PNS DRUGS.docx

PNS DRUGS: CHOLINERGIC AGONITS/ANTAGONIST [CHOLINERGIC DRUGS] Either mimic or block acetylcholine. Considerations: should not use in lactating females decrease milk production due to anticholinergic side effects. Not recommended in elderly +-----------------------------------+-------------------...

PNS DRUGS: CHOLINERGIC AGONITS/ANTAGONIST [CHOLINERGIC DRUGS] Either mimic or block acetylcholine. Considerations: should not use in lactating females decrease milk production due to anticholinergic side effects. Not recommended in elderly +-----------------------------------+-----------------------------------+ | Bethanechol- parasympathomimetic | \- oral admin, effects 30-60 min | | agent | | | | \- does not cross membranes | | SELECTIVE AGONIST: MUSCARINIC | easily only a small amount is | | CHOLINERGIC RECEPTOR | absorbed | | | | | Binds reversibly to muscarinic | \- uses: urinary retention, | | cholinergic receptors to cause | investigational GI uses, off | | activation | label for GI reflux | | | | | | \- A/E: hypotension, cramps from | | | inc tone and motility of GI, | | | diarrhea, increased salivation, | | | asthma exacerbation, dysrhythmias | | | in hyperthyroidism AVOID W/ | | | HYPERTHYROID PATIENTS | +===================================+===================================+ | Cevimeline | Treats dry mouth in Sjogren's | | | syndrome | | Derivative of acetylcholine | | +-----------------------------------+-----------------------------------+ | Pilocarpine | Topical therapy of glaucoma | | | | | | Also used to treat dry mouth from | | | Sjogren's syndrome | +-----------------------------------+-----------------------------------+ | Acetylcholine | Rapid miosis after delivery in | | | cataract surgery | +-----------------------------------+-----------------------------------+ Structure: with the exception of pilocarpine, they are quaternary ammonium compounds, always carry a positive charge don't cross membranes easily Muscarinic poisoning: - From ingestion of certain mushrooms or direct-acting muscarinic agonists, and cholinesterase inhibitors. - s/s: profuse salivation, lacrimation, visual disturbances, bronchospasm, diarrhea, bradycardia, hypotension with possible cardiac collapse - Tx: atropine and supportive therapy +-----------------------------------+-----------------------------------+ | Atropine | \- can be given IV, IM or sub Q. | | | AtroPen for poisoning. Drops for | | Causes muscarinic receptor | ophthalmology | | blockade | | | | \- Uses: pre-anesthetic, | | | disorders of the eye, | | | bradycardia, intestinal | | | hypertonicity/motility, | | | muscarinic agonist poisoning, | | | PUD, asthma, biliary colic | | | | | | \- A/E: dry mouth, blurred | | | vision, photophobia, elevation of | | | interocular pressure, urinary | | | retention, constipation, | | | anhidrosis, tachycardia, and | | | asthma | | | | | | \- Avoid combining with other | | | drugs capable of causing | | | muscarinic blockade | +===================================+===================================+ | ANTI-CHOLINERGIC DRUGS FOR | | | OVERACTIVE BLADDER | | +-----------------------------------+-----------------------------------+ | Oxybutynin | \- two short acting pills. Three | | | long acting: patch, topical ER | | Acts primarily at the M3 receptor | tablet | | | | | | \- s/e: dry mouth, constipation, | | | tachycardia, urinary | | | hesitancy/retention, mydriasis, | | | blurred vision, dry eyes, | | | hallucination/agitation in peds | | | and geriatric | | | | | | \- tricyclics, phenothiazine can | | | intensify anticholinergic effects | | | also drugs that inhibit or induce | | | CYP can alter oxybutynin levels | +-----------------------------------+-----------------------------------+ | Darfenacin | Overactive bladder | | | | | M3 selectively (no effect on | s/e: dry mouth, constipation | | other M receptors) | | +-----------------------------------+-----------------------------------+ | Solfenacin | s/e: dry mouth, blurred vision, | | | high doses can cause prolong QT | | NOT M3 selective | interval | +-----------------------------------+-----------------------------------+ | Tolterodine | Can prolong QT | | | | | Non-selective muscarinic | | | antagonist | | +-----------------------------------+-----------------------------------+ | Fesoterodine | s/e: drymouth, constipation | | | | | Tropsium | CYP substrate | | | | | Non-selective muscarinic | | | antagonist | | +-----------------------------------+-----------------------------------+ | Mirabegron | \- 25mg once daily. May increase | | | to 50mg after 4-8 week | | MOA: relaxation during filling | | | and inc bladder capacity, | \- Requires dosage reduction for | | decreases frequency. | renal impairment | | | | | Detrusor relaxation by Beta 3 | \- Can prolong QT and increase BP | | adrenoreceptor activation by | | | norepi | \- Avoid in pts with renal | | | disease or HTN | | First drug class to produce a | | | therapeutic effect without | | | engaging in muscarinic receptors | | | and producing anticholinergic AE | | +-----------------------------------+-----------------------------------+ | Vibegron- 3^rd^ line option for | \- Requires renal dosing | | OAB | | | | 75mg once daily | | (same as above) | | +-----------------------------------+-----------------------------------+ | Botox (onabotulinumtoxina)- 