1 00:00:00,480 --> 00:00:03,330 Dr Emma Hancox: Welcome back to the Synaptic Tails podcast with your 2 00:00:03,330 --> 00:00:08,310 hosts, Emma Hancox, TVM Technical Vet, and Mark Lowrie, RCVS and European 3 00:00:08,315 --> 00:00:12,000 Specialist in Veterinary Neurology, and Co-director of Movement Referrals. 4 00:00:12,690 --> 00:00:13,080 Hi Mark. 5 00:00:13,080 --> 00:00:13,620 How are you? 6 00:00:13,890 --> 00:00:14,280 Dr Mark Lowrie: Hello. 7 00:00:14,280 --> 00:00:14,700 Yeah. 8 00:00:14,799 --> 00:00:15,609 Welcome back everyone. 9 00:00:16,030 --> 00:00:18,430 Dr Emma Hancox: As you hopefully will remember from last time we 10 00:00:18,430 --> 00:00:22,479 introduced our S.M.A.R.T Approach to epilepsy, that's TVMs new guide for 11 00:00:22,479 --> 00:00:25,839 first opinion practitioners, and we were chatting about the importance 12 00:00:25,839 --> 00:00:29,409 of speaking and how communicating with the client is so important. 13 00:00:30,069 --> 00:00:33,389 The next step of the smart approach is going to be Measure. 14 00:00:33,469 --> 00:00:36,520 So measuring is a bit of a minefield I think out there. 15 00:00:37,000 --> 00:00:40,660 What is it that you routinely measure in your epileptic patients Mark? 16 00:00:41,140 --> 00:00:43,060 Dr Mark Lowrie: So if we're thinking about measure when a dog started 17 00:00:43,120 --> 00:00:47,480 medication there are key things that are really important to look at in 18 00:00:47,480 --> 00:00:52,740 these dogs . I think there's a lot of bad press, and I hinted this last time, 19 00:00:52,860 --> 00:00:55,150 about phenobarbital and what it does. 20 00:00:55,190 --> 00:00:57,450 Dr Emma Hancox: You did, you left us on a cliffhanger last time... 21 00:00:57,810 --> 00:00:58,650 Dr Mark Lowrie: Am I gonna clear it up? 22 00:00:58,680 --> 00:00:59,070 Dr Emma Hancox: A spoiler... 23 00:01:00,510 --> 00:01:05,560 Dr Mark Lowrie: So for me, when we're checking bloods, it's all very easy to go 24 00:01:05,890 --> 00:01:09,340 let's check bloods, send them away, check they're okay and we're happy. 25 00:01:10,270 --> 00:01:13,840 And it will be inevitable if you are taking bloods from a dog, and I'm, using 26 00:01:13,840 --> 00:01:17,680 the term bloods loosely right now, but when you get them back, you've probably 27 00:01:17,680 --> 00:01:19,600 measured a selection of liver enzymes. 28 00:01:20,650 --> 00:01:24,550 And those liver enzymes are likely to be very high because we like to look 29 00:01:24,550 --> 00:01:27,410 at our reference range and we like our values to be within the reference range. 30 00:01:27,460 --> 00:01:28,750 It makes us all feel comfortable. 31 00:01:28,885 --> 00:01:29,335 Dr Emma Hancox: Yep. 32 00:01:30,640 --> 00:01:33,340 Dr Mark Lowrie: Now, if the dog's been on phenobarbital for two weeks or 33 00:01:33,345 --> 00:01:35,590 longer, those liver enzymes will be high. 34 00:01:36,160 --> 00:01:40,330 And all I'd say at this moment in time is I disregard liver enzymes a lot. 35 00:01:40,780 --> 00:01:42,280 I don't worry too much about them. 36 00:01:42,450 --> 00:01:44,590 You asked what I measure. 37 00:01:44,590 --> 00:01:49,180 So the things I want to be including on those blood tests is I want to 38 00:01:49,180 --> 00:01:50,950 look at values for liver function. 39 00:01:51,160 --> 00:01:56,290 Liver enzymes tell you about liver structure and by nature of phenobarbital, 40 00:01:56,290 --> 00:01:58,210 it is metabolized by liver. 41 00:01:58,210 --> 00:02:02,020 It makes the liver work harder, the liver becomes damaged. 42 00:02:02,070 --> 00:02:03,600 A small bit of liver damage is fine. 43 00:02:03,780 --> 00:02:07,085 So the things I look for liver function, there are four values 44 00:02:07,115 --> 00:02:08,240 I really, really want to look at 45 00:02:08,320 --> 00:02:08,620 Dr Emma Hancox: Okay. 46 00:02:08,990 --> 00:02:10,115 Dr Mark Lowrie: The first is glucose. 47 00:02:10,865 --> 00:02:13,955 So we want to look at glucose and the liver produces glucose, so we 48 00:02:13,955 --> 00:02:15,185 wanna make sure it's not too low. 49 00:02:15,605 --> 00:02:17,675 So when I'm looking at glucose on my biochemistry, I'm 50 00:02:17,675 --> 00:02:18,725 checking it's not too low. 51 00:02:18,775 --> 00:02:22,375 The others are albumin, cholesterol, and urea. 52 00:02:23,265 --> 00:02:23,555 Dr Emma Hancox: Okay. 53 00:02:23,875 --> 00:02:27,865 Dr Mark Lowrie: Now if any of those are low, again, that alerts you 54 00:02:27,870 --> 00:02:31,225 to the fact there could be some kind of liver damage going on. 55 00:02:32,155 --> 00:02:36,415 So if we measure those four things, if they're at all low, I'm worried. 56 00:02:36,445 --> 00:02:40,975 Now I have to add to that, that we don't just measure them because, I 57 00:02:40,975 --> 00:02:43,765 suppose we'll touch on this when we talk about diagnosis of epilepsy, 58 00:02:43,825 --> 00:02:47,755 but when you’re taking bloods, you always want to do a fasted sample. 59 00:02:47,905 --> 00:02:51,345 So you want to wait until the dog's been starved for 12 hours, very much like 60 00:02:51,475 --> 00:02:54,355 we would, when we go to the doctors, we're told not to have breakfast. 61 00:02:54,355 --> 00:02:57,145 And that's not a weight limiting strategy. 62 00:02:57,145 --> 00:02:59,365 It's not a way of us dieting or the doctors are trying to be good to us. 63 00:02:59,365 --> 00:03:01,580 It's to make sure that like our blood sugar levels are 64 00:03:01,580 --> 00:03:02,840 checked when we've been starved. 65 00:03:03,230 --> 00:03:07,940 Of course, the body should be able to adapt to no intake of food by ensuring 66 00:03:07,940 --> 00:03:09,860 we've got a steady glucose concentration. 67 00:03:09,860 --> 00:03:13,700 So always do a fasted blood sample to look at these things. 68 00:03:14,210 --> 00:03:16,760 Now, if those four values are within normal level, I'm quite 69 00:03:16,760 --> 00:03:18,200 happy about liver function. 70 00:03:19,055 --> 00:03:22,355 If you want to be really thorough or if you've got any concern, then this is where 71 00:03:22,355 --> 00:03:24,305 the bile acid stimulation test comes in. 72 00:03:24,600 --> 00:03:24,875 Dr Emma Hancox: Yeah 73 00:03:25,775 --> 00:03:27,005 Dr Mark Lowrie: A bile acid stimulation test. 74 00:03:27,005 --> 00:03:30,935 We do the fasted bile acids and then we feed the dog and we do a post sample. 75 00:03:31,565 --> 00:03:34,985 I do find as a reasonable screen, a fasting bile acids is fine. 76 00:03:35,645 --> 00:03:36,725 You will miss some cases. 77 00:03:36,725 --> 00:03:40,565 I’ll be very honest if you don't do a full bile acids, but actually the vast 78 00:03:40,565 --> 00:03:44,030 majority of dogs, particularly when it comes to measuring liver function, 79 00:03:44,240 --> 00:03:46,340 doing a fasting bile acids is plenty. 80 00:03:46,550 --> 00:03:48,320 And as long as that's normal, we're fine too. 81 00:03:49,280 --> 00:03:52,700 The only time I really start to worry about the liver and liver enzymes, 82 00:03:52,700 --> 00:03:55,940 and indeed even if bile acids start to creep up, is when dogs are actively 83 00:03:55,940 --> 00:03:57,320 showing signs of liver disease. 