1
Q
NSAIDS - NON-STEROIDAL ANTI-INFLAMMATORY DRUGS:
History
Salix Alba
A
Salix Alba:
Bad side effects of:
- gastric ulceration,
- blood vomiting (can be life threatening).
The revolution came from Felix Hoffmann (German). He found out how to synthesize aspirin from Salix Alba.
2
Q
Drug group A inhibits PLA2 enzyme, While drug group B inhibits C enzyme, Therefore A, B and C are?
A
A= GLUCOCORTICOIDS
B= NSAID’s
C= Cyclooxygenase (COX)
Glucocorticoids inhibits PLA2 enzyme, While NSAIDs inhibits COX enzyme
3
Q
Eicosanoids = Aracidonic acid is the substrate for which enzymes?
A
- Apoxygenase,
- lipoxygenase
- cyclooxygenase.
- Apoxygenase and lipoxygenase have limited significance.
- Lipoxygenase produces leukotrienes and lipoxins which play an important role in asthma i.e. respiratory inflammation.
Therefore, lipoxygenase inhibitors are important in human medicine but are not used in veterinary medicine.
4
Q
Eicosanoids = Arachidonic acid is the substrate for CYCLOOXYGEBASE enzyme, but why is it important?
A
- They produce
- prostaglandins (PGF and PGE),
- prostacyclins (PGI), and
- thromboxanes (TX).
- These mediators will produce
- pain,
- edema, and
- other signs of inflammation.
- This is why we end up with inflammation when we have cellular damage e.g. cut on the skin.
- The function of TX at the site of injury and inflammation is to cause aggregation of the platelets leading to blood clotting.
5
Q
Eicosanoids = Arachidonic acid
How can we inhibit Phospholipase A2
A
- Pharmacologically, we can inhibit phospholipase A2
= entire process will be inhibited.
- These are the best anti-inflammatories and are known as GLUCOCORTICOIDS.
- Most potent anti-inflammatories we know e.g.
- PREDNISOLONE.
6
Q
Eicosanoids = Arachidonic acid
How to inhibit COX enzyme and why?
A
- With cyclooxygenase inhibitors are known as
- NSAIDs.
- These inhibit the function of cyclooxygenase.
COX is increasing inflammation and pain sensation, this phenomenon is known as peripheral sensitization.
This means that at the site of inflammation, we feel pain better or stronger.
7
Q
What is Peripheral sensitization phenomenon
A
COX is increasing inflammation and pain sensation, this phenomenon is known as peripheral sensitization.
This means that at the site of inflammation, we feel pain better or stronger.
8
Q
How many isoenzymes does the cox enzyme have in the body?
A
Cyclooxygenase has at least two isoenzymes in the body
- COX-1
- COX-2
- (COX-3)
9
Q
What is the function of COX-1?
A
COX-1:
This is the housekeeping enzyme that helps to keep us alive.
- It is produced constitutively i.e. all the time.
- It protects our stomach, kidney, and platelets etc.
- They produce prostaglandins (PGE)
- Help the normal function of the stomach wall.
- It decreases HCl secretion
- Increases mucus secretion
- Increases blood perfusion of the stomach wall
- leading to better regeneration.
- It always protects our stomach from our own HCl.
- If these are inhibited,
- gastric ulceration will occur (leading side effect).
10
Q
In case of COX-1 and the kidneys, what does the PGE do?
A
- PGE dilates the vessels and increases renal blood flow (RBF).
- If this enzyme is inhibited,
- vasoconstriction takes place and
- kidney damage will occur
- (second most important side effect).
11
Q
In case of the COX-1 which enzyme affects the platelets?
What is its function?
Inhibition of the enzyme leads to?
A
- Thromboxanes help the aggregation of platelets
- which leads to normal blood clotting i.e.
- inhibition of these enzymes leads to bleeding.
12
Q
Main side effects of COX-1?
A
The three main side effects are:
- Gastric ulceration,
- kidney damage and
- bleeding.
13
Q
What kind of enzyme is COX-2?
What does it inhibit?
What is it produced by?
A
- COX-2: This is the primary enzyme in inflammation. This is the inflammatory enzyme. This enzyme inhibits macrophages and fibroblast COX-1 production. It is produced by macrophages and fibroblasts at the site of inflammation and that is why this is the isoenzyme we want to inhibit.
