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451 Cards in this Set

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Anti Virals

8 Possible Sites of Action
Attachment

Penetration

Uncoating

Transcription

Translation

Replication

Assembly

Release
Pleconaril
Antiviral
`` Receptor Analoque
`` Blocks Attachment

Expensive
`` tf low vet use
`` possible Feline Calici

Oral Administration
`` good absorption
`` crosses BBB

Effective against wide range of
`` Enteroviruses
`` Rhinoviruses
Amantadine
Antiviral
`` Ion channel Blocker
`` Blocks Penetration

Low Cost
`` extensive prophylatic use in Chinese poultry

H5N1 Influenza may be resistant
Remantadine
Antiviral
`` Ion channel Blocker
`` Blocks Penetration

Low Cost
`` extensive prophylatic use in Chinese poultry
siRNA HSV
Antiviral
`` siRNA
`` Blocks Translation

Topical Application Currently in Clinical Trials
Lysine
Antiviral
`` ammino acid
`` Blocks Translation

Feline Herpes Virus

Arginine anatagonist
`` arginine required for hepes virus replication
`` mixed results in animal trials
Ribavirin
Antiviral
`` Nucleoside/Deoxynucleoside Analogue
`` Blocks Replication

Feline Leukaemia Virus
`` FeLV
Feline Immunodeficiency Virus
`` FIV
Feline Infectious Peritonitis
`` FIP

Although targeted at RNA dependent RNA polymerase
`` has side effects
`` mixed results
`` mutagenic
`` toxicity
Acyclovir (ACV)
Antiviral
`` Nucleoside/Deoxynucleoside Analogue
`` Blocks Replication

Equine Herpes Virus
Elephant Herpes Virus

Not Effective
`` FHV
Iododeoxyuridine (IdUdR)
Antiviral
`` Neucleoside/Deoxynucleoside Analoque
`` Blocks Replication

Expensive
`` requires Frequent Use

Some Benefits
`` FHV Ocular Lesions
Triflurouridine (TFU)
Antiviral
`` Neucleoside/Deoxynucleoside Analoque
`` Blocks Replication

Expensive
`` requires Frequent Use

Some Benefits
`` FHV Ocular Lesions
Azidothymidine (AZT)
Anitviral
`` Polymerase Inhiibitor

FeLV
`` Chronic Gingivitis
`` Stomatitis
FIV
`` Encephalitis

Side Effects
`` Anemia
Foscarnate (Phosphonofromic acid)
Antiviral
`` Polymerase Inhibitor
`` Blocks Replication
Oseltamivir
Antiviral
`` Neuraminidase Inhibitor
`` Blocks Release

Very Expensive

Effective against
`` Influenza
Zanamivir
Antiviral
`` Neuraminidase Inhibitor
`` Blocks Release

Very Expensive

Effective against
`` Influenza
Virbagen Omega
Antiviral
`` Interferon
`` Avian Gamma-Interferon

FeLV
FIV
FIP
Canine Parvovirus
Grey Parrots
Imiquimod
Antiviral
`` Interferon

Equine Sarcoids (Paplillomavirus)

TLR7 agonist
`` stimulates release of
`` `` interferon
`` `` other antiviral cytokines
Chemotherapeutics are always dosed by

Why
Body Surface Area

(BW(g)^0.67 * K) / 10^4
`` K = 10 for dogs

Low Therapeutic Index (TI)
`` tf better to use body surface area bc
`` `` more accurate estimate of animals metatbolic capacity
Larger Animals are at which end of the dose range
Lower
`` lower ratio of SA to BW
4 Chemotherapeutic Friendly Features of Neoplasms
^ metabolic rate

^ Replication Rate

^ Blood Supply
`` via angiogenic factors from tumor

Different Surface Antigens
6 Categories of Chemotherapeutic Agents
Alkylating Agents

Antimetabolites

Alkaloids

Antimicrobials

Platinum Complexes

Others
Name 6 Alkylating Agents in 2 Categories
Nitrogen Mustards
`` Mechlorethamine HCL
`` Cyclophosphamide (Cytoxan)
`` Mephalin
`` Chlorambucil

Nitrosoureas
`` lomustine
`` Carmustine
Name 3 Anitmetabolites in 2 Categories
Folic Acid Analogues
`` Methotrexate

Pyrimidine Analogues
`` Cytarabine
`` Fluorouracil
Name 3 Alkaloids in 2 Categories
Vinca Alkaloids (Periwinkles)
`` Vincristine
`` Vinblastine

Yew Alkaloid
`` Taxol (paclitaxel)
Name 2 Chemotherapeutic Antimicrobials
Doxorubicin

Bleomycin
Name 2 Platinum Complexes
Cisplatin

Carboplatin
Name 5 Chemotherapeutics in the Other Categorie
Estrogens
`` Diethystibestrol
`` Estrodiol

Corticosteroids

Mitotane

Hydoroxyurea

Piroxicam
Major Cytotoxic effects of

Alkylating Agents
Alkylation of DNA
`` crosslinking at Guanines
`` inappropriate pairing of Guanines
`` loss of Guanines

Mutogenic

Very Low TI

Toxic Metabolites
`` excretion
`` secretion
I say radiomimetic

You say

Why
Akylating Agents

Have similar effects on cells as does Radiation
Nitrogen Mustards

What

Name 4

3 Key Effets
Chemotherapeutic Agents

Mechlorethamine HCL

Cyclophosphamide (Cytoxan)

Mephalin

Chlorambucil

Particularly Toxic To
`` Lymphocytes
`` Bone Marrow Cells

Profoundly Immunosuppresive
Mechlorethamine HCL
Chemotherapeutic
`` Alkylating Agent
`` `` Nitrogen Mustard

Severe Blistering Agent

First Antitumor Agent
`` not routinely used bc
`` `` toxicity
Cyclophosphamide
aka Cytoxan

Chemotherapeutic
`` Alkylating Agent
`` `` Nitrogen Mustard

Frequent Use in Vet Med

Activity via Metabolites

Stable
`` Oral Dosing

Toxicity
`` immunosuppression
`` severe necrotizing cystitis
`` `` `` urinary secretion
`` `` `` `` toxic urine
`` `` hematuria
`` `` pain
Mephalin
Chemotherapeutic
`` Alkylating Agent
`` `` Nitrogen Mustard

Main Use
`` Myeloma

Side Effects
`` Anorexia
`` nausea
`` vomiting
`` anemia
`` leukopenia
Chlorambucil
Chemotherapeutic
`` Alkylating Agent
`` `` Nitrogen Mustard

Main Use
`` Lymphocytic Leukemia
`` oral dosing
`` better toleated in dogs and cats than
`` `` Cyclophosphamide
`` `` `` less cystitis

Side Effects
`` immunosuppression via bone marrow
`` cystitis
Lomustine
Chemotherapeutic
`` Alkylating Agent
`` `` Nitrosoureas

Lipid Soluble

Main Use
`` dogs
`` `` Lymphosarcoma
`` `` Brain Tumors

Very Short t1/2
`` liver metabo within minutes

Side Effects
`` Mylelosuppression
`` Leukopenia
Carmustine
Chemotherapeutic
`` Alkylating Agent
`` `` Nitrosoureas

Lipid Soluble

Main Use
`` dogs
`` `` Lymphosarcoma
`` `` Brain Tumors

Very Short t1/2
`` liver metabo within minutes

Side Effects
`` Mylelosuppression
`` Leukopenia
`` nausea
`` vomiting
Methotrexate
Chemotherapeutic
`` Antimetabolite
`` `` Folic Acid Analogue

Inhibits Nucleic Acid Synthesis
`` depletes content of tetrhydrofolates via
`` `` binding dihydrofolate reductase
`` `` `` decreases conversion of doxyuridine monophosphate (dUMP) to
`` `` `` `` thymidine monophosphate (TMP)
`` `` `` `` `` impedes synthesis of
`` `` `` `` `` `` adenine
`` `` `` `` `` `` guanine
`` must be transported into cell
`` resistance via enzyme induction

Reversed via Leucovorin Calcium
`` replaces Methotrexate in cell
`` tf give almost fatal dose
`` `` quickly reverse

Main Use
`` lymphoma
`` osteosarcoma

Side Effects
`` myelosuppression
`` GI toxicity
`` `` hemorrhagic diarrhea
`` `` oral ulcers
`` Nephrotoxicity
`` `` urinary excretion
`` `` fluids
`` `` `` high amount alkaline urine
Cytarabine
aka cytosine arabinoside

Chemotherapeutic
`` Antimetabolite
`` `` Pyrimidine Analogue

Intracellular Activation
`` inhibits DNA synthesis
`` `` incorporated into DNA strand

Main Use
`` Leukemia
`` CNS tumors
`` slow IV infusion

Side Effects
`` bone marrow suppression
`` nausea
`` vomiting
Fluorouracil
Chemotherapeutic
`` Antimetabolic
`` `` Pyrimidine Analogue

Inhibits DNA and RNA synthesis
`` intracellular incorporation

Main Use
`` Dogs Only
`` `` slow IV for GI tumors
`` `` topical for squamous cell carcinomas

Side Effects
`` bone marrow suppression
`` GI irritation
`` `` stomatitis
`` CNS toxicity
`` photosensitization
Vincristine
Chemotherapeutic
`` Alkaloid
`` `` Vinca alkaloid (periwinkle)

Microtuble assembly inhibitor
`` cochicine like action
`` interferes with
`` `` cellular transport
`` `` mitotic spindle formation

Main Uses
`` Dogs - Transmissible Venereal Tumor (TVT)
`` Other tumors
`` `` usually in combination with other drugs
`` IV
`` expensive

Side Effects
`` Cardio Vascular
`` `` thrombocytopenia
`` CNS
`` Excretion
`` `` Bile
`` `` Feces
``
Vinblastine
Chemotherapeutic
`` Alkaloid
`` `` Vinca alkaloid (periwinkle)

Microtuble assembly inhibitor
`` cochicine like action
`` interferes with
`` `` cellular transport
`` `` mitotic spindle formation

Main Uses
`` Mast Cell Tummors
`` IV
`` expensive

Side Effects
`` less than Vincristine
`` Cardio Vascular
`` `` thrombocytopenia
`` CNS
`` Excretion
`` `` Bile
`` `` Feces
Taxol
aka paclitacel

Chemotherapeutic
`` Alkaloids
`` `` Yew Alkaloid

Inhibits Cell Division
`` stabilizes microtubules
`` impedes
`` `` cellular transport
`` `` mitotic spindle formation

Main Uses
`` mammary tumors

Side Effects
`` ??
Doxorubicin
Chemotherapeutic
`` Antimicrobial

Causes DNA fragmentation
`` intercalation into helix
`` `` inhibits Topoisomerase
`` also inhibits DNA dependent RNA systhesis

Main Uses
`` wide variety of tumors
`` `` diffuse
`` `` solid
`` Very Popular

Side Effects
`` Acute
`` `` head shaking
`` `` skin irriation
`` `` `` histamine
`` Short Term
`` `` anorexia
`` `` vomiting
`` `` bone marrow suppression
`` Chronic
`` `` hair loss
`` `` testicular atrophy
`` `` cardiac dysrhythmias
Blenomycin
Chemotherapeutic
`` Anitmicrobial

Main Use
`` little vet use
`` combination agent

Toxicity
`` Pulmonary fibrosis
`` skin effects
`` Low
`` `` bone marrow suppression
`` `` GI toxicity
Cisplatin
Chemotherapeutic
`` Platinum Complex

Interferes with DNA function
`` crosslinks
`` inappropriate pairing
`` deletions

Main Uses
`` Wide Range of Tumors
`` Rapid IV infusion
`` `` long t1/2

Side Effects
`` Nephrotoxicity
`` `` tf diuresis to mitigate
`` nausea
`` vomiting
`` ototoxixity
`` neurotoxicity
`` much more toxic in Cats

NOTE
`` administration through aluminum needle
`` `` INACTIVATES
Carboplatin
Cisplatin Analogue

Chemotherapeutic
`` Platinum Complex

Interferes with DNA function
`` crosslinks
`` inappropriate pairing
`` deletions

Main Uses
`` Osteosarcoma
`` Rapid IV infusion
`` `` long t1/2

Side Effects
`` Bone Marrow Suppression
`` less than Cisplatin for
`` `` Nephrotoxicity
`` `` `` tf diuresis to mitigate
`` `` toxic in Cats
`` `` nausea
`` `` vomiting


NOTE
`` administration through aluminum needle
`` `` INACTIVATES
Dethylstibestrol
Chemotherapeutic
`` Hormone
`` `` Estrogen

Main Use
`` Prostaitic tumors
`` Anal Adenocarcinomas
Estrodiol
Chemotherapeutic
`` Hormone
`` `` Estrogen

Main Use
`` Prostaitic tumors
`` Anal Adenocarcinomas
Prednisone
Chemotherapeutic
`` Hormone
`` `` Corticosteroid

Main Uses
`` Lymphoid tumors
`` palliative treatment
`` `` reduce inflammatory changes
Mitotane
Chemotherapeutic
`` Hormone

Main Uses
`` Adrenal Carcinoma
`` but mainly
`` `` Adrenal Hyperplasia
Hydroxyurea
Chemotherapeutic
`` Antimetabolite

Slows DNA Sysntesis
`` Inhibits ribonucleotide reducase

Side Effects
`` hematological toxicity
`` polycythemia
`` `` dogs
Piroxicam
Chemotherapeutic

Main Uses
`` Dogs
`` `` Transistion Cell Carcinoma
`` `` Squamous Cell carcinoma
`` `` Mammary carcinoma
Emesis

7 Areas of Eminence
Cortex

Vetibular System

Chemoteceptor Trigger Zone (CTZ)
`` 3rd Vent

Viscera

Pharynx

Stomach

Vomition Centre
`` LRF of Medulla
Emesis

Cortex Inputs and Outputs
Pain
Taste
Vision
Olfactory
Excitement

ACh
Histamine
Emesis

Vetibular System Inputs / Outputs
Motion
Histamine

Dopamine
Serotonin (5HT)
Emesis

CTZ Inputs / Outputs
Uremia
Toxins
Drugs
`` many sites of action
Dopamine
Serotonin (5HT)

ACh
Emesis

Visera Inputs / Outputs
Pain
Inflammation
Distension

ACh
`` via Vagus
Emesis

Pharynx Inputs / Outputs
Tactile Stimulation

ACh
`` via CN9
Emesis

Stomach Inputs / Outputs
Irritants
`` mustard

ACh
`` via Vagus
Main Transmitters Associated with Vomition 4
ACh

Hiatamine

Dopamine

Serotonin (5HT)
Most Drugs used to control vomition are
Antagonists to
`` ACh
`` Histamine
`` Dopamine
`` Serotonin (5HT)
Apomorphine
Dopamine Agonist

Handy for inducing Emesis
`` via CTZ
Drug class to mitigate GI induced vomiting
Anticholenergics
Drug class to mitigate Nephro or Hepato toxicity induced vomiting
Serotonin Antagonists
Most Cholenergic Agonists produce ...
Nausea
Emetics 13
Apomorphine

Morphine

Histamine

Cholenergic Agonists
`` Bethanechol
`` Pilocarpine
`` Nicotine
`` Carbachol

AChE Inhibitors
`` Edrophonium
`` Neostigmine
`` Pyridostigmine
`` Echothiphate
`` Organophosphates
`` Carbamates
Antemetics 13 in 5 Groups
Anti-Muscarinics
`` Atropine
`` Glycopyrrolate
`` Iprotropium
`` Propatntheline
`` Tropicamide

Antihistamines
`` Diphenhydramine
`` Chlorpheniramine
`` Tripelennamine
`` Promethanzine
`` Chromoglycates

Dopamine Antagoinists
`` Domperidone
`` Haloperidol
`` `` mainly a neuroleptoanalgesic