84 00:03:57,575 --> 00:03:58,540 Dr Emma Hancox: Yeah, definitely. 85 00:03:58,780 --> 00:04:00,490 Dr Mark Lowrie: So a yellow dog, that's a concern. 86 00:04:00,850 --> 00:04:01,960 Potbellied, all these things. 87 00:04:03,070 --> 00:04:06,160 The other thing to say about phenobarbital here when we're talking about measurements 88 00:04:06,160 --> 00:04:07,900 is measuring those clinical signs. 89 00:04:07,900 --> 00:04:10,565 Phenobarbital can do two things to liver. 90 00:04:10,745 --> 00:04:14,135 The first is just its chronic use can cause liver disease. 91 00:04:14,285 --> 00:04:15,575 Now that's really, really rare. 92 00:04:15,855 --> 00:04:19,355 when we're doing serum concentration measuring, we do want to keep it at the 93 00:04:19,360 --> 00:04:25,795 right level because if you are above, 35 to 40 Mgs per litre, that is when 94 00:04:25,975 --> 00:04:30,485 we need to be worried that we could be pushing the dog into a hepatotoxicity. 95 00:04:30,505 --> 00:04:34,225 So we do try and keep below the sort of 35 to 40 level on our 96 00:04:34,225 --> 00:04:36,895 phenobarbital concentration to make sure we don't go there. 97 00:04:37,585 --> 00:04:39,075 If we do that's really safe. 98 00:04:39,825 --> 00:04:43,845 Now the other thing that phenobarbital can do is there's an idiosyncratic 99 00:04:43,845 --> 00:04:48,545 reaction where it just causes a really nasty acute hepatotoxicity. 100 00:04:49,545 --> 00:04:53,540 Now I’ve said the chronic phenobarbital abuse of the liver is fairly rare. 101 00:04:53,750 --> 00:04:55,800 This idiosyncratic reaction is even rarer 102 00:04:56,040 --> 00:04:56,280 . Dr Emma Hancox: Okay. 103 00:04:56,900 --> 00:04:59,420 Dr Mark Lowrie: These are dogs that have gone on to phenobarbital and they, within 104 00:04:59,480 --> 00:05:03,500 weeks, they develop what can only be described as horrendous liver disease. 105 00:05:04,430 --> 00:05:06,800 They go jaundiced, they become Ascitic. 106 00:05:07,160 --> 00:05:09,020 They really don't look very well at all. 107 00:05:09,955 --> 00:05:10,830 Dr Emma Hancox: Is this reversible? 108 00:05:11,060 --> 00:05:11,810 Dr Mark Lowrie: It's not. 109 00:05:12,020 --> 00:05:17,270 So when we see that, that is a real concern, but this is so, so rare, and 110 00:05:17,330 --> 00:05:20,930 what I want to pick up on here is if you are checking your blood values 111 00:05:20,960 --> 00:05:23,990 after two weeks and you’re seeing high liver enzymes, do not worry about that. 112 00:05:24,080 --> 00:05:27,380 Because I think I’ve come across a number of situations where vets 113 00:05:27,380 --> 00:05:30,860 will stop phenobarbital because the liver enzymes are a bit high. 114 00:05:31,460 --> 00:05:34,040 As we've said, that's completely normal. 115 00:05:34,230 --> 00:05:36,030 we expect the liver enzymes to be high. 116 00:05:36,300 --> 00:05:39,030 You could make an argument that if they're normal, that's possibly because 117 00:05:39,030 --> 00:05:42,180 the liver's already really badly damaged And there's no more liver to destroy. 118 00:05:42,220 --> 00:05:42,480 Dr Emma Hancox: Yeah. 119 00:05:42,550 --> 00:05:45,460 Dr Mark Lowrie: So high liver enzymes is actually not a bad thing, and 120 00:05:45,460 --> 00:05:47,050 that makes me a lot more happy. 121 00:05:47,530 --> 00:05:50,990 Dr Emma Hancox: Yeah, I'm really glad that you've picked up on the liver 122 00:05:50,990 --> 00:05:55,070 monitoring because that is, as the Tech Vet at TVM, obviously I do get quite 123 00:05:55,075 --> 00:06:01,070 a few calls about phenobarbital, for instance, and when they've done liver 124 00:06:01,075 --> 00:06:06,710 values and say, I'm just picking out ALP is usually the perpetrator I will 125 00:06:06,710 --> 00:06:11,860 say, we expect as a rough guideline about three to five times a reference 126 00:06:11,860 --> 00:06:17,155 range, but I’ve seen cases where it is often dramatically higher than that. 127 00:06:17,725 --> 00:06:20,785 And you’re so right in that actually, I really don't worry 128 00:06:20,785 --> 00:06:24,205 about it in the vast majority of cases caveat that with of course. 129 00:06:24,745 --> 00:06:26,125 But you’re right. 130 00:06:26,125 --> 00:06:28,495 The first things I'm gonna be asking them is, has the dog 131 00:06:28,495 --> 00:06:30,085 actually got any clinical signs? 132 00:06:30,625 --> 00:06:34,415 I'm gonna look at other, clues on bloods. 133 00:06:34,435 --> 00:06:37,165 So you mentioned things like the albumin et cetera. 134 00:06:37,975 --> 00:06:40,145 But just coming back to these liver values. 135 00:06:40,205 --> 00:06:44,625 One of the ones that is interesting to me is the AST. 136 00:06:45,245 --> 00:06:46,925 Do you ever use that in practice? 137 00:06:46,955 --> 00:06:48,065 Do you rely on it at all? 138 00:06:48,115 --> 00:06:50,490 Dr Mark Lowrie: I'm not gonna say this because you’re sat in opposite 139 00:06:50,490 --> 00:06:54,150 me but I would say about liver disease and phenobarbital there is 140 00:06:54,155 --> 00:06:57,480 a great resource on the TVM website and she hasn't told me to say this. 141 00:06:57,480 --> 00:06:58,060 This is just me 142 00:06:58,080 --> 00:06:58,860 Dr Emma Hancox: I actually haven't 143 00:06:59,970 --> 00:07:01,870 Dr Mark Lowrie: I would guide you that way to get a lot more information 144 00:07:01,870 --> 00:07:04,680 because it does explain these liver values far better and more eloquently 145 00:07:04,685 --> 00:07:06,150 than I'm likely do right now. 146 00:07:06,400 --> 00:07:09,730 But AST yes, it is something that is less effected by phenobarbital, 147 00:07:09,970 --> 00:07:11,230 but personally I don't use it. 148 00:07:11,380 --> 00:07:14,290 I think the other measures that are better to look at liver function, because 149 00:07:14,290 --> 00:07:17,130 AST it's a measure of liver structure. 150 00:07:17,420 --> 00:07:19,510 I know it's involved in muscles as well. 151 00:07:19,510 --> 00:07:24,290 So you get muscle disease, AST can increase so it's not specific to 152 00:07:24,290 --> 00:07:28,060 the liver and when it is high, you shouldn't therefore blame the liver. 153 00:07:28,060 --> 00:07:29,530 You should think there may be another cause. 154 00:07:29,647 --> 00:07:33,157 But I'm, I honestly hand on heart, I don't look at it very much but I would 155 00:07:33,157 --> 00:07:36,337 also say hand on heart, I don't look at the other liver enzymes very much either 156 00:07:36,787 --> 00:07:40,717 So liver enzymes to me aren't particularly useful. 157 00:07:40,922 --> 00:07:45,255 and it's those liver function, values that I'm looking at in more detail. 158 00:07:45,815 --> 00:07:46,025 Dr Emma Hancox: Yeah. 159 00:07:46,545 --> 00:07:50,920 And just picking up on what you just said, looking for other causes, don't forget 160 00:07:50,925 --> 00:07:53,590 there are other causes for ALP to go high. 161 00:07:53,590 --> 00:07:59,380 So things like undiagnosed Cushing's, if they've been on phenobarbital for years 162 00:08:00,100 --> 00:08:04,225 don't rule out or forget those, steroid use, whether that be oral or topical, 163 00:08:04,225 --> 00:08:05,845 can sometimes cause that to increase. 