14
Q
When we are using NSAIDs, which enzyme are we trying to inhibit?
Give an example of a COX-2 selective NSAID(s)
A
- Inhibit COX-2 while keeping COX-1 intact i.e.
- we want drugs that are selectively COX-2 acting.
- ASPIRIN is NOT COX-2 selective i.e.
- it can cause gastric ulceration.
- ASPIRIN is NOT COX-2 selective i.e.
- we want drugs that are selectively COX-2 acting.
- An example of a COX-2 selective NSAID is
- MELOXICAM or CARPROFEN.
15
Q
Where is COX-3 enzyme pressent?
What does it produce and what will it cause?
A
COX-3:
- A unique enzyme as it is present in the CNS and mainly in the hypothalamus and thalamus of the brain. It will produce prostaglandins, causing fever and enhancing pain sensation.
16
Q
What happens if you inhibit COX-3?
Which drugs can inhibit COX-3?
A
Inhibiting COX-3
- Very good antipyretic (reduces fever) effect
- Analgesic effect
- NOT causing anti-inflammatory action
- e.g. PARACETAMOL (METAMIZOLE).
- These two drugs are not called NSAIDs,
- but minor analgesics (major being morphine derivatives) as they do not have any anti-inflammatory drug properties.
- e.g. PARACETAMOL (METAMIZOLE).
17
Q
COX-2 to COX-1 inhibition rates:
Groups
A
(COX-2 inhibition: COX-1 inhibition)
The higher the ratio, the better the drug.
According to this ratio, we put the drugs into groups.
- Older drugs
- Second generation = more-selective COX-2 inhibitors
- Third generation (the best drugs) = COXIBS.
18
Q
1st group of drugs = OLDER DRUGS
- Drug?
- Ratio?
- Inhibition?
- Safe?
- Called?
A
- KETOPROFEN and ASPIRIN.
- These have a ratio of less than one.
- These inhibit both COX-1 and COX-2
- Therefore, they are considered UNSAFE
- We call these classical NSAIDs.
Ketoprofen, Aspirin
<1
19
Q
The second generation of drugs = more-selective COX-2 inhibitors.
- Drugs?
- Ratio?
- Inhibition?
- Safety?
A
- These include MELOXICAM and CARPROFEN.
- These drugs have a ratio of around 10, meaning
- They can inhibit COX-2 ten times as much as they inhibit COX-1.
- Carprofen (RIMADYL) is lethal in humans?????
Meloxicam
3-10
Carprofen
7-17
20
Q
The third generation (the best drugs)
- Called
- Drugs
- Ratio
- Sideeffects
- Inhibit
- Species specificity
A
- COXIBS (best drugs)
- DERACOXIB and FIROCOXIB
- These usually have extreme ratios.
- They cause side effects extremely infrequently because they
- ONLY inhibit COX-2.
Deracoxib
22-37
Firocoxib
384
- These drugs and their data are for dogs. They have interspecies, interbreed, and interindividual differences.
21
Q
NSAIDS - NON-STEROIDAL ANTI-INFLAMMATORY DRUGS:
Pharmacological effects (when it is beneficial)?
A
Pharmacological effects (when it is beneficial):
The most important pharmacological effects are
- anti-inflammatory,
- analgesic
- antipyretic (fever reduction)
- Platelet aggregation inhibition:
- Antiendotoxin:
- Spasmolytic:
- Antineoplastic:
22
Q
NSAIDS - NON-STEROIDAL ANTI-INFLAMMATORY DRUGS:
Pharmacological effects (when it is beneficial):
- Platelet aggregation inhibition:
A
Platelet aggregation inhibition:
This is useful in the case of thrombosis where we use ASPIRIN.
23
Q
NSAIDS - NON-STEROIDAL ANTI-INFLAMMATORY DRUGS:
Pharmacological effects (when it is beneficial):
Antiendotoxin
- Main component and where
- Importance
- Drugs
- Side effects
- Bacterial infections
- Most frequent drug in horses
A
Antiendotoxin:
- Endotoxin = main component of the gram-negative bacteria cell wall.
- In serious gram-negative bacterial infections when bacteria die,
- endotoxins are released that can kill the patient.
