Antihypertensives Flashcards
The alpha-2 adrenergic receptor agonist, clonidine, acts where centrally to produce what therapeutic effect?
It stimulates alpha-2A receptors in the inhibitory neurons in the vasomotor center of the medulla in the brain stem and inhibits sympathetic nervous system outflow. This action decreases blood pressure.
Alpha-2 adrenergic receptor agonists antagonize the sympathetic nervous system peripherally. How?
Alpha-2 receptors are found peripherally in the presynaptic nerve terminals of sympathetic postganglionic neurons. Stimulation of these receptors decreases the release of norepinephrine from the presynaptic nerve terminal, decreasing blood pressure.
How much does pretreatment of patients with clonidine decrease MAC?
By about 50%.
What are 3 common side effects of clonidine?
1) sedation 2) bradycardia 3) dry mouth
What 3 hormones are involved in rebound hypertension associated with discontinuation of clonidine?
Since clonidine decreases sympathetic outflow with a resulting decrease in catecholamines and renin activity, rebound hypertension is associated with an increase in circulating catecholamines, and probably also an increase in renin, and an increase in angiotensin II.
Should beta-blockers be given to a patient withdrawing from clonidine? Why or why not?
No, beta-blockade may exaggerate the magnitude of rebound hypertension by blocking beta-2 vasodilating effects, leaving unopposed alpha vasoconstriction action This can also result in heart failure.
In addition to beta-blockers, what other group of drugs may exaggerate the rebound hypertension after discontinuation of clonidine? Explain.
Tricyclic antidepressants. TCAs inhibit the reuptake of norepinephrine and serotonin increasing the concentration of these neurotransmitters in the circulation. This can potentiate rebound hypertension.
Other than rebound hypertension following sudden withdrawal of clonidine, what is your anesthetic concern for the patient on chronic clonidine therapy?
Clonidine is likely to promote perioperative hypothermia because it alters thermoregulatory control.
How do vasodilators, nitroprusside and nitroglycerin, relax vascular smooth muscle?
They donate nitric oxide which activates guanylate cyclase, with converts GTP to cyclic GMP, a second messenger that relaxes vascular smooth muscle, thereby promoting vasodilation and a decrease in blood pressure.
On what segments of the vascular tree does nitroprusside work to decrease blood pressure.
It causes VENOdilation which decreases preload and arterial dilation which decreases SVR. These actions lower arterial blood pressure.
What are four contraindications for using sodium nitroprusside?
1) liver disease 2) kidney disease 3) hypothyroidism 4) vitamin B12 deficiency.
How is cyanide produced?
With high doses of nitroprusside, the ferrous ion of nitroprusside reacts with sulfahydrl groups in red blood cells and releases cyanide.
What three reactions may cyanide ions undergo in the body?
1) They can bind to methemoglobin to form cyanomethemoglobin 2) React with thiosulfate in the liver to prodoce thiocyanide 3) Bind to tissue cytochrome oxidase and impair normal oxygen utilization by the tissues.
How do cyanide ions interfere with oxygen utilization at tissue cytochrome oxidase?
Binding to tissue cytochrome oxidase uncouples oxidative phosphorylation, preventing the formation of ATP.
What are four hallmark signs of cyanide toxicity?
1) Metabolic acidosis (base deficit) 2) cardiac arrhythmias, increased venous oxygen content (SvO2) due to impaired O2 utilization of the tissues and 4) TACHYPHYLAXIS
