VPha 102 Lab Notes

MODULE 1: ANTI-INFLAMMATORY DRUGS, ANTI- ALLERGY, STEROIDS
Cardinal Signs of Inflammation

• Heat (Calor)
• Redness (Rubor)
• Swelling (Tumour)
• Pain (Dolor)
• Loss of Function (Functio Laesa)
Review on Inflammation
• Inflammation only occurs when there is a stimulus which could be endogenous or

exogenous.
• The stimulus causes damage on the membrane-bound phospholipids
• Enzyme Phospholipase A2 acts upon the membrane-bound phospholipids which breaks
down the membrane-bound phospholipids into Arachidonic Acid.
• Arachidonic Acid will be acted upon COX 1 and COX 2 (Cyclooxygenase) which further
makes a conformational change making it subunits PGGs and PGH2.
• PGGs and PGH2 will be subjected to another enzyme which makes tissue-specific
isomerases which will now be called PGD2, PGE2, PGF2, PGI2, PGI2, and TXA2. These
are responsible for the cardinal signs of inflammation.
• The PGD2 breakdown in macrophages.
• PGE2 will cause pain, fever, edema increased through PGE 1-4 receptors.
• PGF2 Alpha is responsible for corpus luteum.
• TXA2 is responsible for platelet aggregation
• PGJs Ligands, which are produced by macrophages which is anti-inflammatory, inhibitors
of cell proliferation, binds to PPAR gamma transcription factor promote NF-Kappa B
which promotes apoptosis of Cytokine producing macrophage.
• NF-Kappa B then reduces Cytokine production which reduces the inflammation response.
• Inflammation can be reduced through Granulocyte apoptosis, Increased CD36 and
Phagocytosis of apoptotic neutrophils.
• Phospholipase A2 can be controlled by Corticosteroids
• COX 1 and COX 2 can be inhibited by NSAIDs and Aspirin
• Coxibs inhibit COX 2 alone
Anti-inflammatory drugs
- Are any pharmacologic compound that can inhibit one or several of the various stages
of inflammation.
- Reduces the cardinal signs of inflammation.
Two major groups
• Non-steroidal (NSAIDs)
- Phenylbutazone, meclofenamic acid, naproxen, flunixin
- Decoction during Ancient Egypt “arthritis”
- Eber papyrus (3500 years ago)
- Hippocrates, Father of Medicine (460-377 BC)
o Proposed Analgesic properties of the willow bark (Salix alba) which was
prescribed to mothers giving birth and others for treating pain and inflammation
(post-birth pain)
- 1763 – Reverend Edward Stone
o On fevered(redness) patients
o Cases of rheumatism
- 1829 – Leroux
o Extracted salicin from willow bark
- 15 years later 1844 – Cahours

o Prepared salicylic acid from oil of wintergreen (methyl salicylate)
- 1860 – Synthetic production of salicylic acid
o Used as a decoction on ancient Egypt and for treatment of rheumatism, and other
pain related to inflammation.
- 1876
o Proofs of antipyretic anti-inflammatory and analgesic properties of salicylic acid
o Berlin’s Charite Hospital
o Shortcoming: appalling taste and irritant to stomach
- 1897 – Felix Hoffman
o Less irritant and soluble acetylsalicylic acid
- 1899 – Dreser
o Aspirin was introduced to medicine
o “a” – acetyl; “spir” – Spirsaure (German for acid)
- Classification of NSAIDs
Phenylbutazone
Oxyphenbutazone
Pyrazolones Dipyrone
Enolic
Isopyrine
acids
Azapropazone
R-COH
Piroxicam
Oxicams Meloxicam
Tenoxicam
Diflunisal
Salicylic Aspirin
acids Benorylate
Sodium salicylate
Fenoprofen
Flurbiprofen
Propionic
Ibuprofen
acids
Naproxen
Carboxylic Ketoprofen
acids Indomethacin
R-COOH Fenamates Meclofenamic
acid
Sulindac (Prodrug
– undergo
Acetic acid
chemical change
derivatives
to become drug)
Tolmetin
Aminonicotenic Flunixin
acids Clonixin
Enolic & Carboxylic acids – older versions
of NSAIDS
Selective inhibitors of COX 2
Celecoxib, Rofecoxib, Etoricoxib
Coxibs Deracoxib
(newer) Firocoxib
Mavacoxib
Robenacoxib
Lumiracoxib – human use;
exceptional; carboxylic acid
similar structure with diclofenac;
limits COX 1
Repoxalin & LIcofelone – dual

COX or 5-LO inhibitors
- Common Features of NSAIDs

o Acidic drugs – reason why they have unappealing taste
o Highly protein bound in plasma (lower absorption rate) – not as affective; limited
effect
o Act by inhibiting prostaglandin synthesis
o Reduce pain in inflamed tissues by reducing tissue prostaglandin levels.
o Reduce fever
o Accumulate in stomach, kidney, and small intestine and tend to produce lesions
in these tissues (ulcers)
o Carefully given to geriatric patients more than 65 age
- Pharmacokinetics of NSAIDs (what happens)
o Oral absorption is favorable
o Highly distributed to exudates
▪ Highly bound to “plasma” proteins” that becomes exudate
▪ Proteins are present in exudate in inflammation site
▪ Drug in site
o Easily excreted in alkaline urine but takes time for acidic urine
- Pharmacodynamics of NSAIDs (effects of drugs)
o Principal action is inhibition of COX
o Central effect (dorsal root ganglis, dorsal and ventral grey matter) for COX 1 and
COX 2
- COX Inhibitor classification
Classification Example Comment
Preferential/Selective COX -1 Aspirin COX – 1 inhibitory potency at
inhibitors Carprofen least 5-fold greater than COX
Ketoprofen – 2 inhibition
Vedaprofen
Repoxalin
Nonspecific COX inhibitors Carprofen NO significant biological or
Flunixin clinical differences in
Ketoprofen concentrations producing COX
Meloxicam – 1 and COX – 2 inhibition
Ohenylbutazone
Tolfenamic Acid
Vedaprofen
Preferential and moderately Carprofen • COX-2 inhibition potency 5 to
selective COX – 2 inhibitors Celecoxib 100 fold greater than COX -1
Deracoxib inhibition
Etodolac • Some anti-inflammatory and
Meloxicam analgesic activity may be
Nimesulide obtained at concentrations
Tolfenamic acid inhibiting COX -2 but not
Mavacoxib COX 1
• At higher concentrations,
significant inhibition of COX
– 1 may occur
Highly selective COX – 2 Etoricoxib • More than 100 fold greater
inhibitors Firocoxib potency for COX-2 inhibition
Lumiracoxib • Little or no inhibition of COX
Robenacoxib -1 in vivo (normally no GIT
ulceration or antiplatelet
effect) even at maximum
therapeutic dose
- Mechanism of Action
Inhibition of Cyclooxygenase in the Arachidonic Acid Cascade Leading to Bloackade of
Synthesis of Proinflammatory Mediators – is the PRINCIPAL MECHANISM OF ACTION OF
NSAIDS
Additional Actions of Some Drugs Examples
Inhibit 5-LO LIcofelone, Tepoxalin
Inhibit prostanoid release from cells (by 2-arylpropionic acids, indomethacin
blockade of MRP4)
Inhibit lxB kinases or NFxB to inhibit COX Aspirin, Carprofen, Flunixin, Indomethacin,
expression Diarylheterocycles (COXIBs)
Inhibit the actions of eicosanoids on their Fenamate subgroup (tolfenamic acid)
receptors
Inhibit the actions of bradykinin Flunixin, Ketoprofen, Tolfenamic acid
Modulate the release of proinflammatory Carprofen (IL-6), Tepoxalin (IL-1, IL-6, TNF-
cytokines (IL-1, IL-6, TNF-alpha) alpha)
Stimulate nuclear receptors (PPAR-gama) Salicylates, 2-arylpropionic acids, arthranilic
acids, indene acetic acids
Increase intracellular breakdown of ATP to Salicylates
adenosine
Modulate the synthesis of nitric oxide Several drugs
Inhibit neutrophil chemotaxis and/or Vedaprofen, salicylates
chemokinesis
Inhibit neutrophil activation, thereby Flunixin, Ketoprofen, Piroxican, Tolfenamic
preventing: acid
Release of oxygen radicals (superoxide,
hydroxyl
Release of both lysosomal and
nonlysosomal enzymes
Increased synthesis and reduced breakdown Carprofen, Licofelone
of cartilage matrix (proteoglycans)
Increased apoptosis and inhibition of Sulphone metabolite of sulindac
carcinogenesis by a non-COX mechanism
- Therapeutic uses of NSAIDs

o Acute pain and inflammation
o Chronic pain and cancer
o Atherosclerosis
o Mastitis, metritis and endotoxemia
o Respiratory diseases
o Calf and piglet scours
- Toxicity of NSAIDs
o Gastrointestinal irritation associated with vomiting, ulceration, erosions, leading to
plasma protein losing enteropathy and melena
o Renotoxicity including occasional acute renal failure (precautions in combination
with anesthetics and loop diuretics, geriatric and patients with history of kidney
diseases)
o Hepatotoxicity (cholestatic or parenchymal)
o Inhibition of hemostatic (clotting factors are hindered) mechanism leading to
hemorrhage
o Blood dyscrasias (phenylbutazone and aspirin)
o Delayed parturition (rofecoxib)
o Delayed soft tissue healing
o Delayed fracture healing
• Steroidal (derived from endogenous corticosteroids/ glucocorticoids)
- Prednisolone, dexamethasone, betamethasone
Prostaglandins – hormones created during chemical reaction at injury site
- unlike chemical messengers; not secreted from gland since they are created at time
they are needed
- create reactions – pain, fever & inflammation (which sparks healing process)
- stimulate blood clot formation & contraction of blood vessel when body is bleeding
Lesson 1.2: Drugs Against Allergy
Allergy – a condition which is caused by the release of histamine from the mast cells as
stimulated by immunoglobulin E (IgE).
Histamine – a biogenic amine detected in the early 1900s as a common bacterial-source
contaminant of ergot extracts (Dale and Laidlaw 1910; Skidgel and Erdos 2006), Origin:
Decarboxylation of histidine decarboxylase.
Uses of Histamine:
- Dilatation of small blood vessels
- Itching
- Increased permeability of capillaries
- Smooth muscle spasm
- Increased gland secretions
- Example: allergic rhinitis – itching, sneeze, increased gland secretion, goblet cells are at
play because of excessive mucin secretion
Histamine reactions in specific species – because of different receptors
• Carnivores: Hypotension and Hepatomegaly
• Rabbits: Pulmonary artery constriction and right heart dilatation.
• Guinea pig: Bronchial constriction and asphyxiation
• Humans: Responds like carnivores and guinea pigs
Drugs that may induce histamine release:
- Curare-alkaloids – generic
- Anesthetics: Morphine; Codeine
- Antibiotics: Doxorubicin; Vancomycin; Polymyxin
Histamine receptors – 1 to 4
• H1 receptor is mainly responsible for inflammations, anaphylaxis, allergies, and certain
types of drug reactions.
• H2 receptor regulates gastric secretion
• H3 receptor modulate neurotransmitter release in the neuron
• H4 for inflammation involving eosinophils and other inflammatory cell types.
Antihistamines (Anti-allergy)
- Drugs that are used to inhibit the effects or spread of the inflammatory process
- Do not inhibit formation of prostaglandins or other inflammatory mediators
- Work by preventing histamine from combining with tissue receptors or by displacing
histamine from receptor sites – “antagonism”
Antihistamines: Clinical uses
- Control pruritus/itching
- Urticaria and angioedema associated with acute allergic reactions
- Laminitis in horse and cattle
- Motion sickness
- Anaphylactic shock
- Upper respiratory tract conditions
Antihistamines: Dosage forms
- Injectables
- Oral preparations
- Topical agents
H1 blockers
- Pyrilamine maleate
- Tripelennamine hydrochloride
- Pyrilamine maleate, phenylephrine hydrochloride (decongestant and expectorant)
- Diphenhydramine
- Dimenhydrinate
- Miclizine
- Promethazine
- Terfenadine
- Hydroxyzine
- Chlorpheniramine maleate
H2 blockers
- Cimetidine
- Ranitidine
Adverse side effects:
- Drowsiness
- Weakness
- Dry mucous membranes
- Urinary retention
- CNS stimulation on overdose
Important to note: Anti-histamines are not as effective in controlling pruritus in animals as they are
in humans
Lesson 1.3: Steroids
The Origin of Steroids
- Cholesterol is where steroids originated
- When cholesterol is acted upon by an enzyme it becomes pregnenolone. If acted by
another enzyme it becomes progesterone. Progesterone after undergoing
conformational changes because of enzymatic degradation it will now become
deoxycorticosterone then will become corticosterone, then after undergoing another
conformational change it will become aldosterone then mineralocorticoid. In summary as
illustrated below:
- Cholesterol -> pregnenolone -> progesterone -> deoxycorticosterone -> corticosterone -
> aldosterone -> mineralocorticoid
Subcellar cortisol biosynthesis

- Occurs in the adrenal cortex
- In the mitochondrion of the adrenal cortex will then synthesize cholesterol and
undergoes several conformational changes. Starts from the mitochondria then goes to
the endoplasmic reticulum then goes back to the mitochondria
Corticosteroids
• Classification
o Glucocorticoids -Affects the metabolism of carbohydrate, lipid and protein.
o Mineralocorticoids
▪ Aldosterone – water and electrolyte balance
• Can be natural and synthetic
o Common qualitative features which differ in
▪ Anti-inflammatory potency
▪ Biological half-life
▪ Propensity toward mineralocorticoid activity (?)
▪ Side effects
▪ Adrenal suppression (?)
• Classification based on duration of action
o Short-acting
▪ Cortisone
▪ Hydrocortisone
o Medium-acting
▪ Prednisolone
▪ Triamcinolone
o Long-acting
▪ Betamethasone
▪ Dexamethasone
▪ Flumethasone
• Some of the steroids are prodrugs
o Prednisone is converted to active prednisolone (liver)
o Cortisone to hydrocortisone
• Free bases (cortisone, hydrocortisone, prednisone, prednisolone, etc.) can be used in the
same way as water-soluble sodium phosphate or sodium salicylate esters for IV
• Biotransformation of water-soluble is needed to release the active form
• Water-soluble esters – rapid IV for shock treatment; higher dose
• Water-insoluble esters
- Used as depot
- Long-acting
o Release is slow and duration is long
- IM or intra-articular administration
- May cause adrenal insufficiency
o Remember the negative feedback mechanism or servomechanism (?) – When
corticosteroid is given the hypothalamus would give a negative feedback to the
adrenal cortex to stop producing hormones because there is too much in the
blood. It is in order to maintain homeostasis.
- Must be used with great care when there is infection (bacterial especially) (?)
• Mechanism of action as anti-inflammatory
o Inhibit
▪ Capillary dilation
▪ Migration of leukocytes
▪ Phagocytic activity
o Contribute to maintenance of normal circulation
o Maintain cell membrane stability
▪ Prevents the release of vasoactive amines, proteases and hydrolases System
o Act on the higher level of the arachidonic acid cascade than NSAIDs (Phospholipase
A)
▪ Blocks both cyclooxygenase and lipoxygenase enzyme systems.
o Steroids stimulate formation of lipocortin in cells that are affected by various
traumatic, mechanical, infectious, or toxigenic agents
▪ Lipomodulin – Suppress the release of phospholipase A
▪ Macrocortin
• Immunosuppressive effect
o Inhibit antibody formation
o Decrease the concentration of lymphocytes and eosinophils
o Suppress the migration of neutrophils
o Inhibit phagocytosis
• Caution: May mask the signs of serious infections that are simultaneously present
- This suppresses the immunity or the anti-inflammatory process thus masking the effect
of other underlying diseases making the animal look healthy when it is apparently not.
• Clinical uses
- Allergic reactions
- Inflammatory conditions of the musculoskeletal system
- Shock / Toxemia
- Laminitis
- Inflammatory ocular conditions such as conjunctivitis and uveitis
- Addison’s disease
- Autoimmune diseases: autoimmune hemolytic anemia, lupus, and rheumatoid arthritis
- Lymphocytic neoplasms
• Dosage forms
o Injectable
▪ IV-emergency situations
▪ IM or SC: water-soluble formulation in life-threatening conditions
o Oral
o Topical-common method
o Sometimes in combination with
▪ Antibiotics
▪ Antifungal
o Site of application
▪ Skin or mucous membrane
▪ Into lesions
• Adverse side effects
o Polyuria and polydipsia – related to glucocorticoid action
o Thinning of the skin and muscle wasting
▪ Glucocorticoids converts protein to glucose
o Depressed healing
o Polyphagia and resulting weight gain
o Iatrogenic hyperadrenocorticism, iatrogenic Cushing syndrome
o Hypoadrenocorticism (iatrogenic)
o Gastric ulcers with or without bleeding
o Osteoporosis
o Abnormal behavior
o Edema – mineralocorticoid activity
o Increases urinary potassium – hypokalemia and metabolic alkalosis
• Other contraindications
o Diabetes mellitus
▪ Steroids are antagonists to insulin
o Ocular problems – glaucoma fluid retention
o Infection – Sepsis
o Pregnancy
▪ Induce parturition in late pregnancy
o Bone healing
o Immunosuppression
o Degenerative joint disease
o Fractures
• To counteract the adverse side effects
o Alternate-day dosing may help prevent iatrogenic hypoadrenocorticism
o Administration should never be stopped abruptly. But tapered off gradually
o Very large doses may be used in emergency situations
Module 2: RESPIRATORY SYSTEM

• Situations in which drugs be used to influence the respiratory system
o Presence of Inflammation
o Occurrence of interference with the mechanics of respiration
• Three general goals In treating respiratory diseases after diagnosis has been made
(McKiernan, 1988):
o Control of secretions
▪ Increase elimination
▪ Decrease production
▪ Make secretions more viscid with an expectorant or nebulization of mucolytics
▪ Removal of causes with antibiotic, antifungal, antiparasitic, etc.
o Control reflexes
▪ Suppression of coughing if non-productive-antitussive or bronchodilator
▪ Control of sneezing-removal of offending agent or through the use of
vasoconstriction
▪ Control of bronchospasms – bronchodilators or corticosteroids.
o Maintaining normal airflow to the alveoli
▪ Maintained by reversing bronchoconstriction
▪ Removal of edema or mucus from alveoli and air passages
▪ Oxygen therapy
▪ Positive-pressure ventilation
EXPECTORANTS
• Liquefy and dilute
o Liquefy and dilute secretions of the respiratory tract
• Aid in
o Aids in the elimination of the respiratory secretions
• Relieve
o In the early stages of inflammation can relieve pain; chronic inflammatory conditions
will also benefit
~ Route of Administration
• Oral (common)
• Inhalation
• Parenteral
~ Mechanisms of action
• Act directly on the mucus-secreting glands – reducing adhesiveness of mucus
• Lessening the tackiness of the mucus
~ Indications
• Productive cough - wet
• Combined with other substances
o Ammonium chloride
o Antihistamines
o Dextromethorphan
~ Saline
• Potassium iodide
o Highly irritating to use in the treatment of acute inflammatory conditions
o Best to be used in the later stages of bronchitis to loosen tenacious secretions of the
respiratory mucosa
o Convulsions
• Ammonium Chloride/carbonate
o Act by a reflex expectorant action arising from the stomach
o Signs of toxicity
▪ Dyspnea
▪ Muscle fasciculations
▪ Convulsions
~ Demulcent
• Has soothing, demulcent effect
• Relieve mild irritation of the pharynx
• Syrup alone has no expectorant effect but may serve as a vehicle for an expectorant drug
~ Expectorants – Sedative
• Nauseant
o Antimony potassium tartrate
▪ Increases secretion of the respiratory tract by producing nausea that loosen a
dry, harsh cough.
▪ Too toxic
• Ipecac
o Administered orally
o Increases the respiratory rate of cats
o Reflex secretions are due to nausea induced by the drug
o Has toxic effects and is seldom used in veterinary medicine
o Death can result if administered in cats
~ Expectorants – Stimulant
- Increases respiratory secretions
- Stimulate or support repair of chronic inflammatory processes
✓ Guaifenesin (Glyceryl guaiacolate)
o Commonly used in equine practice to induce or maintain general anesthesia
o Clinical uses
▪ Relief of cough symptoms associated with upper respiratory tract conditions
o Common dosage forms
▪ Tablet
▪ Liquid (Syrup)
o Adverse side effects
▪ Rare but may include drowsiness or nausea
~ Expectorants – Anodyne Stimulant
• Camphorated tincture of opium (paregoric)
o Act by reflex action through the GI tract thus resulting in an increase in respiratory
tract secretions
o Seldom used because of the availability of other preparations
~ Expectorants- Miscellaneous drugs
▪ Steam
▪ With the use of a nebulizer
▪ Water is applied in a form of steam or a cool nebulized mist
▪ Particle size should be of 5µ to penetrate the smaller bronchioles
▪ For acute respiratory tract ailments
▪ Mechanisms of action
▪ Warmth and moisture tend to liquefy the secretions already present
▪ Induce hyperemia that increases the volume but decreases the viscosity of
the secretions
▪ Disadvantages
▪ May cause heat stroke
▪ Steam may be turned over by the patient
▪ May cause burns
▪ Gases
▪ Carbon dioxide
▪ For patients with thick tenacious secretions on the lower respiratory tract
• Mode of action
o Induces hyperemia - recommended since the gas reaches the lower recesses of the
respiratory tract
• Stimulates respiration thus increasing respiratory movements which aids in the removal of
the secretions.
Note: Oxygen is an antiexpectorant
MUCOLYTICS
~ MUCOLYTICS – ACETYLCYSTEINE
• Only mucolytic of clinical significance in veterinary medicine
• Effective against purulent or nonpurulent pulmonary secretions
• Route of administration
o Nebulization – pulmonary uses; 2 – 3 days
o Face mask – 5 minutes, 3 times daily and increased to 15 minutes, 3 times daily
o Oral – antidote for acetaminophen toxicity
• Clinical uses
o To break inspissated respiratory mucus
o Animals are encourage to exercise after administration to stimulate coughing
o Coughing can also be stimulated by applying sharp percussion on both sides of the
thorax
o Kennel cough
o Treat acetaminophen toxicity
• Interaction with other drugs
o Inactivates penicillin and tetracyclines, thus should not be administered together via
aerosol
o Systemically administered penicillin are not inactivated by the inhalation of
acetylcysteine
o High concentrations of oxygen can inactivate acetylcysteine
• Adverse effects
o Nausea
o Vomiting
~ MUCOLYTICS – PANCREATIC DORNASE
- Enzyme preparation consists of purified deoxyribonuclease from beef pancreas
• Mechanism of Action
o Depolymerizes DNA, thus liquefying the purulent sputum
o Antibiotics and bronchodilators can be added without inactivation
ANTITUSSIVE
~ Antitussive – Narcotic
- Centrally acting antitussive
- Codeine phosphate
o Clinical uses are similar to hydrocodone
o Adverse side effects:
▪ Sedation
▪ Constipation
- Butorphanol Tartrate
o Synthetic opiate partial agonist with antitussive property
o Class IV controlled substance
o Clinical uses
▪ Dogs
• Relief of chronic nonproductive cough
• Preanesthetic
• Analgesia
▪ Cats
• Preanesthetic
• Analgesia
▪ Sedation
▪ Ataxia
- Hydrocodone bitartrate
o Opiate agonist; schedule III
o Clinical use
▪ For harsh, nonproductive coughs
▪ Sedation
▪ Constipation
▪ Gastrointestinal upset
~ Antitussive – non-narcotic
- Dextromethorphan
o Chemically similar to codeine
o No analgesic and addictive properties
o Centrally acting antitussive
o Elevates the cough threshold
o cats
o Clinical use
▪ To suppress nonproductive cough
o Adverse side effect
▪ Rare when administered properly (drowsiness or gastrointestinal upset)
- Trimeprazine tartrate + prednisolone (Temaril – p)
o Combination of centrally acting antitussive (t) and corticosteroid (p)
o Clinical uses
▪ Antitussive
▪ Antipruritic
▪ Sedation
▪ Depression
▪ Minor central nervous system signs
- Diphenhydramine hydrochloride
o An antihistamine
o Used to treat allergic conditions
▪ Sedation
▪ Gastrointestinal effects (occasionally
BRONCHODILATORS
~ Bronchodilators – Cholinergic blockers
- Prevents the bronchoconstriction effect of acetylcholine
- Drugs (in cases especially of organophosphate or carbamate toxicity)
o Atropine
o Glycopyrrolate
o Aminopentamide
~ Bronchodilators – Antihistamines
- Block the effects of histamine
- Clinical uses
o Heaves in horses
o Pneumonias in cattle
o Feline asthma
o Insect bites
- Generic names usually end in the suffix –amine
- Route of administration
o Oral
o Parenteral (injectable)
- Drugs include
o Pyrilamine
o Tripelennamine
o Diphenhydramine -----
o Loratadine (Claritin)
o Fexofenadine (Allegra)
o Pyrilamine (Histagranules, Hist-Eq, Histall)
o Tripelennamine (Re-Covr)
o Probahist syrup
o Antihistamine injection
o Diphenhydramine; human-approved
o Doxylamine
o Hydroxyzine (Atarax)
o Clemastine (Tavist)
o Cyproheptadine (Periactin). May be used in cats to block bronchoconstriction and
also as an appetite stimulant.
o Cetirizine (Xyrtec)
~ Bronchodilators – Beta-2 Adrenergic Agents
- Mechanism of action
o Combine with specific receptors thus results in relaxation of the smooth muscle
fiber of the respiratory tract
- Stabilize mast cells and reduce the amount of histamine
- Drugs include
o Epinephrine
▪ For life- threatening situations – anaphylactic shock
o Isoproterenol
o Albuterol
o Clenbuterol
▪ For horses not intended for food
- Adverse side effects
o Tachycardia
o Hypertension
~ Bronchodilators – Methylxanthines
o Inhibit the enzyme phosphodiesterase
o Phosphodiesterase inhibits cyclic AMP (cAMP) resulting to bronchoconstriction
- Normal: beta- 2 receptor stimulation → release of cAMP in the smooth muscle cell→
relaxation → dilation
- Products include
o Aminophylline
o Theophylline
- Adverse reactions
o Gastrointestinal upset
o CNS stimulation
o Tachycardia
o Ataxia Arrhythmias
- May interact with the following drugs:
o Phenobarbital
o Cimetidine
o Erythromycin
o Thiabendazole
o Clindamycin
o Lincomycin
DECONGESTANTS
- Reduces the congestion of nasal membranes by reducing the associated swelling
- Route of administration
o Spray
o Nose drops
o Orally (liquid or tablet)
o May act directly or indirectly in reducing congestion by producing vasoconstriction
of nasal blood vessel
- Drugs include
o Orally, act systematically
▪ Ephedrine
▪ Pseudoephedrine
o Phenylpropanolamine
o Topically
▪ Oxymethazoline
▪ Phenylephrine
STIMULANTS –
✓ Doxapram hydrochloride
- Central nervous system stimulant
- Primary use – stimulation of the respiratory system
- Clinical uses
o Stimulation of respiration during and after anesthesia
o Speed awakening and restoration of reflexes after anesthesia
o Neonates – respiratory stimulant especially after dystocia or caesarean section
o Hypertension
o Arrhythmias
o Hyperventilation
o CNS excitation
o Seizures
LEUKOTRIENE ANTAGONISTS
- Naloxone
o To stimulate the respiratory system in cases of narcotic overdose
- Yohimbine
o Stimulate respiration in xylazine overdose
MAST CELL STABILIZERS
- Cromolyn Sodium – inhibit release of histamine and leukotrienes from mast cells in
nasal and lung mucosa and in eyes; inhibit bronchospasm; used primarily to treat RAO
(heaves) in horses
MODULE 3: CARDIOVASCULAR DRUGS

