Arawali Veterinary College

Agra-Bikaner, NH-52, Bajor, Sikar, Rajasthan-332403

cvas908@gmail.com

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Department of veterinary Pharmacology and Toxicology offers undergraduate courses to students in third professional year preparing for B.V.Sc.&A.H. degree. The courses of study envisage study of actions, mechanism of action and therapeutic and side or adverse effects of drugs in animals. Emphasis is given so that the students gain enough knowledge to select and prescribe a drug of choice for the treatment of an animal.

Students are given practice in pharmacy practical class to prepare some commonly used drug formulations. As per mandate of CPCSEA guidelines, practical classes in experimental pharmacology are conducted using software, simulation, video clips for demonstration of observation of effects of various classes of drugs in both intact laboratory animals and isolated organs/tissues as an alternate to use of animals.

The Department has following sanctioned strength of Faculty:

Professor - 1

Associate Professor – 1

Assistant Professors – 1

COURSES and SYLLABI

THEORY

UNIT-1 (GENERAL PHARMACOLOGY)

Introduction, historical development, branches and scope of Pharmacology. Sources and nature of drugs. Pharmacological terms and definitions, nomenclature of drugs. Principles of drug activity: Pharmacokinetics - Routes of drug administration, absorption, distribution, biotransformation and excretion of drugs. Pharmacodynamics - Concept of drug and receptor, dose-response relationship, terms related to drug activity and factors modifying the drug effect and dosage. Adverse drug reactions, drug interactions.

UNIT-2 (DRUGS ACTING ON AUTONOMIC NERVOUS SYSTEM)

Neurohumoral transmission, Pharmacology of neurotransmitters. Adrenoceptors agonists and antagonists, adrenergic neuron blockers, cholinoceptor agonists and antagonists. Autacoids: Histamine, histamine analogues and antihistaminic agents, 5-Hydroxytryptamine and its agonists and antagonists, eicosanoids, platelet activating factors, angiotensin, bradykinin and kallidin.

UNIT-3 (DRUGS ACTING ON CENTRAL NERVOUS SYSTEM)

Classification of drugs acting on CNS. History, mechanism and stages of general anaesthesia. Inhalant, intravenous and dissociative anaesthetics. Hypnotics and sedatives; psychotropic drugs, anticonvulsants, opioid analgesics, non-steroidal anti-inflammatory drugs, analeptics and other CNS stimulants. Drugs acting on somaticnervous system: Local anaesthetics, muscle relaxants. Euthanizing agents.

UNIT-4 (DRUGS ACTING ON DIFFERENT BODY SYSTEMS)

Drugs acting on digestive system: Stomachics, antacids and antiulcers, prokinetics, carminatives, antizymotics, emetics ,antiemetics, purgatives, antidiarrhoeals, choleretics and cholagogues. Rumen pharmacology. Drugs acting on cardiovascular system: Cardiotonics and cardiac stimulants, antiarrhythmic drugs, vasodilators and antihypertensive agents, haematopoietic drugs, coagulants and anticoagulants, Drugs acting on respiratory system: Expectorants and antitussives, respiratory stimulants, bronchodilators and mucolytics. Drugs acting on urogenital system: Diuretics, drugs affecting urinary pH and tubular transport of drugs, ecbolics and tocolytics. Pharmacological basis of fluid therapy. Pharmacotherapeutics of hormones. Drugs acting on skin and mucous membranes: Emollients, demulcents and counter irritants

UNIT-5 (VETERINARY CHEMOTHERAPY)

Introduction and historical developments of chemotherapy. Antimicrobial agents: Classification, general principles inantimicrobial chemotherapy, antimicrobial resistance, combined antimicrobial therapy. Sulphonamides and theircombination with diaminopyrimidines. Penicillins, cephalopsorins, cephamycins and other beta lactams, beta lactamaseinhibitors. Aminoglycosides and aminocyclitols, tetracyclines, amphenicols (chloramphenicol, thiamphenicol, florfenicol), macrolides, quinolones and fluoroquinolones, polypeptides (polymixins, bacitracin) and glycopeptide antibiotics, miscellaneous agents: Lincosamides, novobiocin, virginiamycin, tiamulin, nitrofurans and methenamine, Antitubercular drugs. Antifungal agents: Topical and systemic agents including anti-fungal antibiotics. Antiviral and anticancer agents. Anthelmintics: Drugs used against nematodes, cestodes, trematodes. Antiprotozoal agents: Drugs usedin trypanosomosis, theileriosis, babesiosis, coccidiosis, amoebiosis, giardiosis and trichomoniasis. Ectoparasiticides, Antiseptics and disinfectants. Pharmacology of drugs of abuse in animals Pharmacology of indigenous medicinal plants: Scientific name, common name, active principles, pharmacological actions and therapeutic uses of Ginger, ocimum, neem, piper longum, withania, leptadenia, tinospora, embilica,eucalyptus, glycerrhiza, trichospermum, curcuma, adhantoda, butea, aloes, sena, rheubarb, catechu etc.