164 00:08:05,895 --> 00:08:08,295 Is that the actual drug that they're on or is that something else? 165 00:08:08,300 --> 00:08:08,985 Don't ever forget. 166 00:08:08,985 --> 00:08:10,875 Those are the co-morbidities that might be happening. 167 00:08:10,875 --> 00:08:12,220 Or other treatments as well. 168 00:08:12,410 --> 00:08:14,760 Dr Mark Lowrie: I think that's really valid because you've just mentioned 169 00:08:14,765 --> 00:08:15,900 the word that I don't understand. 170 00:08:15,960 --> 00:08:17,190 So Cushing's, I don't know what that means. 171 00:08:17,190 --> 00:08:17,655 Dr Emma Hancox: What was that? 172 00:08:18,435 --> 00:08:19,725 Again, we need a medic in the room. 173 00:08:19,830 --> 00:08:20,220 Dr Mark Lowrie: No. 174 00:08:20,500 --> 00:08:23,230 so I dunno what that means and that's why I don't look at liver values 'cause 175 00:08:23,230 --> 00:08:26,450 they scare me too much but in the context of phenobarbital the other 176 00:08:26,450 --> 00:08:27,850 values are far more helpful for you 177 00:08:27,850 --> 00:08:32,015 Dr Emma Hancox: Yeah, I guess I don't, this is now just for my own peace of mind 178 00:08:32,020 --> 00:08:37,525 to be honest, are they not going to be reduced later on in the disease process? 179 00:08:37,785 --> 00:08:43,105 So my worry there would be actually, if I'm looking at things like glucose 180 00:08:43,135 --> 00:08:47,150 or albumin for instance, are we not going to, have we mentioned at the 181 00:08:47,150 --> 00:08:51,740 beginning, 70% or more loss of liver kind of function at that stage? 182 00:08:51,770 --> 00:08:53,660 Is that not a concern for you or? 183 00:08:54,010 --> 00:08:54,310 Dr Mark Lowrie: It is. 184 00:08:54,310 --> 00:08:55,010 So there's two things. 185 00:08:55,010 --> 00:08:59,640 In end stage liver disease, these products of the liver would be so 186 00:08:59,640 --> 00:09:01,890 reduced that they're incredibly low. 187 00:09:02,220 --> 00:09:05,670 But I'd like to think with regular monitoring, we'd pick up on that in time. 188 00:09:05,870 --> 00:09:09,840 So this is where measuring every three to six months is a good idea. 189 00:09:10,020 --> 00:09:13,200 And that way you would be able to pick up that decline before it gets too far. 190 00:09:13,680 --> 00:09:17,130 But similarly, liver enzymes in end stage liver disease, 191 00:09:17,160 --> 00:09:18,690 liver enzymes can become normal. 192 00:09:18,750 --> 00:09:21,330 They can even get low because you've got no liver left. 193 00:09:21,330 --> 00:09:24,150 Yeah, So the same is true of liver enzymes. 194 00:09:24,250 --> 00:09:27,460 But they definitely go sky high before they go anywhere close to dropping. 195 00:09:27,970 --> 00:09:29,320 And hence, I don't worry. 196 00:09:29,740 --> 00:09:32,260 But regular monitoring is vital. 197 00:09:32,455 --> 00:09:33,745 Dr Emma Hancox: So you’re getting that trend. 198 00:09:34,210 --> 00:09:37,150 Dr Mark Lowrie: You are, and I think that brings in the 199 00:09:37,360 --> 00:09:39,970 serum concentration monitoring 200 00:09:39,970 --> 00:09:40,030 Dr Emma Hancox: Yeah. 201 00:09:41,090 --> 00:09:43,690 Dr Mark Lowrie: So serum concentrations are the other 202 00:09:43,780 --> 00:09:45,400 measure that we do in these dogs. 203 00:09:47,260 --> 00:09:51,580 This is with phenobarbital, it's fair to say with many of the other medications 204 00:09:51,580 --> 00:09:57,190 available for epilepsy, we're not quite as set on measuring the concentrations. 205 00:09:57,490 --> 00:09:58,870 I appreciate bromide, we do. 206 00:09:59,060 --> 00:10:01,790 But the other medications, we don't really monitor them in the same way. 207 00:10:02,270 --> 00:10:05,870 Now, the reason for that is phenobarbital is metabolized by the 208 00:10:05,870 --> 00:10:08,560 liver, the P450 cytochrome system. 209 00:10:08,590 --> 00:10:09,200 Dr Emma Hancox: Oh goodness. 210 00:10:09,200 --> 00:10:11,350 You've just given me flashbacks to uni. 211 00:10:11,650 --> 00:10:13,990 Dr Mark Lowrie: I'm not gonna say it again 'cause I felt a bit scared saying it too. 212 00:10:13,990 --> 00:10:14,830 It made me nervous. 213 00:10:15,010 --> 00:10:19,885 Um, But this is, like an enzyme induction where the enzymes that 214 00:10:19,885 --> 00:10:24,025 break down phenobarbital work harder and harder with time. 215 00:10:24,505 --> 00:10:28,855 So you can start a dog on phenobarbital at your standard dose. 216 00:10:28,925 --> 00:10:32,255 I choose three mgs per kg twice a day as my starting dose for 217 00:10:32,255 --> 00:10:38,135 phenobarbital, and then it takes about 10 to 14 days to reach steady state. 218 00:10:38,135 --> 00:10:40,775 So again, an owner would need to understand if you started that 219 00:10:40,775 --> 00:10:44,810 medication, it will be, A good couple of weeks before it's really 220 00:10:44,810 --> 00:10:46,790 at its effective working levels. 221 00:10:47,090 --> 00:10:49,340 Now that doesn't mean it isn't working after a few days, it's just 222 00:10:49,340 --> 00:10:54,070 not working at its optimal, position until that time now at two weeks. 223 00:10:54,070 --> 00:10:57,910 We then measure the phenobarbital serum concentration because every 224 00:10:57,910 --> 00:11:01,750 dog, and indeed every person's liver metabolizes things at different rates. 225 00:11:01,780 --> 00:11:02,800 So there'll be some dogs. 226 00:11:03,415 --> 00:11:06,355 That can metabolize phenobarbital really effectively. 227 00:11:06,595 --> 00:11:09,205 We don't like that 'cause that not working as well. 228 00:11:09,535 --> 00:11:12,205 but that would mean in those individuals they'll need a higher dose. 229 00:11:13,405 --> 00:11:15,665 I don't worry about what I'm putting into the dog 230 00:11:16,215 --> 00:11:16,585 Dr Emma Hancox: Okay. 231 00:11:16,795 --> 00:11:19,825 Dr Mark Lowrie: So I'm not too interested in the dose going in. 232 00:11:20,455 --> 00:11:24,655 I'm much more interested in the serum concentration, so if I'm measuring the 233 00:11:24,655 --> 00:11:30,640 serum concentration after two weeks and serum concentration is low, that 234 00:11:30,640 --> 00:11:34,930 tells me that dog needs a higher dose to achieve the therapeutic range. 235 00:11:35,770 --> 00:11:35,830 Dr Emma Hancox: Yeah. 236 00:11:36,230 --> 00:11:37,730 Dr Mark Lowrie: Therapeutic range is big 237 00:11:37,920 --> 00:11:38,995 Dr Emma Hancox: It's massive, isn't it? 238 00:11:39,230 --> 00:11:44,120 Dr Mark Lowrie: I would aim at going somewhere between 25 to 30 mgs per litre. 239 00:11:44,765 --> 00:11:45,215 Dr Emma Hancox: Yeah. 240 00:11:45,515 --> 00:11:47,015 Why would you aim for that range? 241 00:11:47,015 --> 00:11:48,765 The 25 to 30 mgs per litre? 242 00:11:48,785 --> 00:11:51,005 Is that where most dogs you find are controlled? 