- FLUNIXIN and MELOXICAM are good antiendotoxins.
- Endotoxin shock can occur when we are administering antibiotics in gram negative bacterial infection e.g.
- e coli enteritis,
- salmonella enteritis,
- e coli mastitis in cattle
- colic in horse.
- This explains why flunixin is the most frequently used drug in horses.
24
Q
NSAIDS - NON-STEROIDAL ANTI-INFLAMMATORY DRUGS:
Pharmacological effects (when it is beneficial):
Spasmolytic
- Causes
- Leading to
- Drug
- Beneficial in
A
Spasmolytic:
- It causes smooth muscle inhibition,
- leading to decreased spasms in the
- GI tract,
- urinary tract,
- genital tract.
- leading to decreased spasms in the
- The drug here is also FLUNIXIN, as well as METAMIZOLE.
- These spasmolytics are beneficial in
- colic (any type) and
- during menstruation (genital spasms).
25
NSAIDS - NON-STEROIDAL ANTI-INFLAMMATORY DRUGS:
Pharmacological effects (when it is beneficial):
***_Antineoplastic:_***
1. When is it caused
2. What does it produce to require what?
3. What happens if we inhibit COX?
4. Drugs used in treatment of Prostate tumors and Urinary bladder tumors
**Antineoplastic:**
* This is caused because **some tumors produce COX enzymes**
* Produce **prostaglandins** for themselves
* **required for the growth of the tumors** i.e.
**Inhibit COX = no prostaglandins produced = tumor cannot grow**.
* We use **PIROXICAM** which has **proven useful** in the treatment of
* **prostate tumors**
* **urinary bladder tumors.**
26
***_NSAIDS - NON-STEROIDAL ANTI-INFLAMMATORY DRUGS:_***
*_Pharmacokinetics:_*
*_Absorption:_*
1. NSAIDs are
2. Forms in the body
3. Absorbtion through
4. Production in
5. Taken with or without food
1. Types of drugs
*_Absorption:_*
These are **weak acids**
They have two forms in the body: **Ionised form & Non-ionized form.**
* **The non-ionized form** has **good absorption through the membranes**
* **Overproduced in the stomach - HCl**
* **NSAIDs absorption first in the stomach**
* ASPIRIN = Quick onset
NSAIDS and FOOD
* Difference in absorption **with or without food**
* **Week acids = irritable to stomach = WITH FOOD**
* **KETOPROFEN**, **feed decreases its absorptio**n i.e. it is given on an empty stomach.
* **CARPROFEN** and **MELOXICAM** can be given with or without food.
* **MAVACOXIB** (canine) has a much **better bioavailability** when **given with food** (empty stomach: 20%, full stomach: 80%).
27
NSAIDS - NON-STEROIDAL ANTI-INFLAMMATORY DRUGS:
*_Distribution:_*
1. Clinical consequences due to what?
2. Which clinical consequenses?
3. Do not combine which drugs?
4. Why is Loading dose required?
5. Which drug cannot enter the milk due to the binding of albumin?
*_Distribution:_*
* **Extensive albumin binding** = has some clinical consequences.
1. The first one is that in **hypoalbuminemia,**
* the **free drug levels are much higher** i.e.
* toxicity is enhanced.
* We draw blood and measure the albumin level before administering these drugs.
* If you give two drugs with high albumin binding, they will compete for the albumin and they can push down the other from albumin leading to increased toxicity i.e.
* do not combine drugs of high albumin binding.
* Do not combine **NSAIDs** or **FUROSEMIDE** (**diuretic**) which is also a **high albumin binding drug**. If this is combined with NSAIDs, you must **decrease the dose** in order to **decrease toxicity.**
1. The other consequence is that **loading doses are required** i.e.
* we have to **load a higher dose** in order to **saturate albumin** and then we administer a **maintenance dose.**
**MELOXICAM:**
Loading dose
Maintenance dose
Dog
0. 2 mg/kg
0. 1 mg/kg
Cat (more sensitive)
0.1 mg/kg
as low as 0.02 mg/kg
**CARPROFEN:**
Loading dose
Maintenance dose
Dog
4. 4 mg/kg
2. 2. mg/kg
**These cannot enter the milk because they are bound to albumin** and only the free form of the drug can penetrate the blood-milk barrier.
