analgesic-antipyretic drugs 343

7/28/2019 Analgesic-Antipyretic Drugs 343

1/29

V. Analgesic-antipyretic drugsAspirin-like drugs

Mediators of inflammation:

I. Plasma-derived:1. Clotting-fibrinolytic system : fibrin split products.2. Kallikrein-kinin system : Kinins.3. Complement system: C3a, C5a.

II. Cell-derived:1. Mast cells, basophils: histamine.2. Platelets : serotonin.3. Inflammatory cells : PGs, Leukotrienes, PAF.4. Macrophages, lymphocytes, endothelial cells, fibroblasts:cytokines. All are vasoactive mediators that increase,directly ore indirectly, increase vascular permeability.

Cytokines1. Different peptides.2. Produced mainly from macrophages and lymphocytes.3. Regulate inflammatory and immune reactions.4. Main cytokines are:a) Interleukin 1 to 8b) Interferons.c) Tumor necrosis factord) Various colony stimulating factors.


2/29

Mechanism of action of NSAIDs

1. The main postulated mechanism is inhibition ofcyclooxygenase enzymes (COX). This can be:

A) Rapid, reversible, competitive inhibition of COX, aspropionic acid derivatives.

B) Rapid, reversible, non-competitive inhibition of COXasfenamates.

C) Slow, irreversible inactivation as aspirin.

2. Most NSAIDs block both COX-I and COX-II. Others asmeloxicam show a variable and always incomplete degree ofselectivity.

3. Since COX-II is the isozyme thought to be responsible forthe production of inflammatory PGs, efforts to developselective COX II inhibitors are underway. The block ofcyclooxygenase leads to the inhibition of PG biosynthesis (butnot of leukotrienes biosynthesis.

Other postulated mechanisms include inhibition of:a) Superoxide generation (diclofenac, piroxicam).b) Leucocyte migration (naproxen).c) Leukotriene production (diclofenac, ketoprofen).

d) Transmembrane ion transport.e) Cartilage metabolism.f) Lysosomal enzymes.


3/29

Analgesic effect of NSAIDs:

1. The effect is evident in pain due to inflamed tissues(arthritis), surgery, dysmenorrheal, bone metastases,toothache, headache (some kinds).

2. The effect is low or even absent in severe ischemic andvisceral pain.

3. The intensity of analgesic effect is generally lower than thatobtained by opioids and is not linked to a change in theaffective response to pain.

4. The analgesic effect does not undergo tolerance.

5. Mechanisms include inhibition of PG-induced sensitizationof peripheral pain receptors and of PG mediated inflammatoryprocesses. A central depressive action likely at thehypothalamic level is also postulated.


4/29

Anti-inflammatory Effect of NSAIDs:

1. NSAIDs inhibit mainly the early phase of inflammatoryreaction (vasodilation, increased vascular permeability,oedema..)

2. NSAIDs have only limited effects on cellular accumulationeither in acute or chronic inflammation.

3. NSAIDs have negligible effects on the proliferative phase ofinflammation (fibrotic repairing is not affected).

4. NSAIDs have no direct effects on the specific immunologicalresponse.

The postulated mechanisms include:

A) Inhibition of PG and thromboxane biosynthesis.

B) Stabilization of lysosomal membranes (thus preventing theescape of lysosomal enzymes into the cytoplasm).

C) Inhibition of plasmin, a plasma proteolytic enzyme whichmay activate kinin formation.

D) Inhibition of the activation and function of neutophils,macrophages and mast cells.


5/29

Pharmacodynamics of salicylates:

1. CNS:a) After moderate doses: central antipyretic effect.

b) After high doses: stimulation of CRTZ

2. Respiratory system:a) After moderate doses: negligible effect.

b) After high doses: stimulation of respiration indirectly byincreased production of CO2 and directly by a direct effect onthe respiratory center in the medulla oblingata.

c) After very high doses: direct depression of the respiratorycenter.

3. CVS:

a) After moderate doses: negligible effect.

b) After high doses: direct dilating effect on peripheral bloodvessels and increase of circulating plasma volume.

