Classification of drugs acting on

Central Nervous System

Dr. Kumari Anjana

Assistant Professor
Deptt. of Veterinary Pharmacology & Toxicology
Bihar Veterinary College, Bihar Animal Sciences University,
Patna
 Classification of drugs acting on
Central Nervous System
 The CNS is an extremely Complex and
heterogeneous system. It is the major coordinating
system of the body & source of adjustment of an
organism to its environment.
 Function-rapid communication system and is
responsible for moment to moment control of various
body activities.
 It regulates-rapidly changing visceral events, muscle
contractions, secretions of some endocrine glands
 Classification of drugs acting
contd…

on sensitive
 The CNS is more CNS to effects of drugs than
any other system of the body.
 A large number of drugs influence the CNS as a
major part of their therapeutic effect (e. g,.
anaesthesia), side effect & toxic effect, divided
into two major groups:
CNS stimulants drugs
CNS depressant drugs
 CNS stimulants drugs
Classification
1. On the basis of part of CNS where drug
act:
 Spinal Stimulants or convulsants:
Strychnine, picrotoxin
 Medullary Stimulants: Doxapram, Bemegride,
Picrotoxin, Nikethamide, Leptazol
 Cortical Stimulants: Cocaine, amphetamine,
methylxanthines.
 CNS stimulants drugs contd…

Classification
2. On the basis of action (Direct or Indirect):
 Direct acting stimulants : Strychnine,
picrotoxin and xanthenes derivatives.
 Indirect (Reflexly) acting stimulants:
lobeline, ammonia, Veratrum, nicotine.
 CNS stimulants drugs contd…

Classification
3. On the basis of clinical uses:
 Analeptics: Nikethamide, bemegride,
doxapram.
 Psychostimulents: Amphetamines,
methylphenidate, cocaine, methylxanthines,
caffeine, theophylline.
 Cerebroactive drugs: Piracetam,
 CNS depressant drugs

Classification
 Tranquillizer sedatives : Chlorpromazine,
Azaperone, Droperidol, Haloperidol.
(Neuroleptics, Ataractics,
Tranquillizers)
 Hypnotic sedatives : Chloralhydrate, Xylazine,
Detomidine, Medetomidine, Phenobarbitone,
Diazepam, Zolazepam.
 CNS depressant drugs contd…

Classification
 General Anaesthetics: Ether, Halothane,
Enflurane, Isoflurane, Chloroform,
Methoxyflurane
 Analgesics : Acetylsalicylate, Salicylate,
Phenylbutazone, Isopyrin, Ibuprofen
 CNS depressant drugs contd…

Classification
 Central muscle relaxants: Guaiphenesin,
Mephenesin.
 Anticonvulsants : Phenobarbitone, Phenytoin,
Diazepam, Carbamazepine, (Antiepileptics)
Ethosuximide
 Neuroleptanalgesics: Fentanyl + Droperidol
Thank You
 Mechanism of
General Anaesthesia

Dr.Kumari Anjana
Assistant Professor
Deptt. of Veterinary Pharmacology & Toxicology
Bihar Veterinary College, Bihar Animal Sciences University,
Patna
Theories of General Anaesthesia
(Mode of action)
 MOA of GA has been studied for many
decades but still there is no clear
explanation.
 GA belong to different chemical classes and
can produce anaesthesia in variable ways.
 Anaesthetics appear to act principally on
the cell membrane.
 Theories of General Anaesthesia focus
primarily on the interaction of anaesthetics
 Lipid solubility theory of Overton and Meyer (1901)
 Compounds with high lipid solubility easily penetrate
the CNS, being rich in lipids, and alter the function of
nerves.
 Theory: Potency of an anaesthetic is directly
proportional to its affinity and solubility in lipid
portion of the nerves.
 Higher the partition coefficient, higher the potency of
anesthetics
Figure: Interpretation
 Solubility in Fat / Solubility in Water = Partition of the
Coefficient. cut-off effect in the
frame off lipid
hypothesis of
anesthetic mechanism.
 Surface Tension or Adsorption Theory of
Traube (1904)
 Ability of the agent to reduce the surface tension of
the neuronal membrane by adsorption.
 Alters the transmembrane ionic permeability across
the neuronal membrane and interfere with nerve
function (generation of AP), resulting into anesthesia.
 Warbung (1921, 1930) : Accumulation of narcotic
agent on cell surface caused alteration of metabolic
processes, permeability and neuronal transmission
resulting in anaesthesia.
 Elements and Wilson (1962) : Nitrous oxide,
cyclopropane, halothane and chloroform lower the
 Microcrystal Theory of Pauling and Miller
(1961)
 Anesthetics facilitate formation of microcrystals
or iceberg/clathrates: (anesthetics hydrate
crystals) ice crystals within the nerve cells and
thus disrupt conductance of impulses.
 Impede ionic mobility, electrical charge, and
chemical and enzymatic activity of the brain,
(produce depression and unconsciousness).
 This theory does not explain anesthesia
produced by barbiturates and some other
anesthetics.
Protein Binding Theory of Frank and Lieb
(1982)
 Anaesthetics act by
reversibly binding to a
hydrophobic domain of a
protein or by concentrating
at the lipid-protein
interface in the nerve cell
membrane.
 The binding causes
expansion of the nerve
membrane and thus
interferes with the function
 Bulky and hydrophobic anaesthetic molecules
accumulate inside the neuronal cell
membrane causing its distortion and expansion
(thickening) due to volume displacement.

 Membrane thickening reversibly alters

function of membrane ion channels thus providing
anaesthetic effect.

 Actual chemical structure of the anaesthetic agent

was not important, but its molecular volume plays
the major role: the more space within
membrane is occupied by anaesthetic - the
greater is the anaesthetic effect.
 Receptor Theory
 Anaesthetics act by interacting with the NT receptors (as
agonists of inhibitory transmitters, GABA and
glycine or antagonist of excitatory transmitter,
glutamate, Ach and 5-HT,) in the CNS.
 Anaesthetic agents affect synaptic transmission rather
than axonal conduction.
GABAA receptors - Halogenated anaesthetics (halothane,
enflurane, isoflurane & sevoflurane) and some
injectable anaesthetics like barbiturates, propofol,
etomidate and neurosteroids.
Glycine receptors - Propofol, Barbiturates.
NMDA (N-methyl-D- aspartate) receptors -Ketamine, N2O.
 Ion Channel Theory

 Anaesthetic bind to voltage-gated ion

channels and reduce excitability or
promote inhibition of nerve membrane.
Thank You
 Intravenous Anaesthetics
(Dissociative & other
anaesthetics)

Dr.Kumari Anjana
Assistant Professor
Deptt. of Veterinary Pharmacology & Toxicology
Bihar Veterinary College, Bihar Animal Sciences University,
Patna
 Dissociative anaesthetics
 These are the agents that induce a state of
altered CNS activity in which the anaesthetised
patient feels totally dissociated from its
surroundings during induction.
 These agents produce marked sensory loss,
analgesia, amnesia and paralysis of movements
without apparent loss of consciousness ( patients
appears to be awake but actually is
unconsciousness).
 The term Dissociative anaesthetics is derived
primarily from use of ketamine in man and
 Dissociative anaesthetics contd…

