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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
In the pursuit of nurturing healthy, fulfilling relationships, we often focus on understanding our partners, communicating effectively, and navigating conflicts. However, a crucial element is frequently overlooked: self-awareness.
Understanding ourselves is the foundation upon which successful relationships are built. Imagine being in a relationship where every conversation feels like a minefield, and every disagreement leaves you wondering if you are truly understood.
Now, picture a relationship where you feel seen, heard, and valued—not because your partner has magically figured you out, but because you have taken the time to understand yourself. This is the transformative power of self-awareness in relationships.
What is Self-Awareness?
Self-awareness is the ability to recognize and understand our thoughts, feelings, and behaviors. It is the capacity to reflect on ourselves, acknowledging our strengths and weaknesses, and taking responsibility for our actions. With self-awareness, we are better equipped to manage our emotions, respond to situations more thoughtfully, and make informed decisions that align with our values.
How Self-Awareness Impacts Relationships
- Improved Communication:
When we are aware of our own emotions and needs, we can communicate them more effectively to our partner, reducing misunderstandings and conflicts. By recognising our tendency to become defensive in certain situations, we can take a step back, breathe, and respond more constructively. - Increased Empathy:
Self-awareness allows us to recognise and manage our own biases, enabling us to be more empathetic and understanding towards our partner’s perspective. By acknowledging our own emotional triggers, we can respond to our partner’s needs with more compassion. - Healthier Boundaries:
By understanding our own needs and limits, we can establish and maintain healthy boundaries, preventing codependency and resentment. Self-awareness helps us communicate our boundaries clearly and respectfully, fostering mutual respect in relationships. - Personal Growth:
Self-awareness fosters personal growth, enabling us to work on our flaws and become a better partner, friend, and individual. As we develop self-awareness, we become more resilient, adaptable, and better equipped to navigate life’s challenges with confidence and purpose.
Cultivating Self-Awareness
- Mindfulness and Reflection:
Regular mindfulness practices and self-reflection can help you develop a deeper understanding of yourself. Schedule time for reflection, whether through journaling, meditating, or simply taking a quiet walk in nature. - Journaling:
Writing down your thoughts, feelings, and experiences can provide valuable insights into your motivations and behaviors. Reflect on your journal entries to identify patterns, gain clarity, and develop a greater understanding of yourself. - Seek Feedback:
Ask trusted friends, family, or a therapist at Counselor Prince & Associates Consult (CPAC) for feedback on your strengths and areas for improvement. Be open to constructive criticism and use it as an opportunity for growth and self-awareness. - Embrace Imperfection:
Recognise that nobody is perfect, and it is okay to make mistakes. This mindset allows you to approach self-awareness with kindness and compassion, fostering a more positive and growth-oriented relationship with yourself.
As we cultivate self-awareness, we embark on a journey of growth, discovery, and transformation. By understanding ourselves, we can build stronger, more resilient relationships, and live a more authentic, meaningful life. Self-awareness is not a destination; it is a continuous process of learning, growing, and evolving—and one that requires patience, kindness, and compassion towards ourselves and others.
In conclusion, self-awareness is the cornerstone of healthy, fulfilling relationships. By understanding ourselves, we can communicate more effectively, empathise with our partner, and cultivate personal growth. As we strive to build stronger relationships, let us prioritise self-awareness, embracing our true selves, and loving ourselves for who we are. By doing so, we will become better partners, friends, and individuals—capable of building more profound, lasting connections with others, and living a life that truly reflects our values and aspirations.
To be continued …
By Counselor Prince Offei
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ONE profession which society has battled with is prostitution. Prostitutes can’t be stopped in their tracks. Soldiers have tried, policemen have doubled and redoubled to keep them off the streets. But the prostitute is like the cockroach. Sack it from the kitchen and it moves to the toilet where it can enjoy self-contained facilities. Drive it away from there and it scurries to the bedroom to become the landlord.
