SCRIPT module Flashcards by Anna McHugh

Agonist

Agonist: A chemical (which could be a drug, hormone, chemical messenger, or other signalling molecule) that binds to its target and activates it to increase its activity

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Non-competitive antagonist

Non-competitive antagonist; prevents the agonist from producing a response at its receptor

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Partial Agonist

Partial Agonists bind and activate a receptor but produce a lower maximal response than full agonists

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Allosteric Modulator

A drug that binds to a site on the receptor different from the active site (allosteric site), which can either enhance (positive modulator) or inhibit (negative modulator) the receptor’s response to its natural agonist

positive allosteric modulators= increase the potency of the agonist

negative allosteric modulators= decrease the potency of the agonist

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Affinity

Affinity: The strength of binding between a drug and its receptor.

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Efficacy

Efficacy: The ability of a drug, once bound, to produce a biological response (its “effectiveness”).

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Potency

Potency: The amount of drug required to produce a given effect. A more potent drug requires a lower dose. (Note: Potency is often confused with efficacy; a drug can be highly potent but have low maximal efficacy if it’s a partial agonist).

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What is up-regulation and down-regulation of receptors? Provide a clinical consequence of each.

Down-regulation: A decrease in the number of receptors, often due to prolonged exposure to high levels of an agonist. Consequence: Can lead to drug tolerance (e.g., needing higher doses of an opioid for the same pain relief).

Up-regulation: An increase in the number of receptors, often due to prolonged receptor blockade by an antagonist. Consequence: Can lead to withdrawal symptoms or rebound effects if the antagonist is abruptly stopped (e.g., super-sensitivity to catecholamines after stopping a beta-blocker).

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A patient presents unconscious, with pinpoint pupils and a low respiratory rate, alongside track marks. What is the mechanism of action of the likely intoxicant and its antidote?

Intoxicant (Agonist): Heroin (or another opioid). It is a full agonist at opioid receptors (mu-opioid receptors), causing CNS depression.

Antidote (Antagonist): Naloxone. It is a competitive antagonist at opioid receptors. It displaces the opioid, reversing respiratory depression and sedation.

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Why is understanding a drug’s mechanism of action key to predicting its side-effects?

Side-effects are often just the other (non-therapeutic) pharmacological actions of the drug. For example, the non-selective beta-blocker propranolol blocks beta-adrenoceptors in the heart (therapeutic for hypertension) but also in the lungs (side-effect of bronchoconstriction) and blood vessels (side-effect of cold extremities)

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Why is L-Dopa (Levodopa) given in combination with Carbidopa for Parkinson’s disease?

Mechanism: L-Dopa is a dopamine precursor that crosses the blood-brain barrier to replenish dopamine in the brain. Carbidopa is a peripheral dopa decarboxylase inhibitor.

Reason for Combination: Carbidopa does not cross the BBB. It inhibits the enzyme that converts L-Dopa to dopamine in the periphery.
Consequences:

Therapeutic: More L-Dopa is available to enter the brain, increasing efficacy.
Side-effect Reduction: Greatly reduces peripheral side effects like nausea, vomiting, and cardiovascular effects caused by dopamine formed outside the CNS.

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Why can neostigmine be used to reverse the non-depolarising blocker vecuronium, but not the depolarising blocker suxamethonium?

Neostigmine’s Mechanism: It is an acetylcholinesterase inhibitor. This increases synaptic acetylcholine (ACh) levels.

Reversing Vecuronium: Vecuronium is a competitive antagonist at nicotinic receptors. The increased ACh from neostigmine competitively displaces vecuronium from the receptors, restoring neuromuscular function.

Not Reversing Suxamethonium: Suxamethonium is an agonist that causes prolonged depolarisation. Increasing ACh with neostigmine would potentiate, not reverse, its action, worsening the blockade.

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What is the pharmacological basis for using naloxone to treat a heroin overdose?

Mechanism: This is a classic agonist-antagonist interaction.

Heroin (Agonist): A full agonist at mu-opioid receptors, causing profound CNS and respiratory depression.

Naloxone (Antagonist): A competitive antagonist with very high affinity for mu-opioid receptors but no efficacy.

Result: Naloxone rapidly displaces heroin from the receptors, reversing the toxic effects. Its short duration of action relative to some opioids is a key clinical consideration (risk of re-narcotisation).

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Using the example of propranolol, explain how a drug’s mechanism of action explains its side-effect profile

Mechanism: Propranolol is a non-selective beta-adrenoceptor antagonist.

Side-effect Logic:
- Bronchospasm: Blockade of β₂-receptors in the lungs.
- Bradycardia & Heart Block: Blockade of β₁-receptors in the heart.
- Cold Extremities & Fatigue: Blockade of β₂-receptors mediating vasodilation in skeletal muscle and metabolic effects.

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A patient with a chronic heroin use disorder and an opiate-naïve patient both present with an acute heroin overdose. How will their physical responses to naloxone likely differ, and what is the pharmacological mechanism?

Chronic User: Will likely require a higher dose of naloxone and will experience an acute, severe withdrawal syndrome (precipitated withdrawal) upon reversal.