Heart pumps blood, provide nutrient (oxygen), removes co2 and metabolic wastes to lungs; when
compensated naay -→
Cardiac compensatory mechanisms:
Factors of cardiac reserve/compensation
• Increasing heart rate (if not enough oxygen or blood mureach sa tissue)
• Increasing stroke volume
• Increasing efficiency of heart muscle (to compensate work load)
• Cardiac remodeling or Physiologic heart enlargement or myocardial hypertrophy
Classification of disorders
• Valvular disease
• Cardiac arrythmias
• Myocardial disease
• Other causes – congenital defects, abnormalities of cardiac innervation, vascular disease
(hypertension), heartworm disease
Stages and Treatment of cardiac Disease page 21
Goals / Targets in treating the disorders:
• Control rhythm disturbances (abnormal blood blow)
• Maintain or increase cardiac output
o Increase the strength of contraction
o Decrease the afterload
- Arteriolar dilator
- Decrease the preload
- Venodilator
- Relieve fluid accumulations
o Diuretics
o Dietary salt restriction
• Relieve fluid accumulations (in areas with hyperfusions but lesser return of blood into heart)
• Increase oxygenation of the blood
o Bronchodilation
• Ancillary (additional) treatment
o Narcotics/ Sedatives
o Oxygen
1) POSITIVE INOTROPIC DRUGS
General mechanism of action: Enhance the contraction strength of the heart thus increasing cardiac
output
1a. CARDIAC GLYCOSIDES (DIGITALIS) – obtained from dried leaves Digitalis purpurea (Foxglove, Purple
Foxglove, or Lady’s Glove); include digoxin and digitoxin (rarely used)
- William Withering: postulates that digitalis cures drowsy (edema caused by congestive heart
failure) among 20 herbs
Mechanisms of Action:
• Positive inotropic: increases cardiac contractility and increasing the availability of calcium to
contractile proteins (calcium impt ion in contracting heart, shortening of sarcomeres, calcium
adhesion to actin-myosin complement)
• Antiarrhythmic - decreasing the heart rate by increasing the parasympathetic tone to the sino-atrial
(SA) node and atrioventricular (AV) nodes and the atria
• Decrease signs of dyspnea
Pharmacokinetics
✓ Digoxin
- Absorption:60% tablet form; 75% elixir form; 20% oral bioavailability in horses
- Absorption is decreased by the following:
Food, Kaolin- pectin compounds, Antacids, Malabsorption syndromes
- Fate: about 27% of drug is protein bound; hepatic metabolism is minimal
✓ Digitoxin (rarely used)

- Absorption - well absorbed orally; nonpolar and highly fat soluble
- Fate: abt 90% bound in the serum; half-life is 8- 12 hours in dogs; should not be used in cats
because of very long half-life (>100 hrs)
- Elimination: cleared by the liver; can be tolerated in the presence of liver disease and renal
failure
Clinical uses – For the treatment of congestive heart failure (CHF) associated with myocardial dysfunction
• Digoxin
o Increases cardiac output
o Decreases cardiac filling pressures
o Decreases heart size
o Decreases venous and capillary pressures
o for supraventricular arrhythmias (tachycardia)
o Atrial fibrillation
o Atrial arrhythmias
Administration – fatal myocardial toxicity may occur if there is myocardial failure
• Initial dosage
o oral maintenance doses of digoxin should be used to initiate therapy for loading doses can
cause toxic serum concentrations
o Slow intravenous administration (over at least 15 minutes) can be used in emergency cases
o Rapid injection may result in peripheral vasoconstriction
o ideal- full dose is divided and given slowly over several hours
• Maintenance dosage
o After 1 week of initial therapy or dosage alteration, serum concentration can be measured
o Blood can be obtained 8 – 10 hours after dosing
o The therapeutic serum concentration range is considered to be 1.0 – 2.4 ng/ml
o If serum level is <0.8 ng/ml, the dose can be increased by no more than 30%; serum
concentration should be rechecked the following week
• Factors affecting dosage
o Renal disease
o Heart disease
o Weight – Cachexia, Obesity
o Liver disease
Adverse side effects:
• Myocardial toxicity
o Causes: Cardiac overload
o Toxic levels of digoxin – increase sympathetic tone to the heart thus causing an increase in
automaticity
o Induce and potentiate late after- depolarization
o Predisposing factors
• Hypokalemia
• Hypercalcemia and hypernatremia
• Abnormal thyroid hormone levels
• Hypoxia
o Therapy: Atrioventricular conduction abnormalities
• drug withdrawal
• anticholinergic agent (sometimes is needed)
o Ventricular tachycardia – lidocaine or phenytoin (diphenylhydantoin) 2
o Cholestyramine
o Intravenous potassium supplementation + intravenous fluids + propranolol
o Digoxin immune Fab (Digibind) 5
o Gastrointestinal upset 6
- Signs may appear before myocardial toxicity
- Anorexia
- Vomiting
- Borborygmus
- Diarrhea
o Due to direct effects of the digitalis glycosides on the chemoreceptors in the medulla 7
o Respond to drug withdrawal and correction of fluid or electrolyte disturbances 8
Contraindications:
o Hypertrophic cardiomyopathy
o Pericardial disease
o Sinus or AV nodal disease
o Ventricular tachyarrhythmias
Drug Interactions
✓ Digoxin
o Concentration is increased by
o Quinidine, Verapamil and amiodarone; Possibly diltiazem, prazosin, spironolactone and
triamterene
o Metabolism is altered by drugs affecting hepatic microsomal enzymes
o Bioavailability is decreased by neomycin and sulfasalazine
o Toxicity may be potentiated by thyroid and electrolyte disturbance (especially hypokalemia)
o Incompatible with
o Dobutamine HCl, Acids, Alkalis
✓ Digitoxin
o Clearance is increased by phenylbutazone, primidone and phenobarbital
o Clearance is decreased by chloramphenicol, quinidine and tetracycline
1b. CATECHOLAMINES / SYMPATHOMIMETIC AGENTS

Mechanism of action
◦ Stimulate cardiac β1- adrenergic receptors
◦ Leads to increased calcium influx:
◦ Increases cardiac contractility → increase cardiac output
◦ Peripheral vasoconstriction → increase blood pressure
◦ Increase blood glucose level
Drug preparations
✓ Epinephrine p.22
o Preferred drug for providing stimulation for contraction of the heart and for supporting the
circulatory system after cardiac arrest
o Can be administered by the intracardiac, intratracheal or intravenous route
o Not used for therapy of chronic heart failure
✓ Isoproterenol
o Seldom used in the treatment of cardiac disease
o Indicated in atropine-resistant bradycardia
✓ Dobutamine
◦ Increases cardiac contractility but does not affect produce vasodilation in selected vessels
◦ It is a direct beta 1- adrenergic agent
◦ Increases cardiac output but with little possibility of causing cardiac arrhythmias or
increased cardiac rate
◦ Biosynthetic precursor of norepinephrine
◦ Occurs as a white to off-white crystalline powder
◦ Freely soluble in water and alcohol
◦ Stimulates dopaminergic receptors in coronary, mesenteric, renal and cerebral vascular
beds
◦ Also capable of stimulating adrenergic receptors thus increasing heart contractility, heart
rate and blood pressure
◦ Use in correcting heart failure associated with anesthetic emergencies or after cardiac
resuscitation
Pharmacokinetics
◦ Not administered orally due to rapid metabolism in the GIT
◦ After IV- onset of action is within 5 minutes; persist for less than 10 minutes after infusion is
stopped
◦ Distribution
◦ wide distribution in the body
◦ does not cross blood- brain barrier
◦ unknown to cross the placenta
◦ plasma half-life is approximately 2 minutes
◦ Metabolism
◦ Kidney
◦ Liver
◦ Plasma
Clinical uses
◦ Used for adjunct treatment of acute heart failure and oliguric renal failure
◦ For the supportive treatment of shock
Adverse side effects
◦ Vomiting
◦ Tachycardia
◦ Dyspnea
◦ Variations in blood pressure
Compatibility is dependent on
◦ pH
◦ Concentration
◦ Temperature
◦ diluents used
Compatible with IV fluids:
◦ D5LRS,
◦ D5 in normal saline
◦ D5 in half-normal saline
◦ D 5W
◦ Mannitol 20% in water
◦ Lactated Ringer’s
◦ Normal saline
◦ 1/6M sodium lactate
Compatible with Drugs:
◦ Aminophylline
◦ bretylium tosylate
◦ calcium chloride
◦ carbenicillin disodium
◦ cepalothin sodium neutral
◦ chloramphenicol sodium succinate
◦ dobutamine HCl
◦ gentamicin sulfate
◦ heparin sodium
◦ hydrocortisone sodium succinate
◦ methylprednisolone sodium succinate
◦ kanamycin sulfate
◦ lidocaine HCl
◦ oxacillin sodium
◦ potassium chloride
◦ tetracycline HCl
◦ veparamil HCl
Incompatible with
◦ Amphotericin B
◦ Ampicillin sodium
◦ Iron salts
◦ Metronidazole with sodium bicarbonate
◦ Penicillin G potassium
◦ Sodium bicarbonate
Contraindications
◦ Pheochromocytoma
◦ Ventricular fibrillation
◦ Uncorrected tachyarrhythmias
1c. BIPYRIDINE DERIVATIVES
◦ Mechanism of action - Inhibits enzymes (phosphodiesterase III) that ultimately lead to an increase in
cellular calcium
◦ Drug Preparations/ Pharmacokinetics/ Clinical Use
✓ Amrinone – given intravenously; for short-term inpatient use; for acute inotropic support in dogs
and cats with severe myocardial failure
✓ Milrinone – given orally; for long-term use
◦ Adverse side effects
◦ has a wide margin of safety
◦ may intensify ventricular arrhythmias
1d. INOTROPIC, MIXED DILATOR
✓ Pimobendan - Increase calcium sensitivity of cardiac myofilaments and inhibit enzyme
phosphodiesterase
o Clinical uses - Treatment of atrio-ventricular insufficiency or dilated cardiomyopathy in dogs
o Dosage form - Chewable tablets 1.25, 2.5 or 5 mg sizes
o Adverse effects
▪ Anorexia
▪ Lethargy
▪ Diarrhea
o Contraindications
▪ Hypertrophic cardiomyopathy
▪ Aortic stenosis
▪ Diarrhea
Arrhythmia – abnormal beating of the heart
2) ANTI-ARRHYTHMIC DRUGS – for tachyarrhythmias
o Class I (Local Anesthetics)
o IA – quinidine, procainamide, disopyramide
o IB – lidocaine, phenytoin, tocainide, mexiletine
o IC – flecainide, encainide, propafenone
o Mechanisms of action
o Agents have local anesthetic effects – changing the automaticity, excitability, conduction
and refractoriness of the cardiac membranes
o Some Class I agents are dependent on extracellular potassium concentration
Class Agents Mechanism of Action ECG Effects
CLASS I – Decrease fast inward Na+ current; stabilize membrane by decreasing
conductivity, excitability and automaticity
o Quinidine Moderately decrease
Prolonged QRS and
IA o Procainamide conductivity; increase action
QT intervals
o Disopyramide potential duration
o Lidocaine Decrease action potential
o Phenytoin duration with little change in Unchanged QRS and
IB
o Tocainide conductivity QT intervals
o Mexiletine - Block sodium
Markedly decrease conductivity
o Flecainide
without changing action
IC o Encainide
potential duration
o Propafenone
-not common
o Propanolol
Beta-adrenergic blockade
o Atenolol
(reduce wympathetic
CLASS o Esmolol
stimulation with no direct
II o Metoprolol
effects on myocardium at
o Nadolol
clinical dosages)
o Pindolol
Selectively prolong action
o Bretylium potential duration and
CLASS Prolonged QT
o Amiodarone refractory period antiadrenergic
III intervals
o Sotalol effects
-not common
Decrease slow inward Ca2+
CLASS o Verapamil current (greatest effects on SA
IV o Diltiazem and AV nodes)
- Blocks calcium
CLASS ABSORPTION FATE ELIMINATION

By hepatic
20% protein bound
IA – Procainamide Well absorbed orally metabolism and
in dog
renal excretion in
proportion to
creatinine clearance
Hepatic metabolism
is not greatly
dependent on liver Metabolized in the
Well absorbed orally
IA – Quinidine blood flow livers and excreted
with first pass effect
Highly protein in the urine
bound in dogs and
cats
Undergoes rapid
Almost complete
hepatic metabolism
firs-pass hepatic
Metabolites may
IB – Lidocaine elimination, thus
contribute to
administered
antiarrhythmic
through IV route
effects and toxicity
Well absorbed Eliminated via the
orally; does not liver and the kidney;
IB - Tocainide undergo extensive clearance is not
first-pass significantly affected
metabolism by liver blood flow
Elimination is
Poor oral
Metabolism in the facilitated by
IB – Phenytoin bioavailability; thus
liver hepatic microsomal
given intravenously
enzymes
Undergoes liver
metabolism,
Via the urine;
influenced by liver
Good oral alkaline urine
IB – Mexiletine blood flow; half-life
absorption prolongs the
in dogs is 4.5-7
elimination
hours, depending on
urine pH
Pharmacologic Effects:
o CLASS IA DRUGS
o Procainamide and quinidine
o depress automaticity and conduction velocity
o prolong the effective refractory period
o due to electrophysiologic (direct) and vagolytic (indirect) effect of the drugs
o Disopyramide
o similar to quinidine and procainamide electrophysiologically
o can depress the canine myocardium
o CLASS IB DRUGS
o Lidocaine
o suppresses automaticity in both normal Purkinje fibers and diseased myocardial tissue
o slows conduction and reduces the supernormal period
o Produces minimal hemodynamic effects
o Has little effect on sinus rate, AV conduction rate and refractoriness
o Tocainide - similar to lidocaine in electrophysiologic and hemodynamic properties
o Phenytoin
o similar to lidocaine
o some slow calcium channel inhibitory and central nervous system (CNS) effects
o Mexiletine - similar to lidocaine in its electrophysiologic, hemodynamic and antiarrhythmic
properties
Clinical Uses:
• Primarily for frequent ventricular premature contractions and ventricular tachycardia
o Class IA
• Procainamide and quinidine may also be effective for atrial premature depolarizations and
tachycardias
• quinidine may cause conversion to sinus rhythm in horses, cattle and large dogs
• procainamide is less effective than quinidine for atrial arrhythmias and not effective in
converting chronic atrial fibrillation to sinus rhythm
o Class IB
• Lidocaine
▪ intravenous ventricular antiarrhythmic agent of choice in the dog
▪ generally ineffective for supraventricular arrhythmias
• Phenytoin
▪ used only in dogs
▪ for digitalis glycoside- induced ventricular arrhythmias that are not responsive to lidocaine
▪ Not used in cats and horses
o Class IC
• Flecainide and Encainide
▪ associated with increased mortality rate in humans
▪ thus they are used only with caution and for life- threatening ventricular arrhythmias
unresponsive to more conventional therapy
Administration:
• Class IA
- Procainamide
▪ Oral and IM administration are not associated with hemodynamic effects
▪ Constant Intravenous infusion - should be slow so as not to result in hypotension and cardiac
depression; steady state is achieved in 12 – 22 hours
- Quinidine
▪ Oral and IM administration
o Slow-release sulfate, gluconate, and polygalacturonate salts prolong the absorption and
elimination
o sulfate salt is more rapidly absorbed than the gluconate salt
o adverse hemodynamic effects are not common but may occur in patients with underlying
cardiac disease
▪ Intravenous administration - can cause vasodilation, cardiac depression and hypotension
▪ Nasogastric intubation – preferred administration in horses
• Class IB
- Lidocaine - administered by slow intravenous boluses; followed (if effective) by constant rate
infusion
- Phenytoin - rapid IV injection should be avoided so as not to depress myocardial contractility and
cause vasodilation, hypotension, exacerbation of arrhythmias and respiratory arrest
• Class IC – administered orally
- IV administration of flecainide and encainide may result in hypotension and myocardial
depression
Adverse side effects - All antiarrhythmic drugs, especially the Class IC agents may aggravate arrhythmias
• Class IA
✓ Procainamide – most serious toxic effects include: Hypotension, Depressed AV conduction,
Worsening of arrhythmias, Toxic effects are similar to quinidine
✓ Quinidine
▪ Toxicology occurs as an extension to the electrophysiologic and hemodynamic actions
▪ Severe hypoalbuminemia predispose to toxicity
▪ Negative inotropic and vasodilation results in:
▪ Lethargy and weakness
▪ Congestive heart failure
▪ Gastrointestinal signs can be observed with oral administration: Vomiting, nausea,
Diarrhea
▪ Horses – Apprehension, Depression, Diarrhea, Anorexia
▪ Dogs and Cats – reversible thrombocytopenia
• Class IB
✓ Lidocaine
▪ The most common toxic effect – CNS excitation: agitation, disorientation, muscle twitches,
nystagmus, generalized seizures, nausea (less frequently)
▪ Cats are sensitive to lidocaine toxicity and may suffer respiratory arrest with seizures
▪ Horses are also sensitive
✓ Tocainide
▪ Similar to lidocaine
▪ Gastrointestinal effects (common)
▪ nausea
▪ vomiting
▪ Occasional- neurotoxic signs
▪ Ataxia
▪ Disorientation
▪ Twitching
✓ Phenytoin
▪ IV administration is associated with bradycardia, AV blocks, ventricular tachycardia, and
cardiac arrest
▪ Neurotoxicity signs
▪ Depression
▪ Nystagmus
▪ Disorientation
▪ ataxia
✓ Mexiletine
▪ Toxic effects are similar with lidocaine
▪ Dogs- vomiting and disorientation
• Class IC
✓ Flecainide and encainide can worsen ventricular arrhythmias
▪ Signs that can be observed:
▪ Bradycardia
▪ Intraventricular conduction disturbance
▪ Consistent hypotension
▪ Nausea
▪ Vomiting
▪ Anorexia
Contraindications:
▪ All Class I drugs are contraindicated in the presence of complete heart block
▪ Class I agents should be used carefully in patients with
▪ sinus bradycardia
▪ sick sinus syndrome
▪ 1st- or 2nd- degree AV nodal block
Drug Interactions
✓ Positive interactions
o The use of Class I drug with drugs from other classes may increase the antiarrhythmic efficacy in
cases refractory to a single agent
✓ Negative interactions
o Class IA
▪ Cimetidine
- renal tubular secretion of procainamide is blocked
- predisposes patient to quinidine toxicity by slowing elimination
▪ Quinidine
- can precipitate digoxin toxicity
- displaces digoxin from the skeletal muscle binding sites
- decreases digoxin’s renal clearance
▪ Anticonvulsants and other drugs
- induce hepatic microsomal enzymes thus making the metabolism of quinidine faster,
thus increased dose is needed
o Class IB
▪ Propanolol, cimetidine and other drugs that decrease liver blood flow
- slow the metabolism of lidocaine
- reduced liver blood flow associated with heart failure may also predispose toxicity
▪ Cimetidine, chloramphenicol and other drugs that inhibit microsomal enzymes- may result in
toxic serum concentrations of phenytoin
3) VASODILATOR DRUGS – act by dilating arteries, veins, or both though blockage of sympathetic
stimulation to smooth muscle or preventing conversion of Angiotensin 1 to Angiotensin 2
3a. Angiotensin-Converting Enzyme (ACE) Inhibitors
Mechanism of Action - Impede with the conversion of angiotensin I to angiotensin II resulting in volume
retention and vasodilation
Drug Preparations – Captopril, Enalapril maleate, Lisinopril, Benazepril
Pharmacokinetics
Drug Absorption Fate Elimination
Approximately 75%
is rapidly absorbed
after oral Dogs: 40% protein
administration, bound; acute
presence of food hemodynamic
Captopril reduces absorption; effects las for <4 Via the kidneys
the drug is a weak hours, thus should
organic acid with an be given 2-3x daily
active sulhydryl PO
group (not found in
other ACE inhibitors)
Slower onset but
longer duration than
Parent drug and
Presence of food captopril; can be
metabolites are
Enalapril maleate does not affect given 1-2x daily PO;
excreted unchanged
absorption converted in the
in the urine
liver into enalaprilat
(active metabolite)
Lysine analog of
Lisinopril Once a day
enalaprilat
Approximately 40%
Converted in the
is absorbed after
liver into
oral administration; 50% - biliary; 50% -
Benasepril benazeprilat;
presence of food renal
administered once a
does not affect
day
bioavailability
Pharmacologic Effects
- Arteriolar and venous dilation
- If locally produced ACE in the vascular walls is inhibited= local vasodilating effect even if renin is
absent
- Vasodilating effect is enhanced by vasodilator kinins (bradykinin and kallidin) which are normally
degraded by ACE
- Reduced water and sodium retention
- Decrease in aldosterone production
- There is a corresponding decrease in sodium excretion
Clinical Uses
- Vasodilating effect is enhanced by vasodilator kinins (bradykinin and kallidin) which are normally
degraded by ACE
- Reduced water and sodium retention
- Decrease in aldosterone production
- There is a corresponding decrease in sodium excretion
- For treating heart failure due to valvular insufficiency and other volume overloads
- For cats with right– sided CHF secondary to chronic hypertrophic or restrictive cardiomyopathy
- For vasodilation in the treatment of Class II, III, and IV heart failure
Adverse Effects
- Hypotension
- Gastrointestinal upset
- Renal failure or worsening of renal function
- Hyperkalemia, if administered with potassium- sparing diuretics or potassium supplements or the
animal is having renal insufficiency
Drug Interaction
- Effectiveness maybe reduced with non- steroidal anti-inflammatory drugs (NSAIDs)
3b. HYDRALAZINE
Mechanism of Action
- Directly relaxes the arteriolar smooth muscle by
- Interfering the movement of calcium
- Inhibiting the contractile state
- Has little effect on the venous system
- Intact vascular endothelium is necessary
Pharmacokinetics
- Absorption - food decrease bioavailability by more than 60%
- Fate
• Undergo first- pass effect in the liver
• High doses saturate the metabolism thus increasing bioavailability
- Pharmacologic Effects
• Decreases mean arterial pressure and vascular resistance, thus increasing cardiac output
Clinical Uses
- Mitral valve insufficiency + severe pulmonary edema = administered together with furosemide
- Myocardial failure
- Hypertension
Adverse Side Effects
- Hypotension- most common
- Reflex tachycardia
- Increase sodium and water retention by enhancing the neurohormonal mechanism of overcoming
heart failure
- Gastrointestinal upset – vomiting and diarrhea
3c. NITRATES /
Mechanism of Action
- Sodium nitroprusside (IV)- directly dilates arteriolar and venous smooth muscle
- Nitroglycerine and isosorbide dinitrate (PO or transcutaneously) – dilate venous smooth muscle by
stimulating production of cyclic guanosine 3’5’- monophosphate (cGMP)
Drug Preparations
- Sodium Nitroprusside
- Nitroglycerine ointment – applied at hairless areas of small animals
- Isosorbide dinitrate
Pharmacokinetics
- Undergo extensive first- pass metabolism
Pharmacologic Effects
- Sodium nitroprusside – potent arterial and venous dilator
- Other nitrates- increase venous capacitance and reduce cardiac filling pressures
Therapeutic Uses
✓ Sodium Nitroprusside
o for the treatment of fulminant CHF in dogs
o hemodynamic monitoring should be done since severe hypotension may result
✓ Nitroglycerine and isosorbide dinitrate
o to provide relief for acute cardiogenic pulmonary edema
o one or the other is used for long-term therapy for persistent pulmonary edema despite
diuretic therapy
o hydrazaline may be added to the treatment regimen
o ACE therapy is more advantageous
Administration
✓ Sodium Nitroprusside – IV due to its short duration; dosage should be adjusted to maintain the
mean arterial pressure above 70mmHg
✓ Nitroglycerine
o transcutaneous route- most commonly used every 4 – 6 hours
o application papers or gloves should be used
o sublingual route can also be considered
✓ Hypotension
✓ Cyanide toxicity
3d. PRASOZIN
Mechanism of Action
- Selectively blocks alpha 1- receptors thus resulting in arterial and venous dilation
Clinical Uses
- As an adjunct therapy of CHF
- For cardiac myopathy in dogs
- Systemic hypertension
- Pulmonary hypertension
- Hypotension
- Syncope
- Vomiting
- Diarrhea
3e. DIURETICS
- promote reduction of preload through diuresis
- reduce harmful effects of CHF by reducing plasma volume through various mechanisms
- most work by inhibiting reabsorption of sodium and water in loop of Henle or distal tubules
- If sodium ions remain in the tubules, they exert an increased osmotic “pull” on water molecules to
cause them to remain in the tubules and be excreted as urine.
FUROSEMIDE - most important and efficacious diuretic for removing edema from animals
with heart failure
- IV, IM, SC, orally
- Works rapidly to reduce pulmonary edema and other signs of CHF
- Causes diuresis by reducing reabsorption of sodium and other electrolytes
in kidney tubules
- aka loop diuretic; because much of the reabsorption occurs in loop of henle
- hypokalemia (low blood potassium); dehydration; low blood sodium
(hyponatremia; ototoxicity (cats); weakness; shock
THIAZIDES - ex. Chlorothiazide (Diuril) – act on loop of henle and distal tubules to inhibit
reabsorption of sodium; seldom used
SPIRONOLACTONE - potassium-sparing diuretic (it does not normally cause hypokalemia) and an
antagonist of aldosterone
- By inhibiting aldosterone, it reduces the amount of sodium reabsorbed
from the kidney tubules.
- (Aldactone) usually is not used alone but is combined with a loop diuretic
or a thiazide
DIETARY MANAGEMENT OF HEART DISEASE p.30

