole palm applied to the flexor aspect of the wrist (Your colleagues will be impressed with your clinical skills!). The collapsing pulse is also referred to as Corrigans or a water-hammer pulse, after a 19th century toy that was a vacuum tube containing water or mercury that was flipped creating a tapping or hammer sensation at the finger tips (a most arcane term – perhaps the Game-Boy rumble would be more recognizable today).. This accentuates the tapping quality of the pulse.

When a collapsing pulse is detected look for the following signs, although these are rarely seen in societies where advanced bacterial endocarditis is rare or where advanced cardiac imaging is performed for the mildest of valvular abnormalities.

Duroziez sign: Seen in severe aortic regurgitation. Place the diaphragm of the stethoscope over the femoral artery and press downwards. Initially a systolic murmur will be heard. Gradually increase pressure over the artery- a diastolic murmur will become evident also related to the flow reversal with profound aortic regurgitation. Now tilt the proximal edge of the stethoscope further downwards – if aortic regurgitation is present the systolic murmur is accentuated and the diastolic component is diminished. Now tilt the distal edge of the stethoscope downwards, the diastolic component will now be accentuated and the systolic reduced. This sign has a positive predictive value of close to 100% for aortic regurgitation, and can detect this lesion in some patients in whom it is not possible to hear the characteristic diastolic murmur on auscultation of the heart (e.g. acute aortic regurgitation due to acute bacterial endocarditis).

Traubes sign: A “pistol shot” sound heard over the femoral artery with the aid of a stethoscope. It is necessary to compress the femoral artery distal to the stethoscope head to produce the characteristic double tone sound.

Hills sign: This is a nonspecific sign of aortic regurgitation- it is also seen in other causes of a hyperdynamic circulation, such as thyrotoxicosis, beri-beri, or pregnancy. Check the blood pressures in the upper and lower limbs. If the pressure in the lower limbs exceeds that in the upper limbs by more than 20 mmHg then the sign is positive.

Quinkes sign: Pulsatile blanching of the nail bed

De Musset’s sign: Named after the famous French poet whose head nodded in time with his arterial pulsations due to his syphilis related aortic regurgitation.

Pulsus paradoxus

This is a misnomer. This is an exaggerated physiological phenomenon, rather than a paradox as the name implies. The volume of the pulse rises with expiration with the increase in stroke volume. and falls during inspiration When it is present, it suggests either restricted left ventricular filling during inspiration (associated with a mild increases in pericardial pressure and increased right heart filling that shifts the interventricular septum towards the left ventricle to impair left sided filling) such as in pericardial tamponade, or exaggerated changes in intrathoracic pressure as in

severe asthma.. Other causes of pulsus paradoxus include right ventricular infarction, large pulmonary embolus, and tense ascites or obesity.

Pulsus paradox is quantified by measuring a change in systolic blood pressure from inspiration to expiration of greater than 12 mmHg or 10% of systolic pressure. To successfully measure this, inflate the brachial cuff pressure to beyond systolic pressure. Palpate the brachial pulse and note the pressure it returns on expiration. Slowly decrease the pulse until you can identify the brachial pulse on inspiration. The difference in systolic pressure is used to estimate the magnitude of pulsus paradox.

Pulsus alternans

This abnormality describes a pulse that alternates between a larger and smaller volume on a beat to beat basis. This is a regular pulse and is seen in severe cardiac failure.

Pulsus bigeminus

This is often confused with pulsus alternans. Here after every other normal beat at a shorter than usual interval there is a lower volume beat, usually due to a premature ventricular contraction. It does not imply severe cardiac failure. A common cause now is Digoxin toxicity.

Jerky pulse

This is often seen in hypertrophic cardiomyopathy as the hypertrophied ventricle rapidly empties and then quickly drops its output as the outflow pathway is obstructed.

Fundoscopic ExaminationHypertensive vascular changesArteriosclerotic changes are chronic changes resulting from systemic hypertension. In the retina, atherosclerosis and arteriolosclerosis predominate.

According to Spencer, the normal light reflex of the retinal vasculature is formed by the reflection from the interface between the blood column and vessel wall.[1]Initially, the increased thickness of the vessel walls causes the reflex to be more diffuse and less bright. Progression of sclerosis and hyalinization causes the reflex to be more diffuse and the retinal arterioles to become red-brown. This is known as copper wiring.

Advanced sclerosis of the retinal vasculature leads to increased optical density of the retinal blood vessel walls; this is visible on ophthalmoscopy as a phenomenon known as sheathing of the vessels. When the anterior surface becomes involved, the entire vessel appears opaque (pipe-stem sheathing). The patency of such vessels has been demonstrated by fluorescein angiography. When sheathing encircles the wall, it produces a silver-wire vessel.