243 00:11:51,530 --> 00:11:54,860 Dr Mark Lowrie: It is, I think when you reach that concentration, you 244 00:11:54,860 --> 00:11:57,430 know you’re getting your optimal performance from phenobarbital. 245 00:11:58,205 --> 00:12:00,185 That doesn't mean it's a, it's gonna be perfect. 246 00:12:00,185 --> 00:12:02,195 It doesn't mean you’re gonna have to be delighted with that 247 00:12:02,195 --> 00:12:05,075 performance, but that's the best performance for that individual dog. 248 00:12:05,435 --> 00:12:06,455 So that's what I aim at. 249 00:12:06,995 --> 00:12:10,265 I think the range goes from 15 to 40 mgs per litre. 250 00:12:10,855 --> 00:12:13,745 That worries me a bit because we have talked about the higher end of that 251 00:12:13,775 --> 00:12:18,005 being more of a risk of developing liver problems the lower end of that, 252 00:12:18,155 --> 00:12:22,505 I do consider myself, as being a bit sub therapeutic, so I'm also aware 253 00:12:22,505 --> 00:12:24,700 of dogs that may only be at 15 to 20. 254 00:12:25,585 --> 00:12:29,245 And we're not getting the best out of phenobarbital there in that individual. 255 00:12:29,245 --> 00:12:31,555 So we need to aim a little bit higher. 256 00:12:32,620 --> 00:12:36,370 Dr Emma Hancox: I guess if they're doing well though, so obviously if they're 257 00:12:36,370 --> 00:12:41,590 at say 17, 18 mgs per litre and the dog's doing well, it's not having many 258 00:12:41,595 --> 00:12:46,780 seizures, then I guess it's fine to leave it there, but it's in those that aren't, 259 00:12:46,840 --> 00:12:48,390 obviously we'd want to try and increase. 260 00:12:48,390 --> 00:12:49,650 Is that what I'm getting from this? 261 00:12:49,940 --> 00:12:52,795 Dr Mark Lowrie: Absolutely we need, so we look at the serum concentration, but when 262 00:12:52,800 --> 00:12:56,705 we come to giving advice on what to do with the medication, we need to consider 263 00:12:56,705 --> 00:12:58,265 what the seizure activity's been doing. 264 00:12:59,015 --> 00:13:02,615 Of course, it depends on the historical baseline seizure activity. 265 00:13:02,615 --> 00:13:06,155 It may be this dog only has had one fit every 12 weeks and we've chosen 266 00:13:06,155 --> 00:13:10,170 to start medication with the owner's guidance, well if you’re measuring two 267 00:13:10,170 --> 00:13:13,620 weeks in and it's sub therapeutic, we've probably not given long enough yet to 268 00:13:13,620 --> 00:13:14,970 know if it's being effective or not 269 00:13:14,970 --> 00:13:16,035 Dr Emma Hancox: Yeah, makes sense. 270 00:13:16,085 --> 00:13:19,155 Dr Mark Lowrie: So in that circumstance, I may not change it, but I'd let an owner 271 00:13:19,205 --> 00:13:23,945 know it is below the level where we know it can be most effective, but let's keep 272 00:13:23,945 --> 00:13:27,335 an eye on it and then we can know that we might need to increase it in time. 273 00:13:28,190 --> 00:13:33,710 Dr Emma Hancox: Yeah, and I think, are you likely to see, so say you've 274 00:13:33,710 --> 00:13:38,459 got a dog that is quite happy at, I dunno, 25 mgs per litre, I'm just 275 00:13:38,459 --> 00:13:39,965 plucking this out of thin ai r. 276 00:13:41,265 --> 00:13:42,645 Is it likely to stay that way? 277 00:13:42,795 --> 00:13:45,945 Why do we need to keep measuring them in the future? 278 00:13:45,975 --> 00:13:48,585 Why, once we're settled on it, can't we just stay on it? 279 00:13:49,085 --> 00:13:52,515 Dr Mark Lowrie: So here's the problem, and I think this is sometimes a mistake that's 280 00:13:52,515 --> 00:13:58,140 made or there's been a misunderstanding with it that, over time you can, you can 281 00:13:58,140 --> 00:14:00,090 get a dog on a nice therapeutic range. 282 00:14:00,090 --> 00:14:03,120 The seizures seem controlled and we're all happy and we send that owner home. 283 00:14:03,690 --> 00:14:08,430 Now that owner needs to understand that things might not stay hunky dory forever. 284 00:14:09,540 --> 00:14:11,010 I think we do need to keep monitoring. 285 00:14:11,010 --> 00:14:14,730 Now, there's a question as to whether we check the serum concentration 286 00:14:14,735 --> 00:14:15,870 every three to six months. 287 00:14:15,870 --> 00:14:19,200 Now that is a perfectly viable, sensible thing to do, and you'll 288 00:14:19,200 --> 00:14:20,070 read about that everywhere. 289 00:14:20,070 --> 00:14:21,220 That's the advice that's given. 290 00:14:21,270 --> 00:14:21,540 Dr Emma Hancox: Yeah. 291 00:14:22,690 --> 00:14:25,140 Dr Mark Lowrie: If owners are bit concerned with cost, or indeed, if 292 00:14:25,140 --> 00:14:28,660 there's difficulty with taking bloods from the dog, say it's a, a very nervous 293 00:14:28,660 --> 00:14:33,110 dog, it's a dog that's hard to, to bleed, then what you may consider doing 294 00:14:33,620 --> 00:14:38,060 is just monitor the dog from a seizure activity perspective and just check 295 00:14:38,060 --> 00:14:39,650 the seizures aren't getting worse. 296 00:14:40,520 --> 00:14:42,440 Now, what will happen with phenobarbital? 297 00:14:42,830 --> 00:14:44,180 I’ve got a way of thinking about this. 298 00:14:44,330 --> 00:14:46,580 This is where my alcoholic tendencies come out. 299 00:14:46,800 --> 00:14:47,510 Dr Emma Hancox: Oh goodness. 300 00:14:47,740 --> 00:14:49,390 He's having a confession now on the podcast. 301 00:14:49,885 --> 00:14:52,510 Dr Mark Lowrie: Well, so, so I like red wine 302 00:14:53,220 --> 00:14:53,810 Dr Emma Hancox: Don't we all? 303 00:14:54,280 --> 00:14:56,140 Dr Mark Lowrie: And so phenobarbital well, this will work well. 304 00:14:56,140 --> 00:14:57,100 I mean, it can be any red wine. 305 00:14:57,100 --> 00:14:59,740 It doesn't matter if it's a merlot or a malbac, it's red wine. 306 00:14:59,800 --> 00:15:00,800 Dr Emma Hancox: you’re talking to the right person. 307 00:15:01,140 --> 00:15:01,450 Dr Mark Lowrie: Good. 308 00:15:01,600 --> 00:15:02,000 Good. 309 00:15:02,530 --> 00:15:06,160 So if we had never drunk red wine before, imagine that. 310 00:15:06,190 --> 00:15:07,590 I mean, the deprived life we'd of had 311 00:15:07,590 --> 00:15:08,040 Dr Emma Hancox: Oh wow. 312 00:15:08,620 --> 00:15:09,940 I, I can't remember that time. 313 00:15:11,110 --> 00:15:13,690 Dr Mark Lowrie: But if we'd never had wine before and we had a small glass of 314 00:15:13,690 --> 00:15:18,085 red wine, It would probably give us a little happy feeling once we've drunk 315 00:15:18,085 --> 00:15:21,825 it and we'd feel that nice, fuzzy, warm feeling that wine does for an alcoholic. 316 00:15:22,386 --> 00:15:25,836 The problem is if you then keep drinking that one small glass of wine every 317 00:15:25,841 --> 00:15:30,246 night, it won't quite have that nice, fuzzy, warm feeling in subsequent nights. 318 00:15:30,516 --> 00:15:32,886 And to achieve that nice fuzzy feeling, you have to drink 319 00:15:32,886 --> 00:15:34,836 that little bit more red wine. 320 00:15:35,113 --> 00:15:35,923 You can see where I'm going. 