Lecture 33: Analgesic drugs 2 Flashcards

Question

Describe NSAIDs and Bleeding

Answer 1

_Bleeding time increases_ in patients on aspirin or other NSAID * May _↑__operative blood loss (risk)_ * Epidurals (for pain relief e.g. labour) may be at risk of developing _haematoma_ (compress on spinal cord, emergency!).

Answer 2

a solid swelling of clotted blood within the tissues.

Answer 3

Gastric epithelium produces _gastric cytoprotective prostanoid (PG)_ protecting from acid damage. However, gastric cytoprotective PG synthesis is _inhibited by aspirin_ (& other NSAIDs). The production of this PG is increased by _mucosal injury_ and _irritants_ (e.g. ethanol). It: **_Effects of this prostanoid:_** * _↓ gastric acid secretion_ * _↑ bicarbonate secretion,_ therefore, _↑ pH gradient b_etween epithelial cell surface and lumen * _↑mucus synthesis (_carbohydrate polymer acts as an endogenous cytoprotective substance against the digestive effects of trypsin [duodenum] and HCl [stomach]) * _↑ mucosal thickness_ * _Dilates gastric blood vessels_ and _↑ mucosal blood flow_ So NSAIDs reduces the prostanoid effects. **Other GIT Side Effects Of NSAIDs** Being organic acids, they irritate _gastric mucosa (nausea, vomiting, diarrhoea)_ Compare to oral NSAID, injectable one will not reduce side effect (still block PG production), may reduce some local effects.

Answer 4

injectable one will not reduce side effect (still block PG production), but it may reduce some local effects.

Answer 5

Aspirin-induced asthma (AIA) due to cross-sensitivity with other NSAIDs * Symptoms appears at an average age of 30 years (rare in children). * _May be severe and life threatening_ Asthma triggered within 1-3 hours of ingestion of aspirin or other NSAIDs (Samter's triad) **Aspirin and Asthma Mechanism** Inhibition of COX1 and COX2 enzymes leads to: 1. ↓PGE2 (bronchodilator) (NSAID may precipitate bronchoconstriction in any asthmatic patient) 2. Activation of lipoxygenases → ↑inflammatory mediators (leukotrienes) → bronchospasm

Answer 6

Aspirin Exacerbated Respiratory Disease (AERD), also known as Samter's Triad or Aspirin Sensitive Asthma, is a _chronic medical condition_ that consists of _asthma_, _recurrent sinus disease_ with nasal polyps, and a _sensitivity to aspirin_ and other non-steroidal anti-inflammatory drugs (NSAIDs). **Aspirin (or Samter’s) Triad** _1) Aspirin intolerance (1)_ manifested by: * Rhinitis (nasal obstruction, rhinorrhea and sneezing) * Facial flushing. These symptoms continue for few days then progress to: _2) Severe asthma (2)__._ _3) Nasal polyps (3)_ will then appear at a later stage.

Answer 7

**Aspirin and Asthma Mechanism** Inhibition of COX1 and COX2 enzymes leads to: 1. ↓**PGE2** (bronchodilator) (NSAID may precipitate bronchoconstriction in any asthmatic patient) 2. Activation of **lipoxygenases** → _↑inflammatory mediators (leukotrienes)_ → _bronchospasm_ NSAIDs may precipitate broncho-constriction in any asthmatic patients

Answer 8

**Reye’s Syndrome And Aspirin** Reye’s syndrome is an _acute metabolic encephalopathy_ (following aspirin administration in children). It can affect **brain** (encephalopathy); **liver** (fatty), ↑ammonia, ↑liver enzymes. * Rare with 40% fatality. Infants and young children more prone after a viral illness (e.g. chicken pox) * _The role of aspirin remains very controversial. Avoid aspirin use in children with viral illness!!_

Answer 9

Reye syndrome is a rapidly progressive encephalopathy.[2] Symptoms may include vomiting, personality changes, confusion, seizures, and loss of consciousness.[1] Even though liver toxicitytypically occurs, yellowish skin usually does not. The cause of Reye syndrome is unknown.[2] It usually begins shortly after recovery from a viral infection, such as influenza or chickenpox.[1] About 90% of cases in children are associated with aspirin(salicylate) use.[2]

Answer 10

* Effects are _relatively mild_ and rare in healthy individuals. * In compromised patients, NSAIDs are associated with _renal failure_: * papillary necrosis, * interstitial nephritis, * acute tubular necrosis. * This is called “_analgesic nephropathy._” (mainly due to inhibition of COX1 enzyme)

Answer 11

**NSAIDs, Pregnancy and Lactation** NSAIDs c_ross the placenta_, and _excreted in milk._ _Prostaglandins_ in pregnancy: * Establishing and _maintaining labor_. * ↑Uterine _smooth muscle contraction_ * Maintains patency of the _ductus arteriosus_ in utero NSAIDs (usually _indomethacin_) used for: * Premature labor (_inhibits labour_) * C_losure of patent ductus arteriosus_ in premature infants.

Answer 12

**Paracetamol** Paracetamol is _analgesic_ and _antipyretic_ * Mechanism of analgesic action unknown, may involve central _↓prostaglandin (?COX3 inhibition)_ * Metabolism is via liver _cytochrome P450_ It is _weak anti-inflammatory (weak COX inhibitor),_ but _not considered NSAID_ because it does not exhibit significant anti-inflammatory activity. **Side Effects (Few)** Acute overdose causes fatal hepatic damage due to metabolite _N-acetyl benzoquinone_ (normally conjugated with glutathione)/ Toxicity antidote is _N- acetyl-cystiene_ (augments glutathione reserves in body and, together with glutathione, directly bind to toxic metabolite) **Routes Of Administration** * PO * PR * IV (perfalgan) (good analgesic for mild pain after minor surgery to avoid opioid) **Paracetamol Combinations** * Paracetamol + Codeine * Paracetamol + NSAID