**Carprofen in cattle has a one-month withdrawal period for meat, and 0 days for milk.**
28
NSAIDS - NON-STEROIDAL ANTI-INFLAMMATORY DRUGS:
*_Metabolism:_*
1. With?
2. Which species is this particular acid absent?
3. Why ?
4. How to administer knowing this?
5. Authorized drug for this species?
6. Long term alternative for this species?
*_Metabolism:_*
* **Mainly with glucuronic acid,**
* this is absent in **cats** i.e.
* the **NSAIDs will have a longer half-life** in cats as the **elimination is slower.**
* This is why we usually administer a **smaller dose** in cats, or the drugs are **given less frequently.**
* There is **no drug authorized for cats for more than one week** but, we know from studies that
* **MELOXICAM** is a **good long-term alternative for cats** but, again, no drug can officially be licensed for cats.
29
NSAIDS - NON-STEROIDAL ANTI-INFLAMMATORY DRUGS:
SIDE EFFECTS
MANY!!
1. GI Ulceration
2. Kidney damage
3. Hepatotoxicity:
4. **Platelet aggregation inhibition**
5. Methemoglobinemia
6. **Proteoglycan synthesis inhibition**
7. Foetal damage:
8. Placenta retention:
30
NSAIDS - NON-STEROIDAL ANTI-INFLAMMATORY DRUGS:
SIDE EFFECTS
*_GI Ulceration_*
1. Where will the ulcerations form
2. Causes of ulceration
3. Treatment
4. How serious is the side effect
*_GI Ulceration:_*
* This means that the **stomach and duodenum** will form **ulcers**.
* The two causes of that is firstly,
1. **the local irritation of these weak acids** which fall into an **ion trap within the cells** of the **stomach** and cause **intracellular damage** within the cells.
2. The other reason for **gastric damage** is that the **prostaglandin level will be decreased** i.e.
* **Causing GI ulceration even if they are injected.** The treatment of this is to use a **proton-pump inhibitor** (**OMEPRAZOLE**).
* **This side effect can be life-threatening.**
31
NSAIDS - NON-STEROIDAL ANTI-INFLAMMATORY DRUGS:
SIDE EFFECTS
*_Kidney damage:_*
1. Inhibit what? caused by what?
2. What does it cause? Leading to?
3. How many cases of damages takes place?
4. What is important to remember before you give NSAIDs?
5. Due to surgery, when can you give NSAIDs?
*_Kidney damage:_*
* They **inhibit the vasodilation** caused by **PGE** i.e.
* **causes vasoconstriction**
* **decrease the perfusion of the kidney**
* leading to kidney damage.
There are **3 cases** in which this **damage takes place,**
1. When the patient has **existing kidney failure** i.e.
1. Examine whether the **patient's kidneys are healthy or not.**
2. In cases of **dehydration** i.e.
1. **BEFORE** you give **NSAIDs** - **hydrate them with perfusion.**
3. **During surgery** when the patient has been given a**nesthesia**,
1. **kidney perfusion is decreased.** because of this i.e.
1. **NSAIDs are only given postoperatively** when **speaking about surgery.**
32
NSAIDS - NON-STEROIDAL ANTI-INFLAMMATORY DRUGS:
SIDE EFFECTS
* *_Hepatotoxicity:_*
1. Type of side effect
2. Frequency of the side effect
3. Drugs causing hepatotoxicity
Hepatotoxicity:
* **Gastric ulceration** and **kidney damage** are **outstandingly important side effects** with the remaining being additional side effects.
* HEPATOTOXICITY = **Additional side effect**
* This is **much less frequent.**
* **PARACETAMOL** can lead to hepatotoxicity in **humans** and **dogs**
* Metabolized mainly in the **liver**
* into **NAPQI** (N-acetyl-P-benzoquinoneimine) which is its metabolite.
* This is a very **oxidative and reactive metabolite** that can **damage the hepatic cells**.
