Combined set for Pharm & Anes Final

combined midterm sets for final

Define a seizure:

a sudden, intense discharge in the thalamocortex; makes goal-directed behaviors impossible and may be accompanied by motor movements

Define a convulsion:

a generalized tonic-clonic motor seizure

Define tonus:

increased muscle tone

Define clonus:

alternating, rapid contraction and relaxation (ex paddling)

Define status epilepticus:

• a series of seizures in rapid succession without periods of intervening consciousness

• these can last 30+min and may lead to hyperthermia, brain damage, and death

Define epilepsy:

recurrent, spontaneous impairment of brain function with:

• loss of consciousness (almost always)

• abnormal motor phenomena (usually)

• mental or sensory disturbances

Define a focal seizure:

• aka partial seizures, petit mal

• often unilateral cerebral involvement

• mild abnormalities which may be go unnoticed (eg sensory abnormality, altered consciousness)

Define a generalized seizure:

• aka gran mal

• loss of consciousness (usually)

• bilateral cerebral involvement

• usually tonic-clonic motor activity

What is the most commonly used medication in vet med for long-term seizure prevention?

phenobarbital

What is the goal of anticonvulsant drugs?

to reduce the frequency and severity of seizures (not to abolish them)

What is the main drug used to STOP seizures?

diazepam

Why is diazepam not used for long term treatment?

• tolerance develops within 1-2 months

• in cats hepatic toxicity is likely

Why are so few drugs used in vet med for seizures when so many exist for humans?

• often metabolized very differently - so may need more doses or may have different adverse effects

• cost! as they are life-long drugs and can be very expensive

What are some important considerations with regards to anticonvulsant drugs?

• responses can vary between patients

• steady-state takes a long time to achieve (long drug half-life)

• rechecks and owner logs are important

• plasma concentrations need to be monitored

• if stopping or changing drugs - needs to be slow to avoid rebound activity

• combo drug therapy may yield better results with less adverse effects (as both drugs are at lower doses)

What is phenobarbital and how does it work?

phenobarb is a barbiturate with unique anticonvulsant properties at low concentration; works by facilitating GABA at it’s receptor → hyperpolarizes neurons (increasing the action potential)

Half-life for phenobarbital:

• dogs: ~48h, range 20-140h

• cats: little less than 48h (wide range between cats)

• horse: ~18h

What causes the need for phenobarbital dosages to increase gradually throughout life?

because it induces p450 enzymes (which results in faster metabolism and decreased efficacy); mainly in dogs, less in cats

What can happen after lifelong increases of phenobarbital in an old dog?

the required dosage to treat may be hepatotoxic; means that needs to be given with another medication or switched to KBr instead

Advantages of phenobarbital:

• effective seizure control

• inexpensive

• best outcomes of any monotherapy

• administration q12hr

Disadvantages of phenobarbital:

• sedation

• PU/PD, polyphagia, vomiting (mainly dogs)

• blood levels may stabilize in ~14day (dog) or ~9day (cat) but is highly variable

• P450 induction (enhanced metabolism of PB and other drugs; p450 inhibitors [ketoconazole, chloramphenicol] can potentiate phenobarbital

• potential hepatoxicity in dogs

• blood levels should be monitored

• some animals do not respond

What is the most common anticonvulsant in cats?

phenobarbital

What anticonvulsant cannot be used in cats? Why?

KBr → contraindicated; 30-50% of cats develop asthma-like symptoms that can be fatal

Is phenobarbital used in large animals?

Yes, but only for short-term treatment associated with: head trauma, lead poisoning, and polioencephalomalacia (thiamine deficiency)

MOA of potassium bromide:

Br- hyperpolarizes membranes by flowing through chloride channels in the membrane, inhibiting action potentials

Advantages of KBr:

• Good anti-epileptic effects sometimes as good as phenobarbital

• Br- not metabolized by the liver, excreted in urine w/ no hepatic toxicity

• inexpenisve

• administration q24h

Disadvantages of KBr

• narrow therapeutic index

• CNS depression → hindlimb ataxia, dizziness, lethargy, and sedation

• some small dogs are highly sensitive and are more likely to have an intolerable degree of sedation than with PB

• 30-50% cats develop life-threatening pulmonary inflammation

• PU/PD/PP/vomiting and weight gain possible

• vomiting can persist for months

• takes months to titrate to correct level (24days in dogs)

What is the rare possible outcome when using anticonvulsants?

pancreatitis

How long does it take to reach peak plasma concentration with KBr?

