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-)