Leg Cramps and Quinnine Sulphate

Good evening Dr Agar,

This is part 2 of the double post (see running late = speed it up). As I said In the earlier post I saw my Neph today. I have been getting really bad foot and leg cramps recently and oh boy are they painfull. I now do a fantastic impression of Yoda (The sage in Star Wars movies). I mentioned this to her (not the impression but the cramps) and she prescribed me Quinnine Sulphate (300mg) tablets.

I’m going to try to be subtle about this so please bare with me and also correct me if I’m off-line or wrong here. I thought that quinnine sulphate was a bit lets say (in UK speak) ‘dodgy’ as there are many bad side effects from this. Isn’t it usually for treating Malaria. I have found a link to say that it (quinnine Sulphate) has all but been bared in the USA due to these side effects ( I can post the link if it helps but I don’t want to scaremonger).

So the questions are, is this drug normally prescribed for leg cramps, does it work and do the benifits outweigh the possible adverse effects? What does it actually do and how does it work? Also are there and prefered altenatives to Quinnine Sulphate? I just feel I’m not sure on this one.

I don’t mean to monoploise this board and realise I have taken much of your time recently, but again as always your replies are truely helpful and anticipated.



Cramps are a common symptom of CKD and dialysis treatments – and, in dialysis, this is especially so when prescribing “wham, bam, thank you ma’am” treatment schedules that hurry the dialysis, shorten the sessional time, rack up the blood flow – and especially speed up the UF rate – and, not to put too fine a point on it, that try to make dialysis as unpleasant and as punishing a process as possible.

Cramp commonly occurs in advancing CKD (late stage 3 -5 especially) and can be one of the more distressing symptoms patients have to cope with.

The causes of cramp in advancing or established CKD are still poorly understood but are thought to be due to disturbances of nerve conduction at the ‘motor end plate’ and within the muscle cells themselves – in turn this is due to subtle errors or changes in the flux of sodium, magnesium and potassium (perhaps, but not certainly, potassium) across the nerve-muscle cell interface.

Lets try to do this in layman’s language! Bear with me here …

The muscles that drive our skeleton normally only contract when our brains say ‘contract’.

Let’s say we want to make a certain movement …

Well … our brain works out which muscle groups will ‘create’ and ‘drive’ that movement, then messages (tiny electrical impulses where sodium ions play a game of leap-frog along the (axonal) nerve sheath) are sent zinging down the spinal cord and out into the teeny tiny divisions of the nervous system which, like a twig that supplies a single leaf with its nutrients arises from the ever-dividing structures of the tree trunk and branches, divide into smaller and ever smaller branches to reach individual muscle cells.

Each teeny tiny muscle cell is connected to the teeny tiny nerve that brings it its’ instructions from ‘base-camp Brain’… like each leaf is connected to a twig that brings its nutrition from the ‘base-camp Earth’.

The ‘interface’ between nerve and muscle cell is called the motor-end plate. The impulse sent by the brain to ‘MOVE’ is a tiny electrical impulse (like the computer that I use to send this message to you will send a stream of electrical 1’s and 0’s) … but, how does that ‘impulse’, that ‘instruction’ then cross the ‘gap’ between nerve and muscle when it gets there?

How does the impulse trigger an electrical message to ‘CONTRACT’ within the muscle cell?

Aha … why not use an ‘electrolyte’ solution - a salt (or salts) dissolved in a watery solution - like exists in a common battery and which carries the current that drives a car - or a torch?

The nerve signals the muscle cell across the nerve/muscle cell gap – the motor-end plate – by a teeny tiny current that is driven by ‘flux’ or change in the concentration(s) and electrical behavior of sodium, potassium and magnesium.

Which of these matters most? … to be truthful, I don’t think anyone is sure … certainly I am not! Maybe one, maybe all – at least in some measure. There is some experimental evidence that favors potassium and the key electrolyte … but all matter to a degree.

But, think about it … it is these very electrolytes that are mucked about with in CKD. How often have you heard mutterings about sodium, potassium and magnesium in the course of your journeys through CKD? And it is these very electrolytes that are tossed on their heads during the rapid changes wrought by dialysis.

The poor motor-end plates don’t know if they are Arthur or Martha!

So … to put it in a wholly unscientific way … the motor-end plates ‘discharge’ a current (saying ‘CONTRACT’ when they shouldn’t, or, they don’t when they should – they get very confused.