 Dissociative anaesthetics- ketamine, tiletamine,

Phencyclidine
 It act as antagonists of excitatory amino acid
glutamate( at NMDA type glutamate receptor) and
interfere with neuronal transport of 5- HT, dopamine and
noradrenaline in CNS.
 Act on cerebral cortex.
 At anaesthetic dose no significant effect on respiration,
increase in BP and Heart rate due to sympathetic
stimulation (can be used in patients in CV).
 Preanaesthetic diazepam, acepromazine or xylazine
Ketamine
 It is a general anaesthetic which was first
introduced in 1965 for use in humans.
 In 1970, it was introduced for anaesthesia in the
cat.
 The important features of Ketamine are as below:
o It induces only stage I and II but not III &
IV.
o It does not act on ARS (Ascending
Reticular System) like other general
anaesthetics.
 Ketamine contd…

o It produces depression of thalamoneocortical

system and stimulation of limbic system.
Therefore, due to dual action, Ketamine is
called dissociative anaesthetic.
o It induces anaesthesia and amnesia (loss of
memory) by functional disruption
(dissociation) of CNS through marked CNS
excitation.
o It produces dissociation or complete
unawareness of environment due to amnesia
Actions of Ketamine on Cardiovascular System
(CVS)
 Ketamine increases cardiac output, blood pressure,
central venous pressure and heart rate.
 Cardiac stimulatory properties prove it a good
induction agent for poor risk and hypovolemic
patients.
 It does not depress respiration, there is profound
analgesia and amnesia, muscle relaxation is poor,
induction rapid but recovery is prolonged. There is
only little salivation which is not a problem, swallowing
reflex is impaired.
 It possesses wide margin of safety i.e. 5 times than
 Dosage of Ketamine
 Dog : As anaesthetic – 10 mg/kg IV after diazepam
(0.5mg/kg)
As restraining -- 10 mg/kg after acepromazine (0.5mg/kg)
 Horse: 2 mg/kg IV in combination with diazepam
(0.2mg/kg) and xylazine (0.1mg/kg)
 Cattle: induction- 2 mg/kg rapid IV or IV
maintenance: 0.2 % ketamine in normal saline
solution administered @ 10 ml/min.
 Goat: 10 mg/kg IV after xylazine (0.2mg/kg)
Phencyclidine
 Effect on CNS is species specific.
 Depression in dog and other species.
 Low doses - Depression
High doses – convulsion/ excitation.
 It is used in subhuman primates.

Tiletamine
 It is used with pre-medication of zolazepam
(sheep, pigs, horses, dogs & cats).
 Steroidal anesthetics- saffan/ Althesin
 First injectable steroid anaesthetic - hydroxydione
Na.
 Toxicity (thrombophlebitis), its use was discontinued.
 A Steroidal anaesthetics generally used for induction
of anesthesia.
 It contains two pregnanedions, alphaxalone (steroid
I)-alphadolone(steroid II).
 Produces rapid induction of short duration
anaesthesia.
 Steroidal anesthetics- saffan/ Althesin
contd…
 Althesin is combination of two steroid drugs
solubilized in an aqueous formulation containing
polyethylated castor oil (Cremophor EL).
 Alphadolone has less anaesthetic activity than
alphaxalone but is included to improve the solubility.
 Contraindicated –not used in dogs due to vehicle
surfactant (Cremophor EL) in the preperation causes
excessive histamine release from mast cells resulting
in profound depression.
Propofol
 It resembles thiopentone in being highly lipid
soluble.
 It is an oily liquid introduced as 1% emulsion for IV
induction and short duration of anesthesia.
 Quick recovery - rapidly metabolized.
 No hangover like thiopentone sodium.

Etomidate
 Has potent hypnotic effect but no analgesic effect.
 Has wide margin of safety.
Metomidate
 It is recommonded for anesthesia in birds.
 Also in pig, dog & cats.
 Has wide margin of safety.
 No hangover like thiopentone sodium

Urethane
 Also called Ethyl carbamate.
 Chemically related to urea.
 Commonly used in laboratory animals.
Chloralose
 It is the condensation product of glucose and
chloralhydrate.
 it is transformed to chloraldehyde which is further
metabolized to trichloroethanol.
 Produces dissociative anaesthesia like Ketamine.

Midazolam
 A benzodiazepines derivatives with slower onset of
anesthetic action.
 It has no respiratory or cardiovascular depressant effect.
 In human it is generally used as a preoperative
sedative for endoscopy or other probing
Thank You
 ANTIPSYCHOTIC
S

Dr. Kumari Anjana

Assistant Professor
Deptt. of Veterinary Pharmacology & Toxicology
Bihar Veterinary College, Bihar Animal Sciences University,
Patna
 ANTIPSYCHOTICS
 These drugs are used in psychological disorders
or affective disorders.
 Affective disorders are nervous disorders
characterized by abnormal mood.
 The abnormal mood changes are:
1) Depression and 2) Mania.
 Therefore, these drugs are of two types:
1) Antidepressants and 2) Antimaniac drugs
 Antidepressants
 Are drugs used in the treatment of abnormal mood
and behavior due to depression.
 These drugs are also called as Thymoleptics or Mood
Elevators.
 Depression is characterized by feeling of sadness or
misery, loss of concentration or self-confidence,
disinterest in surroundings, loss of libido, anorexia,
lowered energy and insomnia (sleeplessness) or
hypersomnia (excessive sleep).
 Pharmacologically it is due to deficiency of
monoamines in limbic system in brain.
 Depression is treated by administering antidepressants.
 Classification of Antidepressants

 Tricyclic Anti-depressants :
Impramine, Desipramine, Amitriptyline,
Protriptyline, Clomipramine, Doxepine,
Amoxapine, Mitrazapine, Nifazadone,
Trazodone, Maprotilne.
 Monoamine Oxidase (MAO) Inhibitors-
Phenelzine, Tranylcypromine Isocarboxazid,
Moclobemide, Iproniazid, Selegiline.
 5-HT re-uptake Inhibitors-
Fluoxetine, Fluvoxamine, Paroxetine,
Sertraline, Citralopram, Reboxitine,
Classification of Antidepressants:
Tricyclic Anti-depressants:
 NA+5 HT reuptake inhibitors- Impramine, Protriptyline,
Amitriptyline,
Doxepine, Clomipramine,
Mitrazapine,
Nifazadone, Trazodone, Maprotilne.
 Predominantly NA reuptake inhibitors- Desipramine,
Nortriptyline,
Amoxapine, Reboxetine.
Monoamine Oxidase (MAOA) Inhibitors-- Phenelzine,
Tranylcypromine
Isocarboxazid, Moclobemide,
Iproniazid, clorgyline
 Mode of Action
 Tricyclic Anti-depressants- Act by inhibiting uptake of
noradrenaline and/or 5-HT by monoaminergic nerve
terminals, thus acutely facilitating transmission.

 Monoamine Oxidase (MAO) Inhibitors-- Inhibit one or both

forms of brain MAO: Increase stores of noradrenaline,
dopamine and 5-HT in nerve terminals. Inhibition of both
MAO types correlates with antidepressant activity.

 5-HT re uptake Inhibitors-- Act by inhibiting uptake of 5–HT

by tryptaminergic nerve terminals, thus acutely facilitating
5-HT transmission.
 MAOA enzyme is specific to epinephrine and
norepinephrine and MAOB is specific to dopamine
and 5-HT.
 Cheese, wine and chocolate contain tyramine,
which degraded in liver by MAOA before systemic
absorption.
 Ingestion of these foods in patients under MAO
inhibitor antidepressant therapy results in server
hypertensive crisis (Tyramine is adsorbed and taken
up by the adrenergic nerves, converted to
octopamine, a false transmitter, which releases
 Antimaniac Drugs
 Mania is characterized by excessive exuberance,
enthusiasm, over self-confidence, easy irritability,
aggressive behavior or hyperactivity and improper
judgement. Pharmacologically it is due to
dopaminergic over activity in the limbic system in
brain.
Drugs for treatment of mania are:
1) Lithium carbonate, 2) Carbamazepine and 3)
Valproate.

