Nursing Pharmacology Chapter 26:  Renal Pharmacology

 Mechanism by which lithium compounds may cause a syndrome like diabetes insipidus

• Introduction

  • Vasopressin: regulates water conservation.

  • Synonymous terms: vasopressin: arginine vasopressin (AVP): antidiuretic hormone (ADH)

• Similar peptide: oxytocin, a common vasopressin and oxytocin receptor antagonist

  • Binds to myoepithelial cells in the mammary gland (milk ejection) and on uterine smooth muscle cells (uterine contraction)

• The antidiuretic system consists of

  • CNS component (vasopressin synthesis, transport, storage, release)

    • Supraoptic nucleus (SON)

    • Paraventricular nucleus (PVN)

  • Renal collecting duct system

    • Epithelial cells exhibit increased water permeability in response to vasopressin.

• Increased plasma osmolality: increased vasopressin release

• Factors affecting/modifying vasopressin release

  • Hypovolemia

  • Hypotension

  • Hypoxia

  • Drugs

  • Pain

  • Nausea

  • Certain endogenous hormones

• Regulation of vasopressin secretion

  •  Osmotic Stimulation of Vasopressin Release

    • CNS structures: osmoreceptive complex

      1.  Osmosensitive: magnocellular neurons (SON, PVN)

      2.  Subfornical organ (SFO) project to SON/PVN

      3.  Organum vasculosum of the lamina terminalis (OVLT) project during clearing directly to SON/PVN

  •  Hypovolemic/hypotension stimulation of Vasopressin Release

    •  Baroreceptors

      •  Blood volume (filling pressures)--baroreceptors in:

        • Left atrium

        • Left ventricle

        • Pulmonary veins

      •  Arterial blood pressure: baroreceptors located at the  carotid sinus and aorta.

      •  Nerve impulses from baroreceptors are carried:

        • By the vagus and glossopharyngeal nerves to the nucleus of the solitary tract

        • To the A1-noradrenergic cells in the caudal ventrolateral medulla

        • To the SON and PVN

Hormonal Effects

• Vasopressin release: stimulation

  • Acetylcholine (nicotinic)

  • Glutamine

  • Histamine (H₁)

  • Dopamine (D₁ & D₁)

  • Neuropeptide Y

  • Prostaglandins

  • Aspartate

  • Cholecystokinin

  • Substance P

  • Vasoactive intestinal peptide

  • Angiotensin II

• Vasopressin release: inhibition

  • Atrial natriuretic peptide

  • Gamma aminobutyric acid (gaba)

  • Opioids (dynorphin)

• Drug Effects

  • Vasopressin Release: Stimulation

    • Vincristine (Oncovin)

    • Nicotine

    • Morphine (high doses)

    • Cyclophosphamide

    • Tricyclic antidepressants

    • Epinephrine

    • Lithium (inhibits renal effects of vasopressin; enhances vasopressin release

  • Vasopressin Release: Inhibition

    • Ethanol

    • Glucocorticoids

    • Haloperidol (Haldol)

    • Promethazine (Pherergan)

    • Phenytoin (Dilantin)

    • Morphine (low dose)

    • Fluphenazine (Prolixin)

    • Oxilorphan

    • Carbamazepine (Tegretol)(renal effects -- anti-diuresis; inhibits vasopressin secretion (central effect)

    • Lithium Effects:

      • Inhibits antidiuretic effect of vasopressin

        • Lithium is used widely for management of bipolar disorder (manic- depressive).

        • Lithium uptake by the sodium channel in the collecting duct, causes lithium-induced nephrogenic diabetes insipidus.

        • Lithium polyuria: normally reversible

        • Mechanism of action:

          • reduces V₂ receptor-mediated adenyl cyclase stimulation

      •  Often, the antibiotic demeclocycline (Declomycin) reduces the antidiuretic effects of vasopressin (possibly because of reduced cyclic AMP)

    Jackson, E.K. Vasopressin and Other Agents Affecting the Renal Conservation of Water In, Goodman and Gillman's The Pharmacological Basis of Therapeutics, (Hardman, J.G, Limbird, L.E, Molinoff, P.B., Ruddon, R.W, and Gilman, A.G.,eds) The McGraw-Hill Companies, Inc.,1996, pp.715-732.