Category: NUR1121 (page 1 of 3)

Bismuth subsalicylate antacid versus antidiarrhoeal?

May 9, 2021 / / 0 Comments

Bismuth compounds would aid peptic ulcer disease and acute diarrhoea. But bismuth subsalicylate inhibits prostaglandin production, and prostaglandins are cytoprotective, so wouldn’t the inhibition of prostaglandins lead to more mucosal damage?

Both subcitrate and subsalicylate bismuth salts (and also subgallate and subnitrate salts) are used.

Theoretically, the subsalicylate is better for diarrhoea because the salicylate additionally acts as an NSAID to reduce inflammation and reduce prostaglandin-mediated activation of chloride channels reducing chloride and hence water in the lumen of the bowel (the opposite effect to lubiprostone).

Meanwhile, theoretically, the subsalicylate is worse for peptic ulcer as it is hydrolyzed to salicylic acid, which will act as a COX inhibitor preventing the production of the prostaglandins. The prostaglandins have protective actions in the stomach, increasing mucosal blood flow, increasing mucus secretion, increasing bicarbonate secretion and, at high concentrations, reducing acid secretion.

In practice, both subsalicylate and non-subsalicylate bismuth compounds are used clinically for both gastric acid-related disease and diarrhoea, and there is no clear evidence of a difference. However, there have not been large, well-designed clinical trials to compare them directly.

Dopamine receptor antagonists and prolactin levels

May 9, 2021 / / 0 Comments

Why do dopamine receptor antagonists result in elevated prolactin levels?

Because dopamine is an important neurotransmitter in suppressing prolactin release through the tuberoinfundibular pathway.

The tuberoinfundibular pathway comprises dopaminergic projections from the arcuate and periventricular nuclei of the hypothalamus to the infundibular region, also in the hypothalamus or median eminence. Dopamine is released into the portal circulation from the median eminence with the anterior pituitary gland. Dopamine tonically inhibits prolactin release via D2-like receptors, D2 and likely to a lesser extend D4.

Thus, dopamine D2 receptors antagonists increase prolactin release. This explains why antipsychotic drugs and antiemetic drugs acting as antagonists at D2 dopamine receptors can cause hyperprolactinaemia.

Treatment for nausea and vomiting in pregnancy

May 7, 2021 / / 0 Comments

Which is the best antiemetic for nausea and vomiting in pregnancy?

It is best to avoid drugs, if possible, during pregnancy.

Typically, dietary changes and avoidance of triggers are tried first:

  • Take meals and snack when hungry to avoid empty stomach, which can aggravate nausea.
  • Avoid coffee, odorous, high-fat, acidic and/or very sweet foods.
  • Eat meals and snacks slowly and in small amounts every one to two hours to avoid overly full stomach, which can also aggravate nausea.
  • Choose high-protein, salty, low-fat, bland and/or dry foods.
  • Take fluid at least 30 min before solid food. Sip fluid in small amounts. Avoid triggers (e.g., odours, stuffy rooms, etc.).
  • Ginger-containing foods can suppress nausea and vomiting.

If dietary changes and avoidance of triggers do not work, pyridoxine (vitamin B6) supplementation is usually tried next. This can improve nausea, but is usually less effective at preventing vomiting.

If vitamin B6 supplementation does not work, a first-generation antihistamine (muscarinic antagonist and H1 receptor antihistamine) is used. The choice is usually doxylamine, an old antihistamine. Doxylamine is usually still combined with vitamin B6. Older drugs are preferred, as we have greater historical knowledge of use in pregnancy. Newer drugs are generally avoided as clinical trials rarely include pregnant women and so there is little information available on their safety during pregnancy.

If vitamin B6 supplementation and doxylamine do not work, then any of the other older H1/M1 blockers (e.g. diphenhydramine) or D2 blockers (e.g. metoclopramide) is used alone or in combination. Again the older agents are used as there is more accumulated knowledge giving some confidence of safety in pregnancy. Only if none of these approaches work is the newer class of 5-HT3 antagonists tried and the agent chosen is typically either ondansetron or granisetron (older agents within the class for which there is some history of use in pregnancy).

