Hypertensive effects

Patients receiving monoamine oxidase inhibitors (MAOI) as antidepressant therapy have been especially subject to the hypertensive effects of vasoactive amines (52). These dietary amines have also been impHcated as causative agents ia migraine. Other aaturaHy occurring alkaloids (qv) have been recognized for centuries as possessing neurological stimulant and depressant properties. 

Raymond-Hamet has given much attention to the action of the Rauwolfia alkaloids. Using Siddiqui s ajrhalinine, he found that it provokes hypotension accompanied by renal dilatation and exerts a true sympathi-colytic action. 1 Ajmaline and serpentine also induce hypotension and a decrease in intestinal action serpentinine diminishes the renal constrictive action of adrenaline, but does not alter its hypertensive effects. ... 

Hyperventilation to 25-30 mmHg for brief periods may be considered in refractory intracranial hypertension ° Effect limited to 24 h... 

The use of duloxetine in stress urinary incontinence is complicated by (1) the potential for multiple clinically relevant drug-drug interactions with cytochrome P-450 2D6 and 1A2 inhibitors, (2) withdrawal reactions if abruptly discontinued, (3) high rates of nausea and other side effects, (4) the hepa-totoxicity that contraindicates its use in patients with any degree of hepatic impairment, and (5) its mild hypertensive effect. 

James, J. E., The influence of user status and anxious disposition on the hypertensive effects of caffeine. International Journal of Psychophysiology 10(2), 171-179, 1991. 

JTT-705 (17) is an irreversible inhibitor of CETP (IC50 = 6 (iM) and is believed to affect the function of CETP protein by binding to its Cys13 residue. In rabbits, 17 dose-dependently reduced CETP activity, raised HDL and reduced atherosclerotic lesions [75]. The results from Phase-II clinical trials on 17 show good HDL elevation (26-37% at 600-900 mg/day) during 4 weeks of treatment [64,76-78]. Compound 17 is also reported to lack hypertensive effects. 

There is no doubt, however, that the anti-hypertensive effect of the (3-blocking drugs is not immediate - a characteristic which one must take into consideration in examining some of the proposed mechanisms of action. 

Figure 10. Anti-hypertensive effect of ICI 66082 (300 mg daily) in hypertensive patients, divided according to their plasma renin concentration determined recumbent in the morning (from. Meekers, A. Missotten, R. Fagard, D. Demuynck, C. Harvengt, P. Pas, L. Billiet, and A. Amery in Archives Internationales de Pharma-codynamie et de Therapie)...

Intravenous administration of 4—lOmg/kg produced bradycardia and an initial transient hypertensive effect in the anesthetized dog. Toxicity is thought to occur from the decomposition of decaborane to a stable intermediate that in turn inhibits intracellular pyri-doxal phosphate-requiring enzymes. ... 

Initial dose - 10 mg once daily, alone or added to diuretic therapy. If the desired response is not achieved the dose can be doubled. Increasing the dose to more than 20 mg has not produced a statistically significant additional hypertensive effect however, the 40 mg dose is well tolerated. 

Phenylephrine Acute venoconstriction acute hypertensive effect o... 

C) The hypertensive effects of procainamide would aggravate the hypertension. 

Blood pressure effect. Fruit juice, administered intravenously hy infusion to dogs at a dose of 3 mL/minute for 100 minutes, was active. Initial effect was a decrease in hlood pressure . Oil, administered to male weanling rats at a dose of 10% of diet for 5 weeks, produced significantly higher hlood pressure than other groups. Systolic hlood pressure was found related to the dietary intakes of saturated and unsaturated fatty acids. Prenatal exposure of the rats to a maternal low-protein diet abolished the hypertensive effect of the coconut oil dieH . Butyryl cholinesterase activity. Oil was administered to rats at different doses with or without clofibrate for 15 days. The hypolipidemic action of clofibrate was not... 

The authors concluded that, although a cold-water drench alone provoked a brief rise In pressure, It was only partly responsible for the rise seen during the CS drench. A direct hypertensive effect of CS was ruled out, Inasmuch as the rise In blood pressure came too rapidly to be accounted for by the absorption of a substantial amount of the agent. The rise must therefore have been caused by the Intense Irritant effect of CS. 

Adrenaline, noradrenaline Beta-adrenoceptor blocking drugs Potentiation of hypertensive effect. 

