DRUGS AFFECTING THE CNS

a. Narcotic – produces insensibility or stupor

(suspended sense, diminished responsiveness)
b. Hypnotic – narcotic agent, used to induce sleep
c. Sedative – narcotic agent, calms nerves and
produces drowsiness
d. Tranquilizer – or ataractic, sedation without
drowsiness
e. Neuroleptic – tranquilizer, treatment of
psychoses in human
f. Anesthetic agents – controllable and reversible
loss of consciousness and absence or response
to noxious stimuli
g. Dissociative agents – dissociation from
surroundings, unconsciousness, catalepsy, vivid
dreams and analgesia (in human); produces a
state of anesthesia
h. Analgesic agents – temporarily insensibility to
pain without loss of consciousness
i. Anticonvulsant – inhibit excessive motor
stimulation at the CNS
j. CNS stimulant – increase CNS stimulation
k. Hypnotic, Sedative, and Tranquilizer
CNS depression stages – sedation, hypnosis, and
ataraxia
Drugs that can produce calmness and promote
sleep

DRUGS ACTING ON THE CNS

1. Tranquilizer – Sedative Group

- Phenothiazine derivatives
- Butyrophenone derivatives
- Benzodiazepines
2. Sedative – Hypnotic Group
- Barbiturates
- Chloral hydrate
- Alpha-adrenergic agonist
 Retrograde regional Anesthesia

- IV injection of local anesthetic into a limb with

circulation briefly occluded by a tourniquet

Local Anesthetics

Amino-Ester Amino-Amide
Procaine Lidocaine
Chloroprocaine Mepivacaine
Tetracaine Bupivacaine
Coccaine Dibucaine

Note: Skeletal muscle twitching is the 1 st indicator of

Propofol – 7.6mg/kg induction of anesthesia local anesthetic toxicity

1 to 5 ml – usual dose of local anesthetics

ANALGESICS, ANTICONVULSANTS CNS STIMULANTS

Analgesics

 Opioids
 NSAIDs
 Steroids
 Local Anesthetics

PAIN

Isoflurane, Enflurane, and CO2– commonly used

Opioids

- Opioid receptors: mu (μ), kappa (K), delta (δ)

Epidural Anesthesia
a. Cranial epidural – lumbosacral junction site
b. Caudal epidural – sacrococcygeal junction
- Endogenous Opioid antagonist:
Endorphins, Enkephalins
- Morphine – opiates, drug derived from
opium
- Oxymorphone, codeine – derivatives
- Meperidine, butorphanol, Proxyphene –
substitute
- Fentanyl
 Pharmacologic Effects of Opioids analgesic and anti-inflammatory actions of
NSAIDS
CNS Analgesia, Drowsiness, Excitatory
effects, Euphoria; nausea; emesis STEROIDS
Respi Depression
Cardiac Arteriolar dilatation MOA
Gut Enhance segmental contraction, - blocks the enzyme phospholipase which
increase sphincter tone catalyze conversion of phospholipids to
Antidiarrheal effect
prostaglandin
- reduce inflammation by interfering with
NSAIDS interferon synthesis
- Induced fibroblast activity
- Collagen synthesis and tissue repair
- Inhibit interleukin, chemotactic factors, and
interferon synthesis

Short Acting Hydrocortisone

( < 24hrs) Cortisone, Prednisolone
Methylprednisolone
Intermediate Triamcinolone
Acting (24-48hrs)
Long Acting Flumethasone
( > 48hrs) Dexamethasone
Bethasone
Local Anesthetics

NSAIDS prevents the formation of Prostaglandin
- Produce their analgesic effect by virtue of their
anti-prostaglandin synthetase action
- May have antipyretic and anti-inflammatory
effects
- Major problem: GASTRIC IRRITATION
- Stabilize nerve membranes thereby ingibiting
propagation of action potential
Anticonvulsants
- Used when there is excessive brain stimulation
- IV route but for long term maintenance, the
oral route is preferred

First Line Maintenance

Phenobarbital Dogs/Cats 2-4 mg/kg PO

Phenytoin
Primidone (hepatotoxic)
Diazepam Cats 0.25-0.5 mg/kg PO
Bromide (sodium salt)
Second Line Maintenance

Clonazepam Dogs 0.1 – 0.5 mg/kg PO

Clorazepate Dogs 0.5 -1 mg/kg PO
Felbamate Dogs 15 mg/kg PO
Gabapentin Dogs 10 mg/kg PO
Levetiracetam Dogs 20 mg/kg PO
MOA Valproic acid Dogs 5 to 10 mg/kg PO
- Inhibits the COX-2 to reduce the biosynthesis of Zonisamide Dogs 5mg/kg/day
prostaglandins producing the antipyretic, 10mg/kg following
phenobarbital
CNS STIMULANTS