* In **cats**, this **NAPQI** will **oxidize Fe2+ to Fe3+**, leading to **methemoglobinemia.**
* In **CARPROFEN**, there are very **infrequent idiosyncratic reactions** (individual differences), and **some individuals are sensitive to this.**
* These are more frequently seen in **Labrador** or **golden retrievers.**
**In all, hepatotoxicity is much less frequent.**
33
PARACETAMOL and HEPATOTOXICITY
1. Can it lead to hepatotoxicity
2. In which species
3. Where is it metabolized
4. What is its metabolite
5. Characteristics of the metabolite
6. What happens to the metabolite in cats?
PARACETAMOL **can lead to hepatotoxicity**
* in **humans and dogs**
* Metabolized mainly in the **liver**
* into **NAPQI** (N-acetyl-P-benzoquinoneimine) which is its **metabolite.**
* This is a **very oxidative** and **reactive metabolite** that can **damage the hepatic cells.**
* In **cats**, this **NAPQI will oxidize Fe2+ to Fe3+**, leading to **methemoglobinemia.**
34
CARPROFEN and HEPATOTOXICITY
In **CARPROFEN,**
* Very infrequent **idiosyncratic reactions**
* (individual differences)
* **Some individuals are sensitive to this.**
These are **more frequently seen in**
* Labrador
* Golden retrievers.
35
NSAIDS - NON-STEROIDAL ANTI-INFLAMMATORY DRUGS:
SIDE EFFECTS
*_Platelet aggregation inhibition:_*
1. When is it beneficial?
2. When is it non-beneficial and why?
3. Drugs with potent platelet aggregation inhibition should not be used when?
4. Types of drugs?
*_Platelet aggregation inhibition:_*
* **This is beneficial during thrombosis**
* however, it is very **non-beneficial during surgery.**
* **Drugs that have a potent platelet aggregation inhibitory effect**, are **not recommended after surgery** because after surgery,
* there can still be bleeding in the wounds/injury site
1. **ASPIRIN**
2. **FLUNIXIN**
3. **TOLFENAMIC ACID**
4. **KETOPROFEN**
36
NSAIDS - NON-STEROIDAL ANTI-INFLAMMATORY DRUGS:
SIDE EFFECTS
* *_Methemoglobinemia:_*
1. In which species
2. Caused by what
3. Color of methemoglobinemia, Color of the blood is?
4. Which drug can never be given to this species with methemoglobinemia and Why?
1. In **CATS**,
2. **NAPQI oxidises Fe2+ to Fe3+.**
3. The color of methemoglobinemia is **brown** i.e.
* the **blood** of these **cats** is **chocolate brown.**
4. **PARACETAMOL** can **never be given to cats**,
* **it is LETHAL**
37
NSAIDS - NON-STEROIDAL ANTI-INFLAMMATORY DRUGS:
SIDE EFFECTS
*_Proteoglycan synthesis inhibition_*
1. What does it damage?
2. Why is it so bad?
3. Which drugs causes this damage?
4. Which drugs are ONLY used in humans?
5. Which drugs are WITHOUT this damage?
*_Proteoglycan synthesis inhibition_* = **(cartilage damage):**
* Very bad because most of these drugs are
* **Used for patients of arthritis (joint inflammation)** and that is why we have to know which ones form cartilage damage
* **ASPIRIN,**
* **KETOPROFEN**
* Only used in humans; **IBUPROFEN** and **NAPROXEN**
* **MELOXICAM** and **CARPROFEN**
* have **no effect on the cartilage.**
38
39
NSAIDS - NON-STEROIDAL ANTI-INFLAMMATORY DRUGS:
SIDE EFFECTS
*_Foetal damage:_*
1. NSAIDs recommended during pregnancy?
2. In witch part of the pregnancy is the fetus the most sensitive to NSAIDs
3. Exeption when the pregnant patient has headache - which drug?
*_Foetal damage =_* TERATOGENICITY
* These are not recommended during pregnancy,
* especially during the first trimester.
* Fetus is most sensitive to drugs in the first trimester.
* The exception is that if a patient is pregnant and has headaches,
* **METAMAZOLE** (minor analgesic, COX inhibitor) has been proven to be safe.