UNIT-6 (VETERINARY TOXICOLOGY)

General Toxicology: Definitions, history of toxicology, fundamentals and scope of toxicology. Sources and classification of toxicants, factors modifying toxicity, general approaches to diagnosis and treatment of poisoning. Toxicity caused by metals and non-metals: Arsenic, lead, mercury, copper, molybdenum, selenium, phosphorus, fluoride, nitrates or nitrites, chlorate, common salt and urea. Poisonous plants: Cyanogenetic plants, abrus, ipomoea, datura, nuxvomica, castor, oxalate producing plants, plants causing thiamine deficiency, plants causing photosensitization and lathyrism, oleander, and cotton. Toxicity caused by Agrochemicals: Insecticides - Chlorinated hydrocarbons, organophosphates, carbamates, pyrethroids, newer insecticides. Herbicides, fungicides and rodenticides. Fungal and bacterial toxins: Aflatoxins, rubratoxin,  ochratoxin, sporidesmin, citrinin, F-2 toxin, trichothecenes, ergot, fescue, botulinum toxin and tetanus toxin Venomous bites and stings: Snake, scorpion, spider, bees and wasp, toad and fishes (puffer fish, shellfish). Toxicity caused by food additives and preservatives. Drug and pesticide residue toxicology. Environmental pollutants: Air and water pollutants. Concept of radiation hazards.

PRACTICAL

UNIT-1 (GENERAL PHARMACOLOGY)

Handling and washing of laboratory wares. Handling and operation of commonly used laboratory instruments. Concept of good laboratory practices (GLP). Pharmacy appliances. Principles of compounding and dispensing. Metrology, systems of weights and measures, pharmacy calculations. Pharmaceutical processes. Pharmaceutical dosage forms .Prescription writing, incompatibilities. Drug standards and regulations, custody of poisons. Compounding and dispensing of powders, ointments, mixtures, liniments, lotions, liquors, tinctures, emulsions, and electuaries.

UNIT-2 (ANS PHARMACOLOGY)

Demonstration of the action of autonomic agonists and antagonists on intact or isolated preparations of the laboratory animals. Simulated animal experiments should be preferred over use of live animals. The lab for simulated experiments should be established within a span of one year.

UNIT-3 (CNS PHARMACOLOGY)

Handling of lab animals. Regulatory guidelines for use of lab animals. Demonstration of the effect of CNS active drugs and local anaesthetics in laboratory animals. The lab for simulated experiments should be established within a span of one year.

UNIT-4 (VETERINARY CHEMOTHERAPY)

Demonstration of various chemotherapeutic agents and their dosage forms. Demonstration of antibiotic sensitivity test and its interpretation.

UNIT-5 (VETERINARY TOXICOLOGY)

Collection, preservation and dispatch of material for toxicological analysis. General principles for toxicological analysis. Detection of heavy metals or non-metals or plant poisons. Demonstration of agrochemical toxicity and its antidotal therapy via simulation methods. Demonstration of toxic weeds and plants of local area. Methods of calculation of median lethal dose (LD50) or maximum tolerated dose (MTD).

