#KYJ- Incretin -GLP-1
The Gila Monster is a lizard that packs a nasty bite. It is a rare find in the animal world, this lizard is one of very very few lizards who are venomous. It's saliva harbours a potent neurotoxin similar to that of Coral sea snakes, but unlike snakes, it's venom glands are in the bottom jaw so it must chew its prey to envenomate. Of intense interest to the medical community, this saliva also contains a protein from which the Diabetic drug Exenatide is made.
Marketed under the trade name Byetta, exenatide is classified as a GLP1 mimic.
...
Feel informed yet? No me either. Read on.
We used to believe that you ate food, your blood sugar rose, this stimulated insulin to be released, and the blood sugar dropped. Our concept was that the stimulus for insulin release was sugar..... nope. This simplified cause and effect is not quite correct.
An important stimulant is the act of eating, chewing, smelling or even thinking about yummy food.
Yep.... just thinking about dinner tonight causes insulin secretion.
So this mechanism is fuelled by a protein hormone called glucagon like protein 1 (GLP1, or Incretin).
Incretin is released when eatingsmelling ir thinking about food. As incretin is secreted this has two major effects, it instructs pancreas beta cells to make insulin, and inhibits alpha cells from making glucagon.
It also prepares cells to be sensitive to insulin.
A newer approach to T2DM management is administering drugs that inhibit Incretin degradation (Gliptins) or mimic the effects of natural Incretin - This is where Byetta (Exenatide-manufactured from lizard spit) comes into play. Exenatide is a GLP1 mimic.
Like insulin, Byetta is a subcutaneous injection given daily to weekly. It's not new (2005) just not as popular as the gliptin drugs, but interesting none the less. #ToxSeries #ECT4Health
... bite size chunks of pharmacology education.
Www.ect4health.com.au/whatsWww.ect4health.com.au/whats
Tuesday 21 February 2017
Saturday 18 February 2017
GHB street drug
19 Feb 2017
GHB
Overnight in Melbourne more than 30 people were taken to emergency department suffering effects of GHB intoxication. In this post we refresh what this recreational drug is and look at its effects.
Gamma-hydroxybutyrate, (GHB) is naturally occurring neurotransmitter. It is the precursor to GABA in our brain and has many functions. Principally, it is used as a central nervous system (CNS) depressant .
In the 70s and 80s GHB was synthetically manufactured and used as a pharmaceutical to induce sleep and sedation and to provide peri operative pain relief in painful procedures. It was a complete disaster.
Today, isn't used clinically; it was found, to be ineffective as an analgesic and dangerous. Dosing proved to be unpredictable and with high incidence of seizure, unconsciousness and hyperemesis, you have the perfect storm. Vomiting , seizure and ALOC is a recipe for litigation and coronial inquests.
GHB did not disappear, however, and instead has become popular in the black market. Athletes began taking supplements laced with GHB due to its ability to stimulate human growth hormone, a hormone known to increase muscle mass and reduce body fat.
Where it really gained popularity was the nightclub, rave party and sleazy date rape scene of the 1990s. Like some benzodiazepines and alcohol, GHB was used for its euphoric and sedative effects. Dangerously synergistic with these drugs, it is also commonly combined with Meth (Ice) or its cousin MDMA (Ecstasy) to prolong and enhance the effects of both.
Due to its tasteless, odourless and potent property to produce unconsciousness and disinhibition, the sinister use of GHB slipped into drinks facilitated its use as a date rape drug.
GHB is unpredictable. Profound unconsciousness with fitting and vomiting , is a massive airway risk, and when paramedics arrived to more than 30 people all affected, it must have stretched resources of the prehospital crews and the local EDs.
From ingestion to symptom onset is between 15 and 20 minutes. Effects last 1 to 6 hours. When used along with other intoxicating substances, such as alcohol and methamphetamine, the effects are unpredictable and longer lived. This makes recreational doses difficult to gauge. In its cleanest and pure state, safe doses between 1-2 grams, produce serum concentrations between 80 and 100mg/L.
On the street there is no way for users to tell what dose they are getting when they get GHB illegally.
Common signs of GHB use and intoxication include:
Relaxation / drowsiness
Euphoria, high
Lowered inhibitions
Dizziness/ ataxic /uncoordinated
Confusion loss of time line
Memory loss / amnesia
Nausea vomiting
Slurred speech.
Hallucinations.