4. Urinary system:A) After moderate doses:

Small increase in GFR.

Blockade of tubular uric acid excretion.

B) After high doses:

A) Decrease in GFR mainly in patients with cardiac failure,

renal disease and hypovolemia.


6/29

B) Blockade of tubular uric acid reabsorption.

C) Increased Na+ and K+ reabsorption.

D) Increased water reabsorption

E) After chronic doses (2-3 years of treatment): renal lesions

5. Hematopoietic system:A) After moderate doses:

Decreased platelet aggregation (the effect can last 7-8 days)(cyclooxygenase blockade reduces both the production ofTXA2 which promotes aggregation and of PGI2 which inhibitsaggregation. However, endothelial cells produce newcyclooxygenase in a matter of hours while platelets cannotmanufacture the enzyme).

B) After very high doses: hypoprothrombinemia.

6. GIT:a) Stomach:erosive gastritis.

b) liver: direct stimulation of bile secretion by hepatocytes,dose-dependent hepatic damage, severe hepatic injury (in Rey'ssyndrome).

7. Endocrine system:After high doses: Increased ACTH secretion, stimulation ofadrenaline release.

8. Acid-base balance:After high doses:

1. Uncoupling of oxidative phosphorylation in skeletal muscle

which leads to hyperthermia.


7/29

2. Hypoglycemia due to stimulation of insulin secretion orhyperglycemia and glycosuria due to adrenaline release and toincreased glycogenolysis.

3. Hyperkalemia due to increased K+ reabsorption by thekidney.

Salicylate toxicity:

A) Side effectsDyspepsia, urticaria, angioneurotic edema, laryngeal edemaand shock.

B) Overdosage toxicity:

a) Mild intoxication (salicylism).

1. Plasma salicylate concentration (400-800 mcg/mL).

2. Headache, dizziness, tinnitus, difficulty in hearing, mentalconfusion, sweating, hyperventilation, nausea, vomiting anddiarrhea.

b) Serious intoxication

1. Plasma salicylate concentration greater than 800 mcg/mL.

2. tinnitus, vertigo, diplopia, respiratory depression, tremors,delirium, hallucinations, generalized convulsions and coma.Nausea, vomiting, abdominal cramps, gastric bleeding.Acidosis, marked hyperthermia, dehydration, hyperglycemia,

hypoglycemia in children, hypoprothrombinemia.


8/29

C) Adverse effects after chronic treatment:

1. Chronic erosive gastritis.

2. Increased incidence of peptic ulcer

3. Analgesic nephropathy.

4. Liver diseases.

5. Hemolytic anemia in patients with G6PD.

6. Hypochromic anemia

7. Rey's syndrome in children.

8. Salicylism.

9. Toxicity in pregnancy:

10. Increased occurrence of abortion, prolonged labor.

11. Pre and postpartum hemorrhage.

12. Hemostatic abnormalities in the newborn.

Aspirin hypersensitivity:

1. Vasomotor rhinitis, urticaria, bronchoconstriction,angioneurotic edema, laryngeal edema, vascular shock, thereaction can be lethal.

2. The reaction does not appear to be immunological in natureand therefore it is a paeudoallergic reaction. It seems to berelated to the formation of increased amount of leukotrienes


9/29

and other products of lipooxygenase pathway, due to inhibitionof cyclooxygenase pathway.

3. There is cross sensitivity between aspirin and other NSAIDsand therefore the hypersensitivity to aspirin is acontraindication to the therapy with any NSAIDs.

The Rey's Syndrome:

1. Mainly in children or young adults.

2. Fatty infiltration of liver and other organs as pancreas,heart, kidney as well as cerebral edema.

3. The syndrome develops in two phases:

A) Respiratory depression.

B) After 4-days: nausea, vomiting, sudden change in mentalstatus, liver damage.

Therapeutic uses of salicylates:

1. Local uses:

A). Keratolytic agents.B). Counterirritant.

2. Systemic uses:

A). Antipyresis.

