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MEDICINES AND RISK OF LOWERING THE SEIZURE THRESHOLD
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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
There is a scripture that is found in Matthew 6:22 which says that the lamp of the body is the eye and therefore the eye must see well to enable the body to get to its destination.
What most people do not know is that behind the scenes, there is a strong interaction between the eyes and the brain before a picture becomes clear. The state of mind therefore is crucial to the eye seeing clearly to enable the body to process accurately the information the eyes are feeding it for proper identification of what the eyes see.
This is similar to how a person behaves i.e. what informs the decisions that forms in the mind that results in the actions that a person performs. The actions of a person does not therefore just happen but is as a result of things that went on in the mind, which in most cases resulted from information passed on to it by the eyes either consciously or unconsciously.
There are so many issues that affect our society which makes one wonder, whether the people who displayed such acts were created by someone or something other than God.
How can a person see a beach created by God with beautiful beaches and fresh air blowing all around, decides to defecate at such places, and therefore desecrate the environment? lt is simply mind boggling?
When other people in other countries who dwell on the coast are using their beaches for tourist attraction purposes as a means of livelihood and also to promote environmental health, some people living around our beaches, have turned them into rubbish dumping sites and toilets.
It is a very sad situation and the earlier we did something about it the better. It is a national emergency that must engage the attention, first of the government and then the citizenry, where religious bodies and NGOs must play a critical role.
The things we focus on in this country, needs to be addressed. Our minds which processes the info the eyes send to the brain, must be disciplined. There are certain behaviours that a disciplined mind can ignore even when the eye has provided info to the brain. One of the things a disciplined mind does, is the avoidance of a second look, which is critical for every person who wants to avoid adultery or fornication.
Once a person is not blind, he will see things. The boobs, the ‘shankus’, the coca cola shapes, the light complexioned, the dark complexioned etc. the eyes will definitely see and report same to the brain. What the brain or the mind decides to do or instructs the eye to do is the issue.
It can decide to instruct the eye to take a second look and let the mind drool over it or say ignore it and that will be the end.
If the mind becomes trained to focus on environmental issues like clean environment, the eyes will automatically be reporting on insanitary conditions to the brain as and when it sees them. The mind will pay attention to such data and begin to process them and to identify solutions to deal with the reported insanitary conditions.
There is the need to encourage citizens to train the mind to focus on the right thing so that in tandem with the eyes, focus will be maintained. When the mind is so trained, it communicates with the eye to also focus on hood things that helps in both are spiritual life and our secular lives, for indeed the eyes are the lamp of the body. God bless.
THE relationship between New Times Corporation (NTC) and African Concrete Productions (ACP) is based entirely on matters of the stomach. Each depends on the other in a dietary symbiosis, reinforced by the close proximity of each other
At lunchtime, you’d see a particular set of Times workers marching regimentally to ACP to face the wall. You’d think they are soldiers. It has long been declared that the company manufactures the best kokonte in the Greater Accra Region. ACP is, therefore, a culinary haven for those NTC kokonte fans, both male and female.
As the NTC kokonte warriors cross the border to ACP, you’d see some ACP banku fanatics dancing joyously to NTC. They are lucky folks because they do not have to obtain visa to enter into ‘Times’ to attack the balls of banku with precision and accuracy. They also claim that the lightsoup at ‘Times’ is arguably the best in West Africa.
So the relationship between the two entities was quite cordial and based practically on stomach palaver, until ACP workers staged an industrial revolution, whereupon the managing director, accountant and estate manager were allegedly stripped naked and locked up in a room. An insurgency had began in earnest.
An ACP worker came to ‘Times’, this time not to eat banku and okro. He had come to inform newsmen that juicy stuff awaited them at ACP. It could make a front page lead story.
A camerawoman and a female reporter were accordingly dispatched to go and bring back news, juicy news as juicy as kokonte and groundnut soup.
I was driving to work when I espied the familiar camerawoman clicking away outside the ACP premises. I didn’t see any ‘Times’ reporter but angry workers who were on the verge of getting violent. I slowed down and the driver behind blew his horn at me like a lunatic. I drove on.
Later, I heard the reporter and camerawoman were harassed and brutalised. The report came,. “The camerawoman, Mrs Salome Adonu-Agbottah and reporter Mrs Doreen Allotey, in an attempt to retrieve the camera which the workers had seized from them were severely beaten. They were manhandled and almost pushed into a big gutter opposite the company’s premises.
BRUISES
“….The camerawoman had bruises on her body, her hand bag was destroyed and the money in it stolen. Mrs Allotey’s watch was also snatched and her feet stamped on.”
Luckily, it was not her nose that was trampled upon. She has a beautiful nose.
The bad news was received with extreme sorrow. If the victims had been men, it would not have seemed too bad. But to brutalise women is just unacceptable. The New Times Corporation has not stopped mourning the incident which has been condemned in many circles.
Some people keep asking me why Times sent females to cover a potentially violent demonstration. I tell them they might as well ask why CNN’s amazon, Christina Amanpour, is assigned to cover the carnage in Bosnia-Herzegovina and Rwanda. She is always on the frontline in jeans and jacket.
Journalism is a potentially hazardous profession, and once you accept to study and practise the trade, you might as well bone up to face any assignment as long as your superiors feel you are capable of handling it or you have demonstrated the capacity to handle it. Both males and females can be assigned anywhere, anytime just like policemen and women are assigned.
The only difference between cops and pressmen is that the latter are armed only with a pen and the former with a gun. The question is should newsmen also arm themselves so that in any event of an assault they would not be found wanting in self-defence? They can’t adequately defend themselves with a pen and a jotter. A pen cannot even disfigure an opponent’s upper lip.
Photo-journalists have particularly suffered violence. Spectator ace-cameraman Vincent Dzatse was severely assaulted by AMA men when he attempted to take pictures of their indiscretions.
Sports cameraman, P. K. Arthur has been beaten more than once at the sports stadium when riots errupted and he wanted to capture it on his lenses.
Some sports journalists have been banned from entering the Accra Sports Stadium by supporters because in their comments, they didn’t write “sense”. Some supporters once nearly lynched Christian Abbew, Spectator Sports Editor, near a courtroom. He was stoned like the biblical Stephen. He had gone to defend a contempt charge.
I think it is time journalists met and discussed how best to defend themselves in any event of an attack by individuals or mobs. In the pursuance of their duty, they must be free from harassment and assault.
Some journalists go to work and return home with a black-eye or a double fore-head. It is just not right. Something has to be done about it. I think journalists should be armed. But first we must be trained in the use of firearms so that our warning shot do not hit below the belt. What about training in Kung Fu?
This article was first published on Saturday, October 17, 1998.