 Lithium carbonate
 Lithium is a small monovalent cation (Li+).
 Lithium readily enters excitable cells through the
Na+ channels displacing intracellular K+ and is
nearly equally distributed inside and outside the
cells (Na+ and K+).
 The influx of K+ is reduced by inhibition of Na+/K+
ATPase and the electrical gradient of K+(increased
extracellular K+ level).
 The reversal of K+ levels results in lowered
neuronal excitability causing calming of the
maniac individual.
 Lithium carbonate contd…

 It also reduces release of norepinephrine and

dopamine in brain, without affecting 5-HT
release.
 Lithium is also believed interfere with the
transduction mechanisms of central adrenergic
receptor activation through decreasing the
formation of second messenger cAMP and IP3.
 Thus, lithium is acting through decreasing
neuronal excitability and correcting the
imbalance of turnover and/or actions of
Thank You
Thank You
 ANTICONVULSA
NTS
Dr. Kumari Anjana
Assistant Professor
Deptt. of Veterinary Pharmacology & Toxicology
Bihar Veterinary College, Bihar Animal Sciences University, Patna
 ANTICONVULSANTS

 Anticonvulsants are drugs that depress the CNS

and control convulsions.
 These drugs are intended for the treatment of
various convulsive/ seizure disorders in man and
animals.
 The primary use of anticonvulsants is in epilepsy
hence they are also called antiepileptics.
 Epilepsy
 The term epilepsy refers to a disorder of brain function characterized
by the periodic and unpredictable occurrence of seizures.
 Epilepsy is a collective name given to a group of chronic CNS disorders
(syndrome) manifesting ---
spontaneous occurrence of seizures of brief duration,
loss or disturbance of consciousness,
abnormal body movements,
abnormal and excessive electroencephalographic (EEG) discharges,
and sensory, autonomic and/or behavior phenomenon.
 Seizures are thought to arise from the cerebral cortex in brain and
their manifestations depend on site of the focus or region into which
the discharges spread.
 In veterinary medicine, epilepsy is most common in dogs (1% of all
canine diseases), although cases also occur in cats, horses and cattle.
 Classification
 The epilepsy is classified mainly on the basis of occurrence of seizures in
humans but may also include animals.
 Epileptic seizures have been classified into
1.Generalized Seizures
i) Tonic-clonic seizure/Grand mal epilepsy
ii) Absence seizure/Petit mal epilepsy
iii) Myoclonic seizure

2. Partial (localised or focal) Seizures

i) Simple partial seizure/Cortical focal epilepsy
ii) Complex partial seizure/Psychomotor epilepsy
iii) Partial with secondarily generalized tonic-clonic seizures
 1. Generalized seizures:
 Generalised seizures are bilateral (involve both
hemispheres) and symmetric, and do not have a
specific locus of onset in the brain.
 The most common generalized seizures include:
i) Tonic-clonic seizure/Grand mal epilepsy: It is
characterized by tonic rigidity of extremities
followed by massive clonic jerking for several
minutes. It is the most common form of epilepsy in
dogs.
 ii) Absence seizure/Petit mal epilepsy: It is
characterized by momentary loss of consciousness
associated with staring and cessation of activities.
 There is clonic jerking of eyelids but no motor activity.
 In human beings, absence seizures mainly occur in
children; whether it occurs in dogs is unclear.
 iii) Myoclonic seizure: It is characterised by a brief
(perhaps a second) shock like condition of muscles of a
limb/extremity or the whole body.
 The myoclonic epilepsies occur in dogs but treatment is
usually not undertaken.
2. Partial/Localised seizures:
Partial seizures originate in a specific part of brain and
are often associated with the structural disease of
brain.

Partial seizures are less commonly seen in canines

than the generalized seizures.

In animals, partial seizures are more difficult to

diagnose and treat than generalised seizures and,
therefore, carry a poorer prognosis.

Partial seizures may be subdivided according to the

 i) Simple partial seizure/Cortical focal
epilepsy: It is associated with preservation of
consciousness.

 Seizures are confined to a group of muscles or

localised sensory disturbance depending on the
area of cortex involved in the seizure.
ii) Complex partial seizure/Psychomotor
epilepsy:
 It is characterized by impaired consciousness with
bizarre and confused behaviour, and purposeless
movements.
In this epilepsy, the discharges become more
widespread and complex motor or behavioral
aberrations are seen.
The seizure focus is located in the temporal lobe
of the cerebrum, so it is also called temporal
iii) Partial with secondarily generalized
tonic-clonic seizures:
 In this type, the partial seizure (simple or
complex) occurs first and evolves into
generalised tonic-clonic seizure with loss of
consciousness.
3. Other terms: Apart from epileptic seizures
classification given above, some additional terms
are used to specify type or condition of epilepsy.
These include-
 Idiopathic/Primary epilepsy:
The term idiopathic or primary epilepsy is used
for recurrent seizures resulting from a functional
disorder of the brain.
This includes those cases where no cause for the
seizure can be identified hence no
histopathological lesions can be demonstrated
ii)Secondary/Symptomatic epilepsy:
 This type of epilepsy designates the disorder
when factors like neoplasm, infection,
poisoning, fever, developmental abnormality,
cerebrovascular disease, withdrawal of certain
drugs, or various metabolic disorders
contribute to the cause of the disease.
 
iii) Cluster epilepsy:
 The term 'cluster epilepsy' is used when there are
multiple isolated seizures in a short period
of time.
 Some dogs usually of the large breeds like
German Shepherds or Golden Retrievers
suffer from cluster epilepsy that is 3 to 15
seizures in close succession over 24 to 48 hours
followed by an interval of 1 to 3 weeks.
iv) Status epilepticus:
The term 'status epilepticus' is used to describe
epileptic seizures that are so frequently
repeated or so prolonged as to create a fixed
and lasting epileptic condition.
In this type, patient has a subsequent
generalized seizure before recovering from
the initial seizure.
In status epilepticus, there may be extreme
exhaustion, hyperpyrexia or even death.
 Pathophysiology of Seizures
 Seizures are clinical result of rapid and excessive
neuronal discharge in the brain.
 These usually result from an alteration in normal
neuronal excitability.
 Normally, a balance of neuronal excitation and
inhibition exists such that electrical activity is not
propagated unrestrained.
 If the balance is altered in favour of inhibition,
sedation and anesthesia occurs and if neuronal
excitation predominates over inhibition, the
potential for a seizure increases.
 For excitation to abnormally predominate over
inhibition, one of at least 4 possible events are likely
to occur.
a) There may be increased availability of excitatory
neurotransmitter such as glutamate and acetylcholine
due either to increased production and release or to
impaired metabolism or re-uptake.
 These neurotransmitters bind to their respective
receptors and open cationic channels for Na+, Ca++,
and perhaps K+.
 This causes the resting membrane potential to
depolarize, producing an action potential and
 b) There may be decreased availability of inhibitory
neurotransmitter such as GABA, the most potent
inhibitory neurotransmitter in the CNS.
 The decreased activity of inhibitory transmitters allows
excitatory neurotransmitters to predominate and
produce excitation.
 c)There may be altered neuronal membrane function
that can lead to excessive depolarisation (e.g.,
alteration of the Na+ pump) or permeability changes in
the cell membranes (induced, for example, by hypoxia,
inflammation or trauma).
 A derangement of cellular metabolism alters also
resting membrane potential or ability of the cell to
 d)There may be altered extracellular potassium
and calcium concentrations.
 During a seizure, extracellular potassium
increases and calcium decreases.
 This results in increased neuronal excitability
which facilitates the initiation and spread of
seizure.
Thank You
Thank You
 Opioid analgesics

