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MEDICINES AND RISK OF LOWERING THE SEIZURE THRESHOLD
I am on medications for seizures. Recently I was diagnosed with a urinary tract infection and put on Ciprofloxacin. It was changed when my details showed a history of seizures. Kindly shed more light on this issue. Yes, it is true that Ciprofloxacin can lower the seizure threshold and therefore could precipitate a seizure for someone with a history of seizures and taking medications.
A seizure is the clinical manifestation of abnormal, excessive or synchronous neuronal firing in the brain. The clinical features of seizures may include abnormalities of consciousness, movement, sensation, behaviour and autonomic function. Epilepsy is the enduring tendency to experience seizures. The seizure threshold describes the minimum intensity of a stimulus required to induce a seizure. It is clinically evident in the context of electroconvulsive therapy, but is otherwise primarily an experimental phenomenon, in which seizures are induced by electrical or chemical stimuli.
Seizures occur when there is an excess of excitatory activity relative to inhibitory activity. Glutamate and gamma-aminobutyric acid (GABA) are, respectively, the principle excitatory and inhibitory neurotransmitters in the central nervous system (CNS). Glutamate acts via N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid (AMPA) and kainite receptors to cause an influx of sodium and calcium ions, favouring depolarization. GABA acts primarily through GABAA receptors to cause an influx of chloride ions, inducing hyperpolarization. The mechanisms of action of antiepileptic drugs include interference with sodium (e.g. phenytoin, carbamazepine, lamotrigine) and calcium channels (e.g. ethosuximide); enhancing the effects of GABA(e.g. benzodiazepines); antagonizing glutamate at AMPA receptors; and a combination of these effects (e.g. valproate). Drugs with the opposite effects may induce seizures.
Seizure potential is often evaluated during drug development to quantify the extent to which a drug prevents seizures (if this is the intended therapeutic effect) or induces them (as an unwanted effect). As a broader concept, it is useful in clinical practice as a framework to help understand the complex interplay between the patient, their medicines, and their risk of seizures (Hitchings .W. Drugs that lower seizure threshold. St George’s, University of London and St George’s University Hospitals NHS Foundation Trust. Thundiyil JG, Kearney TE, Olson KR. Evolving epidemiology of drug-induced seizures reported to a Poison Control Center System. Journal of Medical Toxicology 2007;3:15-9).
The propensity of a drug to induce seizures depends on its effects on neurotransmission and their timecourse (e.g. whether it increases seizure risk during use or on withdrawal), the concentration of drug reaching the brain, and the susceptibility of the individual patient. Susceptibility factors include previous seizures, structural or functional brain abnormalities, and concurrent drug use. In the face of such complexity, it is rare that seizures can be ascribed primarily to the effects of a drug (i.e. ‘drug-induced seizures’). Commonly, however, drugs contribute to a shift in excitatory/inhibitory balance which, in that individual at that time, leads to a seizure. In this respect, it is generally more helpful to regard such drugs as having lowered the seizure threshold, rather than having incited seizures.
Many drugs have indirect effects on the seizure threshold, for example by inducing hypoglycaemia, electrolyte disturbances or respiratory depression, or by interacting with antiepileptic therapy. Drugs with potential to lower the seizure threshold are numerous and diverse. Whether they contribute to clinically overt seizures depends on the dosage in which they are taken, the time-course of their effects, and the susceptibility of the patient. It is important to add that the contribution of medicines to seizure risk is potentially modifiable. For antimicrobials, the beta-lactams (penicillins, cephalosporins and carbapenems), interact with the GABAA receptor to interfere with the inhibitory effects of GABA in a concentration-dependent manner. Correspondingly, they have dose-dependent effects on the seizure threshold. However, the CNS penetration of penicillins and cephalosporins is relatively low. As such, most reports of seizures associated with these agents emerge from their use in high doses (often in the treatment of CNS infections) or in renal failure. Carbapenems more readily penetrate the CNS and their use is associated with an increased seizure risk compared with non-carbapenem antibiotics. Among the carbapenems, imipenem is generally regarded to have the highest risk. However, this may be because studies conducted on the newer agents (meropenem, ertapenem and doripenem), informed by earlier experience with imipenem, generally excluded patients with a history of seizures. All cephalosporins have the propensity to lower the seizure threshold but the one often associated with this phenomenon is cefipime. The quinolones are another group with the most common ones being ciprofloxacin and levofloxacin.
