<img src="https://i.imgur.com/gK98l1i.png" alt="A collection of various colored and shaped pills and capsules scattered on a light blue background.">
**DENT 3005:Introduction to Pharmacology**
**Immunomodulators & anti-inflammatory**
Dr Thuy Linh Truong
thuy.truong@uwa.edu.au
# **DENT 3005: Introduction to Pharmacology**
## **Immunomodulators & anti-inflammatory**
**Dr Thuy Linh Truong**
thuy.truong@uwa.edu.au
<img alt="The image displays a text-based slide with the title "Acknowledgement of country" and the logo of "The University of Western Australia". To the right is an abstract black and white artwork, possibly representing Indigenous art." />
# Acknowledgement
of country
The University of Western Australia acknowledges that its campus is situated on Noongar land, and that Noongar people remain the spiritual and cultural custodians of their land, and continue to practise their values, languages, beliefs and knowledge.
Artist: Dr Richard Barry Walley OAM
<div style="text-align: right;">
<img src="university_logo.png" alt="The University of Western Australia logo" style="width: 150px; height: auto;">
</div>
# **Acknowledgement of country**
The University of Western Australia acknowledges that its campus is situated on Noongar land, and that Noongar people remain the spiritual and cultural custodians of their land, and continue to practise their values, languages, beliefs and knowledge.
Artist: Dr Richard Barry Walley OAM
<div style="text-align: right;">
</div>
**Learning Outcomes**
**Learning objectives**
1) Understand the different types of
immunomodulators and anti-inflammatory
drugs
2) Broad understanding of RA, OA and gout and
the pharmacological agents used in these
conditions
3) Recognise oral and dental side effects of
these drugs
4) Understand drugs interactions with dental
medications
5) Applied knowledge to clinical scenarios
![]()
A stylized illustration showing two medical professionals assessing a skeletal image of a hand and a lower leg/foot, suggesting an examination of joint conditions, with a bicycle and plants in the background.
# **Learning Outcomes**
## **Learning objectives**
1) Understand the different types of immunomodulators and anti-inflammatory drugs
2) Broad understanding of RA, OA and gout and the pharmacological agents used in these conditions
3) Recognise oral and dental side effects of these drugs
4) Understand drugs interactions with dental medications
5) Applied knowledge to clinical scenarios
**Immunomodulators**
* **Stimulate or suppress immune system**
* Tx autoimmune & inflammatory diseases: RA, psoriasis, UC, Crohn's, SLE, organ transplantation
* **Rheumatoid arthritis (RA):** autoimmune disease attacking healthy tissue in joints
* **Tx rationale:** provide sx relief, maintain level of function, and prevent damage to bones, joints, and other organs
* **Osteoarthritis (OA):** deterioration of cartilage at the ends of bones in the joints
* **Tx rationale:** Relieve symptoms (pain and stiffness) and improve joint function to enable the patient to exercise and increase strength and mobility
# **Immunomodulators**
- **Stimulate or suppress immune system**
- Tx autoimmune & inflammatory diseases: RA, psoriasis, UC, Crohn's, SLE, organ transplantation
- **Rheumatoid arthritis (RA):** autoimmune disease attacking healthy tissue in joints
- **Tx rationale:** provide sx relief, maintain level of function, and prevent damage to bones, joints, and other organs
- **Osteoarthritis (OA):** deterioration of cartilage at the ends of bones in the joints
- **Tx rationale:** Relieve symptoms (pain and stiffness) and improve joint function to enable the patient to exercise and increase strength and mobility
**Rheumatoid Arthritis**
**• What is it?**
* Autoimmune disease, inflammatory disorder
* Chronic & progressive
* Systemic, significant morbidity and mortality
**• Pathophysiology**
* Lymphocyte mediated inflammatory disease
* Stimulating antigens $\rightarrow$ abnormal inflammatory response
* Inflammatory mediators (cytokines)TNF- $\alpha$, IL-1, IL-6
* Synovial membrane hypertrophies $\rightarrow$ synovial pannus
* Cytokine rich synovial fluid $\rightarrow$ damage to adjacent supporting structures
# **Rheumatoid Arthritis**
## **What is it?**
- Autoimmune disease, inflammatory disorder
- Chronic & progressive
- Systemic, significant morbidity and mortality
## **Pathophysiology**
- Lymphocyte mediated inflammatory disease
- Stimulating antigens → abnormal inflammatory response
- Inflammatory mediators (cytokines)TNF- $\alpha$, IL-1, IL-6
- Synovial membrane hypertrophies → synovial pannus
- Cytokine rich synovial fluid → damage to adjacent supporting structures
**Rheumatoid Arthritis: treatment**
* **Non-pharmacological**
* Exercise, diet, footcare, massage, heat/cold packs etc
