POS Flashcards
What are the 2 benefits of using multiagent chemotherapy?
- decrease dose per agent
- decrease adverse effects on normal cells
How do we prevent cancer cell replicative immortality?
Telomerase inhibitors
What do cancer cells secrete to stimulate angiogenesis?
VEGF
Name an anti-angiogenic drug
Toceranib phosphate (against VEGF)
What are the 2 pathways that lead to cell death?
- Intrinsic pathway: p53
- extrinsic pathway: Caspase
How do cancer cells sustain proliferative signalling?
- make their own GF (ie EGF)
- alter the receptor so that it is constantly activated (i.e. KIT mutations in MCT)
- increase receptor expression (so increased number of receptors, increasing sensitivity to a ligand)
- alter signalling molecules (Ras and Raf)
What type of inflammation can favorise to cancer?
chronic inflammation
What are the hallmarks of cancer
1) induce angiogenesis
2) immune evasion
3) invasion and metastasis
4) replicative immortality
5) genetic instability
6) avoiding apoptosis
7) sustaining proliferative signalling
8) avoid growth suppressors
9) deregulating cell energetics
10) Promote inflammation
If there is a KIT mutation on a MCT, what drugs can we use and what do they do?
- Toceranib phosphate and Masitinib
- These drugs prevent cell receptor auto-phosphorylation. These receptors are switched on in cancer and they enable cell proliferation
How do tumours metastasise to distant sites?
- upregulate metalloproteinases which disrupt surrounding tissues
- alter cell adhesion molecules (such as E-cadherin in mammary tumours)
Why do we use anti-inflammatories in cancer?
Chronic inflammation can promote cancer.
What can we use to prevent genetic instability in cancer cells?
PARP inhibitors
Do tumour cells favour glycolysis or oxidative phosphorylation under aerobic conditions?
Glycolysis (upregulate GLUT 1 receptors to increase glucose intake)
what is ONCEPT vaccine meant to do?
Increase immune response to destroy cancer cells (ie NK cells, CD8 and CD4 T helper cells)
Collies and Collie-like breeds have an adverse reaction to which drug?
Ivermectin
Why do Collies have Ivermectin toxicity?
The MDR1 gene mutation leads to a lack of Glycoprotein which is an efflux pump on the brain. BBB is more permeable.
Permethrin is toxic to which species? What is the side effect?
Cats
Hyperexcitability and convulsions
A drug that has a high therapeutic index is safe or unsafe …?
safe
A drug with a low therapeutic index is safe or unsafe?
unsafe
What physiological factors influence drug metabolism in the neonate?
- increased water in body
- decreased gut motility
- immature liver enzymes
- reduced GFR
- less gut enzymes
What is the likelihood of an idiosynchratic drug reaction?
1/2000
Who do you report adverse drug reactions to?
VMD
What is the main physiological roles of PGE2 and PGI?
1) Protect the GI:
- prevent gastric acid secretion
- increase cell turnover via cell to cell messaging
2) Protect the kidneys:
- maintain renal perfusion if dehydration occurs
Name 2 non-selective NSAIDs
ketoprofen and Aspirin
Name two preferential NSAIDs
meloxicam and Carprofen
Name 2 selective NSAIDs
rubenocoxib and firocoxib (Previcox)
What are the 3 indications for use of NSAIDs?
1) To treat inflammation and pain in NON-ALLERGIC inflammatory disease
2) perioperative and postoperative management
3) Decrease platelet aggregation
Can NSAIDs be used for cats with CKD
Yes- may increase survival time
What adjustments can you make when giving NSAIDs to a patient with liver disease?
Only use if necessary.
Increase dosing to compensate for the decreased metabolism
The main route of NSAID elimination
The Liver
No NSAID is … safe
renally
Name some factors that increase the risk of GI damage with NSAID use
- corticosteroids
- decreased BF to GIT
- hypovolaemia
- dehydration
- pharmacokinetics
- pancreatitis and inflammation of the GIT
If you suspect a patient has pancreatitis should you give them NSAIDs?
