Drugs acting on CNS (veterinary)

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Overview of the drugs acting on the CNS of animals.

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Presented by-

Sindhu K,

M. V. Sc. Scholar, Dept. of VPT, COVAS, Pookode.

Greek: an = without

aesthesia = sensation

Anesthesiology is defined as art & science of administration of anesthesia.

Anesthesia term coined (1846) by an American physician Oliver Wendell Holmes, Sr. (1809-1894)

In 1975, The American College of Veterinary Anesthesiologists was officially recognized by the American Veterinary Medical Association as the body to certify veterinarians as specialists in veterinary anesthesia.

To apply methods to

minimize / eliminate pain,

relax muscles,

Facilitate patient restraint during surgical, obstetrical, medical, diagnostic & therapeutic procedures.

To monitor & support

Life functions in patients during the operative as well as in critically ill, injured, / seriously ill patients.

Elimination of sensibility to noxious stimuli.

Humane restraint (protect animal, facilitate diagnostic/surgical procedure).

Technical efficiency (protect personnel, facilitate diagnostic/surgical procedures).

Specific biomedical research tool (sleep time).

Control convulsions.

Euthanasia.

Prevention of the perception of noxious stimuli (pain) during surgery is the primary justification for anesthesia.

A noxious stimulus = stimulus that potentially damages the body tissue.

Nociception has no emotional/perceptional connotation.

Pain is an unpleasant sensory & emotional experience; it is a perception, not a physical entity.

Perception of pain depends functioning cerebral cortex.

• Sensory

• Discriminative

• Motivational

• Affective

Anesthesia is produced by

Chemicals (drugs)

Physical (sensory nerve destruction)

According to route of administration:

Topical.

Injection.

Gastrointestinal tact.

Respiratory system.

I. Cutaneous.

II. Mucous membrane.

I. Intravenous

II. Subcutaneous

III. Intramuscular

IV. Intraperitoneal

V. Intraosseous

Oral

Rectal

I. Inhalation

Based on extent of loss of sensation

1. Local/regional: drugs placed in close proximity to nerve membranes, causing conduction block.

Eg: topical, area infiltration, perineural, peridural, subarachnoid.

2. General anesthesia: state of controlled, reversible CNS depression including unconsciousness produced by one/multiple drugs.

Eg: injectable, inhalation, balanced.

Administered usually to conscious or mildly sedated animals, to desensitize a localized or regional area of the body.

It is deposited in close proximity to nerve membrane causing nerve conduction blockade.

GA is a condition induced by pharmacological or other means that results in controlled, reversible CNS depression.

Basic elements of GA:

I. Reversibility

II. Unconsciousness

III. Amnesia

IV. Analgesia

V. Muscle relaxation

VI. Immobility

A favorable anesthetic course begins with good plan – a plan based on sound pharmacological & physiological principles.

Anesthetic management = physiology of respiration + circulatory + central + autonomic nervous system.

Pre-anesthetic period.

Anesthetic period/ peri-anesthetics period.

Post-anesthetic period.

Tranquilizer-sedative (Acepromazine, benzodiazepines).

Hypnotic sedatives (pentobarbital & chloral hydrate).

Opioid (agonist-morphine & meperidine, agonist-antagonist-butorphanol).

Alpha-adrenergic agonist (xylazine, detomidine, medetomidine).

Dissociative (ketamine)

Parasympatholytics (atropine & glycopyrrolate).

Sedative drugs (telozol = tiletamine + zolazepam).

Administration of anesthesia requires a combination of knowledge + skill+ ingenuity.

Given by inhalation / injections.

Classification

Hypnotic sedatives

Dissociative

Opioid

Tranquilizer-sedatives

Balanced anesthetics.

Also known as anesthetic recovery period.

Hazards of immediate postanesthetic period:

Circulatory system complication arterial hypo- & hypertension, cardiac dysrhythmias.

