Missing Pharma

Question 1

What are anti-inflammatory effects of GCs?

Answer 1

Decreased transcription of inflammatory cytokines: IL-1,-6, TNF-alpha, GM-CSF, IFNs, IL-12, IL-23, IL-2, -4, -5, -13, TSLP
Decreased transcription of inflammatory chemokines: CCL1, CCL5, CCL17 (TARC), CXCL8
Decreased expression of adhesion molecules for cell recruitment: ICAMs, VCAM-1
Decreased transcription of inflammatory enzymes: iNOS,COX2
Increased transcription of anti-inflammatory molecules: IL-10, GILZ (inducing FOXP3 expression)

Question 2

What is Cannabidiol?

Answer 2

-non competitive allosteric modulator of the G protein-coupled cannabinoid receptor - CB1
-inverse agonist of CB2

Question 3

Were are CB1 found ?

Answer 3

-CNS
-regulate neurotransmiitter release

Question 4

Where are CB2 found?

Answer 4

-cells of the immune system- intestine, tonsils, spleen
-plays a role in cytokine release

Question 5

What is the end result in stimulating CB1 and CB2 ?

Answer 5

-negative modulation of these receptors by CBD aids in homeostasis and ATTENUATION of inflammation

Question 6

Name other receptors that CBD interacts with ( Corsato Alvarenga, 2023)?

Answer 6

○ fatty acid hydrolase (FAAH; inhibits enzyme hydrolysis of anandamide)
○ G-protein coupled receptor 55 (GPR55; bone metabolism)
○ transient receptor potential vanilloid 1 (TRPV1; analgesic and antiepileptic)
○ peroxisome proliferator-activated receptor gamma (PPARγ; anti-inflammatory and antioxidant)
○ serotonin 5-beta hydroxytryptamine receptors 1 and 3 (5-HT1A and 5-HT3A; antidepressant and anxiolytic

Question 7

What was the tolerabiloty of long term (9 months) cannabidiol supplementation to helathy dogs (Corsato Alvarenga, 2023)

Answer 7

-better tolerated at 5 mg/kg PO than 10 mg/kg
-both dosages caused an INCREASE in ALP
-monitor liver function

Question 8

Is CBD metabolized through p450?

Answer 8

YES!!
-be careful of CsA, ketoconasole, fluconasole

Question 9

Are CB1 and CB2 expressed in canine KC (Loewinger, 2021)?

Answer 9

YES
-immunoreactivity to CB1 and CB2 is HIGHER in atopic dogs than in healthy ones

Question 10

What was the effect of CBD oil and cannabidiolic acid in AD dogs (Loewinger, 2021)

Answer 10

-no effect on CADESI-04 score
-pVAS was significantly lower
-received 2 mg/kg

-no difference is IL-6,IL-8, MCP-1, IL-31, IL-34
-elevated ALP in 4/17 dogs

Question 11

What were the side effects of CBD and cannabidiolic acid 2 mg/kg (Loewinger, 2021)

Answer 11

-lethargy and calmness

Question 11

What is cannabidiolic acid (CBDA)?

Answer 11

-precursor of cannabidiol
-better resporption than CBD
-both have immunomodulatory and anti-inflammatory properties
-reduce osteoarthritis and seizures

Question 12

Does cannabidiol interacts directly with CB1 and CB2?

Answer 12

NO
-implicated in altering endogenous levels of naturally derived ENDOCANNABINOIDS such as ANANDAMINE
PEA is endocannabinoid like molecule (works on CB1 and CB2)

Question 13

What is PEA and how it works (Noli, 2015)

Answer 13

=palmitoylethanolamid
-naturally occurring bioactive compound
-DOWNREGULATE MAST CELL DEGRALUATION through AUTACOID local injury antagonism

Question 14

What is ultra-micronized PEA (Noli, 2015) ?

Answer 14

=pharmaceutical grade formulation in which >99% by weight of PEA has particles sizes below 6 microm.
-it is used to improve the bioavailability and efficacy of a very low water solubility molecules through and increased dissolution rate of the micron-size substance
-superior

Question 15

What was the conclusion of PEA in cAD (Noli, 2015)

Answer 15

-significantly improved pruritus, skin lesions and QoL in dogs with moderate cAD
-nearly 80% improved in first month
-36% reduction in the mean pruritus score
-8 weeks of PEA induced remission of skin lesions in 62% of dogs with moderate cAD
-low adverse effects- 7% (emesis, diarrhea)

Question 16

What is entourage effect?

Answer 16

hypothesis that cannabis compounds other than tetrahydrocannabinol (THC) act synergistically with it to modulate the overall psychoactive effects of the plant.

Question 16

What are ALIAmides?

Answer 16

-family of fatty acid amides sharing a common mechanism of action
- i.e., the autacoid local injury antagonism (ALIA)

-term “autacoid” comes from the Greek “autos” (self), “acos” (healing or remedy)

Question 17

What is autacoid?

Answer 17

=refers to cell-produced factors that act locally near their site of synthesis
- act like local hormones, have a brief duration,

Question 18

What is the main AE of Vit D and how can we avoid it?

Answer 18

• Hypercalcemia
  When giving cholecalciferol systemic

+giving fex paricalcitriol (Vit D R agonist) is safer, as it does not induce hypercalcemia, but has the same effect, which is:
Influencing barrier function, immune response and production of AMP it influences bacterial growth on the skin surface

(in vet med study (Klinger et al.) cholecalciferol was safer than vitamin D analogue