* **Pharmacological**
* **Analgesics:** paracetamol, NSAIDs, opioids
* Manage symptoms but do not alter course of disease
* **Corticosteroids:** not first line, short duration of tx due to adverse effects
* Anti-inflammatory, immunosuppressant and disease modifying effects
* **DMARDs:** biologicals and non biologicals
* DMARDs: aka conventional antirheumatic drugs
* Biological DMARDs: TNF alpha antagonists and cytokine modulators
# **Rheumatoid Arthritis: treatment**
## **Non-pharmacological**
- Exercise, diet, footcare, massage, heat/cold packs etc
## **Pharmacological**
- **Analgesics:** paracetamol, NSAIDs, opioids
- Manage symptoms but do not alter course of disease
- **Corticosteroids:** not first line, short duration of tx due to adverse effects
- Anti-inflammatory, immunosuppressant and disease modifying effects
- **DMARDs:** biologicals and non biologicals
- DMARDs: aka conventional antirheumatic drugs
- Biological DMARDs: TNF alpha antagonists and cytokine modulators
**(DMARDs) Conventional antirheumatic drugs**
<table>
<thead>
<tr>
<th><strong>Generic name (brand name)</strong></th>
<th><strong>Drug class</strong></th>
<th><strong>Selected ADR</strong></th>
<th><strong>Drug interactions (dentally related)</strong></th>
</tr>
</thead>
<tbody>
<tr>
<td>Azathioprine (Azapin, Imuran)</td>
<td>Purine antimetabolite</td>
<td>Dose-related myelosuppression, infection, GI irritation, mouth ulceration</td>
<td>Nil</td>
</tr>
<tr>
<td>Ciclosporin (Neoral)</td>
<td>Calcineurin inhibitors</td>
<td>Gingival hyperplasia, opportunistic infections</td>
<td>Increases toxicity risks of calcineurin inH: Azole antifungals, clarithromycin, erythromycins, NSAIDs</td>
</tr>
<tr>
<td>Hydroxychloroquine (Plaquenil)</td>
<td>Anti-inflammatory and immunosuppressive Antimalarial</td>
<td>Retinal damage, rash, GI irritation</td>
<td>Drugs that prolong QT interval: clarithromycin, erythromycin, fluconazole</td>
</tr>
<tr>
<td>Leflunomide (Arava, Ataris)</td>
<td>Pyrimidine synthesis inhibitor</td>
<td>(common) pharyngitis, dyspnea (infrequent) oral candidiasis, stomatitis, taste disturbance</td>
<td>Hepatotoxic, adhere strict dosage for paracetamol to prevent increase risk of hepatotoxicity</td>
</tr>
<tr>
<td>Methotrexate (Methoblastin)</td>
<td>Antimetabolite</td>
<td>Myelosuppression, mucosal ulcers, GI irritation, infections</td>
<td>Hepatotoxic May increase risks of MTX toxicity: NSAIDs, penicillins, nitrous oxide</td>
</tr>
<tr>
<td>Sulfasalazine (Salazopyrin, Pyralin)</td>
<td>5-aminosalicylate</td>
<td>Myelosuppression, rash (infrequent) yellowing of skin</td>
<td>Nil</td>
</tr>
<tr>
<td>Auranofin (Ridaura)</td>
<td>Gold Salt</td>
<td>Dyspepsia, stomatitis, mouth ulcers, dry mucous membranes, gingivitis</td>
<td>Nil</td>
</tr>
</tbody>
</table>
# **(DMARDs) Conventional antirheumatic drugs**
| **Generic name (brand name)** | **Drug class** | **Selected ADR** | **Drug interactions (dentally related)** |
| :--- | :--- | :--- | :--- |
| Azathioprine (Azapin, Imuran) | Purine antimetabolite | Dose-related myelosuppression, infection, GI irritation, mouth ulceration | Nil |
| Ciclosporin (Neoral) | Calcineurin inhibitors | Gingival hyperplasia, opportunistic infections | Increases toxicity risks of calcineurin inH: Azole antifungals, clarithromycin, erythromycins, NSAIDs |
| Hydroxychloroquine (Plaquenil) | Anti-inflammatory and immunosuppressive Antimalarial | Retinal damage, rash, GI irritation | Drugs that prolong QT interval: clarithromycin, erythromycin, fluconazole |
| Leflunomide (Arava, Ataris) | Pyrimidine synthesis inhibitor | (common) pharyngitis, dyspnea (infrequent) oral candidiasis, stomatitis, taste disturbance | Hepatotoxic, adhere strict dosage for paracetamol to prevent increase risk of hepatotoxicity |
| Methotrexate (Methoblastin) | Antimetabolite | Myelosuppression, mucosal ulcers, GI irritation, infections | Hepatotoxic May increase risks of MTX toxicity: NSAIDs, penicillins, nitrous oxide |
| Sulfasalazine (Salazopyrin, Pyralin) | 5-aminosalicylate | Myelosuppression, rash (infrequent) yellowing of skin | Nil |
| Auranofin (Ridaura) | Gold Salt | Dyspepsia, stomatitis, mouth ulcers, dry mucous membranes, gingivitis | Nil |
# Calcineurin inhibitors
- **MOA**: form complexes with cytoplasmic immunophilins
- Block the action of calcineurin in activated T cells
- Prevents production of interleukin-2 and other cytokines
- **Ciclosporin**: gingival hyperplasia [common in children & adolescent]
- **Tacrolimus**: gingival hyperplasia a [rare ADR]
- **Drug interactions: increases toxicity risks of calcineurin inH**
- Azole antifungals
- Clarithromycin & erythromycins
- NSAIDs
| Generic name | Brand Name |
| :--- | :--- |
| Ciclosporin | Neoral |