- Sodium restriction
- Maintenance of good body weight and condition
SUPPLEMENTAL TREATMENT OF HEART FAILURE
1. Bronchodilator - aminophylline and theophylline; sometimes used in the treatment of heart failure.
These agents increase the size of lung passageways to allow more efficient oxygenation of blood, to
exert a mild positive inotropic effect on heart muscle, and to obtain a mild diuretic effect
2. Oxygen therapy - Animals with pulmonary edema benefit greatly from the administration of 40% to
50% oxygen via cage, mask, or nasal cannula.
3. Sedation – Animals with pulmonary edema caused by heart failure often experience a great deal of
anxiety because of the dyspnea that they encounter. This anxiety often leads to hyperventilation
and even greater oxygen demand and anxiety. To break the cycle and calm the animal, sedative
drugs are often administered. The clinician may choose morphine, meperidine, diazepam, or other
drugs.
4. Aspirin - reduce pain and inflammation, fever, and platelet aggregation; sometimes used in heart
disease when clot formation may be a potential problem; to reduce the tendency for clot formation
in heartworm treatment and for the same purpose in congestive cardiomyopathy in cats.
5. Thoracocentesis and Abdominocentesis - When heart failure is accompanied by excessive fluid
(effusion) in the thoracic cavity, drawing fluid from the cavity may be lifesaving. Removal of ascitic
fluid is controversial but may relieve pressure on the diaphragm and improve ventilation.
4) DRUGS AFFECTING BLOOD COAGULATION

BLOOD COAGULATION CASCADE
Intrinsic & Extrinsic Pathways
Factor XII – fribrinogen to fibrin for blood clot
1. Vascular Phase – spasm in damaged smooth muscle; injury in tissue
2. Platelet Phase – platelet aggregation and adhesion
3. Coagulation Phase – activation of clotting system and clot formation
Merging of Clotting factors 8, 9, 10, 11 & 12 ; Platelet factors, Calcium ions, platelet thromboplastin in Intrinsic
Pathway and the tissue thromboplastin, clotting factor 7, calcium ions, and tissue factors from extrinsic pathway
which creates a common pathway for the creation of prothrombin, thrombin, fibrinogen to fibrin which forms
the bulk of the blood clot
4. Clot Retraction – contraction of blood clot
5. Clot Destruction – enzymatic destruction of clot.. plasmin
4a. ANTICOAGULANTS – interrupts cascade; Inhibit clot formation or coagulation by inactivating one of the clotting
factors
Clinical uses
o Prevent coagulation of blood samples
o Preserve blood for transfusions
o Inhibit clotting in intravenous catheters
o Prevent or treat thromboembolic disorders
✓ Heparin – anticoagulant; Found in many tissues of the body; Produced and stored by mast cells; Obtained from
intestinal mucosa of pig, Heparin units: strength
Mechanism of action
- Inhibit conversion of prothrombin (Factor II) to thrombin
- Cannot break down clots but prevent from increasing the clot size
- Administered IV; SC
Clinical uses
- Preserve blood samples for testing
- Prevent clots in intravenous catheters
- Preserve blood for transfusions
- Treatment of disseminated intravascular coagulation (DIC)
Adverse side effects
▪ Bleeding
▪ Thrombocytopenia
▪ White blood cell morphology is affected
o Not recommended when blood is used for differential counting
▪ Heparin tubes have green top (color coded)
Protamine: antidote for heparin poisoning
✓ Ethylenediaminetetraacetic Acid (EDTA) – chelates calcium (Factor IV)
Clinical uses
o Preserve blood samples
o Anticoagulant of choice for differential blood count
o With lavender-topped tubes
o
Calcium salt of EDTA (calcium disodium versenate): for lead poisoning (not related with coagulation
process)
✓ Coumarin derivative – commonly used in human medicine
Preparations
o Dicoumarol: sweet clover (cattle)
o Warfarin: rat poisoning products
Mechanism of action: Bind Vitamin K
o Inhibit synthesis of Vitamin K- dependent factors
o Prothrombin (Factor II)
o Factors VII, IX, X
Clinical Uses – thromboembolic conditions
Adverse side effect – hemorrhage
✓ Acid citrate dextrose (ACD) solution and Citrate phosphate dextrose adenine (CPDA-1)
o Chelates calcium
o Preserves blood for 3 to 4 weeks (ACD)
o 6 weeks (CPDA-1
✓ Antiplatelet Drugs
o Inhibit platelet activity (thromboxane)
o Thus, inhibit clotting
Aspirin – prevent thromboembolism associated with:
o Heartworm treatment in dogs
o Cardiomyopathy in cats
4b. HEMOSTATICS
o Substances that promote blood clotting
o Two categories (based on mode of administration) – T & P
✓ Topical hemostatics
Mechanism of action
o Providing a framework in which a clot may form: absorbed after clot formation
▪ Gelatins
▪ Collagens
o By coagulating blood protein to initiate clot formation
▪ Styptics
▪ Hemostatic powders
▪ Hemostatic solutions
Clinical Uses
o Control capillary bleeding
o Surgical Sites
o Superficial Wounds
Adverse Side Effect
o Minimal
o Delayed wound healing
✓ Parenteral hemostatics – do not directly activate clotting; thus anticoagulant antagonists
Mechanism of Action
- Promote the synthesis of clotting factors depleted during poisoning or disease
- Not used to control surgical or traumatic bleeding
Preparations
Protamine sulfate
• Source - Sperm or testes of salmon of related species
• Clinical uses - Heparin toxicity
• Adverse side effects: Hypotension; Bradycardia
Vitamin K (Phytonadione)
o Necessary for the production of the following factors in the liver
o Factor II (Prothrombin)
o Factor VII (Proconvertin)
o Factor IX (Plasma thromboplastin component)
o Factor X (Stuart factor)
o Response is not immediate
o Adverse Side Effects: Anaphylactic reactions (IV); bleeding at injection site
Aminocaproic Acid
- inhibits fibrinolysis through its effects on plasminogen activator and possibly via antiplasmin activity.
It may be used to inhibit bleeding in certain conditions like thrombocytopenia. It is contraindicated in
patients with active intravascular clotting.
4c. FIBRINOLYTIC (THROMBOLYTICS) DRUGS
- Used to break down or dissolve thrombi
- Stimulates conversion of plasminogen to plasmin
Clinical Uses
- Treatment of pulmonary embolism
- Treatment of arterial thrombosis and emboli
- Treatment of coronary thrombosis
- Intravenous catheter clearance
Preparations
- Streptase, streptokinase
- Abbokinase, urokinase
- Activase, alteplase
Adverse Side Effects – Bleeding episodes
MODULE 4: DRUGS ACTING ON THE DIGESTIVE SYSTEM

- Gastrointestinal tract therapy
- Digestants
- Anti-ulcers
- Antiemetics
- Emetics
- Laxatives and cathartics
- Antidiarrheal drugs
- Appetite stimulants
- Oral products
Anatomy and Physiology Review
GASTROINTESTINAL TRACT THERAPY
• Correction of fluid and electrolyte balance: fluid therapy
o Prolonged vomiting and diarrhea
▪ Dehydration
▪ Electrolyte loss
▪ Disturbances in acid-base balance
o Severe vomiting -> metabolic acidosis because acids of GIT can be evaded as
vomiting/diarrhea
▪ Loss of sodium, chloride, potassium, hydrogen and bicarbonate
o Pyloric obstruction -> metabolic alkalosis
• Ensure rest of the gastrointestinal tract
o Acute gastrointestinal disturbances (vomiting and diarrhea): fasting 24-48 hrs
o Fasting
▪ Decreased gastric secretion
▪ Increased time for mucosal healing
▪ Fewer osmotically active particles in the gut lumen.
• Diet modification
o Bland diet
▪ Easily digested (soft foods) to provide immediate food na di na kailangan sa pet mu
exert ug energy
▪ Low-fat
• Unabsorbed fatty acid: hydrolxylated by colonic bacteria -> increases fecal
water loss
o Decreased absorption
o Decreased water absorption
▪ Offered after 24-48 hrs of fasting
o Lactose-free diet
▪ For animals with lactose intolerance
▪ Loss of mucosal brush border lactase due to invasive enteritis
o Insoluble fiber
▪ Absorbs water -> normalize intestinal transit
▪ Treatment of
• Constipation
• Chronic diarrhea
• Idiopathic colitis
o Gluten-free fiber
▪ Gluten-sensitive enteropathy is seen in some breeds of dogs (Irish setters)
- Provision of nutritional support
o Calories
o Proteins
o Vitamins
That are easily digested gihapon or grinded
- Alleviation of visceral pain
o Mild visceral pain
▪ Protective or absorbants
• Decrease gastric acidity
• Coating the inflamed mucosae
• Absorbing noxious agents
▪ Ex. Bismuth containing substance (Bismuth Subnitrate)
o Severe visceral pain
▪ Opiates
▪ NSAIDS
▪ Sedatives
APPETITE STIMULANTS or Gastrointestinal Prokinetics / Stimulants
- inappetent – way gana mukaon
- Enteral alimentation with liquid supplements feeding tubes
- Small amounts of palatable food (warm especially for carnivores liver spread, royal canin
- Drugs for inappetent animals
o Benzodiazepines (Diazepam, oxazepam)
o Cyproheptadine
o Glucocorticoids (Prednisolone, dexamethasone)
o Bitters
o Zinc – immune and appetite stimulant element
o Abdo – dry gall bladder
- Preparations
o Diazepam
o Oxazepam
o Increase GABA Activity
▪ Antiserotogenic effect
▪ Depresses the satiety center (hypothalamus)
▪ Mukaon na siya kay di man siya busog
- Therapeutic uses
o Short term stimulation of appetite
▪ Cats- most frequently
▪ Less in dogs, horses, and goats
▪ Diminishing effects: after 2 to 3 treatments
- Administration: oral, IM, IV
o Sedation
o Ataxia
Appetite stimulant: Cyproheptadine
o Acts as a serotonin and histamine1 (H1) antagonist
o Suppress the satiety center in the hypothalamus
- Therapeutic use: In cats and humans (not in dogs)
o CNS excitement
o Aggressive behavior in cats (20% of those administered.
Appetite stimulant: Glucocorticoids
- Preparations
o Prednisolone
o Dexamethasone
o Glucocorticoid- induce euphoria
- Administration
o IM: small and large animals
o Immunosuppression
o Gastric ulcers: decreased gastric mucus production
Appetite stimulant: Bitters
- Contains alkaloids (Nux vomica) by active bitter compound of plant
o Stimulate salivation
- Therapeutic uses
o Seldom used
o Component of tonics for appetite stimulation in large animals
Appetite stimulant: Zinc
- For the sensation of taste
- Increase appetite in zinc deficient animals
- Can boost immunity together with Vit C
ANTIULCER MEDICATIONS
- Gastric ulcer may occur in animals through:
o Stress
o Metabolic disease
o Gastric hyperacidity
o Drug therapy (corticosteroids or NSAIDS)
o Increased gastric acid production (most cases)
- Five classes of drug most commonly used to treat gastric ulcers:
o H2 receptor antagonist H2 blockers
o Proton pump inhibitors
o Antacids
o Gastromucosal protectant
o Prostaglandins E1 analogs
H2 Receptor Antagonists / Histamine2 (H2) - blockers
- Block H2 Receptors
- Reduce hydrochloric acid in the stomach
o Decrease irritation of eroded mucosa
o Promotes healing of ulcers
- Preparations
o Cimetidine
o Ranitidine
o Famotidine
o Nizatidine
- Structurally similar to histamine
o Competitively block the H2 receptors on parietal cells -> decrease hydrochloric acid secretion
- Pharmacokinetics
o Absorption: well-absorbed by the GIT
o Fate: Widely distributed in body tissues; 50% metabolized in the liver
o Excretion: Kidney (parent drug and metabolites)
- Therapeutic uses
o Dog and cats
▪ Gastritis
▪ Gastric ulcers
▪ Esophagitis
▪ Gastrinomas
o Horses: Gastritis and gastric erosions
- Administration
o Cimetidine: PO, IM, IV Tablets (Tagamet) 100, 200, 300, 400, and 800 mg Oral solution
(Tagamet) 60 mg/ML Injectable (Tagamet)
o Ranitidine: PO, IM, IV tablets (Zantac) 75, 150, and 300 mg Oral syrup (Zantac) 15 mg/mL,
Injection (Zantac) 25 mg/mL
o Famotidine: IV, PO, Film-coated tablet) Pepcid or Pepcid AC) 10,20, 40 mg Oral powder
(Pepcid) Injection (Pepcid IV)
- Drug interactions
o Cimetidine: inhibits hepatic microsomal enzymes, slowing the metabolism of drugs requiring
hepatic metabolism
o Ranitidine: little effects on hepatic microsomal enzymes
o Famotidine: Fewer drug interaction compared to the first two; less bioavailability
Proton-pump inhibitors
- Preparations: Omeprazole and Lansoprazole
o Reduce hydrogen secretion by inhibiting H+ -K+ -ATPase pump on the luminal membrane of
parietal cells
- Pharmacokinetics
o Absorption: good- oral
o Omeprazole: metabolized by hepatic microsomal enzymes
o Fate: protonated when inside parietal cells
▪ Active form
o Excretion: Kidneys
- Therapeutic uses
o Dogs, cats, and horses
▪ Gastritis
▪ Gastric ulcers
▪ Esophagitis
o Prevention and treatment of gastric erosions by NSAIDs
- Administration: Oral
- Drug interaction
o Inhibit hepatic microsomal metabolism
o Prolong the action of drugs requiring hepatic metabolism
- Preparation: Oral
- Dosage form
o Omeprazole oral sustained- release capsule (Prilosec), 10 and 20 mg
o Omeprazole (Losec) Canada
o Omeprazole Oral Paste
o Gastrogard (Equine Product)
o Lansoprazole (Prevacid)
Antacids
- Non-absorbable salts of aluminum, calcium and magnesium
o Used to decrease hydrochloric acid levels
o Treat rumen acidosis
o Chelate intestinal phosphorus and reduce hyperphosphatemia (patients with renal failure)
- Preparations
Veterinary Prep
o Magnesium hydroxide (Magnalax)
Human Prep
o Magnesium oxide (milk of magnesia) Human prep
o Aluminum hydroxide
o Aluminum carbonate
o Aluminum silicate
- Therapeutic uses
o As adjunct to H2 – blockers or proton pump inihibitors to treat gastric and duodenal ulcers
o Small animals: Nonspecific therapy of
▪ Acute gastritis
▪ Gastroenteritis
o Treatment of hyperphosphatemia
▪ Increases decal excretion of phosphate
o Rebound HCl secretion
▪ With magnesium salts (raising gastric pH to 7)
o Constipation
▪ Aluminum salts
▪ Combined with laxatives to avoid constipation
o Impaired absorption of other drugs: those administered orally
- Contradictions
o CNS depression: magnesium salts
▪ Do not use in the presence of renal disease
▪ Excretion: Kidneys
Gastromucosal Protectives
- Preparations
o Sucralfate: sucrose sulfate-aluminum hydroxide complex ONLY
o Polymerizes to m=viscous gel at pH less than 4
o Sulfate group
▪ Binds to proteins in ulcerated tissue
▪ Protect ulcers from acid and pepsin
- Therapeutic uses
o Gastric and duodenal ulcers
▪ Dogs
▪ Cats
▪ Foals
o Constipation: long-term therapy
Prostaglandin E-1 Analogs
- Directly inhibits the parietal cell form secreting hydrogen ions
- Protects gastric mucosa by increasing the production of mucus and bicarbonate
- Clinical Uses
o Prevention of gastric ulcers associated with NSAIDs use
- Dosage form
o Mitoprostol oral tablets (Cytotec) 100, 200 g.
- Adverse Side Effects
o Diarrhea, Vomiting, flatulence and abdominal pain, abortion (be careful sa pregnant)
DIGESTANT – aid in digestion OR digestive enzymes
Pancrelipase
- Composed of pancreatic enzymes
o Lipase
o Amylase
o Trypsin
- Therapeutic uses
o Exocrine pancreatic insufficiency in
▪ Dogs
▪ Cats
▪ Birds
- Administration
o Powder preparation: oral, mixed with food
o Enteric-coated preparations or pre-treatment with H2-blockers -> prevents destruction by
gastric HCl
DIGESTANTS: Bile acids and Salts
- Preparations
o Bile acids
▪ Cholic acid
▪ Chenodeoxycholic acid
o Semisynthetic bile acid derivatives
▪ Dehydrocholic acid
o Sodium salts of bile acids
o Bile acids: stimulate choleresis (bile flow)
o Bile salts: Emulsify dietary lipids
▪ Enhance fat digestion
▪ Enhance absorption of long chain fatty acids
o Therapeutic uses
▪ Maldigestion syndromes characterized by steatorrhea (fats in feces)
• Pancreatitis
• Bile salt deficiency
EMETICS
-
- General considerations
o Triggered by the vomiting center due to central or peripheral stimulation from
▪ Chemoreceptor trigger zone (via dopaminergic input)
▪ GIT (via vagal and sympathetic afferent pathways)
▪ Vestibular apparatus (via cholinergic and histaminergic afferent pathways
o Vomiting reflex
▪ Developed in
• Carnivores
• Primates
• Swine
▪ No vomiting reflex: do not administer emetics
• Horses
• Rodents
• Rabbits
- Indications
o In conscious individuals, removes ~80% of stomach contents
▪ To remove noncorrosive poisons
▪ Prior to induction of anesthesia
1. Centrally acting emetic
a. Apomorphine – class II controlled substance
▪ Mechanism of action
• Stimulate CRTZ
• Not effective in swine
▪ Administration
• IV: do not give second dose, CRTZ becomes depressed
• IM, SC, Conjunctival routes
▪ Adverse side effect: excitement in cats (do not use in this species!)protracted
vomiting, restlessness, depression
b. Xylazine also pre-anesthetic agents
▪ Administration: IV or IM
▪ Vomiting is induced within 3-5 minutes in cats; occasionally dogs
▪ Sedation may follow for 30-90 minutes
2. Peripherally / Locally acting emetic
- Preparations
o Sodium chloride (crystals or solution)
o Syrup of ipecac (emetine alkaloids) -cardiotoxic drug if in high doses
o Copper sulfate (1%)
o Zinc sulfate (1%)
o Hydrogen peroxide (3%) – primary agent
o Mustard and water
o Syrup of ipecac
o Warm salt water
o Stimulate sympathetic and vagal afferent receptors in the pharynx and stomach
- Therapeutic uses
o Sodium chloride: Induce vomiting in cases of poisoning (dogs)
o Syrup of ipecac
▪ Induce vomiting in 15-30 minutes
▪ Commonly used in human medicine
- Administration
o Oral, single dose (!)
- Adverse effect for ipecac
o Cardiotoxicity, lacrimation and salivation
ANTIEMETICS – parvovirus na mu induce ug vomiting

o Prolonged vomiting (metabolic alkalosis)
▪ Electrolyte imbalance
▪ Acid-base imbalance
▪ Dehydration (death if condition progresses)
o Cause of vomiting should be known before an antiemetic is administered (if dog has
swallowed something since it will obstruct)
o Symptomatic treatment
- Most frequent causes of prolonged vomiting
o GIT
▪ Inflammed
▪ Distended
▪ Contains poisonous substances or drugs
o Labyrinthine disease or motion sickness (donamine for humans)
o CNS
▪ Edema
▪ Inflammation
▪ Tumors
o Stimulation of the CRTZ
▪ Drugs
▪ Bacterial endotoxins
▪ Toxic endogenous metabolites (urea)
1. AE: Phenothiazines Derivatives
• Preparations
1. Chlorpromazine
2. Prochlorperazine
3. Acepromazine
• Mechanisms of action
1. Block dopamine receptors in the CRTZ
2. High doses: block dopamine in the vomiting center
ANTIEMETIC: Antidopaminergic Phenothiazines

- Pharmacokinetics
o Absorption: well absorbed orally
o Fate: widely distributed to tissues; metabolized by the liver (glucuronide or sulfate
conjugates)
o Excretion: kidneys
- Therapeutic uses
o Dogs and cats
o Limited effectiveness if cause of vomiting is severe inflammation of the GIT or inner ear
- Administration
o Oral or IM
o Hypotension and bradycardia: alpha-adrenergic blockade
o Mild sedation
- Dosage Forms
o Chlorpromazine tablets (Thorazine), various sizes
o Chlorpromazine extended-release capsules (Thorazine Spansule), various sizes
o Chlorpromazine oral solution (Thorazine), 2 mg/ml, 30mg/ml, and 100mg/ml
o Rectal suppositories (Thorazine), 25 mg and 100 mg
o Chlorpromazine injection (Thorazine), 25mg/ml in ampules and vials
o Prochlorperazine- injection, oral syrup, sustained release capsules and suppositories
(Compazine)
o Prochlorperazine/isopropamide – injectable and capsule (Darbazine)
ANTIEMETIC: Antidopaminergic Metoclopramide (common)
o Central action: blockade of dopamine receptors in the CRTZ
o Peripheral action: stimulation of the stomach and doudenum motility
▪ Increased smooth muscle sensitivity to ACh
- Pharmacokinetics
o Absorption: rapid through GIT
o Fate:
▪ first-pass effect is needed
▪ 50-70% bioavailability
▪ Widely distributed to tissues
o Excretion: urine- conjugated and unchanged
- Therapeutic uses
o Severe vomiting in cats and dogs
o Dogs, cats and foals
▪ Gastric motility disorders
▪ Esophageal reflux
▪ Parvoviral infection
▪ Uremic vomiting
▪ Chemotherapy associated vomiting
- Administration
o PO, SC, IM
o Prior to feeding (tx of gastric motility disorders and esophageal reflux)
- Dosage forms
o Metoclopramide HCl tablets (Reglan), 5 and 10 mg
o Metoclopramide HCl oral solution (Reglan), 1mg/ml in containers of various sizes
o Metoclopramide HCl injection (Reglan) 5 mg/ml
o Gastric hemorrhage or perforation (X gastric outlet obstruction)
o Behavioral changes
ANTIEMETIC: Antidopaminergic Butyrophenones
- Preparations
o Droperidol
o Haloperidol
o Pimozide
o Capable of blocking the CRTZ and the vomiting center
- Pharmacokinetics
o Absorption: well absorbed by the GIT
o Fate: not been studied in animals
- Therapeutic uses: motion sickness in dogs
- Administration: oral
- Adverse side effect
ANTIEMETIC: Anticholinergic agents
- Preparations
o Aminopentamide hydrogen sulfate
o Propantheline
o Block cholinergic pathways from the GIT to the vomiting center
o Reduced GI spasms, intestinal motility, and intestinal secretions.
- Therapeutic uses: Treat vomiting and diarrhea
- Administration: PO, IM, SC
o Xerostomia
o Xerophthalmia
o Loss of visual accommodation
o Tachycardia
o Urine retention
o Paralytic ileus
o Constipation
- Contraindications: patients with glaucoma
- Dosage forms
o Aminopentamide hydrogen sulfate tablets (Centrine), 0.2 mg
o Aminopentamide hydrogen sulfate injection (Centrine), 0.5 mg/ml, 10-ml vials
o Propantheline bromide tablets, 7.5 and 15 mg (Pro-Banthine)
o Aminopentamide hydrogen sulfate injection (Centrine), 0.5 mg/ml, 10-ml vials
ANTIEMETIC: Antihistamines
- Trimethobenzamide HCl
- Dimenhydrinate
- Diphenhydramine
- Meclizine
- Promethazine
- Mode of Action -
o - Block vomiting at the level of CRTZ
- Therapeutic use
o Most effective in motion sickness or inner ear abnormalities in dogs and cats
- Adverse Effect
o Sedation
- Dosage Forms-
o Trimethobenzamide HCl (Tigan)
indicated for dogs only
o Dimenhydrinate (Dramamine)
for motion sickness in dogs and cats (tablet, liquid and injectable)
o Diphenhydramine (Benadryl) tablet, capsule, oral elixir and injectable forms
o Meclizine (Antivert)
o Promethazine (Phenergan)
LAXATIVES AND CATHARTICS

o Relief of acute non-dietary constipation
o Removal of poisons from the GIT
o Prevention of tenesmus (utong) in advanced pregnancy or prolapse
o Evacuation of the bowel prior to surgery or radiography
LAXATIVES AND CATHARTICS: Osmotic cathartics or SALINE/HYPEROSMOTIC AGENTS

- Preparations
o Magnesium sulfate (Epsom salt), magnesium oxide (horses and birds)
o Sodium sulfate (Glauber’s salt)
o Sodium phosphate and sodium tartrate sodium (Fleet enemas) dogs and foals
o Osmotically retain water in the intestinal lumen
o Rapid onset of action
- Therapeutic use: cathartic of choice for the removal of poisons
- Administration
o Oral
o Rectal
LAXATIVES AND CATHARTICS: Irritant cathartics
- Preparations
o Castor oil
o Aloe
o Senna
o Cascara sagrada
o Castor oil: results in the formation of irritant ricinoleates after cleaved by the pancreatic
lipases- stimulate peristalsis and reduce fluid absorption
o Others: irritant anthraquinones
▪ Stimulate smooth muscle and increase colonic motility
- Therapeutic use
o Relieve acute constipation in small and large animals
LAXATIVES AND CATHARTICS: BULK-PRODUCING AGENTS
- Preparations
o Methylcellulose
o Agar
o Psyllium
o Wheat bran
o Contain hydrophilic colloids- absorb water and increase bulk- stimulate large bowel
peristalsis
LAXATIVES AND CATHARTICS:
- Lubricants: mineral oil (liquid petrolatum) and white petrolatum
o Lubricate and soften feces
- Surfactants or Stool softeners
o Docusate
o Hydrate and soften feces through emulsifying action
ANTIDIARRHEAL DRUGS
- Indications
o Symptomatic therapy for acute diarrhea
- Oral rehydration therapy
AD: OPIATES / NARCOTIC ANALGESIC
- Preparations
o Paregoric: camphorated tincture of opium
o Diphenoxylate
o Loperamide
o Codeine
o Inhibit ACh release
o Directly stimulate absorption of fluid and electrolytes
- Therapeutic use: symptomatic treatment of acute diarrhea
o Bacterial overgrowth: slowed intestinal transit time
o Cats: excitation
o constipation
AD: ANTICHOLIGERNICS or ANTISPASMODICS
- Preparations
o Methscopolamine
o Aminopentamide
o Propantheline
o Isopropamide
o Inhibit propulsive and nonpropulsive GIT motility
o Inhibit GIT secretions
- Therapeutic uses
o Diarrhea treatment
o Gastrointestinal spasm
- Administration: oral, IM, SC
- Adverse side effects: same as anticholinergic as antiemetic
AD: PROTECTANT AND ADSORBENT AGENTS
- Preparations
o Kaolin-pectin suspensions
o Bismuth salicylate
o Adsorb toxins
o Provide coating on inflamed mucosa
o Bismuth salicylate- anti-PG effect to mucosa
MODULE 5: FLUID THERAPY AND CHEMOTHERAPY