The antituberculous agent isoniazid inhibits pyridoxine phosphokinase, the enzyme which converts pyridoxine to its active form, pyridoxal-5-phosphate. Pyridoxal-5-phosphate is an essential cofactor in the synthesis of GABA from glutamate. The resulting fall in inhibitory activity and rise in excitatory activity leads to a dose-dependent reduction in the seizure threshold. Isoniazid toxicity is characterised by a triad of altered mental status, metabolic acidosis and refractory seizures. Treatment with pyridoxine and a benzodiazepine usually results in prompt seizure termination.
The antimalarial agents mefloquine and chloroquine can precipitate seizures in people with epilepsy. This effect has been reported even in healthy individuals.Antipsychotics are another group with the most common ones being chlorpromazine and clozapine. Some antidepressants also have this tendency with the notable ones being Amitriptylline and Venlafaxine..Seizures are common in cases of antidepressant overdose, particularly with venlafaxine and TCAs.
Narcotics such as Meperidine, Fentanyl and tramadol have also been associated with lowering of the seizure threshold.Many drugs can adversely affect the seizure threshold, although whether this leads to overt seizures depends on the concentration of drug reaching the brain, the susceptibility of the individual to its effects, and how these effects vary over time. In managing patients with epilepsy or other risk factors for seizures, one must be mindful of the potential for medications to lower the seizure threshold, so as not to precipitate avoidable seizures. Likewise, in evaluating patients with seizures, consideration must be given to the seizure-provoking potential of their medications. As noted by Hitchings information on the intended medicine’s risk to lowering the seizure threshold becomes an important factor in the decision to withhold or stop the medication to improve seizure control or prevent it in the first place.
As always use medicines safely. Always consult your pharmacist on safe use of medicines.
DR. EDWARD O. AMPORFUL
CHIEF PHARMACIST
COCOA CLINIC
Features
How marital infidelity and excessive arguing lead to divorce
- Marital Infidelity (Marital Unfaithfulness)
Marital infidelity (adultery) is one of the most significant challenges facing families in our society.
Many divorces are due to (in one way or another) marital infidelity of spouses. In a 2019 study by the American Psychological Association (APA): “Infidelity was found to be the cause of 20-40 per cent of US divorces.”
Infidelity and divorce are very old, yet their levels seem to increase with time. One wonders why people are unable to learn from the past and eradicate infidelity in their marriages—which would, in turn, reduce the divorce rates.
The institution of marriage is based on deep trust between the two partners that enter it. Adultery (marital infidelity) is considered a violation of that faith in each other and a severe betrayal. This violation of trust is not to be taken lightly, as it can profoundly affect both parties and the marriage as a whole.
While many instances of marital infidelity are the results of a volatile family situation, there are also personal factors that can push one to commit adultery. Christians and society see the act as a sin, immoral, and an abomination.
This societal view can put great pressure on individuals, making them feel guiltier and less likely to seek reconciliation, thereby increasing the likelihood of divorce.
In some cases, mental conditions can influence people and lead to self-destructive behaviours such as sexual infidelity.
In such cases, the person typically knows that the act will harm the family but commits it regardless. Marital infidelity as revenge after learning of one’s spouse’s unfaithfulness should also be considered part of this category. Sometimes, infidelity can even push the other spouse who is committed to the relationship into adultery out of the belief that in doing so, they will share the burden.
Marital infidelity, regardless of the reasons behind it, inflicts deep wounds on both parties and the marriage as a whole. The betrayed spouse often feels inadequate and begins to question their worth, while the adulterer is burdened with guilt and mental weakness. These profound effects underscore the gravity of marital infidelity and its potential to shatter a marriage. Looking for personal faults that drove their spouse to act as they did.
Unfortunately, marriages frequently end after adultery is discovered, partly due to the tendency of cheaters (adulterers) to do so repeatedly. Often, this leads to one or both spouses seeing the act as the dissolution of their marital relationship.
Children are likely to be affected adversely as a result, especially because adultery-related divorces tend to end with the adults not being on good terms. Ultimately, adultery (marital infidelity) is highly destructive to marriages regardless of the cause and may often lead to their dissolution in the case that the other spouse learns about the act.
- Excessive Arguing and Lack of Effective Communication
Most arguments in marriage happen because of a communication breakdown. Excessive arguing and a continuous lack of effective communication have been cited as causes of divorce in many cases. Therefore, improving communication can make a big difference between a happy marriage and one that experiences separation or divorce.