40
NSAIDS - NON-STEROIDAL ANTI-INFLAMMATORY DRUGS:
SIDE EFFECTS
*_Placenta retention_**_._*
1. What is Placenta retention?
2. What does NSAIDs to the which synthesis?
3. What is Prostaglandins responsible for and why is it so important?
4. What can take place if this doesn't happen?
5. Due to this, when is it not recommended to use NSAIDs to prevent this effect?
6. What is the only exception?
*_Placenta retention:_*
* This is when the **placenta stays in the womb.**
* **NSAIDs inhibit prostaglandin synthesis.**
* The **responsible substance for uterus contraction** in order for the **placenta to be removed from the womb are prostaglandins** i.e.
* if you **remove the synthesis of these prostaglandins =**
* then the **uterus cannot contract and placenta retention will take place.**
* **Infection and metritis** can form from this because it is **sensitive to bacterial infections.**
* Because of this, **NSAIDs are not recommended 48 hours before** and **36 hours after parturition** to prevent this side effect.
* The only exception to this is **MELOXICAM**.
41
NSAIDS - NON-STEROIDAL ANTI-INFLAMMATORY DRUGS:
***_Active substances:_***
*_Acidic substances:_*
*_Acidic substances:_*
* These are **more irritant to the stomach** i.e.
* more or less **causing gastric ulceration** more frequently than non-acidic substances
* **All substances contribute to this ulceration.**
1. *_Salicylates:_*
2. *_Propionic acids:_*
3. *_Heteroaryl acetic acids:_*
4. *_Anthranilic acids:_*
5. *_Butyl pyrazolidines:_*
6. *_Oxicams:_*
42
NSAIDS - NON-STEROIDAL ANTI-INFLAMMATORY DRUGS:
Active substances:
Acidic substances:
*_Salicylates:_*
*_**Salicylates**::_*
1. *_Acetylsalicylic acid:_*
2. *_Na salicylate:_*
3. *_Sulfasalazine, Mesalazine:_*
43
NSAIDS - NON-STEROIDAL ANTI-INFLAMMATORY DRUGS:
Active substances:
Acidic substances:
Salicylates:
***_1. Acetylsalicylic acid:_***
*_Acetylsalicylic acid:_*
* **ASPIRIN**,
* it is **infrequently used in practise, more so for HUMANS.**
* **In dogs,** it is **safe short-term** i.e.
* for a **few days**.
* **If the owner cannot go to the practice** to be administered **MELOXICAM**, they can be **administered aspirin.**
* **It is not recommended in cats.**
* In **farm animals**, mainly in **swine** and **poultry**,
* these are **mixed into the water**
* **G**ood painkillers
* Not that safe.
44
NSAIDS - NON-STEROIDAL ANTI-INFLAMMATORY DRUGS:
Active substances:
Acidic substances:
Salicylates:
***_2. Na salicylate:_***
*_Na salicylate:_*
* **This is much safer**
* **More COX-2 selective** i.e.
* Affects the **COX-2 enzyme** and **not the COX-1 enzyme**
* Makes it safer.
* **It is used only in farm animals** (**poultry**, **swine**, **calves**)
* **mixed into the water.**
45
NSAIDS - NON-STEROIDAL ANTI-INFLAMMATORY DRUGS:
Active substances:
Acidic substances:
Salicylates:
**3. *_Sulfasalazine, Mesalazine:_***
*_Sulfasalazine, Mesalazine:_*
* **ONLY** used in **dogs and humans**
* **Treatment of chronic colitis.**
* **Crohn's disease** is an **painful colitis.**
* These drugs are **given orally**
* **Large intestine** (where the problem is taking place)
* **Release amino-salicylic acid**
* Because **drug absorption in the large intestine** is of a **low level,**
* it will **act locally** i.e.
**These drugs are very safe.**
46
NSAIDS - NON-STEROIDAL ANTI-INFLAMMATORY DRUGS:
Active substances:
Acidic substances:
***_Propionic acids:_***
1. **Ketoprofen:**
2. **Vedaprofen:**
3. **Carprofen:**
47
NSAIDS - NON-STEROIDAL ANTI-INFLAMMATORY DRUGS:
Active substances:
Acidic substances:
Propionic acids:
**_1. Ketoprofen:_**
*_Ketoprofen:_*
* An **older drug,**
* **NOT COX-2 selective**,
* significantly **inhibiting platelet aggregation** i.e.
* **NOT use in bleeding animals** or **after surgery.**
* ****Interestingly, in **cats**,
* it is **one of the safest drugs short-term**
* because **in cats** it has a v**ery short half-life**.