No
If you suspect a patient has inflammation of the GIT should you give them NSAIDs?
No
Should you use NSAIDs in a patient with CHF?
Best not due to Na retention
What diseases increase sodium retention
- cirrhosis
- Cardiac failure
- nephrotic syndrome
What other drugs should you NOT use in a patient with renal disease?
- ACEi (as angiotensin has a protective effect on the kidneys)
- alpha 2 agonist (decreased BP)
- ACP (decrease BP)
If a racing horse is given intra-articular steroid how many days withdrawal are required prior to racing?
14 d
If a racing horse is given an NSAID (except flunixin), how many days must he withdraw before racing?
8 d
Whats drugs are licensed in cattle for respiratory disease and mastitis?
- ketoprofen
- meloxicam
- flunixin
- carprofen
Why is it difficult to treat brain tumours with chemotherapeutics?
chemotherapeutics are hydrophilic so do not cross the BBB readily
How can we improve antibiotic penetration to brain tissue?
increase dose so that the difference between concentration gradient is increased
When can we say a patient has epilepsy?
If they have has 2 epileptic seizures MORE THAN 24hours apart
How do we treat epilepsy?
AED
Is reactive seizure a sign of epilepsy?
No
What is the best way to treat a reactive seizure?
treat the underlying cause
/- AED
When GABA binds to GABA A receptor what happens?
Cl- comes into the neuron
Cl is negatively charged so the neuron is hyperpolarised –> reduced neuronal excitability
What happens when GABA binds to GABA B receptor?
K flows out
Loss of positive charge, neuron becomes hyperpolarised—>
reduced excitability
What is the 3 mechanism of action of AEDs?
- increase GABA
- decrease neuron excitability
- modulate cation conductance
When should you start AED treatment?
- cluster seizure
- status epilepticus
- structural change (tumour)
- 2 seizures in less than 6 months
- severe post ictal signs ( aggression, blindness, severe disorientation)
AED treatment is a balance between… and ….
improving quality of life and eliminating seizures
How many dogs respond to AEDs?
2/3rds
How many idiopathic epileptic dogs are seizure free with AEDs?
15-30%
List the AEDs from safest to least safe
Leviracetam
Imepitoin
Phenobarbital
Potassium Bromide
What is the first line therapy for treating seizures? (2 drugs)
- Phenobarbital
- Imepitoin
When may you consider to use Potassium bromide instead of Phenobarbital?
- Liver disease
When may you consider using Potassium Bromide with Phenobarbital?
If Phenobarbital is at maximum dose but seizure control is not sufficient.
What is the mechanism of action of Phenobarbital
GABA R Agonist
Phenobarbital is contraindicated in dogs with
HEPATIC DYSFUNCTION
How does Phenobarbital damage the liver?
it increases p450 enzyme in the liver which increases ROS
Imepitoin is not licensed for what type of seizure?
cluster seizure
If phenobarbital serum concentration is <30mg what can we do?
Increase the drug dose
If phenobarbital concentration is between 30-35mg/l what can we do?
add Potassium Bromide
How long does it take to acquire a steady state when starting treatment with Phenobarbital?
14 days
What is the mechanism of action of Imepitoin?
low affinity partial agonist of the benzodiazepine on GABA A receptor
Do we need to monitor serum concentration in Imepitoin?
No
Do we need to monitor Phenobarbital serum concentration?
Yes- target is 35mg/L
Do we need to monitor Potassium Bromide serum concentration?
Yes- target is 1000-3000mg/L
How long does it take to reach a steady state with Imepitoin?
1-2 days
How long does it take to reach a steady state with Potassium Bromide?
120d!!!
How long does it take to reach a steady state with Phenobarbital?
14 days
What it Potassium bromide MoA?
Not well understood- thought to be act like a Cl- ion (in competition with Cl-)
What are some of the acute side effects of Phenobarbital?