Arteriovenous Nicking

AV, or arteriovenous nicking (also known as arteriovenous nipping in the UK) is the phenomenon where, on examination of the eye, a small artery (arteriole) is seen crossing a small vein (venule), which results in the compression of the vein with bulging on either side

of the crossing. This is most commonly seen in eye disease caused by high blood pressure (hypertensive retinopathy).

It is thought that, since the arteriole and venule share a common sheath, the arteriole's thicker walls push against those of the venule forcing the venule to collapse. This makes the venule form an hourglass shape around the arteriole. Other theories suggest that this results not from compression from the arteriole but from sclerotic thickening or glial cell proliferation at the site where the two vessels cross.

Type of hypertensive drug

Diuretics

Hydrochlorothiazide, a popularthiazide diuretic

Diuretics help the kidneys eliminate excess salt and water from the body's tissues and blood.

Loop diuretics: bumetanide ethacrynic acid furosemide torsemide

Thiazide diuretics: epitizide hydrochlorothiazide and chlorothiazide bendroflumethiazide

Thiazide-like diuretics: indapamide chlorthalidone metolazone

Potassium-sparing diuretics: amiloride triamterene spironolactone

Only the thiazide and thiazide-like diuretics have good evidence of beneficial effects on important endpoints of hypertension, and hence, should usually be the first choice when selecting a diuretic to treat hypertension. The reason why thiazide-type diuretics are better than the others is (at least in part) thought to be because of their vasodilating properties.[citation

needed] Although the diuretic effect of thiazides may be apparent shortly after administration, it takes longer (weeks of treatment) for the full anti-hypertensive effect to develop. In the United States, the JNC7 (The Seventh Report of the Joint National Committee on Prevention of Detection, Evaluation and Treatment of High Blood Pressure) recommends starting with a thiazide diuretic if single therapy is being initiated and another medication is not indicated.[7] This is based on a slightly better outcome for chlortalidone in the ALLHAT study versus other anti-hypertensives and because thiazide diuretics are relatively cheap.[8] A subsequent smaller study (ANBP2) published after the JNC7 did not show this small difference in outcome and actually showed a slightly better outcome for ACE-inhibitors in older male patients.[9]

Despite thiazides being cheap, effective, and recommended as the best first-line drug for hypertension by many experts, they are not prescribed as often as some newer drugs. This is because they have been associated with increased risk of new-onset diabetes and as such are recommended for use in patients over 65 where the risk of new-onset diabetes is outweighed by the benefits of controlling systolic blood pressure.[10] Another theory is that they are off-patent and thus rarely promoted by the drug industry.[11]

Adrenergic receptor antagonists

Propranolol, the first beta-blocker to be successfully developed

Beta blockers atenolol metoprolol nadolol nebivolol oxprenolol pindolol propranolol timolol

Alpha blockers: doxazosin phentolamine indoramin phenoxybenzamine prazosin terazosin tolazoline

Mixed Alpha + Beta blockers: bucindolol carvedilol labetalol

Although beta blockers lower blood pressure, they do not have a positive benefit on endpoints as some other antihypertensives.[12] In particular, beta-blockers are no longer recommended as first-line treatment due to relative adverse risk of stroke and new-onset of type 2 diabetes when compared to other medications,[3] while certain specific beta-blockers such as atenolol appear to be less useful in overall treatment of hypertension than several other agents.[13] A systematic review of 63 trials with over 35,000 participants indicated β-

blockers increased the risk of mortality, compared to other antihypertensive therapies.[14] They do, however, have an important role in the prevention of heart attacks in people who have already had a heart attack.[15] In the United Kingdom, the June 2006 "Hypertension: Management of Hypertension in Adults in Primary Care"[16] guideline of the National Institute for Health and Clinical Excellence, downgraded the role of beta-blockers due to their risk of provoking type 2 diabetes.[17]

Despite lowering blood pressure, alpha blockers have significantly poorer endpoint outcomes than other antihypertensives, and are no longer recommended as a first-line choice in the treatment of hypertension.[18] However, they may be useful for some men with symptoms of prostate disease.

BenzodiazepinesAlthough controversial over this off-label purpose, benzodiazepines may play a role in lowering blood pressure. They work as an agonist of the GABA-a receptors in the brain, thus slowing down neurotransmission and dilating blood vessels. GABA is an abbreviation forgamma-aminobutyric acid. It is an inhibitory neurotransmitter among others (glycine, adenosine, etc.) GABA-a receptors are ion channels that are the primary target for benzodiazepines. When an agonist binds to this receptor site, the protein channel opens, allowing negative chloride ions entering the channel and penetrating the voltage-gated ion site. Thus, giving negative feedback in neurotransmission and easing stress, anxiety and tension in patients that can be associated with elevated blood pressure.[19] In addition to GABA, benzodiazepines inhibit the re-uptake of a nucleoside chemical called Adenosine, which serves as an inhibitory chemical mentioned above. It also serves as a coronary vasodilator, allowing the cardiac muscle to relax and dilating cardiac arteries.[20]

