Drug Antagonism and PA2 Values

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Questions and Answers

What is the mechanism of action for Avastin?

It inhibits VEGF by preventing its binding to the kinase receptor. (correct)

It enhances the signaling of the VEGF protein.

It binds to the ES complex of VEGF and enhances its action.

It acts as a competitive antagonist by binding to the same site as VEGF.

Which type of antagonist competes directly with the agonist for the same receptor?

Un-competitive antagonist

Competitive antagonist (correct)

Non-competitive antagonist

Desensitization antagonist

What is the duration of validity for Schedule 2 and 3 controlled drugs?

Valid for 3 months

Valid for 28 days (correct)

Valid for 12 months

Valid for 6 months

Which of the following is NOT part of the accuracy check before dispensing medication?

Patient’s medical history Signup and view all the answers

What must occur when collecting a Schedule 2 or 3 drug on behalf of someone else?

Identity must be checked and noted. Signup and view all the answers

What type of receptors are primarily responsible for mediating smooth muscle contraction in the guinea pig ileum?

M3 receptors Signup and view all the answers

What occurs when the interfacial region is saturated with amphiphilic molecules?

Formation of micelles Signup and view all the answers

What effect does atropine have on the ACh-induced response at lower concentrations?

Enhances the response Signup and view all the answers

What is the critical micelle concentration (CMC)?

The concentration where no further decrease in surface tension is possible Signup and view all the answers

Where is aspirin located in the micelles formed by sodium dodecyl sulfate (SDS)?

In the inner core of the micelles Signup and view all the answers

What substance acts as a surfactant to reduce surface tension between molecules?

Sodium dodecyl sulfate (SDS) Signup and view all the answers

Which factor affects the solubility of substances most notably?

Temperature and polarity Signup and view all the answers

What is a saturated solution?

A solution that cannot dissolve any more solute under given conditions Signup and view all the answers

What is the first step to take when assessing a casualty?

Ensure safety by checking for danger Signup and view all the answers

What does the 'R' in DRABCs stand for?

Response Signup and view all the answers

When should a rescuer start CPR?

If agonal breathing is observed Signup and view all the answers

What is the recommended rate for chest compressions during adult CPR?

100-120 compressions per minute Signup and view all the answers

What indicates that CPR should be stopped?

All of the above Signup and view all the answers

How should surfactants orient themselves at an interface?

Polar end exposed to the aqueous environment Signup and view all the answers

What type of surfactant is sodium dodecyl sulfate (SDS)?

Anionic Signup and view all the answers

What is the importance of checking for circulation only if the casualty is breathing?

It prevents unnecessary delays in CPR Signup and view all the answers

What is the role of atropine when acting as a competitive antagonist?

Reversibly binds to muscarinic receptors to block ACh actions Signup and view all the answers

How does the dose-response curve shift in the presence of a competitive antagonist like atropine?

Shifts to the right without affecting the maximal response Signup and view all the answers

What is the dose-ratio when calculating the effect of an antagonist?

EC50 with atropine / EC50 without atropine Signup and view all the answers

What effect does an antagonist evoke on its own?

0% effect Signup and view all the answers

What formula is used to calculate the molar concentration of a substance?

Dose (g) / Body weight (kg) x MW (g/mol) Signup and view all the answers

What is the primary function of aeration in a tissue organ bath system?

Provide oxygen to enhance tissue viability Signup and view all the answers

What physiological response does acetylcholine (ACh) enhance in the ileum?

Increases rate and strength of contraction Signup and view all the answers

What is a major distinction between an agonist and an antagonist?

Agonists enhance biological responses while antagonists block them Signup and view all the answers

What is the predicted effect of adding an additional methyl group to a surfactant according to Traube's Rule?

Decrease surface tension by 3.2 Signup and view all the answers

Which of the following surfactants would likely form an insoluble monolayer due to insufficient water solubility?

