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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
THE typical itinerant salesman in Sikaman is a herbalist. He is normally a slim macho with the capacity to perambulate the expanse of area covering the triangle of Accra-Tema-Ashiaman. In short, he can walk a total of 60 miles a day, marketing a product that cures every disease, including poverty. 
The door-to-door herbal pharmacist advertises his product by word of mouth. He has nothing to do with the Food and Drugs Board (FDB). After all, his concoctions do not feature on FM stations.
Those herbalists who cannot walk to propagate the herbal gospel, liaise with drivers of mass transportation and their mates. They are, therefore, given the chance to sell their products on Benz buses that ply the routes.
Normally, the herbalist starts his sales message with a prayer and Bible study. He asks the passengers to bow down their heads in supplication to God the father, the son, the Holy Spirit.
When a herbalist asks the passengers to close their eyes and bow their heads, Moslems on board naturally feel offended. They feel that the herbalist has no right to assume that every passenger is a Christian. They think such an assumption is an affront to Islam.
So a Moslem on board will raise the hand for a point of order. He’ll remind the herbalist that it would be in his own interest to mind his language.
“Be careful the way you address people in a public place. Not every person here is a Christian,” he’d state assertively.
Of course, the herbalist will promptly ignore him, but would all the same “watch” his tongue. Who knows whether or not the Moslem brother is inspired by Quoranic zeal to defend the tenets of Islam to the hilt?
When he starts saying, “Wallahi!” and “Inshallah!” it could be the beginning of proclaiming Islam as supreme, a point which must be driven home with talibanic precision.
So the herbalist must tread carefully lest he steps on fire.
The herbalist could even add a measure of mirth to it all, by announcing that Christians on board today have very interesting company on the journey, but that should not detract from the business of the day.
The Moslem brother will weigh the words carefully and offer a wry smile.
He must be careful the occasion does not degenerate into the use of semantics and proverbial oration to deride his conviction that public utterances must be mindful of religious sensibilities. He has made his point very clear and expects that it is taken in good faith in the interest of a peaceful journey.
The herbalist will now open the New Testament and preach salvation, stating clearly that salvation can come only through Jesus Christ and NOBODY else.
The Moslem brother will now start twitching his moustache. The visible and almost revolutionary reflexes of his upper lip can be an indication that sentiments have begun superseding reason, and the outcome could well be tragic now shift uneasily in his seat.
The time has come for him to also express his right to the religion of his fore-bears. He’ll put his hand into his pocket and rise to his feet. The time has indeed come!
This article was first published on Saturday, September 9, 2006
When the cause of a particular problem like sickness, disease, sudden illness, a social issue etc. are not known, it stands to reason that resolving it becomes a huge challenge.
Citizens would understand the government when public announcements are made to the effect that government is trying to find a solution to the issue, even though it is taking a while for it to be resolved because citizens are rational beings.
On the other hand, if the solution to a particular issue is known to everybody but the government for whatever reason, is dragging its feet in resolving it, citizens become frustrated and begin to lose trust in their leaders.
One such issue is the heavy traffic along a section of the Kasoa – Odokor road. A short stretch of bad road between the traffic light at the Weija Government Hospital and the entrance to the entrance of the overhead that leads to the N1, is the cause of the problem but nothing is being done about it, day after day, week after week, month after month. Thus is clearly unacceptable.
Another issue that requires urgent attention is the lack of pavements along a lot of streets in parts of the various Municipal Assemblies. Exercise is a prerequisite for long life and healthy living and for those of us who it has become a way of life, this issue of people putting up structures right to the edge of the drains beside the roads, are making life difficult for us.
We are compelled to walk along the roads, putting our lives at serious risk. Pedestrians should never be compelled to compete with vehicles on our streets and roads. Roads and streets are made for vehicles and pavements are made for pedestrians. That is the norm. Any attempt to normalise a situation where pedestrians are mingling with vehicles is insanity.
It is the road regulations that makes it so and therefore district or municipal assemblies are to take responsibility and ensure that spaces for pavements are not encroached upon. Citizens have rights that must be protected by their leaders and making pavements available to pedestrians, is one of them.
When we hear of teachers having sex with students, it appears it is something recent. It is not a new phenomenon. It has been there since Adam. Perhaps this issue is getting much attention due to the proliferation of social media. It was an open secret in times past when Teachers were in relationships with female students and some married them immediately after completion of school.
Some teachers were also known to be having unholy interactions with female pupils but due to the times that these acts occurred, human rights issues and the awareness around it, allowed such unscrupulous teachers to get away with their crimes.
Now we are in a different era and so a Headmaster is now in hot waters. He is alleged to have raped about 19 female students and as usual, some officials tried to cover it up and are also in hot waters and their actions or inactions in the matter are under investigation.
Why the man has been allowed to roam freely without being arrested is simply mind boggling. It appears that the law applies differently, depending on who you are. This issue came to public attention sometime in August this year, yet the police had not arrested or invited this man for question regarding the rape allegation.
It has come out that he is a Constituency Secretary of the ruling party and the question in the public domain is that, is it because he is a political figure that is why he is still walking around without questioning? I believe in the rule of law so let us hold our breadth and let the proper thing be done.
The police must however be seen to be active in this matter. God bless.
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