Serotonin (5HT) Antagnonists
`` Odansetron

Phenothiazines
Antemetic that effects 3 (which) of Main NTs
Acepromazine
`` anticholenergic
`` antidopaminergic
`` antiserotonergic

Use at low dose
Odansetron

Effect

Indications
Antemetic
via serotonin antagonist

Useful for nausea and vomiting associated with
`` radiation
`` minimal sedation
Gastric Acid Secretion

Stimulators, Inhibitors, Mechansim
Stimulators
`` ACh
`` `` PNS
`` Gastrin
`` `` Endocrine
`` Histamine
`` `` H2 Receptors

Inhibition
`` Prostaglandin (PGE2)
`` `` contitutive via COX1
`` `` inflammatory via COX2

Proton Pumps
`` H+/K+ATPase
Gastric Acid Secretion Inhibition

5 Ways / Drugs
Muscarinic Blockers
`` Atropine

H2 Receptor Antagonists
`` Cimetidine
`` Ranitidine

Proton Pump Inhibitors
`` Omeparzole

PGE2 Analogue
`` Misoprostol

Mechanical
`` Sucralfate
NSAIDs for Gastric Ulcer Pain are a...
BAD IDEA

Inhibit Prostaglandin production tf
`` stimulate HCL production

Irritate Gastric Mucosa

Usually Antithrombitic

tf triple whammy on the gastric mucosa
GI Motility 7 Agents
ACh

Histamine

Serotonin (5HT)

Prostaglandins

NO

Hormones
`` Motilin

Local Peptides
Bethanechol
Cholenergic Agonist
`` muscarinic action

Rarely used for stimulating GI Motility
Increase GI Motility is a common sign of
Organophosphate Toxicity
`` anti AChE activity
Arecoline - claim to fame
Cholinomimetic

Produces sufficiently violent GI contractions such that
`` tape worms are ripped off of their scolecies

Showing up in Herbal Remedies
`` natural cestode decapitation
Metoclopramide
Cholinomimetic
`` tf induces gastric emptying in
`` `` cats
`` `` dogs

Antidopaminergic
`` tf Antiemetic via central action (CTZ)
`` may also act directly on GI muscle

Short Duration of Action
Domperidone
Cholinomimetic
`` tf induces gastric emptying in
`` `` cats
`` `` dogs

Antidopaminergic
`` tf Antiemetic via central action (CTZ)
`` may also act directly on GI muscle

Short Duration of Action
Your Best Cow Dog has just been rolled on by a Heifer ...

Dont laugh it happens...
Dx Traumautic Diaphragmatic Hernia via Radiographs

Then you reach for
`` Metoclopramide
`` must overcome impaired gastric emptying before
`` `` surgery
Opiods and GI Motility

3 Ways of Action

General Effects etc

and of course the "Gradient"
Mimick Edogenenous Opiods produced within GI Wall

Mu Receptors
`` species variations

Modify Gastrin Release

Inhibit ACh Release

Gradient
`` decreasing effect along tract

Generally act to reduce peristlolic action
`` after initial stimulation
`` inhibit secretions
`` `` indirect effect
Diphenoxylate
Opiod Drug used to
`` Reduce GI Motility
Loperamide
Opiod Drug used to
`` Reduce GI Motility
2 Things to watch for after Opiod administration
Respiratory Depressant
`` note at LOW doses may increase respiration via
`` `` reducing pain

Constipation
`` tf not very handy with post surgical ileus
GI Motility Protectants and Absorbents

Mechanism of Action

Name 6
Protect GI Tract from irritants by
`` Coating
`` Absorption

Magnesium Aluminum Trisilicate

Kaolin
`` Diatomaceous Earth

Aluminum Hydroxide

Bismuth Salts
`` ie Subcarbonate

Pectin

Charcoual
`` finely ground
`` `` tf ^ SA
Laxatives 4 Types
Lubricating
`` minearl oil

Bulk
`` absorb water and swell
`` `` distend GI wall
`` `` `` stimulate parastolsis
`` methyl cellulose
`` psyllium

Osmotic
`` retain water withing GI
`` `` distend GI wall
`` `` `` stimulate parastolsis
`` Saline
`` Mg Salts
`` `` mildly irritating
`` Mannitol

Neuromuscular
`` Muscarinic agonists
Cathrtics 2
Irritate Mucosa
`` stimulate parastolsis
`` avoid to avoid compromising mucosa
`` `` bacteremia

Castor Oil

Phenolphthalein
Ruminant Bloat

5 Ways to Blimpdom and handy Tx
Obstructive
`` blockage of Esophagus
`` mainly resolve mechanically
`` Phenothiazines may help relax

Decreased Surface Tension
`` ^ foam > v gas cap
`` silicate compounds restore surface tensions

Overproduction of Microbial Gas
`` diet, pH > ^ distension > motility > ^^^ distension
`` Antizymotics
`` `` formaldehyde or AMs
`` `` `` reduce microflora #s

Histamine
`` ingestion via plants
`` histamine inducing agents
`` REDUCES ruminal movement
`` `` opposite of monogastrics
`` Antihistamines
`` `` Cimetidine
`` `` Ranitidine

Iatrogenic
`` Xylazine
`` AM therapy
`` Abdominal Surgery
IL-2
Occular Squamous Cell Carcinoma in Cattle
Muscle Relaxants

2 Catagories
Centrally Acting

Peripherally Acting
Centrally Acting Muscle Relaxants 3 Categories
Benzodiazapines

Alpha 2 Agonists

Guaifenesin
Benzodiazapine Muscle Relaxants
Centrally Acting

General Sedation
`` good muscle relaxation occurs at
`` `` anesthetic plane close to midbrain suppression

GABA Agonists
Muscle Relaxants Xylazine
aka Rompun

Alpha 2 Agonist

Inhibits transmitter release
`` Adrenergic Terminals
`` Cholenergic Terminals
Guaifenesin
Central Muscle Relaxant

Glycine Mimimetic
`` tf inhibitory at spinal interneurones
`` blocks spinal reflexes

CNS Depression
`` blocks ascending input

Respiratory Effects
`` minimal

Hypotensive
`` tf do not combine with other hypotensive

Hemolytic
`` tf 5 - 10% infusion
`` large volumes
Convulsing Dog

Top 3 Order of Go
IV best or IM

Benzodiazapines
`` reduce convulsions
`` tf reduce stress

Alpha 2 Agonists
`` Xylazine
`` `` CV affects

Pentobarbatone
Strychnine
Competitive Glycine Antagonist

Constant Spinal Reflex
`` >
`` `` Muscle Damage
`` `` `` >
`` `` `` `` > ^ spinal relex response

Death via shock induced by muscle damage via constant tetany

Excruciating Pain
Peripherally Acting Muscle Relaxants

2 Categories
Depolarizing

Competitive
NMJ Function

9 Steps
Depolarization of Motor Neuron

Ca++ influx to Motor Neuron

ACh vesicles released from Motor Neuron

ACh diffuses across cleft to bind Nicotinic Receptor/Channel

(AChE breaks down ACh in Cleft)

Na+ influx into Myocytes

Depolarization of Myocyte Membrane

Ca++ influx into Myocyte from SR via T-Tubule System

Actin/Myosin Cycling
3 Ways to

Stop Muscle Contraction
Stop ACh Release
`` ie Botulium Poisoning

Prevent ACh from Binding Nicotinic Receptor

Non Competitively Inhibit ACh
`` if Nicotinic Receptor remains bound
`` `` muscle contracts once
`` `` `` cant repolarize
`` `` `` `` tf relaxes but will not contract again
Increased Muscle Enervation

results in __________

response to drug
Increased
Muscle Relaxants (most)

Sequence of Effect - 7
Tongue and Tail

Neck and Lower Limbs

Upper Limbs

Pharynx
`` inhibits swallowing reflex
`` `` tf intubate

Abdominal Tone

Thoracic Tone

Diaphragmatic Tone
Succinylcholine
aka Scoline

Depolarizing Muscle Relaxant

Non-Competitive Binding of Nicotinic Receptors
`` NMJ
`` Autonomic Ganglia
`` Muscarinic
`` `` M2 > M1

Non Reversible Depolarization
`` one powerful and painful contraction
`` followed by relaxation
`` wide spead paralysis
`` `` including respiratory
`` `` `` feeling of suffication
`` `` `` `` risk of anoxia

Duration
`` Minutes via breakdown via esterase
`` tf infusion for longterm use

Uses
`` After animal anesthetized
`` Fracture Reduction
Competitive Muscle Relaxants

Name 3

Mechanism of Action
Curare

Atracurium

Vecuronium

Mechanism - Non Depolarizing
`` Phase II Block
`` inhibts binding of ACh
`` `` tf antagonist
`` `` Nicotinic Sites
`` `` `` NMJ
`` `` `` Ganglia
Atracurium
Competitive Muscle Relaxant

Duration
`` 15 - 25 Mins

Side Effect
`` wide distribution
`` `` protein bound
`` ganglion blocking results in
`` `` Hypotension
`` `` `` Histamine Release
`` seizures in dogs
`` `` via breakdown products

breakdown
`` spontaneous hydrolysis
`` `` pH dependent
Vecuronium
Competitive Muscle Relaxant

Duration
`` 15 - 25 Minutes

Side Effects
`` Hypotension
`` `` more potent than Atracurium

Breakdown
`` Liver > Bile

Unstable Solution
`` tf reconstitute before use
Neostigmine
Reverses Competitive NMJ Blockers
`` inhibition of AChE
`` `` tf ^ ACh [] at NMJ
3 Ways to Potentiate Competitive NMJ Blockers
Inhibit or Block Ca++ Release
`` ie local anesthetics
`` ie Ca++ channel blockers

Gas Anesthesia
`` membrane effects impede channel opening

Antimicrobials
`` Tetracylines and Aminoglycosides
`` `` modify Ca++ Channels
`` Lincomycin and Clindamycin
`` `` block Ca++ Channels
I say Train of Four

You say
Method to Evaluate Muscle Relaxants via Stimulation of Muscle

Stimulate muscle with
`` 4 pulses
`` @ 2 Hz

Measure
`` Twitch
`` or tension

Effect is seen from last twitch towards first twitch with
`` increasing dose

Record as Ratio of
`` Last Twitch : First Twitch
`` ie 0.2/1 = 80% reduction

Clinical Effect Requires
`` minimum of 50% reduction
Tranquilizers

Definition
Drugs that Ability to calm
`` hyperactive
`` agitated
individuals without causing
`` confusion
`` drowsiness
`` disorientation

CNS Depressants
`` greater selectivity for sedation
`` little tendancy at high doses for
`` `` mental blurring
`` `` lethargy
`` `` sleep
Tranquilizers and Behaviour Modifiers

4 Categories
Phenothiazine Compounds
`` Neuroleptics
`` `` Promazine
`` `` Acepromazine

Butyrophenone Derivatives
`` Neuroleptics
`` `` Azoperone
`` `` Droperidol

Benzodiazepine Derivatives
`` Anxiolytics
`` `` Diazepam
`` `` Midazolam

Antidepressant Drugs
`` Mood Elevating Agents
`` `` Tricyclic Antidepressants
`` `` `` Imipramine
`` `` `` Doxepin
`` `` SSRI
`` `` `` Fluoxetine
Phenothiazine Derivatives

Structure
Triple Ring

Side Chains at N10 (R1)and C2 (R2) Determines Pharmalogical Activity
`` Promethazine
`` `` R1 = dimethylaminoethyl
`` `` antihistaminic
`` Promazine
`` `` R1 = longer aliphatic
`` Mepazine or Perphenazine
`` `` R1 = heterocyclic
`` `` Tranquilizers
`` Chlorpromazine
`` `` R2 = Chlorine
`` Acepromazine
`` `` R2 = Acetyl Group

Generally Acylation
`` increases Activity and Potency
Phenothiazines - Pharmalogical Properties

5 Systems
Mainly Effect Dopamine Systems

CNS
`` selective sedation
`` muscle relatation
`` `` via depression of Cerebral Gamma Motor System
`` antiemetic
`` `` antidopaminergic > v CTZ

ANS
`` strong Alpha Antiadrenergic (blocker)
`` depresses vasopressor carotid sinus reflex
`` weak anticholinergic
`` poikilothermic effect
`` `` hypothermia via inhibition of
`` `` `` shivering
`` `` `` peripheral vasoconstriction
`` `` esp Chlorpromazine

Cardio Vascular System
`` slight decrease BP
`` slight increase HR

Respriation
`` therapeutic dose
`` `` no effect
`` high dose
`` `` respiratory depression

Miscellaneous
`` Potentiates activity of Anesthetics
`` weak anithistamimic
`` `` NOTE except Trimeprazine
`` `` `` potent antihistaminic
Phenothiazines Absorption
IV
`` Rapid

IM
`` 20 min in advance of anesthesia

SC
`` Readily Absorbed

Oral
`` Readily Absorbed
Phenothiazines Distributions
Well in all Tissues
Phenothiazines Metabolism and Excretion
Liver
`` Hydroxylation and sulfide formation
`` `` 45% glucoronides
`` `` 30% others
`` `` metabolites may have side effects

Good TI
Phenothiazines Side Effects 7
Tachycardia

Sedation

Hypothermia

Atropine Like Effects
`` eye - mydriatic (dilation)
`` bladder - urinary retention
`` GI - inhibited salivation, motility

Hypersensitivity Reactions
`` associated with metabolites
`` `` tf delayed
`` Blood Dyscrasia (pathology)
`` `` bone marrow > immature cells
`` Skin Reactions
`` `` pruritis
`` `` erythemia

Renal Dz
`` exaggerated response
`` less significant

Hepatic Dz
`` impaired liver function
`` most significant
`` via metabolites

Penil Prolapse in Horses
`` Acepromazine
`` dose dependent
`` reversible
Phenothiazines - Contraindications 4
Epinephrine
`` will not be effective
`` phenothiazines block alpha1 receptors

Show Rings, Competitions, Fairs etc
`` illegal, immoral etc

Caution when
`` weak
`` debilitated
`` cardiac dz

Toxicity Potentiated
`` organophosphates
`` `` physostigmine
`` `` dichlorovos
Phenothiazines - Therapeutic Uses 4
Preanesthetic Medication
`` helps calm induction
`` reduces amount of anesthetic
`` prevention of emesis
`` relaxation of skeletal muscle

General Restraint
`` facilitates
`` `` handling
`` `` physical exam
`` `` simple manipulations

Psychoneurotic Conditions
`` Behavioural Problems
`` `` TCA-Imipramine
`` `` Doxepin

Specific Dz
`` ie reduce self mutilation
`` `` via reducing symptoms of pruritis
Phenothiazines

Name 5 Handy for Final Exam
Promazine
`` aka Sparine

Chlorpromazine
`` aka Thorazine

Acepromazine (ACP)
`` aka AtraVet

Prochlorperazine Edisylate
`` Darbazine

Trimeprazine
`` Temaril
Promazine
Phenothiazine

aka Sparine

Sedation
`` 4 - 6 hrs
`` IM or IV

Application
`` safe all species
`` labeled
`` `` dog
`` `` cat
`` `` horse

Old Drug
`` replaced by Acepromazine
Chlorpromazine
Phenothiazine

aka Thorazine

Sedation
`` 8 hrs
`` IM
`` `` preferred
`` Oral

Application
`` Small Animals ONLY
`` lableled
`` `` Dogs
`` `` Cats
`` manic episodes in horses

Side Effects
`` long term use
`` `` Dopamine / Serotonin effects produce unconsious jerky motions
`` `` `` upregulated dopamine receptors