321 00:15:35,923 --> 00:15:36,613 This is my life. 322 00:15:36,613 --> 00:15:41,473 So night after night, if I want to achieve that same effect, I have to drink more. 323 00:15:42,103 --> 00:15:45,553 Over the period of say, six weeks, I might have gone from being 324 00:15:45,553 --> 00:15:48,703 teetotal to a raving alcoholic. 325 00:15:49,123 --> 00:15:53,473 And that's because I felt, this is on me, that I need more red 326 00:15:53,473 --> 00:15:55,663 wine to achieve the same feeling. 327 00:15:55,693 --> 00:15:57,933 Now, phenobarbital, there is a reason for me... 328 00:15:57,933 --> 00:15:59,198 Dr Emma Hancox: I gonna say, where's this going? 329 00:16:00,193 --> 00:16:01,853 Dr Mark Lowrie: It's suddenly becomes something very different. 330 00:16:02,353 --> 00:16:06,043 Phenobarbital is exactly the same, that if you put a dog on a low dose 331 00:16:06,043 --> 00:16:10,528 of phenobarbital on day one, six to eight weeks later, it is very 332 00:16:10,528 --> 00:16:14,698 possible the serum concentration in that dog has steadily decreased. 333 00:16:15,808 --> 00:16:19,288 That is very normal, and it's because the liver's working harder to get 334 00:16:19,288 --> 00:16:21,268 rid of the medication from the body. 335 00:16:22,108 --> 00:16:26,338 So over time, and it varies with individuals, I can't say this is 336 00:16:26,368 --> 00:16:30,298 necessarily gonna happen over weeks, months, or years, but in a dog in general, 337 00:16:30,508 --> 00:16:34,518 the serum concentration will steadily drop despite keeping the same dose, 338 00:16:34,518 --> 00:16:38,048 So we're putting the same drug in but the dose is decreasing. 339 00:16:38,968 --> 00:16:42,838 So six months into management, if you start to breakthrough seizures 340 00:16:42,838 --> 00:16:46,498 or seizures become worse, the most common reason for that would be that 341 00:16:46,498 --> 00:16:48,568 you’re now at a sub therapeutic range. 342 00:16:48,958 --> 00:16:52,798 So if you recheck the phenobarbital serum concentration, you may find it is 343 00:16:52,798 --> 00:16:54,218 below the level where we want it to be 344 00:16:54,218 --> 00:16:54,673 Dr Emma Hancox: Right, 345 00:16:55,198 --> 00:16:56,938 Dr Mark Lowrie: And you've got scope to increase it. 346 00:16:57,808 --> 00:17:01,708 Even if the dog is on a really high dose of phenobarbital, that's fine. 347 00:17:01,708 --> 00:17:05,518 And I’ve known dogs that have been on nine mgs per kg twice a day. 348 00:17:05,573 --> 00:17:06,473 That's a huge dose. 349 00:17:06,488 --> 00:17:07,628 Dr Emma Hancox: That is a huge dose, yeah. 350 00:17:07,643 --> 00:17:10,493 Dr Mark Lowrie: And it's not a starting dose, but it might be a dose you end 351 00:17:10,493 --> 00:17:14,365 up at in the future, provided the serum concentration allows you to do it. 352 00:17:15,113 --> 00:17:18,923 Dr Emma Hancox: So it sounds like you don't really mind how high the 353 00:17:18,923 --> 00:17:20,813 dose goes that you’re putting in. 354 00:17:21,233 --> 00:17:23,693 It's all about what those serum concentrations and 355 00:17:23,693 --> 00:17:25,433 obviously how the dog is doing. 356 00:17:25,433 --> 00:17:26,033 Is that right? 357 00:17:26,078 --> 00:17:28,238 Dr Mark Lowrie: It's absolutely that and It's such easy maths. 358 00:17:28,358 --> 00:17:33,078 I can't do maths, but if the therapeutic concentration we're achieving is 25 359 00:17:33,078 --> 00:17:36,988 and we're on, say that's what we wanna achieve, level 25 and our therapeutic 360 00:17:36,988 --> 00:17:40,208 concentration says 12, we just double the dose that we're giving the dog and 361 00:17:40,208 --> 00:17:43,913 hopefully that gets up to about 24 or so, which will be a nice place to be. 362 00:17:44,153 --> 00:17:46,243 Dr Emma Hancox: I didn't realise it was quite that simple maths. 363 00:17:46,763 --> 00:17:47,453 Dr Mark Lowrie: Very easy. 364 00:17:47,543 --> 00:17:51,443 Very easy, and if I can do it, then everybody listening to this can because 365 00:17:51,448 --> 00:17:54,773 they can clearly operate a smartphone and load a podcast, which I can't do. 366 00:17:55,793 --> 00:17:57,113 Dr Emma Hancox: So you'll never be able to listen to this. 367 00:17:57,503 --> 00:18:01,763 So it is interesting that you say different dogs or different individuals 368 00:18:01,763 --> 00:18:06,623 will metabolize it differently 'cause then I remember back in practice, 369 00:18:06,703 --> 00:18:10,813 having, being concerned that I had a little Jack Russell dog on the same 370 00:18:10,813 --> 00:18:13,903 dose as a probably fat Labrador. 371 00:18:13,993 --> 00:18:16,543 Um, but that's sounds okay. 372 00:18:16,543 --> 00:18:18,733 It doesn't really matter then I guess. 373 00:18:18,873 --> 00:18:19,623 Dr Mark Lowrie: It doesn't matter. 374 00:18:19,623 --> 00:18:21,433 And I think, it is important in those cases. 375 00:18:21,433 --> 00:18:24,283 We're doing all the other testing, so we're looking at liver function, 376 00:18:24,593 --> 00:18:25,818 we're doing the blood tests there. 377 00:18:26,238 --> 00:18:28,548 Ideally when they're on the high dose, I would be saying every 378 00:18:28,548 --> 00:18:30,968 three months, then we can make sure we're doing the right thing. 379 00:18:31,688 --> 00:18:35,668 But absolutely, that's absolutely fine to do and I'd have no concern about it. 380 00:18:35,963 --> 00:18:36,113 Dr Emma Hancox: Great. 381 00:18:36,953 --> 00:18:41,903 You mentioned that you could look at seizure frequency as a way of monitoring 382 00:18:41,903 --> 00:18:46,523 these patients, if we are recommending these guys come in every three, six months 383 00:18:46,523 --> 00:18:50,543 for blood samples, that can get quite expensive alongside their treatments. 384 00:18:50,543 --> 00:18:54,893 So is there a way to, as it were, do epilepsy on a budget? 385 00:18:55,593 --> 00:18:58,513 Dr Mark Lowrie: Yeah, there, there is a question here of what are 386 00:18:58,513 --> 00:19:00,733 we expecting from the medication? 387 00:19:00,738 --> 00:19:00,878 Dr Emma Hancox: Yeah 388 00:19:01,448 --> 00:19:04,568 Dr Mark Lowrie: And people don't talk about this, and I find when you bring 389 00:19:04,568 --> 00:19:08,288 this up with an owner, they can often be a bit horrified by this, if I'm honest. 390 00:19:08,708 --> 00:19:11,048 Now I'm gonna speak very freely with this and 391 00:19:11,273 --> 00:19:11,723 Dr Emma Hancox: Please do. 392 00:19:11,858 --> 00:19:13,928 Dr Mark Lowrie: Pretend it's not a TVM podcast. 393 00:19:14,318 --> 00:19:17,078 But I think with medication in general, part of the reason these 394 00:19:17,078 --> 00:19:20,348 medications are used is we find that they reduce seizure frequency. 395 00:19:20,348 --> 00:19:23,408 Many of the drug companies have done the testing and they know these drugs can 396 00:19:23,408 --> 00:19:26,018 reduce seizure frequency by at least 50%. 397 00:19:26,918 --> 00:19:29,138 Now what they've done in the trials, and these aren't the drug companies, 398 00:19:29,138 --> 00:19:32,018 these are people like myself who have gone out and tested these medications. 399 00:19:32,358 --> 00:19:35,618 That means that maybe the dog that's had one fit every two 400 00:19:35,618 --> 00:19:37,958 weeks will go onto medication. 