Pharm Week 2

Propranolol and Verapamil

• Propranolol has been discontinued in some cases due to its side effects and less effective management of certain conditions.
• Verapamil is often favored over propranolol as it offers better efficacy in managing certain cardiovascular conditions, such as hypertension and angina.

Receptors and Ligands

• A receptor is a protein molecule that receives and transmits signals in response to ligands.
• A ligand is a molecule that specifically binds to a receptor to initiate a biological response.
• Receptors determine the interaction of drugs with biological systems, affecting therapeutic outcomes.
• Drug response is proportional to the concentration of the drug that binds to the receptor.

Functions and Mechanisms

• Receptors provide a specific binding site for ligands, leading to various cellular responses.
• They mediate the actions of neurotransmitters, hormones, and various drugs.
• The natural form of THC in the brain is anandamide, which plays a role in signaling.

Antagonists and Agonists

• Non-competitive antagonists bind to receptors without preventing ligand binding, effectively inhibiting receptor activity.
• Competitive antagonists compete directly with agonists for receptor binding sites.
• Chemical antagonists are drugs that neutralize the effects of another substance; examples include naloxone and flumazenil.
• Physiological antagonists counteract the effects of an agonist through different pathways, e.g., glucagon vs. insulin.

Receptor Classifications

• Agonists for gene-activated intracellular receptors activate these receptors to elicit a response.
• Antagonists inhibit the action of gene-activated intracellular receptors.
• Ligand-gated ion channel antagonists prevent the opening of ion channels, affecting ionic currents across membranes.

Pharmacology Concepts

• Coupling refers to the relationship between receptor activation and subsequent intracellular signaling, involving effectors.
• An effector is a molecule that mediates the physiological effects initiated by receptor activation.
• EC50 is the concentration of a drug that produces 50% of its maximum effect.
• Kd represents the dissociation constant, indicating the affinity between a ligand and its receptor.

Spare Receptors and Agonists

• Spare receptors are unoccupied receptors that contribute to the maximum effect even when a small fraction of receptors are activated.
• A partial agonist is a drug that activates a receptor but produces a lower response than a full agonist.
• Buprenorphine is a safer analgesic option compared to traditional opioids like morphine.

Antagonist Characteristics

• An antagonist that binds to opioid receptors but causes no biological response is naloxone.
• The active receptor conformation is the state that allows for ligand binding.
• Full agonists have high intrinsic efficacy, while drugs with low intrinsic efficacy are classified as partial agonists.

Receptor Forms and Binding

• Receptors can exist in active (Ra) and inactive (Ri) conformations, influencing drug effects.
• Agonists typically stabilize the Ra form, while certain drugs might maintain a natural balance between Ra and Ri.
• The Ri form is stabilized by inverse agonists, producing opposite effects to those of full agonists.

Antagonist Types

• Competitive antagonists share the same binding site as agonists; if they occupy the site, they block biological responses.
• An example of an irreversible antagonist is phenoxybenzamine, which permanently binds to receptors.

Intracellular Signaling

• Nitric oxide stimulates intracellular enzyme guanylyl cyclase, producing the second messenger cGMP.
• Certain drugs bind to intracellular DNA regulator proteins to initiate transcription and alter protein synthesis.

Receptor Regulation

• Receptor desensitization occurs when receptors become less responsive to ligands after prolonged exposure.
• Receptor downregulation involves the reduction in receptor number on the cell surface, often due to overactivation.

Specific Receptor Functions

• Beta-1 adrenergic receptors increase heart rate, while alpha-1 adrenergic receptors are primarily responsible for vasoconstriction.
• Potassium channels are opened by certain receptors to regulate neuronal excitability.

Therapeutic Considerations

• The therapeutic index is a measure of drug safety, calculated as the ratio of the toxic dose to the effective dose.
• The therapeutic range for theophylline is narrow, usually around 10-20 mg/L.
• The therapeutic range for digoxin varies, typically 0.5-2 ng/mL, to ensure effectiveness while avoiding toxicity.

Test your knowledge about the reasons behind the discontinuation of propranolol. This quiz covers various aspects of the drug's history, usage, and the factors leading to its cessation. Learn about its implications in the medical field.