Old Human Drug
Acepromazine
Phenothiazine

aka AtraVet

Sedation
`` 8 hours
`` potentiates anesthetics
`` cheap

Application
`` Safe and Usefull in All Species
`` Labled
`` `` Dogs
`` `` Cats
`` `` Horses
`` `` Cattle
`` Note if large animals become unstable they may
`` `` panic
Prochlorperazine Edisylate
Phenothiazine

aka Darbazine

Antiemetic via Vagal and Histamine Block
`` Emotionally associated GI disturbances

Application
`` Labeled
`` `` Dogs
`` `` Cats

Sedation
`` weak
Trimeprazine
Phenothiazine

aka Temaril

Antihistamine
`` potent
`` useful for skin conditionns in association with
`` `` Predinisolone

Application
`` labeled
`` `` Dogs

Sedation
`` 1 - 2 hrs
Butyrophenones

What are they

Name 3
Dopamine Antagonists
`` Mainly D2
`` tf Behaviour and Emotions
`` tf NOT Antiemetic
`` tf NOT hypothalamic

Azaperone
`` Stresnil

Droperidol
`` Droleptan

Haloperidol
`` Haldol
`` not used vet spp
Butyrophenones - Pharmacology
Resemble Phenothiazines

Potent Tranquillizing Activity
`` Droperidol 400x > Chlorpromazine
`` Azaperone 30 - 50 x Chlorpromazine

Vasodilation
`` < chlorpromazine

Antiemetic
`` <<< chlorpromazine

Potentiates
`` Anesthetics
`` Analgesics
`` `` some mu opiods
`` `` `` ie Fentanyl
Butyrophenones

Name 3 Differences from Phenothiazines
Weak alpha adrenergic blocking

Less Hypothermia

Antagonizes Respiratory Depressant Effects of
`` Narcotics
Azaperone
Butyrophenone

aka Stresnil

Neuroleptic Tranquilizer
`` 3 - 4 hr duration
`` rapid detoxified and eliminated

Application
`` Labled to control aggressiveness in pigs
`` combine with Metomidate
`` `` Neuroleptanalgesic
`` `` C Sections
Droperidol
Butyrophenone

aka Droleptan

Potent Tranquilizer
`` 1 - 2 hr duration
`` was combined with Fentanyl
`` `` Neuroleptanalgesic
Neuroleptanalgesia

What is it

How do you get it
General quiescence, immobilization, greatly reduced response to pain and tactile stimuli
`` A state of
`` `` Sedation and Analgesia
`` `` `` without Loss of Consciousness

Azaperone and Metomidate
`` neureoleptanalgesia in pigs
Benzodiazepines

What Are They

How Do they Work

4 Actions

Name 4
Tranquilizers

GABA Receptor Agonists
`` GABA is a major CNS inhibitor
`` `` tf reduce excitatory inputs
`` mainly Cerebral Cortex
`` `` tf Anxiolytic
`` also
`` `` Sensory Cortex
`` `` Motor Cortex
`` Dose Response
`` `` Low dose
`` `` `` Higher Centres
`` `` High Dose
`` `` `` Motor Centres

Diazepam
`` Valium

Chlordiazepoxide

Midazolam

Zolazepam
`` combined with Titelamine = Telazol

Actions CNS
`` Highly Selective Depressant
`` Muscle Relaxation
`` Anticonvulsant
`` Minimal Effect on
`` `` CV
`` `` Respiration
Which Benzodiazepine are

Approved for Use in Animals
None

But widely used
`` esp Diazepam (Valium)
Benzodiazepines

Pharmokinetics
Readily absorbed after oral administration
`` Poorly Soluble
`` High Potential for Precipitation when mixed
`` `` tf NOT IV
`` `` `` except Midazolam


Extensive Tissue Distribution

Metabolized in Liver
`` Diazepam > Oxazepam (active) metabolite + innactive metabolites

Excretion
`` Renal as Glucuronides

Side Effects
`` low toxic side effects
`` some affects
`` `` hepatic
`` `` renal
Diazepam
Benzodiazepine

aka Valium

Tranquilizer

Anxiolytic

Sedative

Anticonvulsant Effects
`` epilepsy

Anesthesia Pre Med

Ataranesthesia
`` combine with Ketamine
`` traquilizer + anesthesia

Muscle Relaxant

Oil Base IV formulation
Midazolam
Benzodiazepine

aka Versed

Tranquilizer

Total Anesthetic for SA
`` combined with Ketamine
`` `` may still get muscle spasms in response to stimuli

Water Soluble
`` tf IV
Zolazepam
Benzodiazepine

aka Telazol when combined with
`` Tiletamine

Tranquilizer

Total Anesthetic for SA
`` combined with Tiletamine
Why Do we Care about Dopamine
> 1/2 CNS Catecholamine is Dopamine

Large Amounts found in Basal Ganglia
`` esp Caudate Nucleus
What are the two main types of Dopamine receptors
D1 and D2

Display different affinities for
`` Endogenous Dopamine
`` other compounds
Neuroleptic
Modifying Psychotic Behaviour

Drugs which have prominent antagonism of
`` D2 Dopamine Receptors

Antagonism of dopamine mediated synaptic neurotransmission is
`` important action of Neuroleptic Drugs
Molecular Target of

Phenothiazines

Butyrophenones
Block D2 Receptors

Binding affinity strongly correlated with
`` Antipsychotic activity
Molecular Target of

Benzodiazepines
Inhibitory Neurotransmitter GABA Receptors

GABAa Receptor in Brain
`` integral membrane Chloride Channel
`` mediates
`` `` most rapid inhibitory neurotransmission in CNS
`` Benzodiazepines bind chloride channel
`` `` tf potentiate effect of GABA throughout CNS
Name the Neurotransmitters

5 Stimulatory

2 Inhibitory
Stimulatory
`` ACh
`` NE
`` Serotonin
`` Glutamate
`` Dopamine

Inhibatory
`` GABA
`` Glycine
Name 4 Glutamate Receptors
NMDA
`` CNS
`` Glycine subinding site
`` `` required for full activation

AMPA
`` CNS

Kanaite
`` CNS

Metabotropic
`` mainly periphery
Name 2 Drugs that bind the

NMDA Receptor
Ketamine

Tiletamine
Why is it tricky to

Block Glutamate Receptors

or

Inhibit Reuptake of Glutamate

What to do about this
Glutamate is heavily involved in
`` Energy Metabolism

Go after GABA receptors
`` 2 receptors
`` `` tf specific effects
Name the 4 Catecholamines operating in CNS

Indicate Prevalence
Dopamine
`` Main: 40 - 50%
`` D2 Main Receptor

Serotonin (5HT)
`` 30 - 40%
`` mood
`` response to environment

NE
`` 20%
`` alpha 1 = Alertness
`` `` ie propranolal is
`` `` `` calming
`` `` `` blocks emotional reflex tachycardia
`` alpha 2
`` `` sedation
ACh Receptors and the CNS
Low presence

Hypothalamus

Central Cardio Vascular Control
Dopamine Deficits first manifest as ____________

because ______________
Fine Motor Control Deficits

Striated Muscle part of Caudate Nucleus has
`` exclusively Dopamine Receptor

tf Treat Parkinsons via
`` Dopamine Reuptake inhibitor
`` L-Dopa
`` `` Dopamine precursor
Drugs that block NE reuptake or inhibit MAO

Have the same effect on ...
Dopamine
One More time

The 3 Routes of Presynaptic interference with NT action
Inhibit Reuptake
`` slowly builds level
`` `` tf medium effect

Mimic Effect at Receptor
`` Rapid effect

Inhibit Breakdown
`` slower effect
3 Ways to cross the BBB
Be in the lungs or Venus Blood
`` high blood volume to brain
`` all blood passes through lungs

Be Lipophilic
`` indeed everybody is a FAT head

Be Neutral
`` charged particals dont get in
What is a neuromodulator

Name some
Modifies response of neuron to NT

Peptides
`` enkephalins
`` endorphins

Prostaglandins

Leukotrines

Glial Cells produce
`` Cytokine NMs
`` `` NGF
`` `` TNF
General Anesthetics

Generally Proposed Mechanism
Accumulate in Lipid Rich Membranes
`` ie excitable membranes

Operate on Cl- channels
`` normally bound by GABA
`` increase Cl- influx
`` `` tf hyperpolarization
`` `` tf inhibits depolarization
`` tf inhibitory effect
General Anesthetics

Anatomical Progression

Why
Cortex

Motor Centres

Autonomic Systems

Medulla

Distributed relative to blood flow
`` high energy areas (cortex) have highest blood flow
`` medulla is most protected
General Anesthesia

Name the 4 Stages of the

Law of Descending Paralysis

aka CNS Depression
Sedation

Hypnosis

Narcosis

Anesthesia
4 Fondnesses of the Surgen
Freedom from Pain

Good Muscle Relaxation

Stable
`` Respiration
`` Cardia Vascular System

Least Interference
`` GI
`` other body systems
3 Triumphs of the Anesthetists
Smoothness
`` induction
`` recovery

Safety of Patient

Maneuverability
`` ie rapidly adjust plane
Sedative
General CNS Depressant

Relieve anxiety
`` patient awake
`` calm
`` free from nervousness
Hypnotic
General CNS Depressant

induces sleep
`` resembles normal sleep
Narcotic
General CNS Depressant

induce profound sleep
`` usually some depression of
`` `` medullary centres
Anesthetic
General CNS Depressant

Produce loss of
`` consciousness
`` sensation to external stimuli
Ataractics
Specific CNS Depressant

aka Tranquilizers

induce a state of tranquillity
`` Ataraxia
`` `` not disturbed
`` `` calm and quiet
Analgesic
Specific CNS Depressant

Abolish or diminish
`` awareness of pain
`` without loss of consciousness
Anticonvulsant
Specific CNS Depressant

prevent or arrest convulsions
4 Stages of Anesthesia
Voluntary Excitement
`` struggle against losing consciousness

Involuntary Excitement
`` unconscious struggle against unconsciousness
`` `` violent
`` `` unrestrained

Surgical Anesthesia
`` good place to stop

Medullary Paralysis
`` good place to check your malpractice insurance
Inhalation Anesthetics

Absorbtion and Distribution

3 Keys
[] is proportional Pressure which is proportional to Solubility

High Water Solubility
`` promotes [] in blood
`` SLOW
`` `` induction
`` `` recovery

High Lipid Solubility
`` promotes [] in tissues
`` FAST
`` `` induction
`` `` recovery
Name 6 Inhalation Anesthetics

in Order of Increasing Lipid Solubility
Ether

Methoxyflurane

Chloroform

Halothane

Cyclopropane

Nitrous Oxide
Inhalation Anesthetics

Advantages
High Degree of Control via
`` []
`` flow rate
`` rapid gas exchange lung/brain

Recovery usually
`` rapid
`` smooth
Inhalation Anesthetics

Disadvantages
Slower Induction
`` finite time for transfer
`` lung > blood > brain

Long Recovery if
`` > 1 hr surgery
`` `` via accumulation in body
`` `` `` slow release to blood

Toxicity
`` halogenated metabolites toxic
`` Hepatotoxic
`` teratogenic
`` `` long term exposure
Name 8 Preanesthetics
Guaifenesin

Pancuronium

Atropine

Acepromazine

Trimeprazine

Morphine

Hexamethonium
Preanesthetic Muscle Relaxants

3
Guaifenesin

Pancuronium

Succinylcholine

Increase Muscle Relaxation
Preanesthetics

Parasympatholytic
Atropine

Decrease Secretions
`` handy for respiration

Decrease Vagal Tone

Decrease GIT Motility
Preanesthetics

Tranquillizers
Acepromazine

Trimeprazine

Control and Quieten Animal
Preanesthetics

Tranquillizers and Narcotic Analgesics
Acepromazine

Trimeprazine

Morphine

Facillitate
`` induction
`` recovery

Decrease Anesthetic Dose
Preanesthetics

Ganglion Blockers
Hexamethonium

Decrease Hemorrhage
`` operative
`` post op
General Anesthetics

Inhalation Volatile Liquids

Name 6
Ether

Chloroform

Halothane

Methoxyflurane

Enflurane

Isoflurane
General Anesthetics

Gases

Name 4
Nitrous Oxide

Cyclopropane

Ethylene

Xenon
General Anesthetics

Intravenous

Name 6
Barbiturates

Chloral Hydrate

Magnesium Sulphate

Ketamine

Alfaxalone

Propofol
Halothane
General Anesthetic
`` Volatile Liquid
`` inhalation

aka Fluothane

Ethane substituted with
`` 3 F
`` 1 Br
`` 1 Cl
Halothane Actions
CNS Depressant
`` Sedation > Anesthesia
`` `` Induction
`` `` `` 2 - 4%
`` `` Maintenance
`` `` `` 1 - 2%
`` `` may show delerium in recovery

Respiration
`` depressant

Cardiovascular System
`` hypotensive via
`` `` Reduced CO
`` `` `` cardiotoxic
`` `` `` `` decreased contractive force
`` `` decreased peripheral resistance
`` `` `` vasodilation
`` `` Epi sensitization

Thermoregulation
`` hypothermia

Skeletal Muscle
`` weakness

Uterus
`` readily crosses placenta

`` Analgesia
`` `` POOR
Halothane

Advantages 6
Safe

Potent

Maneuverability
`` 30 sec depth change

Nonflammable

Non irritiating

Mixes Well
`` O2
`` N2O

Smooth Recovery
`` short surgeries
Halothane Disadvantages

7
Hypotension
`` decreased inotropy
`` `` dropped ventricular beats

Episensitization
`` risk of ventricular fibrullation

Poor Analgesia

Unpleasant Order

Requires Sophisticated Delivery System

Worker Safety
`` Hepatoxic metabolites
`` `` regular liver function tests
`` Renaltoxic Metabolites
`` `` full time anesthetists
`` high exposure during equine surgery
`` `` large SA of visceral surfaces
Halothane - Contraindications

3
Head Injury
`` edema risk via vasodilation

Concurrent Ca++ channel blockers

Cardiac Dz
`` cardiotoxic
Isoflurane
General Anesthetic
`` volatile liquid
`` inhalation

Ether Based
`` 5 F
`` 1 Cl
`` reduced hepatotoxicity
`` `` mainly excreted unchanged via lungs

Mainly Vet Use
Isoflurane

Pharmalogical Effects
CNS
`` surgical anesthesia
`` less potent than Halothane
`` `` maintenance
`` `` `` 2 - 3%
`` Recovery
`` `` Rapid and Smooth

CVS
`` Hypotensive
`` `` reduced inotropy
`` `` vasodilation
`` little or no Epi-sensitization

Respiratory
`` depression

Thermoregulation
`` hypothermia

Skeletal Muscles
`` good relaxation
Isoflurane

Advantages 7
Smooth
`` induction
`` recovery

Maneuverability
`` good

Less Cardiotoxic than Halothane
`` no heart block effects
`` no epi-sensitization

TI
`` better than halothane

Toxicity
`` lower
`` `` hepato
`` `` renal

Little or No
`` increase in CSF pressure

Muscle Relaxation
`` better than Halothane
Isoflurane

Disadvantages 6
Analgesia
`` < Halothane

Odor
`` > halothane

Cost
`` 2 X Halothane

Respiratory Depressant

Hypotensive

Increased Interaction with
`` Sodalime
`` `` CO2 removal
Sevoflurane
General Anesthetic
`` volatile liquid
`` inhalation

Pleasant smell
`` for humans

Manueverabliity
`` very good
`` `` fastest transfer across alveoli

Induction
`` rapid

Elimination
`` similar to Halothane

Stability
`` not as good as Isoflurane

CVS
`` < depression than
`` `` halothane
`` `` isoflurane
`` `` hypotensive
`` `` minimal decreased chronotropy

Muscle Relaxation
`` potentiates competive relaxants

Minimum Alvelolar Concentration (MAC)
`` 2 - 5%
`` `` prevents gross/purposefull response to pain