* It is maybe the **best anti-pyretic in cats against fever** (cats have fever very frequently).
* **Long-term, there can be problems.**
48
NSAIDS - NON-STEROIDAL ANTI-INFLAMMATORY DRUGS:
Active substances:
Acidic substances:
Propionic acids:
***_2. Vedaprofen:_***
***Vedaprofen:***
* **Exclusively for horses**.
* An **oral paste**
* **COX-2 selective** i.e.
* **Relatively safe.**
49
NSAIDS - NON-STEROIDAL ANTI-INFLAMMATORY DRUGS:
Active substances:
Acidic substances:
Propionic acids:
***_3. Carprofen:_***
***_Carprofen:_***
* **It can be given life-long,**
* **very safe (COX-2 selective).**
* It **can cause liver damage** in **Labradors** and **golden retriever**s i.e.
* **monitor** those **liver** **functions**.
* If given **together with other hepatotoxic drugs** e.g.
* **PHENOBARBITAL, can be dangerous.**
* **In cattle,**
* it has a **very long action (4-5 days),**
* leading to a very **long withdrawal time (one month)** and
* because of the **high albumin binding,**
* **milk withdrawal is 0 days.**
* **One of the safest drugs we know**.
* It has **no cartilage damage**
* Can be used in **exotic animals.**
50
NSAIDS - NON-STEROIDAL ANTI-INFLAMMATORY DRUGS:
Active substances:
Acidic substances:
* *_Heteroaryl acetic acids:_*
***_Diclofenac:_***
## Footnote
* A **very potent** and **effective in humans** for **pain** and **inflammation**
* **Highly** **toxic** for:
* **dogs**,
* **cats**
* **birds**
* **Avoid its usage.**
51
NSAIDS - NON-STEROIDAL ANTI-INFLAMMATORY DRUGS:
Active substances:
Acidic substances:
***_Anthranilic acids:_***
*_Anthranilic acids:_*
* 2 drugs
1. Flinixin
2. Tolfedine
*_**Flunixin**:_*
* A platelet aggregation inhibitor i.e.
* enhances bleeding,
* anti-endotoxin (colic),
* **Spasmolytic** i.e.
* frequently used in **horses**.
* In **cattle**, the **half-life is very short** i.e.
* they produce **flunixin-containing pour-on**
* On the **back of the anima**l to **provide slower absorption** i.e.
* **Onset of action (2-3 days).**
***_Tolfenamic acid (Tolfedine):_***
* This also **causes bleeding**
* **Similarly to ketoprofen** = **very short half-life** in **cats** i.e.
* **safe short-term drug for cats.**
52
NSAIDS - NON-STEROIDAL ANTI-INFLAMMATORY DRUGS:
Active substances:
Acidic substances:
***_Butyl pyrazolidines:_***
***_1. Phenylbutazone:_***
*_Phenylbutazone:_*
* This is used in **HORSES** and **not in other animals.**
* This has **two indications** in **horses**,
* mainly as an **ointment** (topically) for **orthopedic injuries.**
53
NSAIDS - NON-STEROIDAL ANTI-INFLAMMATORY DRUGS:
Active substances:
Acidic substances:
***_Oxicams:_***
***_Oxicams:_***
1. *_Piroxicam:_*
2. *_Meloxicam_*
***_Piroxicam_***
* A **human drug** with **oncological indications**
* **Prostate tumors**
* **Urinary** **bladder** **tumors**.
* It is **NOT** used as a **painkiller** or **anti-inflammatory**
* because it is an **old classical NSAID** = Lots of **side effects.**
*_**Meloxicam**:_*
* **It is very safe in all species,** humans included.
* * It is also an **anti-endotoxin** i.e.
* useful in:
* **enteritis,**
* **mastitis and**
* **colic.**
* **Meloxicam can be injected and given orally.**
* Its dose in dogs is
* 0.2 mg/kg loading dose
* 0.1mg/kg maintenance dose.
* In cats,
* the loading dose is 0.1 mg/kg.
* In large animals, the dose is
* 0.4-0.6 mg/kg.
54
NSAIDS - NON-STEROIDAL ANTI-INFLAMMATORY DRUGS:
Active substances:
***_Non-acidic substances:_***
***_Non-acidic substances:_***
* These have a much more **limited effect on the stomach**.
