Internal medicine case applications for the

veterinary pharmacist Carly A. Patterson, DVM, DACVIM (SAIM)

Texas A&M University

Society of Veterinary Hospital Pharmacists June 11, 2019

Learning objectives

Identify the challenges associated with empiric antimicrobial selection

Describe the nuances of corticosteroid therapy

Explain measures by which the veterinary pharmacist complements chronic case management

Disclosures

• I will be discussing and/or referencing off-label uses of drugs

Slido instructions

We will be using Slido.com

• Use any device (phone, tablet, computer) • Go to slido.com • Enter event code #6828• Use the “Polls” heading to answer the poll

I will open the poll when it is time

There are several questions within each poll: they all relate to the same case

Slido instructions: Case 1choose one option per drug

• The drug is safe and effective for this patient’s infection?

• The drug may be used but there are minor concern for safety issues?

• The drug may be used with extreme caution?• The drug is not indicated for treatment of this patient’s infection?

• Your decision should be based on drug safety and efficacy, considering:

• Patient signalment• Site of infection (likely types of bacteria to occur at that

site and tissue penetration of the antimicrobial)• Any ancillary therapies already present

Slido poll: Case 1• A 10-year-old, male neutered domestic shorthair (DSH)

cat is presented to your emergency clinic with extreme lethargy, anorexia, and a wound of the left thoracic limb.

• His clinical signs started two days prior to presentation and have progressively worsened. He is an indoor-outdoor cat and is up to date on vaccinations. FeLV/FIV status is negative/negative.

•• On physical examination, the cat is listless, dull, and pale.

Vital signs reveal hypothermia, bradycardia, and hypotension; the wound on the left thoracic limb is painful with a subcutaneous pocket over the left carpus.

• Based on the physical exam and clinical presentation, you are concerned that the cat is in septic shock.

Sepsis • Systemic inflammatory response syndrome: SIRS

• Widespread activation of the inflammatory system; can be sterile or infectious insult

• Sepsis• Clinical manifestation of SIRS secondary to an infectious

organism

• Septic shock • Shock that persists despite appropriate volume resuscitation

How do we choose a drug before we have culture results?

• Which pathogens are likely involved?

• Which drugs are likely effective against the pathogens likely involved?

• Which of the effective drugs will get to the site of infection?

Courtesy Dr. Sara Lawhon

Pathogens • Gram (+) aerobes

• Staphylococcus • Streptococcus

• Gram (-) aerobes • E. coli • Pasteurella

• Anaerobes

Effective drugs?

Gram (+) coverage

Gram (-) coverage Anaerobes

Cell wall synthesis

Nucleic acids

Protein synthesis

Beta-lactams

Beta-lactams: penicillins

Group Spectrum Examples

Natural penicillins Gram (+)Gram (-) Some anaerobes

Penicillin G

Aminopenicillins Gram (+)Gram (-)Wimpy anaerobes

Ampicillin Amoxicillin

Potentiatedpenicillins

Extends spectrum against beta-lactamase producing bacteria

Amoxicillin-clavulanateAmpicillin-sulbactam

Cell wall synthesis

Nucleic acids

Protein synthesis

Fluoroquinolones:Inhibit DNA gyrase

FluoroquinolonesSpectrum Examples

Aerobic Gram (-)

SOME activity: • Mycoplasma• Mycobacteria• Rickettsia • Ehrlichia

Enrofloxacin PradofloxacinMarbofloxacin Orbifloxacin

(do not use ciprofloxacin)• Papich, AJVR 2012 • Papich, JVIM 2017

High variability Suboptimal antimicrobial exposure

Fluoroquinolones:Adverse effects

Cartilage deformities:

young animals

Retinal degeneration:

cats

Rapid IV injection:

CNS adverse effects

Drug interaction…

Cell wall synthesis

Nucleic acids

Protein synthesis

Lincosamides: 50s ribosomal subunit

LincosamidesSpectrum Examples

Gram (+)AnaerobesSome Gram (-)

Clindamycin Lincomycin

Cell wall synthesis

Nucleic acids

Protein synthesis

Chloramphenicol: 50s ribosomal subunit

Chloramphenicol

Spectrum

•Gram (+)•Gram (-)•Anaerobes •Intracellular

Notes

•CNS•Prostate •Bone

Cell wall synthesis

Nucleic acids

Protein synthesis

Carbapenems

Meropenem Spectrum Notes

• Gram (+) • Gram (-) • Aerobes • Anaerobes

Drug of last resort in human medicine

Veterinary use is rarely warranted

Serious, life-threatening, documented resistant infection

Sick patient

Resistant organism

Case 2: Opportunity for self assessment

• The drug is safe and effective for this patient’s infection?

• The drug may be used but there are minor concern for safety issues?

• The drug may be used with extreme caution?• The drug is not indicated for treatment of this patient’s infection?

