Graded And Quantal Dose-Response, Theapeutic Index, Window | Parasympatholytics | Central Sympathoplegic Drugs

Question 1

Graded and Quantal Dose-Response curves, Therapeutic Index and Therapeutic Window

Answer 1

Graded DR: Relation between log of dose/concentration of drug and its effect on a single receptor/person, where EC50 is the dose at which 50% of effect is reached by the drug

Quantal DR: Relation between dose/concentration of drug and its wanted effect on a % of population, where ED50 is the dose at which 50% of the population will show the known effect of the drug

In Quantal DR we can find the Median Effect Dose, Median Toxic Dose and Median Lethal Dose for a population

Therapeutic Index: Ratio of ED50 and TD50 that is used to classify safety of a drug. Closer the ratio to 1, more toxic and lethal the drug, and lesser is the safety

Therapeutic Window: The range between ED1 to TD1 used to determine how safely we can administer a drug to the general population without worrying about its toxicity. Larger the window, higher is the safety margin of the drug

Question 2

Parasympatholytics

Answer 2

These are Acetylcholine antagonists that work on both Nicotinic and Muscarinic receptor, however they show more effect on Muscarinic receptors [Nicotinic receptors more targeted by Centrally acting Sympatholytics and Indirect Acetylcholine agonists]

These agents are:
- Atropine: Ach Esterase inhibitor OD antitode, antidiarrheal, antispasmodic, antisecretory | Enters CNS
- Scopalamine: Used in motion sickness | Enters CNS | Sedation and short-term memory loss
- Ipratropium, Tiotropium: Astham, COPD inhalation drugs causing bronchodilation
- Oxybutynin: Urge Incontinence drug, overactive bladder treatment | Relaxes smooth muscles of bladder

Major effects are in: [think opposite effect to REST and DIGEST, almost like sympathetic NS activity]
- Eye
- Heart
- Glands [ALSO sweat]
- Lungs
- GI
- Bladder

Question 3

Centrally acting Sympatholytic drugs

Answer 3

Antagonism centrally/level of brain towards postganglionic Sympathetic neurons or neurons using NE/E/Dopamine as a neurotransmitter [former also includes nAchR]

These agents are:
- Ganglion Blockers [Hexamethonium]
- Methyl-p-tyrosine [blocks rate limiting step in dopa synthesis]
- Reserpine
- Guanethidine
- Alpha 2 agonists [Clonidine, alpha-Methyldopa]

NOTE - Dopamine antagonists are Antipsychotic and Antiemetic drugs | COMTi and MAOi are sympathomimetic drugs as these INCREASE the NE and E synthesis/availability

These drugs are also Sympathetic modulators in addition to MAOi, COMTi