Dr. Kumari Anjana

Assistant Professor
Deptt. of Veterinary Pharmacology & Toxicology
Bihar Veterinary College, Bihar Animal Sciences University, Patna
 Opioid analgesics

 Are the drugs that significantly relieve pain by acting in central

nervous system or on peripheral mechanisms without affecting
consciousness.
 Agents that relieve pain by nonselective desensitization of tissues
(local anesthetics), protective and soothing effects(demulcents),
chemical neutralizations (antacids) or by alerting consciousness
(general anesthetics) are not called analgesics.
 The analgesics are divided into 2 main groups:
Opioid analgesics (narcotic or morphine like
analgesics)
Non- Opioid analgesics (non-narcotic or aspirin like
analgesics)
 Differences between Narcotic
Analgesics & Non Narcotic
Analgesics
Narcotic Analgesics Non Narcotic Analgesics
 CNS depression- Narcosis.  No significant CNS depression.
 Deep –seated (visceral) intense pain  Superficial pain
 Antipyretic effect Absent.  Antipyretic effect Absent
 Anti-inflammatory effect Absent  Anti-inflammatory effect Absent
 Antirheumatic, antiarthric and  Antirheumatic, antiarthric and
uricosuric or antigout effects- Absent. uricosuric or antigout effects-
 Toxicity high. Absent
 Addiction high  Toxicity high.
 Addiction Absent.
 Pain
 Algesia or pain is protective mechanism of body, it is
produced by damage of tissue and subsequent
liberation of various chemicals (bradykinin, serotonin,
histamines, prostaglandins, Ach and substance-P).
 These chemicals interact with pain receptor
(noceiceptors) present in skin or other tissues are all
free nerve ending that respond to noxious stimuli.
 noceiceptors are very few in deeper tissue.
 Pain classify in two parts: Fast pain, Slow pain
 Pain

On the On the basis of

basis of Pathophysiolog
duration y

Noceiceptiv Neuropathic
Acute Chronic e
Chronic: Pain that
extends beyond the Noceiceptive:
Acute: Usually Pain that arises Neuropathic:
probable period of
associated with tissue from activation of Pain arises from
healing ( 3 or 6
damage, Increased sensory receptors damage to
months beyond
autonomic nervous (noceiceptors). peripheral or
inception)
activity. Pain disappear E.g. central nervous
Depressed mood,
with healing of injured Musculoskeletal system tissue.
health and
tissue. disorders
functional capability
 Differences between fast pain and slow
pain
Fast pain Slow pain
 It stars within 0.1 sec after  It stars after a second or
application of stimulus. more and increases slowly.
 It is not felt in deeper  It is felt in both skin and
tissue. deeper tissue or organ.
 Pain signals are transmitted  Pain signals are transmitted
from peripheral nerves to by “large diameter non -
spinal cord by “small myelinated C fibers”.
diameter myelinated A  Velocity of pain- 6-30m/s.
fibers”.
 Velocity of pain- 6-30m/s.
 Neurophysiology of pain
Nociceptors

A-Delta fibres
C-Fibres
(Myelinated)
(Unmyelinated)

Dorsal Column Ventrolateral Column

Reticular activating System Thalamus Post-central gyrus

(Arousal) (Differentiation)

Hypothalamus
(Autonomic response)
Fig. Schematic representation of pain pathways
 Opioids
 Opium : opium is air dried milky exudates obtained from of poppy plant,
Papaver somniferum, unripe seed capsules.
 Only two have clinical value ( morphine and codeine).
 It contains 32 alkaloids, divided into 2 distinct group:
Benzylisoquinoline group Phenanthrene group

 E.g.: Papaverine, Noscapine and Narcine. E.g. Morphine, codeine and thebaine
 It has significant effect on CNS. CNS: depression or Excitation.
 Analgesia: insignificant Analgesia: significant except
thebain.
 Spasmolytic. Spasmogenic.
 Addiction: uncommon. Addiction: common.
 Morphine

Morphine is principal
alkaloid of opium.
Friedrich Wilhelm A.
Serturner:
A German Pharmacist – Isolated
Morphine in 1803 and named it
after “MORPHEUS”, the Greek
god of Dreams .
 Opioid receptors

Receptor type Physiological role

Analgesia, indifference, cough suppression, respiratory

m depression, cardiovascular depression, physical dependence,
hypothermia.

d Probably analgesia and indifference.

k Analgesia, sedation and ataxia.

s Euphoria or dysphorea, hallucinations, excitement and

probably analgesia.
 Mechanism of Analgesic Effect of Opioids

 The analgesic effect - is through their action

on opioid receptors.
 These are G-protein coupled receptors and
the action is involved through inhibition of
adenylate cyclase causing decrease in
intracellular second messenger cAMP.
 They are also linked to ion channels (G-
protein coupled ion channels), interaction
with which results in opening of K channels
and inhibition of opening of Ca++ channels
causing hyper polarization and non release
of pain inducers.
 Thus the opioid analgesics block nociception
neuronal pathway.
 Hence the pain sensation is not felt.
 Pharmacological effect of morphine

On CNS: Depression or Excitement depending on species.

 Depression in man, monkey and dog.
 Excitement in cat, cattle, sheep, got and horse.
 convulsions in a spinal dog (only spinal cord intact: stimulatory
effect on spinal cord; hence not used to counteract strychnine
convulsions).
 Has analgesic effect due to central (supraspinal) and peripheral
actions, blocks the nociception transmission i.e. antinociception).
 Relieves acute or chronic deep seated pain (due to tissue injury,
inflammation or tumors growth) without impairing motor activity.
On GIT (severe constipation):
 First morphine causes emptying of GIT through vomiting and
defecation.
 persistent and intense spasmogenic effect on smooth muscles of
intestines
 constriction of sphincters interfering with peristalsis causing delayed
passage of ingesta, increased absorption of water and dryness of
ingesta.
 suppresses the defecation reflex and causes constriction of anal
sphincter causing severe constipation.
On Respiration:
 Depression, accompanied by reduced sensitivity of respiratory centre
to PCO2,
 Higher doses causes direct depression of medullary respiratory
centre.
 On CV system:
 No significant effect at analgesic doses.
 No effect on medullary vasomotor centre.
 Hypotension due to histamine release.
 At higher doses causes fall in BP and bradycardia due to
depression of vasomotor centre.
 On Cough Centre:
 Potent antitussive (cough suppressant) by depression of cough
centre.
 On Emetic Centre:
 Nausea and vomition through stimulation of CTZ at analgesic
doses.
 Morphine causes simulated vomition following local application
to the floor of IV ventricle in dogs from which GIT is removed,
showing central emetic action, but not due to effect on GIT.
 On Pupil (Eye):
 Marked dilatation in horse, monkey, sheep, cattle etc.
 Pin point constriction in man (diagnostic), dog, rat and rabbit.
 Bird’s pupil size is not altered due to presence of nonresponsive skeletal muscle
(sphincter muscle of iris).
 Body Temperature:
Hypothermia in man, monkey, dog and rabbits, but in other animals
hyperthermia. Hypothermia is due to release of 5-HT in hypothalamus which i
reversed by TRH, (physiological antagonist of morphine).
 On Kidney:
 In dog morphine initially causes urination and later oligouria or anuria
(release of ADH)
 increase in tone of urinary bladder and
 constriction of bladder sphincter.
 Neuroendocrine Action: Morphine interferes with hypothalamic activity and
decreases the release of FSH, LH and ACTH
increases the release of prolactin and GH.
 Opioid receptor agonist and antagonist