| Tacrolimus | Prograf |
# **Calcineurin inhibitors**
- **MOA**: form complexes with cytoplasmic immunophilins
- Block the action of calcineurin in activated T cells
- Prevents production of interleukin-2 and other cytokines
- **Ciclosporin**: gingival hyperplasia [common in children & adolescent]
- **Tacrolimus**: gingival hyperplasia a [rare ADR]
- **Drug interactions: increases toxicity risks of calcineurin inH**
- Azole antifungals
- Clarithromycin & erythromycins
- NSAIDs
| Generic name | Brand Name |
| :--- | :--- |
| Ciclosporin | Neoral |
| Tacrolimus | Prograf |
**Corticosteroids**
* **Recap:** we have discussed a few in respiratory & adrenal insufficiency
* **MOA:** regulate gene expressions (glucocorticoid & mineralocorticoid effects)
* **ADR:** remember **steroids adverse reactions** slide
* **Drug interactions**
* (Methylprednisolone, dexamethasone) + azole: increase steroid adverse effects
* Aspirin: decrease salicylate concentration
* NSAIDs: increase risk of gastric ulceration
| Generic name | Brand Name |
| :--- | :--- |
| **Betamethasone** | **Celestone inj** |
| **Cortisone** | **Cortate** |
| **Dexamethasone** | **Dexmethsone** |
| **Hydrocortisone** | **Solu-Cortef Inj** |
| **Methylprednisolone** | **Solu-Medrol inj** |
| **Prednisolone** | **Predsolone...** |
| **Triamcinolone** | **Kenacort-A inj** |
# **Corticosteroids**
- **Recap:** we have discussed a few in respiratory & adrenal insufficiency
- **MOA:** regulate gene expressions (glucocorticoid & mineralocorticoid effects)
- **ADR:** remember **steroids adverse reactions** slide
- **Drug interactions**
- (Methylprednisolone, dexamethasone) + azole: increase steroid adverse effects
- Aspirin: decrease salicylate concentration
- NSAIDs: increase risk of gastric ulceration
| Generic name | Brand Name |
| :--- | :--- |
| **Betamethasone** | **Celestone inj** |
| **Cortisone** | **Cortate** |
| **Dexamethasone** | **Dexmethsone** |
| **Hydrocortisone** | **Solu-Cortef Inj** |
| **Methylprednisolone** | **Solu-Medrol inj** |
| **Prednisolone** | **Predsolone...** |
| **Triamcinolone** | **Kenacort-A inj** |
**Corticosteroids**
**ADRs**
* Infection
* Delayed wound healing
* Steroid rosacea
* Perioral dermatitis
* Skin atrophy
* Bruising
* Acne
* Facial flushing
* Pupura
* Depigmentation
* Telangiecstasia
* Steroid induced crushing's
<caption>Four images showing the various adverse effects of corticosteroids on the skin, including rosacea-like lesions, perioral dermatitis, and facial flushing, along with diagrams illustrating 'common face proportion' and a 'round face due to fat deposit buildup' (a sign of Cushing's syndrome).</caption>
# **Corticosteroids**
## **ADRs**
- Infection
- Delayed wound healing
- Steroid rosacea
- Perioral dermatitis
- Skin atrophy
- Bruising
- Acne
- Facial flushing
- Pupura
- Depigmentation
- Telangiecstasia
- Steroid induced crushing's
<caption>Four images showing the various adverse effects of corticosteroids on the skin, including rosacea-like lesions, perioral dermatitis, and facial flushing, along with diagrams illustrating 'common face proportion' and a 'round face due to fat deposit buildup' (a sign of Cushing's syndrome).</caption>
**Janus Kinase (JAK) inhibitors**
* MOA: inh Janus kinase (JAK) $\rightarrow$ suppress immune response
* ADR: infections (serious and opportunistic)
* Drug interaction
* **Azoles, clarithromycin, erythromycin:** increase toxicity risk of tofacitinib & upadacitinib
| Generic name | Brand Name |
|--------------|------------|
| Baricitinib | Olumiant inj |
| Tofacitinib | Xeljanz inj |
| Upadacitinib | Rinvoq inj |
# **Janus Kinase (JAK) inhibitors**
- **MOA:** inh Janus kinase (JAK) → suppress immune response
- **ADR:** infections (serious and opportunistic)
- **Drug interaction**
- **Azoles, clarithromycin, erythromycin:** increase toxicity risk of tofacitinib & upadacitinib
| Generic name | Brand Name |
| :--- | :--- |
| Baricitinib | Olumiant inj |
| Tofacitinib | Xeljanz inj |
| Upadacitinib | Rinvoq inj |
** (bDMARDs) TNF alpha antagonists**
* MOA: Bind to TNF alpha and inhibit its activity.
* ADR: [common >1%]
* Infections (opportunistic or serious)
* Mouth ulcers, sore that do not heal, pain or excessive bleeding of gums
* Drug interactions: not dentally related drugs (phew)
* Not to be used with other bDMARDs
<table>
<tr>
<th><b>Generic name</b></th>
<th><b>Brand Name</b></th>
</tr>
<tr>
<td>Adalimumab</td>
<td>Humira inj</td>
</tr>
<tr>
<td>Certolizumab</td>
<td>Cimzia inj</td>
</tr>
<tr>
<td>Etanercept</td>
<td>Enbrel inj</td>
</tr>
<tr>
<td>Golimumab</td>
<td>Simponi inj</td>
</tr>
<tr>
<td>Infliximab</td>
<td>Remsima inj</td>
</tr>
</table>
# **(bDMARDs) TNF alpha antagonists**
- **MOA:** Bind to TNF alpha and inhibit its activity.