Opiate-Naïve User: Will likely respond to a standard naloxone dose and will simply wake up, without experiencing withdrawal.

Pharmacological Mechanism:

The difference is due to tolerance and dependence in the chronic user. Chronic opioid exposure causes:

Receptor Down-regulation: A decrease in the number of opioid receptors.
Cellular Adaptation: Neurons adapt to the constant presence of the agonist.

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A patient is successfully revived from an opioid overdose with a single dose of naloxone but leaves the hospital. Why are they at high risk of a recurrent, fatal overdose shortly after?

This is due to the pharmacokinetic mismatch between naloxone and the opioid (e.g., heroin).

Naloxone: Has a very short half-life and duration of action (20-90 minutes). It is cleared from the body quickly.

The Opioid: Often has a much longer half-life (especially methadone or sustained-release formulations) and remains in the system.

Result: The naloxone wears off and is cleared from the opioid receptors while a significant amount of the opioid agonist is still circulating. The opioid can then re-bind to the unblocked receptors, causing re-narcotisation—a return of respiratory depression, unconsciousness, and potential death, often occurring after the patient has left a place of safety.

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competitive antagonist

competitive antagonist; will bind to the receptor binding site preventing the agonist from binding. The effects of a competitive antagonist can be reversed by increasing the concentration of the agonist

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What is an allosteric modulator? Using the example of cinacalcet, describe its mechanism of action and a key clinical advantage

Definition: An allosteric modulator is a drug that binds to a site on a receptor different from the active site (the allosteric site). This binding changes the receptor’s shape, which can either enhance (positive modulator) or inhibit (negative modulator) the receptor’s response to its natural agonist.

Mechanism of Cinacalcet: Cinacalcet is a positive allosteric modulator of the calcium-sensing receptor (CaSR). It increases the receptor’s sensitivity to extracellular calcium.

Clinical Advantage: Allosteric modulators do not directly activate or inactivate cell signaling. Instead, they “change the set-point for normal activity,” allowing for a more subtle and physiologically responsive regulation compared to a direct agonist or antagonist.

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What is the difference between affinity, efficacy, and potency?

Affinity:Binding strength.Efficacy:Ability to produce effect once bound.Potency:Dose required for given effect (e.g., EC₅₀).

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Effect of a competitive antagonist on a dose–response curve?

Parallel rightward shift → ↓ potency (same maximal effect).

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Effect of a non-competitive antagonist?

↓ maximal response (↓ efficacy).

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What is an allosteric modulator? Give an example.

Binds non-agonist site to modify receptor activity.Example: Cinacalcet (positive CaSR modulator).

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Main types of drug targets (receptors)?

GPCRs, ion channels, nuclear receptors, carrier molecules, enzymes.

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Which Ca²⁺ channel is targeted in cardiac & vascular muscle?

L-type calcium channel

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How do DHP CCBs differ from Verapamil/Diltiazem?

Dihydropyridines/DHPs (Amlodipine, Nifedipine) are a type of CCB that are vascular selective → potent vasodilators of whole body. Whereas non-DHP CCBs are cardiac-selective vasodilators e.g. Verapamil/Diltiazem: cardiac selective → ↓ HR, ↓ AV conduction.

Main monoamine transporters and inhibitors?

DAT (dopamine): Cocaine, amphetamine, methylphenidate. NET (noradrenaline): Cocaine, TCAs, SNRIs. SERT (serotonin): SSRIs, TCAs, SNRIs, MDMA.

Why are SSRIs preferred to TCAs?

Fewer antimuscarinic/cardiac side effects, safer in overdose.

Mechanism of Aspirin and Captopril.

Aspirin: Irreversible non-selective COX inhibitor Captopril: Reversible competitive ACE inhibitor.

Mechanism & benefit of Statins.

Inhibit HMG-CoA reductase → upregulate LDL receptors → ↓ plasma LDL. (NICE: Atorvastatin 20 mg primary, 80 mg secondary prevention).

What receptors do steroid hormones act on?

Intracellular nuclear receptors; lipophilic drugs.

Unlicensed vs off-label medicine?

Unlicensed: No UK marketing authorisation. Off-label: Licensed but used outside licence (e.g., dose, indication, age).

Three stages of Medicines Reconciliation?

1. Verification 2. Clarification 3. Reconciliation (NICE NG5: within 24 h of admission).

Essential details for each medicine in history?

Name, formulation, strength, dose, frequency, duration, indication.

Commonly forgotten drugs?

Contraceptives, topical meds, eye/ear drops, inhalers, herbal/OTC.

DRUGS mnemonic?

Doctors (prescribed), Recreational, User (OTC/CAMs), Gynaecological, Sensitivities.

If >48 h Clozapine missed?

Restart titration from initial dose (risk: hypotension/cardiac arrest).

Which drugs not in MDS (Monitored Dosage Systems)?

PRN, cytotoxics, weekly doses (e.g., Methotrexate), effervescent/dispersible, buccal/sublingual forms.

Warfarin admission checklist?