 Opioid agonists - Morphine, Codeine,

Hydromorphone, Oxymorphone, Meperidine,
Methadone
 Opioid antagonists – Naloxone, Diprenorphine,
Naltrexone, Nalmefene
 Partial opioid agonists- Buprenorphine, Tramadol
 Opioid agonist – antagonist (Mixed)-
Nalbuphine, Pentazocine, Butorphanol, Nalorphine
Morphine Metabolism
 It is metabolized through conjugation in liver to
form glucuronides morphine-3-glucuronide and
morephine-6-glucuronide.
 The later has more analgesic effect than
morphine and the former is morphine antagonist.
The conjugates are excreted through bile in
intestines (glucuronides are hydrolyzed in
intestines and morphine is reabsorbed through
enterohepatic recycling).
Clinical uses of morphine
 As analgesic
 In preanaesthetic medication.
 To relieve post-operative pain
 To treat Severe diarrhoea.
 Morphine Toxicity
 Opium toxicity results due to grazing on stems or capsules of
opium.
 The toxic signs are CNS excitation and constipation.
 Long term use of morphine in dogs causes addiction/physiological
dependence, when sudden withdrawal results in appearance of
abstinence syndrome characterized by hyper irritability, excessive
motor activity (body shakes, writhing, jumping and sings of
aggression), teeth chattering and weight loss.
 Addiction is common in man (in addition to above, also show
frequent yawning, dilated pupil, fever, sweating, pilo-erection,
nausea, diarrhea and insomnia.
 The subject is extremely restless and distressed and has strong
craving for the drug).
CODEINE:
 It is used as the phosphate salt to relieve coughing , and as
analgesic and cough suppressant in the man.
DIAMORPHINE (Diacetylmorphine or Heroin):
 It is about 5 times as potent as morphine as an analgesic,
narcotic and respiratory depressant.
 It has addictive properties.

METHADONE:
 It is a synthetic compound, approx. equipotent with morphine
as an analgesic.
 It is a powerful antitussives agent and used in horses & dog
for cough suppression.
PETHIDINE (Meperidine):
 It is about 1/10th as active as morphine as an analgesic.
 It is less likely than morphine to produce narcosis,
vasodepression, emesis and depression of the medullary
cough and respiratory centers.
 Thus, it is more suitable for use in dog and pregnant animals
than morphine.
 So, pethidine is certainly suitable for routine use in these
species.

APOMORPHINE:
 It is less potent than morphine as an analgesic and narcotic,
but the central stimulant effects are increased.
 It is particularly potent as a centrally acting emetic acting as a
stimulant on the CTZ of the medulla. It has been used as an
DEXTROMETHORPHAN:
 It lacks most of the properties of morphine including the
analgesic, addictive, narcotic and spasmogenic actions.
 It does however, depresses the cough centre in the medulla and
is used clinically as an antitussive in dogs when control of the
dry productive cough is required.

FENTANYL:
 It is approximately 50-100 times more potent than morphine as
an analgesic.
 The main use of fentanyl is in neuroleptanalgesia.
 Thebaine Derivatives:
Etorphine :
 These drugs cause neuroleptanalgesia (analgesia + neurolepsia
i.e. tranquility).
 Etorphine is 1000 times more potent than morphine and is used
to immobilize wild animals for trapping.
 1-2 mg/kg IM (dose for an elephant can be accommodated in a
chart).

Buprenorphine:
 Buprenorphine is a partial agonist on mu receptors.
 Dog 0.01-0.02 mg/kg SC twice day.
 Cat: 0.01 mg/kg SC or IM twice a day.
Thank You
 Non-steroidal anti-inflammatory drugs

Dr. Kumari Anjana

Assistant Professor
Deptt. of Veterinary Pharmacology & Toxicology
Bihar Veterinary College, Bihar Animal Sciences University, Patna
 Non-steroidal anti-inflammatory
drugs (NSAIDs)
 NSAIDs are heterogeneous group of drugs having
analgesic, anti-inflammatory and antipyretic effect.
 Unlike morphine they do not depress CNS, do not
produce physical dependence, have no abuse liability
and are weaker analgesics.
 They are also called non-narcotic, non-opioid or aspirin
like analgesics.
 They act primarily on peripheral pain mechanism, but
also in the CNS to raise pain threshold.
 History
• White Willow bark (Salix alba) had been used for
many centuries.
• Salicylic acid was prepared by hydrolysis of the
bitter glycosides obtained from White Willow
plant.
• Sodium salicylate – 1875 (pain and fever).
• Acetylsalicylic acid (aspirin)– 1899 (Also
phenacetin and antipyrine).
• Phenylbutazone – 1949 (anti-inflammatory
activity almost similar to corticosteroids), The
term NSAIDs coined to designate such drugs.
• Indomethacin - 1963
 Classification
Classification of NSAIDs based on chemical groups
 Salicylates : Sodium salicylate, Acetylsalicylic acid (aspirin), Methylsalicylate.
 Aniline or : Paracetamol (acetaminophen), Acetanilide, Phenacetin,
 p- aminophenol derivatives: Aminopyrine, Antipyrine.
 Pyrazolone derivatives: Phenylbutazone, Oxyphenbutazone,
Sulphinpyrazone.
 Indole & related drugs: Indomethacin, Sulindac.
 Phenyl acetic acid derivatives: Diclofenac.
 Propionic acid derivatives: Ibuprofen, Naproxen, Fenoprofen, Ketoprofen.
 Fenamates: Mefenamic acid.
 Oxicams derivatives : Piroxicam, Tenoxicam, Meloxicam.
 Sulfonanilide derivatives: Nimesulide.
Classification of NSAIDs based on selectivity of COX Inhibition:
 Non-selective COX Inhibitors (Conventional NSAIDs):
 Salicylates: Aspirin, Diflunisal.
 Pyrazolone derivatives: Phenylbutazone, Oxyphenbutazone.
 Indole derivatives: Indomethacin.
 Propionic acid derivatives: Ibuprofen, Naproxen, Ketoprofen, Flurbiprofen.
 Anthranilic acid derivatives: Mefenamic acid.
 Aryl acetic acid derivatives: Diclofenac.
 Oxicam derivatives: Piroxicam, Tenoxicam.
 Pyrrolo-pyrrole derivatives: Ketorolac.
 Preferential COX-2 Inhibitors: Nimesulide, Meloxicam, Nabumetone.
 Selective COX-2 Inhibitors: Celecoxib, Rofecoxib, Valdecoxib.
Analgesic-antipyretic with poor anti-
inflammatory action:

 p-aminophenol derivatives: Paracetamol

(Acetaminophen).
 Pyrazolone derivatives: Metamizol.
 Benzoxacine derivatives: Nefopam.
 Arachidonic acid

