Overseas Registration Exam (ORE) Human Disease, Pharmacology and Therapeutics Syllabus

What dental precautions apply to a patient on renal dialysis (haemodialysis)?

Treat on the day after dialysis (not the same day) when the patient is least uraemic and heparin has worn off; avoid nephrotoxic drugs; be aware of bleeding tendency, anaemia, hypertension and risk of hepatitis/bloodborne infection.

What is a bleeding diathesis, and name three examples relevant to dentistry.

A bleeding diathesis is an increased tendency to bleed due to a defect in haemostasis. Examples: haemophilia A (factor VIII deficiency), haemophilia B (factor IX deficiency), von Willebrand disease, and thrombocytopenia.

How does haemophilia A differ from von Willebrand disease in inheritance and deficiency?

Haemophilia A is X-linked recessive (affecting males) with a deficiency of factor VIII. Von Willebrand disease is usually autosomal dominant (affecting both sexes) with a deficiency or defect of von Willebrand factor, which also impairs platelet adhesion.

What laboratory tests assess the intrinsic, extrinsic and platelet pathways of haemostasis?

APTT (activated partial thromboplastin time) assesses the intrinsic pathway; PT/INR (prothrombin time) assesses the extrinsic pathway; platelet count and bleeding time/function assess platelet-related haemostasis.

What dental considerations apply to a patient with epilepsy?

Identify triggers and seizure frequency/control, avoid stress and flashing lights, be aware of gingival hyperplasia from phenytoin, secure airway/instruments, and know the management of a seizure (protect from injury, do not restrain, time the seizure).

When does a tonic-clonic seizure become status epilepticus, and how is it managed in the dental setting?

When a seizure lasts more than 5 minutes or seizures recur without recovery. Management: protect the patient, give oxygen, give buccal midazolam 10 mg (adult) and call emergency services.

Why are dental patients with liver disease at increased risk of bleeding and drug toxicity?

The liver produces clotting factors (II, VII, IX, X — vitamin K dependent) so bleeding risk rises; and impaired hepatic metabolism reduces clearance of many drugs (e.g. lidocaine, paracetamol, sedatives), increasing toxicity risk.

What infection-control and prescribing concerns relate to a patient with hepatitis B or C?

Risk of bloodborne transmission requires strict cross-infection control; impaired liver function affects drug metabolism (reduce/avoid hepatotoxic drugs like paracetamol overdose risk), and bleeding tendency from reduced clotting factors must be assessed.

Define pharmacokinetics and pharmacodynamics.

Pharmacokinetics is what the body does to the drug — absorption, distribution, metabolism and excretion (ADME). Pharmacodynamics is what the drug does to the body — its mechanism of action and the relationship between concentration and effect.

What are the four processes of pharmacokinetics (ADME)?

Absorption (drug entering the bloodstream), Distribution (drug spreading to tissues), Metabolism (biotransformation, mainly hepatic), and Excretion (elimination, mainly renal).

Define a drug's elimination half-life ($t_{1/2}$) and its relationship to the elimination rate constant.

The half-life is the time taken for the plasma concentration of a drug to fall by half. It relates to the elimination rate constant $k$ by $t_{1/2} = \frac{0.693}{k}$, where $0.693 = \ln 2$.

State the formula relating clearance ($CL$), volume of distribution ($V_d$) and elimination half-life.

$$t_{1/2} = \frac{0.693 \times V_d}{CL}$$ Half-life increases with a larger volume of distribution and decreases with greater clearance.

Define bioavailability and give the formula for absolute bioavailability ($F$).

Bioavailability is the fraction of an administered dose that reaches the systemic circulation unchanged. Absolute bioavailability is $$F = \frac{AUC_{oral} \times Dose_{IV}}{AUC_{IV} \times Dose_{oral}}$$ Intravenous drugs have $F = 1$ (100%).

What is first-pass metabolism and why is it important?

First-pass metabolism is the metabolism of an orally-administered drug by the gut wall and liver before it reaches the systemic circulation, reducing bioavailability. It explains why some drugs are far less effective orally than intravenously.

What is the difference between zero-order and first-order kinetics?

In first-order kinetics a constant fraction of drug is eliminated per unit time (rate proportional to concentration) — most drugs. In zero-order kinetics a constant amount is eliminated per unit time regardless of concentration (saturated enzymes), e.g. alcohol, phenytoin, high-dose aspirin.

Distinguish a drug agonist from an antagonist.

An agonist binds a receptor and activates it to produce a response (has affinity and efficacy). An antagonist binds the receptor but produces no response, blocking the action of agonists (has affinity but no efficacy).

What is the difference between drug efficacy and potency?

Efficacy is the maximum effect a drug can produce regardless of dose. Potency is the amount (dose/concentration) of drug required to produce a given effect; a more potent drug achieves the effect at a lower dose (lower $EC_{50}$).

