Autonomic pharmacology

Adrenergic Receptor Signal Transduction (α₂-receptor system is outlined)²³⁵

The mechanism of adrenergic receptors.^{236 (text slightly modified)} Epinephrine and norepinephrine are receptor ligands to either α₁, α₂ or β-adrenergic receptors. α₁ couples to G_q, which results in increased intracellular Ca²⁺ which results in smooth muscle contraction. α₂, on the other hand, couples to G_i, which causes a decrease of cAMP activity, resulting in e.g. smooth muscle relaxation. β receptors coupled to G_s, and increases intracellular cAMP activity, resulting in for example heart muscle contraction, smooth muscle relaxation and glycogenolysis.²³⁶

Pheochromocytoma

gross pathology illustrating pheochromocytoma, an adrenal gland tumor (ref. 12)

Vasocontrictors added to local anesthetic solutions
Purpose of adding epinephrine to a local anesthetic solution: Increased duration: addition of epinephrine (1:2000,000 or 5 ug/ml) to cause vasoconstriction Reduced systemic absorption Higher anesthetic concentration near nerve fibers Prolongation of conduction blockade (about 50% longer) Reduced systemic absorption (by about 33%) Factors influencing the effectiveness of epinephrine on local anesthesia: Dependencies -- Which anesthetic is used: Reduced effect of epinephrine on duration of conduction blockade and systemic absorption comparing mepivacaine (Carbocaine) and etidocaine (Duranest) [these are more lipophilic] with lidocaine (Xylocaine), which is less lipophilic More lipophilic local anesthetics will tend on their own to associate strongly with tissues Level of sensory blockade needed for spinal or epidural anesthesia Duration of lower extremity sensory anesthesia extended by epinephrine or phenylephrine (Neo-Synephrine); this effect is not observed for abdominal region anesthesia Conditions: epinephrine (0.2 mg) or phenylephrine (Neo-Synephrine) (2 mg) added to mepivacaine (Carbocaine) or lidocaine (Xylocaine) -- placed in subarachnoid spaces Spinal anesthesia -- tetracaine (pontocaine): duration of action extended by vasoconstrictors Condition 1: epinephrine plus tetracaine (pontocaine) (6 mg, low-dose)- result: increase in spinal anesthesia success rate Condition 2: epinephrine plus tetracaine (pontocaine) (10 mg, higher dose)- result: no increase in spinal anesthesia success rate Prolongation of local anesthetic action (no effect by epinephrine on time-to-onset): Mechanisms -- Decreased systemic absorption Increased local anesthetic concentration in the vicinity of sensory nerves Increased uptake of the local anesthetic Advantages of reduced local anesthetic systemic absorption: Local anesthetic absorption rate more likely to match metabolic rate resulting in less local anesthetic systemic toxicity Toxicities associated with systemic epinephrine absorption: Local anesthetic + epinephrine: increased cardiac irritability which may cause an increased risk of cardiac arrhythmias Increased possibility of hypertensive response in susceptible patients Other agents which may be added to local anesthetics that affect duration of action Dextran (low-molecular-weight) when added to local anesthetic solutions result in increased peripheral nerve block anesthesia duration (probably due to a reduction in local anesthetic systemic absorption) Primary Reference: Stoelting, R.K., "Local Anesthetics", in Pharmacology and Physiology in Anesthetic Practice, Lippincott-Raven Publishers, 1999, pp 158-181. Miller, R.D., Local Anesthesia, in Basic and Clinical Pharmacology, (Katzung, B. G., ed) Appleton-Lange, 1998, pp 425-433. White, P. F. "Anesthesia Drug Manual", W.B. Saunders Company, 1996.

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