Prostitutes can live on land and sea. They are mysterious and defy gravity, a feat—even birds of the air have not successfully accomplished. They can change form and appear as bar girls; they dress like students; act like scholars and speak Oxford English. They are also like the chameleon but once their clients can identify them, no problem. The Sikaman prostitute normally enters the business as an amateur, having been introduced by a professional or a caricature of a pimp. But she learns quickly.
In a short time, she is able to take any size without wailing, unless of course the size is “international”.
Prostitutes are of every tribe, height, weight, colour and notoriety. These days, some are well-schooled with diplomas and degrees. They enter into the world’s oldest profession due to factors ranging from poverty to nymphomania.
Most prostitutes in Sikaman are often not sophisticated in outlook and modus operandi. Often, they easily betray themselves with their gaudy appearance, over-painted faces, skimpy skirts, cigarette in hand, walking with that kind of bottom-wriggling gait that can instantly turn a devoted clergyman into a he-goat.
In developed countries like Spain, prostitution takes different forms. Apart from those you can grab from the cheap bars and ghettos for single night stands and those managed by shameless pimps, there are some who are organised by well-established syndicates and specialised agencies.
If you need a girl for the night, you only have to telephone an agency, describing the kind and breed you want—race, height, size, colour (chocolate?), rudeness, smoking type, strip-teasing, shyness, whatever.
You give your address and the girl on time. You pay by the hour and cost per hour can make you feel dizzy without falling down. You’ll still be steady for the showdown.
The girls have been trained to use tricks and communication skills to make their clients spend several hours without really doing anything. A typical prostitute will make you drink, chat at length (they are very knowledgeable), cook for you, bathe you and breast-feed you. That takes some three hours and you have to pay if you still want her services.
If you grow a bit wiser and protest, and insist vehemently that you are tired of being babied and want some real action now, she’ll do another hour of strip-tease and belly-dance by which time you’re either bored or charged to bursting point.
And finally you will do it but never without a condom. And the kind of condom she’ll give you can’t be torn by any knife around the globe, not even okapi. Before you’re finally through, you’ve got some five-hour helluva bill to pay. Next time round, you’ll think twice and go in for the cheap-side who’ll even allow you to do it without condoms if you are tired of living and want to die of AIDS.
In Sikaman, apart from those who operate from hotels and bars, some operate in private homes. The clients come and line-up, each with a hard-on. When the queue is not moving fast some begin to sweat because they have a very low sexual boiling point. If they are not ushered in quickly they can cause problems.
They’ll start grunting and stamping and can disrupt the peaceful and orderly procedure. As it were, such clients need priority attention so that they do not cause a riot and disturb the public peace.
Incidentally, prostitutes don’t like dealing with such clients because they are bad business. They have no biblical patience at all. They rush too much, and that was why a prostitute once asked a client whether he was a Russian because he rushed a bit too much and messed up things.
Prostitution in Sikaman has taken a new turn. Girls as little as sixteen are selling their bodies sometimes with the passive connivance of their mothers. When the girls go out at 9.00 p.m. and return at 3.00 a.m, their mothers let them in without asking questions. Next day, the house is properly fed from the proceeds of the night adventure and everybody is happy and nobody talks. If you talk, no breakfast for you tomorrow morning.
The police are doing quite a job trying to get them off the streets but they go and return just like the cockroach. Many of them are surely agents for the transmission of the AIDS virus because they permit clients to forgo the condom. They only have to pay extra for the “raw” service.
Now, the idea of legalising prostitution has been a very controversial one. If prostitutes can hardly be gotten off the streets since they are defiant and are now very many, why not legalise the profession, issue licences (not to kids), offer them health services and health education, teach them how to protect themselves and others from sexually transmitted diseases and then compel them to pay tax?
That would force children out of the trade because the legal operators will themselves force out the kids who will be competing with them. They would even assist the police to kick out the 15 and 16 year olds.
If a bad phenomenon cannot be wiped out, a way must be found to make it less and less harmless, so that while it doesn’t benefit society in any grand way, it does not also harm it.
Any suggestions?
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