Indication, target INR, duration, current dose, date/result of last INR.

Who prescribes oral cytotoxics (e.g., Capecitabine)?

Only oncology/haematology specialists.

Why is a hospital inpatient drug chart a PSD, not a prescription?

It’s an instruction to administer to a named patient, not a supply order.

Legal requirement for age on NHS prescriptions?

Must be stated if under 12 years.

Which drug must be prescribed by brand name?

Tacrolimus (to prevent toxicity/graft rejection).

Key safety check before prescribing Naseptin®?

Contains arachis (peanut) oil → contraindicated in nut allergy.

What must be documented before prescribing?

Allergy status (“No Known Allergies” if none).

Define adherence.

Degree to which patient follows agreed treatment plan.

Difference: adherence vs compliance?

Compliance = passive following; adherence = active agreement.

Define concordance.

Shared decision-making between prescriber & patient. (NICE NG197)

Ways to improve adherence?

Simplify regimen, switch formulation, use MDS, provide clear info.

Patient stops metformin due to GI effects — what next?

Switch to MR metformin or alternative (e.g., sulphonylurea).

Objective measure of adherence?

Plasma drug concentration (e.g., Clozapine, Lithium).

Should you inform patients of side effects?

Yes — improves safety and engagement; does not reduce adherence.

Preferred formula for renal drug dosing in extremes of weight/muscle?

Cockcroft–Gault (Creatinine Clearance). Avoid relying solely on eGFR.

Why are NSAIDs nephrotoxic?

Inhibit renal prostaglandins → afferent vasoconstriction → ↓ renal perfusion.

IV fluid for AKI with hypovolaemia & acidosis?

NICE NG148: Use balanced crystalloids (e.g., Plasma-Lyte 148). Use 1.26% NaHCO₃ only in severe metabolic acidosis (pH < 7.1).

Why stop thiazide (e.g., Indapamide) if eGFR < 30?

Ineffective in severe CKD — switch to loop diuretic (Furosemide).

Why avoid ACEi in bilateral renal artery stenosis?

Why avoid ACEi in bilateral renal artery stenosis? ACEi block efferent vasoconstriction → sharp drop in GFR → AKI.

Triad for severe hyperkalaemia?

1. Protect heart — IV Calcium Gluconate. 2. Shift K⁺ — Insulin + Glucose ± Salbutamol. 3. Remove K⁺ — stop K⁺-sparing drugs, Calcium Resonium ± dialysis.

Preferred strong opioid in CKD?

Fentanyl — lacks renally cleared active metabolites.

Statins cause which nephrotoxic state?

Rhabdomyolysis → myoglobin-induced AKI

Purpose of Child–Pugh score?

Grades severity of chronic liver disease (A mild, B moderate, C severe).

Why avoid ACE inhibitors in severe (Child–Pugh C) liver disease?

Patients rely on RAAS to maintain BP → risk of severe hypotension/renal failure.

Drugs linked with Drug-Induced Liver Injury (DILI)?

Paracetamol, Flucloxacillin, Co-amoxiclav, NSAIDs (e.g., Diclofenac).

Antidote for paracetamol overdose & mechanism?

Acetylcysteine — replenishes hepatic glutathione to detoxify NAPQI.

Effect of cirrhosis on oral morphine?

↑ Bioavailability (↓ first-pass metabolism) → reduce dose.

Effect of enzyme inducers (e.g., Rifampicin)?

↑ Drug metabolism → ↓ plasma level/effect.

Effect of enzyme inhibitors (e.g., Erythromycin, Fluconazole)?

↓ Metabolism → ↑ plasma concentration → toxicity risk.

Why is Diclofenac contraindicated in severe liver disease?

↑ Risk of GI bleed, fluid retention, renal impairment.

Half-life 12 min — time for 75% elimination?

24 minutes (2 half-lives).

Does Metoclopramide increase or slow absorption?

Increases absorption — accelerates gastric emptying.

High volume of distribution — serum concentration high or low?

Low — drug mainly in tissues.

Example of prodrug activated by first-pass metabolism?

Codeine → Morphine.

If Digoxin F = 0.7, what IV dose = 250 µg oral dose?

175 µg (IV dose = Oral × F).

Which ONE type of documentation is legally classified as a prescription form in the NHS (England)?

FP10 form (or electronic FP10). It is the legal authorisation for the supply of medicines under the Human Medicines Regulations 2012. (Inpatient drug charts and TTOs are Patient Specific Directions, not prescription forms.)

What is the therapeutic target of lidocaine and amlodipine

lidocaine and amlodipine act on ion channels

What is the therapeutic target of adenosine and oxymetazoline

adenosine and oxymetazoline act on G protein couple receptor (GPCR)

What is the therapeutic target of beta-blockers and alpha-blockers

Beta-blockers (e.g. bisoprolol) and alpha-blockers (e.g. doxazosin) act on adrenoreceptors.

What is the therapeutic target of insulin and levothyroxine.

insulin and levothyroxine act on tyrosine kinase receptors

SCRIPT module Flashcards

(77 cards)