COX-1 COX-2 COX-3

(normal constituent) (inducible)) (normal constituent)
CNS, Heart, Aorta

Nonselective Selective
NSAID COX-2 inhibitor
Body homeostasis Inflammatory Site Normal Constituent
• Stomach • Macrophages • CNC Pain
• Intestine • Synoviocytes • Kidney Fever
• Kidney • Endothelial cell • Female U/G tract
• Platelet
Mechanism: COX-1, COX-2 & COX-3 inhibition
Beneficial effects (inhibition of PG
synthesis)
 Analgesia
 Antipyresis
 Anti-inflammatory
 Antithrombotic
 Closure of ductus arteriosus in newborn
 Antipyresis
 Normal body temperature is maintained by thermoregulatory
centre (thermostat) in hypothalamus, which ensures a balance
between heat production and heat loss.
 Fever occurs due to disturbance in the hypothalamic
thermostat, which is set at a high temperature.
 The antipyretics act by resetting the thermostat to normal set-
point and then the body temperature regulating mechanisms
(dilatation of superficial blood vessels, sweating and increased
respiration, promoting heat loss) operate to lower the elevated
body temperature to normal level.
 Normal body temperature is not affected by NSAIDS or
antipyretics (at therapeutic doses).
 During infections and inflammatory reactions the pathogenic
microbial endotoxins cause release of pyrogen interleukin-I from
macrophages, which stimulates the generation of prostaglandins
(E series) in hypothalamus, which set the thermostat at a higher
level resulting in pyrexia or lever.
 The NSAIDs exert antipyretic effect by irreversibly inhibiting the
enzyme cyclo-oxygenase 1 or cyclo-oxygenase 2 or both which
catalyze the initial reaction of prostaglandin formation from
arachidonic acid in the hypothalamus or through inhibition of a
specific COX isoenzyme in the CNS.
 COX-1 is a constitutive enzyme responsible for physiological
synthesis of prostaglandins for tissue homeostasis (including
protection on gastric mucosa; PGI2 and PGE2). Whereas, COX-2 is
an inducible enzyme responsible for synthesis of prostaglandins
which have a role in fever, pain and inflammation.
 Anti-inflammatory
 The inflammatory reactions such as vasodilatation,
increased vascular permeability, cell proliferation,
pain etc are mediated by the release of a multitude of
chemical mediators having varied mechanisms of
action.
 The inflammatory stimuli in the inflammatory cells
induce synthesis of prostaglandins through COX2.
 The NSAIDS exert anti-inflammatory effect by
inhibition of prostaglandin synthesis by irreversible
inhibition of this enzyme.
 Analgesics

 The NSAIDS are mainly effective against pain

associated with arthritis, bursitis, muscular pain,
vascular pain, toothache, dysmenorrhoea and
bone pain, in all the conditions there is increased
synthesis of pain inducers and prostaglandins.
 The prostaglandins sensitize nociceptors to pain
inhibiting prostaglangin synthesis through
irreversible inactivation of COX-1 or COX-2 or
both.
 Antiplatelet aggregator

 TXA2 is pro-aggregator (COX-1)

 PGI2 is anti-aggregator
 Most NSAIDs - effects on TXA2 predominates and
inhibits aggregation – prolonged bleeding time
 Aspirin is highly active and acetylates COX in circulation
– before hepatic 1st pass metabolism
 Even small dose Antithrombotic effect – Myocardial
Infarction and other cardiac conditions
Ductus arteriosus
• It is a shunt connecting the pulmonary artery to the
aortic arch
• Maintained by local PGE2 and PGI2
• Closes at birth
• Failure to close – small doses of NSAIDs (aspirin or
indomethacin) – closes. (
• NSAIDs is not used in late pregnancy in late pregnancy –
premature closure)
Other action of NSAIDs:
Aspirin can reduce diarrhea that occur after radiation
therapy.
 Relative Potency of NSAIDs

 Antipyretic Effect: Aspirin = Paracetamol >

Phenacetin > Phenylbutazone
 Analgesic Effect: Aspirin > Phenacetin & Paracetamol
> Phenylbutazone
 Anti-inflammatory Effect: Phenylbutazone > Aspirin
Thank You
Thank You
 Analeptics and other CNS
stimulants

Dr. Kumari Anjana

Assistant Professor
Deptt. of Veterinary Pharmacology & Toxicology
Bihar Veterinary College, Bihar Animal Sciences University, Patna
 C N S stimulants
• Central nervous system stimulants are drugs that stimulate the CNS
and/or improve specific brain functions.
• These drugs are relatively non-specific in action and affect all parts of the
CNS when given in sufficient dosage.
• Although stimulation of CNS can be produced by large heterogeneous
groups of natural and synthetic substances, only few are used
therapeutically because of lack of selectivity, side/adverse effects, or
potential for abuse in humans.
• These drugs are used to counteract the excess depression of CNS
caused by over dosage of anaesthetics and toxicity of CNS depressant
drugs or some poisonings.
• Death under these conditions results from central respiratory or
vasomotor failure or both.
• Over dosage of CNS stimulants causes convulsions, can be counteracted
 1.Psychostimulants/Cerebral stimulants--methylxanthines (caffeine),
amphetamines and
methylphenidate.
 
2.Brain stem stimulants/Analeptics--doxapram,
bemegride,
leptazol and
nikethamide.

3. Convulsants- strychnine,
brucine,
picrotoxin,
bicuculline and
leptazol.

4. Psychotomimetics/Hallucinogens-- cannabis,
lysergic acid diethylamide and
mescaline
 Methylxanthines:
 Group of naturally occurring alkaloids present in certain beverages and include caffeine,
theophylline and theobromine.
 These drugs have xanthine nucleus and are related to purines and uric acid.
 Caffeine is present in coffee (Coffea arabica), tea leaves (Thea sinensis), cocoa bean
(Theobroma cacao), and kola nut (Cola acuminata).
 Theophylline is present in tea.
 Theobromine in cocoa.
 The xanthine’s stimulate all parts of the CNS, acting principally on higher centres to
increase mental activity, alley drowsiness and fatigue, and reduce reaction time to
sensory stimuli.
 Caffeine and theophylline also stimulate a number of medullary centres including
respiratory, vagal and vasomotor centres.
 Out of these naturally occurring methylxanthines, caffeine is mainly used as a CNS
stimulant.
Amphetamines:

 Amphetamines are synthetic central sympathomimetic agent having

marked CNS stimulant and anorectic effects.
 These drugs include dextro-amphetamine (d-amphetamine) and
methamphetamine.
 It acts by release of endogenous nor-adrenaline.
 Also relaxes the bronchi due to sympathetic actions.
 Small animals: 2 mg/kg sc.
 Large animals: 100-300 mg/ animal sc.
Methylphenidate:

 Methylphenidate is chemically and pharmacologically similar to d-

amphetamine.
 It produces increase in mental activity at doses which have little action
on other central and peripheral functions.
 It is used primarily in human medicine for hyperkinetic children
(attention deficit disorder) in whom it improves behaviour and
learning ability.
 Analeptics

 Analeptics are drugs that act at the level of brain stem and stimulate medullary
respiratory centre.
 These agents have resuscitation value in respiratory depression, coma or
unconsciousness.
 The term analeptic is derived from Greek word ‘analeptikos’ that means restorative.
Doxapram

 Primarily a respiratory stimulant like nikethamide (relatively more

selective on respiratory centre than other analeptics).
 dose in dog:
1-2 mg/kg IV after inhalational anaesthetics
2-5 mg/kg IV after intravenous anaesthetics
1-5 mg (total) IV, SC for apnoea in new bourns.

 For calves and foal - 40-100 mg (total) IV, SC or by sublingual root.