Hepatometabolism
`` 1 - 2%
`` `` some toxic metabolites
`` `` `` no Br tf reduced toxicity

Side Effects
`` overall lower than Isoflurane

Cost
`` 4 X Halothane
`` Machine Cost
`` `` 2 X isoflurane
Nitrous Oxide
General Anesthetic (sort of)
`` gas
`` inhalation

CNS
`` Sedation to Light Anesthesia

Induction
`` Smooth at 80%
`` `` but 16% O2 for life
`` `` tf anoxia with induction
`` tf best use as carrier gas with other anesthetic
`` `` provides analgesia
`` `` `` Other Inhalation Anesthetic + N2O:O2 (1:2)

Analgesia
`` Good

CVS
`` mild decrease inotropy

Respiration
`` mild ^ minute volume

Skeletal Muscle Relaxation
`` poor

Toxicity
`` hepato
`` `` none
`` renal
`` `` none
Animal Stops Breathing with Inhalation Anesthetic

What do you do

Why
Shut off machine - DO NOT ADD O2
`` allows
`` `` CO2 level to rise
`` `` O2 level to drop
`` increases hypoxic drive

Respiration normally driven by CO2 level
`` but reduced medullary function
`` > control via pO2
`` `` tf ^ O2 reduces respiratory drive
Basal Anesthesia
state of narcosis
`` produced by pre meds
`` reduces amount of anesthetic required to produce
`` `` surgical anesthesia
Balanced Anesthesia
Combination of Drugs that
`` produces desired anesthetic effect
`` minimizes side effects
Barbiturates
General Anesthetic
`` Intravenous

Bitter White (thios- Yellow)Powders
`` derived from barbituric acid
`` long, branched linear side chains
`` `` rapidly metabolized
`` `` `` unless thio
`` short, cyclic side chains
`` `` slowly metabolized
`` `` `` hepatometabolism

Virtually Insoluble
`` tf Na Salts
`` becomes extremely alkaline in solution
`` `` tf extremely irritating
`` `` `` necrosis if extravascular

GABA Receptor Agonists
`` ^ Cl- influx
`` `` hyperpolarization
`` `` `` inhibition
`` ^ blood supply sensory and motor cortex tf
`` `` unconsciousness
`` `` muscle relaxation

Analgesia
`` poor

Respiratory
`` depressant
`` `` apnea at clinical dose

CVS
`` hypotnesive
`` `` mainly via vasodilation
Barbiturates

Distribution

5 Points
All Body Fluids
`` mild lipid affinity
`` main distribution to brain
`` `` via ^ blood flow

Latent Period of Action
`` time required in order to
`` `` accumulate in brain

Thiobarbiurates
`` Ultrashort Duration
`` `` low affinity for brain tf
`` `` `` rapidly redistributed to body fats
`` slow release and metabolism
`` tf FAT effects
`` `` fat dog duration
`` `` `` 15 - 20 min
`` `` thin dog duration
`` `` `` 30 - 60 min

Protein Binding
`` low

Glucose Potentiation
`` esp thiobarbiturates
Barbiturates

Biotransformation

The long and the short of it
Oxidation of R1 and R2 via
`` Hepatic Enzymes

Fast Oxidation
`` Long Chains
`` Branched Chains
`` Unsaturated
`` Active Groups

Slow Oxidation
`` Short Chains
`` aromatic rings
Barbiturates

Excretion
Mainly Urine

Alkaline Form
`` more rapid excretion
Barbiturates

Duration of Action

5 Determinants
Dose

Normal Kinetics

Metabolism
`` liver function
`` Kidney function

Cumulation
`` Fat depots saturable
`` `` tf prolonged CNS effect
`` `` `` because cant redistribute
`` `` tf multiple doses >
`` `` `` non linear recovery period

Enzyme Induction
Barbiturates

Name 4
Thiopentone

Methohexitone

Pentobarbitone

Phenobarbitone
Thiopentone
Barbiturate General Anesthetic
`` induction agent

Short Action
`` 10 - 15 min
`` reduced with increasing Fat stores

Induction
`` smooth
`` rapid
`` `` 10 - 15 min

Irritant
`` ^ pH (10)
`` tf MUST BE IV

Low Cost
Methohexitone
Barbiturate General Anesthetic
`` casting agent for the brave

Short Duration
`` 10 - 15 min post bolus

Recovery
`` fast
`` violent

Idiosyncratic Fatalities

Whats not to love
Pentobarbitone
Barbiturate General Anesthetic
`` Euthanasia Agent

Terminal Respiratory Depression
`` 4 X Anesthesia Dose
`` often combined with
`` `` K+ Salts

Induction
`` smooth transition to death

Non Irritating
`` tf intra thoracic / peritoneal
`` `` pocket pets
`` `` small birds
Phenobarbitone
Barbiturate Anticonvulsant

Oral Dose
`` acid form

Long Duration of Action

Sedative Side Effects
Ketamine HCL
General Anesthetic
`` induction agent

Phencyclidine Derivative
`` tf Halucinogenic
`` `` at therapeutic doses

Duration
`` 20 - 30 mins surgical anesthesia
`` can be topped up
`` `` ie no saturation kinetics

Absorption
`` IM most common
`` `` non irritating tf
`` `` `` pocket pets
`` `` `` birds
`` `` `` cats
`` IV
`` `` lower dose

Distribution
`` all bady tissues
`` primarly
`` `` adipose
`` `` liver
`` `` lungs
`` `` brain
`` Protein binding

Biotransformation
`` heptatic enzyemes
`` Enzyme induction
`` `` tf ^ dose with repeated use

Excretion
`` Urine
`` t1/2
`` `` cat 67 min
`` `` horse 42 min
`` `` human 4 hours

TI
`` 5 X barbiturates
Ketamine HCL

Mechanisms of Action

8 Wonders of Wackydom
NMDA (Glutamate) Receptor Blockade
`` blocks central pain sensitization

Decreased Neuronal Transport of
`` Serotonin
`` dopamine
`` NE

Amine Reuptake Blocker

Atropine Like
`` ACh blocker

GABA Antagonist
`` decreased GABA binding
`` `` some proconvulsant effects

Increased Cerebral Blood Flow
`` vasodilation

Increased Cerebral O2 Consumption

Increased CSF
`` its enough to make your head explode
Ketamine HCL

Recovery - 2 Words
Prolonged

Stormy
Ketamine HCL

Pharmalogical Action CNS
Dissociative Anesthesia
`` via blocking NMDA (glutamate) receptor
`` aware of surroundings
`` `` but not related to self

Sedation
`` low dose

Muscle Relaxation
`` poor
`` reflexes intact
`` `` GABA antgonist action vs alpha 2 antagonism

Amnesia

Analgesia
`` good
`` NMDA Glutamate Receptor Blocker
`` `` tf blocks central pain sensitization
`` `` including post surgical

Reflex Activity System (RAS)
`` remains intact tf
`` `` Pedal and Pinnal Reflexes
`` `` `` remain INTACT
`` `` reactions to loud noises
Ketamine HCL

Pharmalogical Action CVS
+ve Chronotropic

+ve inotropic

tf
`` ^ CO
`` ^ BP

Myocardium
`` ^ O2 demand
Ketamine HCL

Pharmalogical Action Respiration
Depression of Ventilation
`` minor

Pharyngeal and Laryngeal Reflexes
`` intact tf
`` `` coughing
`` `` swallowing

Salivation
`` ^

Succinylcholine Potentiation
Ketamine HCL

Pharmalogical Action Thermoregulation
Hypothermia
Ketamine HCL

Pharmalogical Action Ocular
Eyes Remain Open

Fixed Stare

Mydriatis
`` dilated pupil

Intraocular Pressure
`` ^
`` tf bulging
`` `` esp rats and ferrets
`` tf glaucoma contraindicated
Ketamine HCL

Pharmalogical Action Skeletal Muscles
Rigidity / Extension Forelimbs

Opisthotonus
`` high dose

Convulsive Seizures
`` occasionally cats
`` therapeutic dose
`` Control with
`` `` Diazepam
Ketamine HCL

Pharmalogical Action Dose
Dose Response Effect
`` tf good utility

Chemical Restraint and Minor Manipulations
`` 22 mg/Kg

Major Surgical Procedures
`` 33 mg/Kg

Induction
`` 11 mg/kg
Ketamine HCL

11 Kool Kombinations
Atropine
`` preanesthetic

Methiothepin
`` anitserotonin agent
`` flaccid paralysis

Halothane
`` potentiates Ketamine effect

Methyoxyflurane, N20
`` good combination

Thiopental
`` synergistic
`` `` not advised
`` abolishes cerebral effects of ketamine

Diazepam / Midazolam
`` good muscle relaxant
`` prolonged recovery
`` sedation
`` `` tf decreased anxiety

Triflupromazine and Opiates
`` very fung shu

Opiates Alone
`` little or no value in cats

Xylazine and Other alpha2 Agonists
`` decreased muscular hypertonicity
`` ^ duration of Analgesia
`` decrease ketamine dose
`` decrease recovery time
`` ketamine counters vasopressor effects

Chloramphenical
`` prolongs sleeping time
`` love those doggie ket dreams
Ketamine HCL

7 Contraindications
Food Animals

Sole Anesthetic Major Surgery

Insufficiency
`` hepatic
`` renal

Head Injury
`` ^ CSF action

Epilepsy / Convulsions

Optho Issues
`` surgery
`` glaucoma
After surgery with Ketamine one should watch for
Hemorrhage
Propofol
General Anesthetic
`` intravascular
`` induction agent

aka Rapinovet

Low CNS effects ala
`` Thiopental

Induction and Recovery
`` smooth and rapid
`` better than Thiopental

Irritation
`` low tf stab away

X-Reactions
`` compatible with wide range of preanesthesia and anesthesia compounds

Muscle Relaxation
`` better than Barbiturates
`` and none of that nasty malignant hyperthermia

Allergic Reactions
`` none

Hepatometabolism
`` tf not distributed in fat
`` `` tf no Fat Effects
Propofol

Whats the Catch
Very Expensive

Cannot Store Open Vial
`` organic solvent / egg white carrier
`` `` tf bacterial banquet

Not Water Soluble
`` tf no mixing with other drugs in syringe

Hypotensive
`` up to 40%
`` tf contraindicated
`` `` hypovolemic
`` `` `` or USE Fluids
Hyperalgesia
Increased peripheral sensistization to pain
`` decremental spread from site of injury
`` `` cytokine diffusion
Allodynia
Pain produced from a Non Noxious stimulus
Central Pain Sensitization
Exposure to Pain increases Pain sensation throughout body

Chronic pain increases sensitivity to acute pain
Neuropathic Pain
Pain NOT associated with a discernable lesion
`` amputated limb pain
`` `` esp traumatic
Pain Pathways 4
Nociception
`` naked nerve endings
`` transmit pain to high centres
`` enter dorsal horn of spinal grey matter

General Somatic Afferents
`` transmit deep or superficial paine
`` bone
`` skin
`` muscle
`` tendons

General Visceral Afferents
`` transmit deep pain from viscera

Spinothalamic Pathway
`` pain stimulus ascends via
`` lateral spinothalamic tracts
`` > medulla > thalamus > internal capsule > cerebral Cortex
`` > perception of pain
`` descending inhibition of pain
Pain Mediation 4 Sites
At Receptor

Transmission

Within CNS

Descending Inhibition
Why Target Central Pain Mediation
CNS has many Pain Regulatory Mechanisms
Opiates
Natural and Semi Synthetic derivatives of Morphine and Opium
Opiods
All natural and Synthetic drugs with
`` morphine like effects
`` ie BIND to Opiod Receptors

May or may not be derivatives of opium
Narcotic
Primarily used to classify
`` controlled substances

No Pharmalogical Context
Endognenous Opiods

Name 3
Enkephalin

Dynorphins

Endorphins
Enkephalins
Pentapeptides

Found in brain and spinal cord areas responsible for
`` mediation of pain

Precursors though to be responsible for
`` perception of pain
`` modulation of behaviour
`` regulation of ANS

2 Types
`` leu-enkephalin
`` met-enkephalin

Action
`` bind specific opiate receptors
`` inhibit release of NT
`` `` esp NT of pain transmitting pathways
Dynorphins
17 aa Peptides

Wide Distribution CNS
`` released from Hypothalamus

Effects related to action of
`` leu-enkephalin

Homeostatic Mechanisms
`` may have role

Analgesia
`` role poorly understood
Endorphins
31 aa Peptide (beta endorphin)

Limited Distribution
`` hypothalamus
`` pituitary
`` `` released from pituitary

Distribution
`` pain relief areas

Action
`` via met-enkephalin at terminal end
`` precursor (POMC) released during flight or fright response
5 NTs of Pain
Stimulus
`` substance P
`` `` most important
`` ACh
`` Serotonin (5HT)
`` NE
`` Dopamine

Descending Inhibition
`` NE
Opiod Receptors

Name 3
mu for morphine

kappa for ketersacine

delta for vas defernes
mu Receptor

important pain location

Actions

Compounds
Supraspinal

Actions
`` euphoria
`` sedation
`` analgesia
`` respiratory depression
`` GI mainly inhibition
`` Addiction

Met-enkephalin

Endorphins
Kappa Receptor

Primary Pain Location

Actions

Compounds
Spinal

Actions
`` analgesia at spinal level
`` sedation - potent
`` miosis - constricted pupil

Dynorphins
Delta Receptor

Primary Pain Location

Actions

Compounds
Periphery
`` vas deferens for sure

Actions
`` poorly understood
`` inhibitory to Smooth Muscle
`` analgesia
`` various physiological effects

Leu Enkephalin
Opiod Receptor Actions

Morphine
mu
`` ++

delta
`` +

Kappa
`` +
Opiod Receptor Actions

Fentanyl
mu
`` +++

delta
`` +

kappa
`` +
Opiod Receptor Actions

Pentazocine
mu
`` -

delta
`` na

kappa
`` ++
Opiod Receptor Actions

Butorphanol
mu
`` -

delta
`` na

kappa
`` ++
Opiod Receptor Actions

Nalbuphine
mu
`` -

delta
`` na

kappa
`` ++
Opiod Receptor Actions

Buprenorphine
mu
`` partial agonist

delta
`` na

kappa
`` -
Opiod Receptor Actions

Naloxone
mu
`` -

delta
`` -

kappa
`` -
Opiod Receptor Actions

Nalorphine
mu
`` -

delta
`` na

kappa
`` +
mu agonists are...
Controlled Drugs
Name 4 Drug Classes derived from Opium
Morphine
`` heroin
`` hydromorphone
`` apomorphine
`` codeine

Codeine

Thebaine
`` etorphine
`` naloxone
`` oxymorphone
`` oxycodone
`` nalbuphine
`` buprenorphine

Papaverine
`` muscle relaxants
`` `` Ca++ channel blockers
Name 6 Synthetic Opiods

What do they all do
Pentazocine

Butorphanol

Meperidine

Diphenoxylate

Methadone

Levorphanol

All bind Opiate Receptors
Opiod Angonists

CNS Effects 9
Analgesia
`` binding of mu and kappa receptors
`` brain and spinal cord

Euphoria or Dysphoria
`` mu and kappa receptors

Sedation
`` typical
`` `` dogs
`` `` primates
`` dose dependent
`` `` low sedation
`` `` high analgesia
`` neuroleptanalgesia via
`` `` potentiation combination with tranquilizers

Excitement
`` typical
`` `` cats
`` `` cattle
`` `` horses
`` high dose convulsions
`` decreased GABA release

Respiratory Depression
`` direct mu receptor effect on medullary respiratory centre

Cough Suppression (anittussive)
`` lower dose than sedation
`` Dextromethorphan
`` `` same potency as codeine
`` `` `` without analgesia or addiction