When daily users of GHB are stopped abruptly. Discontinuation or withdrawal symptoms can begin in 12- 24 hours and last as long as 3 weeks. They mimic alcohol or antidepressant withdrawal syndromes. Common signs of GHB withdrawal include:
Fever
Extreme fatigue.
Anxiety / mood swings
Paranoia, hallucination (like Delirium tremens)
Insomnia and vivid dreams
Tremors
Confusion, irritation, aggitation.
In OD the margin separating a tolerable amount of drug and a potentially fatal dose is very low. Accidental overdose is very common.
Expect
Vomiting with unconsciousness
Loss of a gag reflex.
Seizures
Double incontinence
Shaking, tremors,
Sternal rubs (not that they are acceptable) are less effective because GHB causes absence of pain response, even in conscious patients).
Nystagmus (rapid side-to-side eye movements)
Bradypnoea
Profuse sweating but hypothermic (T>35)
Treatment of OD
What kills these patients is airway and breathing compromise. A secondary issue is electrolyte imbalance.
Priority is ABCD.
Airway secured, vent if needed.
Antiemetics, NG tube.
Fluids and watch gases and electrolytes
Supportive care.
#ECT4Health
Hope you enjoyed the timely read on GHB.
GHB
Overnight in Melbourne more than 30 people were taken to emergency department suffering effects of GHB intoxication. In this post we refresh what this recreational drug is and look at its effects.
Gamma-hydroxybutyrate, (GHB) is naturally occurring neurotransmitter. It is the precursor to GABA in our brain and has many functions. Principally, it is used as a central nervous system (CNS) depressant .
In the 70s and 80s GHB was synthetically manufactured and used as a pharmaceutical to induce sleep and sedation and to provide peri operative pain relief in painful procedures. It was a complete disaster.
Today, isn't used clinically; it was found, to be ineffective as an analgesic and dangerous. Dosing proved to be unpredictable and with high incidence of seizure, unconsciousness and hyperemesis, you have the perfect storm. Vomiting , seizure and ALOC is a recipe for litigation and coronial inquests.
GHB did not disappear, however, and instead has become popular in the black market. Athletes began taking supplements laced with GHB due to its ability to stimulate human growth hormone, a hormone known to increase muscle mass and reduce body fat.
Where it really gained popularity was the nightclub, rave party and sleazy date rape scene of the 1990s. Like some benzodiazepines and alcohol, GHB was used for its euphoric and sedative effects. Dangerously synergistic with these drugs, it is also commonly combined with Meth (Ice) or its cousin MDMA (Ecstasy) to prolong and enhance the effects of both.
Due to its tasteless, odourless and potent property to produce unconsciousness and disinhibition, the sinister use of GHB slipped into drinks facilitated its use as a date rape drug.
GHB is unpredictable. Profound unconsciousness with fitting and vomiting , is a massive airway risk, and when paramedics arrived to more than 30 people all affected, it must have stretched resources of the prehospital crews and the local EDs.
From ingestion to symptom onset is between 15 and 20 minutes. Effects last 1 to 6 hours. When used along with other intoxicating substances, such as alcohol and methamphetamine, the effects are unpredictable and longer lived. This makes recreational doses difficult to gauge. In its cleanest and pure state, safe doses between 1-2 grams, produce serum concentrations between 80 and 100mg/L.
On the street there is no way for users to tell what dose they are getting when they get GHB illegally.
Common signs of GHB use and intoxication include:
Relaxation / drowsiness
Euphoria, high
Lowered inhibitions
Dizziness/ ataxic /uncoordinated
Confusion loss of time line
Memory loss / amnesia
Nausea vomiting
Slurred speech.
Hallucinations.
When daily users of GHB are stopped abruptly. Discontinuation or withdrawal symptoms can begin in 12- 24 hours and last as long as 3 weeks. They mimic alcohol or antidepressant withdrawal syndromes. Common signs of GHB withdrawal include:
Fever
Extreme fatigue.
Anxiety / mood swings
Paranoia, hallucination (like Delirium tremens)
Insomnia and vivid dreams
Tremors
Confusion, irritation, aggitation.
In OD the margin separating a tolerable amount of drug and a potentially fatal dose is very low. Accidental overdose is very common.
Expect
Vomiting with unconsciousness
Loss of a gag reflex.
Seizures
Double incontinence
Shaking, tremors,
Sternal rubs (not that they are acceptable) are less effective because GHB causes absence of pain response, even in conscious patients).