- Used for overdose of anesthetics during

surgeries, CS

Doxapram HCl Stimulate chemoreceptors of

carotid and aortic regions
Given UV, SC, SL in neonates
Nikethamide
Yohimbine HCl Block alpha-adrenergic receptors
capable of antagonizing the action
of xylazine
Block cholinergic, serotonergic and
GABAnergic receptors
Carbon Dioxide Mild hypercapnia can improve
cardiac output and arterial blood Trivia Question:
pressure
Naloxone Opioid antagonist Nicotinic receptors sites are found in all of the following
locations, except:

Classes of NMJ-blocking agents a. Parasympathetic ganglia

b. Sympathetic ganglia
A. Non-depolarizing Neuromuscular blocking drug c. Skeletal muscle
- Compete with acetylcholine for cholinergic d. Bronchial smooth muscle
receptors in the end plate
- Does not cause depolarization at the end plate Answer: D
potential
Which of the following is not a direct acting cholinergic
Non-depolarizing agent?

D-tubocurarine -5min onset of action IV a. Metacholine

(curare) -Cause paralysis for 20-30 min b. Carbachol
-Use for setting bone fracture c. Physostigmine
-Can cause transient hypotension d. Bethanecol
due to release of histamine e. Muscarine
Gallamine 20% as potent as curare
Has little tendency to stimulate Answer: C
the release of histamine
Rationale: Physostigmine doesn’t bind directyly to the
Pancuronium 5% more potent than curare
receptor instead they inhibitd acetylcholinesterase. So
Contraindicated in renal failure
by interfering with the metabolism of Ach,
and cardiovascular shock
physostigmine indirectly stimulates both nicotinic and
muscarinic receptors due to the increase in available
Depolarizing NM Blocking Agent Ach at the synapse.
Succinylcholine -Causes end-plate potential, Pilocarpine – indication for glaucoma (accumulation of
muscle action potential fluids in the eye)
(cannot be reverse by -Caused prolong
AchE inhibitor depolarization, does not Pilocarpine stimulates muscarinic receptors thus
(neostigmine), but allow subsynaptic contraction of the iris sphincter muscle and ciliary
degraded slowly by membrane to completely muscle
pseudocholinesterase) repolarize
-Cause transient contraction
of muscle
Scopolamine Indirect acting Adrenergic Agents

- Interferes the transmission of nerve impulses by Amphetamine

acetylcholine in the parasympathetic nervous  Metamphetamine
system  Ephedrine
- Used as pre-anesthetic agents because it  Pseudoephedrine
prevents the release of acetylcholine but it  Phenylpropanolamine
decreases the heart rate, that’s why atropine is  Metaraminol
preferably used
- Used in ophthalmic examination because it Amphetamine Cns stimulant
enlarges the pupil Metamphetamine
- Antidote for Organophosphate Poisoning Ephedrine Activates adrenergic
receptors
- Antispasmodic therapy esp in GI tract spasms
Inhibits NE reuptake and
and peristalsis
increase the release of
NE from vesicles
Pseudoephedrine Acts on alpha adrenergic
receptors in the
respiratory producing
vasoconstriction
Phenylpropanolamine Same with pseudo
Metaraminol Peripheral
vasoconstriction