MAOIs have the most serious pharmacodynamic interactions of any antidepressant class. As discussed earlier, they can cause a hypertensive crisis and the serotonin syndrome. They potentiate the hypertensive effects of most sympathomimetic amines, as well as tyramine, which is the reason for the avoidance of over-the-counter preparations containing such agents, in addition to the tyramine-free diet ( 508, 509). The serotonin syndrome occurs most often when MAOIs are used in combination with SSRIs and venlafaxine but it can also occur when MAOIs are used with tryptophan, 5-hydroxytryptophan, and some narcotic analgesics. In addition, MAOIs can also significantly potentiate the sedative and respiratory depressant effects of narcotic analgesics. 

Both adrenaline and noradrenaline stimulate smooth muscles throughout the body and have a hypertensive effect. Their postsynaptic receptors are 7-helix transmembrane proteins (Fig. 11-6). A comparison of the effects of various analogs led to the classification of these receptors into classes a, a2, P, and P2, which are discussed briefly on pp. 553-555. The a receptors, which are structurally closely related to rhodopsin,753/754 are coupled via Gq /11 proteins to a phosphoinositide-activated phospholipase C (Figs. 11-9, 30-19).755 They usually provoke an excitatory response. However, in intestinal smooth muscles they are inhibitory. Adrenaline is usually more active at a receptors than is noradrenaline. A specific antagonist... 

Blood Pressure Lowering. The hypertensive effect of several expl compds has been reported by Salle (Refs 1,2, 3). Dinitroglycerol, NGc, bis(hydroxy-methyl)nitroethane dinitrate, dimethylol nitroethane dinitrate, bis(hydroxymethyl)nirropropane dinitrate dimethylol nitropropane dinitrate were studied. These compds were found to be vasodilators, less active than NG but excercising a more lasting effect(Ref 3). Nitrated sorbitol has a vasodilator effect similar to hexanitromannitol(HNMnt) but is si more toxic than HNMnt(Ref 2)... 

The effects induced by the H3-receptor agonist can also be prevented by NO-synthase blockade with L-NAME, thus indicating the partecipation of the L-arginine-NO pathway (Ea-Kim et al., 1993, 1996). This pathway is probably located at the neuronal ending level, since (R)a-methylhistamine does not modify the hypertensive effects induced by exogenous noradrenaline (Ea-Kim et al., 1996), thus excluding the involvement of endothelial receptors (see below). 

Contrastingly, it was found that presynaptic histamine H3-receptor activation lowers the hypertensive effect evoked by nicotinic stimulation of sympathetic ganglia (Oudart et al., 1995), or by electrical stimulation of the spinal sympathetic nerves (Malinowska and Schlicker, 1991, Godlewski et al., 1997a). In spontaneously hypertensive rats, these receptors are probably activated by endogenous histamine, since thioperamide increases arterial pressure. Therefore, histamine H3-receptors appear to be operative in hypertension, where histamine could play a modulatory role in the control of sympathetic system hyperreactivity (Godlewski et al., 1997a). 

Inukai T, Inukai Y, Matsutomo R, et al. Clinical usefulness of doxazosin in patients with type 2 diabetes complicated by hypertension effects on glucose and lipid metabolism. J Int Med Res. 2004 32 2 06-213. 

The drug should not be given to patients who are at risk for mental depression and should be withdrawn if depression occurs during therapy. Concomitant treatment with tricyclic antidepressants may block the anti hypertensive effect of clonidine. The interaction is believed to be due to cr-adrenoceptor-blocking actions of the tricyclics. 

Guanethidine increases sensitivity to the hypertensive effects of exogenously administered sympathomimetic amines. This results from inhibition of neuronal uptake of such amines and, after long-term therapy with guanethidine, supersensitivity of effector smooth muscle cells, in a fashion analogous to the process that follows surgical sympathectomy (see Chapter 6 Introduction to Autonomic Pharmacology). 

Hydralazine, a hydrazine derivative, dilates arterioles but not veins. It has been available for many years, although it was initially thought not to be particularly effective because tachyphylaxis to hypertensive effects developed rapidly. The benefits of combination therapy are now recognized, and hydralazine may be used more effectively, particularly in severe hypertension. 

Hendel MD, Collister JP. Renal denervation attenuates long-term hypertensive effects of angiotensin II in the rat. Clin. Exp. Pharmacol. Physiol. 2006 33 1225-1230. 

H. Yasuda, Y. Kuriyamoto, and T. Nisbino. Plasma bradykinin concentration in patients with essential hypertension, effect angina and other cardiac diseases. Folia PhamacoL Jpn. 82.159 (1983). 

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