Plasma Concentrations After Loading And Maintanence Dose | Chatecholamines Metabolism, Drug Modulation | Bronchial Asthma Treatment

Question 1

Formulas and Concept

Steady State Concentration | Loading Dose | Maintanence Dose

Answer 1

Steady State:
- Concentration at which the rate of dose entering the body/reaching plasma = rate of elimination
- Depends on T1/2
- Reached within 4-5 half lives for a drug
- To increase Css, you need to increase the infusion/taken dose but the time to reach Css is always the same

Loading Dose:
- The first, high amount of dose given to reach the desired steady state concentration in one dose
- Used in situations where we need to reach target plasma concentration immediately
- Loading Dose = [Cp * Vd]/F OR = [Cp * Body weight * Vd]/F
- Cp is target plasma concentration or Steady state concentration | Vd is of drug
- Loading dose changes based on if given drug has a HIGH Vd [higher loading dose compared to LOW Vd drug for same Cp] or LOW Vd

Maintenance Dose:
- Dosage required to maintain the Steady state plasma concentration
- Maintenance Dose = [Cp * CL * tau]/F
- Cp is target plasma concentration or steady state concentration | CL is clearance of the drug | tau is dosing intervals in x number per x hours
- Liver or Kidney diseases will need lower Maintenace doses compared to healthy individual for same steady state concentration, as CL is affected in these diseases

Question 2

Metabolism of Catecholamines and its modulation

Answer 2

Catecholamines are neurohormones mainly produced by Postganglionic Sympathetic system fibers, and chromaffin cells of Adrenal medulla

Catecholamines are NE, E, Dopamine

Breakdown Products of NE and E - Vanillylmandelic Acid [VMA], excreted in urine
Breakdown Products of Dopamine - Homovanilic Acid [HVA], excreted in urine

Degradation done by:
- MAO: Deaminating enzyme, has A [Liver and everywhere, also NE, 5HT, Tyramine breakdown] and B [Brain] subtypes
- COMT: Methylation enzyme found in synaptic clefts and cytosol

Drugs modulating Catecholamines:
MAO-inhibitors: prevents removal of catecholamines, increases availbility
- Isoniazid, Isocarboxazid [Non-selective]
- Tolaxaton [Selective MAO-A, Antidepressant]
- Rasagiline [Selective MAO-B, Parkinson drug]

COMT-inhibitors: prevents synaptic cleft breakdown, increases avaibility
- Entacapone [Peripheral, non-hepatotoxic]
- Tolacapone [CNS and Peripheral, hepatotoxic]
- Both are Parkinson drugs

Question 3

Bronchial Asthma Treatment

Answer 3

5 ways to target Bronchial Asthma:
- Selective Beta-2 agonists [Albuterol, Metaproterenol, Terbutaline - short and fast acting | Salmeterol - long, slow acting]
- Parasympathetic Antagonists of M3 receptor [Ipratropoium, Thiotropium]
- PDE inhibitor [Theophylline - increases cAMP - Bronchodilation]
- Antileukotrienes [Zafirlukast, Montelukast - LTD4 receptor blocker]
- Immunosuppressants [Prednisone, Budanisone]