Integrated Pharmacology & Toxicology
Blocking β₁ receptors produces what two primary cardiovascular effects?
What is decreased heart rate and contractility?
Which phase of metabolism increases polarity without conjugation?
What is Phase I metabolism?
This interaction between aromatic rings and receptor residues stabilizes drug binding.
What is π–π stacking?
Drugs with high polarity and low logP typically fail to cross the BBB via what mechanism limitation?
What is lack of passive diffusion through lipid membranes?
This receptor type allows rapid synaptic transmission via ligand-gated ion channels and is associated with GABA.
What is GABA A (ionotropic Cl⁻ channel)?
Why do ACE inhibitors reduce blood pressure mechanistically?
What is reduced angiotensin II → decreased vasoconstriction + aldosterone?
Why does glucuronidation enhance drug excretion?
What is increases water solubility for renal/biliary elimination?
Why might increasing chain length beyond optimal reduce drug activity?
What is steric hindrance and reduced receptor fit?
Given two drugs with identical logP, which additional parameter most strongly influences BBB permeability?
What is molecular size or polar surface area (TPSA)?
Activation of NMDA receptors requires both glutamate binding and this additional condition.
What is membrane depolarization to remove Mg²⁺ block?
How do calcium channel blockers reduce cardiac workload?
What is decreased Ca²⁺ influx → reduced contraction force and vasodilation?
Compare first-order vs zero-order kinetics in terms of enzyme saturation.
What is first-order = not saturated (rate ∝ concentration); zero-order = saturated (constant rate)?
Explain why one enantiomer of a drug may be active while the other is not.
What is receptor stereospecificity (3D binding differences)?
Why does dopamine fail to effectively cross the BBB despite being biologically active in the CNS?
What is low lipophilicity and lack of transporter-mediated uptake?
Explain how excitotoxicity occurs at the molecular level.
What is excess glutamate → Ca²⁺ influx → activation of degradative enzymes → neuronal damage?
Explain how HERG channel inhibition leads to arrhythmia.
delayed repolarization → prolonged QT interval → disrupted cardiac rhythm?
A CYP450 inhibitor is co-administered with a drug. Predict pharmacokinetic outcome.
What is increased drug levels → potential toxicity?
A tertiary amine is often protonated at physiological pH. Why is this important for receptor binding?
What is formation of ionic interactions with negatively charged residues?
A drug has high protein binding and high lipophilicity. Predict onset and duration.
What is slow onset, prolonged duration?
A decrease in dopamine relative to acetylcholine in the basal ganglia produces what functional outcome?
What is motor dysfunction (Parkinsonian symptoms)?
Design problem: A drug binds HERG strongly. Suggest two SAR strategies to reduce cardiotoxicity.
What is reduce lipophilicity AND modify/remove tertiary amine pharmacophore features?
Explain the biochemical basis of paracetamol toxicity at high doses.
What is excess NAPQI formation + glutathione depletion → covalent binding to proteins → liver damage?
A drug loses activity after replacing an OH group with CH₃. Provide a mechanistic explanation.
What is loss of hydrogen bonding capability → decreased receptor interaction → reduced activity?
Design challenge: propose two structural modifications to improve BBB penetration of a polar drug.
What is increase lipophilicity (add aromatic groups/alkyl chains) AND reduce polarity (mask polar groups/prodrug strategy)?
Describe the enzymatic mechanism of acetylcholine synthesis including the type of reaction.
What is Choline + Acetyl-CoA → acetylcholine via ChAT through nucleophilic attack on a carbonyl (ester formation)?