Respiratory system complications hypoxemia, hypercapnia

Pain nociception

Emergency excitement physical trauma

Hyper-/hypothermia

Vomiting

Delayed awakening.

• Used clinically act by interfering with the effectiveness of the endogenous neurotransmitter Ach to activate nicotinic cholinergic receptors of skeletal muscle cells, thereby inhibiting receptor-coupled transmembrane ion movements necessary for muscle contraction. (Bouzat et al. 2004: Unwin 2005).

• End result = skeletal muscle paralysis + muscle relaxation.

• Most often used as adjuvants to anesthesia to facilitate tracheal intubation, abdominal muscle relaxation, orthopedic manipulations & as a part of balanced anesthesia procedure to reduce the amount of GA required in high-risk patients.

A direct alteration of the effectiveness of Ach to activate postjunctional receptors.

According to the mechanisms of postjunctional action, neuromuscular blocking agents are classified as

I. competitive (nondepolarising) agent.

II. depolarizing agent.

Drugs compete with Ach for available cholinergic receptors at postsynaptic membrane & by occupying these receptors, prevent the transmitter function of Ach.

Prototype: d-tubocurarine (Tubocurarine chloride, USP, Tubarine).

Metocurine Iodide, USP (Metubine).

Gallamine Triethiodide, USP, (Flaxedil) gallamine.

Pancuronium Bromide, Pavulon, Pancuronium.

Synthetic compound: alcuronium, atracurium.

Vecuronium, a derivative of pancuronium.

Drugs exert their skeletal muscle paralyzing effects by interfering with Ach-mediated depolarization of the post synaptic membrane.

Prototype: Succinylcholine chloride USP (quelcin, anectine, sucostrin, suxamethonium).

Decamethonium bromide, USP (syncurine, C-10)

Muscle paralysis head & neck muscles (head drop) tail limb muscles deglutition & laryngeal muscles abdominal muscles intercostal muscles diaphragm.

Recovery usually proceeds in the reverse sequence (Hall, 1971).

Unique among anesthetic drugs

because of ease in administration & in large part removed from the body, via the lungs.

Used widely for anesthetic management of animals due to their pharmacokinetic characteristics favors predictable & rapid adjustment of anesthetic depth.

Specialized apparatus is used to deliver the inhaled agents, helps minimize patient morbidity/mortality facilitates accurate & controlled anesthetic delivery, lung ventilation & improved arterial oxygenation.

Group I : agents in current use for animals.

Volatile halothane, isoflurane, desflurane, sevoflurane.

Gas nitrous oxide (N2o)

Group II : gaseous agent under investigation

Xenon

Group III : volatile agents of immediate past use/ interest.

Enflurane

Methoxyflurane

Diethylether

Provide rapid means of producing sedation/anesthesia in veterinary patients.

Advantage of injectable anesthetic over inhalation the ability to proceed more rapidly through stage II anesthesia (the excitement stage).

These agent allows a more rapid control of airway, smooth induction of anesthesia, rapid control & reduction in CNS activity, unobstructed visualization of URT for surgical procedures.

For large animal (horses), preventing the excitement stage is paramount for the animal’s safety + medical personnel.

Physiological properties unconsciousness, amnesia, analgesia & skeletal muscle relaxant.

Pharmacological properties margin of safety/ therapeutic index, short duration of action & noncumulative, readily metabolized & excreted ideally by > one route, a specific & complete reversal of anesthesia.

Ideal drug chemically stable, long shelf life, physiological pH, nontoxic vehicle & inexpensive.

I. Barbiturates. (thiopental, pentobarbital, amobarbital & phenobarbital.)

II. Non barbiturates – non dissociative anesthetics.

a. Phenol derivatives (propofol & fospropofol)

b. Imidazole derivatives (etomidate & metomidate)

c. Neurosteroids (alfaxalone-alfadolone & alfaxalone-CD)

d. Benzodiazepines (midazolam, diazepam & lorazepam)

e. Opiods, neuroleptanalgesics & neuroleptanalgesthics.

