BDS Dental Pharmacology Syllabus

Chemically, into what two classes are local anesthetics divided, and how are they metabolized?

Esters (e.g., procaine, benzocaine, tetracaine) — metabolized by plasma pseudocholinesterase. Amides (e.g., lidocaine, articaine, bupivacaine, mepivacaine, prilocaine) — metabolized mainly in the liver. Amides have 'i' in their name before '-caine'.

Why are ester local anesthetics more likely to cause allergic reactions than amides?

Esters are metabolized to para-aminobenzoic acid (PABA), a known allergen. True allergy to amide local anesthetics is rare, so amides are preferred in patients with LA allergy history.

What is the mechanism of action of local anesthetics at the molecular level?

Local anesthetics reversibly block voltage-gated sodium ($\ce{Na+}$) channels on the internal side of the neuronal membrane, preventing $\ce{Na+}$ influx and thereby blocking depolarization and propagation of the action potential.

Which form of a local anesthetic crosses the nerve membrane, and which form blocks the sodium channel?

The uncharged, lipophilic (non-ionized) base form penetrates the nerve membrane; once inside, the charged (ionized, protonated) cationic form binds and blocks the sodium channel from the intracellular side.

Why do local anesthetics work poorly in inflamed or infected (abscessed) tissue?

Inflamed tissue is acidic (low pH), which shifts the equilibrium toward the charged ionized form. Less non-ionized base is available to cross the nerve membrane, so anesthetic penetration and efficacy are reduced.

Why is a vasoconstrictor (e.g., adrenaline) added to local anesthetic solutions? Give three benefits.

Adrenaline causes local vasoconstriction, which (1) prolongs the duration of anesthesia, (2) reduces systemic absorption and toxicity, and (3) decreases bleeding at the surgical site by reducing local blood flow.

State the maximum recommended dose of lidocaine with adrenaline in mg/kg.

Lidocaine with adrenaline: up to $7\ \text{mg/kg}$ (max ~500 mg). Plain lidocaine without adrenaline: up to $4.4\text{–}5\ \text{mg/kg}$ (max ~300 mg).

List the clinical uses of local anesthesia relevant to dentistry.

Pain control for restorative procedures, extractions, endodontics, periodontal surgery, and minor oral surgery. Techniques include topical, infiltration, nerve block (e.g., inferior alveolar nerve block), and intraligamentary/intraosseous injection.

What is the mechanism of action of non-opioid analgesics (NSAIDs)?

NSAIDs inhibit cyclooxygenase (COX-1 and COX-2) enzymes, reducing conversion of arachidonic acid to prostaglandins, thereby producing analgesic, anti-inflammatory, and antipyretic effects.

How does paracetamol (acetaminophen) differ from classic NSAIDs in action and effect?

Paracetamol has analgesic and antipyretic effects but little peripheral anti-inflammatory action. It acts mainly centrally (thought to inhibit COX in the CNS/COX-3) and does not cause gastric ulceration or platelet inhibition, but is hepatotoxic in overdose.

What is the antidote for paracetamol overdose and why does it work?

N-acetylcysteine (NAC). It replenishes hepatic glutathione, allowing detoxification of the toxic reactive metabolite NAPQI (N-acetyl-p-benzoquinone imine) that causes hepatocellular necrosis.

Which NSAID irreversibly inhibits COX, and what is the clinical consequence?

Aspirin irreversibly acetylates COX. Because platelets cannot synthesize new COX, its antiplatelet effect lasts the ~7–10 day lifespan of the platelet, unlike reversible NSAIDs.

Why is aspirin contraindicated in children and after dental surgery in bleeding-risk patients?

In children with viral infections aspirin is linked to Reye's syndrome (encephalopathy and liver failure). Its irreversible antiplatelet effect increases post-operative bleeding risk.

Name the principal adverse effects of chronic NSAID use.

Gastrointestinal ulceration and bleeding (COX-1 inhibition reduces protective gastric prostaglandins), renal impairment, increased cardiovascular risk (especially selective COX-2 inhibitors), and hypersensitivity/bronchospasm.

What is the mechanism of action of opioid analgesics?

Opioids act as agonists at opioid receptors — mainly mu ($\mu$), also kappa ($\kappa$) and delta ($\delta$) — which are G-protein coupled. They inhibit adenylyl cyclase, open $\ce{K+}$ channels (hyperpolarization), and close voltage-gated $\ce{Ca^2+}$ channels, reducing neurotransmitter release and pain transmission.

List the classic adverse effects (triad and others) of opioid analgesics.

Respiratory depression, sedation/CNS depression, and miosis (pinpoint pupils), plus constipation, nausea/vomiting, euphoria, physical dependence and tolerance, and pruritus.

What drug reverses opioid overdose and by what mechanism?

Naloxone, a competitive antagonist at $\mu$ (and other) opioid receptors. Given IV/IM it rapidly reverses respiratory depression; its short half-life may require repeat dosing.