401 00:19:38,918 --> 00:19:44,028 And these studies would say that that dog would have one seizure every four weeks 402 00:19:44,388 --> 00:19:46,038 as a result of successful treatment. 403 00:19:46,228 --> 00:19:49,518 Now that isn't necessarily great news for an owner. 404 00:19:49,688 --> 00:19:51,668 A seizure a day is not a good outcome. 405 00:19:52,118 --> 00:19:54,188 But it would be considered successful. 406 00:19:54,188 --> 00:19:56,918 So owners need to know about that with these medications. 407 00:19:56,948 --> 00:19:57,908 That's what we're aiming at. 408 00:19:58,778 --> 00:20:04,538 Now doing things on a budget, phenobarbital is a really inexpensive 409 00:20:04,538 --> 00:20:08,348 medication and I think even with a budget, it's the right first 410 00:20:08,348 --> 00:20:09,998 line medication to be trying. 411 00:20:10,538 --> 00:20:13,568 So blood tests aren't expensive. 412 00:20:14,618 --> 00:20:18,128 If we get a dog that has one or more seizures and the owners haven't got 413 00:20:18,128 --> 00:20:22,653 very much money, I would recommend doing very basic blood tests. 414 00:20:23,133 --> 00:20:26,073 I know we're gonna talk about the blood tests that we would consider doing 415 00:20:26,073 --> 00:20:30,843 in a future podcast with diagnosing epilepsy, but we do those blood tests. 416 00:20:31,113 --> 00:20:34,533 If everything seems normal, it's fine to start phenobarbital at the 417 00:20:34,533 --> 00:20:38,883 standard starting dose of 3 Mgs per kg twice a day and monitor. 418 00:20:39,483 --> 00:20:43,113 Now if that dog's doing all right with its seizure frequency and it's achieved 419 00:20:43,113 --> 00:20:46,473 that 50% or more reduction in seizures, we don't need to do anything more 420 00:20:46,478 --> 00:20:47,703 and we can leave things well alone. 421 00:20:48,543 --> 00:20:51,963 It would be advisable, and we should always advise, checking 422 00:20:52,053 --> 00:20:53,913 bloods every three to six months. 423 00:20:54,693 --> 00:20:57,963 Now they may not be able to afford that and that's fine 'cause you can 424 00:20:57,963 --> 00:20:59,223 say, alright, let's do it annually. 425 00:20:59,613 --> 00:21:02,733 But if you’re gonna do it annually or if you’re not gonna do it at all, 426 00:21:02,733 --> 00:21:06,583 let's be honest, the owner needs to be aware of the risks of that entails. 427 00:21:06,603 --> 00:21:09,873 And so all this discussion we've had about liver disease, we 428 00:21:09,873 --> 00:21:11,283 have to broach that with them. 429 00:21:11,793 --> 00:21:13,233 There is a lot of conversation there, 430 00:21:13,338 --> 00:21:16,758 I'm always trying to empower the owners to make the right decision for them. 431 00:21:17,718 --> 00:21:21,348 And as we talk about this, it's probably becoming more and more obvious. 432 00:21:21,348 --> 00:21:22,398 There isn't a right answer 433 00:21:22,668 --> 00:21:22,998 Dr Emma Hancox: Yeah. 434 00:21:23,328 --> 00:21:23,598 Yeah. 435 00:21:23,698 --> 00:21:26,818 Dr Mark Lowrie: You try and do the right thing for that particular pet 436 00:21:27,598 --> 00:21:30,478 and the right thing takes on board all sorts of different things, including 437 00:21:30,478 --> 00:21:34,198 the owner's financial circumstances, their living arrangements, everything, 438 00:21:34,558 --> 00:21:36,448 even the age of the dog is important. 439 00:21:36,558 --> 00:21:39,968 And these things help us to make the right call, but the right call is 440 00:21:40,028 --> 00:21:41,768 ultimately with the owner, not with us. 441 00:21:41,888 --> 00:21:44,258 Dr Emma Hancox: Yeah, no, that makes a lot of sense. 442 00:21:44,426 --> 00:21:48,116 So we've spoken a lot about phenobarbital and everything makes sense. 443 00:21:48,116 --> 00:21:52,196 Liver monitoring, when to do it, what we're looking for, all of those things. 444 00:21:52,201 --> 00:21:52,796 Makes a lot of sense. 445 00:21:53,186 --> 00:21:56,546 just thinking, obviously it's not the only anti-epileptic drug out there, so 446 00:21:56,771 --> 00:21:57,641 Dr Mark Lowrie: Others are available. 447 00:21:57,641 --> 00:21:59,336 Dr Emma Hancox: Others are available, just so you know. 448 00:21:59,666 --> 00:22:01,736 Do you measure the same things in those? 449 00:22:01,736 --> 00:22:04,856 What, do you measure serum concentration for other drugs? 450 00:22:04,916 --> 00:22:07,466 Like what, what would differ basically? 451 00:22:08,021 --> 00:22:10,046 Dr Mark Lowrie: I think the main drug to bring up when it comes to 452 00:22:10,046 --> 00:22:11,896 serum concentration is bromide. 453 00:22:12,026 --> 00:22:15,291 That is the other medication out there that would require some 454 00:22:15,291 --> 00:22:18,861 kind of monitoring, but there's huge differences with bromide. 455 00:22:19,101 --> 00:22:23,201 First is bromide takes, I want to say it takes forever to reach a steady state. 456 00:22:23,391 --> 00:22:23,961 Dr Emma Hancox: Feels like that 457 00:22:24,351 --> 00:22:26,241 Dr Mark Lowrie: but it's two, two to three months. 458 00:22:26,291 --> 00:22:29,241 But yes, it would feel like that for an owner with a dog with epilepsy, 459 00:22:29,961 --> 00:22:33,381 and you start that medication, waiting three months may not be appropriate. 460 00:22:33,386 --> 00:22:35,271 So there's, it's not great. 461 00:22:35,381 --> 00:22:40,011 But the main reason for bringing it up is when you read the insert on bromide and 462 00:22:40,011 --> 00:22:43,791 you see what they suggest is it actually recommends you check blood levels after 463 00:22:43,791 --> 00:22:46,311 one month and then again at three months. 464 00:22:46,911 --> 00:22:51,291 Now here's another top tip and where big mistakes happen because if we said 465 00:22:51,291 --> 00:22:55,011 it takes three months to reach steady state and we start the dog on a standard 466 00:22:55,016 --> 00:22:59,721 maintenance dose, say 20 mgs per kg once a day or divided twice a day, if 467 00:22:59,721 --> 00:23:04,001 you wish, after a month, we know that serum concentration will still be low. 468 00:23:04,181 --> 00:23:07,781 It'll be higher than at the beginning, but it won't be up to the therapeutic range. 469 00:23:07,781 --> 00:23:12,011 So if we are measuring at one month as the insert recommends we do, we're gonna 470 00:23:12,011 --> 00:23:13,871 have a sub therapeutic concentration. 471 00:23:14,381 --> 00:23:19,061 So very often I’ve seen dogs that then get an increased dose into 472 00:23:19,061 --> 00:23:22,661 the patient at one month, and of course that's the wrong thing to do 473 00:23:22,781 --> 00:23:24,341 because we're heading into toxicity. 474 00:23:25,031 --> 00:23:28,121 I personally don't recommend checking the serum concentration 475 00:23:28,121 --> 00:23:29,681 on bromide until three months. 