(fentanyl, fentanyl+droperidol, methadone+acepramazine+nitrousoxide.)

f. Miscellaneous i/v anesthetics [chloralhydrate, Guaifenesin (triple drip), chloralose, propranidid, tribromoethanol, urethane]

III. Dissociative anesthetics (ketamine, phencyclidine & tiletamine).

Classification Compounds Clinical

applications

Ultra short acting Thiopental, thiamylal,

thialbarbital, hexobarbital,

methohexital.

As general anesthetic

Short acting Pentobarbital, secobarbital. As hypnotic, pre-anesthetic &

emergency management of

seizures.

Intermediate acting Amobarbital, aprobarbital,

mephobarbital.

As hypnotic, pre-anesthetic &

emergency management of

seizures.

Long acting Barbital, phenobarbital. As anticonvulsant &

sedatives.

An anesthetic state caused from interruption of

ascending transmission from the unconscious to conscious part of the brain.

Characterized by catalepsy.

somatic analgesia.

intact ocular+laryngeal+pharengealreflexes.

control of the airway may not be complete, intubation with a cuffed endotracheal tube is recommended.

Commonly used induction + maintenance of anesthesia in cats & dogs.

CNS acting drugs which decreases activity, moderate excitement, produce drowsiness & calm the recipient.

Drugs having capacity to decrease the CNS activity calming & drowsiness.

Clinical indication to produce restrain.

to facilitate handling + transport.

to modify behavior of animals.

Sedative = non specific ~ general CNS depressants.

I. Hypnotic-sedatives/ Classical sedatives.

II. Tranquilliser-sedatives/Tranquillisers (ataractics, neuroleptics).

I. Benzodiazepines diazepam, midazolam, lorazepam.

II. Alpha2 adrenoceptor agonists xylazine, detomidine, medetomidine, romifidine & clonidine.

III. Barbiturates barbital, phenobarbital, amobarbital, secobarbital, pentobarbital.

IV. Chloral derivatives chloral hydrate.

V. Aldehydes paraldehyde.

VI. Inorganic salts sodium bromide, potassium bromide & magnesium sulphate.

VII.Miscellaneous agents ethyl alcohol, ethchlorvynol, glutethimide, methyprylon, ethinamate & meprobamate.

I. Phenothiazines chlorpromazine, acepromazine,

promazine, piperacetazine, triflupromazine.

II. Thioxanthenes chlorprothixene, clopenthixol, thiothixene.

III. Butyrophenones azaperone, droperidol, fluanisone.

Diverse group of drugs used primarily in the treatment of epilepsy.

It is important to 1st approach epilepsy as a manifestation of an underlying disease.

When the underlying cause of disease cannot be identified (idiopathic epilepsy) or treated management of epilepsy is primarily based on control of seizures with anticonvulsant drugs.

Major molecular target of commercially available drugs

Voltage gated sodium channels.

GABA a receptors.

The GAT-1 GABA transporter.

GABA transaminase.

I. Barbiturates phenobarbital, pentobarbital & mephobarbital.

II. Deoxybarbiturates primidone

III. Hydantoins phenytoin, mephenytoin, ethotoin, fosphenytion.

IV. Benzodiazepines clonazepam, diazepam, lorazepam, oxazepam, clorazepate.

V. Aliphatic carboxylic acids valoproic acid & sodium valproate

VI. Bromides potassium bromide & sodium bromide

VII.Succimides ethosuximide, methsuximide, phensuximide & mesuximide

VIII.GABA analogues gabapentin, vigabatrin, pregabalin, progabide

IX. Dicarbamates felbamate & meprobamate

X. Sulphonamides zonisamide, acetazolamide, methazolamide & sultiame

XI. Pyrrolidines levetiracetam, brivaracetam & seletracetam

XII. Carboxamides carbamazepine, oxcarbazepine, eslicarbazepine& rufinamide

XIII. Oxazolidinediones trimethadione, paramethadione & etadione.

XIV. Miscellaneous agents topiramate, lamotrigine, valpromide, beclamide, lacosamide, paraldehyde, tiagabine, stiripentol & valnoctamide.

