---

VPT Short Notes - 3 Mark Answers

---

1. Mechanism of Action (MOA) of Cardiac Glycosides (with Diagram)

1. Glycoside binds to and inhibits Na⁺/K⁺-ATPase → intracellular Na⁺ accumulates
2. Elevated intracellular Na⁺ reduces the Na⁺/Ca²⁺ exchanger (NCX) activity → less Ca²⁺ is extruded from cell
3. Intracellular Ca²⁺ increases → stored in sarcoplasmic reticulum
4. During systole, more Ca²⁺ is released → stronger myocardial contraction (positive inotropy)

Cardiac Glycoside
       ↓
Inhibits Na⁺/K⁺-ATPase
       ↓
↑ Intracellular Na⁺
       ↓
↓ Na⁺/Ca²⁺ exchanger activity
       ↓
↑ Intracellular Ca²⁺
       ↓
Positive Inotropy (stronger contraction)

---

2. Ammonium Chloride and Sodium Bicarbonate as Modifiers of Urine pH

• Metabolized in liver to urea + HCl → HCl is excreted by kidneys → urine becomes acidic (pH <6)
• Acidic urine ionizes basic drugs (alkaloids, amphetamines) → ion trapping → enhanced urinary excretion
• Used in: struvite urolithiasis in cats, alkaloid poisoning, urinary tract infections caused by urease-producing bacteria
• Dose: 100-200 mg/kg orally in cattle; 20 mg/kg in cats

• Absorbed and excreted by kidneys → raises urine pH (>7)
• Alkaline urine ionizes acidic drugs (barbiturates, salicylates, sulfonamides) → ion trapping → increased excretion
• Used in: barbiturate or aspirin toxicity, prevention of urate/oxalate uroliths, cystitis treatment
• Metabolic alkalosis is a side effect with overdosage

---

3. Uses of Cyclosporine and BCG as Immunomodulators in Veterinary Practice

• Mechanism: Inhibits calcineurin → prevents IL-2 production → suppresses T-lymphocyte proliferation
• Uses in veterinary practice:
  • Atopic dermatitis in dogs (Atopica® - approved)
  • Feline hypersensitivity skin disease
  • Inflammatory bowel disease (IBD) in dogs and cats
  • Perianal fistula (anal furunculosis) in German Shepherds
  • Organ transplant rejection prophylaxis (experimental in veterinary medicine)
  • Immune-mediated hemolytic anemia (IMHA) as adjunct therapy

• Mechanism: Attenuated Mycobacterium bovis; activates macrophages, NK cells, and T-cells (non-specific immunostimulation)
• Uses in veterinary practice:
  • Adjuvant in cancer immunotherapy (bovine ocular squamous cell carcinoma - intralesional injection)
  • Bovine respiratory diseases (immunostimulation)
  • Feline fibrosarcoma and melanoma (experimental)
  • Enhancement of vaccine efficacy

---

4. Drugs Affecting Synthesis, Storage, Release and Action of Norepinephrine

---

5. Classification of Laxatives/Purgatives with Examples

• Absorb water, increase stool bulk, stimulate peristalsis
• Examples: Methylcellulose, ispaghula (psyllium), bran

• Non-absorbable salts retain water in intestinal lumen
• Examples: Magnesium sulphate (Epsom salt), sodium sulphate (Glauber's salt), lactulose, PEG (polyethylene glycol)

• Directly stimulate intestinal smooth muscle and enteric neurons
• Examples: Castor oil (converted to ricinoleic acid), aloes, cascara, bisacodyl, senna, phenolphthalein

• Lubricate intestinal wall and soften feces
• Examples: Liquid paraffin (mineral oil), glycerin suppositories, docusate sodium (DSS)

• Produce copious watery evacuation
• Examples: Magnesium sulphate (high dose), castor oil (high dose)

---

6. Types and Uses of Insulin Preparations

• Insulin lispro, insulin aspart, insulin glulisine
• Onset: 15 min; Peak: 1-2 hr; Duration: 3-5 hr
• Use: Prandial control, diabetic ketoacidosis (DKA)