• Your decision should be based on drug safetyand efficacy, considering:

• Patient signalment• Site of infection (likely types of bacteria to occur at

that site and tissue penetration of the antimicrobial)• Any ancillary therapies already present

• A 6-year-old, intact male Doberman pinscher presents with a 5-day history of stranguria, hematuria, and pollakiuria.

• His appetite is slightly reduced. There has been no change in his thirst. He has no prior history of medical problems. He is on heartworm preventative, but not other medications.

• He seems uncomfortable on palpation of his caudal abdomen. The remainder of his physical examination is normal.

• His CBC and chemistry panel are within normal limits. His urinalysis shows hematuria, pyuria, and bacteriuria, and the USG is 1.020.

• A 6-year-old, intact male Doberman pinscher presents with a 5-day history of stranguria, hematuria, and pollakiuria.

• His appetite is slightly reduced. There has been no change in his thirst. He has no prior history of medical problems. He is on heartworm preventative, but not other medications.

• He seems uncomfortable on palpation of his caudal abdomen. The remainder of his physical examination is normal.

• His CBC and chemistry panel are within normal limits. His urinalysis shows hematuria, pyuria, and bacteriuria, and the USG is 1.020.

How do we choose a drug before we have culture results?

• Which pathogens are likely involved?

• Which of the effective drugs will get to the site of infection?

• Which drugs are likely effective against the pathogens likely involved?

Courtesy Dr. Sara Lawhon

Where is the infection?

Urinary tract

Intact male dog

We must assume

the prostate is involved

Urinary tract

Uncomplicated

Sporadic bacterial

No comorbidities

First line drug options

Amoxicillin Trimethoprim-sulfonamides

Complicated

Anatomic abnormality

Comorbidity

Prostate

Use C&S data

UTI with prostatic involvement:Properties of ideal antimicrobials

• Un-ionized • Able to cross membranes

• Basic • They get “trapped” in prostatic fluid • Achieve higher tissue concentrations

• Lipid-soluble • Able to cross membranes

Antimicrobials:prostatic concentrations

Fluoroquinolones

Trimethoprim-sulfas

Chloramphenicol

Clindamycin

The power of prednisone

Hypothalamus

Pituitary gland

adrenal adrenal

CRH

ACTH

Cortisol

(-)

(-)

Aldosterone

Exogenous glucocorticoids

Cortisol • Metabolism • Water, electrolyte balance• Hemolymphatic • Inflammatory/immune• Cardiovascular• Bone, cartilage• Skeletal muscle • Central nervous system • Respiratory • GI tract • Reproduction

Glucocorticoids: Adverse effects

• Endocrine • Iatrogenic hyperadrenocorticism (HAC)• Insulin resistance and secondary diabetes mellitus

• Gastrointestinal• Polyphagia

• Renal • PU/PD• UTI

• Musculoskeletal• Muscle atrophy • Myotonia

• Skin • Opportunistic infections*** • Calcinosis cutis • Alopecia

Glucocorticoids:small animal medicine

• Dose references: prednisone in the dog

• Physiologic 0.2 mg/kg/day

• Anti-inflammatory 0.5-1 mg/kg/day

• Immunosuppressive 2 mg/kg/day

Did you make a reasonable tentative

dx?

Are glucocorticoids indicated? • If so, which one?• Which dose?

Which adverse effects are to be

expected?

When should the patient be re-

examined?

What criteria is determining success

of therapy?

Glucocorticoids: Case 1

• 4 yo FS Jack Russell Terrier (JRT)• Chief complaint: 2 weeks of inappetence • History:

• Previously normal dog • 2 weeks of progressive inappetence • Hyporexia anorexia • One episode of vomiting & diarrhea

• Owner is very concerned

Glucocorticoids: Case 1continued

• ACTH stimulation results: TAMU GI Lab

Sample Results Units

A (pre) <1 μg/dL

B (post) <1 μg/dL

Glucocorticoids: Case 1thought questions

• Are glucocorticoids indicated?• If yes, which one?• Which dose?

• When should the patient be re-examined?

• What adverse effects do you anticipate?

• How do you monitor therapy?

Glucocorticoids: Case 2• 4 yo MC mixed breed dog • Chief complaint:

• Mixed bowel diarrhea• 6 months’ duration; progressively worse

• History:• Diet trials • Antibiotic trials • No improvement noted • Lost 33% of body weight

Glucocorticoids: Case 2thought questions

• Are glucocorticoids indicated?• If yes, which one?• Which dose?

• When should the patient be re-examined?

• What adverse effects do you anticipate?

• How do you monitor therapy?

Learning objectives

Identify the challenges associated with empiric antimicrobial selection

Describe the nuances of corticosteroid therapy

Explain measures by which the veterinary pharmacist complements chronic case management