Brimonidine for glaucoma

May 5, 2021 / / 0 Comments

If brimonidine is an adrenergic agonist, how and why does it reduce glaucoma?

Brimonidine acts at postsynaptic alpha-2 adrenoreceptors on blood vessels to cause vasoconstriction, reducing aqueous humour production. Long-term, there are also effects on uveoscleral drainage, perhaps secondary to reduced blood flow to the ciliary muscle.

Brimonidine alone is not as potent at reducing intraocular pressure (IOP) as beta-blockers or prostaglandin F2alpha analogues (e.g., latanoprost). The primary reason that brimonidine has come back into use is that it also has a neuroprotective action, reducing the death of retinal ganglion cells through mechanisms that remain poorly understood.

Ganglionic blockers versus depolarising NMBAs

May 5, 2021 / / 0 Comments

High-dose nicotine induces depolarising blockade and subsequent secondary non-depolarising blockade at autonomic ganglia. Meanwhile, depolarising NMBAs induce depolarising block consisting of Phase I and Phase II. Is it the same thing?

Yes, they are essentially the same mechanisms as far as the nicotinic receptors go. It is primarily a difference in terminology. Although secondary non-depolarising block is a more scientifically descriptive term than Phase II, the depolarising NMBAs are already called “depolarising” to contrast with the non-depolarising NMBAs (direct nicotinic receptor antagonists). It would therefore be confusing to say that depolarising NMBAs have a secondary non-depolarising block. Hence, the common usage of the Phase I and Phase II terminology.

Depolarising versus non-depolarising NMBAs

May 5, 2021 / / 0 Comments

What is the difference between a depolarising and a non-depolarising NMBA? Do both result in flaccid paralysis?

Depolarising neuromuscular blocking agents (NMBAs) are potent agonists at nicotinic receptors that cause depolarising block (and necessarily also the secondary desensitising/non-depolarising block). In contrast, non-depolarising NMBAs are direct competitive nicotinic receptor antagonists.

An important difference is that non-depolarising NMBAs can be reversed by increasing acetylcholine (ACh) levels by using an acetylcholinesterase inhibitor such as neostigmine. Depolarising NMBAs cannot be reversed in the same way since increasing ACh availability just causes more depolarizing block (and inevitably secondary desensitising/non-depolarising block).

As depolarising NMBAs initially cause activation, they will cause twitching/fasciculation followed by rigid paralysis on onset (although this phase is over quickly) before switching to flaccid paralysis. In contrast, non-depolarising NMBAs will go straight to progressive flaccid paralysis.

How does ageing impact on drug dosing

May 5, 2021 / / 0 Comments

Physiological changes associated with ageing can impact the appropriate dosing for many drugs. General principles to keep in mind include:

Absorption:

  • Absorption usually does not change with normal ageing.

Distribution:

  • Concentrations of water-soluble drugs are usually higher as there is less water and so a lower volume of distribution.
  • Concentrations of free or active (unbound) drug are usually higher due to lower serum proteins.

Metabolism:

  • The half-life of lipophilic drugs is usually higher due to more fat resulting in an increased volume of distribution and prolonged duration of action.
  • There is slower Phase I metabolism (e.g., oxidation, reduction and dealkylation) due to cytochrome P450 pathways resulting in higher levels of drugs dependent on these pathways for metabolism (e.g., warfarin).
  • However, Phase II reactions (e.g., conjugation, acetylation, and methylation) are usually unchanged in normal ageing.
  • There is a greater risk of drug-drug interactions in metabolism due to increased numbers of drugs for multiple medical problems.

Excretion:

  • Hepatic excretion may be impaired.
  • Renal clearance may be impaired, and serum creatinine may not be an accurate reflection of renal clearance in elderly patients due to decreased lean body mass (muscle mass).
  • Active drug metabolites can accumulate, resulting in prolonged therapeutic actions and a greater risk of adverse effects.