- sedation
- ataxia
- immune mediated thombocytopenia/ neutropenia (STOP TX)
- acute hepatotoxicity (STOP TX)
- pancreatitis
what are some of the chronic side effects of Phenobarbital?
PU
PD
PPhagia
Hepatotoxicity
If the liver enzymes are mildly elevated whilst treating an animal for seizures, should we be concerned?
- mild elevations in liver enzymes are to be expected
What happens if a dog treated for epilepsy with Potassium Bromide has a large intake of Cl-? (ie seawater)
increased excretion of Potassium Bromide- risk of seizure
Which AED is contraindicated in Cats?
- Potassium bromide
What is the 1st line treatment for AED in cats?
- Phenobarbital (same as dogs)
- Leviracetam
How do you withdraw AEDs?
20% decrease every month
If left untreated status epilepticus can lead to…
multiple organ failure
What Is your approach to status epilepticus emergency?
1) stabilise patient
ABC, Get an IV catheter in, and active cooling if temp above 40
2) emergency diagnostics
- CBC, biochem- look at electrolytes, if any toxins,
- ECG
3) Drug treatment
- glucose and electrolyte correction
- diazepam and midazolam
- pheno or levi
(if persists consider propofol, benzo,…)
colostrum and anti-serum are examples of …. immunisation
passive
If we give an intra-nasal vaccine which antibody do we stimulate
IgA
An individual is immunologically immature till what age?
6 weeks
MDA can influence up until when
12 weeks (maybe 14?)
When do we give dogs their first, second and third (primary course)
8 weeks, 12 weeks and 14-16 weeks
Poor vaccine responder breeds
Doberman and Rottweilers
When is the 1st booster after the primary vax course?
1 year
Boosters for non core vaccines (lepto, KC, and leishmania) are recommender every …
year
(they are not very immunogenic compared to MLV vaccines)
MLV vaccines are said to have a duration of —- years
3!!
WSAVA recommends that we do serology for MLV core vaccines for dogs over the age of .. so that we can decide whether a booster is necessary
2 years old
If a dog/ cat has missed its MLV booster - do we need to start the primary course again?
no! Memory lymphocytes do not forgeti
What does the FHV protect against?
- protects against clinical signs
- does not protect from infection and shedding
What are the core vaccines for cats?
- Colicivirus (cat flu)
- Herpes Virus (cat flu)
- Panleukopenia virus
Remember Cats Hate People
What are the core vaccines for dogs?
- Distemper
- Hepatitis
- Parvovirus
Remember Dogs Hate people
List some passive vaccines for horses
- tetanus antitoxin
- hypermune serum
- rotavirus (mare vaccinated)
What combined vax do we have for rabbits?
- myxomatosis
- Rabbit Viral Hemmoragic Disease (RVHD2)
What are some vaccines we have for horses (active immunisation)
- equine influenza virus
- EHV 1 and 4
- Tetanus toxoid
- Other: West Nile Virus, Strangles, EAV
What are the WSAVA’s guidelines for serology?
- 3-4 weeks post vaccination (typically primary course)
- prior to deciding booster requirements
It is no longer a legal obligation to test for rabies via serology- should we still do it?
yes
You suspect an animal has been recently infected, what test can you do? and what will you be testing?
Look for antigen
Test at site of infection
PCR, C and S, ..
You suspect an animal has been infected with a virus for 7 days, what test can you do?
Look for antibody.
Paired acute and convalescent sera- 2-3 weeks apart.
look for a rise in antibody titres
If you test for antibody and there is more IgM than IgG, what does that suggest?
a recent exposure to the antigen (IgM is made before IgG)
If you have a patient with anemia without hypovolaemia what transfusion would you give him?
