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        New Message Board Archives >> Medications, Treatments, Therapies 2003 >> Atacand?
        
(Message started by: athos12 on May 18^th, 2003, 2:31am)

Title: Atacand?
Post by athos12 on May 18^th, 2003, 2:31am

Anyone have any usefull info on Atacand? I heard this is making a name for itself in fighting vascular headaches.

--Athos

Title: Re: Atacand?
Post by Ueli on May 18^th, 2003, 7:38am

Candesartan cilexetil (Atacand) is an ACE (angiotensin converting enzyme) inhibitor, that is, it reduces the enzymatic conversion of angiotensin I to angiotensin II. The later is a potent vasoconstrictor, it increases blood pressure. Therefore, ACE inhibitors reduce blood pressure by reducing the production of the vasoconstricting angiotensin II.
To prevent or abort a cluster attack this mechanism is not very useful, quite in the contrary: Sumatriptan (Imitrex) gives a strong signal to constrict the vessels and oxygen rich blood (due to breathing pure O2) provokes an autonomous signal to constrict the arteries in the head.

I can't remember that anybody reported success against CH from ACE inhibitors.

PFNADs
Ueli

Title: Re: Atacand?
Post by athos12 on May 18^th, 2003, 2:42pm

Thanks!

Title: Re: Atacand?
Post by Tom on May 18^th, 2003, 6:56pm

Oxygen rich blood doesn't constrict the blood vessels, thus breathing pure oxygen doesn't have any effect on their diameter. The abortive effect of O2 (=higher partial pressure of O2 in the blood) on CH attacks is still a pathophysiological riddle !

Only the partial pressure of CO2 in the blood is responsible for the blood vessels' diameter: Breathing a CO2 rich air mixture widens the vessels - reciprocally hyperventilation (= decrease of the CO2 partial pressure in the blood) causes a vasoconstriction. These effects are regularly used and easily proven in special clinical diagnostic procedures, the so called transcranial Doppler examination.

But: Hyperventilation = vasoconstriction of the brain vessels does never abort a CH attack, as we know, and the effects of vasoconstriction a n d/or vasodilatation are n o t the crucial factors for the abortion or origin of the CH pain - corresponding to the findings and conclusions of Prof. Goadsby's group:
------------------------------------
Brain 2002 May;125(Pt 5):976-84

Persistence of attacks of cluster headache after trigeminal nerve root section.

Matharu MS, Goadsby PJ.

Headache Group, Institute of Neurology, University College London, UK.

... We report a patient with a trigeminal nerve section who continued to have attacks. A 59-year-old man described a 14-year history of left-sided episodes of excruciating pain centred on the retro-orbital and orbital regions. These episodes lasted 1-4 h, recurring 2-3 times daily. The attacks were associated with ipsilateral ptosis, conjunctival injection, lacrimation, rhinorrhoea and facial flushing. From 1986 to 1988, he had trials of medications without any benefit. In February 1988, he had complete surgical section of the left trigeminal sensory root that shortened the attacks in length for 1 month without change in their frequency or character. In April 1988, he had further surgical exploration and the root was found to be completely excised; post-operatively, there was no change in the symptoms... Sumatriptan 100 mg orally and 6 mg subcutaneously aborted the attack after approximately 45 and 15 min, respectively. He was completely anaesthetic over the entire left trigeminal distribution. Left corneal reflex was absent. Motor function of the left trigeminal nerve was preserved. Neurological and physical examination was otherwise normal. MRI scan showed a marked reduction in the calibre of the left trigeminal nerve from the nerve root exit zone in the pons to Meckel's cave. An ECG-gated three-dimensional multislab MRI inflow angiogram was performed. No dilatation was observed in the left internal carotid artery during the cluster attack. Blink reflexes were elicited with a standard electrode and stimulus. Stimulation of the left supraorbital nerve produced neither ipsilateral nor contralateral blink reflex response...

... Lack of ipsilateral vessel dilatation makes the role of vascular factors in the initiation of cluster attacks questionable. With complete section of the left trigeminal sensory root the brain would perceive neither vasodilatation nor a peripheral neural inflammatory process; however, the patient continued to have an excellent response to sumatriptan. The case illustrates that cluster headache may be generated primarily from within the brain, and that triptans may have anti-headache effects through an entirely central mechanism.
--------------------

Thus it's postulated that:

- triptans most probably have an entirely central pain blocking mechanism

- also the action of verapamil as a so called L-type Ca++ channel blocker in CH has
nothing to do with its vascular effect ( apart from that: it c a u s e s an arterial
d i l a t a t i on, which apparently doesn't matter for the CH pain !) - it most probably
prevents the central nervous development and transmission of pain blocking the influx
of Ca++ a n d centrally also that of Na+ into certain neurons.

Thomas

Title: Re: Atacand?
Post by CJohnson on May 18^th, 2003, 7:37pm

Salient point, all. I'll be pouring over that info for a while. 1 question. Do blood vessels dilate to bring more oxygen to a region? If so, would blood which has suddenly been enriched with oxygen negate the need for dilation?

PFDANs
-Curtis

Title: Re: Atacand?
Post by Tom on May 18^th, 2003, 8:43pm

From

http://www.emedicine.com/ped/topic16.htm :

Respiratory acidosis is a process where the arterial partial pressure of carbon dioxide (PaCO2) is elevated above the normal range (greater than 44 mm Hg) leading to a blood pH less than 7.35. Respiratory acidosis results when the level of carbon dioxide (CO2) excreted from the lungs does not match the level of CO2 produced by the body.

Acute elevations in PaCO2 increase intracranial pressure by increasing cerebral blood flow (CBF) and cerebral blood volume secondary to vasodilatation. Between PaCO2 values of 40-80 mm Hg, CBF increases 1-2 mL per 100 g brain per minute for each 1-mm Hg increase in PaCO2. A PaCO2 of 80 mm Hg or more produces a maximal increase in CBF
------------------------------------------------------------------

The dilatation of the brain arteries is caused by a (relative) acidosis of the neuronal tissue (acidosis = increased acidity = lowered pH). This increased acidity is caused by higher levels of carbon dioxide (CO2) -> higher levels of carbonic acid:

CO2 + H2O -> H2CO3 = carbonic acid

Acidosis causes an immediate synthesis and output of NO (= nitric oxide), which is one of the most potent vasodilatators of the organism (BTW: sildenafil =Viagra® is a mighty NO donator !)

Consequently: Changes of the pH of the brain tissue essentially alterate the diameter of the brain arteries and thus also the blood flow, respective - and those changes are o n l y caused by alterations of the partial pressure of CO2.

As changes of the partial pressure of O2 in the blood/tissue don't cause an alteration of the pH, consequently breathing of pure O2 doesn't cause a vasoconstriction.

PFDAN ! Thomas