• Review on fluid physiology!
– Fluid compartments
– Water metabolism: kidneys; ADH
– Dehydration
– Major extracellular fluid cation/ anion
– Major intracellular fluid cation/ anion
– Osmotic vs hydrostatic pressure
– Acid-base balance
Body Fluid Compartments:
Movement of Fluid between compartments:
Composition of Plasma and Interstitial Fluid:

Fluid therapy
• Diseases are often characterized by acid-base balance and fluid disturbances
• There is a need for parenteral or oral fluid and electrolyte replacement, in severe cases
• Dehydration: loss of water and electrolytes
Osmolarity
– Expressed as the number of milliosmols per kilogram/ liter of fluid
– Made up of from all the particles in solution
– Each molecule or ion contributes 1 mOsm
– Isotonic: 300 mOsm per litter of body fluid
– Hypertonic: >300 mOsm
– Hypotonic: < 300 mOsm
Tonicity
• Expressed in milliosmols
• Measures the concentration of dissolved particles in the body fluids
Osmotic Effects of Fluids:
• Hypertonic solution
o Intracellular fluid (fluid inside cells) will go out
o plasma or outside of cell has more non peritable solutes
• Isotonic
o Balanced inflow and outflow of water
• Hypotonic
o Nonperitable solutes present in plasma is lesser than the inside of cell
o Fluids go inside cell
Acid-base balance:
• Important since chemical and metabolic reactions of the body that is controlled by enzymes are influenced by
small changes in pH
• Blood pH: 7.35 – 7.45, ave: 7.4
• Death: below 6.8 or above 7.8
• Replenish acid-base balance before it’s too late for the animal
• Balance depends on the ratio between bicarbonate and carbonic acid in the blood – metabolic, respiratory
alkalosis & acidosis
• Carbonic acid: controlled by respiration (resp. acidosis)
• Bicarbonate: controlled by renal and non-respiratory processes
Acidosis:
• Causes
– Loss of bicarbonate ions into the feces by intestinal secretion
– Common in cases of severe deliberation
– Build-up of lactic acid produced in under perfused tissues
– Production of organic acids by an abnormal gut flora
– Depressed renal excretion of hydrogen ions and reduced regeneration of bicarbonate in the kidney
• Two pathogenic mechanisms causing metabolic acidosis
– Loss of bicarbonate-rich secretions
– Endogenous production of excess organic acids
• Ketoacids
• Lactic acid
• Uremic acids
Metabolic Acidosis:
• Conditions resulting in metabolic acidosis
– Diarrhea with considerable losses of bicarbonate, sodium and potassium ions
– Intestinal obstruction leading to sequestration of ions in the lumen of the gut
– Inadequate tissue perfusion (hypoxia) leading to the production of acid metabolites
– Renal disease or inadequate renal perfusion (severe shock), hydrogen ions are retained
– Increased production of acid metabolites
• Myositis
• Starvation
• Severe infection
Respiratory Acidosis:
• Due to inadequate alveolar exchange resulting in retention of carbon dioxide; may also be due to
– Anesthesia
– Inadequate ventilation
– Increased dead space
– Obstructed airway
– Lung pathology
• Congestion
• Pneumonia
• Emphysema
Metabolic alkalosis:
• Low serum chloride; high serum bicarbonate values
• Conditions that result in metabolic alkalosis
– Vomiting
– Displacement or torsion of the abomasum/ stomach
– Atony or impaction of abomasum
Fluid therapy:
• Disturbance of the different parts of the digestive system results in different conditions
• Therefore, fluid therapy to be given must be different for every clinical case
6 questions to consider in fluid therapy

• When should fluid therapy be given?
• What solution(s) to administer?
• How much of the solution(s)
• What is the infusion rate?
• Which route of administration to use?
• How is success evaluated?
ACIDEMIA – DISEASE
• Corrected by administering
- Bicarbonate ions
o Sodium bicarbonate: most economical
▪ Readily available
▪ Consistent alkalinizing effect
o Bicarbonate precursors, salts of weak organic acids
▪ Lactate and acetate
• Poorly metabolized
• Less effective
▪ Gluconate
▪ Citrate
Fluid Therapy:
• Administration of fluids alone will not completely correct the condition; very true when there is an
underlying disease already; needed symptomatic therapy and antibiotics; antiemetics; antidiarrheal or
antiviral
• Electrolyte should be supplemented
• Bicarbonate solutions (PO) sometimes inappropriate
– Raises the pH of the stomach
– Destroys natural barrier of the stomach against infection
• Administration of citrate for acedemia
– Converted to three bicarbonates in the liver
– Advantage of citrate: dual function
• Stimulate water and sodium absorption at cell surface
• After absorption, citrate metabolized to form ATP for sodium transport; add
bicarbonate for acidosis correction
Evaluation of dehydration:
• 6% water loss: symptoms of dehydration are seen – less turgor of skin; sunken eyes; dried mucous membrane
• 8-9% : collapse
– Loss of blood volume → reflex release of aldosterone → kidneys conserve water and sodium (at the
expense of potassium) RAS phenomenon in conserving water – increases blood volume and blood
pressure (persistent loss of blood volume – cannot be compensated by RAS)
– Other effects of aldosterone
Water reabsorption in the colon
– There is hemoconcentration results in
Impairment of tissue perfusion
If brain is affected and there is inadequate oxygenation → death
Means on assessing the degree of dehydration

Consideration of the body weight
❖ 70% of the body is water (lesser in obese/ fat animals; higher in younger animals)
❖ Change in body weight reflects fluid status
Clinical signs exhibited by the animal
❖ 5% dehydration
• Animal is thirsty and drinks readily
• Dull eyes
• Cold skin and extremities
❖ 10% dehydration
• Lifeless
• Unwilling to stand; lethargic (tired)
• Body warm, extremities are cold
• Skin begins to lose elasticity
• Rectal temperature rises
❖ > 10% dehydration (critical condition)
• Circulation worsen
• Cold extremities and mucous membrane
• Eyes Sunken
• Dry and dull corneas
• Comatose
• Wet area around the mouth
❖ Definite clinical signs
Degree of dehydration Clinical signs
0-5% Little clinical change
7% Loss of skin elasticity
(contraction of lubricating ECF)
Dry mouth; Injected conjunctivae
Eyes dry and sunken
Reduced urine volume
10% Hidebound
Apparent loss of weight
Cold; Weak
Unable to stand
Pale mucous membranes
Decreased temperature
Sluggish capillary refill time
(hypovolemia)
Weak pulse
Minimal urine formation
Concentrated urine
12% - FLUID THERAPY! Recumbent; Weak pulse
this will lead to death Rapid shallow respiration
Unable to sit up unassisted
Body weight loss
Muscle tremors
Subnormal temperature
Hypovolemia; Shock
Circulatory failure
Use of certain laboratory aids
• Hematocrit
– Most direct indicator
– Compare hematocrit readings between the affected animal and that of another animal of same age and
breed
– PCV (packed cell volume) increases with dehydration since less body fluids
– Important to know the normal PCV range and average of animals (!)
– ! Concurrent anemia may masked dehydration
• Plasma protein levels
– Values above normal is an indication of dehydration
• Urine specific gravity
– Increased SG (because of ADH – vasopressin
• Plasma electrolyte concentration
• Blood gas analysis
• Plasma potassium levels
Dehydration: Therapy
• Four phases
– Correction of life-threatening hypovolemia (decrease in blood volume due to loss of body fluids)
– Restoration of accumulated deficits of fluids and correction of electrolyte and acid-base balance
disturbances (loose stool, small vomiting/emesis episodes)
– Provision of sufficient fluids and electrolytes to meet continuing losses each day
– Meeting the normal daily requirements
Fluid solutions: Temperature should be close to body temperature

• Classification
– ECF replacers
• Hartmann’s
• Ringer’s lactate
– ECF acidifiers
• Normal saline (bicarbonate-free)
• Dextrose-saline (hypertonic)
• Ringer’s solution
– ECF alkalinizers
• Lactated Ringer’s
• Hartmann darrow’s
• 1.3% sodium bicarbonate
– ECF diluent
• 5% dextrose
– Maintenance solutions
• N/5 Saline (0.18%) + 4.3% dextrose (isotonic)
– Composite/ nutrient fluids
• Glucose
• Amino acids
1. Normal saline (isotonic saline -0.9% sodium chloride)

• Same osmolarity with ECF
• Useful in most cases of replacement therapy
• May act as ECF acidifier (no bicarbonate)
• Useful in cases of metabolic acidosis (diarrhea)
2. Isotonic dextrose-saline (0.18% sodium chloride [N/5 saline] + 4.3% dextrose)

• Isotonic
• Good for maintenance therapy
– Low sodium and energy content
3. 5% dextrose
• Isotonic
• Contains water and glucose
• Good for hypertonic dehydration due to
– Heat stroke
– Water deprivation
• Poor source of energy; but can reverse temporarily hypoglycemia
4. Compound sodium lactate (Hartmann’s solution, Ringer’s lactate)
• Universal replacement solution
• Isotonic
• Good for treating metabolic acidosis
• Good as initial therapy for
– Gastrointestinal problems (diarrhea, vomiting)
– Hemorrhage
– Burns
5. Darrow’s solution
• Contains
– 0.4% sodium chloride
– 0.27% potassium chloride
– 0.58% sodium lactate
• Contains more K than lactated Ringer’s
• Good for metabolic acidosis
– Diarrhea
– Potassium loss
6. Dextrose saline (0.95 sodium chloride + 5% dextrose)
• Hypertonic solution
• Therapeutic uses
– Emergency treatment of dehydration
– Immediate treatment of hypoglycemia
7. Sodium bicarbonate
• For severe acidosis
8. Whole blood
• For reversing blood loss associated with anemia
• First time is usually successful
• 2nd transfusion- possible reactions due to mismatching
9. Plasma expander:
Dextran
• Derived from glucose polysaccharide
• Expensive but effective in cases of hemorrhage or shock with loss in blood osmotic property
• Formulation in different molecular weights: 40, 70, 110, 150
• Infused at a rate of 10-20mml/kg in 24 hrs
• May impede clotting and blood matching
Gelatin colloidal solution
• Plasma substitute
• Isotonic
• From degraded gelatin with sodium, potassium, calcium, sulfate, phosphate ions, water
• Less expensive than dextran
• >20 ml/kg every 12 hrs
• Good for
– Hypovolemic shock
– Burns
– Blood loss
– Diarrhea
Infusion rate
• Rate is based on severity of dehydration
• Usually rapid at first and gradually slowed down till recovery
• Too fast- fluid overload – detrimental to patients
• Usual rate is at 13-14 ml/kg/hr or 15 ml/kg/hr
– For the first 40-60 mins or
– Until urine flow is restored
• After urine flow restoration- 10 ml/kg/hr
• Reduce by 1/3 if no urine flow after 60 mins- 9 ml/kg/hr
Fluid administration
• Common sense and clinical judgment are important
– Severe dehydration? Severe shock?
– Almost normally dehydrated?
– To check if kidneys (GF) are working- injection of 50% glucose; check urine every 5 minutes for the
presence of glucose (glomerular filtration)
Route of administration
• Depends on
– Type and severity of disease or condition
– Degree of dehydration
– Patient’s condition
– Type of electrolyte imbalance
– Organic functions of the patient
– Time and equipment available
Oral or NG
• Easiest
• Most physiologic
• Most overlooked
• Least dangerous- tonicity, volume and sepsis
Per rectum
• Can be done in young animals
• Warm solution are well absorbed
• Difficult for the animal to retain when there is GI problem
Parenteral routes
• Most common and most practical
– Intravenous
– Subcutaneous
– Intraperitoneal
Intravenous
• Most versatile
• For severe fluid and electrolyte imbalance
• Toxicity is related to rate of infusion
• Not indicated for hypotonic solutions
• Problems associated
– Maintenance and asepsis in indwelling catheters
– Clotting
– Hematomas
– Locating the veins of small or severely sick animals
Subcutaneous
• Also known as hypodermoclysis
• Good for small animals with small fluid volume to be administered
• Rapid and easy to use
• Only for isotonic solutions
Intraperitoneal
• Almost same restrictions with SC route
• May predispose to peritonitis
• Faster than SC but more hazardous (organ puncture)
• Practical for large animals where large volumes are to be infused
• Greatest application if for peritoneal lavage
CHEMOTHERAPY
• The use of antineoplastic drugs to cure or lessen the effect of neoplasms (cancer).
• Other methods to cure neoplasms include surgery, radiation and immune modulation.
Goal of Chemotherapy:
• Keep neoplasia under control
• Increase survival time in animals
• Improve quality of life of the patient
Cancer
• Cells replicate in unlimited way (initiation)
• Form mass of cells (promotion)
• Invade adjacent tissues (progression)
• Undergo five to six genetic mutations (hallmarks)
o Self-sufficiency in the production of cell growth signals
o Insensitivity to antigrowth signals
o Ability to evade programmed cell death
o Unlimited potential to replicate
o Sustained ability to promote angiogenesis
o Capacity to invade tissue and metastasize
How?
• Proto-oncogenes is enhanced through abnormal regulation
• Activation or upregulation of an enzyme telomerase
• Defects in suppressor oncogenes or anti-oncogenes like p53 gene
• Factors like viruses, chemical, physical and hormonal influence contribute to cancer formation
Principles of chemotherapy
• Chemotherapy is most effective against rapidly growing tumors because actively dividing cells are more
sensitive to DNA damage and cell cycle processes.
• Chemotherapy can be directed toward a specific phase of the cell cycle or can be cycle nonspecific
• All rapidly dividing cells are affected by antineoplastic drugs

o Bone marrow
o GIT
o Reproductive organs
o Hair follicles
Uses of chemotherapy
• Treating tumor with known sensitivity to a drug or drugs
• To make cancer cells more sensitive to radiation or other therapy method
• To reduce or eliminate metastasis
• To reduce tumor size for the purpose of relieving pain or improving function
• To reduce tumor size to facilitate surgical removal
Effectiveness of Chemotherapy
Depends on:
• Length of time the tumor is exposed to an effective dose of the drug
• Development of specific resistance to a drug by a tumor
• Dosage and time period of administration
• Maximum tolerated dose (MTD) for shortest time possible base on estimated body surface
• But for less than 10 kg dog and cat dosage is based on body weight rather that SA
• Frequent low dose over a longer time (metronomic method)
CHEMOTHERAPY DRUGS
• Often given in combination to increase their overall effectiveness
• Different tumors are treated with specific combination of drugs at doses, duration and intervals determined by
carefully designed treatment protocols.
• Indiscriminately target rapidly dividing cells and often have high therapeutic index.
• Toxicity is possible and side effects are often seen (GIT and hemopoietic systems)
• Anorexia, nausea, vomiting, and diarrhea soon after treatment (CRTZ) or 3 to 5 days later because of injury to
GIT
• Bone marrow depression (myelosuppression)
• Breeds with continuously growing hair may loss hair (Poodles, terriers, and Old English Sheepdogs)
• Cats may lose their whiskers and guard hairs.
• Cystitis, cardiomyopathy, anaphylactic reactions and tissue damage due to extravasations of the drug/s
(vesicant drugs).
• For vesicant drugs pretreatment of antihistamines, steroids, and for GIT upsetting drugs, pretreatment of
antiemetics and or analgesics are necessary
Antineoplastic drugs:
Classifications:
• Alkylating agents
• Anthracyclines
• Antimetabolites
• Antitubulin agents
• Corticosteroids
• Miscellaneous agents
Alkylating Agents:
• Cell-cycle nonspecific
• Mode of action: Able to cross-link strands of DNA to change its structure and inhibit its replication which
brings protein synthesis and cell division toa halt; cell death often follows.
• Clinical use:
o Treatment of various neoplastic disorders, including lymphoproliferative neoplasms, osteosarcoma,
hemangioma and squamous cell carcinoma.
o Treatment of certain immune-mediated diseases (immunosuppression)
• Dosage Forms:
o Cytoxan, cyclophosphamide injection
o Leukeran, chlorambucil tablets
o Alkeran, melphalan tablets
o Nitrosoureas, lomustin and carmustine
o Dacarbazine
o Ifex, Ifosfamide
• Adverse Effects:
o Neutropenia
o Nephrotoxicity
o Thrombocytopenia
o Vomiting
o Hemorrhagic cystitis
Anthracyclines:
• Derived from soil fungi of genus Streptomyces
• Non-cell-cycle specific
• Mode of action
o Binds with DNA and interfering with RNA and protein synthesis
• Clinical uses:
o Treatment of lympho-proliferative neoplasms and various carcinomas and sarcomas
• Dosage forms:
o Adriamycin, doxorubicin hydrochloride for injection (vesicant)
o Bleomycin
o Dactinomycin
o Mitoxantrone
o Idarubicin
• Adverse side effects:
o Bone marrow suppression, cardiotoxicity (cardiomyopathy), gastroenteritis, and anaphylaxis
Antimetabolites
• Cell cycle-specific
• Affect the S-phase (DNA synthesis)
• Mode of action:
o Analogs of purine and pyramidines (naturally occurring bases in DNA) that may be incorporated into
the DNA molecule to inhibit protein and enzyme synthesis. Cellular function needed for normal
activity are thus blocked.
• Clinical uses:
o Treatment of lymphoproliferative neoplasms, gastrointestinal and hepatic neoplasms and treatment of
CNS lymphoma
• Dosage Forms:
o Methotrexate, oral tablet or injection
o Cytosar-U, cystosine arabinoside injection
o 5-Fluorouracil cream or solution (X in cat)
• Adverse Side Effects:
o Anorexia
o Nausea
o Vomiting
o Diarrhea
o Bone marrow suppression
o Hepatoxicity
o Neurotoxicity
Antitubulin
• Cell cycle-specific, plant alkaloids
• Affect the M-phase
• Mode of Action:
o Inhibit mitosis by binding to microtubular proteins and inhibit formation of the mitotic spindle, thus
suspending mitosis which leads to cell death.
• Clinical Uses:
o Treatment of lymphoproliferative neoplasms, carcinomas, mass cell tumors and splenic tumors
• Origin:
o Alkaloids of periwinkle plant (Vinca rosea, Linn)
o Vincristine and Vinblastine (Vesicants)
• Dosage Forms:
o Oncovin, vincristine sulfate injection
o Alkaban-AQ, vinblastine sulfate for injection
o Paclitaxel, investigational drug
o Navelbine, vinorelbine
• Adverse Side Effects
o Gastroenteritis
o Bone marrow suppression
o Stomatitis
o Alopecia
o Peripheral neuropathy
Miscellaneous Antineoplastics
• Platinum Drugs
• Asparaginase
• Glucocorticoids
Miscellaneous Antineoplastics: Platinum Drugs

• Mode of action:
o Interrupt replication of DNA just like alkylating agents
• Clinical Use:
o Variety of solid tumors including osteosarcoma and carcinomas
• Dosage forms:
o Cisplastin (Platinol)
o Carboplatin (Paraplatin)
o Renal toxicity, nausea, anorexia, vomiting
o Dyspnea, pulmonary edema, and death in cats
o Carboplatin has less nephrotoxicity, nausea and vomiting than cisplatin
Miscellaneous Antineoplastics: Asparaginase

• Most commonly used, cell-cycle specific (G-1)
• An enzyme extracted from E. coli
• Mode of action:
o Acts as catalyst in the breakdown of asparginine, an amino acid required by cancer cells
• Clinical uses
o Usually used in combination protocol because it do not have effect on normal cells
o Used for treatment of lymphoproliferative neoplasms
• Dosage Forms
o Elspar, asparaginase for injection
o Immediate hypersensitivity and gastrointestinal disturbances
Miscellaneous Antineoplastics: Glucocorticoids

• Cell cycle nonspecific
• Mode of action
o Has lympholytic action
• Clinical use:
o Helpful in management of secondary complication of neoplastic disease such as hypercalcemia and
immune mediated problems (thrombocytopenia)
o Used in combination with other antineoplastic drugs
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Diuretics
• General mechanism of action
– Increase urinary excretion of sodium ions and
water
Loop (High-Ceiling) Diuretics
Thiazide Diuretics (Benzothiadiazides)
– Removes fluid that has accumulated in the
Osmotic Diuretics interstitial spaces
Carbonic Anhydrase (CA) Inhibitors
Potassium- sparing Diuretics – Restores normal tissue perfusion and organ
Methylxanthines function
Acidifying Salts (Ammonium Chloride)
Diuretics Diuretics: Proximal convoluted tubule

• Sites of action- act directly on renal tubular
epithelia at specific sites in the nephron • Segment for reabsorption of
Nephron segment DIuretics –Water and sodium (65%)
Proximal convoluted CA inhibitors –Bicarbonates
tubule Osmotic agents
Xanthines –Chloride and potassium ions
Ascending loop of Henle Loop diuretics (passive)
Early distal convoluted Thiazides • Isoosmotic absorption
tubule
Late distal convoluted Potassium- sparing
tubule and collecting duct diuretics 3 4
Diuretics: Proximal convoluted tubule Diuretics: Descending loop of Henle

• However, if there is volume depletion/ fall in • Sodium and chloride ions are not reabsorbed -
BP → RAA system activation→ increase in concentrated in the luminal fluid
sodium and water retention
• Fluid is hypertonic
• Na+- H+ antiport = hydrogen ions are
exchanged with sodium ions
5 6
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Diuretics:
Diuretics: Distal convoluted tubule
Thick portion of the ascending loop of Henle
• 25% of filtered sodium • Transported out of the • Diluting segment
is reabsorbed lumen • 10% of filtered sodium is reabsorbed
– Sodium • Sodium – chloride symport
• Tubule is impermeable – Potassium
• Calcium reabsorption is influenced by
to water – Chloride
parathyroid hormone
• Epithelium is impermeable to water → further
• Passively reabsorbed
• Luminal fluid is dilution of urine
hypotonic – Calcium
– Magnesium
7 8
Diuretics:
Late distal tubule and collecting duct
Diuretics: Therapeutic uses
• Prevention and treatment of edema or
• 4% of filtered sodium is reabsorbed
severe local edema
– Generalized edema – Localized edema
• Potassium and hydrogen are secreted
• Congestive heart • Cerebral,
failure pulmonary,
• Sodium absorption and potassium excretion- • Liver disease ocular,mammary
action of aldosterone • Due to infection,
• Renal disease
• Protein-losing inflammation,
• Water is reabsorbed if there is antidiuretic trauma or
enteropathies
hormone poisons
9 10
Loop (High-Ceiling) Diuretics:

Loop (High-Ceiling) Diuretics
Mechanism of action
• Preparations • Inhibit electrolyte reabsorption: calcium and
– Furosemide- magnesium in the thick ascending loop of
• most commonly used in veterinary medicine Henle
• Also known as frusemide
– Bumetanide
• Inhibit sodium-potassim-chloride cotransport
– Ethacrynic acid
at the luminal surface of the epithelial cell
– Reduced electrolyte reabsorption
11 12
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Loop (High-Ceiling) Diuretics: Loop (High-Ceiling) Diuretics:

Mechanism of action Pharmacokinetics
• Diuretic action is • Absorption
dependent on pH – Well absorbed orally
• Diuretic effect is achieved in 5 minutes after
administration
• Increase venous • Fate
capacitance – Actively secreted into the urine
– Stimulation of – Rapid onset of action: readily reach the loop
prostaglandin – Peak diuresis is greater compared to other diuretics
production of JG • Excretion
apparatus – Excreted unchanged (80%); glucuronide (20%)
13 14

Therapeutic uses Therapeutic uses
• Drug of choice for the rapid mobilization of • Drug of choice for the rapid mobilization of
edema in all species edema in all species
– Small animals – Cattle- udder edema
• Congestive cardiomyopahty – Race horses: exercise-induced pulmonary
• Pulmonary edema hemorrhage (EIPH)
• Hypercalcuric nephropathy and hypercalcemia • Inreased blood vessel capacitance
• Uremia • Decreased left atrial pressure
• Adjunct therapy in hyperkalemia
• Antihypertensive drug
15 16
Check Veterinary
Loop (High-Ceiling) Diuretics: Loop (High-Ceiling) Diuretics: Pharmacology books
for the dosage rates
Therapeutic uses Administration for particular species!
• Combined with osmotic diuretics (mannitol) • Oral and intravenous- • Exercise-induced

– Maintain urine flow: oliguria and acute renal increases urinary hemorrhage: prior to
failure calcium secretion race (1-2 hrs)
• Treatment of oliguric • Treatment of

renal failure: IV at hypercalcemia: IV
hour intervals until with potassium
diuresis occurs chloride
17 18
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Adverse side effects Adverse side effects
• Lower doses should be given to cats • Deafness and renal toxicity
• Fluid and electrolyte imbalance – If administered with ototoxic drug (aminoglycoside)
– Hypokalemia (with corticosteroids and – Disrupting the electrolyte balance of the endolymph
amphotericin B) → digitalis toxicity of the inner ear
– Dehydration (vomiting and diarrhea)
– Muscle weakness • Transient thrombocytopenia and
– Central nervous system depression granulocytopenia occurs (aspirin: renal excretion)
– Volume depletion
– Cardiovascular collapse
• Enhancement of theophylline pharmacologic
– Anuria
effects
19 20

Loop (High-Ceiling) Diuretics Monitoring parameters
• Compatible with • Incompatible with
– Ascorbic acid • Serum electrolytes, BUN, creatinine, glucose
– All common IV fluids solutions
– Amikacin sulfate • Hydration status
– Dobutamine HCL
– Cimetidine HCl – Epinephrine • Blood pressure
– Kanamycin sulfate – Gentamicin sulfate • Symptoms of edema, patient weight
– Tobramycin sulfate – Netilmicin sulfate
– Tetracyclines • Evaluation of ototoxicity (especially with
– Verapamil – Antihistamines prolonged administration in cats)
– Local anesthetics
– Alkaloids
– Hypnotics
– Opiates 21 22

Thiazide Diuretics (Benzothiadiazides)
Ethacrynic Acid
• For the treatment of nephrogenic diabetes • Preparations
insipidus – Chlorothiazide
– Hydrochlorothiazide
• Adjunct therapy of hypercalcemia – Trichlormethiazide
• Bromide toxicity (increased bromide excretion)
• Have greater incidence of ototoxicity and GI

effects than furosemide
23 24
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Thiazide Diuretics (Benzothiadiazides): Thiazide Diuretics (Benzothiadiazides):