• Regular crystalline insulin (CZI - Crystalline Zinc Insulin)
• Onset: 30-60 min; Peak: 2-4 hr; Duration: 6-8 hr
• Use: DKA in dogs and cats (IV/IM), acute management

• NPH (Isophane insulin), Lente insulin (IZS)
• Onset: 1-2 hr; Peak: 6-12 hr; Duration: 18-24 hr
• Use: Routine management of diabetes mellitus in dogs and cats

• PZI (Protamine Zinc Insulin) - commonly used in cats
• Insulin glargine (Lantus), insulin detemir
• Duration: 24-36 hr
• Use: Feline diabetes mellitus (cats prefer long-acting); once daily dosing

---

7. Side Effects of NSAIDs

• GI ulceration, erosion, bleeding, vomiting, diarrhea
• Due to inhibition of COX-1 → ↓ gastroprotective PGE₂ and PGI₂ → reduced mucus and bicarbonate secretion

• Papillary necrosis, acute renal failure, reduced GFR
• Prostaglandins maintain renal blood flow in dehydrated/hypotensive animals; NSAIDs block this

• Idiosyncratic hepatitis, elevated liver enzymes (especially carprofen, meloxicam)

• Inhibition of TXA₂ (thromboxane) → impaired platelet aggregation → prolonged bleeding time

• Some NSAIDs may inhibit proteoglycan synthesis

• Dizziness, ataxia (rare in animals)

---

8. MOA of ACE Inhibitors (with Diagram)

Renin (from kidneys)
       ↓
Angiotensinogen → Angiotensin I
       ↓ [ACE - in lung endothelium]
       ↓ ← BLOCKED by ACE Inhibitor
Angiotensin II (NOT formed)
       ↓
(Normal effects of Ang II that are PREVENTED:)
- Vasoconstriction ← blocked
- Aldosterone secretion ← blocked → ↓ Na/water retention
- ADH release ← blocked
- Sympathetic stimulation ← blocked

ADDITIONALLY:
Bradykinin (normally degraded by ACE)
       ↓ ACE INHIBITED
↑ Bradykinin → vasodilation, cough (side effect)

---

9. Classification of Expectorants with Suitable Examples

• Act on gastric mucosa → reflex increase in bronchial secretion via vagus nerve
• Examples: Ammonium chloride, ipecacuanha (emetine), potassium iodide, sodium citrate, guaifenesin (glyceryl guaiacolate - also muscle relaxant in horses), terpin hydrate

• Absorbed and directly stimulate bronchial glands
• Examples: Potassium iodide (also direct), volatile oils (eucalyptus oil, turpentine oil, thymol), creosote, iodinated glycerol

• Break disulphide bonds in mucoproteins → reduce viscosity
• Examples: Bromhexine (most used in veterinary practice), acetylcysteine (NAC), carbocisteine

• Increase ciliary activity
• Examples: Bromhexine, dembrexine (equine use)

---

10. Difference Between Ecbolics and Tocolytics with Examples

---

11. Classification of Anti-emetic Drugs with Suitable Examples

• Examples: Chlorpromazine, acepromazine, prochlorperazine
• Use: Motion sickness, drug-induced vomiting; also tranquilizer in dogs, cats

• Examples: Droperidol, azaperone, haloperidol
• Use: Vomiting associated with anaesthesia, neuroleptic use in pigs

• Acts at CRTZ + peripherally; also 5-HT₄ agonist
• Use: Canine vomiting, GI stasis, reflux esophagitis

• Examples: Ondansetron, dolasetron, granisetron
• Use: Chemotherapy-induced vomiting, parvoviral enteritis in dogs

• Example: Maropitant (Cerenia®) - most effective in dogs and cats
• Use: Motion sickness, chemotherapy-induced vomiting, general vomiting

• Examples: Diphenhydramine, meclizine, dimenhydrinate
• Use: Motion sickness in dogs

• Example: Atropine (limited efficacy as anti-emetic)

