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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
A haircut I had about a week ago didn’t go down well with many. Someone quite close to my heart saw it, examined it critically and felt dizzy.
“What’s this?” she proceeded to ask me.
“An international hairdo,” I replied.
She was disgusted, in fact disappointed. The problem with the haircut is that the style is neither Punk, Tokyo Joe nor Show Your Back. If anything, it is a combination of all—and I liked it, for a change.
It was when I bounded downtown that someone called me and enquired whether I was no longer a journalist. He said I looked like a well-fed Warrant Officer.
“Class One or Class Two?” I asked.
Another studied my head as if he was studying physical geography and pronounced that I looked like a boxer who can throw dangerous punches. Still, someone was of the opinion that the haircut didn’t quite fit me, but admitted that I looked like a prosperous merchant.
Commendation
I remember some three months ago, I had a haircut that made two girls fall in love with me. In spite of the fact that the barber was not a graduate, the cut was such that they couldn’t help admiring it. One of them actually ‘checked out’ the style and commended the barber.
The other was more bent on the ‘love matter’ but I was too busy to give her any attention. LOVE!
I was reminded of this when I viewed a premier showing of the latest Sikaman film titled THE POWER OF LOVE. The film kept me thinking. Some of us have long forgotten about what it is like to be head-over-heels in love. When we were students, we had such experiences because there was nothing doing anyway.
We were either learning how stylishly to smoke ‘jot’ or how romantically to fall in love. Anyhow, I was intrigued by this latest movie because of the way love unlimited was portrayed on screen. It took my memory back many years to relive those youthful days when we felt we’d really die if jilted by our lovers.
The storyline of THE POWER OF LOVE is really an exciting one. The combination of love, treachery and intrigue made me feast my eyes intently on the screen, unbelieving the extent the force of love can reach.
Ama and Afua are good friends. But when it comes to matters of the heart, they have different tastes; Ama is content with only her boyfriend (a student) and Afua samples the bigwigs around town. Afua, not satisfied with the shots in town, wants Ama’s boyfriend Joe in addition. She lies to Joe that Ama has often been picked by a man on four-wheels, whereupon Joe dismisses Ama and takes on Afua.
Ama doesn’t realise that it is her best friend Afua who is destroying her relationship with Joe until she catches her having sex with him. She collapses and goes out of her mind from the broken heart. But before then, she had been made pregnant by Joe.
Having escaped from a psychiatric hospital, she roams town murmuring Joe’s name. Heavily pregnant now, she espies Joe boarding a mini bus and runs towards him. Joe, seeing her approaching, quickly disembarks and takes off.
Ama pursues him furiously, and he runs to his home where he finds his bosom friend Frank making love to Afua. He immediately realises the treachery of Afua who instigated him to leave Ama.
He intends leaving the home in disgust and meets mad Ama at the door and embraces her despite her madness. Instantly, she regains her sanity.
Love indeed heals the wounds of the mind and it is the greatest positive force in the world. Incidentally, the greatest negative force is hatred.
Greatest force
Now coming to talk about love, I reiterate it is the greatest force imaginable. That is why a man will butcher his rival to death if he catches him climbing his wife without asking permission; and a woman will go mad if jilted.
It is also for this reason that a young boy who is scared stiff of cemeteries and under normal circumstances would not dare go near one, will this time walk boldly through a cemetery at midnight if that is the only way to his lover’s abode.
The Bible describes love for our neighbours as the surest way to heaven: Love thy neighbour as thyself.
Unfortunately, what Ghanaians are more interested and skilful in is loving the opposite sex. Romance under the cover of darkness is what we understand love to be all about. When it comes to loving our fellow human beings, we are found wanting.
People hate others just because they are of another tribe and do not speak the same native language. Too much grudge-bearing that does not augur well for national development.
War in Liberia, carnage in Rwanda are the results of the absence of love for one’s fellow being. If everybody could express a little bit of love for his fellow being irrespective of tribe, race, politics or religion, Sikaman—and indeed, the world—will be a more habitable place.
This article was first published on Saturday, October 29, 1994
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“Sir,” Ms. Odame said when David Asante answered the call, “my name is Victoria Odame. I’m a teacher at Research School in Koforidua. I would like to come and see you concerning a student called Sarah.”
“Okay, madam. I would be very glad to meet you. How can I make your trip easier?”
“I was going to join a bus to Accra.”
“Here’s what we will do. Take a taxi and ask them to bring you to Accra. I will speak to the driver, give him the directions, and pay him when you get here.”
The taxi stopped in front of the house. The gate opened, and the driver moved to the long driveway and stopped.
“What a beautiful house,” he said.