- **ADR:** [common >1%]
- Infections (opportunistic or serious)
- Mouth ulcers, sore that do not heal, pain or excessive bleeding of gums
- **Drug interactions:** not dentally related drugs (phew)
- Not to be used with other bDMARDs
| **Generic name** | **Brand Name** |
| :--- | :--- |
| Adalimumab | Humira inj |
| Certolizumab | Cimzia inj |
| Etanercept | Enbrel inj |
| Golimumab | Simponi inj |
| Infliximab | Remsima inj |
**(bDMARDs) Cytokine modulators**
* **Abatacept**: binds to CD80 and CD86 on antigen-presenting cells
* Prevent full activation of CD28 T lymphocytes $\to$ reducing cytokine production and inflammation
* **Anakinra**: neutralises the activity of IL-1
* **Rituximab**: reduce T cell activation and resulting cytokine production
* **Tocilizumab**: inhibits the activity of IL-6
* **Drug interactions**: not dentally related drugs (phew)
* Not to be used with other bDMARDs
<table>
<thead>
<tr>
<th style="background-color: #0b4f6c; color: white;">Generic name</th>
<th style="background-color: #0b4f6c; color: white;">Brand Name</th>
</tr>
</thead>
<tbody>
<tr>
<td>Abatacept</td>
<td>Orencia inj</td>
</tr>
<tr>
<td>Anakinra</td>
<td>Kineret inj</td>
</tr>
<tr>
<td>Rituximab</td>
<td>Riximyo inj</td>
</tr>
<tr>
<td>Tocilizumab</td>
<td>Actemra inj</td>
</tr>
</tbody>
</table>
<table>
<thead>
<tr>
<th style="background-color: #0b4f6c; color: white;">Selected ADR</th>
</tr>
</thead>
<tbody>
<tr>
<td>Dizziness</td>
</tr>
<tr>
<td>Infections (opportunistic or serious)</td>
</tr>
<tr>
<td>Mouth ulcers</td>
</tr>
<tr>
<td>Vertigo</td>
</tr>
</tbody>
</table>
# **(bDMARDs) Cytokine modulators**
- **Abatacept**: binds to CD80 and CD86 on antigen-presenting cells
- Prevent full activation of CD28 T lymphocytes → reducing cytokine production and inflammation
- **Anakinra**: neutralises the activity of IL-1
- **Rituximab**: reduce T cell activation and resulting cytokine production
- **Tocilizumab**: inhibits the activity of IL-6
- **Drug interactions**: not dentally related drugs (phew)
- Not to be used with other bDMARDs
| Generic name | Brand Name |
| :--- | :--- |
| Abatacept | Orencia inj |
| Anakinra | Kineret inj |
| Rituximab | Riximyo inj |
| Tocilizumab | Actemra inj |
| Selected ADR |
| :--- |
| Dizziness |
| Infections (opportunistic or serious) |
| Mouth ulcers |
| Vertigo |
Additionall reading: for fun!
* **Not to be assessed** ☺
* Systemic Lupus Erythematosus (SLE)
* Spondyloarthropathies (seronegative arthritis)
* Ankylosing spondylitis
* Psoriatic arthritis
* Juvenile arthritis
* Fibromyalgia
* Infectious arthritis (chronic and acute)
* Osteomyelitis
* Raynaud’s syndrome
# **Additional reading: for fun!**
- **Not to be assessed** ☺
- Systemic Lupus Erythematosus (SLE)
- Spondyloarthropathies (seronegative arthritis)
- Ankylosing spondylitis
- Psoriatic arthritis
- Juvenile arthritis
- Fibromyalgia
- Infectious arthritis (chronic and acute)
- Osteomyelitis
- Raynaud’s syndrome
**Rheumatoid
arthritis drugs
Dental
implications**
* DMARDs: dose related myelosuppression
* Patient at risks of infections
* Check slide 6 for selected ADR
* Calcineurin inhibitors
* Ciclosporin: gingival hyperplasia in youth
* Check slide 8 for selected ADR
* Corticosteroids: interactions and ADRs
* ADRs relating to dental
* JAK inh (slide 11)
* Gold Salt (slide 7)
* bDMARDs: TNF alpha antagonists & cytokine
modulators (slide 12, 13)
# **Rheumatoid Arthritis Drugs: Dental Implications**
- **DMARDs:** dose related myelosuppression
- Patient at risks of infections
- Check slide 6 for selected ADR
- **Calcineurin inhibitors**
- Ciclosporin: gingival hyperplasia in youth
- Check slide 8 for selected ADR
- **Corticosteroids:** interactions and ADRs
- **ADRs relating to dental**
- JAK inh (slide 11)
- Gold Salt (slide 7)
- bDMARDs: TNF alpha antagonists & cytokine modulators (slide 12, 13)
**Osteo-arthritis**
- **What is it?**
- Gradual breakdown of cartilage, the smooth, protective tissue that covers the ends of bones in joints
- Commonly affects joints in your hands, knees, hips and spine
- **Pathophysiology**
- "wear and tear"
- Breakdown of cartilage, destruction of articular cartilage
- Remodelling of bone
- Loss of joint space $\rightarrow$ bone rub on bone