3^rd^ | \- persists until motor endplate | | line option for OAB | units regenerate after 3-24 | | | months | | MOA: injected in detrusor muscle | | | inhibits calcium dependent | A/E: voiding dysfunction, UTIs | | release of acetylcholine, | | | adenosine triphosphate, and | | | substance P and reduces | | | expression of capsaicin receptors | | | on motor neurons flaccid | | | paralysis | | +-----------------------------------+-----------------------------------+ | SNRIS | Duloxetine- cannot be given with | | | MAOIs and is metabolized by CYP | | Venlafaxine and Duloxetine- | | | nontraditional therapy | | | | | | Facilitates urine storage, | | | augment PNS innervation, and | | | inhibiting sympathetic | | | innervation | | +-----------------------------------+-----------------------------------+ OTHER MUSCARINIC ANTAGONISTS (ANTI-CHOLINERGIC) +-----------------------------------+-----------------------------------+ | Scopolamine- similar to atropine | \- Therapeutic doses produce | | | sedation | | | | | | \- uses: suppresses emesis and | | | motion sickness, | | | cycloplegia/mydriasis for eye sx, | | | pre-anesthetic sedation/obstetric | | | amnesia | +===================================+===================================+ | Ipratropium bromide | Uses: asthma, COPD, rhinitis from | | | allergies or common cold | +-----------------------------------+-----------------------------------+ | Antisecretory anticholinergics | \- reduce salivation | | | | | Glycopyrrolate, Mepenzolate, | \- all oral except Glyco which | | Methscopolamine, propantheline | can be given IV or IM as well | +-----------------------------------+-----------------------------------+ | Dicyclomine | \- for IBS, diarrhea or | | | hyper-motility | +-----------------------------------+-----------------------------------+ | Mydriatic-cycloplegics | \- Produce mydriasis and | | | cycloplegia for eye procedures | | Atropine, homatropine, | | | scopolamine, cyclopentolate, and | | | tropicamide | | +-----------------------------------+-----------------------------------+ | Centrally acting anticholinergics | \- Parkinson's | | | | | Benztropine and trihexyphenidyl | | +-----------------------------------+-----------------------------------+ [Anti-Muscarinic poisoning] - From natural products such as belladonna or selective anti-muscarinic drugs such as atropine and scopolamine or drugs with pronounced anti-muscarinic prosperities such as antihistamines, phenothiazines, and tricyclic anti-depressants - s/s: dry mouth, blurred vision, photophobia, hyperthermia, CNS effects and hot, dry/flush skin, and death from respiratory depression due to blockade of cholinesterase receptors in the brain - Tx: physostigmine. Inhibitor of acetylcholinesterase [Cholinesterase inhibitors ] - Drugs that prevent the degradation of acetylcholine by acetylcholinesterase increase levels of acetylcholine enhancing cholinergic transmission Reversible cholinesterase inhibitors - Pyridostigmine - Does not cross membranes readily, Absorbed poorly with oral admin, Minimal effects on the brain and fetus - Used for myasthenia gravis - MOA: decreases breakdown of acetylcholine - CNS - Therapeutic: mild stimulation - Toxic: depression - Neuromuscular effects - Therapeutic dose: increases force of contraction - Toxic: decreases force of contraction - A/E: excessive muscarinic stimulation, neuromuscular blockade, treatment with antagonist (atropine) - Precautions/contra: obstruction of GI or urinary tract, PUD, asthma, coronary insufficiency, hyperthyroid - Other reversible: neostigmine, physostigmine, ambenonium, edrophonium, Alzheimer's meds Irreversible cholinesterase inhibitors - Highly toxic. Primarily used as insecticides. - Only clinical indication: glaucoma - Lipid soluble - Poisoning: by organophosphate cholinesterase inhibitors excessive muscarinic stimulation and depolarizing neuromuscular blockade. Known as "cholinergic crisis" (too much acetylcholine) give atropine and respiratory support - Muscarinic: excessive secretions from salivary and bronchial glands, involuntary urination/defecation, laryngospasm, and bronchoconstriction. - Nicotinic: muscle weakness, cramps, twitching, convulsions - Atropine will reduce muscarinic stimulation/ pralidoxime will reverse inhibition of cholinesterase/ benzodiazepine can suppress convulsion [Myasthenia Gravis] Fluctuating muscle weakness and predisposition to rapid fatigue. - s/s: ptosis, dysphasia, weakness. An autoimmune process where antibodies attack the nicotinic M receptors on the skeletal muscle (block or destroy muscle receptor site for acetylcholine) so deficient - tx: reversible cholinesterase inhibitors by preventing inactivation, anticholinesterase agents can intensify the effects of acetylcholine increasing muscle strength - can give atropine to suppress muscarinic responses if excessive - signs its working: ease of swallowing, ability to raise eyelids - overmedication: excessive salivation and other muscarinic responses - Myasthenic crisis treat with cholinesterase inhibitor such as NEOSTIGMINE You can distinguish cholinergic crisis vs myasthenia crisis by administering a dose of edrophonium (short acting cholinesterase inhibitor) IF IT ALLEVIATES SYMPTOMS THE CRISIS IS MYASTHENIC. \*have O2 and atropine ready because the drug can make symptoms of cholinergic crisis worse!