5 half-lives → 120days

How is KBr sold?

not sold as pharmaceutical; prep as industrial powder, may be flavored by veterinary compounding pharmacies

How does the body treat Br-?

the same as Cl-

→ so increased intake of NaCl leads to increased Br- secretion in urine (urinary diets meant to prevent bladder calculi can do this)

→ avoid changes in dietary Cl-

What is levetiracetam (Keppra)?

• anticonvulsant with unknown MOA

• often used in combination with PB in cats/dogs, may allow dose reduction for other anticonvulsants

• not effective in controlling seizures alone in humans, unclear if works alone in other species

• TID admin typically

How is gabapentin used with anticonvulsants?

• synthetic analogue of inhibitory neurotransmitter GABA

• well tolerated in dogs and cats

• often TID

• may allow dose reduction of other anticonvulsants

What is diazepam? How is it used for seizures?

• diazepam a highly lipophilic benzo that rapidly crosses the BBB

• used to stop seizures or abort impending seizures

• controlled drug

What can occur if diazepam is used long-term in dogs for seizures?

• short half-life results in use 3-4x per day

• within 1-2 months tolerance develops

• no longer effective in emergencies

What can occur if diazepam is used long-term in cats for seizures?

• can be used in ~75% of cats

• may be recommended in refractory (not treated by other meds) cases

• hepatic toxicity worse that phenobarbital

• potentially fatal ADR when administered orally → idiosyncratic hepatic necrosis

How to give diazepam in case of emergency?

• IV admin in clinic

• syringe w/ teat cannula per rectum

• at first sign (prodromal and then q 20-40min if no seizure

What can be used if diazepam fails?

IV phenobarbital; if that fails then general anesthetics

What drugs are used in humans but are not indicated in animals?

• primidone: phenobarbital precursor → hepatic toxicity worse than PB

• phenytoin: half-life in dogs too short to be useful (3-4h)

• clonazepam: ineffective after 1-2 months (tachyphylaxis)

MOA: Penicillin

Inhibition of cell wall synthesis

Adverse effects: Penicillin

• hypersensitivity (including contact hypersensitivity)

• potentially fatal colitis in hindgut fermenters with oral admin.

• reduction of seizure threshold

General spectrum: penicillin G

Gram positive aerobes, anaerobes

General spectrum: amoxicillin

Gram positive aerobes, anaerobes, and several Gram negative aerobes

Prudent use penicillin

first line: penicillin G, amoxicillin

second line: potentiated penicillin

Penicillin metabolism

• excreted intact in the urine

• penicillin G is not acid stable

• oral availability of amoxicillin is ~90%

MOA: Cephalosporins

inhibition of cell wall synthesis

Adverse effects: Cephalosporins

• hypersensitivity (including contact hypersensitivity)

• oral administration may cause potentially fatal colitis in hindgut fermenters

• reduction of seizure threshold

General spectrum: Cephalosporin

first gen: similar to amoxicillin

third gen: a mix but mainly Gram negative aerobes

Prudent use: cephalosporins

first line: first generation

second line: third generation

Metabolism: cephalosporin

• only a few are acid-stable (ex. cephalexin)

• not destroyed by penicillinases, but may be inactivated by some beta-lactamases

• some third-gen drugs enter CNS readily

MOA: aminoglycosides

inhibition of protein synthesis (bactericidal effect)

Adverse effects: aminoglycosides

• nephrotoxicity

• ototoxicity

General spectrum: aminoglycosides

• Gram negative aerobes

• Staph

• Mycoplasma

Prudent use: aminoglycosides

first line: topical administration

second line: systemic administration

Metabolism: aminoglycosides

• highly ionized → negligible oral or topical absorption

• food residues → 1 year with parenteral administration

MOA: Tetracycline

inhibition of protein synthesis (bacteriostatic effect)

Adverse effect: Tetracycline

• incorporation into growing long bones & teeth

• nephrotoxicity in dehydrated patients

• tissue irritation (pain on injection; vomiting oral dose)

• risk of esophageal damage in cats

• etc

General spectrum: tetracycline

• all species: atypical bacteria (usually drug of choice)

• livestock: broad spectrum

Prudent use: Tetracycline

first line

Metabolism: tetracycline

lipid-soluble tetracyclines (ex. doxycycline) are useful against intracellular pathogens

MOA: TMS

inhibition of folic acid synthesis

Adverse effect: TMS

• lacrimotoxicity in dogs (KCS)

• Nephrotoxicity in dehydrated patients

• hypersensitivity (including contact dermatitis)

Prudent use: TMS

first line

Metabolism: TMS

ineffective in presence of pus; distributes to all tissues

MOA: macrolides

inhibition of protein synthesis (bacteriostatic effect)

Adverse effects: macrolides

• tissue irritation; pain on injection (all macrolides); nausea & vomiting (oral erythromycin)

