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    hi everyone , i realy need help at the mo! im trying to do one of my assisgnment n i have to relate the mode of action of a drug to its side effects , im doin h2 receptor agonists and trying to see why they cause headaches/ dizziness and rashes , if anyone has any idea i would really aprechiate it . thank you

  • #2
    Side effects

    One of my pet theories is that there are two side effects to any drug.
    1) caused by the molecule itself.
    2) caused by its' pharmacological action.

    An example would be the sulphonamides and their derivatives.

    Chlorothiazide (saluric) was one of the early diuretics derived from sulphonamides. It had the side effects of the sulphonamides plus those resulting from it's diuretic action. Greater potency drugs were synthesised, eg hydrochlorothiazide which lost most of the side effects of sulphonamides as given in much lower dosage. Other examples could be sumatrtan and naratriptan.

    Resulting from all this is the theory that the more potent a drug is compared with the parent compound, then the class (1) side effects should be reduced.

    another example could be frusemide and bumetanide. Weight for weight, bumetanide is worst than frusemide for side effects, but at the dosage of 1/40, then the molecular side effects are reduced.
    johnep

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    • #3
      what about non-steroidal anti-inflammatories and cyclo-oxygenase inhibition? that's the msot obvious example of a drug's mode of action causing side-effects; Or what about the diarrhoea brought about by antibiotics killing one's intestinal flora as well as the harmful bacteria it was targeting? anti-cancer drugs that make your hair fall out because they kill all fast-replicating cells, whether they be malignant tumour cells or hair follicles?
      Ze genuine Article, present & perfect!

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      • #4
        H2s aren't really a good choice - they are pretty well tolerated. Why not change to one of the ones that Zoggite mentioned, or something like orlistat, where the side effects are clearly and easily related to the mechanism of action.

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        • #5
          Originally posted by love View Post
          hi everyone , i realy need help at the mo! im trying to do one of my assisgnment n i have to relate the mode of action of a drug to its side effects , im doin h2 receptor agonists and trying to see why they cause headaches/ dizziness and rashes , if anyone has any idea i would really aprechiate it . thank you
          I would think that the headaches/dizzuness were caused from CNS stimulation, and the rash was a bizarre side effect. I can't even really think of any drugs that are used as H2 agonists. What would they do - increase acid secretion in the stomach?

          Can't you change to a drug that has a lot of clinical use, and side effects that are easily explained? Maybe one of the ones mentioned, or beta blockers might be a good one. You could discuss the difference between propranolol and atenolol for example, and why they can effect asthmatics etc.
          Last edited by admin; 13, February 2007, 10:48 PM.
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          • #6
            Um err, What exactly are the differences between atenolol and propranolol?
            johnep

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            • #7
              Originally posted by johnep View Post
              Um err, What exactly are the differences between atenolol and propranolol?
              johnep
              Well atenolol is more cardio selective isn't it (Beta1 selective)? So if you gave propranolol and had breathing problems, using a beta2 agonist wouldn't do much to reverse the effects. If this happened with atenolol then using the agonist should help.

              In reality, it's not as simple as B1 receptors in the heart and B2 in the lungs, as people do have B1 receptors in the lungs too, thus possible breathing problems with atenolol as well as the non selective propranolol, but like I say at least a B2 agonist can help with atenolol.

              Love says in the first post that they have to relate the mode of action of a drug to it's side effects, and I just thought that as beta blockers have a lot of side effects that can be easily explained by their pharmacology it might be a good example to use. I was thinking of things like breathlessness, peripheral circulatory problems, bradycardia, diabetes etc etc - all reasons not to take beta blockers and all easily explained by their pharmacology. Ok that's off the top of my head, but I thought it could be used as an example.

              It's been years since I learned this stuff, so apologies if any of this is wrong - check everything up first Love if you use this as an example!
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              • #8
                Oh dear, I didn't know we had different receptors in the lungs and heart.

                cardioselective means effects confined to heart without giving you a cough,
                or does it?
                johnep

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                • #9
                  Beta Blockers

                  Originally posted by johnep View Post
                  Oh dear, I didn't know we had different receptors in the lungs and heart.

                  cardioselective means effects confined to heart without giving you a cough,
                  or does it?
                  johnep
                  Thats the idea John. We have Beta 1 receptors in the heart, and Beta 2 receptors in the lungs. Like I said before, people do have Beta 1 in the lungs, but as I understood it's mainly Beta 2.