Nikethamide:
 stimulates chemoreceptor activity in the carotid and aortic bodies, which reflexly
stimulates respiratory centres primarily and vasoconstrictor and vagal centres
secondarily.
 Dose- 22-44 mg/kg, PO, IV, IM, SC 

Bemegride:
 Direct stimulant of respiratory centre. Dog: 15-20mg/kg IV

Strychnine:
 Alkaloid of seeds of Strychnos nuxvomica.
 It is a powerful stimulant of CNS causing severe spinal convulsion (convulsive poison).
 Acts through antagonism of postsynaptic inhibition mediated by glycin in CNS
(competitive antagonist of glycine in motoneurons and interneurons in spinal
cord).
Picrotoxin:
 It is a non-nitogenous substance obtained from seeds of Anamirta cocculys (fish
berries).
 A potent convulsive agent acts by antagonism of presynaptic inhibition in CNS
mediated by GABA.
 
Pentylenetetrazol:
 A potent convulsive.
 It acts through marked reduction in neuronal recovery time resulting in repetitive
discharge following a single stimulus; interferes with GABAergic inhibition.
 Pentylenetetrazol, strychnine and picrotoxin have no therapeutic use, but
used only as experimental tools to produce convulsions.
Thank You
 DRUGS ACTING ON SOMATIC NERVOUS
SYSTEM
(Skeletal muscle relaxants, Local
anaesthetics)

Dr. Kumari Anjana

Assistant Professor
Deptt. of Veterinary Pharmacology & Toxicology
Bihar Veterinary College, Bihar Animal Sciences University,
Patna
 Skeletal muscle relaxants
 
• Skeletal muscle relaxants are drugs that act either peripherally at the
neuromuscular junction/ skeletal muscle fibre or centrally in the
cerebrospinal axis to reduce skeletal muscle tone and/or cause paralysis.

• These agents are clinically useful during surgery to produce complete muscle
relaxation (e.g., neuromuscular blockers) or in the treatment of neurological
spastic disorders and muscle spasms.
 Classification

On the basis of site of action, skeletal muscle relaxants have been divided into 2 major
groups

1. Peripherally acting muscle relaxants Neuromuscular blocking drugs Nondepolarising

Depolarising

Directly acting drugs

2. Centrally acting muscle relaxants

 Peripherally acting muscle
relaxants
1. Neuromuscular blocking drugs
a) Non-depolarising/Competitive neuro-muscular blocking drugs
Long acting drugs; --d-tubocurarine,
pancuronium,
gallamine
doxacurium
Intermediate acting drugs--vecuronium,
atracurium
rocuronium
Short acting drugs:-- mivacurium
 
b) Depolarising/ Non-competitive neuromuscular blocking drugs-
suxamethonium and
decamethonium.
2. Directly acting drugs--e.g., dantrolene and quinine.
Centrally acting muscle relaxants

 Carbamate derivatives
 methocarbamol, carisoprodol and meprobamate.
 Glyceryl ethers
 guaiphenesin, mephenesin, chlorzoxazone and chlormezanone.
 Benzodiazepines
 diazepam and chlordiazepoxide.
 Gamma-aminobutyric acid derivatives
 baclofen.
 Centrally acting muscle relaxants
 These are also called skeletal muscle spasmolytiçs, act through by interfering with
internuntial pathways in spinal cord and reticular activating system.
 These are given either orally or parenterally.
Mefenesin and Guaiafenesin:
 Act as glycine agonists and thus antagonize strychnine or tetanus but not those
of picrotoxin or pentylenetetrazol (GABA antagonism).
 Guaifenesin has wide and used 5% in 5% dextrose as IV infusion in horses for casting.
Dose of Guaifenesin: Dog: 45-90 mg/kg IV;
Large animals: 60-120 mg/kg IV.
 Diazepam:
 Causes paralysis of muscles through GABA facilitation, and thus antagonizes
convulsions of picrotoxin or nikethamide.
 Dog: 0.5-1 mg/kg IV or 1M.
 Cat: 2.5-5 mg/kg orally, thrice a day.
 
Baclofen:
GABAB agonist.
 Causes paralysis of muscles by inhibition of motor neurons in spinal cord.
 
Methocarbamol:
 Mechanism of action unknown. Used in tetanus and strychnine poisoning.
 Dog & Cat 45 mg/kg IV
 Horse: 5-20 mg/kg IV.
  Centrally acting muscle relaxants Peripherally acting muscle
relaxant
1 Selectively inhibit polysynaptic Block neuromuscular transmission
. reflexes in CNS
2 Decrease muscle tone without Cause muscle paralysis, voluntary
. reducing voluntary power movement lost
3 Cause some CNS depression. No effect on CNS
.
4 Given orally sometime parenterally Practically always given iv
.
5 Used in chronic spastic condition Used for short-term purposes
.
 Peripherally Acting Muscle Relaxants

 
Non-Depolarising/Competitive Neuro-muscular Blocking Drugs:
 Non-depolarising drugs are competitive antagonists of acetylcholine at nicotinic
receptors on the motor end plates.
 They do not cause depolarisation, but protect receptors from depolarisation by
acetylcholine, so they cause flaccid paralysis.
 The non-depolarising or competitive neuromuscular blockers generally have thick bulky
and rigid molecule and are termed Pachycurare.
 Most of the non-depolarising neuromuscular blocking agents have two or more
quaternary atoms, which provide necessary attraction to the negatively charged
anionic sites of the nicotinic receptors.
 Mechanism of action:
 Non-depolarising neuromuscular blocking agents combine with nicotinic receptors in the
neuromuscular junction and prevent the binding of acetylcholine.
 Normally, binding of the cationic head of ACh with the negatively charged sites of
nicotinic receptors causes opening of Na+ channels allowing depolarisation of muscle
cell membrane and contraction of skeletal muscle cell.
 Occupation of these sites by the molecularly rigid competitive neuromuscular blockers
do not allow conformational changes in the nicotinic receptors needed for
opening of the channel and subsequent depolarisation of cell membranes and
muscular contraction.  
 As the antagonism is of competitive type, the actions of non-depolarising blockers can
be overcome by increasing concentration of acetylcholine at the
neuromuscular junction, for example, by administration of anticholinesterase
agents like neostigmine or edrophonium.

 At very high concentration, non-depolarising agents directly block Na+ channels

to produce non-competitive neuromuscular blockade.
 This reduces ability of acetylcholinesterase inhibitors to reverse the actions of non-
depolarising muscle relaxants.
Mechanism of action of non-depolarising neuromuscular blocker.
a.Nicotinic receptor without ligand: Na+ channel closed.
b.Acetylcholine occupying nicotinic receptor: Na+ channel opened.
C. Non-depolarising drug displaces acetylcholine and occupies nicotinic
receptor:Na+ channel closed.
Depolarising/ Non-competitive neuromuscular blocking drugs:

 
Fig. Schematic representation of mechanism of action of depolarising
neuromuscular blocking drugs.
(a) Nicotinic receptor with closed sodium channel.
(b) Depolarising neuromuscular blocker occupying nicotinic receptor.
Sodium channel opens to produce depolarisation (Phase-I)
(c) Depolarising neuromuscular blocker still occupying nicotinic receptor.
Sodium channel closes as persistent depolarisation changes to
repolarisation (Phase Il).
NR = nicotinic receptor
 Differences between Competitive and Non-competitive NMBs:

Featurs Competitive NMBs Non-competitive NMBs

 

1. Action at motor end No depolarization Persistent depolarization

plate

Initial effect on No effect Transient fasciculation’s

muscles
Type of muscle Flaccid Tonic
paralysis
Effect of Anti-ChE Antagonism Synergistic effect
agents
Species sensitivity Rat > Rabbit > Cat Cat > Rabbit > Rat
LOCAL
ANAESTHETICS
Local anaesthetics