Packed RBC
If you have a patient requiring a transfusion with a rodenticide poisoning- what may you give him?
plasma
Frozen plasma transfusion is rich in…
clotting factors
If your patient has Von willebrand disease and requires a transfusion what may you give him?
cryoprecipitate
What is contained in cryosupernatant?
anti-thrombin
Vit k dependent CF
albumin
What is in cryoprecipitate?
vWf
VIII
fibrinogen
A patient has had a hemmorhage what transfusion would you give him?
whole blood
When do you know if a blood transfusion on a dog has been successful?
after 4 days
Cat blood type A has which antibodies
B
Cat blood type AB has which antibodies?
none
What are the contraindications for inducing emesis?
- neurological signs : animal cannot maintain its airway
- toxin is:
1) caustic
2) detergent
3) petroleum
What is the main risk with inducing emesis?
- aspiration pneumonia
What are the risks associated with gastric lavage?
- hypothermia
- aspiration pneumonia
When may you use activated charcoal for an intoxication?
- if the substance binds to AC
- improved with enterohepatic metabolism
When would you not so a gastric lavage?
- caustic substance
When would you perform diureses?
If the toxin is nephrotoxic
What would the contraindications be for diuresis for intoxication?
- anuric- oliguric (risk of fluid overload)
- cardiac problems
- respiratory problems
How do you do dermal contamination?
vegetable oil and fairy soap!
What are the adverse effects of using intra-lipids?
- hypersensitivity
- lipaemia
- pancreatits
If your patent is intoxication but is showing neurological signs- how will you treat him?
- gastric lavage/ enema
What does activated charcoal NOT bind?
- ethylene glycol
- alcohol
- petroleum
- heavy metals
- xylitol
What are the complications of activated charcoal?
- if it contains sorbitol can lead to dehydration
- aspiration pneumonia
When would we use dermal decomtamination?
Permethrin in cats,
oil spill,
engine oil
For which toxins can we use intralipid?
- mycotoxins,
- marijuana
- permethrin
- ivermectin
- LA
What clinical signs can you see with metaldehyde poisoning?
- CNS excitation
- heat stroke
- vomiting
What are the clinical signs with mycotoxins?
- Tremors
- hepatopathy
- vomiting
Methylxanthines intoxication- what are there mechanism of action and resulting clinical signs?
- inhibits adenosine—> seizure, tremor, tachycardia and vasocontriction
- inhibits phosphodiesterase–> increases calcium–> increased cardiac contractility and muscle contraction
Permethrin intoxication- mechanism of action , clinicals signs, and treatment.
toxic to cats due to lack of glucoronidase
bind to Na channels—> repeated stimulation —> hyperexcitability and tremors
treatment:
- wash with dishwashing liquid
- intralipid
- midazolam
Misoprostal can we used in which species and for which toxicity?
NSAID toxicity (PG analogue)
- used in dogs
What are the different stages for ethylene glycol toxicity?
Stage 1: GIT and CNS, PU/PU
Stage 2: transient recovery
Stage 3: renal signs
If you don’t catch ethylene glycol toxicity … they die
fast
3 hours window
Paracetamol created which toxic metabolite in cats?
NAPQI
What are the consequences of paracetamol toxicity in cats?
- hemolysis
- methaeglobinemia
- Heinz bodies
- hepatocellular damage
How can you dx ethylene glycol toxicity?
- Calcium oxalate crystals in urine
- azotemia
- EG test
- woods lamp on urine
- high anion gap metabolic acidosis
What can you use to treat ethylene toxicity?
- 4 methylpyrazole (this inhibits the alcohol dehydrogenase)
- ethanol (competes for substrate binding)
For which intoxications may you consider diuresis?
- grape
- lillies
What are the clinical signs associated to lilly poisoning?
- GIT,
- PU
- oliguria
How does xylitol cause toxicity?
- increases insulin–> hypoglycemia
- causes hepatic necrosis (increased ALT, decreased Alb, )
How do you treat xylitol toxicity?
- emesis
glucose bolus
liver protectants
What can cause hepatotoxicity?