 

                                             ANNUAL EXAMINATION

PAPERS              U N I T S     MAXIMUM MARKS                   WEIGHTAGE

THEORY

Paper-I                         1, 2, 3 and 4                              100                                           20

Paper-II                        5 and 6                                     100                                           20

PRACTICAL

Paper-I                         1 and 2                                      60                                            20

Paper - II                      3, 4 and 5                                  60                                            20

 INTERNAL ASSESSMENT.                                                                                          20

 

 

NEUROHARMACOLOGY PRACTICAL MANUAL

NEUROPHARMACOLOGY

 

CHAPTER - 10

 

Gross observable effects of cns active drugs

The gross observable effects of drugs can be demonstrated in mice by using multidimensional screening procedure devised by Irwin (1963). The screening procedure is simply based on observational techniques following administration of the drug. The scoring of different signs or effects or characters is done as under:

a. Normal signs: Normal score is 4 for all the normal signs. For stimulation or enhancement of intensity of signs, scoring is done from 4 to 8, whereas the decrease of intensity of effects or sign is scored from 4 to 0.

b. Abnormal signs: Normal scores is 0. If any abnormal sign or some effects appear, scoring is done between 0 and 8 depending on the intensity of the abnormal signs.

The gross observable effects or activity profiles have been placed into four main groups.

a. Behavioural profiles

b. Neurological profiles

c. Autonomic profiles

d. Miscellaneous.

Behavioural profiles:

These effects are divided into three sub-groups. (i) awareness, (ii) mood and (iii) motor activity.

(I)  Awareness:

The effects on awareness can be judged from the following parameters:

1. Alertness (4): indicates stimulation of CNS

2. Stupor (0): indicates depression of CNS

3. Visual placing (4): measures the animals’ response and its ability to orient itself without bumps or falls when placed in a difficult position, like on a rotating rod or a fine rope. Subnormal ability may indicate motor in-coordination.

4. Stereotypy (0): is frequent mechanical repetition of only one kind of movement, e.g. searching movements of head with amphetamine, circling or circular movement with morphine, self-biting with apomorphine and tail-lashing with spinal stimulants.

 

5. Passivity (0) measures the struggle behaviour of the animal when placed in un-accustomed or unusual position.

                                                 

Unaffected (normal) mouse struggles (moves head and limbs) to escape the unusual position and orients itself back to normal position. The scoring is done to indicate abolition of struggle behaviour. The scheme of scoring is as under:

 i). Score 1 - when mouse is suspended vertically by loose fold of skin over the neck,

ii). Score 2 – when mouse is rotated horizontally on its back,

iii). Score 3 – when suspended by fore limb, and

iv). Score 4 – when mouse does not struggle to escape when suspended by hind limb.

Passivity indicates tranquillization, CNS depression, myorelaxation, paralysis or anaesthesia.

  1. Catalepsy/Catatonia indicates the tone of limb muscles of the animals. If one of the fore limbs is placed  on a piece of wood at height of 4 cm in mice and 8 cm in rats and the animal is unable to remove the limb for more than one minute, the presence of  catalepsy is indicated.


                                          Fig. shows catalepsy in rabbit

(II)  Mood:

Following activities determine the mood of the animals.

1. Grooming (4): Generally grooming behaviour is prevalent in unaffected, normal mice. But excessive grooming indicates central stimulation or sympathetic stimulation

2. Vocalization (0): Mice generally do not utter any sound. Vocalization such as ‘squeaks’ indicates discomfort or noxious stimuli.

3. Restlessness, irritability, aggressiveness and fearfulness are normally absent in mice. Their presence indicates CNS stimulation or discomfort.

 

(III)  Motor activity:

1. Spontaneous motor activity (4): Normally animals exhibit spontaneous motor activity (SMA) to explore its surroundings i.e. exploratory behaviour. The drugs may increase or decrease the SMA.

Reduction in SMA is scored as under:                       The increase in SMA is scored as under:

b. Slight reduction- 3                                                  a. Constant walking - 6

c. Occasional spontaneous movements – 2                b. Walking with running - 7

d. Very rare spontaneous movements – 1                   c. Agitated and vigorous running – 8

e. Absence of spontaneous activity – 0

Decrease in SMA indicates CNS depression, blockade of ganglia or neuromuscular junctions, whereas increased SMA indicates stimulation of CNS, ganglia or neuromuscular junctions.

2. Reactivity (4): Reactivity is scored on the basis of intensity of locomotor response and spontaneous activity following snapping of fingers and gentle manipulation of animals. An increase or decrease in reactivity indicates stimulation or depression of CNS, ganglia or neuromuscular junctions.

3. Touch response (4): The touch response is scored on the basis of intensity of locomotor activity by touching the animals with a pencil or forceps at various parts of the body e.g. on the side of the neck or abdomen or on the groin. No response to touch indicates CNS depression.

