Pharmacology workbook Flashcards
What are the three main structural components of local anaesthetics?
Aromatic ring (usually benzene), amide or ester link, and terminal amine.
What is unique about articaine’s structure?
It has a thiophene ring instead of benzene and an ester group attached.
How do local anaesthetics work?
They bind to sodium (Na⁺) channels, inactivating them and preventing action potential propagation along the neuron.
Why must LA cross the neuron membrane to work?
It must first diffuse into the neuron to reach the Na⁺ channel from the intracellular side.
In what two forms do local anaesthetics exist in solution?
Non-ionised (fat-soluble) and ionised (water-soluble).
Which form of LA diffuses into neurons, and which binds Na⁺ channels?
Fat-soluble (non-ionised) diffuses in; water-soluble (ionised) binds Na⁺ channels.
How does low tissue pH (e.g., in inflamed tissue) affect LA efficacy?
More LA remains ionised, reducing diffusion into the neuron, leading to reduced efficacy.
What does the Henderson-Hasselbalch equation describe?
The relationship between pH, pKa, and the proportion of ionised/non-ionised LA.
What happens if tissue pH is lower than the pKa of an LA?
A higher proportion of the LA is ionised, reducing neuron penetration.
How is LA used in dentistry?
- Infiltration anaesthesia
- Inferior alveolar nerve blocks
- Topical anaesthesia (e.g., 5% lidocaine gel)
What is EMLA cream used for?
Topical analgesia for anxious patients before IV or general anaesthesia.
What LA can be used for post-op pain relief?
Longer-lasting LAs such as bupivacaine or levobupivacaine.
How can systemic toxicity of LA present?
- Cardiac arrhythmias
- CNS depression (altered consciousness)
How does LA affect blood vessels?
Some cause vasodilation, while others (like prilocaine) have mild vasoconstrictor activity.
Is allergy to LA common?
No, and it is even rarer with amide-based LAs.
Can LA be used in pregnancy?
Yes, but should be avoided in the 1st and 3rd trimesters unless clinically urgent.
Is LA present in breast milk?
Yes, but not at harmful levels.
How are most LAs metabolised?
In the liver.
How are ester LAs metabolised?
By plasma pseudocholinesterase, leading to faster breakdown.
What is adrenaline and where is it secreted?
It is an endogenous catecholamine secreted by the adrenal medulla.
How does adrenaline affect blood vessels?
α₁ receptor activation → Vasoconstriction → Raises BP.
How does adrenaline affect the heart?
β₁ receptor activation → Increases contractility & heart rate → Increases cardiac output.
How does adrenaline affect the lungs?
β₂ receptor activation → Bronchodilation → Reduces airway resistance.
How does adrenaline affect glucose metabolism?
α₂ activation in the pancreas → ↓ Insulin & ↑ Glucagon → Raises plasma glucose.
How is adrenaline broken down?
By Monoamine Oxidase (MAO) and Catechol-O-Methyltransferase (COMT).
Where is adrenaline metabolised?
In the brain, muscle, lungs, blood vessels, and liver.
What are the side effects of adrenaline in LA?
- Palpitations
- Increased heart rate
- Anxiety
- Tremor
In which patients should adrenaline be used with caution?
Those with severe cardiac disease or uncontrolled hypertension.
How do MAO inhibitors (MAOIs) affect adrenaline metabolism?
They inhibit adrenaline breakdown, increasing its effects.
Can adrenaline-containing LA be used in pregnancy?
Yes, at recommended doses, if clinically indicated.
Is adrenaline found in breast milk?
Yes, but not at harmful levels.
How does warfarin work?
Inhibits Vitamin K reduction, preventing activation of clotting factors II, VII, IX, X, leading to depletion of active clotting factors → Reduced clotting capacity.
How is warfarin metabolised and cleared?
Metabolised in the liver by Cytochrome P450 enzymes, exhibits genetic variability in metabolism, small therapeutic index → Requires frequent monitoring and dose adjustments.
Why is warfarin monitoring important?
Measured using Prothrombin Time (PT), expressed as International Normalised Ratio (INR). Target INR depends on indication (e.g., 2.0–3.5 for most cases).
What is the formula for INR?
INR = Test PT / Average Normal PT
What are the main side effects and cautions of warfarin?
Major risk: Abnormal/prolonged bleeding, interacts with many drugs & foods, NSAIDs increase bleeding risk by inhibiting platelet function, antibiotics/antifungals can alter warfarin metabolism.
How is warfarin reversed?
Vitamin K (restores clotting factor production, takes time), Fresh Frozen Plasma (FFP) (provides active clotting factors, for urgent cases).
What is the basic structure of penicillins?
β-lactam ring (essential for antibacterial activity).
How do penicillins work?
Bind to Penicillin-Binding Proteins (PBPs), prevent peptidoglycan cross-linking in bacterial cell walls → Bacterial lysis.
What factors affect penicillin activity and absorption?
- Penicillin G (Benzylpenicillin) is acid-sensitive, given IV/IM
- Penicillin V (Phenoxymethylpenicillin) is acid-stable, given orally
- Gram-negative bacteria resist entry due to outer phospholipid membrane
- Amoxicillin & ampicillin are more hydrophobic, allowing better Gram-negative penetration.
How do bacteria resist penicillins?
Produce β-lactamase enzyme, which breaks the β-lactam ring. Flucloxacillin is resistant to β-lactamase, clavulanic acid inhibits β-lactamase (used in co-amoxiclav).
How are penicillins metabolised and cleared?
Excreted unchanged by the kidney, dose adjustments needed in renal failure.
What are the main side effects and cautions of penicillins?
Allergy: Rash, anaphylaxis (cross-reactivity with cephalosporins), altered gut flora: Risk of Clostridium difficile infection, safe in pregnancy & breastfeeding.
How do aminoglycosides, tetracyclines, and macrolides work?
Target bacterial ribosomes (30S & 50S subunits) → Inhibit protein synthesis.
What is the mechanism of action for macrolides?
Erythromycin (50S) inhibits amino acid transfer.
What is the mechanism of action for tetracyclines?
Blocks tRNA binding (30S).
What is the mechanism of action for aminoglycosides?
Misreads mRNA sequence (30S).
How do macrolides compare to penicillins?
Erythromycin has a similar spectrum to penicillin, used as an alternative in penicillin allergy.
How are erythromycin, gentamicin, and tetracycline metabolised and cleared?
- Erythromycin: Liver metabolism, inhibits Cytochrome P450 → Risk of warfarin accumulation
- Gentamicin & tetracycline: Cleared by kidneys.
What are the side effects and cautions for erythromycin?
GI upset, warfarin interaction.
What are the side effects and cautions for gentamicin?
Risk of hearing loss (ototoxicity).
What are the side effects and cautions for tetracycline?
Tooth discoloration (avoid in pregnancy & children).
What infections is metronidazole used for?
Anaerobic bacterial infections, including dentoalveolar infections.
How does metronidazole work?
Inactive until reduced inside bacteria, binds microbial DNA, preventing replication → Bacterial death.
How is metronidazole metabolised and cleared?
Metabolised in the liver, some metabolites still have antibacterial activity, cleared by kidneys.
Does metronidazole interact with alcohol?
Historically believed to cause a Disulfiram-like reaction (nausea, vomiting), evidence is weak but many doctors still advise avoiding alcohol.
What are the main side effects and cautions of metronidazole?
Well tolerated, avoid in pregnancy & breastfeeding unless necessary.