Emesis
`` release of dopamine at vomition centre

Pupils
`` Miosis
`` `` dogs
`` `` primates
`` Mydriasis
`` `` horses
`` `` cats
`` `` sheep

Heat Regulatory Centre
`` Hypothermia
`` `` dogs
`` Hyperthermia
`` `` cats
`` `` horses
`` `` cattle
Opiod Agonists

GI Effects 3
Increased Intestinal Tone
`` ^segmental contractions
`` decrease propulsive contractions
`` `` tf constipation
`` mu and delta receptors in myenteric plexi and circular SM
`` `` Loperamide (Imodium)
`` `` diphenoxylate (Lomotil)

^ Sphincter Tone

Fluid Transport
`` net ion and water absorption
`` decreases fluid loss
`` `` in secretory diarrhea
Opiod Agonists

CVS 3
Generally safe for CVS

Hypotensive
`` inital PB ^ in dogs

Vasodilation
`` via Histamine release

Bradycardia
`` common
Opiod Agonists

Other Effects 9
Opiod Receptors are Involved with regulation and function of

`` Reproductive Hormone Release

`` Ciracdian Rhythms

`` Control of Pregnancy

`` Cortisol Release

`` Insulin release

`` Circulatory Shock

`` Spinal Cord Ischemia

`` alcohol dependence

Behavioral Abnormalities
Morphine Pharmacokinetics
Absorption
`` rapid and complete
`` `` GI tract
`` `` `` hepatic first pass metabolism limits bioavailability
`` `` sub Cutaneous
`` IM and IV most common routes
`` some show enterohepatic recirculation

Distribution
`` rapid in most tissues
`` slow diffusion across BBB

Metabolism
`` free hydroxyl groups conjugated with glucuronidation
`` excreted in urine
`` active metabolite (morphine-6-sulphate)
`` `` prolong action

Elimination Rates (t1/2)
`` dog 75 min
`` horse 88 min
`` cat 180 min
Opiod Agonists

Clincal Uses 5
Analgesia
`` surgical or trauma

Sedative / Hypnotic
`` calm hard to handle patients

Preanesthetic
`` potentiate other anesthetics

Epidural or Spinal Injection
`` local analgesia in hind limbs via spinal opiod receptors
`` avoid loss of function
`` `` `` sensory
`` `` `` motor
`` `` `` sympathetic

CNS Stimulation
`` illegal in competitions
`` `` ie "Better Racing Through Chemistry"
`` `` `` no kidding this is the motto of the Association of Racing Chemists
Morphine
Morphine Sulphate
`` standard to which other opiods are compared
Oxymorphone
Opiate Agonist
`` 10 - 15 X morphine

Fewer CVS effects

^ Analgesic Potency

^ Addictive Potency

^ Respiratory Depression
Apomorphine
Opiate Agonist

Emetic
`` ^ dopamine release
`` stimulates vomition centre

No Analgesia

May cause respiratory depression
Meperidine
Opiate Agonist

aka Demerol

1/3 potency of morphine

Short Duration
`` 30 min

Fewer effects on GI with repeated use
Fentanyl
Opiate Agonist

aka sublimaze
`` aka Innovar when combined with
`` `` Droperidol

400 X Morphine

99% mu action

Short Acting - 30 min
`` tf constant rate infusion
`` tf dermal patches (Duragesic)
`` `` ^ residue
`` `` ^ dose in patches
`` `` minimum patch size
`` `` `` tf not for small dogs / cats

Low dose
`` microg / kg
Etorphine
Opiate Agonist

aka M-99

800 - 10,000 X Morphine

Receptors
`` mu
`` delta
`` kappa

Reversed with
`` `` Diprenorphine (M-50-50)
`` `` `` but partial agonist for humans
`` enterohepatic circulation
`` `` 30 min oscillations

Exotic Animal Knockdown
`` violent recovery

Withdrawn from Market
Codeine
Opiate Agonist

Action
`` Antitussive
`` Analgesic
`` `` 10% converted to morphine
`` decreased respiratory depression
`` decreased addiction

Dose
`` antitussive dose << analgesic dose

Combined with Acetaminophen
`` Tylenol
Sufentanil
Opiate Agonist
`` structurally similar to Fentanyl

2000 X Morphine

Receptors
`` specific for mu
`` no effect at kappa

Highly Lipophilic

TI
`` very high (25,000)
Alfentanil
Opiate Agonist
`` structurally similar to Fentanyl

2000 X Morphine

Receptors
`` specific for mu
`` no effect at kappa

Highly Lipophilic

TI
`` very high
Carfentanil
Opiate Agonist
`` structurally similar to Fentanyl

Extremely Potent
`` 5000 X Morphine
`` handle only with
`` `` antagonist loaded in syringe

Receptors
`` specific for mu
`` no effect at kappa

Highly Lipophilic

TI
`` very high 10,000

Application
`` wild life capture
`` small volumes
`` easily reversible
Hydromorphone
Opiate Agonist

aka Dilaudid

8 X Morphine
Buprenophrine
Partial Opiate Agonist

< Morphine

Receptors
`` mu
`` delta
`` kappa

No Antagonistic Effects

Slow Receptor Binding
`` tf slow onset
`` `` 15 - 20 min

Potent
`` microg / kg
`` `` tf transdermal

Mild to Moderate pain
Butorphanol
Mixed Opiate Agonist / Antagonist

aka Stadol
aka Torbugesic
aka Torbutrol

5 X Morphine
1/40 X Naloxone

Receptors
`` mu antagonist
`` `` tf cant top up with other opiods
`` `` `` opoid toxicity when Butorphanol clears
`` kappa Agonist
`` `` tf Sedation

Application
`` Strong Sedative
`` Horses
`` `` > Pentazocine or Meperidine
`` Dogs
`` `` antitussive
`` `` "analgesic"
`` `` `` really just sedation
Pentazocine
Mixed Opiate Agonist / Antagonist

1/3 X Morphine

Agonist Actions Predominate
Name 4 Opiate Antagonists
Naloxone

Diprenorphine

Natrexone

Nalorphine
Naloxone
Opiate Antagonist

aka Narcan

No Agonist Action

Receptors
`` mu antagonist
`` `` low doses
`` delta antagonist
`` `` higher doses
`` kappa antagonist
`` `` higher doses

Application
`` Reverse Effects of Opiates
`` Antagonist of Choice
`` High Doses
`` `` reverses
`` `` `` sedation
`` `` `` analgesia

Duration
`` relatively short acting
`` < 1 hr
Diprenophine
Opiate Antagonist

aka M-50-50, Revivon

Reverses Etorphine
Naltrexone
Opiate Antagonist

Longer acting than Naloxone
Nalorphine
Opiate Antagonist / Agonist

aka Nalline

Antagonistic Properties Predominate

Application
`` antagonizes
`` `` morphine
`` `` morphine derivatives
Name 2 Opiate Antagonists used for

Compulsive / Obsessive Behaviour Problems

Mechanism
Naloxone

Naltrexone

Block release of Endogenous Endorphins
`` tf remove reward for compulsive behaviour
`` `` tf break addiction cycle
Adverse Effects of Opiates

Name 8 Signs of Toxicity
Signs of Toxicity
`` extension of pharmalogical effects

Respiratory Depression

Excessive Sedation

Excitement
`` cats
`` cattle
`` horses

Convulsions

Constipation
`` GIT does not develop tolerance

Tolerance and Physical Addiction

Hypotension

Vommiting
`` mainly dogs
`` occasionly cats
`` via dopanergic neurons
Opiods

3 Mechanisms of Tolerance
Decrease in number of Opiate Receptors

Over long term opiates lose ability to decrease release of neurotransmitters

Induction of Hepatic Enzymes
Opiod Tolerance Specificity

7 that do

2 that dont
Tolerance
`` respiratory depression
`` sedation
`` euphoria / dysphoria
`` analgesia
`` nausea
`` vomiting
`` atussion

No Tolerance Develops
`` constipation
`` miosis
Alpha-2 Adrenergic Receptors in Brain and Spinal Column are associated with
Inhibition of Nociceptive Pain Pathways
Neurons that have Post Synaptic

Alpha-2 Adrenergic Receptors

Also have

Which means
Enkephalon/Opiod Receptors

tf Drugs that bind Post Synaptic alpha-2 receptors are
`` synergistic with mu agonists
Name 8 Locations and Effects of

Alpha-2 Adrenergic Receptors
Presynaptic NE Nerve Terminal
`` inhibit NE release

CNS
`` decrease NT release
`` sedation
`` anesthesia
`` analgesia

Postsynaptic Vascular SM
`` vasoconstriction
`` `` via hypothalamic ciruit
`` `` esp if ^^ alpha 1

Platelets
`` Aggregation

Kidney
`` inhibit renin release

Pancreatic Islets
`` decrease insulin release

Adipocytes
`` anti-lipolysis

Heart
`` Bradycardia
Name 4 CNS NTs inhibited by activation of

Presynaptic Alpha-2 Receptors
NE

ACh

Serotonin (5HT)

Dopamine
Alpha-2 Agonists

CNS Effects 3
Generalized CNS Depression

Sedation

Anesthesia

Mechanism - Unknown
`` inhibitory G protein
`` `` decreased adenylate cyclase
`` activation of K+ channel
`` `` stabilization of neuronal membrane
Alpha-2 Agonists

Systemic Effects 2

How
Reduced Sympatetic Outflow from CNS results in

Decreased BP

Bradycardia

via decreased NE
Stimulation of Alpha-2 Receptors in

Spinal Cord results in
Analgesia
Naloxone fails to antagonize

the _________ and _________

effects of _______________

Meaning
Sedative and Analgesic

Effects of

Alpha-2 Agonists

tf action of Alpha-2 agonists is not
`` via Opiate Receptor Binding
Alpha-2 Agonists are particularly Effective in ___________

and

Are at least as effective as opiods in ____________
Rumminants

Horses
Sheep
Mice
Rats
Locus Coeruleus
Area of Brain Associated with
`` Sympathetic Outflow
`` location of Alpha-2 Receptors

Binding Alpha-2 Receptors in this location
`` diminishes sympathetic outflow
`` `` tf reduces pain perception
Alpha-2 Receptors and

The Spinal Cord
Alpha-2 Receptors are Also Located in the Spinal Cord

Epidural Alpha-2 Agonists
`` significantly decrease pain sensation
`` without ataxia of hindlimbs
`` `` unlike epidural local anesthetics
NE and Alpha-2 Receptors are associated with ...
Descending Inhibitory Systems which
`` limit pain perception
What are the 2 Key locations of

Alpha-2 Receptors

Regarding Pain Perception
Locus Coeruleus in Brain
`` Sympathetic Outflow

Spinal Cord
`` descending pain inhibition
Name 4 Alpha-2 Adrenergic Agonists
Xylazine
`` Rompun

Detomidine
`` Dormosedan

Medetomidine

Romifidine
Xylazine
Alpha-2 Andrenergic Agonist

Actions
`` Sedation
`` `` all species
`` `` `` via inhibition of NT release
`` Analgesia
`` `` superior to opiods for visceral
`` `` potent in Cattle (10 x Horses)
`` `` low potency Pigs
`` long duration of action
`` Anesthesia
`` `` not true unconciousness

Receptors
`` alpha-1
`` ^^^^ alpha-2
Xylazine

Drug Synergism
Sedatives and Analgesics

Opiods
`` ie Butorphanol in Horses

Ketamine
`` many species

Barbiturates

Inahlant Anesthetics

Atropines
Xylazine Side Effects

In 4 Systems
CVS
`` initial ^ BP via vasoconstriction
`` overall CV Depression
`` `` via presynaptic receptors
`` `` via decreased sympathetic outflow
`` `` via ^ vagal tone
`` Bradycardia
`` Heart Block
`` Decreased BP
`` Arrhythmogenesis
`` Decrease PO2

GI
`` Emesis
`` `` especially CATs post poisoning
`` `` via CTZ? or alpha-2?
`` decreased motiltiy
`` `` increased transit time
`` `` dereased rumminal motility
`` `` Stomach Bloat in some dogs

Endocrine
`` transient hyperglycemia
`` `` via insulin inhibition
`` `` cats, cattle, dogs, horses
`` Polyuria

Reproductive
`` generally safe in pregnancy
`` `` Except Cows
`` `` `` induces contractions late preg
Detomidine
Alpha-2 Adrenergic Agonist

aka Dormosedan

Lipid Solubility
`` > Xylazine
`` `` tf faster to brain
`` `` tf ^ [] brain

Potency
`` 30 X Xylazine

Duration
`` > Xylazine

Receptor
`` mainly Alpha-2

Application
`` prefered for horses

Contraindications
`` potentiated sulfonamides
`` shock
`` `` traumatic
`` `` endotoxic
Medetomidine
Alpha-2 Adrenergic Agonist

Sedation
`` > Xylazine

Analgesia
`` > Xylazine

Lipid Solubility
`` > Xylazine
`` `` tf faster to brain
`` `` tf ^ [] brain

Potency
`` 20 X Xylazine

Receptor
`` mainly Alpha-2

Application
`` prefered for SA
`` better hemodynamic stabilization than Xylazine
Romifidine
Alpha-2 Adrenergic Agonist

Sedation

Analgesia

New and Potent

Application
`` horses
`` Cattle
`` `` knock down agent
Alpha-2 Adrenergic Receptor Antagonists

Name 4
Atipamazol
`` Antisedan

Yohimbine
`` Yobine

Tolazoline
`` Priscoline

Idazoxan
`` new experimental
What should one remember when reversing

Alpha-2 Sedation

With Alpha-2 Antagonists
The Analgesia will be removed as well
Atipamazol
Alpha-2 Adrenergic Receptor Antagonist

aka Antisedan

Antagonizes
`` alpha-2 receptors
`` Medetomidine
`` all other Alpha-2 Agonists
`` Specific to Alpha-2
Yohimbine
Alpha-2 Adrenergic Antagonist

aka Yobine

Antagonizes
`` alpha-2 receptors
`` xylazine
`` `` many species
`` `` sedative effects may remain
`` `` `` esp in cattle
Tolazoline
Alpha-2 Adrenergic Antagonist

aka Priscoline

Antagonizes
`` alpha-1
`` alpha-2
`` Xylazine
`` `` better than Yohimbine in Cattle
`` `` `` alpha-1 effect?
What 2 Drug Groups avoid

Hind Limb Ataxia with Epidural
Opiods

Alpha-2 Agonist
Name 5 Features of the Finest of Local Anesthetics
Reversibility
`` effects should not be permenant

Rapid Onset of Action

Low Systemic Toxicity

Low Tissue Reactivity
`` non irritating

Reasonable Duration of Action
Name 6 Local Anesthetics
Procaine
`` Ester
`` aka Novacain

Tetracaine
`` ester
`` aka Pontocaine

Lidocaine
`` Amide
`` aka Xylocaine

Mepivacaine
`` amide
`` aka Carbocaine, Isocaine

Bupivacaine
`` Amide
`` aka Marcaine

Properacaine
`` aka Alcaine, Ophthaine
Local Anesthetics

Mechanism of Action
Esters or Amides
`` Weak Bases
`` `` pKa 7.6 - 8.9
`` `` tf lower pKa Drugs have
`` `` `` faster onset of action

Penetrate Cell Membrane
`` bind Na+ Channels
`` `` inhibit depolarization
`` minimal effects on K+ channels
`` ^ lipidsolubility
`` `` ^ potency

Duration
`` ^ protein binding
`` `` > ^ duration of action
`` `` `` via better binding to membrane proteins
`` also vascularity
Local Anesthetics

Metabolism

A tale of 2 types
Esters
`` `` Procaine
`` `` Tetracaine
`` Hydrolyzed by Esterases in
`` `` Blood
`` `` Liver

Amides
`` `` Lidocaine
`` `` mepivacaine
`` `` bupivacaine
`` Liver
`` `` Hepatic Enzymes
`` `` `` N-dealkylation
`` `` `` Hydrolysis
`` mainly excreted as metabolites
Local Anesthetics