# **Osteo-arthritis**
## **What is it?**
- Gradual breakdown of cartilage, the smooth, protective tissue that covers the ends of bones in joints
- Commonly affects joints in your hands, knees, hips and spine
## **Pathophysiology**
- "wear and tear"
- Breakdown of cartilage, destruction of articular cartilage
- Remodelling of bone
- Loss of joint space → bone rub on bone
**Osteo-arthritis: treatment**
* Non-pharmacological
* Exercise, diet, footcare, massage, heat/cold packs etc
* Pharmacological
* Supplements
* Paracetamol: preferred drug cf to NSAIDs
* NSAIDs
* Topical can be use but costly
* Oral: aim for the lowest effective dose for the shortest duration
* Opioids
* Intra-articular corticosteroids
* Short-term relief of pain for moderate-to-severe flare of symptoms
* Adjunct to oral therapy
# **Osteo-arthritis: treatment**
## **Non-pharmacological**
- Exercise, diet, footcare, massage, heat/cold packs etc
## **Pharmacological**
- Supplements
- Paracetamol: preferred drug cf to NSAIDs
- NSAIDs
- Topical can be use but costly
- Oral: aim for the lowest effective dose for the shortest duration
- Opioids
- Intra-articular corticosteroids
- Short-term relief of pain for moderate-to-severe flare of symptoms
- Adjunct to oral therapy
**Rheumatoid arthritis Vs Osteo-arthritis**
| Features | Rheumatoid arthritis | Osteoarthritis |
|---|---|---|
| **Affected joints** | Smaller, multiple, proximal finger, bilateral | Large, often one, distal finger, unilateral |
| **Age of onset** | 30-50 | Typically older population |
| **Inflammation** | Yes | Maybe |
| **Other associated sx** | Systemic illness involving other organs | None |
| **Blood tests** | Usually elevated ESR, CRP, RF and anti-CCP | Usually none |
| **Pharmacological treatment** | NSAIDs, DMARDs, bDMARDs, corticosteroids | Paracetamol, maybe NSAIDs & opioids |
# **Rheumatoid arthritis Vs Osteo-arthritis**
| Features | Rheumatoid arthritis | Osteoarthritis |
| :--- | :--- | :--- |
| **Affected joints** | Smaller, multiple, proximal finger, bilateral | Large, often one, distal finger, unilateral |
| **Age of onset** | 30-50 | Typically older population |
| **Inflammation** | Yes | Maybe |
| **Other associated sx** | Systemic illness involving other organs | None |
| **Blood tests** | Usually elevated ESR, CRP, RF and anti-CCP | Usually none |
| **Pharmacological treatment** | NSAIDs, DMARDs, bDMARDs, corticosteroids | Paracetamol, maybe NSAIDs & opioids |
**Prostaglandin & COX enzymes**
* **Prostaglandin**
* Synthesized from AA
* Present at site of inflammation
* Augment action of histamine, vasodilation, increase vascular permeability
* **Cyclooxygenase enzymes**
* Convert AA$\to$ prostaglandin & TxA2
* COX 1: constitutive
* Homeostasis
* Regulate renal blood flow
* Platelet aggregation
* Stomach mucous production
* Regulate stomach acid secretion
* COX 2: inducible
* Inflammation
```mermaid
flowchart TD
A[MEMBRANE PHOSPHOLIPIDS] --> B(Phospholipase A₂)
B --> C(ARACHIDONATE)
C --> D[5-Lipoxygenase]
C --> E[Cyclo-oxygenase]
E --> F{Cyclic endoperoxides}
C --> I[Inhibitors: NSAIDs]
I --> E
D --> G(5-HPETE)
G --> H(Leukotrienes)
F --> J(PGE₂: Vasodilator, stops platelet aggregation, hyperalgesic)
F --> K(TXA₂: Platelet aggregator, vasoconstrictor)
J --> L(PGE₂: Vasodilator, hyperalgesic, increases mucus and decreases acid secretion in stomach, contracts pregnant uterus)
J --> M(PGD₂: Vasodilator, stops platelet aggregation, relaxes most smooth muscle but contracts bronchi)
J --> N(PGF₂α: Spasmogen, luteolytic)
K --> L
K --> M
K --> N
subgraph legend
O[enzymes]
P[5-HPETE = 5-hydroperoxyeicosatetraenoic acid]
end
```
# **Prostaglandin & COX enzymes**
## **Prostaglandin**
- Synthesized from AA
- Present at site of inflammation
- Augment action of histamine, vasodilation, increase vascular permeability
## **Cyclooxygenase enzymes**
- Convert AA→ prostaglandin & TxA2
- **COX 1:** constitutive
- Homeostasis
- Regulate renal blood flow
- Platelet aggregation
- Stomach mucous production
- Regulate stomach acid secretion
- **COX 2:** inducible
- Inflammation
```mermaid
flowchart TD
A[MEMBRANE PHOSPHOLIPIDS] --> B(Phospholipase A₂)
B --> C(ARACHIDONATE)
C --> D[5-Lipoxygenase]
C --> E[Cyclo-oxygenase]
E --> F{Cyclic endoperoxides}
C --> I[Inhibitors: NSAIDs]
I --> E
D --> G(5-HPETE)
G --> H(Leukotrienes)