---

12. What is Atropinisation?

• Eyes: Mydriasis (dilated pupils), cycloplegia (loss of near vision), photophobia
• Mouth: Dry mouth (inhibition of salivation), difficulty swallowing
• Heart: Tachycardia (inhibition of vagal tone on SA node)
• Skin: Dry, flushed, warm skin (due to inhibition of sweat glands)
• Bladder: Urinary retention (relaxation of detrusor, contraction of sphincter)
• GI: Decreased motility, constipation, reduced GI secretions
• CNS: Restlessness, excitement, hallucinations, delirium (at toxic doses)
• Temperature: Hyperthermia (due to loss of sweating)

• Full atropinisation is the goal in organophosphate poisoning treatment
• Used as pre-anaesthetic to dry secretions
• Toxic atropinisation requires physostigmine as antidote

---

13. Fight-or-Flight Response

---

14. Ideal Properties of Gaseous Anaesthesia

1. Non-flammable and non-explosive
2. Stable (does not decompose or react with soda lime or rubber equipment)
3. Low boiling point (easily vaporised at room temperature)
4. High vapour pressure
5. Pleasant odour (non-irritating to airways)

---

15. Counter-Irritants and Their Clinical Uses

• Applied irritant → cutaneous vasodilation, warmth, redness (rubefaction)
• Stimulates sensory nerve endings → gate control theory (pain impulses from deeper tissues are "gated out" by superficial sensory input)
• ↑ local blood flow → improved resolution of deeper inflammation

1. Chronic arthritis and joint stiffness (horses - "blistering")
2. Splints, ringbone, spavin in equines
3. Chronic tendinitis and periostitis
4. Subacute mastitis (counterirritant liniments)
5. Chronic muscle strains and sprains
6. Respiratory conditions (camphor/eucalyptus - counter-irritation of thorax)
7. Wart treatment (caustics - silver nitrate)

---

16. Pharmacological Effects of Oxytocin on the Uterus

• Binds oxytocin receptor → activates phospholipase C → ↑ IP₃ → ↑ intracellular Ca²⁺ → myometrial contraction

1. Rhythmic contractions: Oxytocin increases the frequency, force, and duration of uterine contractions (contractions similar to natural labour)
2. Sensitivity increases with pregnancy: Oxytocin receptors increase dramatically near term (1000-fold ↑ in receptor density) → uterus becomes increasingly sensitive to oxytocin as pregnancy progresses
3. Dose-dependent effects:
   • Low dose: increases frequency of contractions (normal rhythmic pattern)
   • High dose: sustained tetanic contraction (dangerous - can cause uterine rupture)
4. Cervical ripening: Oxytocin (indirectly via PGs) softens and dilates the cervix
5. Ferguson reflex: Stretching of cervix/vagina → neurohormonal reflex → oxytocin release → stronger uterine contractions (positive feedback during parturition)
6. Postpartum uterine involution: Oxytocin contracts the postpartum uterus → reduces bleeding (PPH treatment)

---

17. Dose-Response Relationship

• Measured in a single subject/tissue; response increases gradually with dose
• Sigmoidal (S-shaped) curve on log-dose vs. effect plot
• Parameters derived:
  • EC₅₀ (ED₅₀): Dose producing 50% of maximal effect - indicates potency
  • Emax: Maximum effect achievable - indicates efficacy
  • Slope: Steepness relates to dose range over which drug is effective

• Measures proportion of a population responding (all-or-nothing response)
• Parameters:
  • ED₅₀: Dose effective in 50% of population
  • LD₅₀: Dose lethal in 50% of population
  • TD₅₀: Dose toxic in 50% of population
  • Therapeutic Index (TI) = LD₅₀ / ED₅₀ - measure of drug safety

• A more potent drug has a lower ED₅₀ (curve shifts left)
• A more efficacious drug has a higher Emax
• A drug can be potent but have low efficacy, or vice versa

---

18. Clinical Uses of Muscle Relaxants in Veterinary Practice

• Atracurium, vecuronium, pancuronium, gallamine
• Uses: Facilitate endotracheal intubation; intraocular surgery (to prevent movement); thoracic surgery; control of tetanus convulsions; orthopaedic procedures

• Succinylcholine (suxamethonium)
• Uses: Rapid intubation (rapid onset/offset); capture and restraint of exotic animals; brief surgical procedures