Small Nerve Fibres are

___________ than

________________
Small nerve fibres are
`` more sensitive than
`` `` large nerve fibres
Local Anesthetics

Non-Myelinated Nerve Fibres are
_______________ than

______________
Non-Myelinated nerve fibres are
`` more sensitive than
`` `` Myelinated fibres
Name 4 Types of Nerve Fibres most affected by Local Anesthetics
Type A Delta
`` Pain & temp
`` smallish
`` heavy myelination

Type B
`` Preganglionic Autonomic
`` smallish
`` lightly myelinated

Type C Dorsal Root
`` Pain
`` tiny
`` no myelination

Type C Sympathetic
`` Postganglionic
`` tiny
`` non myelinated
Local Anesthetics

12 Unwanted Side Effects
Tissue Necrosis
`` via local ischemia
`` `` cocaine or epienphrine or maybe lidocaine

CNS
`` rare unless IV or massive qty
`` depresses cortical inhibitory pathways
`` `` restlessness
`` `` tremors and twitching
`` `` convulsions
`` `` `` 20mg/kg dogs
`` `` General CNS depression

CVS
`` via cardiac depression
`` `` decreased conduction
`` `` decreased excitability
`` `` decreased inotropy
`` `` vasodilation and hypotension
`` `` `` except cocaine
`` `` caridac arrest

Hypersensitivities
`` clinical doses
`` `` contact dermatitis
`` `` anaphylactic shock
`` rare in vet spp

Methemoglobinemia
`` cats
`` lidocaine, benzocaine, tetracaine
`` `` oxidants
`` `` `` tf Fe2+ > Fe3+
`` even topical dose
`` `` licking
`` `` damaged skin
Procaine
Local Anesthetic
`` ester
`` pkA 8.9

aka Novocain

Potency
`` least

Duration
`` short
`` metabolized to PABA

CNS
`` litte Excitement
`` EXCEPT HORSES
Lidocaine
Local Anesthetic
`` amide
`` `` liver metabo rapid
`` pkA 7.7

aka Xylocaine

Potency
`` 2 - 4 X Procaine

Duration
`` 90 - 200 min

Onset
`` Rapid

Application
`` IM
`` Topical Jelly
`` Topical Aerosol
`` Ventricular Arrhythmias
Mepivacaine
Local Anesthetic
`` amide
`` pkA 7.6

aka Carbocaine

Potency
`` 2 - 4 X Procaine

Duration
`` 120 - 240 min

Onset
`` Rapid
`` `` faster than Lidocaine

Application
`` Horse Nerve Blocks
Bupivacaine
Local Anesthetic
`` amide

`` pkA 8.1

aka Marcaine

Potency
`` 8 X Procaine
`` ^ lipophilicity

Duration
`` 6 - 8 hrs
`` ^ protein binding

Onset
`` intermeidate
`` ^ pKa

Application
`` pain management
Tetracaine
Local Anesthetic
`` ester

aka Pontocaine

Potency
`` 10 X Procaine

Application
`` Systemic Toxicity
`` Topical Use Only
Properacaine
Local Anesthetic

aka Alcaine, Ophthaine

Onset
`` Rapid

Application
`` Low irritation
`` `` tf Topical Ophthalmic
Local Anesthetics

2 Additives
Vasoconstictors
`` prolong action
`` `` phenylephrine
`` `` epinephrine
`` `` `` extends lidcaine 4 - 6 X

Hyaluronidase
`` ^ local infiltration
`` `` tf ^ spread of anesthetic
Name 2 Local Anesthetics that do not

Vasodilate
Cocaine
`` major vasoconstriction
`` septal necrosis

Lidocaine
`` very minor vasoconstriction
Local Anesthetics

4 Clinical Uses
Topical
`` eyes
`` mucous membranes

Local Infiltration
`` Nerve Blocks
`` Field Surgery

Epidural Anesthesia / Analgesia
`` Anesthesia up to 5th thoracic vert in dogs
`` popular but
`` `` watch the ataxia

Retrograde Venous Local Anesthesia
`` Inject into vein
`` apply tourniquiet proximally
`` whip out the wire saw and
`` `` slice off that cow claw
`` complete anesthesia
`` `` so say the LA clinicians
Alcohol Block
Last Bastion of Bovine Barbaritiy
`` usually 99% propanol
`` epidural
`` prolonged or PERMENANT Nerve block
`` `` recurrent vaginal, uterine prolapse
`` `` `` prevents straining

Nerve Inactivation
`` percipitation of nerve cell proteins
`` demyelination
`` ``
Inflammatory Mediators

Name 5 Key Groups
Vasoactive Amides
`` histamine
`` Serotonin (5HT)

Kinins
`` Bradykinin

Leukocyte Products
`` Enzymes
`` IL-1
`` IL-6
`` TNF

Oxygen Derived Free Radicals

Eicosanoids
`` Prostaglandins
`` Leukotrienes
`` PAF
Kinins

5 Inflammatory Actions

Most Important Kinin
Vasodilation

^ Vascular Permeability

SM Contraction

Pain Stimulation and Sensitization

^ Local Prostaglandin Synthesis
`` potentiate prostaglandins

Bradykinin
`` the big one
4 Inflammatory Products of Leukocytes
Enzymes
`` released or spilt
`` hydrolytic
`` collagenase
`` lysosomal

IL-1
`` activates
`` `` lymphocytes
`` `` neutrophils
`` endogenous Pyrogen
`` stimulates acute inflammatory reaction

IL-6
`` induces acute phase protein synthesis
`` stimulates lymphocytes
`` endogenous pyrogen

TNF
`` released from activated
`` `` macrophages
`` `` mononuclear cells
`` induces release of
`` `` IL-1
`` `` other mediators
`` activates
`` `` neutrophils
`` promotes
`` `` aracchidonic acid cascade
Oxygen Derived Free Radicals

What do the do

Name 3
Released from Leukocyte Respiratory Burst

Major Role in Inflammatory Tissue Injury
`` lipid peroxidation
`` `` via unpaired electron in outer shell

Effects
`` ^ capillary permeability
`` Damage
`` `` cell membranes
`` `` nucleic acids
`` ^ prostaglandin synthesis
`` degrade in joints
`` `` collagen
`` `` hyaluronate

H202
`` hydrogen peroxide

*O2-
`` Superoxide Radical

OH*
`` Hydroxyl Radical
`` baddest of the bad
Eicosanoids

Where Do They Come From

3 Major Paths
Phosopholipase A-2 acts on
`` Phospholipids of
`` `` injured or stimlated
`` `` `` cell membranes
`` producing
`` `` Arachidonic Acid
`` `` Lysophospholipid

Arachidonic Acid
`` Cyclo-Oxygenase Pathways (Cox 1, 2, 3)
`` `` Prostaglandins
`` `` Prostacyclin
`` `` Thromboxane
`` Lypoxygenase Pathway
`` `` Leukotrienes

Lysophospholipid
`` Lysophospholipid Pathway
`` `` Platelet Activating Factor (PAF)
8 Effects of Protanoids
Inflammation
`` PGE and PGI
`` `` acute inflammatory response

Pain
`` PGI2 and PGE1
`` `` evoke pain
`` `` hyperalgesia
`` `` synergism with Bradydinin
`` `` `` ^ pain receptor sensitivity

Vasodilation
`` PGE2, PGI2, PGH
`` `` local vasodilation
`` `` augment Histamine, Bradykinin

Vasoconstriction
`` PGF2a and TXA2
`` `` generally vasoconstrictors

Platelet Effects
`` TXA2
`` `` platelet aggregator
`` PGI2
`` `` inhibits platelet aggregation

Smooth Muscle
`` PGD2 and PGF2a
`` `` SM contraction most species
`` PGD2
`` `` bronchoconstriction in anaphylactic reaction - maybe

Fever
`` IL-1 causes anterior hypothalamus to release
`` `` PFE which acts on posterior hypothalamus to
`` `` `` ^ temperature setpoint

Septic Shock
`` TXA2 and PGI2
`` `` thought to mediate some signs in some animals
Platelet Activation Factor

Not just a pretty Face

Name 5 Actions
Platelet Aggregation

Activates
`` leukocytes
`` macrophages

Induces Oxygen derived Radical Production

Vasodilation

^ Vascular Permeability
Reducing Inflammation does what to the Healing Process
Slows
6 Important Actions of Some (but not All)

NSAIDS
Inhibit Cyclo-Oxygenase
`` Main Effect

Inhibit neutrophil activation

Inhibit Neutorophil migration and aggregation

Inhibit Release of Leukocyte Enzymes

Interfere with generation of Oxygen Derived Free Radicals

Inhibit Lipoxygenase
NSAIDS

4 Clinically Important Effects
Anti Inflammatory

Analgesic

Anti Pyretic

Anit Platelet
NSAIDS

2 GI Mechanisms

6 GI Side Effects
Local Irritation of Mucosa
`` oral admin
`` salicylates

Antiprostaglandin
`` ^ acid secretion
`` decrease bicarb secretion
`` decrease mucosal turnover and repair
`` decrease mucous secretion
`` decrease mucosal blood flow
NSAID

3 Renal Side Effects

Mechanism
Acute Renal Insufficiency

Interstitial Nephritis

Papillary Necrosis

Decrease of
`` Prostaglandin Dependent Blood Flow when
`` `` renal perfusion compromised
`` `` `` hypovolemia
`` `` `` ^ ADH
`` `` `` ^ catecholamines
`` `` `` ^ Angiotensin II
Cyclo-Oxygenase

3 Paths
Cox-1
`` constituitive path
`` PGs mainly associated with
`` `` Normal Physiology

Cox-2
`` induceable path
`` produced by traumatized cells
`` PGs mainly associated with
`` `` response to injury
`` `` some renal functions

Cox-3
`` constituative path
`` `` subunit of Cox-1 Path
`` PGs mainly have
`` `` Cardio Vascular effects in Brain
Coxibs are cool talk for
Cox-2 Inhibitors
Name 6 Salicylates
Acetylsalicylic Acid
`` Aspirin

Sodium Salicylate

Choline Salicylate

Diflunisal
`` Dolobid

Bismuth Subsalixylate
`` Pepto Bismol
`` antidiarrhetic
Salicylates
NSAID

Cox-1 and Cox-2 Pathways

Anti-Inflammatory and Analgesic Effects
`` mainly via prostaglandin inhibition

Analgesia
`` most responsive
`` `` musculaoskeleta
`` `` peripheral
`` least responsive
`` `` deep
`` `` visceral

Pharmocokinetics
`` weak acids (pKa 3.5)
`` `` tf rapid gastric absorption
`` hepato glucuronidation metabolism
`` urinary excretion

Duration
`` t1/2 ponies 1 hr
`` t1/2 dogs 9 hr
`` t1/2 cats 38 hrs

Clinical Use
`` analgesia
`` anti inflammatory
`` anti pyretic
`` anti platelet
`` `` takes out cyclooxygenase for life of platelet
`` `` `` tf low required dose
`` `` `` `` tf low side effects
What is it With Cats and NSAIDs
Cats are POOR GLUCURONIDATORS

tf very slow elimination

tf ^ risk of overdose
Salicylate

Adverse Effects 3
GI
`` direct irritation
`` decrease prostaglandins

^ Bleeding
`` platelet inhibition
`` ok unless cogulopathy

Allergic Reaction
`` less common
Name 3 Pyrazolon Derivatives
NSAIDS

Phenylbutazone
`` Butazolidin
`` Butazone

Dipyrone
`` Novolate
`` Novin

Oxyphenbutazone
`` Tandearil
Phenylbutazone
NSAID

aka Butazolidin, Butazone

Effects
`` Analgesic
`` Antinflammatory
`` prostaglandin inhibition
`` `` mainly Cox-1

Pharmokinetics t1/2
`` cattle 40 - 55 hr
`` cat 18 hr
`` dog 6 hr
`` horse 3.5 hr

Side Effects
`` GI
`` `` ulceration
`` Bone Marrow
`` `` suppression
`` `` `` long term use
`` Platelet inhibition

Clincal Use
`` low $
`` Musculoskeleta inflammation LA, SA
Name 3 Indole (Pyrole) Derivatives
NSAIDS

Indomethacin
`` Indocin

Sulindac
`` Clinoril

Zomepirac
`` Zomax
Indomethacin
NSAID
`` Indole Derivative

Mainly Cox-1
`` potent Cyclo-Oxygenase Inhibitor

Side Effects
`` Mainly GI
`` `` ulceration
Name 7 Propionic Acid Derivatives
NSAIDS

Ibuprofen
`` Advil, Motrin, Nuprin

Naproxen
`` Naprosyn, Equiproxen

Flurbiprofen

Fenoprofen

Ketoprofen
`` Anaphen

Carprofen
`` Remadel

Meloxicam
Ibuprofen
NSAID
`` Propionic acid derivative

Action
`` Cox-1
`` some Cox-2
`` Powerful
`` `` Anti-inflammatory
`` `` Analgesic
`` prostaglandin inhibition

Side Effects
`` GI
`` CNS
`` `` proconvulsant
`` Idiosyncratic Toxicity
`` `` esp Dogs
`` `` `` Sudden Liver Failure

Clinical Use
`` not used SA
`` `` Carprofen is alternate
Naproxen
NSAID
`` proprionic acid derivative

Duration t1/2
`` Horse 5 hrs
`` Dogs 45 - 92 hrs

Application
`` musculoskeletal inflammatory conditions
`` `` Horses
`` `` Dogs
Ketoprofen
NSAID
`` propionic acid derivative

aka Anaphen

Action
`` Cox-1
`` Cox-2
`` Prostaglandin Inhibition
`` other mechanisms
`` `` ie activity beyond PG inhibition

Application
`` Licensed
`` `` Dogs
`` `` Horses
`` `` Cattle
`` used in cats
`` `` 72 hr dosing interval

Dosing
`` 3 days on 2 days off for chronic use
`` `` allow mucosal recovery
Carprofen
NSAID
`` propionic acid derivative

aka Rimadil

Action
`` Cox-1
`` Significant Cox-2
`` Prostaglandin Inhibition
`` other mechanisms
`` `` ie activity beyond PG inhibition

Application
`` `` Dogs

Dosing
`` 3 days on 2 days off for chronic use
`` `` allow mucosal recovery
Meloxicam
NSAID
`` propionic acid derivative

Action
`` Cox-1
`` Significant Cox-2
`` Prostaglandin Inhibition
`` other mechanisms
`` `` ie activity beyond PG inhibition

Application
`` `` Dogs
`` `` Cats
`` `` `` Liquid Oral Form

Slow Elimination

Dosing
`` 3 days on 2 days off for chronic use
`` `` allow mucosal recovery
Why Do NSAIDs usually require a loading dose
Usually ^^ protein bound
`` tf need to load up plasma and other proteins
`` `` before distribution to tissues

Note
`` tf do not give orally with food
`` esp Phenylbutazone with horses
How did NSAIDs used to be dosed

What do we know now
Dosed via Plasma []

Now Known that NSAIDs
`` Accumulate via Protein Binding
`` tf ^ [] in damaaged tissues
Flunixin Meglumine
NSAID

aka Banamine

Action
`` Mainly Cox-1
`` Low Cox-2
`` Prostaglandin Inhibition
`` Neutrophil Function Inhibition

Effects
`` Analgesia
`` Anti-inflammatory
`` 4 X potency Phenylbutazone
`` `` esp visceral pain

Application
`` LA
`` `` septic shock
`` `` laminitis
`` `` pneumonia
`` `` `` licensed in calves
`` `` equine colic
`` `` mastitis
`` `` arthritis
`` SA