Nystagmus (rapid side-to-side eye movements)
Bradypnoea
Profuse sweating but hypothermic (T>35)
Treatment of OD
What kills these patients is airway and breathing compromise. A secondary issue is electrolyte imbalance.
Priority is ABCD.
Airway secured, vent if needed.
Antiemetics, NG tube.
Fluids and watch gases and electrolytes
Supportive care.
#ECT4Health
Hope you enjoyed the timely read on GHB.
Friday 17 February 2017
Seizure versus convulsion
#KYJ. Seizure vs convulsion
Seizure - that is the chaotic electrical discharge . It is in the brain. It is a cerebral event.
Convulsion - that is the motor movement, the shaking/ thrashing , Tonic/clonic jerking, commonly called fitting.
Convulsions are often violent movements of big muscle groups caused by the seizure ( they are not one in the same )
Seizures may not manifest in convulsions. Some experience an absence of alertness or sensory perceptive phenomena like déjà vu, that sense that you've seen or heard the scene before.
Some seizures also manifest in a sensory perceptive phenomena like déjà vu, that sense that you've seen or heard the scene before.
...
No ... my bad!
...
The phenomena called Jamais vu explained as when a person momentarily does not recognize a word, person, or place that they already know. Is commonly seen in epilepsy a major cause of seizures.
Even day dreaming has been described as a form of seizure activity.
So when a convulsion is the manifestation of seizure activity it becomes a safety issue - especially during the often violent Tonic (muscle tensing) clonic (muscle jerking) phases. Head trauma, falls and contacting sharp furniture edges during convulsions is a real risk.
If it should be taken to provide some sort of protection particularly from banging heads on solid firm services like the floor.
Contrary to popular believe airway management is not necessary during a convulsion but the moment that the convulsion stops and the characteristic jerking ceases, Standard protocol is that the patient should be safely rolled onto this site and airway maintained.
Final note: The term status epilepticus is defined as a convulsion that lasts for more than five minutes or more than one convulsion inside five minutes. Status epilepticus is defined by convulsion activity and can exist in patients in the absence of a diagnosis of epilepsy. One of the commonest manifestations of status epilepticus is drug overdose.
Drug therapy of choice if convulsions last longer than five minutes is the Deslan often given intravenously up to 5 mg
Oh
Did I mention the déjà vu.
...
#ECT4Health knowing your jargon blogs.
Find them all on
Www.knowingyourjargon.blogspot.com
Or our Facebook page
Www.facebook.com/ECT4Health
Seizure - that is the chaotic electrical discharge . It is in the brain. It is a cerebral event.
Convulsion - that is the motor movement, the shaking/ thrashing , Tonic/clonic jerking, commonly called fitting.
Convulsions are often violent movements of big muscle groups caused by the seizure ( they are not one in the same )
Seizures may not manifest in convulsions. Some experience an absence of alertness or sensory perceptive phenomena like déjà vu, that sense that you've seen or heard the scene before.
Some seizures also manifest in a sensory perceptive phenomena like déjà vu, that sense that you've seen or heard the scene before.
...
No ... my bad!
...
The phenomena called Jamais vu explained as when a person momentarily does not recognize a word, person, or place that they already know. Is commonly seen in epilepsy a major cause of seizures.
Even day dreaming has been described as a form of seizure activity.
So when a convulsion is the manifestation of seizure activity it becomes a safety issue - especially during the often violent Tonic (muscle tensing) clonic (muscle jerking) phases. Head trauma, falls and contacting sharp furniture edges during convulsions is a real risk.
If it should be taken to provide some sort of protection particularly from banging heads on solid firm services like the floor.
Contrary to popular believe airway management is not necessary during a convulsion but the moment that the convulsion stops and the characteristic jerking ceases, Standard protocol is that the patient should be safely rolled onto this site and airway maintained.
Final note: The term status epilepticus is defined as a convulsion that lasts for more than five minutes or more than one convulsion inside five minutes. Status epilepticus is defined by convulsion activity and can exist in patients in the absence of a diagnosis of epilepsy. One of the commonest manifestations of status epilepticus is drug overdose.
Drug therapy of choice if convulsions last longer than five minutes is the Deslan often given intravenously up to 5 mg
Oh
Did I mention the déjà vu.
...
#ECT4Health knowing your jargon blogs.