• Guaifenesin (glyceryl guaiacolate) - most important in veterinary practice
  • Used in horses for chemical restraint and induction (often combined with ketamine or thiopental - "Triple Drip": GGE + ketamine + xylazine)
• Methocarbamol - used for muscle spasm in dogs/cats (tetanus, intervertebral disc disease)
• Diazepam/midazolam - GABA-A agonists; muscle relaxation + sedation

1. Chemical restraint and cast application (horses, cattle)
2. Capture of wild animals (succinylcholine - CAUTION: narrow TI)
3. Tetanus treatment (methocarbamol, diazepam)
4. IVDD (intervertebral disc disease) in dogs
5. Ophthalmic procedures requiring complete muscle paralysis
6. Facilitation of mechanical ventilation

---

19. Morphine as an Analgesic Drug

• Acts on opioid receptors (μ = mu, κ = kappa, δ = delta) - all are Gi-coupled
• μ-receptor activation: ↓ cAMP, ↑ K⁺ conductance, ↓ Ca²⁺ conductance → neuronal hyperpolarisation → inhibits pain transmission in spinal cord and brain
• Acts at: spinal cord (dorsal horn), supraspinal (PAG - periaqueductal grey, thalamus), and peripheral sites

1. Analgesia - relieves severe visceral and somatic pain
2. Sedation and euphoria (μ-receptor)
3. Respiratory depression (most dangerous - ↓ respiratory center sensitivity to CO₂)
4. Cough suppression (acts on cough center)
5. Emesis then antiemesis (stimulates CRTZ initially, then depresses vomiting center)
6. Constipation (↑ GI smooth muscle tone, ↓ peristalsis) - therapeutic use
7. Miosis (pin-point pupils - via Edinger-Westphal nucleus) - except cats (mydriasis)
8. Bradycardia (vagal stimulation)

• Cats: Morphine causes excitement not sedation (CNS stimulation)
• Horses: Also causes excitement at analgesic doses (use with tranquiliser)
• Dogs: Reliable sedation and analgesia - drug of choice

---

20. CNS Stimulants with Examples

• Stimulate cortex → wakefulness, reduced fatigue
• Examples: Caffeine, theophylline, aminophylline (xanthines); amphetamine, dexamphetamine; cocaine
• Mechanism: Xanthines - adenosine receptor antagonism + PDE inhibition; Amphetamine - ↑ monoamine release

• Stimulate respiratory and vasomotor centers in medulla
• Examples: Doxapram (most used in VPT - respiratory stimulant in neonates), pentylenetetrazol (leptazol), nikethamide, bemegride
• Veterinary use: Doxapram to stimulate respiration in newborn animals (foals, calves, puppies) and in anaesthetic overdose

• Stimulate spinal cord → convulsions
• Examples: Strychnine (glycine antagonist in spinal cord); picrotoxin (GABA antagonist)
• Strychnine: causes "saw-horse" stance, sardonic smile, opisthotonus in poisoning

• Amphetamines, methylphenidate, MDMA
• Increase dopamine/NE/5-HT release; used rarely in veterinary practice (narcolepsy in dogs)

• Pentylenetetrazol (PTZ) - used experimentally to screen anticonvulsant drugs

---

21. Neuro-humoral Transmission

• ACh: choline + acetyl CoA → ACh (enzyme: choline acetyltransferase)
• NE: Tyrosine → DOPA → Dopamine → NE (key enzyme: tyrosine hydroxylase)

• Prevents intracellular degradation by MAO

• Enzymatic degradation: ACh by acetylcholinesterase (AChE); NE by MAO and COMT
• Reuptake: NE and dopamine taken back into nerve terminal (Uptake-1) - major mechanism
• Diffusion: away from synapse
• Re-storage: Taken up transmitter re-stored in vesicles

---

22. Classification of Bronchodilators with Examples

• Mechanism: β₂ receptor → ↑ cAMP → bronchial smooth muscle relaxation
• Short-acting: Salbutamol (albuterol), terbutaline - used for acute bronchospasm
• Long-acting: Salmeterol, formoterol - maintenance in horses with heaves
• Clenbuterol - widely used in horses (also tocolytic); approved equine bronchodilator