Which analgesics are commonly used in dentistry, and what are first-line choices for dental pain?

Paracetamol and NSAIDs (ibuprofen) are first-line for dental pain. Ibuprofen is particularly effective for inflammatory dental pain. Opioids (codeine) are less effective for dental pain and reserved for cases where NSAIDs are contraindicated.

What is the first-line antibiotic for dental infection in a non-penicillin-allergic patient, and the alternative if allergic?

Amoxicillin (or phenoxymethylpenicillin) is first-line. In penicillin allergy, metronidazole or clarithromycin/clindamycin is used. Metronidazole is especially useful for anaerobic infections such as acute periodontal conditions.

What patient advice is essential when prescribing metronidazole, and why?

Avoid alcohol during treatment and for 48 hours after, because metronidazole inhibits acetaldehyde dehydrogenase, causing a disulfiram-like reaction (flushing, nausea, vomiting, headache, tachycardia).

What legal requirements must appear on a valid prescription in the UK?

Patient's name, address and age (if under 12); date; the drug name, form, strength, dose and quantity; clear instructions; and the prescriber's signature and address. Controlled drugs need additional handwritten/specified details and total quantity in words and figures.

What additional requirements apply to prescriptions for Schedule 2 and 3 controlled drugs in the UK?

They must state the drug, form, strength, dose and total quantity in both words and figures, be signed and dated by the prescriber, include the prescriber's address, and (for Schedule 2/3) the prescription is valid for 28 days only.

Define a drug interaction and give an example relevant to dental prescribing.

A drug interaction is when one drug alters the effect of another. Example: NSAIDs increase the anticoagulant effect of warfarin (raising bleeding risk); fluconazole/miconazole potentiate warfarin; erythromycin/clarithromycin inhibit metabolism of many drugs (CYP3A4).

Why should aspirin and NSAIDs be used cautiously with warfarin and in peptic ulcer patients?

NSAIDs inhibit platelet function and can cause gastric erosion/bleeding; combined with warfarin they greatly increase bleeding risk by displacing it from protein binding and adding antiplatelet effect. They are contraindicated in active peptic ulcer disease.

Distinguish a Type A from a Type B adverse drug reaction.

Type A ('Augmented') reactions are dose-dependent, predictable extensions of the drug's pharmacology (e.g. bleeding with warfarin) and are common. Type B ('Bizarre') reactions are unpredictable, not dose-related, often immunological (e.g. penicillin anaphylaxis) and less common.

What is the mechanism of action of local anaesthetics such as lidocaine?

They reversibly block voltage-gated sodium ($\ce{Na+}$) channels on the nerve membrane, preventing depolarisation and propagation of the action potential, thereby blocking nerve conduction and sensation.

Why is a vasoconstrictor (e.g. adrenaline 1:80,000) added to local anaesthetic solutions?

It causes local vasoconstriction, which prolongs the duration of anaesthesia, reduces systemic absorption and toxicity, increases depth of anaesthesia, and reduces bleeding at the surgical site.

State the maximum safe dose of 2% lidocaine with 1:80,000 adrenaline and the calculation basis.

Maximum lidocaine dose is about 4.4 mg/kg (commonly cited up to ~500 mg total with adrenaline). A 2.2 mL cartridge of 2% lidocaine contains 44 mg lidocaine, since $2\% = 20\ \text{mg/mL} \times 2.2\ \text{mL} = 44\ \text{mg}$.

What is the definition of conscious sedation as used in dentistry?

A technique in which drug(s) produce a state of depression of the central nervous system enabling treatment, but during which verbal contact with the patient is maintained throughout. The drugs/techniques used carry a margin of safety wide enough to render loss of consciousness unlikely.

Compare inhalation sedation (nitrous oxide) and intravenous sedation (midazolam) in dentistry.

Inhalation (N2O/O2 'relative analgesia'): rapid onset/recovery, easily titratable, mild, good for children and anxious patients, no amnesia, patient can drive home. IV midazolam: deeper sedation, profound amnesia, used in adults, needs cannulation, longer recovery, patient needs an escort and cannot drive for 24 hours.

What is the reversal agent for benzodiazepine (midazolam) over-sedation, and why must patients still be monitored after its use?

Flumazenil is the benzodiazepine antagonist used to reverse over-sedation. Patients must still be monitored because flumazenil has a shorter half-life than midazolam, so re-sedation can occur as it wears off.

What are the main indications for referral for general anaesthesia in dentistry?

Failed local anaesthesia or acute infection preventing it, extensive surgery, very young children or patients with severe learning disability/uncooperative behaviour where other methods fail, severe dental anxiety unmanageable by sedation, and medical conditions requiring controlled airway management. GA must be carried out in a hospital with critical-care facilities.