 Local anaesthetics are drugs which cause reversible loss of sensation

of a particular area or region of the body.
 The effect is not accompanied by loss of consciousness.
 The local anaesthetic solutions are injected near or in vicinity of the
nerves and applied topically for localized desensitization.
Mechanism of action:
 The local anaesthetics prevent depolarization of the neurons by
interfering with Na+ ion permeability resulting in blockade of impulse
conduction.
 This effect is due to reversible binding to the Na+ ion channels in
the neuronal membrane.
 Differential features of :local and general anaesthetics

Parameters Local anaesthetics General anaesthetics

1. Site of action PNS: Peripheral nerves CNS: Brain
2. Mode of action Blocks axonal Alters synaptic
conduction transmission
3. Consciousness Unaffected Lost
4. Analgesia Localized Generalized
5. Administration Local deposition away Systemic – Inhalation or
from systemic parenteral
circulation
6. Systemic Undesirable, Requisite for action
availability responsible for toxicity

7. Toxic potential & Low, CNS stimulation High, CNS depression

toxicity (convulsive seizures)
 Classification of local anaesthetics

Categories Duration of Examples

action
1. Ultra-short Less than or Proparacaine, Benoxinate
acting equal to 15
min.

2. Short acting Approx. 1 Procaine, Chlorprocaine,

hour Cocaine
3. Intermediate Lidocaine (Xylocaine),
acting 1 – 4 hour Mepivacaine, Prilocaine

4 – 10 hours Bupivacaine, Ropivacaine,

4. Long acting or longer Tetracaine, Etidocaine,
Hexylcaine, Cinchocaine
Clinical applications of local anaesthetic agents:
 Topical anaesthesia (Surface anaesthesia): Eyes-4% Xylocaine jelly, 0.5-1%
Tetracaine solution.
 These are used for catheterization in urethra and endotracheal incubation in the
trachea.
 Infiltration and field block: Local anaesthetics used are Procaine (1% in small
animals and 2% in large animals), Lignocaine (2%).
 Conduction/ Nerve block: Local anaesthetics used are Procaine (2%), Lignocaine
(2%)and Mepivacaine (2%). (Mepivacaine is best suited in case of horse).
 Potentiation of Local Anaesthetics

By decreasing absorption of injected local

anesthetic:
 Adrenaline is added to local anaesthetic solutions at concentrations ranging
from 1:1,00,000 to 1:50,000, which causes constriction of blood vesselsand
reduces the absorption of local anesthetic .

By increasing the spread of local

anaesthetic :
 Addition of Hyaluronidase to local anaesthetic solutions increases the
diffusion or spread of the local anaesthetic and enhances the area of
anaesthetization.
Cocaine:
 It is the “mother of all local anaesthetics”.
 It was the first local anaesthetic alkaloid isolated from the leaves of Erythroxylon coca by
Albert Nieman in the year 1860.
 Due to its marked CNS stimulant (toxicity) limits its use.

Procaine:
 It is used for infiltration , 1% in small animals and 2% in large animals.
 For conduction block (2.5 ml of a 2% solution in small animals and 5-10 ml of 4% solution
in large animals).
 It is also used in epidural anaesthesia as 2%.
 Horse- highly sensitive- convulsive effect.
 Parakeets- highly sensitive- lethal effect.
 It is ineffective topically due to its poor lipid solubility.
 Procaine (Procainamide)is used as an effective antiarrhythmic agent.
 It is not recommended in patient along with sulphonamide therapy.
(it favour growth of pathogens by providing their growth factor PABA. )
Lidocaine (Lignocaine or Xylocaine):
 LAP is about 2 times that of procain.
 It is a multipurpose local anesthetic.
 It is reported to be immunosressant compound (both humoral as well as cell
mediated).
 It is also used as antiarrhythmic agent.
 It is used as 1-2% solution for epidural and nerve block anaesthesia in large and
small animals.
 It is also used i.v. @ 2 mg/kg b.wt. (every 15-30 minutes) to control cardiac
arrhythmia in dog.

Tetracaine:
 It is long acting and one of the most potent ester type local anaesthetic.
 It is one of the choice topical opthalmic anaesthesia (0.5 % in small animals and
1% in large animals), and for spinal anaesthesia.
Benzocaine:
 It is comparatively non irritant and recommonded for use on skin,
dentistry, gums & buccal mucosa.
 It is also used as fast- acting fish immobilizing agent.
 It absorb UV light and has been used in sunscreen creams and lotions.

Bupivacaine:
 It has been recommonded as post-operative topical analgesic, superior to
phenylbutazone.
 Four times more potent than Lidocaine and has duration of action - 3 to 8 hours.
 It has been recommonded also for during labour or during post –operative
period as it tends to produce more sensory then motor nerve blocked.
THANK YOU
 Euthanizing agents

Dr. Kumari Anjana

Assistant Professor
Deptt. of Veterinary Pharmacology & Toxicology
Bihar Veterinary College, Bihar Animal Sciences University, Patna
Euthanasia

  
 Euthanasia (“good death”) is an act of inducing human death.
OR
 It is the process of killing an animal without causing pain.
 Euthanasia is humane killing of animals by a veterinarian upon
request of the owner of the animal under specific circumstances:
 To relieve from undue suffering: incurable disease or extremely
painful conditions.
 If the animal becomes unfit for the purpose of its maintenance.
 If the animal becomes dangerously aggressive or rabid.
 List of Euthanizing agents:
Inhalation agents:
 Carbon monoxide
 Carbon dioxide
 Inhalation anaesthetics (diethyl ether, enflurane, halothane, isoflurane,
methoxyflurane)
 Nitrogen
Injectable agents:
 Barbiturates
 Chloral hydrate and adjuvants
 Ethanol
 Miscellaneous injectable general anaesthetics (used as adjuvants to other, primary
agents in selected circumstances)
Ideal Euthanizing Agent:
 Should cause death smoothly without causing any
struggling or pain.
 The agent is sure to cause death.
 Should be easily administrable
 Should be safe for the handling person
 Should not be a cause of environmental insanitation or
contamination.
 Inexpensive.
Agent Mechanism of action
Inhalation agents
Carbon monoxide Neuromuscular blocking drugs Combines with
hemoglobin, lowering oxygen content of blood
Carbon dioxide Direct depression of CNS and other vital organs;
anaesthetic effects
 
Hydrogen cyanide Direct inhibition of cellular utilization of oxygen
Inhalation agents Direct depression of CNS and other vital organs
Nitrogen Displaces oxygen in the inspired breath: lowers
oxygen content of blood
Injectable agents
Barbiturates Direct depression of CNS; anesthetic effects
Chloral hydrate and Direct depression of CNS; anesthetic effects
combinations
Ethanol Direct depression of CNS
T61 Direct depression of CNS
Neuromuscularblocking Paralysis of respiratory muscles
drug
 Route of administration

 Barbiturates: i/p, i/v or i/cardiac in small animals.

 Chloral hydrate: i/v in large animals.
 Saturated solution of magnesium sulphate (1:1) i/v in
small or large animals.
 Inhalation Anaesthetics: Ether or chloroform in dogs,
cats, birds or rodents (pre-treat with tranquilizers to
prevent, howling, excitement or struggling).
 Carbon Monoxide (Chamber): Dogs and cats (pre-
treat with tranquilizers to prevent excitement or
Ideal Agent:
Pentobarbitone (6.6 G) + Chloral hydrate (30
G) + Magnesium sulphate (15 G) in 1000 ml
water i/v: Rapid respiratory failure and cardiac
arrest without causing muscular twitching’s or
spasms.
Thank You