Mechanism of action Mechanism of action
• Early part of the distal tubule • Urinary excretion is in physiologic ratio=
– Block the Na+- Cl- symport minimal effect on ECF balance
– Increase calcium absorption/ decrease excretion
of calcium
• Reduce urinary output in animals with
– Increase excretion of sodium, chlorine, diabetes insipidus (natriuretic effect)
magnesium and potassium
• Weakly inhibit carbonic anhydrase (no

contribution on its diuretic effect)
25 26

Therapeutic uses Administration
• Long-term diuretic therapy • Oral
– Chlorothiazide and hydrochlorothiazide
• Adjuncts in the treatment of CHF in dogs and cats
• Intravenous
– Hydrochlorothiazide and trichlormethiazide
• Treatment of udder edema in cows
• Nephrogenic diabetes insipidus
• Calcium oxalate uroliths

– Hydrochlorothiazide: Reduction of urinary calcium
excretion
27 28

Adverse side effects Contraindications
• Minimal ECF electrolyte balance disturbance • Lactating animals
• Patients that are hypersensitive to
• Hypokalemia and hypochloremia sulfonamides and with anuria
• Pregnant dams (neonates have
• Hyperglycemia and glycosuria thrombocytopenia)
• Patients with
– Severe renal disease
– Water and electrolyte imbalance (vomiting and
diarrhea)
29 30
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Thiazide Diuretics (Benzothiadiazides):

Monitoring
Osmotic diuretics
• Potassium levels especially in chronic therapy • Preparation
• Serum electrolytes, BUN, creatinine, glucose – Mannitol: most commonly used
• Hydration status – Glycerine
– Urea
• Blood pressure
• Hemograms
31 32
Osmotic diuretics:
Osmotic diuretics: Pharmacokinetics
Mechanism of action
• Filtered at the glomerulus but are poorly • Absorption
reabsorbed from the lumen of the nephron – Poorly absorbed orally
– Cause decrease in reabsorption of water – Needs to be administered intravenously
– Large volume of urine • Fate: distributed to ECF(1/2 life: 1-2 hours)
– Small increase in sodium and chloride excretion • Excretion: Excreted unmetabolized
• Mannitol: increased renal medullary blood

flow (PG-mediated)
33 34
Osmotic diuretics: Therapeutic uses Osmotic diuretics: Adverse effects

• Toxicity • Acute oliguric renal • Water and electrolyte • GI upset: Nausea and
– Aspirin failure imbalances vomiting
– Some barbiturates • Acute glaucoma
– Bromides • Cerebral edema • Cardiovascular • CNS effects
– Ethylene glycol problems – Dizziness
– Pulmonary edema – headache
Usually in combination with furosemide – CHF
– Tachycardia
35 36
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Osmotic diuretics: Contraindications Osmotic diuretics: Precautions

• In animals with • Administration should be stopped when
– Generalized or acute pulmonary edema during therapy, the following conditions
– Intracranial bleeding develop
– Severe dehydration – Progressive heart failure
– Anuria secondary to renal disease – Pulmonary congestion
– Severe pulmonary congestion or edema – Progressive renal failure or damage
37 38
Osmotic diuretics: Monitoring Osmotic diuretics: Glycerine

• Serum electrolytes, osmolality • Therapeutic uses • Monitoring
• BUN, serum creatinine – For acute glaucoma • Intraocular pressure
• Variable effect vs. • Urine output
• Urine output Mannitol • Hydration status
• Central venous pressure • Advantage: can be
admiinistered orally
• Lung auscultation
– For reduction of CSF
pressure
39 40
Carbonic anhydrase (CA) inhibitors CA inhibitors: Mechanism of action

• Preparations • Kidney: proximal convoluted tubules
– Reversibly inhibit CA – Alkaline urine
– Acetazolamide production
enzymes
– Methazolamide • Decreased carbon
– Reduce the number dioxide reabsorption
– Dichlorphenamide • Increased sodium-
of hydrogen ions for carbonate excretion
– Ethazolamide sodium-hydrogen – Chlorine is retained in
exchange the kidney= ionic
balance is maintained=
hyperchloremic
acidosis
41 42
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CA inhibitors: Mechanism of action CA inhibitors: Pharmacokinetics

• Eye • Absorption: absorbed • Excretion
orally – Kidney
–CA is found in ciliary process of the eye • Active secretion
• Distribution
–Involved in aqueous humor formation – To tissues with high
• Passive reabsorption
–If inhibited? = intraocular pressure in CA concentrations

glaucoma cases? • Renal cortex
• Eye
• Erythrocytes
43 44
CA inhibitors: Pharmacokinetics CA inhibitors: Adverse side effects

• Treatment of glaucoma • GI disturbances (vomiting)
• CNS effects
• Adjunct therapy to metabolic alkalosis – Sedation
– Depression
– Excitement
• Hematologic effects: bone marrow depression
• Renal effects
– Crystalluria
– Renal colic
– Dysuria
– Polyuria
45 46
CA inhibitors: Adverse side effects CA inhibitors: Contraindications

• Hypokalemia • Renal or adrenocortical insufficiency
• Hyperglycemia
• Hyponatremia • Water and electrolyte imbalances
• Hyperuricosemia
• Hepatic insufficiency • Severe pulmonary obstruction (incapable of
• Dermatologic effects increasing alveolar ventilation
• Hypersensitivity reactions
47 48
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CA inhibitors: Contraindications CA inhibitors: Monitoring

• Chronic, noncongestive, angle-closure • Intraocular pressure/ tonometry (glaucoma
glaucoma therapy)
• Blood gases (alkalosis therapy)
• Liver disease • Serum electrolytes
– Divert ammonia from the urine to the systemic • Baseline CBC and periodic tests (chronic
circulation- hepatic coma therapy)
• Other adverse side effects
49 50
Potassium- sparing diuretics Potassium- sparing diuretics

• Preparations • Mechanism of action
– Triamterene – Triamterene and amiloride
• Inhibit active sodium reabsorption in the late distal
– Amiloride convoluted tubule and circulating duct
– Spironolactone • Action is independent of aldosterone
– Spironolactone
• Inhibit aldosterone in the distal renal tubules resulting
in
– increased excretion in sodium, chloride and water
– Decreased secretion in potssium, ammonium, phosphate and
titratable acid
• No effect on CA or renal transport mechanism
51 52
K- sparing diuretics: Pharmacokinetics K- sparing diuretics: Therapeutic uses

• Well absorbed orally • Used in patients that develop hypokalemia
after therapy with other diuretics
• Spironolactone
– Slow onset of action; slow elimination (t1/2= 20 hrs) • Chronic edema (CHF)
– Active metabolite: canrenone (having the diuretic
properties)
• Refractory edema
– Together with canrenone may cross the placenta and
mammary gland
• Adrenal gland tumors
53 54
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K- sparing diuretics:
K- sparing diuretics: Contraindications
Adverse effects (usually reversible)
• Hyperkalemia • CNS effects • Hyperkalemia
• Lethargy
• Hyponatremia
• Atazxia
• Dehydration • Headache • Renal disease (anuria, acute renal failure)
• Renal disease • Gynecomastia in
– Increase in BUN males • Hepatic disease
– Mild acidosis
55 56
K- sparing diuretics: Monitoring Methylxanthines

• Serum electrolytes, BUN, creatinine • Preparations
– Aminophylline
• Hydration status – Theophylline
– Caffeine
– Theobromine
• Blood pressure
• Symptoms of edema/ ascites, patient weight
57 58
Aminophylline and theophlylline:

Methylxanthines: Mechanism of action
Mechanism of action
• Increase renal blood flow and GFR • Competitive inhibition of phosphodiesterase
• Inhibit sodium reabsorption in the proximal – Increase amount of cAMP  increase
convoluted tubule epinephrine release, inhibit the release of
histamine
• Alkaline urine (herbivores> carnivores) • Relaxation of the smooth muscles in the bronchi and
• Dilate bronchi (inhibit adenosine receptors) [pulmonary blood vessels
• Stimulate CNS • Weak chronotropic and inotropic action

• CNS stimulation
• Centrally –mediated respiratory stimulation
59 60
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Methylxanthines: Therapeutic uses Methylxanthines: Adverse effects

• Myocardial failure and/or pulmonary edema • Excitement (CNS • Polyphagia
– Aminophylline and theophylline: bronchodilator stimulation) • Polydipsia/Polyuria
• Skeletal muscle • Cardiovascular
• Diuresis fasciculation
toxicity
– Rarely used solely as diuretics • Gastrointestinal upset
• Palpitations
– Vomiting, nausea
– Irritation • Hypotension
– Increased gastric acid
secretion
– Diarrhea
61 62
Methylxanthines: Monitoring Acidifying salts

• Therapeutic efficacy and symptoms of toxicity • Ammonium chloride lowers the pH of ECF and
• Serum levels (only human data is available) urine
• Increase urinary load of chloride= urinary loss
of sodium and chloride= diuresis
63 64
Acidifying salts: Therapeutic uses Acidifying salts: Contraindications

• Urinary acidification • Hepatic disease (ammonia accumulation)
• Urolith dissolution and prevention
• Uremia (intensification of metabolic
• Toxin and drug excretion
– Strontium acidosis)
– Quinidine • Severe renal insufficiency and metabolic
• Enhance efficacy of antimicrobials alkalosis
– Chlortetracycline
– Methenamine • Urate calculi
– Nitrofurantoin • Respiratory acidosis
– Oxytetracycline
– Penicillin G • X SC, rectal, IP
– Tetracycline
65 66
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Acidifying salts Acidifying salts: Monitoring

• Administration: oral • Urine pH (goal of therapy: < 6.5
• Adverse effects • Blood pH
– Severe, uncompensated acidosis (metabolic) • Serum electrolytes
– Nausea and gastric irritation (oral administration)
67 68
12
BETA LACTAM ANTIBIOTICS
- Possess beta lactam ring: responsible for the antibacterial property
- Kills bacteria by inhibiting formation or weakening the cell wall (transpeptidation)
- Binds to penicillin-binding proteins (PBP’s)
- Have better therapeutic to toxic effect ratio
- Enhanced antibacterial spectrum
- Bactericidal against gram-
positive microorganisms in a time
dependent manner
- First Beta lactam antibiotics
a. Penicillin G
b. Cephalosporin C
c. Monobactam
d. Carbapenem
Why gram-positive bacteria?
Mechanism of Action
- Bactericidal
- Disrupt bacterial cell wall by binding to a
variety of proteins (responsible for cell wall
synthesis) → death and lysis of bacterial
cells
- Penicillin binding proteins (PBPs)
o Specific target of beta lactam
o Involved in
▪ Terminal stages of bacterial cell
wall assembly
▪ Reshaping cell wall during
growth and division
o Examples
o Transpeptidases
o Cross-linking of the threads thus strengthens the peptidoglycan layer → weakening
of the cell wall → bacteria continues to grow → increase osmotic pressure →
rupture and death
o Carboxypeptidases
o Endopeptidases
o Rupture is due to intracellular hypertonicity
- Beta-lactamases
o Secreted by gram-positive bacteria extracellularly
o Gram-negative: periplasmic space
- To be effective:
o 1st: penetrate the lipopolysaccharide outer membrane of cell wall
o 2nd: combine with PBPs on inner cell wall (avoiding beta-lactamases)
- Effectivity in Gram-negative bacteria
o Associated with the rate of antibiotic penetration
o Addition of aminobenzyl side chain to penicillin (ampicillin) improves activity
o Amoxicillin (aminobenzyl group): better penetration
- Difference in activity between Gram positive and Gram negative is the thickness of the
outer layer exterior to the peptidoglycan layer
- Gram-negative bacteria: impermeable outer membrane is the major mechanism for
resistance (LPS)
Beta-lactamase inhibition
• Mechanism of bacterial resistance
• To overcome
o Modify the beta lactam nucleus to produce stable antibiotic in the presence of the enzyme
o Find substance that can inhibit beta-lactamases
▪ Addition of beta-lactamase inhibitors (suicide inhibitors)
• Clavulanic acid
• Sulbactam (penicillanic acid sulfone)
• Characteristics of an ideal beta-lactamase inhibitor
o Wide spectrum of activity
o Pharmacologically match closely the antibiotic partner
o Enzyme inactivation is irreversible
• All are met by clavulanic acid and sulbactam
Beta-lactamase inhibitors
• Clavulanic acid
- Resembles closely especially amoxicillin
- Fermentation product of actinomycete
o Streptomyces clavuligerus
- Reuse of two beta lactam antibiotics
o First: bind with PBPs and injure the bacteria
o Second: typing up the beta-lactamase
o Example
▪ Clavulanic + amoxicillin and ticarcillin
• Sulbactam
- Irreversible beta-lactamase inhibitors
- Lesser potency than clavulanic acid
- Semi- synthetic
- In combination with ampicillin
Penicillin
CLASSES
Natural penicillns Penicillinase- Broad-Spectrum
resistant penicillins Penicillins
Penicillin G Methicillin Ampicillin
(aqueous, procaine,
benzathine)
Penicillin V Nafcillin Amoxicillin
Phenethicillin Oxacillin Hetacillin
Cloxacillin Carbenicillin
Dicloxacillin Ticarcillin
Piperacillin
Mezlocillin
Azlocillin
Natural penicillin
• The first antibiotic discovered in 1928 by Sir Alexander Fleming
• Some of the original penicillins produced
• Has limited range of activity
• Highly susceptible to beta-lactamases
• Inactivated by gastric acid
• Only effective against gram-positive bacteria
• Able to achieve concentrations in
o Bone
o Bile
o Soft tissues
o Peritoneum
• Do not accumulate in
o Prostate
o Cerebrospinal fluid
o Aqeous humor
• Not effective in treating intracellular infections
• Pharmacokinetics
o Undergo minimal hepatic metabolism (except ampicillin)
o Plasma clearance through renal excretion
▪ Glomerular filtration
▪ Tubular secretion
o Actively transported in
▪ Kidney
▪ Brain
▪ Liver
• Penicillin
o Not a good choice for treating staphylococcal infection (Beta-lactamase)
• Useful in treating urinary tract infection
o Eliminated in the urine unchanged
• Also effective against infection in
o Respiratory tract
o Skin
✓ Benzylpenicillin (penicillin G)
- Most commonly used betalactam for large and small animals
- Administered through parenteral route
- Hydrolysed rapidly in the stomach (X PO)
- Sodium and potassium forms: given through IV
- Procaine penicillin G and benzylpenicillin G
▪ prolonged plasma concentrations (slow absorption, therefore long-acting)
✓ Penicillin V (phenocymethyl penicillin)
- Resists degradation by stomach acid
- Not commonly used in small animals
✓ Penicillin G (aqueous)
- Potassium or sodium penicillin G
- Used when rapid effect and high plasma concentration is desired
▪ Especially if administered intravenously
▪ IM route: lower plasma concentration of longer duration
Extended-spectrum penicillin
- Starts with the isolation of penicillin nucleus: 6- amino penicillanic acid
- Advantage of the new structure
• Stability in acid media and improved oral absorption
• Protection against the attack of beta-lactamase producing staphylococci
• Gram- negative activity at low levels
✓ E. coli, Salmonella, Proteus
• Activity against P. aeruginosa
✓ Aminopenicillin
o Preparations
▪Ampicillin
• have similar activity; wide range of activity
• Absorbed better PO
• More rapid action
▪ Amoxicillin
• have similar activity; wide range of activity
• Advantages of amoxicillin
o Can be easily made into palatable oral tablet
o Gives to 50 to 100% higher blood levels than ampicillin after oral
administration
o Has a different and much faster bacterial action
o In humans, penetrates some tissues better than ampicillin
(respiratory infection)
▪ Hetacillin
• Pro-drug
• More stable in gastric acid than the above-mentioned penicillins; best
absorption
• Metabolized into ampicillin and becomes active
✓ Cephalosporins
o Chemically related to penicillin
o More resistant to action of beta- lactamase
o Wide margin of safety
o Wider spectrum of activity than penicillin
o First synthesized from Cephalosporium acremonium (fungus)
o High cost
o More active against Pasteurella strains
o Less effective against Corynebacterium pyogenes
o “generation” – based on the invitro antibacterial potency and spectrum of activity
o With every generation
▪ Loss of gram- positive activity
▪ Increase in gram- negative activity and spectrum
▪ Increased resistance to beta- lactamase enzymes
▪ Increase in cost
o Classification:
▪ First Generation
- Introduced in 1960s and 1970s
- Susceptible to beta lactamase
- Active against most Gram-positive bacteria
- Limited activity against Gram-negative bacteria
- Effective alternative to penicillin against infections in patient with
penicillin allergy
• Staphylococcal
• Non-enterococcal streptococcal
- Formulations
• Oral: cefadroxil, cephalexin, cephradine
• Injectable: cephalexin, cephalothin, cephapirin, cefazolin
- Spectrum:
• Most aerobic gram-positive bacteria except enterococci and
methicillin- resistant Staphylococcus aureus
• Most anaerobic gram- positive and gram- negative bacteria
except Bacteroides fragilis
• Common aerobic gram- negative enterics
- Cephalothin
- Cephaloridine
- Cephapirin
- Cefazolin
- Cephalexin
- Cefaclor
- Cephradine
- Cefadroxil
Clinical/Therapeutic Uses
- Surgical prophylaxis (esp cefazolin)
• Vascular
• Orthopedic
• Biliary
• Pelvic
• Intra- abdominal
- Pneumonia (H. Influenza): Cefurozime
- Skin infections: S. Intermedius
- Bovine mastitis
▪ Second Generation
- Extended activity against specific Gram negative bacteria
- More resistant to beta-lactamase
- Used less frequently in veterinary medicine due to cost
- Spectrum:
• Most aerobic gram- negative bacteria, such as indole positive
Proteus and Bacteroides fragilis
- Cefamandole
- Cefoxitin
- Cefotiam
- Cefuroxime
- Ceforanide
▪ Third Generation
- Not that effective against Gram bacteria
- Developed for specialized situations
• Burns
• Cancer
• Complicated surgery patients
• For infections resulting from resistant Pseudomonas, Klebsiella
or other highly resistant G- bacteria
- High cost
- Spectrum:
• Some strains of Pseudomonas aeruginosa as well as some
unusual Enterobacteriaciae
• Less active against gram- negative bacteria
- Ceftriaxone
- Ceftizoxime
- Ceftazidime
- Cefsulodin
- Cefotazime
- Cefoperazone
- Cefmenoxime
- Moxalactam
o Pharmacokinetics:
o Resistant to beta-lactamase
o Have good affinity to PBPs of Gram positive bacteria
o Widely distributed throughout the body
o Penetrate fluids in
▪ Pleura
▪ Pericardium
▪ Synovia
o High levels in urine and bile
o Poor penetration in
▪ Prostatic tissue
▪ Ocular humor
▪ Cerebrospinal fluid
o Less pain is produced during IM injection
o Distribution limited to the extracellular space
o Good for bone infections, e.g. Osteomyelitis
o Cephalothin: drug of choice for measuring susceptibility for all first-generation
agents
New balactams
- Preparations
✓ Monobactams
o Bicyclic structure is absent, instead monocyclic ring
✓ Carbapenems
o Have carbon instead of sulfur on the five-
membered ring attached to the beta
lactam ring
o Example:
▪ Imipenem
▪ Meropenem
▪ Ertapenem
TETRACYCLINES
- Group of four-ringed amphoteric compounds that
differ by specific chemical substitutions at different
points on the rings
- Isolated from Streptomyces in late 1940s and early
1950s
- Fluoresce when exposed to ultraviolet light
- Acidic, hygroscopic compounds in aqueous solutions
and easily forms salts with acids and bases
(hydrochloride for oxytetracycline)
- Form insoluble chelates with cations
- They accumulate in growing teeth and bones
- Antimicrobial spectrum includes both gram+ and gram- aerobes and anaerobes,
Rickettsiae, Spirochetes, Chlamydiae, Mycoplasma and some protozoans such as
Anaplasma spp. and Haemobartonella spp.
- Used for wide variety of diseases

- Abscesses, enteritis, leptospirosis, pneumonia, bovine and swine respiratory diseases,
pododermatitis, treatment of tick-borne pathogen skin and soft tissue infections and uterine
infections.
- Drug Names
✓ Tetracycline
✓ Chlortetracycline
✓ Oxytetracycline
✓ Doxycycline
✓ Minocycline
✓ Tigecycline (Human research)
Mode of Action
- Bacteriostatic & broad spectrum
- Reversibly binds to the 30S ribosomal subunit of susceptible organisms
- After binding to 30S ribosomal subunit, it interferes with the binding of aminoacyl-tRNA to
the messenger RNA molecule/ribosomes complex, thereby interfering with bacterial protein
synthesis in growing or multiplying organisms.
Bacterial Resistance
- Energy dependent efflux
- Altered target (ribosomes are being protected)
- Attack by enzymes liberated by bacteria
- Resistant gene maybe carried by plasmids or
transposons
Pharmacokinetics
- Administration
▪ Can be given via intravenous route for most tetracyclines or intramuscularly for
oxytetracycline (excipients)
▪ Doxycycline is well absorbed orally but the rest is poorly absorbed
▪ Poor orally because they are ionized at gastrointestinal tract
▪ Reduced drastically by presence of food (except doxycycline)
▪ Easily chelates to polyvalent cations which decreases absorption several fold.
▪ Orally or IV every 8-12 hours
▪ IM injections produce pain, irritation and sterile abscesses (special buffered solutions)
▪ Oral therapeutic doses should be avoided in adult ruminants and used with caution in
horses
▪ danger of disrupting ruminal or colonic microflora
- Oral Absorption
▪ Decreased with co-administration of food, dairy products, polyvalent cations (Ca, Mg,
Fe, Al), kaolin/pectin preparations, iron containing supplements and antacids.
▪ Avoid co-administration 3 hours before and after meal
- Distribution
▪ Once absorbed, bind to plasma proteins and distributed to the rest of the body except
for the CNS (lipophilic)
▪ Doxycycline and minocycline can penetrate the CNS, eye and prostate at therapeutic
concentrations
- Metabolism
▪ Minimal metabolism except for minocycline (extensive liver)
- Excretion
▪ Renal by glomerular filtration but small amounts are excreted into feces via bile and/or
diffusion from the blood into the intestine.
▪ Doxycycline-intestinal excretion is major route of excretion
- Biotransformation
▪ Plasma half-life is 6-12 hours
DRUG HALF LIFE POINTS TO CONSIDER
Tetracycline 6-11 Shorter in dogs
Oxytetracycline 6-11 Shorter in dogs
Doxycycline 11-23
Minocycline 11-23 Shorter in dogs
Withdrawal Period
▪ FARAD (food animal residue avoidance databank) recommends:
▪ Cattle- 28 days for intrauterine treatment (milk testing)
▪ Sheep- 28 days after IM and SC oxytetracycline administration
o 98 hours for milk withdrawal
▪ Swine- 14 days following administration of tetracycline product in feed and water
▪ All except doxycycline and minocycline are potentially nephrotoxic
▪ Permanent staining of unerupted teeth (tetracycline-calcium phosphate complex) in
enamel and dentine
▪ Suprainfections of fungi, yeast or resistant bacteria may occur in GI tract (cats)
▪ Oral tetracyclines should not be used with herbivores because of serious effects on
ruminant digestion.
▪ Anti-anabolic effect are seen in large doses because of binding to mitochondrial
ribosomes (elevated BUN) in pre-existing renal disease
▪ Photosensitivity and hepatotoxicity (rare side effects)
Commonly used Tetracyclines
✓ Tetracycline
o Available in market as:
▪ Panmycin
▪ Duramycin powder
✓ Chlortetracycline
o First to be discovered and introduced for clinical use in 1948
o Not used in significant degree to small animals for treatment of disease but as feed
and water additives for food producing animals
o Available in the market as:
▪ Anaplasmosis block
▪ Aureomycin soluble powder
▪ Aureomycin tablets
▪ Aureomycin soluble calf oblets
▪ Calf scour bolus
▪ Fermycin
✓ Doxycycline
o Available in two forms:
▪ hyclate (common)
▪ monohydrate
▪ Vibramycin
▪ Monodox
▪ Doxy caps
✓ Minocycline
o Has more activity against penicillinase-resistant stains of S. aureus
o Increases concentration within cell results in an overall increase in pharmacologic
activity (primary advantage)
▪ Minocin
✓ Oxytetracycline
▪ Biomycin
▪ Oxybiotic
▪ Oxy-Tet
▪ Terramycin
▪ Terramycin scour tablets
▪ Liquamycin-LA 200
▪ Biomycin 200
Other Uses
• Immunomodulating drugs
o Inhibition of inflammatory cell infiltration
• Anti-inflammatory drugs
o Affect COX-2 mediated Pge-2 synthesis during inflammation
• In combination with niacinamide it is used as treatment of dogs with:
o 1. discoid lupus erythematosus (DLE)
o 2.phemphigus foliaceus (PF)
o 3.ulcerative dermatosis in Collies and Shetland Sheepdogs
Clinical dosages used for tetracyclines in animals – Most frequently cited on product labels or in
reputable references based on a consensus of the literature
DRUG SPECIES DOSE
Doxycycline Dogs and cats 5 mg/kg q12h oral
Doxycycline Horses 10-20 mg/kg q12h oral (never IV)
Oxytetracycline Calves, cattle 22 mg/kg q24h added to drinking water or in feed
and Pigs
Oxytetracycline Calves, cattle 6.6-11 mg/kg q24h IM
Oxytetracycline Calves, cattle 20 mg/lkg q24h IM/SC (off label as high as 40 mg/kg)
Oxytetracycline Pigs 6.6-11 mg/kg q24h IM Doses as high as 20 mg/kg IM q24h
are also used
Oxytetracycline Sea turtles 40 mg/kg IM, followed by 20 mg/kg q72h, IM
Tetracycline Calves 11 mg/kg q12h PO
HCL
FLUOROQUINOLONES
• Structure consists of
o Carboxyl group
o Fluorine atom
o Piperazine ring attached to a quinoline
ring
o Weak acids
o Lipophilic
• Mechanism of action
o Inhibit DNA gyrase
▪ DNA gyrase- controls the supercoiling of DNA as replicating strands replicate
▪ Outcome: degradation of chromosomal DNA at the replicating fork
o Bactericidal
o Absorption- Oral: rapid
▪ 1 hour in dogs
o Fate
▪ Distributed wide + CNS, bone and prostate
▪ Metabolism: hepatic
o Excretion
▪ Parent drug and metabolites excreted in urine and bile
o Metabolism
▪ hepatic
• Spectrum of activity
o Broad
o Anaerobes tend to be resistant
• Administration: PO, IM in dogs only
• Bacterial resistance
o Rare
o If present, due to mutation that resist binding of drug to DNA gyrase
• Extra-label use is prohibited in food animals
• Adverse effects
o Erosion of articular cartilage in young dogs
o Do not administer
▪ Small to medium breeds for the first 8 months of life
▪ Large breeds: first 18 months of life
✓ Enrofloxacin
o Infections
▪ Dermal
▪ Respiratory
▪ Urinary tract
o Half-life
▪ 3-5 hours in dog
▪ 6 hours in cats and horses
✓ Danofloxacin
o Treatment of bovine respiratory infections including Mannheimia species
✓ Difloxacin
o Treatment of dermal, respiratory, and urinary tract infections in dogs.
✓ Orbifloxacin
o Treatment of dermal, respiratory, and urinary tract infections in dogs and cats.
o Half-life
▪ 6 hours in dogs and cats and 9 hours in horses
✓ Marbofloxacin
o Treatment of dermal, respiratory, and urinary tract infections in dogs and cats.
o Half-life
▪ 9-12 hours in dogs and cats
✓ Dirofloxacin
o Half-life
▪ 9-12 hours in dogs and cats
AMINOGLYCOSIDES
• Chemistry
o Consist of two or three sugars joined to a hexose (aminocyclitol) by glycosidic bonds
o Polar and basic (amino groups)
o Water soluble sulfate salts
o Bind to 30s ribosomal fragment
o Inhibit protein synthesis and fidelity of messenger RNA (mRNA) translation →
synthesis of abnormal protein
o Uptake by bacteria is dependent on energy (oxygen linked)
o Inhibited by
▪ Anaerobic and acidic environment
▪ Calcium and magnesium ions
o Bactericidal (Gram negative aerobes)
o Synergistic to Beta lactams against may Gram positive pathogens
• Therapeutic Uses
• Administration
o IM or SC
o Pulse therapy (high dose once daily) in systemic infection
▪ Allow full clearance to reduce renal and cochlear toxicity
o For enteric infection, oral dose twice a day
• Absorption
o not absorbed from the gastrointestinal tract
• Distribution
o Extracellular fluid and transcellular fluids (pleural and peritoneal fluids)
o Limited penetration of the CNS or ocular tissue
o Accumulate in the renal cortex and otic endolymph (toxicity)
• Excretion
o Unchanged in the urine by glomerular filtration
o Half-life: 1-3 hrs in most species
• Bacterial Resistance
o Plasmid- mediated
o Quickly developed
o Inactivation by bacterial enzymes: most common
▪ Amikacin: more resistant to enzymatic degradation
o More toxic than other antimicrobials
o Toxicity is reversible: if administration is stopped earlier
o Should not be used with ototoxic drugs
o Ototoxicity: progressive damage to cochlear sensory cells (deafness), vestibular
cells (ataxia) or both
o Nephrotoxicity: damage to membranes of proximal tubular cells:
▪ Loss of brush border enzymes
▪ Impaired absorption
▪ Proteinuria
▪ Decreased glomerular filtration rate
o Neuromuscular blockade
▪ Rare
▪ Prejunctional blockade of ACh release
▪ Decreased presynaptic sensitivity to ACh
▪ Muscle paralysis and apnea: Tx- calcium gluconate
o
• Preparations, Indications, and Antagonistic Drugs
DRUG INDICATION ANTAGONIST COMMENTS
All aminoglycosides Infections caused by Dimenhydrinate and Monitor patients with
susceptible ethacrynic acid affect hearing loss
pathogens, hearing loss;
pneumonias, urinary Do not administer with
tract infections, Methoxyflurane methoxyflurane
endometritis, and
septicemias that are Chloramphenicol
resistant to other
antibiotics
Kanamycin, Kanamycin: not Neuromuscular Administer with
tobramycin, effective against blocking agents calcium and
gentamicin, neomycin, Pseudomonas spp antcholinergic agents
streptomycin as prescribed
Gentamicin Amphotericin B and Monitor renal function

cephalosporins test results frequently
produce when combining these
nephrotoxicity agents
Neomycin For enteric infections; Digitalis glycosides, Dosages may need to