476 00:23:30,221 --> 00:23:34,771 At three months is fairly reliably at the level it needs to be, and we can 477 00:23:34,811 --> 00:23:36,431 then make decisions based on that. 478 00:23:37,631 --> 00:23:41,556 A brief bit here, if I may, about bromide is it's a great medication 479 00:23:41,556 --> 00:23:43,226 and I think there's a lot of times when it should be used. 480 00:23:44,061 --> 00:23:47,001 Actually, when I can, I try and use it as the second line medication, not 481 00:23:47,001 --> 00:23:51,771 only because it's licensed as an add-in with phenobarbital, but also because 482 00:23:51,776 --> 00:23:53,696 it's a pretty good drug long term. 483 00:23:53,756 --> 00:23:56,986 It's well tolerated and seems to manage seizures well. 484 00:23:57,976 --> 00:24:03,166 But there is that issue of waiting two to three months so you can load bromide. 485 00:24:03,226 --> 00:24:06,436 So loading bromide is a very reasonable thing to do. 486 00:24:07,366 --> 00:24:10,216 The problem with loading any anti-epileptic medication is of 487 00:24:10,216 --> 00:24:13,906 course, it doesn't allow a dog to tolerate or to get tolerant to it, 488 00:24:13,936 --> 00:24:15,346 to the side effects of it quickly. 489 00:24:15,346 --> 00:24:18,346 Yeah, so I’ll go back to the alcohol thing. 490 00:24:18,346 --> 00:24:19,276 if you binge drink 491 00:24:19,506 --> 00:24:19,616 Dr Emma Hancox: Oh no. 492 00:24:19,616 --> 00:24:22,991 Dr Mark Lowrie: three bottles of red wine, you’re gonna be all over the place. 493 00:24:22,996 --> 00:24:26,651 Whereas if you drank it steadily over a longer period of time, I 494 00:24:26,651 --> 00:24:28,931 won't specify the length, but if you drank it steady over a long period of 495 00:24:28,931 --> 00:24:30,251 time, you won't be quite as legless. 496 00:24:30,806 --> 00:24:34,796 With bromide, if you did load up to the loading dose very quickly, over 497 00:24:34,796 --> 00:24:39,536 a short period of time, dogs will become very ataxic, so drunk, they 498 00:24:39,536 --> 00:24:42,866 will be falling all over the place and they take a zombie-like state. 499 00:24:43,046 --> 00:24:43,676 I’ll be honest. 500 00:24:44,306 --> 00:24:45,656 Now, that's okay. 501 00:24:46,016 --> 00:24:47,916 If the dog came in status epilepticus 502 00:24:48,316 --> 00:24:51,806 If dog came in on status epilepticus, it had been managed well with 503 00:24:51,806 --> 00:24:58,091 phenobarbital and was on acceptable serum concentration doses then giving 504 00:24:58,091 --> 00:25:00,761 bromide as a loading dose in that scenario is probably a good thing 505 00:25:00,761 --> 00:25:04,511 because you’re facing such bad seizures that those owners will do anything 506 00:25:04,601 --> 00:25:06,011 to try and get the dog through it. 507 00:25:06,881 --> 00:25:10,331 But if you've got a dog that's having a fit once every eight weeks and you load 508 00:25:10,331 --> 00:25:13,931 them with bromide and they don't even manage to walk out the hospital after 509 00:25:13,931 --> 00:25:17,741 that consultation, then owners clearly are going to have something to say about that. 510 00:25:17,741 --> 00:25:21,761 So there is a time and place to load bromide, but it's more in those much more 511 00:25:21,761 --> 00:25:23,591 severe cases where we're really worried. 512 00:25:24,191 --> 00:25:27,941 You can load it steadily over, say, six weeks. 513 00:25:28,211 --> 00:25:31,661 I can say it here, the loading dose, what I try and do is I give 600 514 00:25:31,991 --> 00:25:34,061 mgs per kg over a period of time. 515 00:25:34,691 --> 00:25:38,531 So traditionally when we're giving an emergency, we do it over, say 516 00:25:38,591 --> 00:25:40,361 anything between three to five days. 517 00:25:40,361 --> 00:25:44,381 So we divide 600 mgs per kg over three to five days and give that to the dog. 518 00:25:44,951 --> 00:25:48,101 But over those three to five days, we also give the maintenance dose 519 00:25:48,281 --> 00:25:50,921 of 20 to 30 mgs per kg once a day. 520 00:25:51,496 --> 00:25:51,816 Dr Emma Hancox: I see. 521 00:25:52,171 --> 00:25:55,141 Dr Mark Lowrie: If you did it over, say two weeks, you would put the 522 00:25:55,141 --> 00:25:59,161 600 mgs per kg over the 14 day period and divide it accordingly. 523 00:25:59,621 --> 00:26:03,301 it's the way that we try and manage it to get these dogs loaded if we need to. 524 00:26:03,631 --> 00:26:06,871 And at the end of loading, we take a blood sample to see where we are with 525 00:26:06,871 --> 00:26:08,701 the serum concentration of bromide. 526 00:26:09,001 --> 00:26:12,601 Dr Emma Hancox: It makes so much sense and I think, I think bromide has a 527 00:26:12,601 --> 00:26:17,801 bit of a bad press, again, a bit like phenobarbital we was saying, but it's 528 00:26:17,801 --> 00:26:19,661 seen a little bit as an old school drug. 529 00:26:19,761 --> 00:26:22,411 in that giving those high doses, those loading doses, 530 00:26:22,831 --> 00:26:24,811 it might not always be needed. 531 00:26:25,081 --> 00:26:28,501 If it does, just knowing that you are gonna have those side effects and how 532 00:26:28,501 --> 00:26:33,901 to manage those and warning the owners and potentially spreading it across. 533 00:26:34,411 --> 00:26:36,121 Dr Mark Lowrie: And so I think some of the reasons it's got bad 534 00:26:36,121 --> 00:26:39,391 press is it's an archaic medication as far as human epilepsy goes. 535 00:26:39,421 --> 00:26:42,578 I believe it was used as an epileptic medication in people, but around the 536 00:26:42,578 --> 00:26:44,408 time that people believed in witches too. 537 00:26:44,678 --> 00:26:48,988 So, It's not, not really something that if you mention to doctors 538 00:26:49,048 --> 00:26:51,208 about bromide, they'll laugh you out the room sort of thing. 539 00:26:51,208 --> 00:26:52,288 You really give that to dogs? 540 00:26:52,378 --> 00:26:55,243 Dr Emma Hancox: I actually did to my sister, who's a GP and she was 541 00:26:55,243 --> 00:26:57,253 what, you still use these drugs? 542 00:26:57,303 --> 00:26:57,753 Yes we do. 543 00:26:57,963 --> 00:27:00,408 So yeah, it is a pretty old school drug and I think that's 544 00:27:00,408 --> 00:27:01,398 got a bad press with it. 545 00:27:01,758 --> 00:27:07,398 And I'm not sure I want to open this can of worms, but is there 546 00:27:07,418 --> 00:27:13,143 a risk of pancreatitis with phenobarbital and bromide together? 547 00:27:13,443 --> 00:27:14,653 Dr Mark Lowrie: Yeah, it's hard this one. 548 00:27:14,793 --> 00:27:17,853 There's definitely an association with it and there's papers out there that support 549 00:27:17,853 --> 00:27:19,833 that and suggest it is a risk factor. 550 00:27:19,833 --> 00:27:22,623 So I think I have to say yes based on the evidence out there. 551 00:27:23,253 --> 00:27:25,473 Having said that, I think you've gotta be very careful that 552 00:27:25,473 --> 00:27:28,233 you’re definitely dealing with pancreatitis and not just vomiting. 553 00:27:28,638 --> 00:27:29,148 Dr Emma Hancox: Yes. 554 00:27:29,223 --> 00:27:33,123 Dr Mark Lowrie: What I mean by that is bromide, I find specifically when 555 00:27:33,123 --> 00:27:37,613 you give it, without giving it a nice big bolus of food, It can irritate 556 00:27:37,883 --> 00:27:39,533 the stomach lining and cause vomiting. 