F --> J(PGE₂: Vasodilator, stops platelet aggregation, hyperalgesic)
F --> K(TXA₂: Platelet aggregator, vasoconstrictor)
J --> L(PGE₂: Vasodilator, hyperalgesic, increases mucus and decreases acid secretion in stomach, contracts pregnant uterus)
J --> M(PGD₂: Vasodilator, stops platelet aggregation, relaxes most smooth muscle but contracts bronchi)
J --> N(PGF₂α: Spasmogen, luteolytic)
K --> L
K --> M
K --> N
subgraph legend
O[enzymes]
P[5-HPETE = 5-hydroperoxyeicosatetraenoic acid]
end
```
# **NSAIDS**
## Nonselective NSAIDs (COX1&2-Inh)
| Generic name | Brand Name |
|--------------|------------|
| Aspirin | Solprin |
| Diclofenac | Voltaren |
| Ibuprofen | Nurofen |
| Indomethacin | Arthrexin, Indocid |
| Ketorolac | Toradol |
| Mefenamic Acid | |
| Naproxen | Inza, Naprosyn |
| Piroxicam | Feldene-D, Mobilis |
## Selective NSAIDs (COX2-Inh)
| Generic name | Brand Name |
|--------------|------------|
| Celecoxib | Celebrex |
| Etoricoxib | Arcoxia |
| Meloxicam | Melobic, Mobic |
| Parecoxib | Dynastat inj |
# **NSAIDS**
## **Nonselective NSAIDs (COX1&2-Inh)**
| Generic name | Brand Name |
| :--- | :--- |
| Aspirin | Solprin |
| Diclofenac | Voltaren |
| Ibuprofen | Nurofen |
| Indomethacin | Arthrexin, Indocid |
| Ketorolac | Toradol |
| Mefenamic Acid | |
| Naproxen | Inza, Naprosyn |
| Piroxicam | Feldene-D, Mobilis |
## **Selective NSAIDs (COX2-Inh)**
| Generic name | Brand Name |
| :--- | :--- |
| Celecoxib | Celebrex |
| Etoricoxib | Arcoxia |
| Meloxicam | Melobic, Mobic |
| Parecoxib | Dynastat inj |
html
<table>
<thead>
<tr>
<th>**Precautions**</th>
<th>**Interactions (MANY)**</th>
</tr>
</thead>
<tbody>
<tr>
<td>
<ul>
<li>Existing renal impairment</li>
<li>Worsen renal function</li>
<li>Existing platelet disorder</li>
<ul>
<li>Affect coagulation → **↑** bleeding risks</li>
</ul>
<li>Existing cardiac disease</li>
<ul>
<li>Na and H2O retention → HTN, peripheral oedema, worsening HF</li>
</ul>
<li>Existing GI conditions</li>
<ul>
<li>Ulceration & **↑** bleeding risks</li>
</ul>
<li>Existing asthma: **↑** bronchospasm</li>
</ul>
</td>
<td>
<ul>
<li>Anticoagulants</li>
<ul>
<li>E.g. warfarin, clopidogrel</li>
</ul>
<li>Renally excreted drugs</li>
<ul>
<li>E.g. lithium, ACE inhibitors, digoxin</li>
</ul>
<li>K+ sparing drugs</li>
<ul>
<li>E.g. ACE inhibitors, “sartans”, spironolactone</li>
</ul>
<li>Antihypertensives</li>
<li>Bisphosphonates</li>
<ul>
<li>E.g. alendronate</li>
</ul>
<li>Corticosteroids</li>
<li>“Triple whammy”</li>
<ul>
<li>NSAID + diuretic + ACE/ARB</li>
</ul>
</ul>
</td>
</tr>
</tbody>
</table>
# **NSAIDs: Precautions and Interactions**
<table>
<thead>
<tr>
<th><strong>Precautions</strong></th>
<th><strong>Interactions (MANY)</strong></th>
</tr>
</thead>
<tbody>
<tr>
<td>
<ul>
<li>Existing renal impairment</li>
<li>Worsen renal function</li>
<li>Existing platelet disorder</li>
<ul>
<li>Affect coagulation → <strong>↑</strong> bleeding risks</li>
</ul>
<li>Existing cardiac disease</li>
<ul>
<li>Na and H2O retention → HTN, peripheral oedema, worsening HF</li>
</ul>
<li>Existing GI conditions</li>
<ul>
<li>Ulceration & <strong>↑</strong> bleeding risks</li>
</ul>
<li>Existing asthma: <strong>↑</strong> bronchospasm</li>
</ul>
</td>
<td>
<ul>
<li>Anticoagulants</li>
<ul>
<li>E.g. warfarin, clopidogrel</li>
</ul>
<li>Renally excreted drugs</li>
<ul>
<li>E.g. lithium, ACE inhibitors, digoxin</li>
</ul>
<li>K+ sparing drugs</li>
<ul>
<li>E.g. ACE inhibitors, “sartans”, spironolactone</li>
</ul>
<li>Antihypertensives</li>
<li>Bisphosphonates</li>
<ul>
<li>E.g. alendronate</li>
</ul>
<li>Corticosteroids</li>
<li>“Triple whammy”</li>
<ul>
<li>NSAID + diuretic + ACE/ARB</li>
</ul>
</ul>
</td>
</tr>
</tbody>
</table>
**NSAIDs ADR**
- **Serious ADR**
- Vomiting blood or material that looks like coffee grounds
- Bleeding from your back passage (rectum), black sticky motions or bloody diarrhoea
- Swelling of the face, lips or tongue which may make swallowing or breathing difficult
- Asthma, wheezing, shortness of breath
- Sudden or severe itching, skin rash, hives
- Pain or tightness in the chest
- **Dental related**
- Sore mouth/tongue
- Aphthous ulcers
- Lichenoid drug eruptions
- Drug induced pemphigus
- Prolonged bleeding
# **NSAIDs: Adverse Drug Reactions (ADR)**
## **Serious ADR**
- Vomiting blood or material that looks like coffee grounds