Topical- ear, skin, eye Penicillin V be adjusted when
infection combining these
agents
Gentamicin, Tobramycin: more Carbenicillin, Never mix these two

tobramycin potent ticarcillin, azlocillin, types of antibiotics; if
antipseudomonal mezlocillin, piperacillin a patient is receiving
activity combined therapy,
administer the doses
at least 1 hour apart
✓ Streptomycin and Dihydrostreptomycin

o Oldest members of aminoglycosides
✓ Neomycin
o Used orally for treatment of enteric infections
o Topically for skin, ear, and eye infections
✓ Gentamicin and Amikacin
o Expanded spectrum aminoglycosides (Pseudomonas, Proteus, Staphylococcus
and Corynebacterium spp. as well as gram(-) aerobes.
o Used in all species for the treatment of susceptible infections of the skin,
respiratory tract, ear, eye, urinary tract, and septicemia.
✓ Tobramycin
o Similar to gentamicin but has more potent antipseudomonal activity and reduced
nephrotoxicity
✓ Kanamycin
o Similar to gentamicin but not effective against Pseudomonas spp.
o Used in Vet med only as oral preparation combined with Bismuth subcarbonate
and aluminum magnesium sulfate (bacterial enteritis in dogs and symptomatic
relief of associated diarrhea)
AMINOCYCLITOLS
✓ Spectinomycin & Apramycin
o Chemically similar to aminoglycosides
o Bacteriostatic
o Binds to 30s ribosome and inhibit protein synthesis
o similar to aminoglycosides
• Spectrum of activity: effective against
o Gram- negative aerobes
o Mycoplasma spp
• Bacterial Resistance (rare)
o Plasmid- mediated
▪ Production of enzymes
• Adverse effects
o No significant toxicity
• Preparations and therapeutic uses
✓ Spectinomycin: for enteric and respiratory diseases
✓ Apramycin (swine and calves): enteric diseases such as colibacillosis
SULFONAMIDES AND POTENTIATED SULFONAMIDES

- Sulfa drugs
- Derivatives of p- aminobenzene sulfonic acid
- Structurally similar to p- aminobenzoic acid
(PABA)
o Intermediate in the bacterial synthesis
of folic acid
- Poorly water-soluble unless prepared as
sodium salts
- Structural derivatives differ in R group
component
• Mode of Action
- Inhibit dihydropteroate synthesis
o Enzyme that catalyzes the
incorporation of PABA into dihydrofolic
acid
▪ Folic acid is required for purine
and DNA synthesis
• Combinations
- To potentiate its spectrum of activity sulfas are added with trimethoprim
- Trimethoprim act on dihydrofolate reductase
• Bacterial Susceptibility
- Broad Gram positive, Gram negative, and protozoal organisms
- Combination to trimethoprim or ormetoprim (diaminopyrimidines)
• Pharmacokinetics – has independent solubility
o Absorption – well absorbed orally and parenterally
o Distribution
- Widely distributed to tissues
- High plasma concentration
o Metabolism
- Acetylation of the NH2 group
- More extensive and fast in herbivores than carnivores
o Excretion
- Excreted primarily in the kidneys via GF
- low urine pH encourage tubular reabsorption
- Minimally excreted via tears, feces, bile milk and sweat
• Routes of Administration
o IV
o PO
o SC
o IA (barrows, gilts, and boars)
• Therapeutic Uses
PREPARATION SPECIES INDICATIONS REMARKS
Sulfamethazine Cattle Control of respiratory Slowly excreted
(Sulfadimidine) Sheep and GI infections
Swine Promote growth in Plasma levels are
swine maintained for 24 hrs
with one singledose
Follicular cell
hyperplasia of the
thyroid gland (very
high amounts)
Sulfadimethoxine All species Systemic and soft More soluble and less
tissue infections toxic than
sulfamethazine
Coccidiosis
Sulfathiazole Swine Respiratory and Rapidly excreted
Poultry enteric diseases
Given as feed or
water additive
Acute infections in
food-producing
Animals (+
sulfathiazole,
sulfamethazine,
sulfapyridine)
Sulfachlorpyridazine Cattle Respiratory and Rapidly absorbed and

Swine enteric infection excreted
(colibacillosis)
Sulfisoxazole and Small animals Urinary tract infection Rapidly secreted and
sulfamethoxazole very soluble
High concentrations
attained with minimal
danger of renal
crystalluria
Sulfacetamide Ophthalmic infection The only sulfonamide
that can be prepared
as sodium salt at
neutral pH
Sulfasalazine Dogs Enteric diseases Cleaved into
Cats (colitis and sulfapyridine and 5-
inflammatory bowel aminosalicylic acid
disease) (5-ASA): bacterial
and anti-inflammatory
actions
Potentiated All species In combination with
sulfonamides trimethoprim or
• Sulfadiazine ormethoprim
trimethoprim
• Sulfamethoxazole
trimethoprim
• Sulfamethoxine
trimetoprim
• Dosage Forms
o Solution
o Tablets
o Boluses
o Suspension
• Bacterial Resistance
o Bacteria that is resistant to one sulfonamide is resistant to all.
o Mechanism:
- Increase PABA production
- Decrease affinity of sulfonamide for dihydropteroate synthetase
- Bacterial metabolism of the drug
o Urticaria (hives
o Vomiting
o Diarrhea
o Anorexia
o Fever
o Crystal formation (kidneys) which could result to hematuria, proteinuria, and renal
tubular damage
o Keratoconjunctivitis sicca (dogs)
o Limited use for food producing animals
• Withdrawal Period
o 10-15 days for meat, milk, and egg producing animals
MACROLIDES
• Chemistry
o Basic
o Lipid-soluble compounds
▪ Deoxy sugar + lactone ring
o Prepared as sulfate salts or esterified salts of
▪ Stearate
▪ Tartrate
▪ Estolate
▪ Lactobionate
o Inhibit bacterial protein synthesis
▪ Binding at 50s ribosome
▪ Prevents translocation of amino acids to the growing peptide chain
o Bacteriostatic
o Absorption
▪ Destroyed by gastric acids
▪ Good oral absorption (since gastric acids can be stopped) in combination with
distemper
• Enteric-coated preparations
• Prepared as Esterified salts
o Fate
▪ Widely distributed to all tissues except for CNS
▪ Tilmicosin higher concentration in lung tissue: 60x higher than serum levels
o Excretion
▪ Metabolized in the liver, excreted in the bile
▪ Unchanged in the urine: tilmicosin & tylosin
• Spectrum of Activity (effective against)
o Gram positive aerobes and anaerobes
o Mycopplasma spp
✓ Erythromycin
▪ Alternative to penicillin: Gram positive aerobes and anaerobes = dogs, cats,
and horses
▪ Drug of choice for:
• Enteritis caused by Campylobacter jejuni in dogs and foals
• Rhodococcus equi - causative agent for pneumonia in foals
✓ Tylosin
▪ Cattle, sheep, and swine
• Local and systemic infection
o Mycoplasma
o Gram positive bacteria
o Some gram negative pathogens
• Growth promoter or sometimes feed additive
▪ Dogs and cats
• Chronic colitis
✓ Tilmicosin
▪ Cattle
• Treatment of respiratory disease (caused by Pasteurella spp.)
• Administration
✓ Erythromycin – dogs, cats, foals
▪ PO
▪ IM
✓ Tylosin – swine, calves, lambs, dogs and cats
▪ IM
▪ PO
✓ Tilmicosin – cattle
▪ SC
o Chromosomal or plasmid-mediated
o Effect: decreased binding of drug to 50s ribosome (so ineffective)
✓ Erythromycin & Tylosin
o Mild gastrointestinal upset (PO)
o Pain & irritation at IM injection site
o Edema of rectal mucosa with mild anal prolapse (swine)
o Severe diarrhea
▪ Erythromycin – PO in adult ruminants
▪ Tylosin – PO / parenteral – adult horses
▪ Since these animals rely on bacterial fermentation in their diet and
has the possibility of killing good bacteria leading to severe diarrhea
✓ Tilmicosin
o Cardiovascular toxicity (all animals except in cattle)
CHLORAMPHENICOL
• Chemistry
o From Streptomyces venezuelae
o Now produced synthetically
o With dichloracetate and nitrobenzene in the structure
o With Palmitate salts: to become water-soluble and given PO
o Chloramphenicol sodium succinate: water-soluble for parenteral administration
o Bacteriostatic
o Binds to 50s ribosome
▪ Inhibit peptide bond formation; thus, inhibit protein synthesis
o Absorption
▪ Faster reabsorption in the GIT
o Fate
▪ Distribution: well-distributed throughout the body (+CNS (BBB) and eye)
▪ Metabolism
• Via glucuronide conjugation in the liver
• 75% of dose – cats; 90% in dogs
o Excretion
▪ Half-life
• 1-1.5 hours in dogs and horses
• 4-5 hours in cats
• Spectrum of activity (effective against)
o Broad spectrum – Gram positive and Gram linconegative bacteria
o Most anaerobic bacteria
o Species – dogs, cats, horses, birds
o Local infection
o Systemic infection
▪ Respiratory, CNS, Ocular infection
o Infection caused by
▪ Anaerobes
▪ Salmonella spp
• Administration
o Per os
▪ Every 6-8 hours
• Dogs, birds, horses
▪ Every 12 hours
• Cats
o Bacteria produce acetyltransferase (in liver) and other metabolizing enzymes
• Adverse effects
o Anemia
▪ Dose-related anemia
• Animals and humans
• Inhibit the uptake of iron by erythrocytes
• Slow maturation rate of RBC in bone marrows
▪ Non-dose-related anemia
• In humans
• Aplastic anemia that is often fatal-residue-induced
• Thus, banned in food-producing animals
o Anorexia and diarrhea-prolonged or high doses; in cats
o Should be used with caution
▪ Animals with hepatic or renal function impairment since it may exacerbate the
situation
▪ Neonatal animals since chloramphenicol induces anemia
• kittens
▪ Not for dogs for breeding purposes (some manufacturer)
• Dogs will have aplastic anemia – deprivation of oxygen – abortion –
dogs will lack nutrient – anomaly
FLORFENICOL
• Fluorinated analog of thiamphenicol
• Same MOA with chloramphenicol
• Approved for cattle use (in USA) to treat Bovine respiratory disease caused by P.
hemolytica, P. multocida and H. somnus
LINCOSAMIDES
• Chemistry
- Derivatives of sulfur-containing octose with amino acid-like side chain
• Preparations
- As hydrochloride or phosphate salts (water-soluble)
- Palmitate salts
✓ Lincomycin
o From streptomyces lincolnensis
✓ Clindamycin
✓ Pirlimycin
- Bacteriostatic
- Binds to 50s ribosome
▪ Inhibit protein synthesis
- Should not be combined with antibiotics with the same binding site (overlapping action –
antagonistic effect)
▪ Chloramphenicol
▪ Macrolides
- Absorption
▪ 50% for lincomycin
▪ 90% for clindamycin
- Fate
▪ Distribution
• Wide
• Good in bone and soft tissues
• High CNS levels if meninges are inflamed because of vasodilation (BBB is a tuft of
capillaries na mu inflammation)
▪ Metabolism: liver
• 60% lincomycin
• 90% clindamycin
▪ Excretion: urine, bile feces
• Unchanged
• Metabolites
- Gram positive aerobes and anaerobes
▪ Toxoplasma spp
▪ Mycoplasma spp
▪ Against anaerobes: Clindamycin > lincomycin
✓ Lincomycin
▪ administered IM or added to drinking water
▪ Swine (also for dogs, cats, chickens)
▪ Control and treatment of
• Swine dysentery
• Infections caused by
 Staphylococcal
 Streptococcal
 Mycoplasmal infection
✓ Clindamycin
▪ Administered PO or IM
▪ Dogs and cat
• Periodontal disease
• Osteomyelitis
• Dermatitis
• Deep soft tissue infections caused by Gram positive organisms
• Toxoplasmosis
✓ Pirlimycin (mastitis tubes)
▪ Clinical and subclinical mastitis in dairy cattle
- Altered drug binding
- Cross-resistance between lincosamides and macrolides (! Consider mechanism of action)
• Adverse effects
- Horses, rabbits, hamster, guinea pigs (gut fermenters)
▪ Severe, often fatal diarrhea = altered GI flora
- Dogs, cats, swine
▪ Rare
▪ Neuromuscular blockade
• High doses
• Combined with anesthetics
MISCELLANEOUS ANTIBIOTICS
✓ Bacitracin
o Produced from Bacillus subtilis
▪ Discovered from a contaminated wound of a patient named Margaret Tracy in
early 1940s (B. licheniformis)
o Freely soluble in water (polar and insoluble to lipid loving
o Insoluble in acetone, chloroform, and ether
o Inhibits second step of cell wall synthesis
▪ Inhibits peptidoglycan synthesis by nonspecifically blocking phosphorylase
reactions
o Bactericidal
o Not absorbed orally (poorly absorbed)
o Effects after systemic administration
▪ Careful since it can cause nephrotoxicity, pain, induration, petechiae at
site of injection
o Combined with other antibiotics to enhance effectivity
▪ Zinc bacitracin – increases activity of bacitracin due to astringen effect
(decrease inflammation) of zinc
▪ +polymyxin B/neomycin – widens the spectrum
o Gram positive bacteria (topical and parenteral administration)
o Spirochetes
o Topical infections – skin, ear, and eye
▪ In combination of neomycin and or polymyxin B
▪ Prevent and treat clostridial enteritis
o Added to feeds in swine
▪ Prevent and treat clostridial enteritis
▪ Promote growth (advantage)
✓ Vancomycin
o Blocks the second stage of bacterial cell wall synthesis
▪ Inhibit polymerase release from the cell membrane
o Bactericidal
o Not absorbed orally
o Distributed to ECF and transcellular fluid
o Excreted unchanged by glomerular filtration
o Gram positive bacteria
• Therapeutic use
o Reserve antibiotic (IV) for methicillin-resistant staphylococcal infections of bone
and soft tissue in dogs and cats
o Topical
▪ Treat Gram negative infections of skin, eye, and ear in all species
• Combined with bacitracin to have broad spectrum effect
o Oral (cattle and swine)
▪ Treatment of gram negative enteric infections
o Associated with large doses or prolonged administration
▪ Ototoxicity
▪ Nephrotoxicity
o Systemic toxicity if administered parenterally
✓ Polymyxin B
o Interacts with phospholipids in the bacterial cell membrane which result in
▪ Detergent-like effect
▪ Membrane disruption
o Bactericidal for Gram negative bacteria
o Not absorbed orally
o Too nephrotoxic for systemic use
✓ Metronidazole
• Chemistry
o Nitroimidazoles include:
▪ Metronidazole
▪ Ipronidazole
▪ Dimetridazole
▪ ronidazole.
o heterocyclic compounds containing a fivemembered ring similar to the
nitrofurans.
o Only metronidazole is used in veterinary medicine.
o Metronidazole is taken up by anaerobic bacteria and protozoa and reduced to a
cytotoxic metabolite, which disrupts DNA
o bactericidal against most obligate anaerobes
o active against protozoa
▪ Giardia & Trichomonas spp.
o Nitroimidazoles
▪ demonstrated carcinogenicity in laboratory animals
▪ use is banned in food-producing animals.
o Metronidazolevis
▪ used in dogs, cats, and horses
▪ for the treatment of severe infections caused by anaerobic pathogens,
especially brain abscesses and pelvic, genitourinary tract, and respiratory
infections
o Metronidazole
▪ used to treat protozoal infections
▪ giardiasis and trichomoniasis in dogs and cats
o well absorbed orally and widely distributed, including the CNS
o Hepatic metabolism by oxidation and conjugation occurs for one-third to one-half
of administered drug
o excreted in urine and feces
o The elimination t 1/2 in dogs and horses are 3–5 hours.
• Adverse effects. High or prolonged dosage may produce neurotoxicity with signs that
include nystagmus, ataxia, and seizures.
o Absorption
▪ Bioavailability (PO): 50-100%
▪ Absorption is enhanced with food (increased bile secretion)
▪ Blood level (peak) is achieved 1 hour after administration
o Distribution
▪ Rapidly and widely distributed: lipidsoluble
o Metabolism and excretion
▪ Hydroxylation and conjugation (Liver)
▪ Excretion of metabolites and unchanged drug: feces and urine
o Giardiasis
o Histomoniasis
o Babesiosis
o Trichomoniasis
o Amebiasis
• Toxicity
o Lethargy
o Weakness
o Ataxia
o Rigidity
o Anorexia
o Vomiting
o Diarrhea
o Reversible leukopenia
o Hepatoxicity
✓ Rifampin
o inhibits DNA-dependent RNA polymerase, which prevents initiation of RNA
synthesis
o bactericidal for mycobacteria and Gram positive pathogens
o effective against intracellular infections.
o combined with erythromycin in the treatment of R. equi infections in foals
o used in combination with other antifungal agents to treat fungal infections
▪ aspergillosis or histoplasmosis in dogs and cats when infection involves
the CNS
o absorbed orally and rapidly distributed to cells and tissues
o metabolized in the liver to a deacetylated form that also has antibacterial activity
o Both this metabolite and parent drug are excreted primarily in the bile, but up to
30% may be excreted in the urine
o Parent drug is substantially reabsorbed in the gut, but the metabolite is not.
o Reported elimination t 1/2 for various species
▪ 6–8 hours in horses
▪ 8 hours in dogs
▪ 3–5 hours in sheep
▪ can induce hepatic microsomal enzymes, elimination rates may increase
with repeated doses.
• Administration.
o orally three times a day in foals, dogs, and cats.
• Adverse effects.
o Side effects are rare.
o Hepatotoxicity may occur in animals with preexisting liver disease
o Rifampin may produce red-orange colored urine, sweat, and saliva but this is not
harmful.
✓ Tiamulin
• Binds to 50s ribosome, inhibit protein synthesis
• Spectrum of activity is similar to tylosin
– Gram- positive cocci
– Mycoplasmae
– Spirochetes
– Gram- negative: Haemophilus spp
• Well- absorbed orally
• Metabolized in the liver
• eliminated via
o Feces (70%)
o Urine (30%)
• Therapeutic use
o Swine
▪ Haemophilus pneumonia
▪ Swine dysentery
• Adverse effects
o Metabolites from urine may cause dermatitis in overcrowded pigs
▪ With erythema
▪ prutitus
✓ Nitrofurans
o reduced by bacteria to reactive intermediates that inhibit nucleic acid synthesis
o produce DNA fragmentation and may also block mRNA translation
o broad spectrum and bacteriostatic.
o occasionally used in the treatment of lower urinary tract infections in dogs and
cats
o administered orally every 6–8 hours and is most effective in acid urine.
o Nitrofurazone used topically as an antibacterial ointment, powder, and water-
soluble wound dressings in all species.
o Nitrofurantoin
▪ absorbed orally
▪ rapidly excreted by glomerular filtration and active secretion.
▪ Peak urine levels are achieved less than 1 hour after administration
▪ Plasma t 1/2 is 20 minutes in humans; no information for animals.
• Adverse effects.
Side effects are rare. Nausea, vomiting, and diarrhea may occur in dogs and cats
following oral administration. Nitrofurans may not be used in food-producing animals
(include topically) because they have been shown to be potential carcinogens in
laboratory animals.
✓ Novobiocin
• coumarin antibiotic
• acidic
o blocks binding of ATP to DNA gyrase to inhibit supercoiling of bacterial DNA
o bacteriostatic for Gram positive cocci, especially S. aureus.
o used for wound treatment
o treatment of mastitis particularly Staphylococcus infections
o less potent against Streptococcus infections.
o absorbed orally with peak levels in 2–4 hours
o Tissue penetration is relatively poor
o excreted primarily into bile and feces
o Plasma t 1/2 after oral administration in humans is ∼6 hours; no information is
available for animals.
• Administration
o given by intramammary infusion usually combined with procaine penicillin to limit
the development of resistance
o combined with tetracycline in a proprietary preparation (AlbaPlex®) for oral
administration twice a day in dogs for susceptible infections.
• Adverse effects
o Novobiocin does not produce systemic toxicity when administered topically or
orally
✓ Streptogramins
• Chemistry
o Virginiamycin used for poultry
o mixture of
▪ streptogramin B, a macrolide (virginiamycin M)
▪ streptogramin A, a cyclic hexadepsipeptide (virginiamycin S)
o The human preparation Synercid R is a mixture of the macrolide, dalfopristin,
and the cyclic hexadepsipeptide, quinupristin.
o bind to the 50S ribosome to inhibit protein synthesis
o Virginiamycin is bactericidal against Gram positive aerobic and anaerobic
bacteria.
o Virginiamycin is administered as:
▪ medicated feed additive in broiler chickens
▪ swine as a growth promotant
▪ prevention of necrotic enteritis in broiler chickens
▪ control of swine dysentery in pigs weighing up to 120 lbs
▪ feed additive in cattle to increase feed efficiency
▪ to reduce the incidence of liver abscesses.
o Synercid R is used in humans for treatment of:
▪ vancomycin-resistant enterococcal infection
▪ methicillin-resistant S. aureus.
o Use of virginiamycin in poultry
▪ may lead to transferable resistance to humans and limit the value of
Synercid R .
o administered orally
o Since it is not absorbed, its antibacterial effects are limited to the GI tract.
✓ Ionophore antibiotics
• Chemistry
o polyether antibiotics derived from Streptomyces
o used primarily in poultry and swine for feed efficiency and anticoccidial activity
o Includes monensin, lasalocid, laidlomycin, salinomycin, and narasin.
o act as alkali metal ionophores
o They complex with Na+ in the cell membrane to produce
▪ passive extracellular transport of K+
▪ intracellular influx of H+
▪ killing bacteria and coccidian by lowering intracellular pH.
o In the rumen,
▪ ionophores selectively affect Gram positive organisms resulting in a shift to
Gram negative populations in the rumen microflora
▪ increases the production of propionic acid
▪ decreases the production of acetic and butyric acids by rumen bacteria
▪ This change in volatile acids (VFA) increases feed efficiency by reducing
bacterial energy losses to CO2 and methane, thereby increasing the
energy content per unit of feed.
o administered as premixes or medicated feed for growth promotion, feed
efficiency, and control of coccidiosis in cattle and broiler chickens
▪ Monensin
▪ Lasalocid
▪ laidlomycin
o administered as medicated feed to broiler chickens for prevention of coccidiosis
▪ Salinomycin & narasin
o absorbed orally.
o Monensin
▪ absorption is 50% in ruminants
▪ rapidly and extensively metabolized by the liver
▪ excreted by bile and eliminated in the feces.
o Absorption more complete
o metabolism is slower in monogastric animals (especially horses who has greater
toxicity)
• Adverse effects
o Toxicity of ionophores when used in species for which they are approved is
uncommon, unless mixing errors occur.
o Ionophore toxicity is due to:
▪ cellular electrolyte imbalances,
▪ increased extracellular K+, intracellular Na+ and Ca2+ concentrations =
resulting in cellular damage and death
▪ The increased intracellular Ca2+ concentration is due to the exchange of
Na+ for Ca2+ by Na+–Ca2+ exchanger; this exchange is particularly
prominent in cardiac and skeletal muscles and these are usually the most
severely affected.
o Horses are the most susceptible species to toxic effects when accidentally
exposed to ionophore containing feeds.
Antifungal agents p. 365 - Hsu