Side Affects
`` GI
`` `` via prostaglandin inhibition
Acetominophen
NSAID

aka Tylenol

Action
`` mainly Cox-3
`` `` tf CNS effects
`` `` `` tf more effective for head pain
`` Analgesia strong
`` Anti-inflammatory weak
`` Anti- pyretic

Adverse Effects
`` Glucuronidation Hepatometabolism
`` EXTREMELY TOXIC TO CATS
`` `` rapidly depletes glutathione
`` `` `` tf chronic toxicity all species
`` `` `` `` via accumulation of TOXIC METABOLITES
`` `` Liver toxicity
`` `` Renal toxicity
`` `` rbc Heinz Bodies
`` `` methemoglobinemia
Name 2 Coxibs Licensed for Dogs
Furocoxib

Deracoxib
`` Deramax

^$

Action
`` Inhibit Inflammatory Change
`` Cox-2 Specific
`` tf low GI effects
`` tf low renal effects
`` may ^ duodenal ulceration
`` `` via inhibition of healing
Tepoxalin
NSAID

aka Zubrin

Action
`` Cox Inhibition
`` Lox Inhibition
`` `` tf lower Leukotrine pathway effects
`` `` `` compared to Cox inhibitors

Oral for Dogs
`` disolves 2 - 3 secs
Omega 3 Fatty Acids
Anti-Inflammatory


Competes with arachidonic acid for
`` lipoxygenase
`` cycloxygenase
`` tf decreases
`` `` prostaglandins
`` `` leukotreines
DMSO
Anti Inflammatory

aka Dimethyl Sufoxide

Idiopathic via ?
`` scavenge oxygen derived free radicals
`` `` tf reduced injury to ischemic tissue
`` stabilize lysosommal membranes
`` decrease chemotaxis to inflammed tissue
`` `` PMNs
`` `` monocytes

Extreme Penetration of Anything

May reduce
`` Fibrous Adhesions
`` Collagen Formation

Antimicrobial
`` anti fungal
`` anti bacterial
`` anti viral
DMSO Toxicity and Side Effects

6
Unpleasant Odor

Hemolysis
`` IV administration

Ocular
`` alters refractive index of lens

Cholinesterase Inibitor
`` mitigates antiparasitics

Cutaneous Irritation
`` mast cell degranulation
`` exothermic with water

Headache
`` IV administration
Sodium Hyaluronate "HA"
Intra Articular Anti Inflammatory

aka Hylartil, Hylaovet, Synacid, Equron

Normalizes / Replenishes Synovial Fluid
`` Lubricates Soft Tissue
`` `` `` source of pain
`` decreases prostaglandins in inflammed joints
`` may scavenge free radicals

Clinical Use
`` intra articular injection
`` high molecular weights "thought" to be more efficacious
`` exclusively osteoarthritis in horses
`` max effect
`` `` 7 - 10 post administration

Adverse Effects
`` contains 2 - 3 % protein
`` `` tf may initially induce joint inflammation
Polysufated Glycosaminoglycan GAG

5 Beneifits
Intra-Articular Anti Inflammatory

aka Adequan, Flexequin

Promotes Repair of damaged Cartilage
`` stimulates synthesis
`` `` collagen
`` `` proteoglycan
`` `` hyaluronic acid

Inhibits Lysosomal Degradation of Articular Cartilage
`` inhibits action of
`` `` proteolytic
`` `` lysosomal
`` enzymes within joint

Inhibits local PG synthesis

Decreases Cartilage degeneration in arthritic joints

Promotes Synthesis of Sodium Hyaluraonate

Clinical
`` IM
`` Intra Articular
`` Oral???
`` Treatment and Prevention of Arthritis
`` `` Horses
`` Acute and Chronic Arthritis
`` `` Dogs
Endogenous Steroids

Name the 3 Adrenal Zones and Products
Zona Glomerulosa
`` primarily mineralocorticoids
`` `` ie Aldosterone

Zona Fasciculata
`` Glucocorticosteroids
`` `` cortisol
`` `` `` hydrocortisone
`` `` `` corticosterone

Zona Reticularis
`` Glucocorticosteroids
`` Androgenic Steroids
Regulation of Steroid Secretion
Adenohypophysis releases
`` Adrenocorticotropic Hormone (ACTH)
`` in response to Corticotrophin Releasing Factor (CRF)

CRF Released by Hypothalamus in response to
`` Stress
`` Diurnal rhythm
`` Epinephrine
`` Hypoglycemia

CRF also Stimulated by
`` Cytokines
`` `` IL-1, IL-6

Release of CRF and ACTH is inhibited by
`` endogenous glucocorticoids
`` `` -ve feedback control
`` exogenous corticosteroids
`` tf
`` `` hypothalamic-pituitary-adrenal axis (HPA-axis)
What is it with Synthetic Glucocorticoids
Corticoids have wide ranging physiological effects

Synthetic Glucocorticoids have more potent hormonal effects than endogenous corticosteroids
`` esp via feedback
Glucocorticoids

Cellular Mechanism of Action
Transported by Serum Proteins to Site of Action

Lipid Soluble tf Diffuse through Cell Membrane

Binde Intracellular Steroid Receptors

Stimulate or Inhibit Transcription of specific
`` m-RNA
`` t-RNA

Produced or Inhibited Protein generate pharmacologic effects
`` ie reduction of Cox Enzymes
`` `` `` Anti-inflammation
`` `` `` analgesia
`` `` via reduction of PGs
Glucocorticoids

Pharmacologic Effects

List 10 Areas
CHO Metabolism

Protein Metabolism

Lipid Metabolsim

Electrolytes

Water Balance

Calcium Metabolism

CNS

WBC

Anti Inflammation

Immune Response
Glucocorticoids

Pharmacologic Effects

CHO Metabo
Net Effect
`` Elevation of Blood Glucose

^ Gluconeogenesis
`` via ^ activity of gluconeogenic enzymes

Substrates for Gluconeogenesis via
`` protein catabolsim
`` lipolysis

Also
`` anti insulin
`` decrease peripheral glucose utilization
`` ^ glycogen deposition in liver
Glucocorticoids

Pharmacologic Effects

Protein Metabolism
Net Effect
`` Protein Catabolism

Muscle Wasting

Decreased Muscle Mass

Anati-anabolic
`` delayed growth
`` decreased healing
Glucocorticoids

Pharmacologic Effects

Lipid Metabolism 3
^ Lipolysis of Peripheral Fat stores

Lipotytic Effects of Catecholamine
`` permissive action of glucocorticoids

Redistribution of Body Fat
`` fat moved to abdomen
Glucocorticoids

Pharmacologic Effects

Electrolytes
Glucocorticoids may have some Mineralocorticoid Effects
`` ^ Na absorption
`` ^ K secretion

Minimal Effect
`` prednisolone
`` dexamethasone

Maximum Effect
`` Deoxycorticosterone acetate (DOCA)
`` fludrocortisone
`` `` aka Florinef
Glucocorticoids

Pharmacologic Effects

Water Balance
Polyuria / Polydipsea
`` dogs > cats

ADH antagonism
`` inhibition of ADH release from neurohypophysis
`` `` tf reduced water reabsorption at DT/CD
`` increased Glomeruler Filtration (GFR)
Glucocorticoids

Pharmacologic Effects

Calcium Metabolism
Net Effect
`` loss of Ca

^ Urinary Secretion

Decreased Intestinal Absorption

Ultimately Osteoporosis
Glucocorticoids

Pharmacologic Effects

CNS
Euphoria - Elevation of Mood

Polyphagia

Maintenance of Blood Glucose for CNS
`` critical hypoglycemia
`` `` stimulate gluconeogenesis
What 1 Area of action of

Glucocorticoids

Is Largely Responsible for

Anti Inflammatory

Immunosuppression
Profound effects on WBC
Glucocorticoids

Pharmacologic Effects

Lymphocytes 4
Lymphopenia
`` via margination
`` T-cells > B-cells

Decreased Lymphocyte Responses
`` suppressed response to mitogens (ie no miosis)
`` impaired cytotoxicity
`` decreased lymphocyte proliferation
`` decreased IL-2

B-Cells and AB Synthesis
`` impairment of macrophages and T-helper recognition
`` high doses result in decreased
`` `` IgG
`` `` IgA
`` `` IgM

Lympholysis
`` rats and mice
Glucocorticoids

Pharmacologic Effects

Neutrophils
Neutrophilia via
`` suppressed membrane-endothelial interaction
`` `` tf less egresss
`` decreased response to chemotactic factors
`` ^ release from
`` `` bone marrow
`` `` marginal pool

Various Complex Effects on Neutrophil
`` phagocytosis
`` bacterial killing
`` species variation
`` bact
Glucocorticoids

Pharmacologic Effects

Monocytes and Macrophages
Dose Related Effects

Low Dose
`` anti-inflammatory

High Dose
`` immunosuppressive

Via Decreased
`` chemotactic response
`` antigen processing
`` Cytokine Synthesis
`` `` TNF
`` `` IL-1
`` phagocytic ability

dec
Glucocorticoids

Pharmacologic Effects

Anit Inflammatory Actions
Dose Related

Cell Membrane Stabilization

Improved Capillary Integrity

Decreased accumulation of leukocytes in inflamed tissue

Decreased activity of reticulodnothelial Cells
`` monocytes
`` macrophages
`` reticulum cells

^ sysnthesis of lipomodulin
Glucocorticoids

Pharmacologic Effects

Immune Response
High Doses

via
`` impairment of
`` `` lymphocytes
`` `` macrophages

Reduce inflammatory respones to immune reactions
`` > than anti inflammatory dose
Name 10 Glucocorticoids
Hydrocortisone
`` cortisol

Prednisolone

Prednisone

Methyprednisolone

Triamcinolone

Flumethasone

Dexamethasone

Betamethasone

Fludrocortisone

Desoxycortisone
What makes the difference between Corticosteroids

3 Effects

via 5 Substitutions
Duration of action

Potency

Mineralocorticoid Activity

// bond C1-2
`` ^ anti inflammatory activity
`` ^ glucocorticoid activity
`` decreased mneralocorticoid activity