Veterinary clinical ethology A relatively new branch of vet. Medicine dealing with study of customs & behaviour of animals in their natural habitat.

Behaviour is a complex phenomenon.

It is not easy to define in terms of normal & abnormal behaviour.

Adverse behaviour in animals disease condition (neural disorders).

lack of socialization & training.

genetically determined.

Classification of behaviour disorders on basis of their origin.

Genetic problems, developmental & age related problems, instinctive & species related problems, socialization/ social behaviour related problems, disease related problems & adaptation problems.

Sr. no. Behaviour disorder Etiology

1 Aggression Dominance, competition, fear, learned, idiopathic &

feeling of uncertainty.

2 Anxiety Separation, travelling, new place & unfriendly

environment.

3 Fear/phobia Thunderstorms, gunshots, fireworks, heavy vehicle’s

engine noise.

4 Destruction Fear anxiety, over activity & reaction to arousing

stimuli.

5 Excessive vocalization Frustrated social/sexual environment, aggression &

reaction to external stimuli.

6 Elimination behaviour

(urination/defecation)

Marking territory, urine spraying (cats), submission,

excitement, lack of training & separation.

7 Sexual behaviour Hyper-sexuality, lack of libido, false pregnancy.

8 Self mutilation Attention getting & stress response.

9 stereotypies Stress response & compulsive behaviour.

Abnormal behaviour in man/animal is closely related to alterations in concentrations of various neurotransmitters

Biogenic amines

Acetylcholine

Excitatory AA

Inhibitory AA

A wide variety of drugs from different pharmacological classes are employed to modify abnormal behaviour in animals Psychotropic drugs, anticonvulsants, hormonal preparations, CNS stimulants, artificial pheromones & miscellaneous drugs.

Algesia = ill-defined, unpleasant sensation,

usually evoked by external / internal noxious stimulus.

Physiological pain nociceptive pain.

Pathological pain neurogenic & cancer pain.

Opioids potent analgesic agents, which induces analgesia by stimulation of central opioid receptors.

Classified into

I. Opioid agonists.

II. Opioid mixed agonist-antagonists & partial agonists.

I. Natural opium alkaloids morphine & codeine.

II. Semi-synthetic opioids diacetylmorphine, hydromorphine, oxymorphone, hydrocodone, oxycodone, etorphine.

III. Synthetic opioids

1. Phenylpiperidines (pethidine, ketobemidone, prodine, allylprodine, anileridine).

2. Anilidopiperidines (fentanyl, alfentanil, carfentanil, sufentanil).

3. Diphenylpropylamine derivatives (methadone, propoxyphene, dextromoramide, dipipanone, loperamide & diphenoxylate).

4. Morphinans (levorphanol & levomethorphan).

5. Benzomorphans (phenazocine).

6. Miscellaneous drugs (tramadol, tapentadol & tilidine).

I. Semi-synthetic opioids (buprenorphine & nalbuphine).

II. Synthetic opioids

1. Morphinans (butorphanol).

2. Benzomorphans (pentazocine, dezocine & cyclazocine).

3. Miscellaneous agents (meptazinol).

Drugs which stimulate the CNS/improves specific brain functions.

Classification pyscostimulants / cerebral stimulants

brain stem stimulants / analeptics

convulsants

psychotomimetics / hallucinogens

Small animal clinical pharmacology: D. M. Boothe. (2nd ed.)

Veterinary Pharmacology and Therapeutics: Jim E Riviere & Mark G Papich. (9th ed.)

Veterinary pharmacology and therapeutics: H. R. Adams. (8th ed.)

Essentials of veterinary pharmacology & therapeutics: H. S. Sandhu. (2nd

ed.)

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