• Mechanism: PDE inhibition → ↑ cAMP + adenosine receptor antagonism
• Examples: Theophylline, aminophylline (theophylline + ethylenediamine)
• Uses: Equine heaves, feline asthma, canine bronchitis; also cardiac stimulant (aminophylline)

• Mechanism: Block M₃ receptors in bronchi → reduce bronchoconstriction and secretions
• Examples: Atropine, ipratropium bromide
• Uses: Chronic obstructive conditions, heaves in horses (ipratropium nebulisation)

• Examples: Dexamethasone, prednisolone, fluticasone (inhaled - for horses)
• Adjunct to bronchodilators in heaves management

---

23. MOA of Calcium Channel Blockers with Examples

Depolarisation → L-type Ca²⁺ channels open → Ca²⁺ enters cell → smooth muscle/cardiac contraction

CCB blocks L-type Ca²⁺ channel
       ↓
↓ Intracellular Ca²⁺
       ↓
Vascular smooth muscle: relaxation → vasodilation → ↓ BP
Cardiac smooth muscle: ↓ contractility (negative inotropy)
SA/AV node: ↓ automaticity and conduction (negative chronotropy and dromotropy)

• Diltiazem: atrial fibrillation and supraventricular tachycardia in cats and dogs
• Amlodipine: hypertension in cats (drug of first choice), renal hypertension
• Verapamil: SVT management in dogs
• Nifedipine: less used in animals

---

24. Difference Between Competitive and Non-Competitive Antagonism with Examples

---

25. MOA of Local Anaesthetics

1. Entry into nerve: LAs are weak bases (pKa 8-9). In tissue (pH 7.4), partial ionisation occurs. Unionised (lipid-soluble) form penetrates nerve membrane; ionised form blocks Na⁺ channel from inside.
2. Na⁺ channel blockade:
   • LA enters nerve cytoplasm → re-ionizes
   • Ionised form (LA-H⁺) binds to receptor on the inner side of voltage-gated Na⁺ channel
   • Blocks Na⁺ influx during depolarisation
   • Membrane cannot depolarise → action potential cannot be generated or conducted
3. Frequency-dependent (use-dependent) blockade:
   • LAs bind better to open/inactivated channels → faster-firing nerves are blocked preferentially
4. Order of nerve blockade (smallest to largest fibre):
   • Autonomic (B fibres) → Pain/temperature (C fibres, unmyelinated) → Touch (Aδ) → Pressure → Motor (Aα) - last to be blocked

• Lignocaine (lidocaine) - most commonly used; 2% solution for infiltration, nerve blocks, epidural
• Procaine - short-acting; used in food animals
• Bupivacaine - long-acting; used for epidural in horses and cattle
• Mepivacaine - used in equine nerve blocks (laminitis diagnosis)

---

26. Anti-Adrenergic Drugs with Uses

• Phentolamine (reversible), phenoxybenzamine (irreversible)
• Uses: Hypertensive crises, pheochromocytoma, Raynaud's disease, urethral obstruction in cats (phenoxybenzamine)

• Prazosin, terazosin, doxazosin
• Uses: Hypertension in dogs, functional urethral obstruction, benign prostatic hypertrophy (BPH) in dogs

• Yohimbine, atipamezole
• Uses: Reversal of xylazine (α₂-agonist) sedation in animals - major veterinary use; atipamezole reverses medetomidine/dexmedetomidine

• Propranolol - prototype; sotalol (also Class III antiarrhythmic)
• Uses: Cardiac arrhythmias (SVT, AF), hypertension, hypertrophic cardiomyopathy (HCM) in cats, thyrotoxicosis

• Atenolol, metoprolol
• Uses: Cardiac arrhythmias in dogs and cats, hypertension, HCM in cats (most commonly used)

• Reserpine (depletes catecholamine stores), guanethidine
• Limited veterinary use

---

27. MOA of Amphetamine

1. Reversal of monoamine transporters (main mechanism):
   • Amphetamine enters nerve terminal via DAT (dopamine transporter), NET (NE transporter), SERT (serotonin transporter)
   • Causes reverse transport - transporters run in reverse → catecholamines pumped out of nerve terminal
   • Result: Massive non-vesicular release of DA, NE, and 5-HT into synapse
2. Inhibition of reuptake:
   • Blocks DAT/NET/SERT → prevents recycling of released catecholamines
3. Displacement from vesicles:
   • Enters vesicles (via VMAT2) → displaces stored catecholamines into cytoplasm
4. MAO inhibition:
   • Weak inhibition of MAO → ↓ degradation of catecholamines