Find them all on
Www.knowingyourjargon.blogspot.com
Or our Facebook page
Www.facebook.com/ECT4Health
Tuesday 14 February 2017
Corticosteroids and blood glucose
#KYJ - Corticosteroids & why Blood Glucose goes crazy.
In this episode of knowing your jargon (#KYJ), we look at why steroids muck with blood sugar levels.
At a recent #RustyPills conference I was asked "why is it that when my patients take prednisone (steroids) their blood glucose goes out of control ;particularly diabetics?"
It is a great question and has a fairly straightforward answer.
Let's start with the main hormone in your body that regulates blood sugar. Insulin : secreted from your beta cells in the pancreas reduces blood sugar levels by allowing the channels in cell membranes open so glucose can flush into the cell, where it is used to produce energy. You learned about this energy back in first year; it's called ATP. Insulin function is dependent on many factors, and the ability for insulin to facilitate glucose transport into cells, is adversely affected by hormones that are secreted from the adrenal gland. Particularly cortisol, but the other hormones that we often associate with sex characteristics also play a role . In pregnancy, many of the circulating hormones that support a healthy pregnancy also produce a similar effect to an abundance of cortisol. This affect produces an insulin resistance in cells, meaning that when a patient secretes insulin, their own insulin is not as effective because, under the influence of higher circulating hormone levels, including cortisol, cells become insulin resistant. This causes a reduction in the ability to shift sugar (glucose) from the blood into the cell. Its accumulation therefore, results in hyperglycaemia.
Now let's give the patient a drug that mimics cortisol. Often used as anti-inflammatories, drugs like hydrocortisone, dexamethasone prednisone, prednisolone and many of the inhaled corticosteroids that asthmatics and COPD patient use; all these drugs are analogues of naturally occurring cortisol. Thus, insulin resistance and high BSL is common as a side effect of steroid drugs.
This complicates BSL control when somebody has blood sugar level issues, such as diabetics.
One last issue to consider -
A side question might be : if our body secretes cortisol what's its purpose? Well in short, it regulates inflammation, reducing the inflammatory process when secreted. In stress, along with adrenaline which stimulates fat cells to convert fat to glucose, cortisol is abundantly secreted, giving rise to poor BSL control in diabetics at times of stress or infection.
Remember steroids make you insulin resistant, so you secrete more insulin to try and compensate. This causes hunger, and over eating at times of stress.
I think I need chocolate!
In this episode of knowing your jargon (#KYJ), we look at why steroids muck with blood sugar levels.
At a recent #RustyPills conference I was asked "why is it that when my patients take prednisone (steroids) their blood glucose goes out of control ;particularly diabetics?"
It is a great question and has a fairly straightforward answer.
Let's start with the main hormone in your body that regulates blood sugar. Insulin : secreted from your beta cells in the pancreas reduces blood sugar levels by allowing the channels in cell membranes open so glucose can flush into the cell, where it is used to produce energy. You learned about this energy back in first year; it's called ATP. Insulin function is dependent on many factors, and the ability for insulin to facilitate glucose transport into cells, is adversely affected by hormones that are secreted from the adrenal gland. Particularly cortisol, but the other hormones that we often associate with sex characteristics also play a role . In pregnancy, many of the circulating hormones that support a healthy pregnancy also produce a similar effect to an abundance of cortisol. This affect produces an insulin resistance in cells, meaning that when a patient secretes insulin, their own insulin is not as effective because, under the influence of higher circulating hormone levels, including cortisol, cells become insulin resistant. This causes a reduction in the ability to shift sugar (glucose) from the blood into the cell. Its accumulation therefore, results in hyperglycaemia.
Now let's give the patient a drug that mimics cortisol. Often used as anti-inflammatories, drugs like hydrocortisone, dexamethasone prednisone, prednisolone and many of the inhaled corticosteroids that asthmatics and COPD patient use; all these drugs are analogues of naturally occurring cortisol. Thus, insulin resistance and high BSL is common as a side effect of steroid drugs.
This complicates BSL control when somebody has blood sugar level issues, such as diabetics.
One last issue to consider -
A side question might be : if our body secretes cortisol what's its purpose? Well in short, it regulates inflammation, reducing the inflammatory process when secreted. In stress, along with adrenaline which stimulates fat cells to convert fat to glucose, cortisol is abundantly secreted, giving rise to poor BSL control in diabetics at times of stress or infection.
Remember steroids make you insulin resistant, so you secrete more insulin to try and compensate. This causes hunger, and over eating at times of stress.