Epinephrine

- Acts on alpha 1 receptors

- Adjunct to procaine
- Use as styptics (Stop bleeding)
B1 – mostly seen in the HEART - For cardiac arrest, hypersensitivity reaction and
B2 – seen in the LUNGS asthma
Tranquilizer – Sedative Group
a. Phenothiazine derivatives
- Promazine, acepromazine, chlorpromazine
- Block post-synaptic dopamine receptors in CNS
- Inhibit release or increase turnover rate of
dopamine
- Depress portion of the Reticular Activating
System
- Anticholinergic, antihistaminic, antispasmodic
and alpha-adrenergic antagonist
- Tranquilizers formerly used as antipsychotic
drug
- Neuroleptic – modifying psychotic behavior
Classification
- Sedatives/hypnotics/anxiolytics, a-adrenergic
antagonists
MOA
- Inhibit central dopaminergic receptors (D2),
which produces sedation and tranquilization
In the CNS – depresses the brain stem and connections
to the cerebral cortex
In the CVS – blocks alpha-adrenergic receptors which
results in peripheral vasodilation. Lowered heart rate,
although a mild reflex tachycardia can be seen in
patients with clinical hypotension
In the Respiratory and Musculo – have little effects in
respi but provide good muscle relaxation
Other actions:
- Alter thermoregulation due to decreased
catecholamine in the hypothalamus
- Decrease platelet aggregation
- Reduce hematocrit of animal due to splenic
sequestration
- Antiemetic due to blockade of CRTZ
- Experimental phototoxicity
- Have little or NO ANALGESIC EFFECT
Acepromazine Maleate - Most used phenothiazine
Promazine HCl – given as granular oral medication
Chlorpromazine HCl – primarily used as antiemetic
- Contraindicated in horses due to extreme ataxia
and altered mentation
Species Differences
Horse – associated with prolonged paraphimosis
Dog – should not be used in (generally) brachiocephalic
breed of dogs (boxer, bulldogs) due to exaggerated
reaction (sedation, hypotension)
Pig – prevents malignant hyperthermia associated with
halothane anesthetics
Drug Interaction
- CNS depressants, drugs that produce
vasodilation and hypotension
Contraindication
- Dehydrated, hypovolemic, bleeding, or in shock
because of the drugs’ effect on vessel tone
(vasodilation)
- Patients with coagulopathies or
thrombocytopenia due to their effect on
platelet aggregation
- Used cautiously in brachiocephalic dogs,
breeding stallions and debilitated animals
Tranquilizer – Sedative Group
Butyrophenone Derivatives
- One of the major classes of antipsychotic drugs
in use
- NO ANALGESIC EFFECT
MOA
- Neuroleptic sedative, which has its main effect
mediated via dopaminergic (D2) antagonism
- Have antagonistic activity against alpha 1-
adrenergic, histaminergic, and cholinergic
receptors
Indications
Azaperone – antipsychotic effect in swine for its calming
effects when mixing weanlings and feeder pigs,
transportation, or obstetrical conditions; prevent
aggression of sows directed toward piglets
Azaperone and Droperidol – used as a preoperative
sedative
Droperidol – very effective antiemetic that involves the
CRTZ
Other effects:
In CNS – sedation for restraint
In CVS – reduce arterial blood pressure
Respi – mild effects on ventilation
Musculo – reduced muscle tone
Droperidol – antiemetic, antithrombotic effect, post-
sedation aggression
Benzodiazeperine Derivatives
- Sedative-hypnotics due to their propensity to
cause anxiolysis, sedation, and sleep; classified
as minor tranquilizers
- NO ANALGESIC EFFECT
MOA
- Bind to and activate the benzodiazepine
receptor binding site, which is located on the
gamma subunit of the GABA A
Indications
- Anticonvulsants, adjuncts to anesthetic
induction age, skeletal muscle relaxants, and for
behavioral modification
In CNS – given alone to induce sedation can cause
unpredictable results; paradoxical excitement, agitation,
vocalization, and dysphoria
In CVS – cause minimal cardiovascular depression and
are commonly administered to patients with
cardiovascular disease
Respi – produce a mild, but dose dependent, respiratory
depression
Musculo – potentiate the GABA-ergic-mediated muscle
relaxation of inhibitory neurons at the level of the spinal
cord
a. Propylene glycol vehicle/preparation – may
induce pain when administered IV; lysis of RBC
b. Diazepam
- appetite stimulants, sp. In cats
- highly lipid-soluble which has a much shorter
duration of action in dogs and cats compared
with people
- unwanted side effects of diazepam use are
caused by the vehicle propylene glycol
c. Midazolam maleate
- Water-soluble characteristic due to the
presence of the imidazole ring structure
- Has approximately twice the potency and BZ
receptor affinity as compared with diazepam
d. Lorazepam
- 10x as potent as diazepam
- Absorbed nearly complete by any route given
e. Zolazepam
- Similar to diazepam; only available combi with
tiletamine (Zoletil)
Adverse Effects/Contraindication
- Caution at fear-induced aggression patients, as
the disinhibition caused by the benzodiazepines
may provoke an attack
Benzodiazeperine Antagonists
Flumazenil
- High affinity for BZ receptor site
- Virtually no agonist activity
MOA
- Binding site on the GABA A, thus preventing the
resultant hyperpolarization of the postsynaptic
membrane
Barbiturates
- Synthesized by Adolph von Beyer from
barbituric acid
Classification
Long -acting – Phenobarbital, Barbital
Short-acting – Pentobarbital, Secobarbital
Ultra-short acting – Thiopental, Thiamylal, Methohexital
MOA
- Depression of reticular activating system
- Increase GABA binding by decreasing the
dissociation rate of GABA from receptor
- Blocks glutamate at AMPA receptors
 - Decrease transmission of nerve impulses at
nicotinic Ach receptors in the NMJ

a. Thiopental Na
- Ultrashort acting, No. 2 C has attached Sulfur
- Can be mixed with propofol – produces
synergistic clinical effect, improves induction
and recovery
b. Thiamylal
- Ultrashort acting
- Thiobarbiturate analogue of secobarbital
- Higher incidence of bigeminy (continuous
alteration of long and short heart beats)
c. Pentobarbital
- Short acting oxybarbiturates
- Longer duration of action than thiopental
- For long term anticonvulsant treatment
d. Phenobarbital sodium
- Long acting
- Anticonvulsant and long-term sedation
e. Methohexital Na
- Or Methohexitone
- Ultrashort-acting oxybarbiturates
- 2x potent than thiopental
- Activates abnormal EEG
- Should not be used in px with increased CNS
excitation (E.g. Strychnine Poisoning)
- Causes excitement and activation of epileptic
foci

*Strychnine Poisoning

- due to simultaneous contraction of both groups of

muscles the body gets a typical posture called
opisthotonos

f. Secobarbital

- short acting known as quinalbarbitone

g. Barbital

- or barbitone, first commercially available barbiturate