- Xylitol
- mushroom
- paracetamol
List the different roles of surgery
- diagnosis
- palliative (remove clinical signs)
- curative
- prophylactic
- cytoreductive (leave dirty margins)
What are the 4 points that need to be considered when planning for surgery?
1) histological diagnosis
2) extent of local disease
3) staging: any local or distant metastasis?
4) nutritional status of the patient
the most active and invasive parts of a tumour are at …
the periphery
Why is it important to get the first surgical excision right for cancer resection?
- less normal tissue so more difficult closure.
- incomplete resection leaves the most aggressive parts of the tumour behind.
- can’t predict where cancer cells may have extended to.
- wider resection is required than the first time
fear of reconstruction for a cancer resection should NOT compromise…
excisional margins
What are the two types of needle biopsies?
- FNA
- core (tru-cut)
What is this biopsy technique called? is it incisional or excisional?
Punch biopsy
incisional
With excisional biopsies it is important to remove….
the fascia!!
When inspecting LN during cancer resection, is palpation and inspection enough?
No
Are the nearest LNs to the cancer the drainage LNs?
Not necessarily- you need to know sentinel LN
Why do we want to remove/ or biopsy sentinel LN for oncological surgery?
Will help with staging—> prognosis
What do you do if the sentinel LN is inaccessible?
Just do a biopsy
When labelling a mass for histopathologist, do you indicate the margins that are closest or furthest away from the mass?
closest
What type of information do we get from excisional biopsies for cancer?
1) tumour type
2) tumour grade
3) Vascular or lymphatic involvement
4) margins- clear or not? narrow or wide?
5) LN involvement or not? (staging)
What is the pseudocapsule?
sheath containing compressed viable tumour cell
This is NOT a capsule even though it looks like one.
Excisional margins should include…
Normal tissue
Tumour tissue
Surgical dose needs to match what 2 things?
1) tumour type
2) intended outcome
If in the area of cancer resection there is a layer of fat underneath what may our deep margin measure?
Fat (approx 1-3cm)
If in the area of cancer resection there is a layer of fascia underneath what may our deep margin measure?
it is the layer of fascia
What are the 3 areas of concern when considering deep margins for cancer resection?
1) pectoral
2) biceps femoris
3) platysma
What are the 4 types of radical excisions (surgery)?
- radical local excision
- muscle group excision
- compartmental excision
- amputation
If you have an invasive carcinoma of the nasal planum - what type of surgery would you do?
radical local excision (involves 1 or 2 facial planes)
If you have invasive sarcoma of the chest wall - what type of surgery would you do?
radical local excision (involves removal of 1-2 fascial planes)
If you have invasive ear cartilage cancer what surgery may you consider?
Compartmental excision (use the ear cartilage as a fascial plane)
What are these pictures showing?
Radical muscle group excision
What immune mediated disease could this be?
IMHA
immune mediated disease is otherwise known as a loss of …
self-tolerance
What can trigger an immune mediated disease?
- a drug
- infection
- neoplasia
If a young dog has immune mediated disease is it more likely to be primary or secondary?
primary
If an old dog has acquired an immune mediated disease, is it more likely to be primary or secondary?
secondary
Most immune mediated disease present as waxing and waning except for…
IMHA
Immune mediated Thrombocytopenia
What is this?
Megaesophagus due to myasthenia Gravis.
There is a thymoma–> paraneoplastic syndrome—> MG
Which tests can we use to diagnose IMHA?
- Coombs Test
- In saline Agglutination test
both tell us there is immune mediated destruction if there is agglutination. However does not tell us whether 1ry or 2ndary IMHA.
What test can we use to detect SLE?
ANA
antinuclear antibodies
Immune mediated diseases can be 1ry (idiopathic) or secondary
secondary could be due to infection, neoplasia, drugs
What is the most common acquired immune mediated disease affecting the neuromuscular system?
Acquired Myasthenia Gravis
Name the different types of myasthenia gravis
1- focal ( ie. megaesophagus)
2- generalised (i.e. weakness)
3- paraneoplastic
4- fulminant
