Drug Metabolism and Excretion

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Questions and Answers

What is acetylcholine synthesized from in the cytoplasm of nerve fibers?

acetyl coenzyme A and choline

What happens to acetylcholine when the action potential reaches the terminal?

It is released to the synaptic cleft.

What type of receptors are found on effector cells that bind to acetylcholine?

Cholinergic receptors

What terminates the action of acetylcholine?

Acetyl cholinesterase enzyme Signup and view all the answers

What type of receptors are typically found on autonomic effector cells in peripheral visceral organs?

Muscarinic receptors Signup and view all the answers

What is the neurotransmitter released by post-ganglionic sympathetic nerves?

Noradrenaline Signup and view all the answers

What type of activity is demonstrated by sympathetic nerve stimulation or application of noradrenaline or adrenaline?

Adrenergic activity Signup and view all the answers

What do adrenergic neuron terminals synthesize and store in vesicles?

Noradrenaline Signup and view all the answers

What is the mechanism of action of physostigmine?

Inhibits the enzyme cholinesterase, increasing and prolonging the effect of endogenous acetylcholine. Signup and view all the answers

What is the indication of physostigmine in overdose cases?

Atropine over dosage Signup and view all the answers

What is the main difference in the mechanism of action between physostigmine and neostigmine?

Neostigmine has a direct nicotinic action on skeletal muscles, whereas physostigmine does not. Signup and view all the answers

What is the indication of neostigmine in post-operative cases?

Post operative urine retention Signup and view all the answers

What type of compounds are echothiophate and isofluorophate?

Organophosphates Signup and view all the answers

What is the difference in absorption and distribution between physostigmine and neostigmine?

Physostigmine is completely absorbed and distributed throughout the body, while neostigmine is poorly absorbed and distributed. Signup and view all the answers

What is the use of organophosphates like parathion and malathion?

As insecticides Signup and view all the answers

What is a significant consequence of organophosphate poisoning?

Morbidity and mortality Signup and view all the answers

What is glycine conjugation characteristic for?

Certain aromatic acids Signup and view all the answers

What is the source of the methyl group in methylation?

S-adenosyl methionine Signup and view all the answers

What is the major process of excretion of drugs?

Renal excretion, hepatobiliary excretion, and pulmonary excretion Signup and view all the answers

What is the effect of slow excretion of a drug on its duration of action?

The duration of action is longer Signup and view all the answers

What is the function of glomerular filtration and active tubular secretion?

To remove drug out of the body Signup and view all the answers

What determines glomerular filtration?

Concentration of drug in the plasma, molecular size, shape, and charge of drug, and glomerular filtration rate Signup and view all the answers

What is the effect of congestive cardiac failure on glomerular filtration rate?

It is reduced Signup and view all the answers

What type of drugs can pass through the glomerulus?

Drugs with low molecular weight Signup and view all the answers

What is physiological antagonism, and how does it occur?

Physiological antagonism is when the physiological effect of a drug is antagonized by another drug by acting on two different types of receptors. Signup and view all the answers

What is the importance of drug antagonism in correcting adverse effects of drugs?

It helps to correct adverse effects of drugs by using an antagonist to counteract the effects of the drug. Signup and view all the answers

What happens when a drug is excreted slowly, and how can it be avoided?

The drug concentration in the body builds up, leading to toxicity. It can be avoided by knowing the elimination rate, stopping administration at warning symptoms, carefully selecting the drug form, and monitoring liver and kidney function. Signup and view all the answers

What is drug tolerance, and what is an example of a drug that exhibits tachyphylaxis?

Drug tolerance is when an unusually large dose of a drug is required to elicit an effect. Ephedrine is an example of a drug that exhibits tachyphylaxis, a rapid development of tolerance on repeated administration. Signup and view all the answers

What is a placebo, and what is its original purpose?

A placebo is a tablet that looks like the active treatment but contains no active component. Its original purpose was to please the patient when no specific treatment was available. Signup and view all the answers

What is the effect of acetylcholine on smooth muscle, and how does it differ from its effect on the neuromuscular junction?

Acetylcholine causes constriction of smooth muscle, but it causes contraction on the neuromuscular junction. Signup and view all the answers

What is the purpose of monitoring liver and kidney function during drug administration?

To avoid drug cumulation in the presence of hepatic and renal damage. Signup and view all the answers

What is an advantage of carbachol over acetylcholine?

Longer duration of action Signup and view all the answers

Why can carbachol be given orally and parenterally?

It is completely absorbed from the gastrointestinal tract and is stable towards hydrolysis by cholinesterase enzyme Signup and view all the answers

What is the significance of knowing the elimination rate of a drug in avoiding drug cumulation?

Knowing the elimination rate of a drug helps to determine the dosage and frequency of administration to avoid drug cumulation. Signup and view all the answers

What is a common indication for carbachol and betanechol?

Retention of urine (postoperative) Signup and view all the answers

What is a contraindication for the use of choline esters in patients with bronchial asthma?

They may induce bronchial constriction and increase bronchial secretions Signup and view all the answers

What is a characteristic of cholinergic alkaloids with chiefly muscarinic actions?

They include muscarine, pilocarpine, etc. Signup and view all the answers

How is pilocarpine excreted?

Partly destroyed and partly unchanged in the urine Signup and view all the answers

What is a difference between betanechol and carbachol?