I think I need chocolate!
Tuesday 7 February 2017
Hypodermoclysis - subcutaneous rehydration
#KYJ- Hypodermoclysis
Do you have much experience with this procedure? Let's break it down.
Hypo = below
Dermo =skin
Clysis = to flood or inundate with fluid.
Hypodermoclysis is commonly called Subcutaneous rehydration.
It is a simple procedure that requires the insertion of a cannula (usually a butterfly) into the subcutaneous space, then infusion of an isotonic fluid eg normal saline or Hartmann's.
It was developed for use to rehydrate vomiting children, but has been used in all ages so successfully that it is a common rehydration strategy in debilitated elderly.
As an alternative to IV the other rock star is Intraosseous (IO) infusion; so why would you use Hypodermoclysis over IO?
It's all about speed. If fluid resuscitation is urgent then IO is your alternative to IV; but in the stable mild-moderately dehydrated patient, too nauseated to keep down oral fluids, subcutaneous infusion at 20ml/kg over an hour is a fair approach.
In children Insert 25 Butterfly into subcutaneous tissue between the shoulder blades. In adults, the abdomen is a good site.
There is no hard and fast rule but the age old saying , "pinch up an inch" suggests that anywhere you can pinch up an inch of tissue, AND secure the butterfly safely, is fair game.
Don't go bigger than 25g. The sc tissue absorbs fluid at a rate that is constant, so a bigger gauge cannula won't achieve anything- it doesn't hydrate them faster and just causes swelling to increase discomfort.
Premed ?
Topical anaesthetic creams like EMLA or Angel cream are kind and effective.
Some clinicians use a premed of Hyaluronidase 150units S/C.
This temporarily dissolves (painlessly) the connective tissue glue membrane (Hyaluronic acid) that bonds skin to fat. It accelerates fluid absorption up to 5 times faster. Consider it.
What to expect.
Inflammation is expected, so some swelling and pinkish penumbra around the injection site are normal. It shouldn't be hot to the touch, or itchy or painful, so if these latter symptoms are present, then consider resiting.
Rate- 20ml/kg over an hour is well tolerated and once rehydrated , and nausea/vomiting eases, reattempt oral rehydration.
Secure with occlusive film dressing and leave it in up to 24 hours if needed.
Do you have much experience with this procedure? Let's break it down.
Hypo = below
Dermo =skin
Clysis = to flood or inundate with fluid.
Hypodermoclysis is commonly called Subcutaneous rehydration.
It is a simple procedure that requires the insertion of a cannula (usually a butterfly) into the subcutaneous space, then infusion of an isotonic fluid eg normal saline or Hartmann's.
It was developed for use to rehydrate vomiting children, but has been used in all ages so successfully that it is a common rehydration strategy in debilitated elderly.
As an alternative to IV the other rock star is Intraosseous (IO) infusion; so why would you use Hypodermoclysis over IO?
It's all about speed. If fluid resuscitation is urgent then IO is your alternative to IV; but in the stable mild-moderately dehydrated patient, too nauseated to keep down oral fluids, subcutaneous infusion at 20ml/kg over an hour is a fair approach.
In children Insert 25 Butterfly into subcutaneous tissue between the shoulder blades. In adults, the abdomen is a good site.
There is no hard and fast rule but the age old saying , "pinch up an inch" suggests that anywhere you can pinch up an inch of tissue, AND secure the butterfly safely, is fair game.
Don't go bigger than 25g. The sc tissue absorbs fluid at a rate that is constant, so a bigger gauge cannula won't achieve anything- it doesn't hydrate them faster and just causes swelling to increase discomfort.
Premed ?
Topical anaesthetic creams like EMLA or Angel cream are kind and effective.
Some clinicians use a premed of Hyaluronidase 150units S/C.
This temporarily dissolves (painlessly) the connective tissue glue membrane (Hyaluronic acid) that bonds skin to fat. It accelerates fluid absorption up to 5 times faster. Consider it.
What to expect.
Inflammation is expected, so some swelling and pinkish penumbra around the injection site are normal. It shouldn't be hot to the touch, or itchy or painful, so if these latter symptoms are present, then consider resiting.
Rate- 20ml/kg over an hour is well tolerated and once rehydrated , and nausea/vomiting eases, reattempt oral rehydration.
Secure with occlusive film dressing and leave it in up to 24 hours if needed.
Subscribe to:
Posts (Atom)