                  Propranolol was one of the old Beta blockers that blocked all Beta receptor sites, thus giving more respiratory problems. Atenolol is a newer one, that is Beta 1 selective, so gives fewer respiratory problems.

                  Obviously Beta blockers have effects on lots of other parts of the body apart from the heart, and the side effects can be nicely explained due to their pharmacology, which is why I thought they could be a good example for this project for the member Love.
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                  • #10
                    This is just the sort of info which will be useful when I start my MURs.
                    I was on atenolol but following discussion on prx, I got my Dr to change to bisoprolol. atenolol was giving me so much 'pins and needles' in my hands.
                    johnep

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                    • #11
                      Side Effects

                      Once had to explain to a group of non-pharmacists how side effects arose. Explained it like this. Most of the time the body regulates itself by 'putting out' very small amounts of chemicals not far from the places where they act (thinking about synapses) when they have done their job, the body quickly removes them. This is how the body can use the same chemicals in lots of different places for different purposes. When you take a medicine it enters the bloodstream and marinades all the tissues, so it has the effect that we want but also switches other things on and others off that are not intended, so we get side effects.

                      OK this isn't perfect, as some things are quite specific to tissues, eg hormones and various mechanisms, etc. However, some things aren't.

                      However, you can use it under 'open source license' if you will. (ie if you improve it you have got to share it back)

                      Re: Atenolol/Propranolol.
                      Thought some of the difference was also due to water/lipid solubility differences. Also isn't propranolol a racemate of r/s (l/d) stereoisomers? (might also have something to do with it - possibly?)
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                      • #12
                        Originally posted by johnep View Post
                        This is just the sort of info which will be useful when I start my MURs.
                        I was on atenolol but following discussion on prx, I got my Dr to change to bisoprolol. atenolol was giving me so much 'pins and needles' in my hands.
                        johnep
                        I think that bisoprolol is a much newer one then atenolol, so that probably explains why it worked better. Then again, some drugs just seem to suit some people better then others.
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                        • #13
                          Re: Atenolol/Propranolol.
                          Thought some of the difference was also due to water/lipid solubility differences. Also isn't propranolol a racemate of r/s (l/d) stereoisomers? (might also have something to do with it - possibly?)
                          Possibly, I don't know to be honest - it's been quite a few years since I even had to think about this type of thing. I find pharmacy is a great way to de-skill yourself.

                          I am sure that it's the selectivity of atenolol for Beta1 receptors and the non selectivity of propranolol that explains why propranolol has more effect on the lungs.
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                          Please help keep the forum vibrant by spreading the work to friends and colleagues via word of mouth or social media.
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                          • #14
                            um err--what is effect of propranolol on the lungs ---cough. Seems to be used mainly for 'nerves' these days. Where do beta blockers work in the brain.
                            On 5ht?, gaba? Limbic system?

                            Surely the doses of 80-160 mg would cause side effects.
                            johnep

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                            • #15
                              Originally posted by johnep View Post
                              um err--what is effect of propranolol on the lungs ---cough. Seems to be used mainly for 'nerves' these days. Where do beta blockers work in the brain.
                              On 5ht?, gaba? Limbic system?

                              Surely the doses of 80-160 mg would cause side effects.
                              johnep
                              On the lungs propranolol blocks B2 receptors in smooth muscle which can lead to an increase in airway resistance, hence breathlessness especially in asthmatics. In lower doses used for anxiety (eg 10 - 20mg BD etc) the effect is lesser, but can still cause lung function problems.

                              Propranolol is often used in migraine headache, reducing the frequency and severity of the headaches. I'm not sure of the exact mode of action (without doing searches) but the sympathetic nervous system must be involved for it to work.

                              The most common uses of Beta blockers, as far as I can recall, are hypertension, ischaemic heart disease, cardiac arrhythmias, glaucoma and thats about it off the top of my head.

                              John you're making my brain hurt!

                              Last edited by admin; 19, February 2007, 08:41 PM. Reason: Spelling Mistakes!
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                              Please help keep the forum vibrant by spreading the work to friends and colleagues via word of mouth or social media.
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