- Bleeding from your back passage (rectum), black sticky motions or bloody diarrhoea
- Swelling of the face, lips or tongue which may make swallowing or breathing difficult
- Asthma, wheezing, shortness of breath
- Sudden or severe itching, skin rash, hives
- Pain or tightness in the chest
## **Dental related**
- Sore mouth/tongue
- Aphthous ulcers
- Lichenoid drug eruptions
- Drug induced pemphigus
- Prolonged bleeding
**NSAIDs**
**Dental**
**implications**
Common ADRs
* Gastrointestinal: upset stomach, ulcers, bleeding
* Renal: oedema, hypertension, kidney damage
* Respiratory: bronchospasm, asthma exacerbation
* Cardiovascular: increased risk of heart attack, stroke
Dental ADRs
* Sore mouth/tongue
* Aphthous ulcers
* Lichenoid drug eruptions
* Drug-induced pemphigus
* Prolonged bleeding during procedures
Considerations
* Monitor for bleeding risk (esp. during surgery)
* Check for gastrointestinal and renal issues
* Assess for asthma history
* Be aware of drug interactions with other medications
(e.g., anticoagulants)
# **NSAIDs: Dental implications**
## **Common ADRs**
- Gastrointestinal: upset stomach, ulcers, bleeding
- Renal: oedema, hypertension, kidney damage
- Respiratory: bronchospasm, asthma exacerbation
- Cardiovascular: increased risk of heart attack, stroke
## **Dental ADRs**
- Sore mouth/tongue
- Aphthous ulcers
- Lichenoid drug eruptions
- Drug-induced pemphigus
- Prolonged bleeding during procedures
## **Considerations**
- Monitor for bleeding risk (esp. during surgery)
- Check for gastrointestinal and renal issues
- Assess for asthma history
- Be aware of drug interactions with other medications (e.g., anticoagulants)
# **Drugs for gout**
* **What is it?**
* Progressive inflammatory disease
* **Pathophysiology**
* Persistent hyperuricaemia: serum urate >0.42mmol/L
* Formation monosodium urate crystals
* **Treatment rationale**
* Acute flare: provide sx relief
* Chronic gout: lower serum urate
* **Pharmacological**
* NSAIDs: except aspirin
* Colchicine
* Corticosteroids: oral, IM, IV
* Urate lowering drugs
* Xanthine oxidase inH
* Uricosurics
# **Drugs for gout**
## **What is it?**
- Progressive inflammatory disease
## **Pathophysiology**
- Persistent hyperuricaemia: serum urate >0.42mmol/L
- Formation monosodium urate crystals
## **Treatment rationale**
- **Acute flare:** provide sx relief
- **Chronic gout:** lower serum urate
## **Pharmacological**
- NSAIDs: except aspirin
- Colchicine
- Corticosteroids: oral, IM, IV
- Urate lowering drugs
- Xanthine oxidase inH
- Uricosurics
Xanthine oxidase inhibitors
| Generic name | Brand Name |
| :--- | :--- |
| **Allopurinol** | **Allosig, Progout** |
| **Febuxostat** | **Adenuric** |
* Allopurinol & febuxostat
* MOA: Inhibit xanthine oxidase $\rightarrow$ reduce production of uric acid
* Drug interactions
* Allopurinol & Amoxicillin: increase risks of rash
* ADR (infrequent)
* Allopurinol: altered taste sensation
# **Xanthine oxidase inhibitors**
| Generic name | Brand Name |
| :--- | :--- |
| **Allopurinol** | **Allosig, Progout** |
| **Febuxostat** | **Adenuric** |
- **Allopurinol & febuxostat**
- **MOA:** Inhibit xanthine oxidase → reduce production of uric acid
- **Drug interactions**
- Allopurinol & Amoxicillin: increase risks of rash
- **ADR (infrequent)**
- Allopurinol: altered taste sensation
**Other drugs for gout**
* Colchicine
* MOA: inhibits neutrophil migration, chemotaxis, adhesion and phagocytosis in inflamed tissue
* **Drug interactions**
* Clarithromycin, erythromycin& azole antifungals: increase colchicine concN
* NSAIDs: monitor in patients w/ reduced renal function
* **ADR (common)**
* Diarrhoea, nausea, abdominal discomfort, vomiting, pharyngo-laryngeal pain
| Generic name | Brand Name |
| :--- | :--- |
| **Colchicine** | **Colgout, Lengout** |
# **Other drugs for gout**
- **Colchicine**
- **MOA:** inhibits neutrophil migration, chemotaxis, adhesion and phagocytosis in inflamed tissue
- **Drug interactions**
- Clarithromycin, erythromycin& azole antifungals: increase colchicine concN
- NSAIDs: monitor in patients w/ reduced renal function
- **ADR (common)**
- Diarrhoea, nausea, abdominal discomfort, vomiting, pharyngo-laryngeal pain
| Generic name | Brand Name |
| :--- | :--- |
| **Colchicine** | **Colgout, Lengout** |