Surfactants with a hydrocarbon chain longer than 12 C atoms Signup and view all the answers

What is necessary for weak electrolytes to dissolve into water?

Ion dissociation and hydrogen bonding Signup and view all the answers

Which type of materials can form an insoluble monolayer when injected onto a surface?

Water insoluble amphiphiles and polymeric compounds Signup and view all the answers

Which of the following statements about phenobarb is true?

It is generally used for animals and produced as an oral solution Signup and view all the answers

What is the primary factor that allows weak electrolytes to dissociate in water?

The high dielectric constant of water Signup and view all the answers

In the context of Traube's Rule, which of the following surfactants is an exception?

Polyoxyethylated non-ionic surfactants Signup and view all the answers

What effect does increasing the length of a hydrocarbon chain in surfactants have according to Traube's findings?

Increases surface activity and decreases surface tension Signup and view all the answers

What effect does low-dose adrenaline have on blood pressure?

Decreases blood pressure through vasodilation Signup and view all the answers

Why should non-cardio selective beta blockers be avoided in asthmatics?

They block the beta-2 adrenergic receptors needed for bronchodilation. Signup and view all the answers

What defines the clearance of a drug?

The volume of plasma from which drug is removed per unit time Signup and view all the answers

How is the maintenance dose of a drug calculated?

Css x Cl x t / F Signup and view all the answers

Which type of antagonism involves an antagonist decreasing the overall concentration of an agonist at the active site?

Pharmacokinetic antagonism Signup and view all the answers

What is the formula for calculating the half-life of a drug?

T1/2 = 0.693/ke Signup and view all the answers

What occurs when high doses of isoprenaline are administered?

Increased heart rate alongside vasodilation Signup and view all the answers

What role does glucagon play in physiological antagonism?

It antagonizes the action of insulin. Signup and view all the answers

Study Notes

Drug Antagonism

Four types of drug antagonism
- Chemical antagonism: interaction in solution affects drug availability
- Competitive antagonism: competition for same receptor site
- Physiological antagonism: opposing physiological effects through different pathways
- Non-competitive antagonism: inhibits response without direct competition for agonist binding site

PA2 Value

Represents agonist potency
Value that requires doubling the concentration of Ach (agonist) to get the same response as Atropine (antagonist)
Higher PA2 value (less needed to block agonist) = Higher potency
(the concentration of agonist at EC50 doubles)
pA2 value indicates the concentration of antagonist needed to reduce agonist's effect by half
Formula: PA2= - log[A], where [A] is the concentration of antagonist

Example of PA2 Calculation

Drug X is an antagonist, and 2 x 10^-6 M of Drug X doubles the effective concentration of an agonist needed to produce a response (from 5 μM to 10 μM)
Using the formula, PA2 = - log(2 x 10^-6) = 5.7

Agonist Potency

Depends on affinity and efficacy.
- Affinity: strength of drug binding to receptor, influences receptor occupancy by the drug.
- Efficacy: ability of a drug to produce maximum biological response once bound to its receptor.

Drug Affinity

Determined by specific interactions between drug and target receptor
Influences likelihood and strength of drug binding.
Equilibrium constant (K_A): affinity of agonist for receptor; smaller K_A = higher affinity.
Equilibrium dissociation constant (K_D): tendency of agonist-receptor complex to dissociate.

Drug Efficacy

Receptor activation: efficiency with which a drug activates its target receptor
Intrinsic activity: ability of drug-receptor complex to activate cellular processes; high intrinsic activity = more efficacious responses .
Effector systems: influences downstream pathways.
Receptor reserve: drug may be considered efficacious even if not all receptors are occupied

Competitive Antagonism

Agonist and antagonist compete for same binding site on receptor.
Both bind reversibly
Reaction depends on two equilibrium constants (agonist-KA & antagonist- KAnt)
If K_Ant less than K_A, antagonist has greater affinity for receptor, requiring increased agonist concentration to overcome antagonism.