Betanechol has fewer side effects due to lack of nicotinic actions Signup and view all the answers

What is a common action of carbachol and acetylcholine?

Pronounced effects on the gastro intestinal tract and the urinary bladder Signup and view all the answers

Study Notes

Glycine Conjugation

Glycine conjugation is a characteristic pathway for certain aromatic acids, such as salicylic acid, isonicotinic acid, and p-amino salicylic acid.
These drugs are also metabolized by other pathways.

Methylation

Adrenaline is methylated to metanephrine by catechol-o-methyl transferase.
The source of the methyl group is s-adenosyl methionine.

Excretion of Drugs

Excretion of drugs means the transportation of unaltered or altered form of the drug out of the body.
The major processes of excretion include renal excretion, hepatobiliary excretion, and pulmonary excretion.
The minor routes of excretion are saliva, sweat, tears, breast milk, vaginal fluid, nails, and hair.
The rate of excretion influences the duration of action of a drug.
A drug that is excreted slowly maintains its concentration in the body and continues to produce effects for a longer period.

Renal Excretion

Renal excretion is a major part of excretion, and it involves glomerular filtration, active tubular secretion, and passive tubular reabsorption.
The function of glomerular filtration and active tubular secretion is to remove the drug from the body, while tubular reabsorption tends to retain the drug.
Glomerular filtration is a process that depends on the concentration of the drug in the plasma, molecular size, shape, and charge of the drug, and glomerular filtration rate.
Only the drug that is not bound to plasma proteins can pass through the glomerulus.
All drugs with low molecular weight can pass through the glomerulus, e.g., digoxin, ethambutol, etc.

Physiological Antagonism

Physiological antagonism occurs when the physiological effect of a drug is antagonized by another drug acting on two different types of receptors.
Examples include acetylcholine, which causes constriction, while adrenaline causes dilatation of the pupil.
Importance of drug antagonism includes correcting adverse effects of drugs, treating drug poisoning, and predicting drug combinations that would reduce drug efficacy.

Repeated Administration and Drug Cumulation

If a drug is excreted slowly, its administration may build up a sufficiently high concentration in the body to produce toxicity.
To avoid cumulation, one must know if a drug is eliminated slowly or rapidly, stop the drug administration at the appearance of the first warning symptoms, and carefully select the form in which the drug is to be administered.
It is also important to check liver and kidney function before and during drug administration, as even an otherwise non-cumulative drug would produce cumulation in the presence of hepatic and renal damage.

Drug Tolerance

Drug tolerance occurs when an unusually large dose of a drug is required to elicit an effect ordinarily produced by the normal therapeutic dose of the drug.
Tachyphylaxis is a rapid development of tolerance on repeated administration, e.g., ephedrine, amphetamine, and nitroglycerine.

Emotional Factors

Emotional factors, such as placebo response, can influence the effect of a drug.
Placebo is a tablet that looks exactly like the active treatment but contains no active component, and it is originally used to please the patient when no specific treatment was available.

Cholinergic System

Acetylcholine is synthesized inside the cytoplasm of nerve fibers from acetyl coenzyme A and choline through the catalytic action of the enzyme choline acetyltransferase.
Once synthesized, it is transported from the cytoplasm into the vesicles to be stored, and when the action potential reaches the terminal and the latter undergoes stimulation, acetylcholine is released to the synaptic cleft.
After release from the presynaptic terminal, the molecule binds to and activates an acetylcholine receptor (cholinergic receptor) located on the effector cell.
Finally, it is hydrolyzed into choline and acetate by acetylcholinesterase enzyme, and thereby the action of the transmitter is terminated.
Cholinergic receptors are classified into muscarinic and nicotinic cholinergic receptors.
The response of most autonomic effector cells in peripheral visceral organs is typically muscarinic, whereas the responses in parasympathetic and sympathetic ganglia, as well as responses of skeletal muscle, are nicotinic.

Cholinergic Drugs

Carbachol is a cholinergic drug that is completely absorbed from the gastrointestinal tract and is stable towards hydrolysis by cholinesterase enzyme.
It can be given both orally and parenterally with almost similar dosage.
It has similar actions to those of acetylcholine, with pronounced effects on the gastrointestinal tract and the urinary bladder.
Indications for carbachol include glaucoma, retention of urine (postoperative), and paralytic ileus.

Anticholinesterase Drugs

The commonly used cholinesterase inhibitors fall into three chemical groups: simple alcohols bearing quaternary amines, carbamate and related quaternary or tertiary amines, and organic derivatives of phosphates.
Physostigmine is a cholinesterase inhibitor that is completely absorbed from the gastrointestinal tract and is highly distributed throughout the body.
It can pass the blood-brain barrier and inhibit the enzyme cholinesterase, increasing and prolonging the effect of endogenous acetylcholine at different sites.
Indications for physostigmine include glaucoma and atropine overdose.
Neostigmine is a cholinesterase inhibitor that is poorly absorbed from the gastrointestinal tract and is poorly distributed throughout the body.
It cannot pass the blood-brain barrier and has a direct nicotinic action on skeletal muscles.
Indications for neostigmine include myasthenia gravis, paralytic ileus, reversal of the effect of muscle relaxants, and postoperative urine retention.

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Description

This quiz covers the conjugation of certain aromatic acids and methylation of adrenaline, as well as the excretion of drugs from the body.