Full transcript
0:02hello in this video we're gonna talk
0:05about nonsteroidal anti-inflammatory
0:06drugs also known as NSAIDs this is a
0:09pharmacology video now NSAIDs are very
0:13common drugs used by the public it is
0:16used specifically for pain so in order
0:20to understand its mechanism of action we
0:23need to revise some basic neurology
0:25specifically the pain pathway so here we
0:28have a section of the cortex where
0:32sensation is perceived called the
0:35somatic sensory cortex and again this is
0:37a section of the brain where sensation
0:39is perceived so when you feel pressure
0:42against your skin or when you feel pain
0:44on your arm
0:44those sensation are felt in this part of
0:48the brain and so the somatosensory
0:50cortex can be further divided into areas
0:53representing different parts of your
0:55body your limbs so we'll talk about that
0:59later on now the brain connects to the
1:02brainstem which is made up of three
1:03important parts these are the midbrain
1:05the pons and the medulla these are only
1:08sections of the main of those parts of
1:11the brainstem the brainstem continues on
1:14and forms the spinal cord here I'm only
1:17drawing one section of the spinal cord
1:19the spinal cord have nerves coming in
1:22and out of it are represented here in
1:24yellow
1:28here is the right side and left side of
1:31the spinal cord because remember we are
1:33looking at this from the front so
1:37neurons travel into the spinal cord
1:40through from the back from the dorsal
1:43part of the spinal cord here in yellow
1:46is a first order neuron this first order
1:50neuron is a sensory neuron which brings
1:53in information of or or action potential
1:58of a pain temperature pressure etc the
2:01sensory neurons have many receptors on
2:04their dendrites let's say for example
2:08this first-order neuron is innervating a
2:11tissue of our skin let's just say it's
2:13the right hand our right hand now
2:18imagine there is a cut or damage to that
2:21area of tissue the right hand immune
2:23cells within the area will get activated
2:26and further recruit more immune cells
2:29mounting an inflammatory response here
2:33you have immune cells such as
2:34neutrophils macrophages and mast cells
2:38all these cells as well as the damaged
2:41skin cells will release inflammatory
2:43mediators these are things such as
2:46prostaglandins bradykinin ATP hydrogen
2:51ions as well as serotonin and histamine
2:53and there are many many more all these
2:56mediators will stimulate receptors on
2:59these sensory nerve fibers
3:02prostaglandins for example will bind on
3:05to what's called post annoyed receptors
3:07causing a depolarization of the neuron
3:11thus stimulating essentially this
3:14first-order neuron bradykinin will bind
3:18on to what's called a b2 receptor
3:20causing a depolarization as well and
3:24thus again stimulating this neuron
3:26stimulating the first order neuron and
3:29the other mediators will also somehow
3:32stimulate the first order neuron through
3:34other mechanisms and other receptors
3:36what's fascinating is that when this
3:39first order neuron is stimulated it will
3:41further promote an an inflammatory
3:44response by releasing other chemicals
3:46such as substance P and C GRP thus this
3:52inflammatory process is amplified
4:00because there are many inflammatory
4:01mediators being produced it's important
4:03to remember one of them here which
4:06actually plays one of them one of the
4:08main roles in this pain pathway the one
4:11I'm talking about is prostaglandins
4:13specifically prostaglandin e2 and f2
4:18prostaglandin e2 causes depolarization
4:21and of course will thus cause an action
4:24potential this action potential will
4:27travel all the way to the end to the
4:31back or the dorsal Horn of the spinal
4:33cord at the dorsal Horn of the spinal
4:35cord the first order neuron will synapse
4:38and relay the stimuli to a second neuron
4:43the second order neuron will cross over
4:47to the other side from the right to the
4:50left and will enter what's called the
4:53spinothalamic tract and you have two
4:55spinothalamic tract the anterior and the
4:58lateral spinothalamic tract the second
5:01order neuron will travel up towards the
5:05brain past the brainstem and terminate
5:08at the thalamus the thalamus is a relay
5:12station in the brain in the thalamus the
5:15second order neuron will synapse with a
5:17third neuron called the third order
5:19neuron the third order neuron which is
5:22now stimulated will carry this action
5:26potential stimuli to the somatosensory
5:29cortex and the third order neuron will
5:32actually discern which area of the body
5:36that information originated from so here
5:40it will be the hand and so here the
5:43somatosensory area for the right hand of
5:45the perception of pain is felt
5:49interesting point about sensation
5:51whatever we feel on the right it's
5:54processed on the left side of the brain
5:56and vice versa so let's go to the very
