Neuro Flashcards
role of the thalamus
Processes and relays sensory information to the varying parts of the brain. Plays a major role in motor systems and signals, as well as regulation of consciousness and alertness.
how pain is transmitted
-When tissue damage occurs, algogenic substances are released due to the damage.
-sensory afferents sense these substances and sends signal to brain so will feel pain.
-brain sends a response out on the motor fibres to react to the pain (e.g. the patient jumps away)
What is an algogenic substance and name examples. which ones have key roles in analgesia
-released in pain which are associated with tissue damage. work on nociceptors to send the message of pain to the brain
-K+, H+, histamine, serotonin, bradykinin, substance P, prostaglandins, leukorienes
-Substance P inhibited by opioids
-Prostoglandins inhibited by NSAIDs
difference between, A beta, A delta and C fibres
A beta = thick myelinated. mechanoreceptors - touch and pressure. Fastest
A delta = short sharp pain. Fast myelinated. Larger. Respond to high intensity mechanical stimuli
C = slow dull ache. Unmyelinated. Respond to pressure, mechanical, thermal and chemical stimuli. Exist in vessels so feel pressure
Explain the pain pathway of the trigeminal nerve. where is the trigeminal ganglion located
- Tissue damage
- Release of algogenic substances
- Signal sent to trigeminal ganglion via A delta and C fibres. Ganglion in Meckel’s cave, a cavity in the dura mater of the brain, near the petrous part of the temporal bone
- A sensory root exits ganglion and into brainstem at the level of the pons
- Thalamus
- The brain interprets signals and sense pain.
a descending motor response is sent out
What is nociception convergence and divergence. which causes referred and radiated pain
-Convergence= causes referred pain. when brain struggles to well where an impulse originally came from.
-Divergence = radiation of pain, afferents synapse several different second order neurones so brain interprets the pain to be from a larger area than the original site of stimulation.
Explain sensitisation, hyperalgesia and allodynia
-Sensitisation is caused by progressive increase in response following continual repeated experience of a stimulus/ tissue damage. Releasing continual algogenic substances causes either:
Hyperalgesia – signal that would normally be painful is interpreted as being much more painful. Peripheral sensitisation
Allodynia – something that would normally not be painful is very painful. Central sensitisation
-It is a protective function but can become chronic pain
what pain can depend on and be affected by
-pain: the nocicetive pathway is fixed but it can be interpreted differently by different people due to psychological and social variables (hormone production, physical conditioning, behavioural responses, avoidance of activity, psychology, environment, culture, emotions)
Multidisciplinary management required for dealing with chronic pain
what do most peripheral acting analgesics target in order to inhibit the nociceptive pathway. Are opioids peripheral or central analgesics
-Algogenic substances, released in response to tissue damage that cause trigger the inflammatory and nociceptive pathway
-central
what do COX 1 and 2 do
-COX1 = stimulate prostoglandins that secrete mucous in the stomach. So inhibition of COX1 causes unwanted ulcers.
-COX2 = stimulate prostaglandins that activate inflammatory cells, so inhibition reduces inflammation, pain, fever, platelets.
-Prostoglandins: lipid compounds made at damaged sites to induce inflammation to deal with injury, raise temperature.
-Arachidonic acid is converted to prostaglandins by COX. Thromboxane (platelet aggregation) and prostacyclin (platelet inhibition) are produced in the pathway too
-made form fatty acid metabolism
NSAIDs action and functions
- analgesics, anti-inflammation, anti platelet, antipyretic.
- irreversibly inhibit COX 2 which inhibits prostaglandin production. nociceptors are less sensitive to the effects of chemical mediators (5-HT, kinins)
-Aspirin: all 4 functions. For mild analgesia.
-Ibuprofen: all 4 except anti-platelet.
First choice in inflammatory joint disease. Less gastric irritation, more effective and better tolerated than other NSAIDs.
-Paracetamol: only analgesic and antipyretic.
Effective in mild analgesia, less so in inflammatory conditions.Overdose causes heptatoxicity
Paracetamol maxmimum daily dose, fatal dose, dose causing acute liver damage. what patients to avoid in
500mg to 1g 4 times daily
max is 4g
10-15g = acute liver damage
25g is fatal
Reduce in patients with pre-existent liver disease (2-3g)
Explain phase 1 and 2 metabolism
-Phase 1= decreases lipid solubility, increases the drug’s activity so may become toxic. [reduction, oxidation, hydrolysis]
-Phase 2= Conjugation. Adds hydrophilic component (eg. glucuronyl group via glucuronidation) to further decrease lipid solubility, more water soluble, and also to make it inactive and not toxic. This conjugate can then be excreted in urine or bile.