• CNS: Wakefulness, euphoria, anorexia, ↑ locomotion, stereotypy (DA-mediated)
• Peripheral: Tachycardia, hypertension, vasoconstriction (NE-mediated)
• Anorectic effect: used in obesity (limited veterinary use)
• Dopamine → nucleus accumbens = reward/addiction pathway

---

28. Differentiate Between Affinity, Efficacy and Potency

• A drug can have high affinity but zero efficacy (competitive antagonist - binds but no response)
• A drug can be highly potent but have low efficacy (partial agonist)
• Efficacy is an intrinsic property; potency can be influenced by absorption, distribution, etc.

---

29. Classify Purgatives with Examples

1. Bulk-forming: Absorb water, ↑ stool bulk, mechanical stimulation
   • Examples: Ispaghula, methylcellulose, bran, agar
2. Osmotic/Saline purgatives: Retain water in gut lumen by osmosis
   • Examples: MgSO₄ (Epsom salt), Na₂SO₄ (Glauber's salt) - used in large animals; lactulose (cats/dogs), polyethylene glycol (PEG)
3. Stimulant/Irritant purgatives: Directly stimulate intestinal mucosa/plexus → ↑ peristalsis + ↓ absorption
   • Anthraquinone group: Aloes (most used in horses/cattle), cascara, senna
   • Diphenylmethane group: Bisacodyl, phenolphthalein
   • Castor oil: hydrolysed to ricinoleic acid in small intestine → irritant
4. Lubricant purgatives: Lubricate and soften feces
   • Examples: Liquid paraffin (mineral oil) - most used in horses (impaction colic); glycerin suppository
5. Stool softeners (Emollients): Surfactant action, soften feces
   • Example: Docusate sodium (DSS) - dogs, cats

---

30. Class II Anti-Arrhythmic Drugs

• Block β₁ receptors at SA node, AV node, and ventricular myocardium
• ↓ Automaticity of SA node (negative chronotropy) → slower heart rate
• ↓ AV node conduction velocity (negative dromotropy) → useful for SVT
• ↓ Myocardial contractility (negative inotropy)
• Reduce triggered arrhythmias from sympathetic overstimulation
• Reduce ischaemia-induced arrhythmias by ↓ myocardial O₂ demand

• Prolong PR interval
• No significant effect on QRS or QT interval (differentiates from other classes)

---

31. Dale's Vasomotor Reversal Phenomenon (Brief)

• Adrenaline (epinephrine) normally causes a pressor response (↑ blood pressure) due to α₁-mediated vasoconstriction and β₁-mediated increased cardiac output
• After administration of an alpha (α) adrenergic blocker (e.g., ergot alkaloids, phentolamine, phenoxybenzamine), a subsequent dose of adrenaline causes vasodepressor response (↓ blood pressure) instead of pressor response
• This is called "reversal of adrenaline action" or Dale's phenomenon

• After α-blockade, α₁ pressor effects of adrenaline are blocked
• Unmasked β₂-mediated vasodilation (in skeletal muscle, coronary, splanchnic vessels) predominates
• Net effect: BP falls instead of rising

1. Demonstrates the dual α and β actions of adrenaline
2. Confirms the existence of separate α and β adrenoreceptors
3. Historical basis for development of adrenergic receptor pharmacology
4. Noradrenaline (which has minimal β₂ activity) does NOT show reversal - confirms β₂ role

---

32. Neuroleptanalgesia with Examples

• Neuroleptic: Phenothiazine or butyrophenone (e.g., acepromazine, azaperone, droperidol)
• Opioid analgesic: Morphine, fentanyl, etorphine, butorphanol, buprenorphine

• Animal is sedated, calm, indifferent to environment
• Markedly reduced response to pain
• Maintained consciousness (can be aroused)
• Muscle relaxation
• Reduced anaesthetic requirement (opioid-sparing effect)