557 00:27:39,893 --> 00:27:44,618 So it's quite a normal thing to have and I know vomiting is a sign of pancreatitis. 558 00:27:44,618 --> 00:27:46,598 So you could see how very quickly you go, this must be 559 00:27:46,598 --> 00:27:48,218 pancreatitis, let's avoid bromide. 560 00:27:48,728 --> 00:27:51,968 Actually, for me, the solution there is put it in a much better bolus of food so 561 00:27:51,968 --> 00:27:53,348 it doesn't irritate the stomach lining. 562 00:27:53,378 --> 00:27:55,658 When it then gets into the gut, it's fine, it's absorbed 563 00:27:55,718 --> 00:27:57,188 and everything's working well. 564 00:27:57,548 --> 00:28:01,838 So the big top tip for bromide when it's when does seem to trigger 565 00:28:01,838 --> 00:28:05,513 vomiting is to give it in a big bowl of food and potentially, if the dose 566 00:28:05,513 --> 00:28:09,323 is big, don't be afraid to divide it twice or even three times in the day. 567 00:28:09,323 --> 00:28:10,553 So smaller amounts are given. 568 00:28:10,788 --> 00:28:13,893 Dr Emma Hancox: Right, that irritates less, I guess, it makes sense. 569 00:28:14,213 --> 00:28:17,873 Dr Mark Lowrie: You did ask about serum concentration with other medications 570 00:28:18,563 --> 00:28:22,763 and all I'd want to say to finish off that discussion is that all the 571 00:28:22,763 --> 00:28:26,273 other medications we have out there, and there's lots of them, which 572 00:28:26,483 --> 00:28:28,193 the vast majority are off license. 573 00:28:28,198 --> 00:28:31,853 So things like levetiracetam, dare I say gabapentin, I don't 574 00:28:31,853 --> 00:28:33,118 like it, but we should mention it. 575 00:28:33,698 --> 00:28:36,608 We don't routinely measure serum concentrations in them. 576 00:28:36,608 --> 00:28:40,178 They've got a fairly standard dose that we give, in both of those circumstances 577 00:28:40,178 --> 00:28:44,418 in fact, they're medications that get into, get up to steady state very quickly. 578 00:28:44,498 --> 00:28:45,668 You can test it. 579 00:28:45,848 --> 00:28:47,758 Dr Emma Hancox: I think I’ve seen the tests available, but 580 00:28:48,703 --> 00:28:50,593 Dr Mark Lowrie: Yeah, so I wouldn't worry about doing it because I 581 00:28:50,593 --> 00:28:52,093 don't think it means a huge amount. 582 00:28:52,143 --> 00:28:55,413 And for me personally, I also think 'cause it's got a short half life, the levels 583 00:28:55,413 --> 00:28:59,313 can fluctuate a bit more freely than maybe they do with other medications. 584 00:28:59,593 --> 00:29:03,583 So phenobarbital, we don't worry about the time of day that we do the serum 585 00:29:03,588 --> 00:29:06,793 concentration testing, the advice there as we try and stick with the 586 00:29:06,793 --> 00:29:09,193 same time of day in the same patient. 587 00:29:09,193 --> 00:29:11,263 So whether that's morning or evening, doesn't matter, 588 00:29:11,263 --> 00:29:12,373 as long as we're consistent. 589 00:29:13,073 --> 00:29:15,658 But levetiracetam, because we're giving it three times a day, I can see there 590 00:29:15,658 --> 00:29:16,978 will be a bit of fluctuation there. 591 00:29:17,488 --> 00:29:20,668 And that value could be wildly different depending on the time of day you do it. 592 00:29:20,833 --> 00:29:23,323 Dr Emma Hancox: So you don't care about phenobarbital peaks and 593 00:29:23,323 --> 00:29:24,853 troughs and all of those things. 594 00:29:24,943 --> 00:29:25,163 Dr Mark Lowrie: No, 595 00:29:25,438 --> 00:29:26,248 no, not at all. 596 00:29:26,248 --> 00:29:28,618 So as long as you’re consistent, it's fine. 597 00:29:28,828 --> 00:29:31,168 So yeah, if you, last time you measured it in the morning, well make sure you 598 00:29:31,168 --> 00:29:33,418 measure it in the morning again the next time around, just so you don't 599 00:29:33,418 --> 00:29:35,218 have too much alteration in that way. 600 00:29:36,343 --> 00:29:36,973 Dr Emma Hancox: That makes sense. 601 00:29:37,753 --> 00:29:41,163 I just wanted to pick up on one of the other drugs if possible. 602 00:29:41,163 --> 00:29:43,438 So I’ve mentioned bromide, levetiracetam, phenobarbital. 603 00:29:44,268 --> 00:29:50,113 Imepitoin, It doesn't have the same effect on the liver, does it, as phenobarbital? 604 00:29:50,183 --> 00:29:54,323 I was under the impression that you didn't necessarily need to monitor the liver 605 00:29:54,323 --> 00:29:56,063 as much as you do for phenobarbital. 606 00:29:56,068 --> 00:29:56,903 Do you need to do it at all? 607 00:29:57,528 --> 00:29:59,618 Dr Mark Lowrie: It's really hard with imepitoin because when it came 608 00:29:59,618 --> 00:30:02,503 out there was limited safety data, just what was done in the trials. 609 00:30:02,533 --> 00:30:06,793 So it hasn't had that wider use yet to know exactly what's happening. 610 00:30:06,793 --> 00:30:09,763 But I think it's fair to say there aren't any major reports of 611 00:30:09,763 --> 00:30:11,233 liver disease, though it happens. 612 00:30:11,263 --> 00:30:15,413 So it definitely causes liver problems like with any chronic drug use, I 613 00:30:15,413 --> 00:30:19,453 would recommend doing blood tests every three to six months just in case. 614 00:30:19,453 --> 00:30:21,788 But that goes with every medication we ever prescribe. 615 00:30:21,953 --> 00:30:24,353 So I wouldn't say you need to be any more or less concerned. 616 00:30:24,353 --> 00:30:27,743 I think just that monitoring level is appropriate with the drug. 617 00:30:28,683 --> 00:30:28,928 Dr Emma Hancox: Yeah. 618 00:30:29,618 --> 00:30:30,038 Brilliant. 619 00:30:30,188 --> 00:30:31,178 No, that all makes sense. 620 00:30:31,208 --> 00:30:31,688 Thank you. 621 00:30:32,218 --> 00:30:32,908 Thank you Mark. 622 00:30:32,908 --> 00:30:36,508 I again, I think that's all we've got time for in this episode, but it has been 623 00:30:36,508 --> 00:30:38,098 really great speaking to you once again. 624 00:30:38,458 --> 00:30:40,738 I’ve personally learned a lot from this episode, so I hope 625 00:30:40,738 --> 00:30:42,238 our listeners have as well. 626 00:30:43,048 --> 00:30:46,048 Please tune in for our next episode where we'll be moving on to the third 627 00:30:46,048 --> 00:30:49,608 instalment of the S.M.A.R.T Approach, which is advise, discussing three 628 00:30:49,608 --> 00:30:51,468 key areas for epilepsy management. 629 00:30:52,008 --> 00:30:54,678 Notice I said epilepsy management there not treatment. 630 00:30:54,768 --> 00:30:56,568 Mark, I'm learning, aren't I? 631 00:30:56,988 --> 00:31:00,138 And just a reminder that this was episode two of the S.M.A.R.T Approach. 632 00:31:00,138 --> 00:31:04,458 So if you haven't already, please take a listen to episode one where we introduce 633 00:31:04,458 --> 00:31:07,578 a S.M.A.R.T Approach and discuss the importance of owner communication. 634 00:31:08,118 --> 00:31:08,838 Thanks again, Mark. 635 00:31:08,838 --> 00:31:09,828 I’ll see you next time. 636 00:31:09,833 --> 00:31:10,923 Dr Mark Lowrie: Thanks very much. 637 00:31:10,923 --> 00:31:11,373 Bye.