Compare codeine and tramadol as mild opioids used in dental pain.

Codeine is a prodrug converted by CYP2D6 to morphine for analgesia (variable due to genetic polymorphism). Tramadol is a weak $\mu$ agonist that also inhibits serotonin and noradrenaline reuptake; it carries seizure and serotonin-syndrome risk.

Define adjuvant analgesics and give two examples used for neuropathic dental/orofacial pain.

Adjuvant analgesics are drugs whose primary indication is not pain but which relieve pain in certain conditions. Examples: anticonvulsants such as carbamazepine and gabapentin/pregabalin, and tricyclic antidepressants such as amitriptyline.

Which drug is first-line for trigeminal neuralgia and what is its mechanism?

Carbamazepine is first-line for trigeminal neuralgia. It blocks voltage-gated sodium channels, stabilizing hyperexcitable neuronal membranes and reducing paroxysmal pain discharges.

Describe the WHO analgesic ladder as applied to dental pain management.

Step 1: non-opioid (paracetamol/NSAID) $\pm$ adjuvant for mild pain. Step 2: add a weak opioid (codeine/tramadol) for moderate pain. Step 3: strong opioid (morphine) for severe pain. Adjuvants may be added at any step.

What is the rationale for combining paracetamol with an NSAID (e.g., ibuprofen) for acute dental pain?

They have different, complementary mechanisms (central vs peripheral COX-related action), giving additive/synergistic analgesia superior to either alone, while allowing lower doses and reducing opioid need — a common regimen for post-extraction pain.

Classify antibiotics by their mechanism of action into the major groups.

1) Inhibitors of cell wall synthesis (penicillins, cephalosporins, vancomycin). 2) Inhibitors of protein synthesis (tetracyclines, macrolides, aminoglycosides, clindamycin). 3) Inhibitors of nucleic acid synthesis (fluoroquinolones, rifampicin). 4) Inhibitors of folate synthesis (sulfonamides, trimethoprim). 5) Cell membrane disruptors (polymyxins).

Distinguish bactericidal from bacteriostatic antibiotics with examples.

Bactericidal agents kill bacteria (penicillins, cephalosporins, aminoglycosides, metronidazole, fluoroquinolones). Bacteriostatic agents inhibit growth, relying on host defenses (tetracyclines, macrolides, sulfonamides, clindamycin at usual doses).

What is the mechanism of action of beta-lactam antibiotics (penicillins/cephalosporins)?

Beta-lactams bind penicillin-binding proteins (transpeptidases) and inhibit cross-linking of peptidoglycan in the bacterial cell wall, leading to a weakened wall, osmotic lysis, and cell death. They are most effective against actively dividing bacteria.

Why is amoxicillin the first-line antibiotic for most acute dental (odontogenic) infections?

Odontogenic infections are usually caused by mixed oral flora dominated by susceptible Gram-positive and anaerobic organisms. Amoxicillin has a suitable spectrum, good oral absorption, and is generally well tolerated; metronidazole may be added for anaerobic cover.

State the clinical role of metronidazole in dentistry and one critical patient counselling point.

Metronidazole targets obligate anaerobes and is used for acute necrotizing ulcerative gingivitis, pericoronitis, and severe periodontal infections (often with amoxicillin). Patients must avoid alcohol due to a disulfiram-like reaction (flushing, nausea, vomiting).

Which antibiotic is used for penicillin-allergic patients in dentistry, and what is a notable adverse effect?

Clindamycin (a lincosamide, inhibits the 50S ribosomal subunit) is used in penicillin-allergic patients for serious dental infections. It is associated with pseudomembranous colitis due to Clostridioides difficile overgrowth.

Name the mechanism and dental use of antifungal agents like nystatin and the azoles for oral candidiasis.

Nystatin/amphotericin B (polyenes) bind ergosterol in the fungal membrane, forming pores. Azoles (fluconazole, miconazole) inhibit ergosterol synthesis via CYP450 14-alpha-demethylase. Both treat oral candidiasis (thrush); nystatin/miconazole are used topically, fluconazole systemically.

What antiviral is used for herpetic oral lesions, and what is its mechanism and mode of action?

Aciclovir treats herpes simplex (herpes labialis, primary herpetic gingivostomatitis). It is a guanosine analogue activated by viral thymidine kinase to a triphosphate that inhibits viral DNA polymerase and terminates the viral DNA chain, making it selective for infected cells.

What is the mechanism of action of benzodiazepines and their main dental use?

Benzodiazepines (e.g., diazepam, midazolam) bind an allosteric site on the $\ce{GABA_A}$ receptor, increasing the frequency of chloride channel opening in response to GABA, enhancing inhibitory neurotransmission. In dentistry they are used for conscious sedation and anxiolysis; midazolam is common for IV sedation. Flumazenil is the specific antagonist/reversal agent.