Pharm 1 - Control of Pain 2

martinezdvm's version from 2015-10-25 18:07

α-2 Agonists (control of pain)

Question Answer
What 3 things can an α-2 agonist do?Sedation, Analgesia, Muscle relaxant
When can an α-2 agonist act as a mm relaxant?At a ↑ dose
In what species do α-2s activate the vomiting center?Dogs & cats (Don't feed your cats α-2 sauce)
Species differences: dogs - what can α-2s do?Inhibit GIT motility, induce vomiting (dogs like A1 sauce, but A2 sauce makes them constipated & barf)
Species differences- ruminants- what can α-2s do?Tympany (stasis). Cattle are SENSITIVE & only need 1/10th the dose! (If you knew you were going to be smothered in A2 sauce, you'd lose your appetite & be sensitive about it too)
What are the routes of admin for the ANALGESIC effects of α-2s? (3)Parenteral ("not oral", so usually IV or injection), oral, epidural
When do side effects occur, in terms of the type of administration?Systemic administration
Location of α-2 receptors that produce analgesic effects?In brainstem (locus coeruleus) & Dorsal horn of the spinal cord (substantia gelatinosa) (α-2 has 2 weird locations)
What do α-2 agonists have synergism (combined effect greater than the sum of their separate effects) with?Opioids, local anesthetics, NMDA-antagonists

Local Anesthetics + NMDA antagonists + Tricyclic antidepressants + Anti-Epileptic Drugs

Question Answer
What are the clinical uses (administrations) of local anesthetics (control of pain)? (5)(1) Cutaneous- topical
(2) Infiltration (L-block, local anesthetic for everything under)
(3) Nerve blocks (block nerve, block everything under it)
(4) Spinal
(5) Epidural
What are the 2 major types of local anesthetics?Ester & Amide
What are the 2 portions of every local anesthetic molecule? Why do we like it this way?Lipophilic & hydrophilic portion (lipophilic for xport, hydrophilic for activity)
Explain differences of ester & amide local anesthetics?Ester = broken down/metabolized by tissue so 1/2life is short! Amide = NO metabolism in tissues, metabolized in liver, longer 1/2life (Ester=Easter=dead pretty quick)
What is the active form of the local anesthetics?Hydrophilic: ionized. *poor membrane passage
What is the inactive form of the local anesthetics?Lipophilic: non-ionized. *excellent membrane passage
What is the mode of action of local anesthetics? (5 →'s)lipophilic (non-ionized) can diffuse to inside of nerve fiber → Na+ ion-channel blocked by now-ionized form → this decreases Na+ ion permeability → inhibition of membrane depolarization → inhibition of conductance in nerve fibers
What is the pH of these local anesthetics? What happens if pH of tissue decreases? When would this happen?Weak bases...if pH drops in tissue, more drug is ionized, so it can’t get into nerve, so it's less effective. Implications for INFLAMED TISSUES (inject above, not at site, to avoid ionization for optimum effect)
What are the 2 NMDA antagonists?Ketamine & Tiletamine
How do NMDA antagonists work?Prevent glutamate induced depolarization (Ca++/Na+ channel), which reduces central sensitization
Do NMDA antagonists produce mm relaxation?No
How are tricyclic antidepressants related to control of pain? (Treats what in who?) They are used in the treatment of neuropathic pain in DOGS.
What is the tricyclic antidepressant drug given? What does it do?Amitriptyline, inhibits norepi re-uptake (Ami so depressed, she cant even RE-pick herself UP)
What control system do tricyclic antidepressants deal with?Central descending pain control systems
What do tricyclic antidepressants potentiate?Potentiates inhibitory pathways in dorsal horn of Spinal Cord
What are the 3 anti-epileptics used in control of pain?Gabapentin & Pregabalin, Carbamazepine (PREteens GABbing in a CAR make me want to have a SEIZURE or " a PRE GABA CARB making you Epileptic")
How do gabapentin & pregabalin work? (What do they bind to? cause?)Bind to α-2-delta-1 & α-2-delta-2 subunits of voltage-gated Ca++ channels - which inhibits NT release (it's a lot of gab to say those subunits)
What happens to the α-2-delta-1 & α-2-delta-2 subunits in damaged sensory neurons?(Ca channels) subunits are upregulated (they are involved in transmitting/ducing a signal of PAIN)
What does carbamazepine do? Block?Trigeminal neuralgia- blocks voltage-gated sodium channels (salty car snacks or " Tri Salty Carbs)
What happens to voltage-gated sodium channels in nerve damage?They are up-regulated, which contributes to the sensation of pain
Ion for NMDA?Nonselective (Na or Ca)
Ion for local anesthetics?Na
Ion for antiepileptics?Car = Na & Gab = Ca
Gabapentin/Pregabalin binds to?A2D1 A2D2