---

33. Need for Pre-Anaesthetic Medication (PAM)

• Animals are often stressed → ↑ catecholamines → arrhythmias, ↑ anaesthetic requirement
• Phenothiazines (acepromazine), benzodiazepines (diazepam), α₂-agonists (xylazine, medetomidine)

• Prevents airway obstruction, aspiration pneumonia during anaesthesia
• Atropine, glycopyrrolate (anti-muscarinic agents)

• PAM allows lower maintenance doses → reduces toxicity risk
• Opioids, α₂-agonists provide opioid/anaesthetic-sparing effect

• Pre-treatment with analgesics before painful stimuli reduces central sensitisation
• Opioids (morphine, butorphanol), NSAIDs

• Bradycardia, laryngospasm, cardiac arrest during intubation
• Atropine prevents this

• Sedation ensures smooth, stress-free induction
• Reduces risk of "paradoxical excitement" with some agents (e.g., ketamine without PAM in cats)

• Prevents vomiting during induction (especially in dogs)
• Acepromazine has anti-emetic properties

---

34. Prokinetic Drugs

• Metoclopramide - most commonly used in small animal practice
  • Blocks D₂ receptors (GI tract + CRTZ) + 5-HT₄ agonist
  • Increases LES tone, accelerates gastric emptying, coordinates antrum-duodenum
  • Also anti-emetic (CRTZ blockade)
  • Uses: Gastric stasis, reflux esophagitis, post-surgical ileus, vomiting (dogs, cats)
• Domperidone - peripheral D₂ antagonist (does not cross BBB)
  • Uses: Gastroparesis, agalactia (stimulates prolactin), equine GI problems

• Cisapride - 5-HT₄ agonist + D₂ antagonist
  • Widely used but withdrawn in humans due to QT prolongation; still used in veterinary practice
  • Uses: Feline megacolon, gastroparesis, idiopathic constipation in cats
• Mosapride (newer, more selective 5-HT₄ agonist)

• Erythromycin (low dose) - acts as motilin receptor agonist
  • Uses: Post-surgical ileus in horses and cattle (powerful prokinetic), diabetic gastroparesis in dogs
  • Dose: Sub-antimicrobial 0.5-1 mg/kg IV

• Neostigmine - increases ACh → stimulates intestinal motility
• Uses: Post-surgical paralytic ileus in cattle and horses (limited use - may cause colic)

---

35. Stages of Anaesthesia

• From beginning of anaesthesia to loss of consciousness
• Animal is conscious, reduced pain sensation (analgesia)
• Reduced anxiety, slight drowsiness
• Minor procedures possible (e.g., minor wound dressing)

• From loss of consciousness to onset of regular breathing
• Loss of all voluntary control → involuntary excitement, struggling
• Irregular breathing, breath holding, vomiting, exaggerated reflexes
• Most dangerous stage - risk of laryngospasm, aspiration, injury
• Ideally this stage should be short (rapid-acting IV agents reduce this)

• From regular breathing onset to respiratory paralysis
• Subdivided into 4 planes:

• Respiratory paralysis → apnoea → death if not resuscitated
• Pupils maximally dilated, fixed
• Anaesthetic overdose stage

---

36. Ligand-Gated Ion Channels

• Transmembrane proteins forming a central pore (ion channel)
• Typically pentameric (5 subunits) arranged around a central channel
• Ligand-binding site distinct from ion channel

• Ligand binds → conformational change → channel opens → specific ions flow down electrochemical gradient → rapid change in membrane potential

• Fastest type of receptor response (milliseconds)
• Benzodiazepines and barbiturates act on GABA-A (allosteric modulators)
• Succinylcholine and tubocurarine act on nAChR (NMJ)
• GABA-A is target for general anaesthetics (propofol, halothane)

---

37. Acetylcholinesterase (AChE) Inhibitors

• Physostigmine (eserine) - penetrates CNS; antidote for atropine poisoning; used in equine choke
• Neostigmine - does not penetrate CNS; reversal of non-depolarising NMB; treatment of myasthenia gravis; rumen atony, cecal/colonic impaction in horses
• Pyridostigmine - long-acting; myasthenia gravis treatment (dogs)
• Edrophonium - very short-acting; diagnosis of myasthenia gravis (Tensilon test); reversal agent