Paracetamol: metabolism in overdose, overdose symptoms and treatment
-phase 2 metabolism becomes saturated
-more phase 1 metabolism. Build-up of hepatotoxic NAPBQI
-no immediate symptoms. yellowing of skin,
-Early treatment: (4h) activated charcoal; (12h) with N-acetylcysteine (precursor of glutathione)
* N-acetylcysteine upregulates glutathione, to ‘mop up’ NAPBQ
Aspirin absorption. how it is antiplatlet. and unwanted effects if <16 years old
Rapid absorption via GI
blocks thromboxane A2, which is involved in promoting platelet aggregation.
Reyes syndrome if given in children -affects all organs, mainly increasing intracranial pressure, fat accumulation in liver
Ibuprofen total daily dose
- 1.2g – 2.4g total daily dose
- Adults: 200-400mg orally, 3 times a day
NSAID unwanted effects
-Gastric ulceration (Avoid pts with pre-existent gastric ulcers)
-Non-selective prostaglandin block leads to renal toxicity (avoid in pre-existent renal dysfunction)
-Platelet effects (avoid in other coagulopathies)
-Can induce asthmatic attack (avoid in asthmatics)
-Avoid in 3rd trimester of pregnancy
-Reyes syndrome (Rare childhood disorder, caused by aspirin and infection so do not prescribe aspirin to <16 year olds)
-Extensive protein binding -increased drugs interaction
Opioids mechanism, indications and main uses.
-Agonists on mainly u opioid receptors which are G-protein couples receptors on neurons that regulate pain perception.
-Binding inhibits adenylate cyclase, increasing potassium influx so decreases Ca and causes hyperpolarization which turns off neuronal excitability.
* Causes euphoria and analgesia
* Oral or rectal but usually IV or IM due to unreliable gut absorption and extensive first pass metabolism
-for moderate to severe pain that has major impact on life, terminal illness, severe post-op pain, chronic pain unresponsive to NSAIDs, heart failure pain
Opioid unwanted effects. What is tolerance and dependence
-Drowsiness and sedation
-Respiratory depression, cough suppressive, nausea
-Decrease urinary flow, pinhole pupils
-Constipation (inhibition of smooth muscle in gut) so usually IV than oral
* Tolerance: patient no longer responds to it in the same way so needs a higher concentration to get the same analgesic effect.
* Dependance: sudden withdrawal after chronic treatment causes sweating or tremors for example
effect of alcohol on paracetamol
-Alcohol enhances CYP450 enzyme (more phase 1 into inactive metabolite)
* so decreases drug effectiveness
Interaction of aspirin and warfarin
-It increases risk of bleeding as it is an anti-platelet agent.
-It inhibits COX involved in prostaglandin production so blocks synthesis of prostaglandin and so inhibits platelet-derived thromboxane A2 (used for aggregation) and endothelium-derived prostacyclin (inhibits aggregation)
-Endothelium can make new COX but platelets cannot so net effect of prostacyclin increase which inhibits aggregation.
which antibiotics affect warfarin and to avoid
- penicillins, erythromycin, metranidazole inhibits P450 so inhibits metabolism so enhance anticoagulant activity so increase risk of bleeding.
- Rifampicin induces P450 so decreases its activity
=AVOID
2 NSAID drugs that have the worst CVS risk profile
-Diclofenac & Indomethacin
how to manage opioid addiction, and overdose
-Addiction managed by methaodone - High affinity for µ receptor, Long half life, Reduces withdrawal symptoms
-overdose managed by oxygen and naloxone
Opioid overdose diagnosis and management
-Diagnosis – mioisis (pupil contraction) and bradypnoea (slow breathing)
-Management
ABC 100% high flow oxygen
Naloxone 0.2-0.4 mg IV
Repeat every 2-3 mins (Max 10 mg)
Guided by state of respiration NOT consciousness
Strong and weak opioid drugs
1-Strong:
* Morphine-for severe pain relief, terminal care.
* Pethidine
2-Weak: used for mild to moderate pain.
* Dextroproxyphene
* Dihydrocodeine- cause nausea and constipation
* Codeine
* Tramadol -causes less constipation, dependence, resp depression
* Remifentanyl, alidentanyl
Morphine metabolism, excretion, why decrease dose in kidney disease
-Extensive 1st pass metabolism when taken orally, only 20% reaches systemic circulation
-Hepatic and renal metabolism
-Excreted via kidneys: Pharmacologically active metabolite produced so Decreased dose required for those with renal disease