4. Pain response (4): The response to pain is recorded by applying a small bulldog clamp to the base of the tail. The absence of any response to pain measures analgesia, CNS sedation or depression.

Neurological profiles

(I) CNS excitation:

1. Startle response (0): Shaking of the animal body in response to a sudden loud sound is called startle response. It can be assessed by striking the outside of the observation tray or cage with a metal object. It is rated as below.

a. No response – 0

b. The animal visibly jerks – 2

c. Jerks and jumps – 4

d. Jerks and frantic escape attempts – 6

e. Clonic convulsions – 8

2. Straub tail (0): Generally the mice keep their tail on the floor of cage. The degree of elevation of the animal’s tail is recorded as straub tail response. Spinal stimulant drugs e.g. morphine, strychnine etc. produce such responses.

 

3. Tremors (0):

4. Twitches (0):

5. Convulsions (0): The animals are observed for pre-convulsive seizures and clonic or tonic convulsions.

(II)  Posture (4):

Any deviation in normal posture of the animals is observed, e.g. relaxed, hunched, lying, or stretched. The deviation in body or the limb position from the normal may indicate neuromuscular blockade or central depression.

(III)  Motor in-coordination (0):

Motor in-coordination indicates CNS depression and muscular relaxation, synaptic blockade or anesthetic activity.

1. Ataxia (0): Ataxia, staggering or abnormal gait can be scored as under:

a. Score – 2, when animal’s movements show occasionally detectable in-coordination,

b. Score – 3, constant in-coordination, but animal walks straight,

c. Score – 4, animal does not walk straight stumbles and the course is zigzag.

2. Righting reflex (4): When an animal is placed on its back, it orients itself to correct posture. This reflex is called righting reflex and indicates normal mid brain activity. The scoring is done as under:

a. Score – 4 when corrects immediately

b. Score – 2 sluggish but corrects within five seconds (partial loss of righting reflex).

c. Score – 0 when does not correct within 15 seconds (complete loss of righting reflex). The time elapsed between loss and regain of righting reflex is measured as ‘sleeping time’.

3. Somersault test (0): This is also like righting reflex but procedure of observation is different. In this test mouse is picked up by tail and tossed in the air five times. The scoring is done according to the posture adopted by mouse when it touches the rubber-padded floor.

a. Standing on four feet: score 0, if every time it stands on four legs.

b. Lying on sides: score 1, if 1-2 times, score 2, if 3-4 times and score 3, if 5 times.

c. Lying on the back: score 4, if 1-2 times; score 5, if 3-4 times and score 6 if 5 times.

d. Sluggish regaining of posture from supine or side position: score 7.

e. Remains on the back:  score 8.

(IV)  Muscle tone:

Loss of muscle tone indicates myorelaxation, neuromuscular blockade or CNS depression.

Limb tone (4): Limb tone may be assessed by grasping a foreleg of the mouse and feeling
the resistance on the extension of the leg.

b. Grip strength (4): It can be assessed in two ways:

i. Allow the mouse to grasp a pencil in the horizontal position and then lift the animal and note the ease with which the animal drops the pencil.

ii. Inclined plane test: In this test the mouse is placed on top of an inclined plane, usually a wooden board having rough surface and kept at 45o angle. Normal animals walk down the board while affected animals slide down.

c. Abdominal tone or body tone (4): Body tone can be estimated by noting the muscle tone in comparison to that in normal animals. The body tone can also be estimated by performing Raubichaud test: To perform this test, pick up the mouse by holding between thumb and fore-finger the loose fold of skin on the back of the animal and then suddenly drop the animal on the floor. Now observe the perpendicular skin folds for adopting the body contours. The scoring is done as under:

Score 0, if the perpendicular fold of skin adopts to body contours immediately.
Score 1, if the fold persists for 3-5- seconds.
Score 2, if the fold persists for more than 5 seconds.
(V)  Reflexes:

a. Pinnal reflex (4): Pinnal reflex is observed by touching the external auditory meatus with a hair brush, feather or other soft fine object. Normally mouse withdraws its head from the offending objects and shows pinnal movements.

b. Corneal reflex (4): This reflex is observed by touching cornea with stiff hair. Normally the mouse closes its eye lids or withdraws itself.