* They are **not as ulcerative.**
1. ***_Aniline derivatives_***
1. *_Paracetamol:_*
2. *_**Pyrazolines**:_*
1. *_Metamizole sodium:_*
55
NSAIDS - NON-STEROIDAL ANTI-INFLAMMATORY DRUGS:
Active substances:
*_Non-acidic substances:_* ***_Aniline derivatives_***
*_Non-acidic substances:*_ _*Aniline derivatives_*
1. ***_Paracetamol:_***
* **COX-3 inhibitor,**
* **minor analgesic,**
* do **NOT give to cats** and
* **preferably** **not in dogs.**
* Be careful that, **similarly to carprofen in retrievers**,
* **paracetamol in humans** has **idiosyncratic reactions** of **hepatic damage.**
* L**eading cause of hepatic transplantation in humans.**
56
NSAIDS - NON-STEROIDAL ANTI-INFLAMMATORY DRUGS:
Active substances:
***_Non-acidic substances:*_ _*Pyrazolines:_***
*_**Pyrazolines**:_*
1. ***_Metamizole sodium:_***
* **Non-specific**,
* **COX-3 inhibitor.**
* Mainly **acts** in the **brain**
* Very **low activity on COX-1** and **COX**-2,
* **Very safe**
* **no effect** on the **stomach** or **kidneys**.
* You can give it to
* **dogs,**
* **rodents**
* C**ats react with a nervous system of excitation and salivation.**
* Its dose is 20-30 mg/kg.
57
NSAIDS - NON-STEROIDAL ANTI-INFLAMMATORY DRUGS:
Active substances:
***_Coxibs:_***
***_Coxibs:_***
## Footnote
* **NB NB NB These are the safest.**
* Absolute COX-2 selectivity.
* These are the NSAIDs that inhibit COX-2 100 times more than COX-1.
1. *_Deracoxib:_*
2. *_Firocoxib:_*
3. *_Robenacoxib:_*
4. *_Cimicoxib:_*
5. *_Mavacoxib_*
58
NSAIDS - NON-STEROIDAL ANTI-INFLAMMATORY DRUGS:
Active substances:
**Coxibs**
1. *_Deracoxib:_*
1. *_Deracoxib:_* Similar to meloxicam but safer, licensed for dogs.
59
NSAIDS - NON-STEROIDAL ANTI-INFLAMMATORY DRUGS:
Active substances:
**Coxibs**
*_2. **Firocoxib**:_*
*_2. Firocoxib:_* 384:1 i.e. very safe. It is for dogs and horses, orally.
60
NSAIDS - NON-STEROIDAL ANTI-INFLAMMATORY DRUGS:
Active substances:
Coxibs
1. *_**Robenacoxib**:_* and ***_Cimicoxib:_***
1. *_**Robenacoxib**:_*
* *__*Only coxib licensed for cats
* Also the only one marketed for injection.
* For dogs also.
1. *_**Cimicoxib**:_* Dog tablet.
61
NSAIDS - NON-STEROIDAL ANTI-INFLAMMATORY DRUGS:
Active substances:
Coxibs
***_Mavacoxib_***
1. ***_Mavacoxib_* (NB):**
* **Very long half-life in dogs (5-7 days).**
* The **duration of action is approx. 3-4 weeks.**
* It is **only given to dogs as a tablet.**
* **Empty** stomach **bioavailability is 20%**
* **Full stomach** bioavailability is **80%** i.e.
* **always given with food.**
* It is given **orally with food,**
* **repeat** administration **after two weeks** and
* after that, repetition is **every four weeks.**
* **It is convenient, effective, and safe.**
Veterinary Pharmacology
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Small test 191
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Small Test 244
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Small Test 2 - Additional questions68
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Study for Midtterm 1 - 20pages15
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MIDTERM 1 - Repetition9
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Smalltest nr 397
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Past Q - PHARMA MIDTERM II246
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Smalltest nr 3 part 249
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Midterm II - Topic 19,20,21111
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Midterm II - Pairing20
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Drugs MT II30
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Small Test 473
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PQ small test 30
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DRUGS FINAL84
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PHARMA PPQ Written 2022336