Calcium channel blockersCalcium channel blockers block the entry of calcium into muscle cells in artery walls.--

dihydropyridines: amlodipine cilnidipine felodipine isradipine lercanidipine levamlodipine nicardipine nifedipine nimodipine nitrendipine

non-dihydropyridines: diltiazem verapamil

Renin InhibitorsRenin comes one level higher than angiotensin converting enzyme (ACE) in the renin-angiotensin system. Inhibitors of renin can therefore effectively reduce hyptertension. Aliskiren (developed by Novartis) is a renin inhibitor which has been approved by the U.S. FDA for the treatment of hypertension.[21]

ACE inhibitors

ACE inhibitors inhibit the activity of Angiotensin-converting enzyme (ACE), an enzyme responsible for the conversion of angiotensin I into angiotensin II, a potent vasoconstrictor.

captopril enalapril fosinopril lisinopril perindopril quinapril ramipril trandolapril benazepril

A systematic review of 63 trials with over 35,000 participants indicated ACE inhibitors significantly reduced doubling of serum creatine levels compared to other drugs (ARBs, α blockers, β blockers, etc.), and the authors suggested this as a first line of defense.[14]

Angiotensin II receptor antagonists

Valsartan, an angiotensin II receptor antagonist

Angiotensin II receptor antagonists work by antagonizing the activation of angiotensin receptors.

candesartan eprosartan irbesartan losartan olmesartan telmisartan valsartan

Whether angiotensin receptor blockers may or may not increase the risk of myocardial infarction(heart attack) was announced in BMJ[22] and was debated in 2006 in the medical journal of theAmerican Heart Association.[23][24] To date[when?], there is no consensus on whether ARBs have a tendency to increase MI, but there is also no substantive evidence to indicate that ARBs are able to reduce MI.

In the VALUE trial, the angiotensin II receptor blocker valsartan produced a statistically significant 19% (p=0.02) relative increase in the prespecified secondary end point of myocardial infarction (fatal and non-fatal) compared with amlodipine.[25]

The CHARM-alternative trial showed a significant +52% (p=0.025) increase in myocardial infarction with candesartan (versus placebo) despite a reduction in blood pressure.[26]

Indeed, as a consequence of AT1 blockade, ARBs increase Angiotensin II levels several-fold above baseline by uncoupling a negative-feedback loop. Increased levels of circulating Angiotensin II result in unopposed stimulation of the AT2 receptors, which are, in addition upregulated. Unfortunately, recent data suggest that AT2 receptor stimulation may be less beneficial than previously proposed and may even be harmful under certain circumstances through mediation of growth promotion, fibrosis, and hypertrophy, as well as proatherogenic and proinflammatory effects.[27][28][29]

Aldosterone receptor antagonistsAldosterone receptor antagonists:

eplerenone spironolactone

Aldosterone receptor antagonists are not recommended as first-line agents for blood pressure,[7] but spironolactone and eplerenone are both used in the treatment of heart failure.

VasodilatorsVasodilators act directly on the smooth muscle of arteries to relax their walls so blood can move more easily through them; they are only used in hypertensive emergencies or when other drugs have failed, and even so are rarely given alone.

Sodium nitroprusside, a very potent, short-acting vasodilator, is most commonly used for the quick, temporary reduction of blood pressure in emergencies (such as malignant hypertension or aortic dissection).[30][31] Hydralazine and its derivatives are also used in the treatment of severe hypertension, although they should be avoided in emergencies.[31] They are no longer indicated as first-line therapy for high blood pressure due to side effects and safety concerns, but hydralazine remains a drug of choice in gestational hypertension.[30]

Alpha-2 adrenergic receptor agonistsCentral alpha agonists lower blood pressure by stimulating alpha-receptors in the brain which open peripheral arteries easing blood flow. These alpha 2 receptors are known as autoreceptors in which serves as a negative feedback in neurotransmission (in this case, the vasoconstriction effects of adrenaline) Central alpha agonists, such as clonidine, are usually prescribed when all other anti-hypertensive medications have failed. For treating hypertension, these drugs are usually administered in combination with a diuretic.

clonidine guanabenz guanfacine methyldopa moxonidine

Adverse effects of this class of drugs include sedation, drying of the nasal mucosa and rebound hypertension.

Some indirect anti-adrenergics are rarely used in treatment-resistant hypertension:

guanethidine - replaces norepinephrine in vesicles, decreasing its tonic release mecamylamine - antinicotinic and ganglion blocker reserpine - indirect via irreversible VMAT inhibition

For the most resistant and severe disease, oral minoxidil (Loniten) in combination with diuretic and β-blocker or other sympathetic nervous system suppressant may be used.

Endothelin receptor blockersBosentan belongs to a new class of drug and works by blocking the receptors of the hormone endothelin. It is specifically indicated only for the treatment of pulmonary artery hypertension in patients with moderate to severe heart failure.