Autonomic Neurotransmission-Drugs Flashcards
Drug?
Mech: inactivates synaptci vesicle protein (SNAP-25) required for vesicle docking with presynaptic membrane
- produces a reversible state of cholinergic denervation
- restoration of nerve function requires sprouting of new terminals–> months
- produces flaccid paralysis of skeletal muscle
Thereaputic:
- IM for muscle spasms
- Cosmetic “glabellar lines”
- Intradermal for axillary hyperhidrosis
- overactive bladder
OnabotulinumtoxinA (Botox)
Side effects: distant spread beyond injection site can cause serious dysphagia and breathing difficulties; ptosis, pain, drooling, loss of facial expression, allergic reaction
Cholinergic Receptor Subtype:
- G-protein couple receptors (Gq or Gi); induce changes in cytosolic Ca2+ or cAMP
- Differential tissue expression adn function
- _____ selectively stimulates these receptors
- ______ selectively blocks these receptors
Muscarinic (M1-M5)
- Muscarine stimulates
- Atropine blocks
Cholinergic Receptor Subtype:
- Ligand-gated ion channels; permeability to Na+ and K+ increases causing membrane depolarization (ganglionic EPSP and motor endplate potential EPP)
Nicotinic (Nn, Nm)
Cholinergic Receptor Subtype:
- pentameric structure consisting of 2 alpha and 3 beta subunits
- ____ stimulates this receptor; persistent stimulation of the receptor causes “desensitization” (depolarizing blockade)
- Blocked by _____
Nicotinic–Nn– Neuronal ganglia
- Nicotine stimulates this receptor; persistent stimulation of the receptor causes “desensitization” (depolarizing blockade)
- Blocked by mecamylamine
Cholinergic Receptor Subtype:
- Pentameric structure (2 alpha, beta, gamma and delta subunits)
- ____ also stimulates and blocks this receptor
- ______ is a competive anatagonist of this receptor subtype
Nicotinic—>Nm-neuromuscular junction
- Nicotine also stimulates and blocks this receptor
- d-Tubocurarine is a competive anatagonist of this receptor subtype
______ rapidly terminates cholinergic transmission by hydrylosis
- one of the fastest enzyme activties known in nature
- inactivation necessary to allow for next depolarization and to prevent lateral diffusion
AChE
- Activity in plasma, glial cells and liver
- functions as a drug metabolozing enzymes (choline esters, AChE inhibitors)
- activity is geneticly deficient in some patients—> prolonged apnea
Butyrylcholinesterase (plasma or “pseudo cholinesterase”
Drug:
- oral antihypertensive agent and antipsychotic; seldom used
- inhibition of storage of NE, Epi, and DA
- mechanism: irreversible inhibitor of VMAT-2, transmitters not stored are degraded by MAO; eventually depletes catecholamines from nerve terminals and reduces SNS activity in CNS and peripheral nerves
- non selective in its mechanism
Reserpine
Side effects: sedation, unopposed cholinergic effects (cramping, diarrhea), psychotic depression
Dietary constituent–>version of amino acid
- low oral bioavailability due to GI/hepatic MAO; systemic absorption can occur in patients taking MAO inhibitoyrs
- Mechanism: dispalces NE from vesicles and causes non-vesicular release from nerve terminals by reverse transport through the NET
- High systemic exposures can elicit a hypertensive crisis, from abrupt NE release;
- dietary restrictions for patients on MAOIs prevent this from occuring
Tyramine
Drug:
- oral antihypertensive agent that can be used safely during pregnancy
- mechansim: prodrug converted to methyl-NE (active form) by reactions 2 and 3; methyl-NE is an alpha-2 selective adrenergic receptor agonist
- stimulation of pre-synaptic alpha-2 receptors in the CNS reduces “sympathetic outflow” to the periphery
Methyldopa
- side effects: sedation, dry mouth, parkinsonism, and hyperprolactinemaia; postivie Coomb’s test in long-term use (autoimmune hemolytic anemai)
Drug:
- inhibition of termination–> re-uptake
- stimulant effects in CNS and periphery are due to excess NE remaining in the synapse following SNS nerve stimulaiton
Cocaine
- increased HR and increased vasonstriction, increased BP