Pinnal and corneal reflexes are scored as follows.

i. Normal response - score 4

ii. Sluggish response - score 2

iii. No response - score 0

Loss of these reflexes indicates blockade of sensory nerves, motor nerves or the spinal synapses.

autonomic profiles

(I)  Optical sign:

1. Pupil size (4): Make observations for increase or decrease in the size of the pupil. Enlargement (mydriasis) indicates sympathomimetic or parasympatholytic activity.

Constriction (miosis) indicates parasympathetic stimulation or morphine induced (pin-point pupil) activity.

2. Palpebral opening (4): Observation is made for the degree of opening or closure of eye lids. It is scored as under:

i. Normal opening of eye lids – score 4

ii. Slight closure of eye lids – score 3

iii. Half closure of eye lids – score 2

iv. Three fourth closure of eye lids – score 1

v. Complete closure of upper eye lids (ptosis) – score 0

Wide palpebral openings are signs of sympathomimetic activity and narrow palpebral opening are signs of tranquillization and CNS depression.

3. Exopthalamus (0): Bulging of eye balls indicates sympathetic stimulation.

(III)  Secretory signs: normal scores are as under.

1. Urination – score 0

2. Salivation – score 0

3. Lachrymation – score 0

4. Sweating – score 0

5. Defecation – score 0

Increase in all these secretary signs/scores indicates parasympathetic (musacrinic) stimulation.

IV)  General signs:

1. Writhing (0): Movements with abdomen stretched or rubbing of abdomen with floor indicates irritation of peritoneum or stimulation of sensory receptors.

2.  Piloerection (0): indicates sympathetic stimulation, hypothermia or tranquillizing activity.

3. Colour of skin and mucus membrane:

Red color - indicates vasodilatation or sympatholytic activity.

White color - indicates vasoconstriction or sympathomimetic activity.

Cyanosis - indicates decreased oxygenation.

4. Heart rate:

Tachycardia – cardiotonic or sympathetic stimulation.

Bradycardia –cardiac depression or sympatholytic or parasympathetic stimulation.

  1. Respiratory rate:

Increase - indicates analeptic activity or CNS stimulation.

Decrease - indicates CNS depression.

MISCELLANEOUS PROFILES

1. Snout withdrawal: The scoring is based on the time taken by the animals to withdraw

head when its snout is held between thumb and index finger. Score 4, 3, 2 and 1 is given when time taken by the animal is 1, 2, 6 and 8 seconds, respectively.

2. Head drop: It is produced when a drug has peripheral muscle relaxant action.

3. Hind drop: It is produced when a drug has central muscle relaxant action.

4. Other profiles are: analgesia, anaesthesia, blood pressure, pulse rate, biting, fighting, vision, cage climbing and mortality.

Species of animal_____________ Sex_____________ Body Weight _________________

Name of Drug ________________________________ Dose & Route_________________

  Activity profiles Normal                 Time after drug administration  (min.)
  Score            
    5 10 15 20 30 60
SMA 4            
Ataxia 0            
Passivity 0            
Stereotypy 0            
Reactivity 4            
Startle response 0            
Straub tail 0            
Convulsions (tonic/clonic) 0            
Righting reflex 4            
Pinal reflex 4            
Corneal reflex 4            
Pupil size 4            
Palpebral opening 4            
Urination 0            
Salivation 0            
Defaecation 0            
Lachrymation 0            
Piloerection 0            
Snout withdrawal 4            
Robichaud test 0            
Body posture 4            
Limb tone 4            
Exophthalmia 0            
Any other 0/4            

Interpretation of results:

Type/class of drug __________________________________________
Name of known / unknown drug ________________________________

 

Signature of instructor                                                                        Signature of student

Date:                                                                                                   Date:

  Normal Score                 Time after drug administration  (min.)
               
               
    5 10 15 20 30 60
SMA 4            
Ataxia 0            
Passivity 0            
Stereotypy 0            
Reactivity 4            
Startle response 0            
Straub tail 0            
Convulsions (tonic/clonic) 0            
Righting reflex 4            
Pinal reflex 4            
Corneal reflex 4            
Pupil size 4            
Palpebral opening 4            
Urination 0            
Salivation 0            
Defaecation 0            
Lachrymation 0            
Piloerection 0            
Snout withdrawal 4            
Robichaud test 0            
Body posture 4            
Limb tone 4            
Exophthalmia 0            
Any other 0/4            
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