In 2019, a survey conducted by ‘Your Tango’ found the following lack of communication in divorce statistics:
- ‘Communication problems’ is the most common factor that leads to divorce, at 65 per cent
- This was followed by couples’ ‘inability to resolve issues,’ at 43 per cent.
Open and honest communication with a spouse can show trust, respect, and deference to the other spouse’s thoughts and beliefs. Excellent communication can see a relationship through difficulties, while lack thereof could cause a simple argument to escalate into grounds for a divorce.
It is not surprising that a lack of effective communication in marriage leads to divorce or separation in many instances.Given how crucial communication is to a successful marriage, it is better to work on your communication skills or find a good therapist to assist you than to allow situations to deteriorate in your marriage.
To be continued …
Source: Excerpts from “A COUNSELLOR’S GUIDE TO USING ‘Preparing for a Happy and Fulfilling Marriage’ EFFECTIVELY” Book by REV. COUNSELOR PRINCE OFFEI (Psychotherapist, Lecturer, and Marriage Therapist).
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COUNSELOR PRINCE & ASSOCIATES CONSULT (CPAC COUNSELLOR TRAINING INSTITUTE)
Features
The Water Palaver
When Ghanaman is relaxing at home and hears a knock at the door, he is likely to suspect that a Jehovah Witness man show him the best tax-free way to heaven. If it is not the Jehovah Witness man with the black bag, then it must be the landlord coming to talk nonsense.
“Yes, come in.” “You owe us ¢350,000 in water bills. We’re in to disconnect.”
“Wait a minute. Your presence is giving me heart attack, so come back later for payment.
Fact is I’m allergic to water bills.”
Some people don’t care a damn about electricity disconnection. No light, so what? What they are scared about is water cuts. They can cause instant diarrhoea. And soon, water and electricity costs are going to be increased, and an epidemic of diarrhea is highly expected.
It is, however, very difficult to disconnect some consumers because they make conscious efforts not to get cut off.
One favourite method is to train a dog which can detect a disconnector from a normal human being and do the chasing out accordingly. The dog must have appetite for human leg or human balls.
Another way is to allow yourself to be disconnected and then you can go to the water or electricity company, dressed in suit with a deep-frown on your face. That is where you can blow your horn.
“The interior minister is my brother-in-law. I command you by state power to reconnect me before I change gears. You don’t respect? If you don’t know me go and ask. Kofi Annan was my classmate. If you play, I’ll deal with you at the United Nations level.”
Sometimes, officials can take the bluff as very authentic and proceed to re-connect Kofi Annan’s classmate. But others will feel they are doing their job and the interior-minister’s in-law’s big mouth has nothing to with the execution of official assignments.
“Well, we know the Interior-Minister is related to you. But the bill must be settled anyway. If you can settle half, we’ll re-connect and give you time to settle the rest.”
It turns out that the man finally settles the bill, but doesn’t even know how Kofi Annan like.
As for his relationship with the interior Minister, it can only be at best, a dog’s imagination.
At any rate, Ghanaians are waiting for the new utility rates and are also hopeful that a corresponding raise in salary will be in place to absorb the shock.
Now Electricity Company and Ghana Water Company have many problems they would have to solve. One of them is waste. With electricity, illegal connections are very common and many are using power and paying nothing for it.
Others are using air-conditioners and pay nothing because they connect the wires in such a way that power used does not go through the meter and is, therefore, not recorded. What the company loses in a month countrywide is so huge that if it can be recovered, the company would be on rather good footing
The problem also is that, consumers who are disconnected have become wiser than the serpent. Some have taught themselves Basic Principles in Electricity. Many housewives know the principles better than any electrical engineer at ECG.
When you disconnected power to their homes, they simply wait for five minutes and reconnect. No sweat!
It is a simple procedure they have repeated so many times that they are no longer worried about and disconnection.
So bills pile up and ECG is helpless, and goes whining about the need to increase tariffs without really tackling the waste problem.
With water, it might be worse. People have illegal connections through which they sell water for their own pockets. Some pipes have burst for over six months and no one is bothered. People report leakages and no one is worried.
Ghana Water Company is not doing well because of waste. You can’t import expensive chemicals to purify water and let it go waster. No company can thrive on a system that is not bothered about waste.
So Ghana Water Company better wake up and save water. In some countries, water is imported. If we have it here, we should learn to conserve it.