• Donepezil, rivastigmine, galantamine - CNS-selective; cognitive dysfunction syndrome (CDS) in old dogs (experimental)

• Therapeutic: Echothiophate (glaucoma), DFP (diisopropylfluorophosphate)
• Insecticides/Parasiticides: Malathion, parathion, dichlorvos, fenthion, trichlorfon
• Nerve agents (military): Sarin, VX, tabun

• Salivation, Lacrimation, Urination, Defaecation, GI distress, Emesis
• Plus: Miosis, bradycardia, bronchospasm, seizures (central effects)

---

38. Synthesis, Storage, Release and Metabolism of Noradrenaline

Tyrosine (dietary amino acid)
    ↓ Tyrosine hydroxylase (rate-limiting enzyme, requires BH₄)
DOPA (3,4-dihydroxyphenylalanine)
    ↓ DOPA decarboxylase (aromatic L-amino acid decarboxylase)
Dopamine
    ↓ Dopamine β-hydroxylase (DBH - inside vesicles, requires Cu²⁺, Vit C)
Noradrenaline (stored in vesicles)
    [In adrenal medulla only: NE → Adrenaline via PNMT (Phenylethanolamine N-methyltransferase)]

• Stored in dense-core synaptic vesicles (large dense core granules)
• Vesicular Monoamine Transporter 2 (VMAT2) pumps NE into vesicles
• Also stored with ATP and chromogranin (co-transmitters)

• Action potential → membrane depolarisation → voltage-gated Ca²⁺ channels open → Ca²⁺ influx → vesicle fusion → exocytosis
• Quantal release into synapse
• Regulation: α₂ presynaptic autoreceptors provide negative feedback (NE inhibits its own release)

1. Reuptake (Uptake-1) - MAJOR PATHWAY (75-80%):
   • NET (Norepinephrine Transporter) takes NE back into nerve terminal
   • Blocked by: cocaine, tricyclic antidepressants, amphetamine
2. Enzymatic degradation:
   • MAO (Monoamine Oxidase) - intraneuronal degradation → DOPAC, then MOPEG
   • COMT (Catechol-O-Methyltransferase) - extraneuronal degradation → Normetanephrine
   • Final metabolite: VMA (Vanillylmandelic acid) - excreted in urine
3. Uptake-2 (extraneuronal uptake) - minor, low-affinity, high-capacity
4. Diffusion into blood and lymph

---

39. Advantages and Disadvantages of Intravenous (IV) Administration of Drugs

1. Rapid onset of action - 100% bioavailability; drug reaches systemic circulation immediately (useful in emergencies)
2. Complete bioavailability (F = 100%) - no first-pass metabolism, no absorption variability
3. Precise control of blood levels - exact dose can be titrated
4. Large volumes can be administered (fluids, blood transfusions)
5. Suitable for irritant drugs that cannot be given IM/SC (calcium borogluconate in hypocalcaemia)
6. Suitable for drugs destroyed in GIT (insulin, heparin, proteins)
7. Continuous infusion possible - maintains constant plasma levels (CRI - constant rate infusion)
8. Can be given in unconscious animals
9. Predictable drug levels - not affected by absorption variables

1. Irreversible - once given, drug cannot be recalled or removed if adverse reaction occurs
2. Rapid adverse reactions - anaphylaxis, cardiac arrhythmias, hypotension (too rapid injection)
3. Requires trained personnel and aseptic technique - risk of phlebitis, thrombosis, air embolism, septicaemia
4. Not suitable for oily or insoluble preparations
5. Painful - requires venipuncture; not suitable for irritant drugs if given too fast
6. IV drug interactions more dangerous due to rapid plasma concentration changes
7. Short duration - rapid excretion may require repeated dosing
8. Perivascular injection causes tissue necrosis with certain drugs

---

All answers are based on the syllabus and content of Sandhu's Veterinary Pharmacology & Toxicology, 2nd Edition, aligned with standard 3-mark examination requirements for veterinary pharmacology (VPT).