There is also increased susceptibility to adverse effects. Older adults are also more likely to have multiple chronic medical problems, and disease states can result in physiological changes:

  • Cardiac disease can result in impaired cardiac output resulting in impaired ADME and greater susceptibility to cardiac adverse effects.
  • Liver or kidney disease can decrease metabolism and excretion, reducing drug clearance.
  • Neurological diseases result in greater sensitivity to neurological adverse effects due to diminished neurotransmitter levels and/or impaired cerebral blood flow.

 

What is the difference between pharmacology and pharmacy?

May 8, 2019 / / 1 Comment

What is the difference between pharmacology and pharmacy?

Pharmacology is the study of the sources, uses, and mechanisms of action of drugs. That is what the body does to drugs (pharmacokinetics) and what drugs do to the body (pharmacodynamics).

Pharmacy is the science or practice of the preparation, formulation,  and dispensing of medicinal drugs.

 

Practical guide to good prescribing?

August 8, 2018 / / 0 Comments

I have completed my pre-clinical pharmacology studies. The lecturers helped me to build a framework of understanding of the pharmacological mechanisms of the major drug classes. This has given me a solid foundation of understanding of the pharmacology of the various drug classes on which I can continue to build as I learn more. But now going into my clinical years I feel lost about how to apply this knowledge in practice for clinical pharmacology. Where can I find a clear and practical guide on how to go about good prescribing in clinical practice?

The WHO has an excellent Guide to Good Prescribing – A Practical Manual.

You are likely not alone in feeling a little lost as you progress from pre-clinical theoretical understanding of pharmacology to practical application of clinical pharmacology. As the WHO Guide to Good Prescribing describes in its introduction on “Why you need this book”: “At the start of clinical training most medical students find that they don’t have a very clear idea of how to prescribe a drug for their patients or what information they need to provide. This is usually because their earlier pharmacology training has concentrated more on theory than on practice. The material was probably ‘drug-centred’, and focused on indications and side effects of different drugs. But in clinical practice the reverse approach has to be taken, from the diagnosis to the drug.”

This does not mean that your pre-clinical pharmacology training was wrong. It is just that finishing your pre-clinical years does not mean that you have finished learning pharmacology. Now in your clinical years, you need to learn clinical pharmacological applications and good prescribing. Your pharmacological learning should never end.  Throughout the rest of your career, you will have to continue to update your pharmacological knowledge as new drugs are approved or evidence-based best medical practice changes with new information. That is why your pre-clinical pharmacological training focused on helping you to build a solid foundation of a knowledge framework into which you can continue to integrate new pharmacological understanding as you come across new drugs in clinical practice.

 

Why does overdose of salbutamol cause tachycardia?

March 14, 2018 / / 0 Comments

Salbutamol is beta-2 adrenoceptor agonist used to treat the respiratory symptoms of asthma. We learned that it is beta-2 adrenoceptors in the lungs and beta-1 adrenoceptors in the heart. So why does overdose of salbutamol cause a rapid heart rate? 

Activation of beta-2 adrenoceptors in the airways promotes bronchodilation, reduction of airway secretions, and stimulation of mucociliary clearance.  Thus beta-2 adrenoceptor agonists are used in treating the symptoms of asthma. Meanwhile, in the heart, beta-1 adrenoceptor activation has inotropic and chronotropic effects, increasing contractile force and heart rate, respectively.

For the treatment of the symptoms of asthma without causing cardiovascular adverse effects, selective beta-2 adrenoceptor agonists would be the preferred.  Salbutamol is an example of a selective beta-2 adrenoceptor agonist. However, the beta-2 and beta-1 adrenoceptors are very similar, so salbutamol is not entirely selective. Salbutamol shows dose-dependent selectivity for beta-2 adrenoceptors but does still act as a weak beta-1 agonist.  Thus, on overdose, the beta-1 agonist activity of salbutamol can start to cause cardiovascular adverse effects by activating beta-1 adrenoceptors in the heart to increase the force and rate of heart contractions.

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