# Other drugs for gout
* **Probenecid**
* MOA: Increases renal excretion of uric acid by blocking its renal tubular reabsorption
* **Drug interactions**
* Aspirin: reduced uricosuric effect of probenecid
* Cephalosporins & penicillins: increases half-life and prolongs activity of cephalosporin
* Indomethacin & ketorolac: increases concN of these drugs
* **ADR (infrequent)**
* Sore gums
<table>
<thead>
<tr>
<th style="background-color: #3b87a8; color: white;">Generic name</th>
<th style="background-color: #3b87a8; color: white;">Brand Name</th>
</tr>
</thead>
<tbody>
<tr>
<td>Probenecid</td>
<td>Pro-cid</td>
</tr>
</tbody>
</table>
# **Other drugs for gout**
- **Probenecid**
- **MOA:** Increases renal excretion of uric acid by blocking its renal tubular reabsorption
- **Drug interactions**
- Aspirin: reduced uricosuric effect of probenecid
- Cephalosporins & penicillins: increases half-life and prolongs activity of cephalosporin
- Indomethacin & ketorolac: increases concN of these drugs
- **ADR (infrequent)**
- Sore gums
| Generic name | Brand Name |
| :--- | :--- |
| Probenecid | Pro-cid |
# **Drugs for gout**
# **Dental**
# **implications**
* **NSAIDs:** monitor for gastric ulcers and bleeding risks during procedures
* **Colchicine:** monitor for gastrointestinal discomfort and interactions with antibiotics
* **Corticosteroids:** monitor for delayed healing, oral thrush and infection
* **Allopurinol:** altered taste and oral irritation
* **Probenecid:** sore gums may occur, monitor for oral discomfort
* **Drug Interactions:** review interactions, especially with antibiotics and NSAIDs, in patients with renal issues
# **Drugs for Gout: Dental implications**
- **NSAIDs:** monitor for gastric ulcers and bleeding risks during procedures
- **Colchicine:** monitor for gastrointestinal discomfort and interactions with antibiotics
- **Corticosteroids:** monitor for delayed healing, oral thrush and infection
- **Allopurinol:** altered taste and oral irritation
- **Probenecid:** sore gums may occur, monitor for oral discomfort
- **Drug Interactions:** review interactions, especially with antibiotics and NSAIDs, in patients with renal issues
**References**
* Ritter JM, Flower RJ, Henderson G, Loke YK, MacEwan D, Robinson E, editors. *Rang & Dale’s pharmacology*. 10th ed. Edinburgh: Elsevier; 2023
* Australian Medicines Handbook Online [Internet]. Adelaide (AU): Australian Medicines Handbook Pty Ltd;2000. Immunomodulators and Anti-inflammatories; [updated 2025; cited 2025]. Available from: UWA Onesearch
* Pharmaceutical Society of Australia. Australian Pharmaceutical Formulary and Handbook: A Guide to Best Practice. 25th ed. Canberra: Pharmaceutical Society of Australia; 2021
* Ali K. Clinical dental pharmacology. 1st ed. Oxford: Wiley-Blackwell; 2023
* Bullock S, Manias E. *Fundamentals of pharmacology*. 8th ed. Frenchs Forest, NSW: Pearson Australia; 2017
* MIMS Australia. eMIMSelite: *Consumer medicine information, specific clinical monograph* [Internet]. Sydney: MIMS Australia; [updated 2025; cited 2025 Apr 17]. Available from: UWA Onesearch
<img alt="Illustrations related to health and medicine, including a woman blowing her nose with medication bottles and loose pills, and a second image showing several prescription bottles with colorful pills spilled out." />
# **References**
- Ritter JM, Flower RJ, Henderson G, Loke YK, MacEwan D, Robinson E, editors. *Rang & Dale’s pharmacology*. 10th ed. Edinburgh: Elsevier; 2023
- Australian Medicines Handbook Online [Internet]. Adelaide (AU): Australian Medicines Handbook Pty Ltd;2000. Immunomodulators and Anti-inflammatories; [updated 2025; cited 2025]. Available from: UWA Onesearch
- Pharmaceutical Society of Australia. Australian Pharmaceutical Formulary and Handbook: A Guide to Best Practice. 25th ed. Canberra: Pharmaceutical Society of Australia; 2021
- Ali K. Clinical dental pharmacology. 1st ed. Oxford: Wiley-Blackwell; 2023
- Bullock S, Manias E. *Fundamentals of pharmacology*. 8th ed. Frenchs Forest, NSW: Pearson Australia; 2017
- MIMS Australia. eMIMSelite: *Consumer medicine information, specific clinical monograph* [Internet]. Sydney: MIMS Australia; [updated 2025; cited 2025 Apr 17]. Available from: UWA Onesearch
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