alpha Hydroxy C-17
`` full anti inflammatory properties

Fluoride C-9
`` enhace all glucocorticoid effects

Methylation C-16
`` eliminates Na retaining effects

Methylation C-6
``` ^ anti inflammatory effects
What are the 2 most common

Corticosteroids in Vet Med
Prednisolone

Dexamethasone
Glucocorticoid Formulations - 4
Phosphate and Succinate Esters
`` water soluble
`` rapid onset
`` IV for
`` `` ^[]
`` `` rapid effect

Acetate and Acetonide Esters
`` poorly soluble
`` IM
`` SC
`` Intrarticualar
`` slow onset
`` `` days - weeks
`` long duration

Solutions
`` dissolved in
`` `` propylene glycol
`` `` alcohol

Glucocorticoid Base
`` oral tablets
Glucocorticoid Absorption
Protein Binding
`` 75% bound to plasma Corticosteroid Binding Glbulins CBG
`` 10 - 15% bound to albumin
`` 10 - 15% free fraction

Loss of Protein ^ Free Fraction
`` tf ^ pharmacologic activity
Glucocorticoid Metabolism
Hepatometabolism
`` Reduction of Ketone Groups
`` Conjugation
`` `` glucuronic acid
`` `` sulfuric acid

Inactive Steroids
`` administered in inactive form
`` Cortisone > corticosterone
`` Prednisone > prednisolone
Glucocorticoid Elimination
t1/2 most species
`` 1 - 3 hrs

Synthetic Corticosteroids
`` duration of Effects Persisit much longer
`` `` ie Dexamethasone
Indiscriminate use of Glucocorticoids may result in
Disaster
Corticosteroid Therapy

6 Therapeutic Considerations
Cost

Route of administration

Onset and Duration of Effects

Anti Inflammatory Potency

Short Term vs Long Term
Corticosteroid Therapy

7 Contraindications
Concurrent NSAID

Pre Existing Protein Catabolism

Growing Animal

Bacterial and Fungal Infections

Pregnancy

Corneal Ulcer
`` ophthalmic use

Wound Healing

Diabete Mellitus
Corticosteroid Therapy

Adverse Effects

23 in 7 Systems
CNS
`` Polyphagia
`` Euphoria

Musculoskeletal
`` Osteoporosis
`` Myopathy
`` Fibroblast Inhibition
`` Decreased Intestinal Ca absorption

GI
`` ulceration
`` Pancreatitis
`` Colonic perforation

Fluid Balance
`` Sodium and Fluid Retention
`` Edema
`` PU / PD

Metabolic
`` Hyperlipidemia
`` Lipolysis
`` Protein Catabolism
`` Fatty Liver
`` Steroid Hepatopathy

Endocrine
`` Anit Insulin
`` HPA-axis suppression
`` Decreased Thyroid Synthesis
`` ^ Parathyroid Hormone Synthesis

Host Defenses
`` Decreased Bacterial Killing
`` ^ Risk of Septicemia
`` Recurerent Septic Cystitis
Corticosteroid Short Term Therapy
< 2 Weeks

Dose for Effect

Can be discontinued abruptly
`` minimal adverse effects
Corticosteroid Long Term Therapy
Titrate to Lowest Dose

Every Other Day (EOD) Therapy if possible
`` minimizes HPA axis effects if
`` `` < 48 hr duration of action

Progressive Weaning
`` over period of weeks
`` allow recovery from adrenal atrophy
Corticosteroids

10 Clinical Applications
Hypodrenocorticism
`` replacement therapy

Skin Dz
`` immune mediated
`` allergy
`` minimize self mutilation

Intestinal Dz
`` inflammatory Bowel Dz

Ophthalmologic Dz
`` conjuctivits

Orthopedics
`` osteoarthritis
`` `` systmeic
`` `` intra articular

Reporduction
`` induce parturition
`` `` dexamethasone

Chemotherapy
`` lymphosarcoma
`` mast cell tumor

Neurologic Dz
`` spinal cord compression and trauma
`` Cerebral Trauma / Edema

Shock
`` Endotoxic Shock
`` Hypovolemic Shock

Autoimmune Dz
`` autoimmune hemolytic anemia
`` systemic lupus
`` pemphigus
`` asthma
`` `` decrease allergic response of respiratory system
`` `` long term desensitization to allergens
Name 7 Benzodiazepines used in Behaviour
Diazepam
`` aka Valium
`` Idiosyncratic Hepatic Necrosis in Cats

Alprazolam
`` aka Xanax
`` Agression in Dogs
`` lethargy and incoordination

Chlordiazepoxide
`` aka Librium
`` appetite Stimulant
`` Anxiolytic Cats

Flurazepam
`` aka Dalmane
`` appetite Stimulant
`` Anxiolytic
`` `` Cats
`` `` Dogs

Clorazepate
`` aka Tranxene
`` Phobias ie Thunderstorms
`` Compulsion

Oxazepam
`` aka Serax
`` Appetite Stimulant
`` `` Cats
`` `` Dogs

Triazolam
`` aka Hacion
`` Aggression Cats
Benzodiazepines and Behavior

Mechanisms

2 Adverse Effects
GABA Agonists
`` anxiolytic
`` less reation to surroundings

Interfere with learning and Short Term Memory
`` tf not ideal for behaviour modification
`` Animals become dependent
`` `` tf behaviour resumes after withdrawal

Most Cats become
`` sleepy and uncoordinated at onset
`` excessively friendly
Buspirone
Non-Benzodiazepam Anxiolytic

aka Buspar

Action
`` partial Serotonin Agonist
`` Dopamine Receptor Antagonist
`` may render animal
`` `` less concerned about perceived threats

Application
`` Cats
`` Inappropriate Elimination
`` territorial Marking
`` Can Frequently Break Patterns
`` `` 2 Week Trial
`` `` `` if working continue 2 months

Adverse Effects
`` does not cause incoordination
`` `` ala benzodiazepams
`` a few cats may become excessively sleepy
`` some cats mahy show increased aggression
Carbamazepine
Anxiolytic

aka Tegretol

Action
`` mild anticholenergic
`` `` blocks Muscarinic Synapse
`` `` `` ACh and Adrenergic Pathways
`` weakly blocks
`` `` reuptake and stimulation induced release of NE
`` mild anitconvulsant
`` Mild Sedation
`` `` without muscle relaxation

Appplication
`` Fear Induced Aggression in Cats

Adverse Effects
`` Cholenergic side effects hardly make it worth the trouble
`` `` Dyspnea
`` `` Ataxia
`` `` Clonic/tonic convulsion
`` `` vomiting
`` `` defecation
`` `` CONSTIPATION
Name 3 Ticyclic Antidepressants

And Their uses
Imipramine
`` Tofranil
`` Aggression
`` `` Dogs
`` Narcolepsy
`` `` Dogs
`` `` Horses

Amitriptyline
`` Elavil
`` Inappropriate Urination
`` `` Cats
`` Some Anti-inflammatory
`` `` handy for FLUTD

Clomipramine
`` Anafranil, Clomicalm
`` Stereotypies
`` Seperation Anxiety
`` `` Dogs
`` `` `` Clomicalm approved
Tricyclic Antidepressants

Mechanism

Action

Adverse Effects
Action
`` Inhibit
`` `` serotoinin reuptake
`` `` NE reuptake
`` Blocks
`` `` muscarinic receptors
`` `` histaminic receptors
`` `` adrenergic receptors


Anxiolyitic
`` antidepressants
`` aggression
`` inappropriate elimination
`` stereotypies
`` narcolepsy
`` incontinence

Relapse Common on Discontinuation

Difficult to Find Minimum Dose
`` extensively metabolized
`` long elimination t1/2
`` reuptake inhibitors
`` `` tf slow onset of action

Adverse Effects
`` mild sedation
`` anticholenergic
`` `` dry mouth
`` `` constipation
`` `` diarrhea
`` decreased seizure threshold
`` interference with Thyroid meds
`` No Antidote for Overdose
Fluoxetine
Selective Serotonin Reuptake Inhibitor (SSRI)

aka Prozac

Antidepressant
`` calms behaviour

Mechanism
`` Inhibits Serotonin Reuptake
`` Upregulates GABA receptors
`` Increased Serotonin Activity results in
`` `` Decreased Aggresion

Adverse Effects
`` paradoxical ^ stereotypical behaviour
`` hepatotoxicity cats
`` `` via extensive hepatic metabolism
`` Anorexia
Name 6 Phenothiazines

Used in Behaviour
Acepromazine

Chlorpromazine
`` Thorazine

Fluphenazine
`` Prolixen

Thioridazine
`` Mellaril

Perphanazine
`` Tiavil
Phenothiazines

Behaviour

Mechanism

Action

Adverse Effects
Dopamine Blockade
`` esp Limbic System

Action
`` Antipsychotic
`` calming

Adverse
`` Hypotension
`` extrapyramidal signs in Horses
`` muscle rigidity
`` spasms
`` restlessness
`` lower seizure threshold
Acepromazine Behaviour
Phenothiazine Anitpsychotic

General
`` Tranquillizer
`` Aniemetic
`` Best drug for Thunderstorms

Not useful in Show Animals
`` Prolapse of Nictitating Membrane
`` `` Dogs
`` `` Horses
`` Penile Prolapse
`` `` Horses

^ Safety

Not for Long Term Use
Chlorpromazine Behaviour
Phenothiazine Anitpsychotic

aka Thorazine

Show Cattle Tranquilization

Also SA

Never Horses
`` causes excitement

Adverse
`` decreased ACTH and Gonadotropin
`` `` interferes with embryo transfer
`` 48 hr Hang over period
Fluphenazine Behaviour
Phenothiazine Anitpsychotic

aka Prolixen, "Liquid Lunge"

Illegal and Unethical Use in Race and Show Horses

May cause SEVERE Extrapyramidal signs
`` 12 hrs or more after administration
`` `` huge liability issues - horse unexpectedly goes beserk
`` `` `` Dr Dowling WILL NOT defend you...
`` Diphenydramine is antidotal
Thioridazine Behavior
Phenothiazine Anitpsychotic

aka Mellaril

Dogs
`` stereotypies
`` aggression
Perphenazine Behaviour
Phenothiazine Anitpsychotic

aka Tiavil

Anxiety
`` dogs
`` cats
Selegiline
aka Anipryl

Geriatric Animals
`` ^ Memory
`` ^ Alertness
`` ^ Interest

Mechanism
`` Irreversibly Inhibits MAO
`` `` mainly MAO-A
`` `` tf ^
`` `` `` Dopaminergic Activity
`` `` also ^ Adrenergic Activity
`` `` also ^ Serotonin activity
Methyphenidate and Dextroamphetamine are
aka Ritalin and Dexadrine

are CNS stimulants

Not available for Vet use
Lithium
aka Lithane

Generally Depressive
`` alters Na transport in nerve and muscle cells
`` `` internal catabolism of catecholamines

Dominance Aggression in Dogs

May have mixed results
`` suppresses both
`` `` excitation
`` `` depression
Beta Blockers Behaviour
Anxiolytic
`` incontinence
`` aggression

Block Peripheral Adrenergic Receptors
`` bronchoconstriction
`` decreased CO
`` bradycardia
Name 2 Beta Blockers use for Behaviour
Propranolol
`` Propranolol
`` Anxiolytic
`` `` Dogs
`` `` Cats

Pindolol
`` Visken
`` Anxiolytic
`` `` Dogs
`` `` Cats
Naltrexone Behaviour
Opiod Antagonist

aka Trexan

Prevents Release of
`` beta endorphins
`` no agonist action tf no
`` `` dependence
`` `` tolerance

Application
`` abatement of stereotypies
`` acral lick dermatitis dogs
`` relapse on discontinuation
Naloxone Behavior
Opiate Antagonist

Short Acting via IV

Main use is diagnostic for possible abatement of Sterotypies
`` ie cribbing horses
`` Dx then switch to Naltrexone
Name 8 Euthanasia Agents
Halothane

CO2

Barbiturates
`` Pentabarbitol

T-61

Chloral Hydrate

Trcaine Methane Sufonate
`` TMS, MS 222

Benzocaine Hydrochloride

High Velocity Trauma
`` Captive Bolt
`` Gun Shot
Halothane - Euthanasia

Why

Advantages

Disadvantages

What Should Be Done First
Halothane is least aversive of inhalation anesthetics

Advantages
`` easily acheive high vapour levels in closed vessels
`` fast action
`` relatively non irritating

Disadvantages
`` human health risk
`` `` tf use only in situation where humans are not exposed to vapours

Sedate First
`` avoid loss of consciousness struggle
CO2

Advantages

Disadvantages

Contraindications

Wefare
Euthanasia Agent

>70% = Loss of Consciousness
`` < 1 Min

Advantages
`` inexpensive and readily available
`` relatively rapid onset of unconsciousness
`` minimal risk if human exposure

Disadvantages
`` difficult to ensure optimum [] in chamber
`` irritating to inhale
`` stings mucous membranes
`` aversion in rodents
`` time to unconsciousness > inhalation anesthetics
`` abnormal death responses
`` `` urination
`` `` defecation
`` `` vomiting

Contraindicated for animals with ^ CO2 tolerance
`` neonate mammals
`` amphibians
`` reptiles
`` any animal with prolonged breath holding ability

Welfare
`` difficult to determine optimum [] for rapid loss of consciousness with minimum stress
`` difficulty avoiding reflex respiratory responses to anoxia
`` minimizing chamber loading stress
Pentabarbitol - Euthanasia

Advantages

Disadvantages
Deemed Excellent Euthanasia Agent
`` High IV Dose
`` Depresses CNS

Advantages
`` rapid loss of consciousness
`` smooth induction
`` cost effective

Disadvantages
`` controlled drug for Vets only
`` IV injections may be difficult
`` `` use catheter
`` `` may not be possible in
`` `` `` pocket pets etc
`` `` `` `` intraperitoneal injection may be acceptable
`` Drugs Persist in Carcass
`` `` tf scavanger risk
`` `` `` limited disposal options
T-61

Advantages

Disadvantages
Euthanasia Agent

Composed of 3 Drugs
`` Local Anesthetic
`` Stong Hypnotic
`` Paralytic

IV adminstration only
`` specific
`` `` dose
`` `` rate of administration

Advantages
`` non controlled
`` `` tf wider availability

Disadvantages
`` May become paralyzed before loss of consciousness
`` must be administered per instructions
`` `` slow IV
`` Dogs may upon injection
`` `` vocalize
`` `` experience muscle contractions

Has been used successfully in Horses

Second choice to barbiturates
Chloral Hydrae
Sedative that may be used for Euthanasia

Slow Action
`` Depresses CNS
`` hypoxia via suppression of respiratory centres

Marginally Acceptable in some species
`` IV administration
Tricaine Methan Sulfonate
Anesthetic Agent that can be used for
`` Euthanasia of
`` `` Amphibians
`` `` Fish

Immerse animal in solution until dead
Benzocaine Hydrochloride
Alternative Euthanasia Agent for
`` `` Amphibians
`` `` Fish

Immerse animal in solution until dead
List 9 Unacceptable Euthanasia Agents or Methods
Strychnine

Nicotine

Magnesium Sulphate

Potassium Chloride
`` unless unconscious

Any Paralytic

Other Toxic Chemicals

Decapitation
`` remember the French Physiologist

Esanguination
`` unless unconscious

Drowning
`` long period before CO2 Narcosis
`` diving reflex in neonates
Intracardiac Injection
Euthanasia Technique
`` Technically Difficult

Must Anesthesize First
`` otherwise severe pain response

Will be instant Effect if in heart
Pocket Pet Euthanasia
IV Difficult or Impossible

Halthane Gas Best
`` least irritating
`` soak gauze
`` place in jar
`` place animal in jar
`` seal jar

Ensure Animal is Dead before handing to child for burial
Birds - Euthansia

6 Ways
Halothane soaked Gauze and Jar Best
`` will flap when losing balance
`` tf Sedate and wrap first

If Larger
`` IV in Foramen Magnum
`` Difficult
`` `` must fully flex head

Anesthetize and Restrict Chest Cavity
`` no residual capacity
`` `` tf quick

Cervical Dislocation
`` requires skill
`` violent response
`` remember decapitated birds can still vocalize

T-61 - Very Effective

Shooting
`` very difficut
`` `` extremely small brains
Reptiles - Euthanasia

What is the biggest issue
Pentabarbatol Best
`` breath holders
`` `` tf cant use inhalation anesthetics
`` slow metabolism
`` `` tf hard to overdose
`` IV Preferred
`` `` may be difficult to find vein
`` other wise Sedate
`` `` intracardiac

Very Difficult to verify Death
`` Eye Loses Fluid
`` Leave out for one day
`` `` freeze 4 - 5 days
`` `` `` then thaw
Wildlife - Euthanasia
Often will be done in public

Barbiturates for Large Animals preferred
`` but scavanging problems

May not be able to sedate before Anesthetizing
`` tf violent response to loss of consciousness

May not be able to Anesthetize
`` tf Firearms
`` `` safety issue
`` `` `` esp public
`` `` appropriate
`` `` `` Gun
`` `` `` Ammunition
`` `` Know Head Anatomy
`` `` `` watch out for dished skulls
Captive Bolt
Effective Euthanasia Technique

If only stun can exanguinate

Edible Carcass

Agonal Reflexes
`` tf stay separated by barrier
Horse Euthanasia
Anesthetize First
`` pentabarbatol difficult to admister
`` `` ie takes time to inject required volume
`` avoid excitement phase
Autacoids
Biologically Active Agents
`` Produced in Body
`` give rise to
`` `` Physiological
`` `` Pathological
`` Changes
Name 4 Autocoids of Interest to those writing the Pharm Final
Prostaglandins

Serotonin

Bradykinin

HISTAMINE
What are 3 Places Histamine Can be Found
Granules of Mast Cells

Cells Lining the GIT

Neurons within CNS
What are 6 Vet Friendly Actions of Histamine
Stimulate the Release of HCL from Gastric Mucosa

Act as a NT

Released from Mast Cells in Response to insults such as
`` trauma
`` toxins
`` infection

Stimulates Responses in Skin
`` ie Urticarial

Bronchoconstriction

Anaphylaxis
How Many Histamine Receptors Are There
3

H1

H2

H3
What Tissues are

H1 Receptors

Generally Associated With
Smooth Muscle in Airways

Blood Vessels
What Tissues are

H2 Receptors

Generally Associated With
Gastric Mucosa
What Tissues are

H3 Receptors

Generally Associated With
CNS
What are the General Histaminic Responses for

Contact Agents

Inhalation Agents

Injestion / Ingection Agents
Dermal

Bronchial

Anaphylaxis
Name 2 H2 Blockers

What are they good for
Cimetidine

Ranitidine

Treatment of
`` Acid Reflux
`` Gastric Ulceration

Reported Use in
`` dogs
`` Pigs
`` calves
What are H1 Receptor Blockers Good For
Inhibiting the Effects of Histamine resulting from
`` `` Allergy
`` `` Anapylaxis
`` on
`` `` Airways
`` `` Blood Vessels
Predominant Response of Histamine in

Carnivores
Hypotension
`` ^ permability
`` vasodilation
Predominant Response of Histamine in

Rabbits
Pulmonary Arteriolar Constriction
`` Apnea via anoxia
`` `` shallow resporation
Predominant Response of Histamine in

Guinea Pigs - really i know you care
Bronchoconstriction
Name 5 Drugs that cause

Release of Histamine
Curare Types

Opiods

Polypeptide Antibiotics


Atropine

Snake Venoms
Diphenydramine
Antihistaminic
`` H1 Blocker
Chlorpheniramine
Antihistaminic
`` H1 Blocker
Tripelennamine
Antihistaminic
`` H1 Blocker
Promethazine

3 Handy Applications
Antihistaminic
`` H1 Blocker

Sedation and Tranquilization

Handy For
`` Pruritic Self Mutilation
`` Lick Dermatitis
`` Panic in COPD Horses
Trimeprazine
Antihistaminic
`` H1 Blocker

Sedation and Tranquilization

Handy For
`` Pruritic Self Mutilation
`` Lick Dermatitis
`` Panic in COPD Horses
Name 10 H1 Blockers

What do they all have in common
Diphenhydramine

Chlorpheniramine

Tripelennamine

Promethazine

Dimenhydrinate

Clemastine

Hydroxyzine

Trimeprazine

Astemizole

Terfenadine

Sedative and Anti-motions sickness side effects
Chromoglycates
Histamine Release Inhibitors

ie disodium chromoglycan

Decrease Histamine Release for a
`` Given Allergen Stimulus

Insoluble Powders
`` tf Inhalation Nose Bags for Horses
AntiHistaminics are Most Useful for
Inflammatory Skin Responses
You Have a COPD Horse

List 5 Treatment Strategies

for Bronchoconstriction

in Order of Go
Management
`` avoid exposure to allergens
`` ie ditch the barn or round bale
`` grass pasture

Chromolglycates
`` try to reduce histamine release for problematic allergen

H1 Blockers
`` Promethazine
`` Trimeprazine

Bronchodilators
`` Clenbuterol
`` SM side effects
`` `` uterine contractions
`` `` skeletal muscle vasodilation
`` `` `` watch out for body builders and veal calf mafia

Corticosteroids
`` decrease immune response
Name 5 Autocoids

That you DO NOT want to use to

Mitigate Inflammation

Why
Serotonin (5HT)

Peptides
`` Angiotensin
`` Substance P

Kinins
`` Bradykinin

Cytokines
`` IL-1 through 12
`` TNF

Ultimate Effects Unknown