Non-Surmountable Antagonism

Antagonist cannot be overcome by increasing agonist concentration.
Has persistent effect.
Not easily reversed by higher agonist concentration.

Non-Competitive Antagonism

Antagonist binds to a different site than the agonist.
Reduces the number of available receptors for agonist (affecting overall response)

Irreversible Antagonism

Antagonist binds irreversibly to either agonist or non-agonist binding sites.
Reduces the number of available receptors.
Reduces the slope and overall response.

Does Atropine act as a competitive or non-competitive agonist?

Competitive Antagonist:
- Competes with ACh for binding to muscarinic receptors
- Produces an identical slope that shifts to the right without altering maximal response (efficacy)
- Bind reversibly.

Dose Ratio

Dose-ratio: factor by which the dose of agonist must be increased to produce the same effect when antagonist is present

Full Agonist Effect

A full agonist evokes 100% effect.
Antagonists typically evoke 0% effect on their own

Molar Concentration Formula

Conc(M) = Dose (g) / Body weight (kg) x MW (g/mol)

Acetylcholine (ACh) Action

Increases rate and strength of contraction in ileal smooth muscle.

Agonist vs Antagonist

Agonist: activate or enhance a biological response, mimic endogenous substances.
Antagonist: block or inhibit a biological response.

Potential Receptors for ACh response

Muscarinic Acetylcholine Receptors (mAChRs)
- M3 receptors mediate smooth muscle contraction
- M2 receptors may mediate inhibition and their blockade by atropine could enhance overall response
Cholinergic Neurons: Interactions with pre- and post-synaptic receptors might contribute to observed effects.

Solution

Consists of a single phase of two or more components, where components are dispersed at a molecular level.
Solvent: the substance in which the solute dissolves.

Solubility Factors of Aspirin

Temperature and polarity greatly affect solubility.

SDS (Sodium Dodecyl Sulfate)

Surfactant that reduces surface tension between molecules.
Functions in emulsification, foaming, and cleaning.
Possesses both hydrophilic and hydrophobic groups (amphiphilic)

Micelles

Form when interfacial region of amphiphilic molecules is saturated.
Further reduction in surface tension is not possible
Critical Micelle Concentration (CMC): concentration where surfactant forms micelles.

Aspirin Location in SDS Micelles

Aspirin's aromatic ring is hydrophobic; located in the inner core of SDS micelles.

Traube's Rule

Depends on the balance between hydrophilic and hydrophobic properties.
Homologous series of surfactants: Increased length of hydrocarbon chain = increased surface activity = decreased surface tension.
Every additional methyl = decrease in surface tension by 3.2

Insoluble Monolayers

Surfactants exist in equilibrium with surfactant molecules in the bulk liquid.
If the surfactant has a long alkyl chain, it has insufficient water solubility and forms insoluble monolayers at the surface.
Heads down, tails out of water.

Weak Electrolytes

Drugs that can act as weak acids or bases (often in salt form)
Examples: Phenobarbital

DRABC (Casualty Assessment)

Danger: Don't put yourself at risk
Response: Check for any response (e.g., shouting)
Airway: Open airway (tilt head back, lift chin)
Breathing: Check for breathing (10 seconds)
Circulation: Check for bleeding, but only if breathing is normal
Resuscitation procedures (CPR)

Chains of Survival

Recognize cardiac arrest
Call emergency services
Early basic life support
Early defibrillation
Early advanced life support

Surfactant (Amphiphile)

Distinctive polar and non-polar regions (hydrophilic and hydrophobic)
Polar regions can be: anionic, cationic, zwitterionic, or non-ionic.

Dispensed Drug Checks

Accuracy: Labels, correct medicine, Patient information etc
Legal: prescription details, date, CD requirements etc.
Clinical checks: drug suitability for condition, any contraindications etc.

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Description

This quiz covers the four types of drug antagonism, including chemical, competitive, physiological, and non-competitive antagonism. It also explores the PA2 value, its significance in measuring agonist potency, and how to calculate it using specific examples.