ANTIVIRAL AGENTS o CNS stimulants
o Urinary Acidifiers (methionine,
- Only few veterinary use
ascorbic acid, ammonium chloride)
✓ Acyclovir
▪ Increase excretion
- Inhibition of DNA polymerase & rate of
o TMPS
protein synthesis of viral agent
▪ Decrease excretion,
- Can be given orally, topically or parenterally
Amantadine maintained
- Excreted by the kidneys via:
- Dosages
o Glomerular filtration
o Dogs
o Tubular secretion
▪ 1.25-4 mg/kg PO q12-24h 5-7
- For the treatment of Pacheco’s parrot disease
days
in birds
o Cats
- Feline herpes virus infection of the
▪ 3 mg/kg PO once daily
conjunctiva or cornea
o Horses
- adverse side effects
▪ 5 mg/kg IV q4h
o Cats
▪ For treatment of equine -z
▪ Leukopenia
influenza
▪ Anemia
✓ Famciclovir
o Birds
- For feline herpes (FHV-1)
▪ Necrosis at injection site
- Converted into penciclovir
✓ Amantadine
- MOA: inhibition of virus DNA polymerase via
- N-methyl-D-aspartate (NMDA) receptor (for
competition with deoxyguanosine
pain) antagonist
triphosphate
- Limited effect to influenza A viruses
o Thus, inhibit viral protein synthesis
o Inhibit viral replication by inhibiting
- Pharmacokinetics
M2 protein
o Cats require higher does because of
- Adjunct treatment to chronic pain and
poor conversion to penciclovir
treatment of equine influenza
- Contraindication
o Not commonly used due to variability
o Hypersensitivity
in oral absorption and potential in
o With caution in patients with renal
causing seizures (IV)
problems
- Pharmacokinetics
- Adverse effects
o Not described in dogs and cats
o Not well documented
o Only in horses
o Well tolerated when used up to three
▪ Variable absorption (PO)
weeks
▪ Bioavailability: 40-60%
- Toxicity
▪ Half-life: ~3.5 hours
o Can be removed by hemodialysis
- Contraindications
✓ Interferon Alfa-2A, Human Recombinant
o Hypersensitivity to amantadine or
- For non-neoplastic FeLV disease in cats
rimatidine
- Oral administration – ocular herpes infection
o Patients with untreated, angle-closure
- Effects
glaucoma
o Antiviral – due to inhibition of RNA,
o With caution: liver and renal diseases,
DNA and cellular protein synthesis (+
CHF, active psychoses, eczematoid
antiproliferative agent)
dermatitis, seizure disorders
o Antiproliferative
- Adverse effects
o Immunomodulating
o Dogs
- Well distributed throughout the body except
▪ Agitation
in CNS
▪ Loose stools
- Adverse effects (dose-related)
▪ Flatulence
o Malaise
▪ Diarrhea
o Fever
- Drug Interactions (increase activity)
o Allergic reactions
o Anticholinergics
o Myelotoxicity
o Myalgia o Equine Infectious Anemia
o Anemia ▪ 2 mg/kg PO twice daily for 5
o Leukopenia days
o Thrombocytopenia ✓ Zidovudine (AZT)
o Hepatoxicity - Antiretroviral agent
o Neurotoxicity - Adjunct to treatment of Feline Leukemia Virus
o Taste sensation changes (FeLV) and Feline Immunodeficiency
o Anorexia - Can treat HIV humans
o Vomiting - Converted to active metabolite triphosphate
o Diarrhea o Inhibits viral RNA-directed DNA
o Dizziness polymerase
o Flu-like syndrome - Caution
o Transient hypotension o Renal, hepatic, or bone marrow
o Skin rashes problems
o Dry mouth - Virostatic effect
✓ Interferon Omega - Has activity against bacterial gram negative
- Acts on virus-infected cells by inhibiting mRNA and cytotoxicity
synthesis and protein translation === - Adverse effects
inhibition of viral replication o Non-regenerative anemia – most
- Immunomodulating cytokine for FeLV and FIV common in cats
- Well-tolerated in cats - Well absorbed orally
- Non-terminal clinical stages - 90% bioavailability in cats
o Canine distemper - Widely distributed including the cerebrospinal
o Acute feline calicivirus infections fluid (CSF)
o Feline Infectious Peritonitis - Rapidly metabolized
o Topical: feline herpetic keratitis (less - Excreted in the urine
data) - 1.5 hours half-life
- Adverse effects - Contraindicated in hypersensitive patients
o Decrease RBCs, platelets, WBCs - Use with caution in patients with bone
o Increase Alanine Aminotransferase marrow, renal or hepatic dysfunction
(will return to normal after one week - Drug Interactions:
from injection) o Antifungals, azole
o Soft feces or mild diarrhea ▪ increase level
o Transient fatigue o Atovaquone
o Development of Antibodies (dogs) ▪ increase level
✓ Oseltamivir phosphate (Tamiflu®) o Doxorubicin
- Chemical formula: C16H28N2O4 ▪ antagonism
- Undergoes hepatic metabolism to form o Interferon alfa
oseltamivir carboxylate (ACTIVE) ▪ Increase risk of hematologic
- MOA: and hepatotoxicity
o Inhibits influenza A and B viral o Probenecid
neuraminidase ▪ Increase level
o May be effective against parvoviral o Rifampin
infection and bacterial or viral mixed ▪ May decrease blood levels
infections o Myelo-/cytotoxic drugs
- Drug Interactions (chloramphenicol, flucytosine,
o Probenecid vincristine and vinbiadtine)
▪ Increase tubular secretion ▪ May increase the risk of
o Live influenza vaccines hematologic activity
▪ Reduce immune response - Doses
- Dosage rates o Feline Leukemia Virus
o Canine parvovirus ▪ 5 mg/kg PO or SC q12h
▪ 2.2 mg/kg PO q12h
▪ 5 mg/kg PO 3x daily for 5 ◆ MOA:
weeks
⚫ Actively taken up by growing
o Feline Immunodeficiency virus
dermatophytes
▪ 20 mg/kg PO q12h
✓ Other antiviral agents ⚫ Binds to microtubules
- Trifluorothymidine (TFT)
- Bromovinyldeoxyuridine (BVdU) ◼ Inhibit spindle formation and
- Idoxuridine mitosis
⚫ Fungistatic
Possible Targets for antiviral Chemotherapy in ⚫ Action is slow

Veterinary Medicine ⚫ Cells must be shed and replaced
Target Prototype Drug with uninfected cells (to produce
Attachment of virion to Receptor analogs dermatophytes)
cell receptor
Uncoating Rimantadine ◆ Pharmacokinetics
Primary transcription Transcriptase inhibitors
from viral genome ◼ Absorption
Reverse transcription Zidovudine – AZT ◆ High oral absorption
Regulation of Lentivirus fat inhibitors
transcription ⚫ when given to fat
Processing of RNA Ribavirin foods
transcripts
⚫ Preparation of
Translation of viral Interferons
mRNA into protein microsized particles
Posttranslational Protease inhibitors ◼ Fate
cleavage of proteins
Replication of viral DNA Acycloguanosine ◆ Distributed to keratin
genome (Acyclovir) precursor cells of the
Replication of viral RNA Replicase inhibitors
genome ⚫ Skin
⚫ Hair shafts
ANTIFUNGAL AGENTS ⚫ Nails
Classified as: ◼ Metabolism:
✓ Polyene ◆ In Liver via:
◼ Amphotericin B ⚫ Demethylation
◼ Nystatin ⚫ Glucuronide
✓ Imidazole conjugation
◼ Ketoconazole ◼ Excretion
✓ Anti-metabolic ◆ Urine
◼ Flucytosine ⚫ Glomerular filtration
✓ SUPERFICIAL ◼ Administration
◼ Griseofulvin ◆ PO: dogs, cats, and horses
◆ Synthesized and isolated from Penicillin ◼ Adverse effects

griseofulvum by ---- ◆ Rare
◆ Superficial antifungal antiviral
◆ Idiosyncratic reaction in ◼ MOA
kittens:
◆ Inhibits synthesis of ergosterol in fungi
⚫ Leukopenia cytoplasmic membranes by blocking
cytochrome P-450 enzymes
⚫ Anemia
◆ Fungistatic
IMIDAZOLES
◼ Pharmacokinetics
◼ Have antibacterial, antifungal, antiprotozoal
and antihelmintic activity ◆ Absorbed orally
◼ poorly water soluble except for fluconazole ◆ Well distributed, except in CNS
◼ Members of this group ◆ Metabolized in the liver
◆ Clotrimazole ◆ Excreted in bile
◆ Miconazole ◼ Therapeutic uses
◆ Econazole ◆ Systemic mycoses and severe yeast

infections
◆ Ketoconazole - active ingredient for
drug human use (Canesthen) ⚫ Dogs
◆ Itraconazole ⚫ Cats
◆ Fluconazole ⚫ Horses
◼ MOA ⚫ Birds
◆ Alter cell membrane permeability of ◆ Hyperadrenocorticism (at high dosages)

susceptible yeasts and fungi
⚫ Dogs
⚫ Block synthesis of ergosterol
⚫ Cats
(stabilizing integrity of cell
membrane, therefore makes cell ◼ Adverse effects
membrane permeable to anything
and cause damage to organelles) ◆ Anorexia, vomiting, and diarrhea
◆ Inhibit other enzyme systems ◆ Suppression of adrenal or gonadal

steroids (transient)
⚫ fatty acid synthesis
✓ Fluconazole
◆ Overall effect
◼ Synthetic
⚫ Cell membrane and (membrane-
bound) organelle disruption ◼ Fungistatic
⚫ Cell death ◼ MOA
◆ Lag time happens because effect is on ◆ Cell membrane alteration leading to

synthesis leakage of cellular contents
✓ Ketoconazole ◆ impaired uptake of purine and

pyrimidine precursors
◼ Imidazole antifungal for systemic use
◼ Indication
◼ Some preparations are also for topical use
◆ Systemic mycoses:
◼ Topical imidazoles for parental route
⚫ Cryptococcal meningitis
◆ Micronazole
⚫ Blastomycosis
◆ Clotrimazole
⚫ Histoplasmosis ◼ Poorly soluble in water and common organic
solvents
◆ Superficial candidiasis or
dermatophytosis ✓ Amphotericin B
◼ Contraindications ◼ Polyene macrolide
◆ Hypersensitivity ◼ MOA
◆ Hepatic diseases ◆ Binds to ergosterol of fungal membrane

forming pores or channels which results
◆ Renal impairment
in leakage of cellular contents
◆ Not to be used in pregnant animals
◆ Fungicidal or fungistatic
✓ Miconazole
◼ Ophthalmic preparation
◆ Not absorbed in the GIT
◼ Will penetrate the intact corneal epithelium
◆ Distributed to most tissues except in
◼ First choice agent for horse fungal keratitis CNS, eye, and bone
◼ Delivered by subconjunctival route (some) ◆ Elimination is biphasic (takes within

hours and days)
✓ Itraconazole
◆ Secreted unchanged in the urine
◼ For systemic mycoses of following causative
agents: ◼ Spectrum of activity (effective against)
◆ Aspergillosis ◆ For systemic mycoses
◆ Cryptococcal meningitis ⚫ Aspergilli
◆ Blastomycosis ⚫ Blastomyces
◆ Histoplasmosis ⚫ Coccidiodes
◼ No effects on hormone synthesis, safe to ⚫ Cryptococcus

use, cannot induce adrenocorticism
⚫ Histoplasma species
◼ Adverse effects
◼ Therapeutic uses
◆ Fewer side effects than ketoconazole in
◆ For systemic fungal infection (combined
small animals
with ketoconazole)
◆ Hepatic toxicity
⚫ Dogs
◆ Anorexia
⚫ Cats
◆ Weight loss
⚫ Horses
◆ Vomiting
⚫ Birds
◆ Administered with flucytosine in

POLYENE MACROLIDE ANTIBIOTICS treating CNS < bone and ocular
infections
◼ From various strains of Actinomyces
◼ Adverse effects
◆ Amphotericin B
◆ Renal toxicity
◆ Nystatin
⚫ Renal vasoconstriction
◆ Primaricin (natamycin)
⚫ Decreased renal glomerular ◼ Spectrum of activity (effective against)
filtration
◆ Cryptococcus
⚫ Damage to tubular epithelium
◆ Candida
◆ Renal function should be monitored
◆ Aspergilli
weekly during therapy
◼ Therapeutic uses
✓ Nystatin
◆ Combined with amphotericin B for
◼ Fungistatic or fungicidal
treatment of cryptococcosis (especially
◼ From streptomyces noursei meningeal) in dogs and cats
◼ Combined with other drugs ◆ For aspergillosis and candidiasis in

psittacine birs; slowly given
◆ Neomycin
◼ Adverse effects
◆ Thiostrepton
◆ Low toxicity
◆ Triamcinolone acetonide
◆ Mild gastrointestinal disturbances
◼ For candidiasis infecting the skin, muscous
membranes, and intestinal trct of small ◆ Bone marrow depression: rare
animals and birds
✓ Other antifungal agents
◼ Adverse effects: rare
◼ Chlorhexidine - thrush (birds)
✓ Natamycin
◼ Tincture of Iodine - although antiseptic, can
◼ Ophthalmic preparation be antifungal sometimes to irrigate
◼ Poorly water soluble ◆ 1:10 - 1:20 dilution in saline
◆ Will not penetrate corneal epithelium ◆ Treat Mycotic and bacterial stromal
ulcers
◼ The only approved antifungal for eyes
◆ Presurgical disinfectant
◼ For fungal dermatitis
◼ Tolnaftate
◼ Benzoic acid
ANTIMETABOLIC
◼ Salicylic acid
✓ Flucytosine
◼ Thiabendazole
◼ Fluorinated pyrimidine
◼ Administered orally
◼ MOA
◆ Fungicidal
◆ Inhibits the thymidylate synthetase
⚫ Inhibit DNA and RNA synthesis in

susceptible fungi
◆ Well absorbed orally
◆ Widely distributed, plus CNS
◆ Excreted unchanged in the urine

ANTIPROTOZOAL DRUGS  Broilers
• Not used to treat clinical
❖ Anticoccidial drugs
coccidiosis
➢ Coccidiosis
▪ Effective in the first sporozoite stage
▪ Causes huge financial loss in animal
(Eimeria)
industry
▪ Resistance might be mounted by the
• Impaired feed conversion
protozoa
• Slow growth
▪ Toxicity
• Poor carcass quality ▪ No adverse side effects if used
➢ Therapeutic approaches properly
▪ Broilers 2) Sodium ionophores
• Not vaccinated against coccidia ➢ Preparations
• Amprolium – nonwithdrawal drug ▪ Monensin
(administered 1 week before ▪ Salinomycin
slaughter) ▪ Lasalocid
▪ Layers ➢ Used exclusively as anticoccidial drugs
• Vaccinated with anticoccidial ➢ MOA
• Sulfonamide for outbreaks ▪ Facilitate transport of sodium into cells
▪ Mammals → increase intracellular sodium
• Potentiated sulfonamides concentration → inhibit mitochondrial
• Amprolium functions and ATP hydrolysis
• Decoquinate ➢ Therapeutic uses
• Sodium ionophores ▪ Effective against Eimeria in
➢ Resistance to anticoccidial drugs • Chickens
▪ Minimized by using two or more drugs • Cattle
sequentially • Sheep
• Shuttle program- different drugs ▪ Monensin: Cattle and sheep
are used in one grow-out ▪ Also used as growth promoters
• Rotation (switch) program- ▪ Lasalocid (prevention)
different drugs are used in two • Cattle:
grow-out • Sheep
• Chicken: first generation
trophozoites and schizonts
▪ Salinomycin: chickens only
➢ Adverse effects
▪ Severe cardiovascular side effects:
increased intracellular influx of calcium
➢ Contraindications
▪ fatal to horses and turkeys
3) Amprolium
➢ Quarternary compound
➢ Mechanism of action
▪ Blocks thiamine receptors, thus no
1) Decoquinate
thiamine ulitization by coccidia
▪ Quinolone
➢ Pharmacokinetics
▪ MOA
▪ Poorly absorbed after oral
• Block DNA gyrase, thus inhibit administration
protein synthesis ▪ No preslaughter withdrawal period
▪ Pharmacokinetics ➢ Therapeutic uses
• Withdrawal period: 5 days ▪ Only anticoccidial used for layers and
preslaughter in broilers cattle; used both for prevention and
▪ Therapeutic uses treatment of coccidiosis
• Prevent coccidiosis • First generation trophozoites and
 Calves: E. bovis, E. zuernii schizonts
 Young goats: E. christenseni, • Usually combined with sulfa drugs
E. ninakohlyakimovae
➢ Adverse effects ➢ Pharmacokinetics: levels can be
▪ Thiamine deficiency in host if given in maintained in 24 hours
increased amounts (overdosage) ➢ Therapeutic uses
4) Nicarbazin ▪ Combined with sulfa
➢ Mixture of • Coccidiosis outbreaks
▪ 4, 4’-dinitrocarbanilide (DNC) • toxoplasmosis
▪ 2-hydroxy-4, 6-dimethylpyrimidine ❖ Metronidazole
(HDP) ➢ Mechanism of action
➢ Mechanism of action: unknown ▪ Metabolite disrupts DNA synthesis in
➢ Pharmacokinetics protozoans and bacteria
▪ DNC more absorbed rapidly than HDP ➢ Pharmacokinetics
▪ 4-day withdrawal period is required in ▪ Absorption
broilers • Bioavailability (PO): 50-100%
➢ Therapeutic uses • Absorption is enhanced with food
▪ Prevent coccidiosis outbreaks (increased bile secretion)
▪ Target: second-generation • Blood level (peak) is achieved 1
trophozoites hour after administration
➢ Toxicity ▪ Distribution
▪ Effects • Rapidly and widely distributed:
• Egg production lipidsoluble
 Bleached of brown-shelled ▪ Metabolism and excretion
eggs • Hydroxylation and conjugation
 Mottled eggyolks (Liver)
 Poor hatchability • Excretion of metabolites and
 Impaired egg production unchanged drug: feces and urine
• Broilers become more prone to ➢ Therapeutic Uses
heat stress ▪ Giardiasis
5) Robenidine ▪ Histomoniasis
➢ Effective against first generation schizonts ▪ Babesiosis
➢ For the prevention of outbreaks ▪ Trichomoniasis
➢ Adverse side effects ▪ Amebiasis
▪ Results in unpleasant taste of broiler ➢ Toxicity
meat ▪ Lethargy
▪ Egg taste is also affected ▪ Weakness
6) Sulfonamides ▪ Ataxia
➢ Preparations ▪ Rigidity
▪ Sulfadimethoxine ▪ Anorexia
▪ Sulfachlorpyrazine ▪ Vomiting
▪ Sulfaquinoxaline ▪ Diarrhea
▪ Ethopabate (PABA antagonist but not ▪ Reversible leukopenia
sulfa drug) ▪ Hepatoxicity
➢ Therapeutic uses
▪ Prevention of coccidia, esp intestinal MACROCYCLIC LACTONES
than cecal - Derivatives of soil organisms
▪ Effective against second generation - Avermectin & Milbemycin
schizonts ❖ MOA
7) Antifolate ➢ Binds at the glutamate-gated chloride
➢ Preparations channel receptor in nematode and
▪ Ormetoprim arthropod nerve cells → opening of the
▪ Pyrimethamine channels → influx of chloride ions →
➢ Not approved for food animal use Flaccid paralysis + reproductive function
➢ Mechanism of action suppression in ticks
▪ Block conversion of dihydrofolate to ➢ Not effective against trematodes and
tetrahydrofolate (inhibit thymidine cestodes!
synthesis) ❖ Pharmacokinetics
➢ Well absorbed when administered  Given to pregnant sows
▪ PO ➢ To prevent transmission of
▪ Parenterally Strongyloides ransomi to
▪ As pour-on formulations piglets
➢ Effective levels are reached in the lungs  ~80% efficacy against Trichuris
and skin (regardless of the route of suis
administration) • In horses (paste-PO)
➢ Route of excretion  Intramuscular injection was
▪ Urine used before.
▪ Feces  PO administration is the route
▪ Milk which is now approved for use
➢ Residues (amount) are found on the in horses.
▪ Muscles and kidneys: minimal  Effective against
▪ Liver and fat tissues: high ➢ Trichostrongylus axei
➢ Effective against parasite localizing in/at ➢ Parascaris equorum
the ➢ Oxyuris equi
▪ Respiratory system ➢ Strongylus vulgaris
▪ Skin ➢ Stephanurus dentatus
▪ Gastrointestinal system ➢ Dictyocaulus arnfieldi
❖ Contraindications ➢ S. equinus (adult)
➢ Animals that are producing milk for human ➢ Triodontophorus spp
consumption (except eprinomectin) ➢ Habronema muscae (adult
❖ Avermectins and larvae)
➢ Commercially available avermectins ➢ Strongyloides westeri
▪ Ivermectin, composition ➢ Gastrophilus spp
• ≥90% 22,23 dihydroavermectin ➢ Draschia megastoma
B1a ➢ Onchocerca sp
• ≤10% of the B1b homolog • In dogs
• In ruminants (parenteral, pour-on  For Dirofilaria immitis
& PO) prevention
 Effective against ➢ 6 μg/kg, at 1 month interval
➢ Immature and adult stages  Collies are sensitive:reduced
of GI nematodes ability to efflux the drug from
➢ Adult and larval stages of the CNS
▪ Ostertagia (+ inhibited ➢ Depression
L4) ➢ Muscle weakness
▪ Trichostrongylus ➢ Blindness
▪ Oesophagustomum ➢ Coma
▪ Haemonchus ➢ Death
▪ Dictyocaulus viviparis • In rats, rabbits, and mice
• Less efficacy against  Teratogenic
 Cooperia ➢ Only at or near
 Nematodirus maternotoxic dose levels
• Pour-ons and injection  Mice: most sensitive species at
formulations 0.2-0.4 mg/kg/day
 Ectoparasites ▪ Abamectin
• In pigs (SC) ▪ Doramectin
 Effective against ❖ Milbemycins
➢ Adult and larval stages of ➢ Commercially available milbemycin
▪ Ascaris suum ▪ Milbemycin oxime, composition
▪ Hyostrongylus rubidus • 80% of the A4 5-
▪ Oesophagustomum spp didehydromilbemycin analog
▪ Metastrongylus spp • 20% of the A3 5-
➢ Mange mites didehydromilbemycin analog
➢ Sucking louse ▪ Moxidectin
❖ Avermectin & Moxidectin ▪ Mature and immature gastrointestinal
➢ Potent helminths
➢ Broad-spectrum at low dose levels ▪ Lungworms
➢ Active against ▪ Variable efficacy against Strongyloides
▪ Nematodes (mature and immature) ➢ Dogs: microfilaricide (heartworm)
▪ Hypobiotic larvae ➢ Pigs
▪ Arthropods ▪ Ascarids
❖ Avermectin * milbemycin oxime ▪ Intestinal threadworms
➢ Canine heartworm prevention ▪ Lungworms
➢ GI roundworm prophylaxis ▪ Nodular worms
▪ Hookworm ▪ Kidney worms
▪ Ascarids ➢ Poultry
▪ Whipworms ❖ Why levamisole is used in a number of animal
species?
IMIDAZOTHIAZOLES
➢ Broad spectrum of activity against
❖ Tetramisole and Levamisole nematodes
❖ Tetramisole – marketed in 1965 ➢ Ease of use (due to water solubility)
❖ Levamisole ➢ Wide margin of safety
➢ DL-isomer of tetramisole ➢ Lack of teratogenic effect
➢ Compared to tetramisole ❖ Contraindications
▪ Decreased dosage ➢ Should not be administered together with
▪ Less toxic OP compounds
▪ Broad spectrum against wide range of ▪ Increase toxic effect on the nervous
GI helminths and lungworms system
❖ Administration ➢ Tetrahydropyrimidines
➢ Oral ❖ Adverse side effect
▪ Rapidly absorbed from the GIT ➢ Inflammation at the site of SC
➢ Intramuscular administration (transient)
▪ Peak blood levels are ~ twice ➢ See tetrahydropyrimidines
compared to PO administration ❖ Additional effect
➢ Subcutaneous ➢ Immunostimulant
▪ Efficacy is better than oral ▪ Man
administration if used against ▪ Some animals in severe diseases
lungworms
ORGANOPHOSPHATES
➢ Topical
▪ Especially in cattle -Dichlorvos, Trichlorfon, Haloxon,
➢ Slow-release bolus Coumaphos
❖ Mechanism of Action ❖ Background
➢ Ganglion stimulant of nematode nerves → ➢ Originally used as insecticide for sheep
Neuromuscular paralysis of the parasite and goats
➢ Then as ectoparasiticide
▪ Sheep and goats
❖ MOA
➢ Inhibit acetylcholinesterase →
neuromuscular paralysis (spastic)
➢ Variable susceptibility of
acetylcholinesterase
▪ Humans
➢ Efficacy as anthelmintic is based on ▪ Host
maximum concentration achieved than ▪ Parasite (different species)
duration of concentrations ➢ Different susceptibilities results in the
➢ Not ovicidal formulation of OPs that have
❖ Commonly used in the following species ▪ Maximum effect against parasites
(especially in cases of benzimidazole- ▪ Minimum toxicity against host and
resistant parasite infection) humans
➢ Ruminants
▪ Chronic:
• Demyelination resulting in chronic
neurotoxicity
➢ Acute death due to
▪ Respiratory paralysis
▪ Cardiovascular arrest
❖ Antidote for OP poisoning
➢ Atropine
➢ 2-PAM / pralidoxime
❖ OP and man
➢ Op is absorbed well thorugh intact skin
(high lipid solubility)
➢ Interacts with a lot of drugs
➢ Rapidly degraded in the body
➢ How is toxicity determined in host ➢ Tissue residues are dangerous to man
animals? (withdrawal period should be observed)
▪ Susceptibility of cholinesterase to OPs ➢ Sprays, collars and washes of OP for
▪ Rate of inhibition reversal small animals- hazardous to children when
▪ Rate of inactivation of Ops ingested, inhaled or in contact
➢ Preparations ❖ OP and fish
▪ Haloxon ➢ Fish are susceptible to toxicity
• Safest OP for ruminants ➢ Water pollution (due to careless disposal
• Used to eliminate parasites in the of OP) results in fish kill
 Abomasum and small intestine
(lack efficacy to parasites 1. Dichlorvos
found at the large intestine a) High volatility (versatile OP)
➢ Haemonchus b) Can be formulated into pellets and
➢ Trichostrongylus released slowly as it passes through the
➢ Cooperia GIT
➢ Strongyloides i. Increased concentration against
• Less but good efficacy parasites along the GIT
 Ostertagia ii. Increased safety
 Bunostomum iii. Host can detoxify small amounts
 Nematodirus iv. Drug in the feces can kill fly larvae
• Margin of safety is wide c) Efficacy + trichlorfon
• Administered orally in the form of i. Effective aginst
1. Bots
 Paste
2. Ascarids
 Drench
3. Other intestinal helminths
 Bolus
4. Trichlorfon must be converted
❖ Contraindications
into dichlorvos to be effective.
➢ Weak animals
d) Specific therapeutic uses
➢ Animals exposed to other
i. Pigs, dogs and cats
anticholinesterase agents
1. Whipworms
➢ Animals with gastrointestinal disorders
2. Nodular worms
➢ Respiratory disease
3. Strongyloides
➢ Parturition within one month
4. Hookworms
➢ Use of insecticides, muscle relaxants,
5. Ascarids
phenothiazine derivatives or CNS
6. Little or no effect against
depressants
migrating larvae of ascarids and
➢ Margin of safety is lesser than
hookworms
benzimidazoles.
ii. Horses
❖ Adverse side effects
1. Bots
➢ Toxicity (additive)
2. Strongyles
▪ Acute: SLUD syndrome (due to
3. Ascarids
cholinergic stimulation)
4. Pinworms
2. Trichlorfon • Strongid-T®
a) Specific therapeutic uses • Strongid-P®
i. Used mainly in horses • Nemex®
1. Bots, ascarids, oxyurids • Drontal®
ii. Has efficacy in small animals and • Heartgard®
ruminants ▪ Embonate
iii. Spectrum of activity is similar to ➢ Formulations
dichlorvos ▪ For oral administration
iv. One of the safest Ops • Suspension
v. Can be used in fishponds • Paste
3. Coumaphos
• Drench
a) Specific therapeutic uses
• Tablets
i. For cattle
▪ Aqueous solutions
1. Stomach worms
➢ Spectrum (Effective against)
2. Whipworms
▪ Ascarids
3. Cooperia
▪ Large and small strongyles
ii. Incorporated in the feed to improve
▪ Pinworms
safety
❖ Oxantel
TETRAHYDROPYRIMIDINES
➢ Phenol analog of phenols
- pyrantel, oxantel, morantel
➢ Combined with pyrantel in some
preparations (for dogs and man)
❖ Pyrantel and Morantel
▪ To be effective against whipworms
➢ MOA
▪ Depolarizing neuromuscular blockade:
❖ Morantel
inducing paralysis in parasites
➢ Methyl ester of pyrantel
➢ MOA of antinematodal drugs
➢ Ruminants: safer and more effective than
pyrantel
❖ Pyrantel
➢ Sheep: absorbed rapidly from the
➢ First introduced as a broadspectrum GI
▪ Abomasum
anthelmintic agent
▪ Upper small intestine
▪ Sheep
➢ Liver: site of metabolism
▪ Cattle
➢ Metabolites are excreted in the urine
▪ Horses
▪ Dogs
❖ Morantel + Pyrantel
▪ Pigs
➢ High efficacy against
➢ Preparations
▪ Adult gut worms
▪ Tartrate
▪ Larval stages in the lumen or on the
• Well absorbed in dogs and pigs
mucosal surface (x arrested larvae)
• Less well by ruminants ➢ No withholding periods in some countries
• Metabolism is rapid
• Excretion ✓ Contraindication
 Metabolites: Urine (fast) ◼ Levamisole
 Unchanged: Feces (esp. in ✓ Resistance
ruminants) ◼ There is a crossresistance among
• For horses Strongid-C® pyrantel, morantel, and levamisole.
• For pigs Banminth® ✓ Adverse Reaction
▪ Pamoate salt ◼ Parasympathetic stimulation
• Poor solubility in water ◼ Convulsions
• Reduced absorption from the gut ◼ CNS depression
(advantage) ◼ Asphyxia- the result of respiratory muscle
 Allows drug to be effective paralysis.
against parasites found at the
lower end of the small intestine
 Effective in horses and dogs
VITAMINS AND
ANTIOXIDANTS
SRRabe
1
Vitamins
• B
• C
Stored in the body in