David and Adoma came out to meet them. Adoma paid the driver as David and Sarah stared at each other.
“Please come in and sit down,” Adoma invited. She served them water.
“You are welcome,” Adoma continued. “We have been waiting anxiously since you called this morning. So please, let’s hear you.”
Before she could open her mouth, Sarah rose, moved to David, hugged him, and sat on his lap. They both broke into tears. Adoma and Ms. Odame also broke into tears.
“Sorry, madam,” David said. “This whole episode has been a very difficult one. But let’s do the proper thing. Let’s hear you first, and I will also speak. I’m sure we need to answer some questions immediately.”
“Okay, sir. I have been taking an interest in Sarah because, although she’s brilliant academically, she seemed to be troubled. Following my discussions with her and some whispers I had been hearing, I went to Aboso Senior High School and spoke to your former colleague, Mr. Hanson. He told me that you were an exemplary teacher who was loved by all, and he also told me about the unfortunate events that caused you to leave for Germany. So I returned to Koforidua with the view to finding the appropriate means of helping to solve this problem.”
“Great. Ms. Odame, I have to thank you for finally helping us to solve this problem. Now, let me state the facts. This is what happened.
“Gladys and I met and got married whilst we were both teachers in the school. Some months into our marriage, she told me that she needed to spend some days with her parents, and I agreed.
“It turned out that she was actually spending time in a hotel with her ex-boyfriend, Simon. This happened again after Sarah was born. I got wind of this and told her that I was no longer interested in the marriage.
“I started preparing to travel to Germany. She pleaded for forgiveness, but I stood my ground. Then she told me that she would punish me for rejecting her.
“She came out later to say that Sarah was not my child, but Simon’s. She went and hid her somewhere, obviously expecting that I would fight to take my child. I was actually going to do that, but my parents advised me that it was almost impossible to win such a fight.
“They advised that, difficult as it sounded, I should leave the child with her because she would come back to me eventually. I have absolutely no problem taking care of you, Sarah. I am taking care of quite a number of kids who are not mine. So that is what happened. My hands were tied. I have been trying to find out how you are doing.
“I kept hearing that you were doing well at school. I also heard that Gladys and her husband were having problems, but I kept hoping that my daughter would at least be okay till it was possible for me to go for her.”
“Sarah, now you have met your dad. You will be free to—”
“I’m not going anywhere!” she declared as she held on to him.
“You don’t have to worry about that, Sarah,” Adoma said. “We have been looking forward to the day you come home. This is your home. Now, you have to meet your siblings.” She called Abrefi and Adaawa.
“Girls, we told you that you have a sister who would join us anytime. Now here she is.”
“Sarah?” Abrefi asked.
“Yes,” Adoma replied. The girls hugged her and took her away.
“Now,” David said, “I think it is time to call Madam Gladys.” He dialed the number.
“My name is David Asante. I’m here in my house with my daughter Sarah. I hear you have told her all sorts of crazy stories about me. I could make life very difficult for you, but I won’t.
“You are your own worst enemy. I don’t think you should be expecting her anytime soon. What do you say?”
Gladys stayed silent for over a minute, then cut the line.
“Food is ready,” Adoma announced. “Everybody, please come to the table.”
Sarah chatted excitedly with her siblings as Adoma and David spoke with Ms. Odame. She kept staring at her father.
“Now, Ms. Odame, after you have brought such joy into our home, should we allow you to go back to Koforidua today, or should we wait till we are ready to release you? I could call your husband and ask permission.
“And please don’t tell me you didn’t bring anything for an overnight stay. There are several supermarkets around here. We can fix that problem quickly.”
“I will beg you to release me. Now that I have been so warmly welcomed here, I already feel part of this home. Koforidua is not that far away, so I will visit often.”
“Well, let’s see what the kids have to say. Ladies, shall I release Ms. Odame to go back to Koforidua?”
“No!” they shouted, and all broke into laughter.
“Ms. Odame, I will have mercy on you. But we are going to do something to make it easy for you to visit us. My wife wants to show you something. Please follow her.”
Adoma led her to the driveway as the others followed. They stopped in front of the car.
“This is a Toyota Corolla 1600. It is very reliable and good on petrol consumption. We are giving this to you in appreciation of your help in getting our daughter back to us.
“And here in this envelope is a little contribution to help you with maintenance. And here in this other envelope is a gift to help with your children’s school fees.”
As she stood, stunned, and stared from the car to the envelopes, David put his hand around his family.
“Let’s leave her to take a look at her car. Ms. Odame, one of my drivers will drive you to Koforidua and leave your car with you. We are waiting inside.”
By Ekow de Heer
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