lecture 5 nervous system

what does the CNS do

takes in information and transmits it to the PNS for action

which nervous system controls involuntary things

autonomic nervous system

what are these examples of: HR, BP, rest, GI, repro

autonomic nervous system

-fight or flight

-activated during stress

-increased HR and RR

sympathetic nervous system

what are these neurotransmitters of: acetylcholine, epinephrine, norepinephrine

sympathetic nervous system

what are these receptors of: alpha 1, alpha 2, beta 1, beta 2

sympathetic nervous system

-rest & digest

-decreased HR and RR

parasympathetic nervous system

-activated during stress

-increased HR, RR, blood flow to muscle, pupil dilation

-decreased GI function

sympathetic NS- fight or flight

what is this a neurotransmitter of: acetylcholine

parasympathetic nervous system

postganglionic synapse

Epinephrine or Norepinephrine

blood vessel smooth muscle → arterial constriction

Alpha 1

CNS → inhibit norepinephrine in brain → sedation and analgesia

Alpha 2

heart → Incr HR and Contractility

Beta 1

lungs smooth muscle → bronchodilation

Beta 2

preganglionic and postganglionic synapses

acetylcholine

one of the primary inhibitory neurotransmitters in the CNS of mammals

GABA receptors

-amino acid located in the brain

-one of the primary excitatory neurotransmitters

glutamate

NMDA receptor

glutamate receptor in the brain, affects strength of synapses

-abnormal or uncontrolled electrical activity in the brain

-partial or full

-status epilepticus

seizure

nonstop seizures, >5 minutes-Emergency

status epilepticus

-suppresses transmission of abnormal electrical impulses

-controls, does not cure

-reduce frequency and severity

CNS depression

derived from barbituric acid

barbiturates

MOA:

-binds GABA receptor- neuroinhibitory effect

-inhibits release of acetylcholine, norepinephrine, and glutamate

-induces cytochrome P450 enzymes which cause the liver to clear out this drug faster

phenobarbital

metabolizes drugs so that the body can remove them

cytochrome P450

adverse effects:

-hepatotoxicity and liver failure (avoid if liver disease)

-anxiety/agitation, sedation, ataxia

-PU/PD/PP

phenobarbital

-first choice

-takes longer

-liquid or pills

-once daily

-metabolized by kidneys- not liver

potassium bromide

MOA:

-stimulates GABA receptor

-affects chloride ions and membrane hyper polarization

potassium bromide

adverse effectsf:

sedation, ataxia, hyperactivity, electrolyte imbalance, vomiting, PU/PD/PP, pancreatitis reported

potassium bromide (KBr)

MOA: binds GABA receptor and increases affinity for GABA, neurons action potential is inhibited

benzodiazepines

-C-IV

-given IV during seizure

Diazepam (valium)

adverse effects:

-sedation, CNS excitement

-caution with cats and aggressive animals

-appetite stimulation

Diazepam (valium)

-C-IV

-IV, IM, or intranasal, constant rate infusion (CRI)- water soluble

-use as part of anesthesia protocol

Midazolam

-C-IV

-IV for seizure treatment, IN and Buccal

-not metabolized by liver

Lorazepam (Ativan)

adverse effects:

-increased appetite

-ataxia

-vocalization

Lorazepam (Ativan)

-potentiates the effect of GABA on the receptor

-short-acting anesthetic induction agent

-can be used for status epileptics given IV

Propofol

adverse effects:

-apnea

-arrhythmias

Propofol

a secondary medication or substance given alongside a primary treatment to boost its effectiveness or reduce side effects

adjunct agents

MOA:

-not well understood

-affects release of neurotransmitters from synaptic vesicles

-prevent spread of seizure activity

Levetiracetam (Keppra)

-tablet or oral solution with 100% bioavailability

-not metabolized by liver

Levetiracetam (Keppra)

MOA:

-unknown

-possibly affects Na and Ca

Zonisamide

adverse effects:

-ataxia

-sedation

Zonisamide

MOA:

-inhibit Ca channels resulting in decreased excitatory neurotransmission

Gabapentin

-adjunct agent

-C-IV

-usually with phenobarbital

Clorazepate

-adjunct agent

-C-IV benzodiazepine

-dogs tolerance within a few weeks- short term use

-cats long-term use

Clonazepam

produce CNS depression to reduce irritability and excitement

sedative

used to calm and reduce anxiety and aggression

tranquilizer

reduce anxiety with no drowsiness

anxiolytic

-blocks CNS dopamine receptors for primary effect

-alpha-1 adrenergic receptor antagonist → HYPOTENSION

-no analgesia

Acepromazine

-binds GABA receptor and increases affinity for GABA

-muscle relaxation

Benzodiazepines

reversal agent for Benzodiazepines

Flumazenil

-binds and stimulates Alpha-2 Adrenergic Receptor

-CNS depression

-Bradycardia

-Hypertension

-analgesic

-only use in cardiovascularly stable patients

-reversible

Alpha-2 Adrenergic Agonists

what are these uses of:

-preop

-short procedures

-semi-induction

Alpha-2 Adrenergic Agonists

-dogs and cats

-IV, IM, SQ

-effect within 15 minutes

Dexmedetomidine

-horses and cattle

-combo with equine “Triple Drip“

-combo with cattle “K Stun“

Xylazine (Rompun)

equine “triple drip“

ketamine, xylazine, guaifenesin

cattle “K Stun“

ketamine, xylazine, butorphanol

-alpha-2 antagonist reversal agent

-adverse effects: occasional vomiting, diarrhea, hyper salivation, tremors

Atipamezole (Antisedan)

-alpha-2 antagonist reversal agent

-adverse effects: transient CNS stimulation, muscle tremors, salivation

Yohimbine (Xylazine)

adaptive response

acute pain

pain caused by body tissue damage

nociceptive pain

what type of nociceptive pain is this: muscle, skin, joints, connective tissue

somatic

what type of nociceptive pain is this: organ

visceral

-pain from damage or dysfunction of the nervous system

ex: limb amputation, chemo, brachial plexus injury, IVDD

neuropathic pain

-conversion of noxious stimulus into neuron electrical energy

-mechanical, chemical, thermal

-NSAIDs, lidocaine, opioids

transduction

pain signal travels from transduction site to spinal cord

-lidocaine, alpha-2

transmission

spinal cord enhances or decreases pain signal

ex: endorphins can inhibit pain signal

-lidocane, Alpha-2, opioid, dissociatives

modulation

-brain receives signal

-emotional and physical experience of pain

-general anesthesia, opioid, Alpha-2

perception

medical pain-management strategies used together around the time of surgery to stop pain signals

preventative and multi-modal analgesia

when combining a sedative or tranquilizer with an analgesic

uses: premed, intraop, post sx, minor procedures with other meds, dispensed analgesic, antitussive

neuroleptanalgesia

-high concentration in the nervous system

-also in GI tract, urinary tract, smooth muscle, sites of inflammation

opioid receptors

opioid receptor: analgesia, sedation, euphoria, respiratory depression, Bradycardia

Mu

opioid receptor: sedation, spinal analgesia

Kappa

opioid receptor: spinal cord analgesia

Delta

measure of the strength at which a drug binds to its receptor

affinity

the measure of drug activity in terms of the amount of the drug required to produce an effect

potency

the capacity to produce an effect and refers to the effectiveness of the drug once it is in the patient

efficacy

the ability of the drug to cause action in or on a cell in which the receptor is found

activity

which agonist are these: morphine, fentanyl, hydromorphone, oxymorphone, hydrocodone, remifentanil, meperidine, methadone, codeine

Mu Agonist

which agonist is this: buprenonorphine

Partial Mu Agonist

which agonist is this: butorphanol

Mixed Kappa Agonist and Mu Antagonist

which agonist is this: naloxone

Mu Antagonist

-Mu Agonist

-natural occurring opium derivative

-may cause histamine release- antihistamine with MCT Sx, when given rapidly IV

Morphine

-Mu Antagonist

-synthetic opioid, 100X more potent than morphine

-transdermal, injectable, tablet

-wear gloves

Fentanyl

-Mu Agonist

-synthetic, 5-7X more potent than morphine

-IM, IV, SQ, epidural, CRI

Hydromorphone

-Mu Agonist

-synthetic, 10X more potent than morphine

-IV, IM, SQ

Oxymorphone

-Mu Agonist

-NMDA receptor non-competitive antagonist

-synthetic opioid

-IV, IM, SQ

-less sedating and vomiting than other opioids

Methadone

-Mu Agonist

-synthetic

-oral cough suppressant

Hydrocodone

-Partial Mu Agonist

-IV, IM, epidural, transmucosal (significant first-pass effect - ensure transmucosal)

-one of the primary opioids for cats, not as much in dogs

Buprenorphine (Simbadol)

-Mixed Agonist/Antagonist

-will reduce analgesia of pure mu agonist if given together

-less respiratory dysfunction

Butorphanol

-Opioid Antagonist

-full Mu antagonist

-reverses analgesic effect

Naloxone

-opioid

-metabolite has Mu receptor activity

-dogs may not produce high quantities of the active metabolite

Tramadol

-opioid

-synthetic opioid antidiarrheal

Loperamide

-opioid

-emetic

Apomorphine

without perception/sensation

anesthesia

MOA: inhibit sodium influx into nerve cell → block neuron action potential depolarization

-pain signal stops

local anesthetics

local anesthetic:

-rapid onset and short duration

-accidental IV dangerous- cardiac effort

Lidocaine

-rapid onset and longer duration than Lidocaine

-accidental IV dangerous

Bupivacaine

eye drop applied to cornea

Proparacaine