small amounts
WATER- When fed in excess,
SOLUBLE eliminated via the urine
VITAMINS • Clinical uses
• Enhance biochemical
response of stressed or
debilitated animals
• Replacement for B complex
deficiency
• Allergic reactions
• Pain at the injection site
2
WATER- SOLUBLE
VITAMINS
• Vitamin B- complex
• Thiamine
• Riboflavin
• Niacin
• Pantothenic acid
• Pyridoxine
• Cyanocobalamin
• Biotin
• Choline
• Folic acid
3
WATER- SOLUBLE VITAMINS
• Serve as co- enzymes for many metabolic
reactions in the body
• Clinical uses
• Enhance biochemical response of stressed
or debilitated animals
• Replacement for B complex deficiency
4
• Allergic reactions
• Pain at the injection site
5
WATER- SOLUBLE
VITAMINS
• Thiamine hydrochloride
• Co-enzyme in carbohydrate
metabolism
• First vitamin B identified
• Deficiency
• Bracken fern poisoning
• Thiamine destruction in the rumen
• Thiaminase in raw fish (carp and
gold fish)
WATER- SOLUBLE
VITAMINS
 Clinical uses
 Thiamine deficiency
 Lead poisoning
 Adverse side effects
 Allergy
 Muscle soreness at injection
site
• Vitamin B- complex WATER- SOLUBLE
• Vitamin B12 VITAMINS
(Cyanocobalamin)
• Contains cobalt
• Act as co- enzyme in
protein synthesis
• Important for the
maturation of red
blood cells
• Use for
cyanocobalamin
deficiency
8
Vitamin Sources Signs of Deficiencies
Vitamin C Citrus fruits and Slowed healing, increased

vegetables susceptibility to disease(?)
Vitamin Plants, fruit, Loss of appetite, loss of

B1(Thiamin) vegetables, milk, reflexes, loss of nerve
meat control, weakness
Niacin Meat, meat by- Loss of appetite and weight,
products inflamed gums,
hemorrhagic diarrhea
Vitamin Organ meats and Poor growth, eye
B2(Riboflavi dairy products abnormalities, heart failure
n) 9
Vitamin Sources Signs of Deficiencies

Vitamin Meats and vegetables Hair loss, diarrhea, premature
B5(Pantothen graying
ic Acid)
Vitamin Found in most foods, Anemia, poor growth, skin
B6(Pyridoxin damaged during lesions
e) processing
Folic Acid Organ meats Hypoplasia of bone marrow,

macrocytic anemia
Vitamin Organ meats, animal Macrocytic anemia
B12(Cyanoco sources
balamin,
cobalamin)
Biotin Corn, soybeans, beef Poor hair, dry skin, diarrhea
liver
10
• Vitamin C
• For prevention of hip dysplasia
• Genetic (?)
• Exhibit fewer signs of pain
• Cure feline leukemia (little evidence)
• Prevent urinary tract infections

• Acidifies the urine
11
• Vitamin C
• Forms
• Dehydroascorbic acid
• Ascorbic acid
• Easily hydrolyzed (mixed
with water)
• Easily enters the urine
• Sources
• Diet
• From glucose reserves of the
12
body
• Guinea pigs and

humans cannot
produce vitamin C,
should be provided
in the diet
• No toxicity reported
13
• Vitamin C
• Important for bone formation
• For bone growth and mineralization
• For treatment of scurvy
• Dogs with scurvy (hypertrophic
osterodystrophy)
• weak bones and swollen joints with
severe tissue hemorrhaging
14
 As supplement to
 Growing puppies
 Lactating bitches
 Pregnant bitches
 Stressed animals
 Working animals
 Alleviate pain associated with hip
dysplasia
 Prevention or dissolution of urinary
stones
15
Fat- soluble
vitamins
• Vitamins:
•A
•D
•E
•K
• Stored in special fat storage cells (lipocytes)
1
Fat- soluble

vitamins
Toxic Dose
Recommended (This dose must be
Vitamin Minimum Daily Dose given daily for Sources Signs of Deficiencies
for Dogs months to create
toxicity.)
2272 IU/lb of food 113,600 IU/lb of food Liver, fish liver oil, Night blindness,
consumed on a dry consumed on a dry vegetables, dairy retarded growth, poor
A matter basis matter basis products quality skin and hair
227 IU/lb of food 2272 IU/lb of food Sunshine, dairy Rickets, poor eruption
D consumed on a dry consumed on a dry products, fish liver of permanent teeth
matter basis matter basis oil
23 IU/lb of food 455 IU/lb of food Cold pressed Reproductive failure,
consumed on a dry consumed on a dry vegetable oils, brown bowel
E matter basis matter basis meats, nuts, green syndrome
leafy vegetables
Synthesized in the none Kelp, alfalfa, egg Increased clotting

K body yolk time and hemorrhage
2
Fat- soluble
vitamins
• Vitamin A
• First fat-soluble vitamin that was discovered
• Forms
• Retinol
• Retinaldehyde
• Retinoic acid
• Retinyl palmitate (liver storage form)
• If fed in excess to liver capacity, found in the

bloodstream: may cause toxicity
3
Fat- soluble
vitamins
• Vitamin A
• Main source: carotene- rich food
• Cats must be fed with vitamin A than dogs

• Poor conversion of beta-carotene to vitamin A in the
intestine
• Functions/ roles
• Vision
• Growth
• Skin and hair development
• Reproduction
• Skeletal, nervous and muscular functions
4
Fat- soluble
vitamins
• Vitamin A
• Adverse effect: toxicity (only in experimental
condition)
• Muscle weakness
• Bone abnormalities
5
Fat- soluble
vitamins
• Vitamin D
• Also known as sunshine vitamin
• UV is important for the conversion of vitamin D

precursors into active vitamin D
6
Fat- soluble
vitamins
• Vitamin D
• Functions
• Regulate phosphorus and calcium levels in the blood
• Stimulate conservation of calcium in the kidney
• Important in bone formation, muscle control and
nerve functions
• If in excess
• Calcium deposition: heart, muscles, other soft tissues
7
Fat- soluble
vitamins
• Vitamin E
• Plays a role in
• Formation of cell membranes
• Cell respiration
• Fat metabolism
• Antioxidant
• Protects hormones from
oxidation
8
Fat- soluble
vitamins
• Deficiencies result in
 Cell damage
 Death
 Skeletal muscle
 Heart
 Testes
 Liver
 Nerves
 Brown bowel syndrome
 Ulceration, hemorrhage and
degeneration of the bowel
 Eye and testes: affected 9
Fat- soluble
vitamins
• Vitamin K
• Discovery by Henrik Dam (1929): Nobel Prize
• Three forms
• Vitamin K1: also known as phytonadione, found in
green plants
• Vitamin K2: fish meal and synthesized in the intestine
• Vitamin K3: also known as menadione, synthetic
precursor
• Not needed in high levels since intestinal bacteria can

synthesize
10
Fat- soluble
vitamins
• Vitamin K
• For normal blood functions: clotting
• No toxicity cases reported
11
END
Assignment: Read topics about antioxidants
12
Terms to learn
Intermediate level disinfection: bacterial
Disinfectants spores are resistant
Low level disinfectants Low level disinfection: mycobacteria or

bacterial spores are resistant
Intermediate level disinfectants
- Usually for cleaning the environment
High level disinfectants
Noncritical items:
- Come in contact with intact skin
- No direct contact with the patient
Terms to learn Terms to learn

Antiseptics: chemicals that kill Sanitation: reduction of microorganisms
on an inanimate object below the infectious
microorganisms on living skin or mucous
hazard
membrane
Semicritical items: come in contact with
Bactericidal/ Bacteriostatic
nonintact skin or mucous membranes, but
do not penetrate them
Sterilization: destruction of all microbial life
Terms to learn Ideal disinfectant

Spectrum of activity is broad
Cleaning
Non-irritating
Critical items: instruments or devices that
enter sterile tissues (vascular system) Nontoxic
- High risk of infection is possible if item(s) is/are
contaminated Noncorrosive
- Items are cleaned thoroughly and sterilized before
LOTS) Inexpesive
Terms to learn Criteria in choosing a disinfectant
Decontamination: removal of disease- Effectiveness against potential pathogens

producing microorganisms
Wide margin of safety to humans
Disinfection: inactivation of disease-
producing microorganisms Effect on equipment and environment
- Disinfectants are applied unto inanimate objects
Cost
Factors affecting efficiency of a

disinfectant
Terms to learn
Type of contaminating organism
High level disinfection: - Each disinfectant is unique
- Forms that are destroyed- vegetative bacteria, Degree of contamination

mycobacteria, fungi, viruses
- Not effective against- bacterial spores Amount of proteinaceous material present
» Chemicals are also called chemical sterilants, - Chemical disinfectants are absorb and neutralized
when contact time is extended by materials containing high protein
disinfectant Phenolic disinfectants
Presence of organic matter and other
compounds such as soap (neutralization) Active ingredient found in household
disinfectants
Chemical nature of disinfectant (important
to know the mode of action as one of the Effective against: bacteria (esp G+) and
bases for selection) enveloped viruses
Concentration and quantity of disinfectant
Criteria in choosing a disinfectant Phenolic disinfectants

Contact time and temperature Resistant
- Non-enveloped viruses
* Depends on degree of contamination and amount
- Spores
of organic matter present
Active despite the presence of organic
Residual activity and effects on fabric and material
metal
For decontamination of hospital environment
- Laboratory surfaces
Application temperature, pH and - Noncritical medical items
interactions with other compounds

disinfectant Phenolic disinfectants
Effect on the environment and people Not recommended for semicritical items
exposed to the disinfectant - No valid data on its efficacy
- May cause tissue irritation due to residues
Cost
Generally safe, but prolonged contact with
skin may cause irritation
Young animals are susceptible to toxicity
Quarternary ammonium
Low level disinfectants compounds
Phenolics More used as disinfectants and not as
antiseptic
Quarternary ammonium compounds
Good cleaning agents
Factors that decrease effectivity

a a F-1ce MY VE-1C-16
- Cotton and gauze pads
Phenolic disinfectants
Common
preparations
Pa ColeL Cannes tia)
- Scrub soaps
- Surface
disinfectants
compounds Alcohols
Susceptible microorganisms Effects
- Bacteria (gram+ and gram-, though some gram- are
susceptible) - More bactericidal (vegetative forms of
- Enveloped viruses G- and G+)
- Tuberculocidal
Preparations may contain
NTPag - Fungicidal
» Ammonium chloride - Virucidal (enveloped viruses)
» Benzalkonium chloride
More tissue friendly than ammonium chloride
Alcohols
compounds
Bactericidal concentration range: 60-90%
Strong positive charge (good contact with
negatively charged surfaces): good solution in water (volume/volume)
characteristic - Higher concentrations are less effective
» Protein denaturation is inhibited in the absence of
Low toxicity (but not long contact- irritation) water
Application
- Noncritical surfaces
Floors
ae aaiieley
FI ES
Alcohols
Intermediate level disinfectants
Alcohols
Mechanism of action:
- Denaturation of proteins
Hypochlorites
» Membrane damage
lodine and iodophors
- Inhibit cell metabolism
- Cell lysis
Alcohols Alcohols
Refers to two water-soluble chemicals Needs longer contact time and do not
- Ethyl alcohol penetrate organic material
- Isopropyl alcohol
Uses
* Topical antiseptics
Good substitute for handwashing
Drying effects is counteracted by adding emollients
and skin conditioning agents
- Disinfectant of medical equipment surfaces
Alcohols
Disadvantages
- Damage shellac mountings of lensed
instruments
- Results in swelling and hardening of

rubber and plastic tubings
- Discolor rubber and plastic tiles

Alcohols Hypochlorites
Disadvantages Disadvantages
- Flammable (should be stored in cool, well- - Inactivated by organic matter
ventilated areas)
- Evaporate rapidly (extended exposure time, - Discolor fabrics

or items should be immersed)
- Toxic chlorine gas is releases when
- May cause tissue irritation mixed with ammonia or acid
- Too expensive if used as surface disinfectant
Hypochlorites Hypochlorites
Most widely used for the chlorine
Susceptible organisms
disinfectants - Enveloped and nonenveloped viruses
(correct dilution and contact time)
Forms
» Liquid — sodium hypochlorite CHLORIN > Fungi
* Solid - calcium hypochlorite, sodium B
dichloroisocyanurate LEACH
he oad
- Bacteria
Most common product: household bre
(4-6% sodium hypochlorite) - Algae (not spores)
Hypochlorites
Hypochlorites
Uses Limited activity
Advantages os Piatti(ola CUlac-\or a WYO) OMe TUL Cave mY Ltn
must be clean before rrevOR Nelli and
Broad spectrum antimicrobial activity application) Bip
- Unaffected by water hardness lo] Uhy<)
Community polyethylene
- Inexpensive Preset containers
- Fast — acting - Agent of choice for
surface disinfection
- Low incidence of toxicity for food preparations
and bathrooms

Hypochlorites
Preparations Susceptible
- Time release microorganisms
Disadvantages
formulations » Bacteria
» May cause irritation: skin and ocular - Soaps (surgical - Spores
scrubs) - Fungi
- lodine tinctures - Virus
» May cause burns: oropharyngeal, (dissolved in alcohol,
esophageal, gastric limited activity)
- Corrosiveness to metals in high

concentrations

Disadvantages
- Requires prolonged contact time
- Inactivated by organic material
» Not to be used in silicon catheters
lodine and iodophors Gluteraldehyde
Disadvantages Has wide germicidal spectrum
- lodine tinctures
Irritating to tissues Susceptible organisms
Stain fabric - Bacteria
Corrosive Alaek
- Fungi
- Spores
oe ete | ok} Cos)
lodine and iodophors Ci [Uh ==) (ol=) ahVZol=)

UES
Forms
- Surgical scrubs
» Gaseous
- Surgical antiseptics
* Liquid
* Disinfectant of
Blood culture bottles
Medical equipment Uses
/Hydrotherapy tanks - Disinfectant
Thermometers es) cl siela
Endoscopes
High level disinfectants

Ci [Uh ==) (ol=) ahVZol=)
Hydrogen peroxide Ortho-phthaldehyde
(OPA) Advantages
Gluteraldehyde » Moderate residual activity
mac) (01214 (omr-\e1[6|
- Effective in the presence of limited
Formaldehyde
amounts of organic material
Peracetic acid and
hydrogen peroxide - Potent disinfectant
Hydrogen peroxide
Gluteraldehyde
Uses
* antiseptics to clean wounds (most common)
* Cleaning for surgical sites after closure (sparing
Disadvantages
the suture lines) * Highly toxic
- Disinfect environmental surfaces (hospitals) - Needs trained individuals and well
ventilated setting
Disadvantages
- Personnel need to wear protective
» Damaging to tissues- prolonged healing time
equipment
Hydrogen peroxide
Formaldehyde
Susceptible microorganisms
- Bacteria Forms
» Liquid
Anaerobic — most susceptible » Gaseous
‘Vegetative
Spores IO ISY=ts)
- Disinfectant
mal EU SoS
Ses) Ccleit-lal8
- Fungi
Sold as formalin (37% formaldehyde)
Formaldehyde Peracetic (peroxyacetic) acid
Has rapid action on microorganisms
Effects
- Bactericidal Advantage
* Tuberculocidal » No harmful decomposition products
» No residue
* Fungicidal
- Effective even in the presence of organic matter
- Virucidal - Sporicidal even in low temperatures
* sporicidal
Use in automatic chemical sterilizer of
instruments
* Medical, surgical and dental
Peracetic (peroxyacetic) acid

Formaldehyde Disadvantage
- Corrosion (reduced by additives and pH
modifications)
Copper
DY EsFeTe NVz= 1a) &=18 (215 Sige bsts
- Potential carcinogen (exposure of person not Bronze
more than 8 hours to 0.75 ppm) del ami C1=))
- Irritating and pungent odor Galvanized iron
- Unstable when diluted
Summary of mechanisms of action of

antiseptics and disinfectants
Ortho- phthaldehyde (OPA) Target

Antiseptic or
Parana Mechanism of action
Cellenvelope Glutaraldehyde _Cross- linking of proteins

Similar to gluteraldehyde in some aspects Cell wall
Outer EDTA, other Gram — bacteria: removal
Advantages membrane _ permeabilizers of magnesium, release
of LPS
- Stable on a wide pH range (pH 3 — 9)
- Not irritant to eyes and nasal passages
- Do not require exposure monitoring
- Barely perceptible odor
- No activation
- Excellent material compatibility
Nise) ete
Target Mechanism of action
disinfectant
Ortho- phthaldehyde (OPA) Cytoplasmic

‘(alnt-19)
QACs Generalized membrane damage
involving phospholipid bilayers
aan] De 1aC
Chlorhexidine Low concentrations affect
Disadvantages membrane integrity, high
concentrations cause
- Stains proteins gray including the skin congealing of cytoplasm
» Should be handled with caution PTET als}
Induction of leakage of amino
- Requires protective equipment Phenols acids
- Instrument should be rinsed properly Leakage; some causing

uncoupling

Target Antiseptic or Mechanism of action
erecl
fol rolotoom lal diate eyi Formaldehyde Cross- linking of proteins, RNA
macromolecule and DNA
cS Gluteraldehyde Cross- linking of proteins in cell
envelop and elsewhere in the
cell
DNA intercalation Acridines Intercalation of an acridine

molecule between two layers
of base pairs in DNA
Interaction with Silver compounds Membrane- bound enzymes

thiol groups
Target Antiseptic or Mechanism of action
disinfectant
Effects on DNA Halogens Inhibition of DNA synthesis
Hydrogen peroxide, DNA strand breakage
Sl (oats)
Oxidizing agents Halogens Oxidation of thiol groups to

disulfides, sulfoxides or
disulfoxides
ede) 08 [1h Hydrogen peroxide: activity due to
formation of free hydroxy
radicals, which oxidize thiol
groups in proteins and
Cyaan
Descending order of resistance to

Prions: CUD, BSE (conclusion not universally accepted)
Coccidia: Cryptosporidium
Spores : Bacillus, C. Difficile

Mycobacteria: M. tuberculosis, M. avium
Cysts: Giardia
Small nonenveloped viruses: Polio virus
Descending order of resistance to

Trophozoites: Acanthomoeba
Gram- negative bacteria (non- sporulating):
eet 0 (eg nfe) ge 1)
Fungi: Candida, Aspergillus
Large non enveloped viruses: Enteroviruses,
Adenoviruses
Gram- positive bacteria: S. aureus, Enterococcus
Lipid enveloped viruses: HIV

VPha 102 Lab Notes

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VPha 102 Lab Notes

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MODULE 1: ANTI-INFLAMMATORY DRUGS, ANTI- ALLERGY, STEROIDS

Cardinal Signs of Inflammation

• Inflammation only occurs when there is a stimulus which could be endogenous or

- 15 years later 1844 – Cahours

Repoxalin & LIcofelone – dual

- Common Features of NSAIDs

- Therapeutic uses of NSAIDs

Subcellar cortisol biosynthesis

Module 2: RESPIRATORY SYSTEM

MODULE 3: CARDIOVASCULAR DRUGS

✓ Digitoxin (rarely used)

1b. CATECHOLAMINES / SYMPATHOMIMETIC AGENTS

CLASS ABSORPTION FATE ELIMINATION

DIETARY MANAGEMENT OF HEART DISEASE p.30

4) DRUGS AFFECTING BLOOD COAGULATION

MODULE 4: DRUGS ACTING ON THE DIGESTIVE SYSTEM

ANTIEMETICS – parvovirus na mu induce ug vomiting

ANTIEMETIC: Antidopaminergic Phenothiazines

LAXATIVES AND CATHARTICS

LAXATIVES AND CATHARTICS: Osmotic cathartics or SALINE/HYPEROSMOTIC AGENTS

MODULE 5: FLUID THERAPY AND CHEMOTHERAPY

Body Fluid Compartments:

Movement of Fluid between compartments:

Composition of Plasma and Interstitial Fluid:

Osmotic Effects of Fluids:

6 questions to consider in fluid therapy

Means on assessing the degree of dehydration

Fluid solutions: Temperature should be close to body temperature

1. Normal saline (isotonic saline -0.9% sodium chloride)

2. Isotonic dextrose-saline (0.18% sodium chloride [N/5 saline] + 4.3% dextrose)

• All rapidly dividing cells are affected by antineoplastic drugs

Miscellaneous Antineoplastics: Platinum Drugs

Miscellaneous Antineoplastics: Asparaginase

Miscellaneous Antineoplastics: Glucocorticoids

Diuretics Diuretics: Proximal convoluted tubule

Diuretics: Proximal convoluted tubule Diuretics: Descending loop of Henle

Loop (High-Ceiling) Diuretics:

Loop (High-Ceiling) Diuretics: Loop (High-Ceiling) Diuretics:

Loop (High-Ceiling) Diuretics: Loop (High-Ceiling) Diuretics:

• Combined with osmotic diuretics (mannitol) • Oral and intravenous- • Exercise-induced

• Treatment of oliguric • Treatment of

Loop (High-Ceiling) Diuretics: Loop (High-Ceiling) Diuretics:

Loop (High-Ceiling) Diuretics:

Loop (High-Ceiling) Diuretics:

• Bromide toxicity (increased bromide excretion)

• Have greater incidence of ototoxicity and GI

Thiazide Diuretics (Benzothiadiazides): Thiazide Diuretics (Benzothiadiazides):

• Weakly inhibit carbonic anhydrase (no

Thiazide Diuretics (Benzothiadiazides): Thiazide Diuretics (Benzothiadiazides):

• Nephrogenic diabetes insipidus

• Calcium oxalate uroliths

Thiazide Diuretics (Benzothiadiazides): Thiazide Diuretics (Benzothiadiazides):

Thiazide Diuretics (Benzothiadiazides):

• Mannitol: increased renal medullary blood

Osmotic diuretics: Therapeutic uses Osmotic diuretics: Adverse effects

Osmotic diuretics: Contraindications Osmotic diuretics: Precautions

Osmotic diuretics: Monitoring Osmotic diuretics: Glycerine

Carbonic anhydrase (CA) inhibitors CA inhibitors: Mechanism of action

CA inhibitors: Mechanism of action CA inhibitors: Pharmacokinetics

–If inhibited? = intraocular pressure in CA concentrations

CA inhibitors: Pharmacokinetics CA inhibitors: Adverse side effects

CA inhibitors: Adverse side effects CA inhibitors: Contraindications

CA inhibitors: Contraindications CA inhibitors: Monitoring

Potassium- sparing diuretics Potassium- sparing diuretics