• potentially fatal colitis in hindgut fermenters (most likely with oral admin)

General spectrum: macrolides

• erythromycin: relatively broad

• newer macrolides: a mix, but especially Gram negative aerobes

Prudent use: macrolides

• erythromycin: first line

• newer macrolides: second line

Metabolism: macrolides

• concentrate in lungs

• enters cells

• most newer macrolides have long half-lives

• erythromycin: inhibits P450 enzymes and stimulates motilin receptors (changes half-life of other drugs)

MOA: fluoroquinolones

damage DNA (inhibits DNA gyrases & topoisomerases)

Adverse effects: fluroquinolones

• cartilage damage (immature animals)

• retinal damage (enrofloxacin in cats)

• reduction of seizure thresholds

General spectrum: fluroquinolones

similar to gentamicin (but effective against more atypical bacteria)

Prudent use: fluroquinolones

second line (ongoing issues with prudent use)

Metabolism: fluroquinolones

• most have long half-lives (except enrofloxacin)

• oral absorption ~100%

• concentrate in lung

Accrediting group in Ontario for records:

College of Veterinarians of Ontario (CVO)

What records are required in relation to anesthesia?

1. Controlled drug log

2. Surgical and anesthetic log

3. Medical record

Reasons to keep controlled drug logs:

need to maintain record of how much of a controlled substance was used and who it was given to; to ensure that drug is not being abused/used inappropriately

Why keep anesthetic/surgical records?

• for patient - allows trend monitoring, informs future care

• vet staff - legal doc that ensures done correctly, communication between staff, and trend ID

• owner - ensure that things have been done correctly

Why keep medical records?

• continuity of care

• effective communication between client and staff

• legal documentation of care

How does documentation differ for large animal or ambulatory clinics?

• more often standing, injectable anesthesia

• do still need to maintain all 3 records

• must provide good directions and withdraw times for after care (for animals going into food chain),

What time period is associated with the highest morbidity and mortality in relation to anesthesia? Why?

Recovery! → because this is the time when animal is extubated, they may not be normothermic, and monitoring often stops

What occurs when the anesthesia gets “too deep”?

CNS activity decreases and cardiovascular/respiratory/thermoregulatory systems are below the desirable range = dangerous to patient

How do we ensure that our patient doesn’t get “too deep”?

Monitor! → both human watching and recording & mechanical monitors in place (ex. Doppler or pulseOX)

What do we physically measure to monitor anesthesia?

• eye position

• eyelid movement

• reflexes

• tearing

• muscle tone/relaxation (jaw tone)

• Physiologic variables → HR, RR, and patterns

Where do the eyes roll in a dog/cat that is well anesthetized on inhalant?

ventromedial

When does spontaneous blinking occur in a patient?

• when too light

• with inj ketamine (esp in horses) → may be adequately anesthetized

When is the medial vs lateral palpebral lost in companion animals?

lateral lost first, then medial → gone indicate more adequate level of anesthesia

How is the palpebral assessed in horses as opposed to companion animals?

as one reflex, fanning finger along top eyelashes

What reflex is used only in horses to asses anesthetic plane?

tearing

What does lack of relaxation mean in terms of jaw tone?

no muscle relaxation = light plane of anesthesia

Increase in HR, BP, RR, or resp effort and pattern could all indicate:

light plane of anesthesia

How do signs differ in companion animals under inhalant anesthesia vs injectable?

• eyes remain central in injectable

• palpebral reflex present until deep (as opposed to mod-deep) in injectable

• jaw tone remains tight until medium (as opposed to med-light) in injectable

What physiologic things are we assessing by observation?

• mucous membrane color

• respiratory rate and effort

What physiologic things are we assessing by palpation?

• pulse

• CRT

• temperature of extremities

Equipment for monitoring heart rate:

stethoscope or EKG (standard or esophageal)

Equipment for monitoring pulse rate:

• pulse minder

• pulse oximeter

• Doppler BP monitor

• oscillometer BP monitors

Equipment for monitoring bloop pressure:

• indirect/non-invasive

  • Doppler

  • Oscillometer

• Direct/invasive

Equipment for monitoring blood oxygenation:

• pulse oximeter

• arterial blood gas

Equipment for monitoring CO2 ventilation:

• capnography

• arterial blood gas

Why is it important to maintain adequate body temperature during recovery?

shivering dramatically increases O2 consumption + it is unpleasant and uncomfortable

Describe Phase 1 of GA:

• between admin of anesthetic and loss of consciousness

• can still hear and respond to stimuli but increases the pain threshold (analgesia w/o amnesia)

• end goal = endotracheal intubation

• ideal scenario: quick & smooth loss of consciousness, good muscle relaxation