6:00beginning where the pain pathway started
6:03now because prostaglandins are very
6:06important players important mediators of
6:08inflammation and thus pain let us see
6:11how it is made
6:13periods of trauma or injury many cells
6:17around the area in this case immune
6:19cells and damaged skin cells will
6:20convert their phospholipids their cell
6:23membrane into arachidonic acid
6:25arachidonic acid or double a can be
6:29converted to prostaglandin h2
6:32prostaglandin h2 then becomes
6:35prostaglandin e2 and prostaglandin f2
6:38these prostaglandins are the ones that
6:40that initiate or cause fever enhance
6:44pain and inflammation the enzymes
6:47responsible for the production of these
6:50are cyclooxygenase one coxswain and
6:54cyclooxygenase two [ __ ] - interestingly
6:58cox-1 and cox-2 despite being of the
7:03same name really are very different
7:05you see coxswain is always active to
7:09maintain homeostasis in our body it's a
7:13good guy cox-2 is the one active during
7:16injury stress and trauma for example
7:20let's take a look at platelets when we
7:23cut ourselves we need to stop bleeding
7:25platelets help with this what happens
7:28here is that cox-1 converts arachidonic
7:31acid to prostaglandin h2 prostaglandin
7:34h2 as we have just learned earlier can
7:37then be converted to prostaglandin e2
7:39and f2 however in platelets something
7:43different happens prostaglandin h2 is
7:46actually converted to thromboxane a2 the
7:49remarks in a2 is a chemical causing
7:51platelet aggregation to help stop
7:53bleeding
7:55NSAIDs work by blocking the Cox enzyme
7:59they can be broadly divided into
8:01nonspecific also known as non-selective
8:04NSAIDs where they block both
8:06cox-1 and cox-2 and these drugs include
8:10aspirin ibuprofen and naproxen or it can
8:15be divided into specific also known as
8:17selective NSAIDs which block
8:20specifically cox-2 enzyme this is Cox
8:25herbs such as silicon soup for example
8:29nonsteroidal anti-inflammatory drugs
8:31such as your comment ibuprofen are
8:35non-selective and so they block both
8:37cox-1 and cox-2 thus they are actually
8:42antipyretic analgesic and
8:45anti-inflammatory side effects of these
8:49drugs mean that they are anticoagulants
8:51so you can bleed easily you can also be
8:55partially allergic getting a skin rash
8:57and also NSAIDs can induce bronchospasm
9:01because some prostaglandins have a role
9:04in bronchodilation many people take
9:10aspirin aspirin is unique because they
9:12really mainly work by inhibiting cox in
9:15platelets thus preventing information of
9:18thromboxane a2 from boxin a to normally
9:21causes platelets to clump together a
9:25process known as platelet aggregation
9:28thus aspirin thins the blood so you can
9:32say it reduces clotting unfortunately
9:35cops 1 as mentioned earlier is normally
9:38active and maintains homeostasis of the
9:41body particularly in the stomach and in
9:43the kidneys and so inhibiting cox-1 can
9:47have some bad effects on these organs in
9:50the stomach for example cox one converts
9:53our arachidonic acid to prostaglandin h2
9:56which then forms prostaglandin e2 and
10:00prostaglandin i to these prostaglandins
10:03actually help decrease acid production
10:07in the stomach and so by inhibiting cox
10:10one here you are essentially allowing
10:12more acid to be produced in the stomach
10:14so side effects include dyspepsia nausea
10:18and vomiting gastric ulcers and
10:20hemorrhage are potential long-term hide
10:23those consequences in the kidney
10:26coxswain normally converts arachidonic
10:30acid to prostaglandin h2 which then
10:33makes prostaglandin e2 and prostaglandin
10:35i 2 in the kidney these prostaglandins
10:39help maintain renal blood flow
10:41therefore NSAIDs can actually just cause
10:44nephritis and kidney injury NSAIDs are
10:48also one of three drugs which make up
10:51what's called the triple whammy triple
10:54whammy is a combination of three drugs
10:55you do not want to be on especially if
10:58you have some kidney problem these three
11:01Dougs drugs are diuretics NSAIDs and ACE
11:05inhibitors or angiotensin receptor
11:07blockers so we just talked about non
11:12selective or non specific NSAIDs now
11:15let's focus on selective or specific
11:18NSAIDs now selective NSAIDs were created
11:21to reduce the side-effects of non
11:23selective ones another very common drug
11:26is paracetamol where you can know it as
11:28panadol it's thought to elicit its
11:31mechanism of action in a similar way
11:33however it is unclear actually how it
11:36works but potentially it inhibits an
11:39isoform of the Cox enzyme it is a potent
11:43analgesic and antipyretic but has no
11:47anti-inflammatory role important to note
11:51that high doses of paracetamol can lead
11:54to liver toxicity I hope you enjoyed
11:58this video on the pharmacology of
12:00non-steroidal anti-inflammatory drugs
12:02thank you for watching if you want to
12:04know more about the pain pathway click
12:06on the link