Theme 5 - Pain and inflammation Flashcards
What is the main mechanism of action of NSAIDs?
Inhibition of prostaglandin synthesis
How do NSAIDs inhibit prostaglandin synthesis?
Act mainly peripherally by inhibiting COX1 & COX2 – enzymes
What does NSAIDs stand for?
NON-STEROIDAL ANTI-INFLAMMATORY DRUGS
Name clinical uses of aspirin-like drugs
Anti-inflammatory, Analgesic (pain relief), Antipyretic (lowers fever)
What is the effect of aspirin on bleeding time?
Increased bleeding time
Which Gastrointestinal effects does aspirin have?
epigastric discomfort, nausea and vomiting, gastric ulcerations and bleeding
What effect does aspirin have on Urate excretion?
usual dose: decreases urate exretion
high dose: uricosuric effect
What effect does long-term use of aspirin have on the cardiovascular system?
The haematocrit is lowered and the cardiac output as well as work rate of the heart increased
What effect does aspirin have on the cardiovascular system of patients with carditis?
cardiac failure and pulmonary oedema
What can cause a sever reaction to aspirin?
Aspirin hypersensitivity
What happens indirectly to the respiratory system after an aspirin overdose?
induces the decoupling of oxidative phosphorylation in the skeletal muscles with a resulting increase in CO2-production that stimulates the respiratory centre which leads to hyperventilation
What happens directly to the respiratory system after an aspirin overdose?
direct stimulating effect on the respiratory center in medulla oblongata. This is a more potent stimulus than the indirect mechanism
What happens to the cardiovascular system after an aspirin overdose?
It is only after excessively high doses that the salicylates suppress the vasomotoric center resulting in circulatory collapse.
What happens to the acid-base status and water-electrolyte balance after an aspirin overdose?
respiratory alkalosis that will metabolically be compensated, severe: metabolic acidosis as well as a respiratory acidosis
What happens to the CNS after an aspirin overdose?
convulsions followed by generalised CNS suppression, increase in temperature metabolic rate
Which toxic effects develop during paracetamol overdose?
Fatal hepatic necrosis
Renal tubular necrosis
Where is aspirin absorbed?
Mainly upper GIT, partially in stomach
Where is aspirin hydrolysed?
GIT mucosa , liver, blood
What hydrolyses aspirin in GIT mucosa and blood?
esterases
What is the nature of the hydrolysis of aspirin in the liver?
Vert fast, only present in plasma for short period of time
What happens to aspirin after hydrolysis?
it becomes deacetylated
What is the effect of the fast hydrolysis of aspirin in the blood?
A large portion of the pharmacological effects of aspirin must therefore be attributed to the mode of action of the deacetylated salicylate
What does aspirin bind to in the plasma?
Plasma proteins (albumin)
What does aspirin compete with for binding to proteins?
bilirubin or oral hypoglycemic drugs
What is the effect of the competition for protein binding (aspirin)
This may give rise to undesirable and potentially dangerous interactions
At body-pH is aspirin mostly ionised/unionised?
ionised
What effect does the ionised property have on aspirin?
It cannot cross BBB
Does the biotransformation of aspirin usually follow first-order or zero-order kinetics?
first-order
When does aspirin follow zero-order kinetics?
In higher dosages when the liver’s biotransformation capacity is saturated
What is the main excretory route of aspirin?
Kidneys
What happens to aspirin when urine is at a low pH?
A large portion of the free aspirin is in the unionised form and back diffusion from the glomerular filtrate takes place readily
What happens to aspirin when urine is at a high pH?
Up to 80% of the ingested drug can be excreted as free salicylate
What is the treatment of paracetamol poisoning?
- Prevent further GIT absorption (induce vomiting or perform a gastric lavage).
- Take blood for a plasma level determination of paracetamol. Follow-up determinations are recommended.
- Administer an “antidote”, if the patient presents within 12 hours after ingestion: methionine or N-acetyl cysteine.
- Provide supportive treatment.
- Treat liver failure.
What is the treatment of aspirin poisoning?
activated charcoal, urine alkalinisation, haemodialysis
List the central effects of morphine
- Analgesia
- Euphoria/dysphoria
- Sedation/sleep
- Suppression of: the cough reflex, respiratory centre, vasomotoric centre with hypotension, certain spinal reflexes and facilitation of others
- Releasing of ADH resulting in oliguria
- Decreased release of corticotrophin.
- Miosis (“pin-point” pupils).
- Nausea and vomiting by stimulating of the chemoreceptor trigger zone, followed by the reverse by suppression of the vomiting centre.
- Tolerance
List the peripheral effects of morphine
- Decreased motility and increased tone of the GIT with closure of the sphincters leading to constipation.
- Decreased glandular secretions of the GIT and pancreas.
- Gall duct spasm and contraction of the sphincter of Oddi.
- Increased tone of the detrusor muscle of the urinary bladder, but also increased tone of the sphincter such that urination becomes more difficult.
- Constriction of bronchi – partially as a result of histamine release (only important in emphysema and asthma).
- Dilatation of skin blood vessels (face, neck and upper chest). It causes an increase in skin temperature and sweat.
- Pruritis – particularly of nose and cheeks (possibly as a result of histamine).
- Contraction of erector pili muscles.
- Lengthening of parturition and increased neonatal mortality.
Name the clinical uses of morphine
Relief of visceral and traumatic pain.
Relief of anxiety in a severe crisis such as shock or myocardial infarctions.
Control of diarrhea.
Suppression of cough.
What is the affect of morphine in high doses on pain?
elevate the pain threshold level
What is the affect of morphine in therapeutic doses on pain?
lowers the anxiety component of pathological pain
What is the difference in effect of morphine with and without pain?
With pain: euphoria
Without pain: dysphoria
What is the effect of morphine on the GIT?
increases the non-propulsive peristalsis, causes constipation
What is the effect of morphine on respiration in therapeutic doses?
suppresses respiration
What is the effect of morphine on respiration in overdoses?
patient dies because he ceases breathing
Describe the uses of opioid antagonist
Less addictive than morphine, saves the lives of patients with morphine overdose
Describe the mechanism of action of opioid analgesics
They act as agonists on the encephalin and endorphin receptors. The neurons of both apparently have an inhibitory effect on other neurons of the central nervous system
What happens when someone becomes tolerant to morphine?
Duration of effects decrease, absorption, distribution and excretion of morphine are not changed in tolerant persons
What is the mechanism of action of corticosteroids?
- Glucocorticoid binds to receptor inside cell = nuclear receptor (inside nucleus)
- Involved in regulation of genes that induce specific mRNA synthesis which leads to synthesis of specific proteins
- Acts on DNA transcription
