NEET MDS Lessons
Pharmacology
Example calculations of maximum local anesthetic doses for a 15-kg child
Articaine
5 mg/kg maximum dose × 15 kg = 75 mg
4% articaine = 40 mg/mL
75 mg/(40 mg/mL) = 1.88 mL
1 cartridge = 1.8 mL
Therefore, 1 cartridge is the maximum
Lidocaine
7 mg/kg × 15 kg = 105 mg
2% lidocaine = 20 mg/mL
105 mg/(20 mg/mL) = 5.25 mL
1 cartridge = 1.8 mL
Therefore, 2.9 cartridges is the maximum
Mepivacaine
6.6 mg/kg × 15 kg = 99 mg
3% mepivacaine = 30 mg/mL
99 mg/(30 mg/mL) = 3.3 mL
1 cartridge = 1.8 mL
Therefore, 1.8 cartridges is the maximum.
Prilocaine
8 mg/kg × 15 kg = 120 mg
4% prilocaine = 40 mg/mL
120 mg/(40 mg/mL) = 3 mL
1 cartridge = 1.8 mL
Therefore, 1.67 cartridges is the maximum
Pharmacodynamic Effects of NSAIDs
A. Positive
analgesic - refers to the relief of pain by a mechanism other than the reduction of inflammation (for example, headache);
- produce a mild degree of analgesia which is much less than the analgesia produced by opioid analgesics such as morphine
anti-inflammatory - these drugs are used to treat inflammatory diseases and injuries, and with larger doses - rheumatoid disorders
antipyretic - reduce fever; lower elevated body temperature by their action on the hypothalamus; normal body temperature is not reduced
Anti-platelet - inhibit platelet aggregation, prolong bleeding time; have anticoagulant effects
B. Negative
Gastric irritant
Decreased renal perfusion
Bleeding
(CNS effects)
Adverse effects
The two main adverse drug reactions (ADRs) associated with NSAIDs relate to gastrointestinal (GI) effects and renal effects of the agents.
Gastrointestinal ADRs
The main ADRs associated with use of NSAIDs relate to direct and indirect irritation of the gastrointestinal tract (GIT). NSAIDs cause a dual insult on the GIT - the acidic molecules directly irritate the gastric mucosa; and inhibition of COX-1 reduces the levels of protective prostaglandins.
Common gastrointestinal ADRs include:
Nausea, dyspepsia, ulceration/bleeding, diarrhoea
Risk of ulceration increases with duration of therapy, and with higher doses. In attempting to minimise GI ADRs, it is prudent to use the lowest effective dose for the shortest period of time..
Ketoprofen and piroxicam appear to have the highest prevalence of gastric ADRs, while ibuprofen (lower doses) and diclofenac appear to have lower rates.
Commonly, gastrointestinal adverse effects can be reduced through suppressing acid production, by concomitant use of a proton pump inhibitor, e.g. omeprazole
Renal ADRs
NSAIDs are also associated with a relatively high incidence of renal ADRs. The mechanism of these renal ADRs is probably due to changes in renal haemodynamics (bloodflow), ordinarily mediated by prostaglandins, which are affected by NSAIDs.
Common ADRs associated with altered renal function include:
salt and fluid retention,hypertension
These agents may also cause renal impairment, especially in combination with other nephrotoxic agents. Renal failure is especially a risk if the patient is also concomitantly taking an ACE inhibitor and a diuretic - the so-called "triple whammy" effect.
In rarer instances NSAIDs may also cause more severe renal conditions.
interstitial nephritis, nephrotic syndrome, acute renal failure
Photosensitivity
Photosensitivity is a commonly overlooked adverse effect of many of the NSAIDs. These antiinflammatory agents may themselves produce inflammation in combination with exposure to sunlight. The 2-arylpropionic acids have proven to be the most likely to produce photosensitivity reactions, but other NSAIDs have also been implicated including piroxicam, diclofenac and benzydamine.
ibuprofen having weak absorption, it has been reported to be a weak photosensitising agent.
Other ADRs
Common ADRs, other than listed above, include: raised liver enzymes, headache, dizziness.
Uncommon ADRs include: heart failure, hyperkalaemia, confusion, bronchospasm, rash.
The COX-2 paradigm
It was thought that selective inhibition of COX-2 would result in anti-inflammatory action without disrupting gastroprotective prostaglandins.
The relatively selective COX-2 oxicam, meloxicam, was the first step towards developing a true COX-2 selective inhibitor. Coxibs, the newest class of NSAIDs, can be considered as true COX-2 selective inhibitors and include celecoxib, rofecoxib, valdecoxib, parecoxib and etoricoxib.
Antiemetics
Antiemetic drugs are generally more effective in prophylaxis than treatment. Most antiemetic agents relieve nausea and vomiting by acting on the vomiting centre, dopamine receptors, chemoreceptors trigger zone (CTZ), cerebral cortex, vestibular apparatus, or a combination of these.
Drugs used in the treatment of nausea and vomiting belong to several different groups. These include:
1. Phenothiazines, such as chlorpromazine, act on CTZ and vomiting centre, block dopamine receptors, are effective in preventing or treating nausea and vomiting induced by drugs, radiation therapy, surgery and most other stimuli (e.g. pregnancy).