They fire ‘CONTRACT’ messages when they shouldn’t and the muscles contract when they aren’t meant to. Your brain didn’t send a message - the locally disturbed electrolyte soup did!

And, so, cramps happen. And, those cramps happen most … and are worst … when the changes in sodium, potassium (probably potassium most) and magnesium reach a peak … and, in turn, that peak happens most when fast, sudden dialysis turns the electrolyte soup that controlls nerve/muscle function is under maximum threat and disturbance.

I hope you get the idea. It is awfully complex and it’s not well understood (maybe especially by me) – but I think that’s the gist of it.

Now, for the solution(s) …

1. For dialysis cramp

The key aim must be to diminish the rate and severity of the disturbing factor …and the disturbing factor is the dialysis.

Slow the dialysis.
Reduce the UF rate.
Diminish the perturbation of the electrolyte soup!
Move to longer, slower, more frequent dialysis!
Don’t muck with the concentrations of Na+, K+, and Mg++ more than or faster than you absolutely need to.
And … note that nocturnal HD and PD are both relatively (note, relatively) cramp-free c/w facility HD.

2. For CKD cramp

There are medications that help. They don’t cure, but they lessen. But there is some common sense stuff that helps, too.

To answer, first, your question re: quinine sulphate.

Quinine sulphate has long been used to treat cramp since the British ‘Raj’ worked out that a few stiff gins and tonics worked marvelously well to reduce their salt-deprivation cramps in the tropics of their 19th Century Empire. I don’t think they actually initially drank the G&T’s to solve cramp – perhaps it was more to drown boredom and dislocation from the mother-country and, even more, for the alcohol - but they did notice that when they had a G&T (or 3, or 4), their cramps lessened. Incidentally, they also drank tonic water to access its active ingredient (quinine) as quinine is (or was) also is a very effective anti-malarial … hence the linkages between G&T’s, quinine, malaria and cramps.

But, yes … quinine sulphate has an unhappy knack of causing thrombocytopenia … a low platelet count – and while this isn’t a hugely common problem, it can be nasty and very dangerous. As a result, we now no longer use quinine to treat CKD or dialysis cramp. There are better ways.

You are right – quinine IS ‘on the nose’ and is now not used in Australia (or the US, I think). Indeed, our own hospital refuses to stock or supply it. So, no, you haven’t missed something there. Quinine is ‘on the nose’. Perhaps the UK still has a twilight ‘affair’ with it through the G&T … but I wouldn’t go that way myself.

Other than in the clear, electrolyte-perturbing situation of dialysis, CKD cramp often occurs in bed at night.

Let’s deal with common sense things first … and people often don’t think of the simple solutions … heavy doona’s (duvets?) or blankets actually mechanically press down on the feet, ‘extending’ the feet but thereby simultaneously contracting the calf muscles and thus promoting cramp.

Here, think of the footballer who cramps in the last few minutes of the match … how does he ‘self-solve’ his cramp? - he pulls his toes up towards himself, lengthening (stretching) the calf muscle to relieve the cramp. The weight of bed clothes does the opposite - pushing down on the feet and shortening the calf - promoting the ‘milieu’ for cramp. Lift the weight away from the foot and the foot remains more flexed and un-extended … and cramp is not augmented.

So … simple mechanical steps help! And … so do simple mechanical solutions.

If nocturnal bed cramps are a problem, try cutting the side out of a cardboard box, place it under the blankets, doona (or duvet) at the foot of the bed and over the feet to lift the mechanical weight of the covers off the feet so that they do not get ‘extended’ by the down-pressure of the covers. It maybe sounds silly – but it’s amazing how little things like that can escape us in this magic world of ‘pills’ and technology …

Codeine helps some people – like when in paracetamol - paracetamol + codeine, in Australia, = Panadeine. Two before bed (if they don’t cause itch or drive constipation – as they can, in some) may help those who have no ‘issues’ with taking codeine.

My absolute personal favorite, and the thing I find works much the best, is a drug which, in Australia, is on the PBS only for epilepsy … yes, it’s an anti-epileptic … but it’s also a member of the benzodiazepine family. The drug is clonazepam (marketed here as Paxam).

Clonazepam really does seem to help - a lot. It changes, subtly, the electrical conductivity of the nervous system (it’s why it works as an anti-epileptic agent!) and it seems to work really well in CKD cramp. Our ‘crampy’ patients take 1 to 2mg, at night, and it often does wonders.

Shaymon … sorry, but that’s been a long ramble. However, I hope it serves to answer some of the questions you posed.