GREEN PACOP BIOCHEM

Pharmacology Study Notes

Cyclic Adenosine Monophosphate (cAMP)

• cAMP is generated as a secondary messenger by the action of the enzyme Adenylyl Cyclase
• The substrate for the synthesis of cAMP is ATP (Adenosine Triphosphate)

Beta-adrenoceptor Stimulation

• Stimulation of Beta-adrenoceptor, a G-protein-linked receptor, involves the generation of a secondary messenger known as cAMP
• This is in contrast to IP3 (Inositol Triphosphate), DAG (Diacylglycerol), and calcium ions, which are secondary messengers involved in other receptor stimulation

Sildenafil (Viagra) Mechanism of Action

• Sildenafil, a drug popularly known as Viagra, inhibits Phosphodiesterase (PDE) leading to an increase in cGMP (Cyclic Guanosine Monophosphate)

Phospholipase C-Inositol Phosphate System

• Activation of alpha-adrenergic agonists like phenylephrine primarily causes an increase in intracellular calcium ion levels

Competitive Antagonism

• Competitive antagonism is characterized by a shift of the agonist log concentration-effect curve to the right without a change in slope or amplitude
• This is in contrast to other types of antagonism, which exhibit different effects on the agonist log concentration-effect curve

Pharmacological Principles

• Potency refers to the minimum dose that produces the maximum achievable response
• ED50 (Effective Dose 50) is the dose required to produce 50% of the maximum response

Drug Absorption and Distribution

• Pinocytosis is a mechanism of absorption for certain substances, including Vitamin K and Cyanocobalamin
• The apparent lipid-water partition coefficient of a drug can be calculated based on its concentration in an aqueous solution and octanol

Pharmacokinetics

• The rate of infusion of a drug to achieve a desired plasma concentration depends on the clearance of the drug
• The biologic half-life of a drug determines the time it takes for the drug concentration to decrease by half
• Compartmental analysis of serum drug concentration versus time plots can be used to determine the pharmacokinetic behavior of a drug

Nitrovasodilators

• Nitrovasodilators, such as nitroglycerin, have a bioavailability of about 100% when administered sublingually
• The primary mechanism of action of nitrovasodilators involves the release of nitric oxide, which activates guanylyl cyclase leading to an increase in cGMP
• Nitrovasodilators exhibit the greatest sensitivity in veins, followed by arterioles and arteries

Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)

• Pyrazolone derivatives like Phenylbutazone are associated with hepatotoxicity and hematologic toxicities
• Ketorolac is an NSAID that is useful as an analgesic and has been used successfully to replace morphine in some situations involving mild to moderate post-surgical pain
• COX-2 inhibitors like Celecoxib and Etoricoxib have a lower incidence of gastric irritation or ulceration compared to traditional NSAIDs

Disease Management

• Methotrexate is currently used as a first-line DMARD (Disease-Modifying Anti-Rheumatic Drug) in the management of Rheumatoid Arthritis
• Anti-cholinergic agents are used in COPD and bronchial asthma, but their use is limited due to side effects