They are generally ineffective in motion sickness.
Droperidol had been used most often for sedation in endoscopy and surgery, usually in combination with opioids or benzodiazepines
2. Antihistamines such as promethazine and Dimenhyrinate are especially effective in prevention and treatment of motion.
3. Metoclopramide has both central and peripheral antiemetic effects. Centrally, it antagonizes the action of dopamine. Peripherally metoclopramide stimulates the release of acetylcholine, which in turn, increases the rate of gastric. It has similar indications to those of chlorpromazine.
4. Scopolamine, an anticholinergic drug, is very effective in reliving nausea & vomiting associated with motion sickness.
5. Ondansetron, a serotonin antagonist, is effective in controlling chemical-induced vomiting and nausea such those induced by anticancer drugs.
6. Benzodiazepines: The antiemetic potency of lorazepam and alprazolam is low. Their beneficial effects may be due to their sedative, anxiolytic, and amnesic properties
Local anesthetic selection
Local anesthetics are typically divided into 3 main categories:
short, intermediate and long acting local anesthetics.
Based on duration of the procedure and the duration of the individual agents
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Infiltration |
Nerve block |
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Pulpal |
Soft tissue |
Pulpal |
Soft tissue |
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Short |
30 min |
2-3 hrs |
45 min |
2-3 hrs |
|
Intermediate |
60 min |
2-3 hrs |
75-90 min |
3-4 hrs |
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Long |
40 min |
5-6 hrs |
3-4 hrs |
6-8 hrs |
Short acting agents
1. Mepivacaine 3 %
2. Lidocaine 2%
Intermediate acting agents
1. Lidocaine 2% 1:100000 epi
2. Lidocaine 2% 1:50000 epi
3. Mepivacaine 2% 1:20000 neocobefrin
4. Prilocaine 4%
5. Articaine 4% 1:100000 epi
Long acting agents
1. Bupivacaine 0.5% 1:200000 epi
Estimation of the risk of anesthesia (American Society of Anesthesiologists scale)
• ASA 1: healthy patient.
• ASA 2: patient with stable, treated illness like arterial hypertension, diabetes melitus, asthma bronchiale, obesity
• ASA 3: patient with systemic illness decreasing sufficiency like heart illness, late infarct
• ASA 4: patient with serious illness influencing his state like renal insuficiency, unstable hypertension, circulatory insuficiency
• ASA 5: patient in life treatening illness
• ASA 6: brain death- potential organ donor
Hypothalamic - Pituitary Drugs
Somatropin
Growth hormone (GH) mimetic
Mechanism
agonist at GH receptors
increases production of insulin growth factor-1 (IGF-1)
Clinical use
GH deficiency
increase adult height for children with conditions associated with short stature
Turner syndrome
wasting in HIV infection
short bowel syndrome
Toxicity
scoliosis
edema
gynecomastia
increased CYP450 activity
Octreotide
Somatostatin mimetic
Mechanism
agonist at somatostatin receptors
Clinical use
acromegaly
carcinoid
gastrinoma
glucagonoma
acute esophageal variceal bleed
Toxicity
GI upset
gallstones
bradycardia
Oxytocin
Mechanism
agonist at oxytocin receptor
Clinical use
stimulation of labor
uterine contractions
control of uterine hemorrhage after delivery
stimulate milk letdown
Toxicity
fetal distress
abruptio placentae
uterine rupture
Desmopressin
ADH (vasopressin) mimetic
Mechanism
agonist at vasopressin V2 receptors
Clinical use
central (pituitary) diabetes insipidus
hemophilia A (factor VIII deficiency)
increases availability of factor VIII
von Willebrand disease
increases release of von Willebrand factor from endothelial cells
Toxicity
GI upset
headache
hyponatremia
allergic reaction
Gastric acid secretion inhibitors (antisecretory drugs):
HCl is secreted by parietal cells of the gastric mucosa which contain receptors for acetylcholine (muscarinic receptors: MR), histamine (H2R), prostaglandins (PGR) and gastrin (GR) that stimulate the production, except PGs which inhibit gastric acid production.
Therefore, antagonists of acetylcholine, histamine and gastrin inhibit gastric acid secretion (antisecretory). On the other hand, inhibitors of PGs biosynthesis such as NSAIDs with reduce cytoprotective mechanisms and thus promote gastric mucosal erosion. Also, the last step in gastric acid secretion from parietal cells involve a pump called H+ -K+-ATPase (proton pump). Drugs that block this pump will inhibit gastric acid secretion. Antisecretory drugs include:
1. Anticholinergic agents such as pirenzepine, dicyclomine, atropine.
2. H2-receptors blocking agents such as Cimetidine, Ranitidine, Famotidine, Nizatidine (the pharmacology of these agents has been discussed previously).
3. Gastrin-receptor blockers such as proglumide.
4. Proton pump inhibitors such as omeprazole, lansoprazole.
Major clinical indications of antisecretory drugs:
• Prevention & treatment of peptic ulcer disease.
• Zollinger Ellison syndrome.
• Reflux esophagitis.