B). Analgesia.


10/29

C) Inflammatory diseases as acute rheumatic fever,rheumatoid arthritis, ulcerative colitis.

D) Thromboembolic diseases as myocardial infarction,unstable angina, cerebrovascular disorders.

Contraindications

1) Gastritis, gastric and duodenal ulcer.

2) Other ulcerative diseases of the upper GIT3) Alcohol consumption.

4) Methotrexate toxicity.

5) Coagulation disorders as hemophilia,hypoprothrombinemia.

6) G6PD deficiency.

7) Decreased hearing capacity or administration of ototoxicdrugs.

8) Renal insufficiency.

9) Advanced heart failure.

10) Severe hypertension.

12) Serious hepatic disease.

13) Asthma, hay fever, nasal polyps, urticaria.

14) NSAIDs hypersensitivity.


11/29

15) Viral febrile illness in children.

16) Pregnancy.

Classification of NSAIDs

1) Salicylates as Aspirin.

2) Arylalkanoic acids as Diclofenac, Ketorolac, Indomethacin,Sulindac.

3) Arylpropionic acids (Profens) as Ibuprofen, Ketoprofen,Naproxen, Tiaprofenic acid.

4) N-arylanthranilic acids (fenamic acids) as Mefenamic acid.

5) Pyrazolidine derivatives as Phenylbutazone,oxyphenbutazone.

6) Oxicams as Piroxicam, Tenoxicam, Meloxicam

7) COX-2 inhibitors as Celecoxib, Rofecoxib.8) Sulphonanilides as Nimesulide.

9) Others as Omega-3 fatty acids.


12/29

Characteristic features of other NSAIDs

1) The analgesic, antipyretic, anti-inflammatory andantiplatelet effects are qualitatively similar to aspirin.

2) The efficacy of some compounds as analgesic agents(Ketorolac) or anti-inflammatory agents (Indomethacin,Diclofenac) seems higher than others

3) GI and CNS effects are less than those of aspirin.

4) Effects on acid/base balance or uric acid secretion areminimal compared to aspirin.

Mechanisms of action of different NSAIDs

1) COX-1 inhibition as aspirin, indomethacin, sulindac, andpiroxicam.

2) Equal COX-1 and COX-2 inhibition as Ibuprofen, naproxenand Diclofenac.

3) Mainly COX-2 inhibition as Meloxicam

4) Inhibition of leucocyte migration as Naproxen.

5) Inhibition of production of H2O2 by activated neutrophils asDiclofenac, Piroxicam.

6) Inhibition of leukotriene production as Diclofenac,Ketoprofen.


13/29

Important information about Acetaminophen:

1) It is a very weak, reversible, non-competitive inhibitor ofCOX in vitro, or in inflamed tissue.

2) It is a good COX inhibitor in the CNS.

3) Analgesic and antipyretic effects are qualitatively similar tothose of other NSAIDs.

4) Antiinflammatory effect, inhibition of platelet aggregation,gastric erosion, and bleeding, decreased Na+ and waterclearance are absent.

5) There is some speculation that Paracetamol acts throughinhibition of COX-3 isoform

6) It has negligible anti-inflammatory activity and so it is notan NSAID.

Clinical pharmacology of NSAIDs:

1) Aspirin remains the prototype of NSAIDs.

2) None of the newer NSAIDs proved more effective thanaspirin in controlled studies.

3) Aspirin however is less safe than other NSAIDs (at least inthe GIT) and it has been largely replaced by ibuprofen.

4) In patients prone to develop peptic ulcer who are takingaspirin, PGE2 analogue (Misoprostol) may be used(unfortunately the drug causes diarrhea in many patients).

5. Patients who develop adverse effects from one NSAID maybe treated with another NSAID belonging to a different group.


14/29

6) The newer NSAIDs have been responsible for manyinstances of acute renal failure and nephritic syndrome whichis neither dose-dependent nor time-dependent.

7) The choice of a NSAID in an individual patient remains anempirical issue as it is not possible to know which patient willrespond in a specific way to which NSAIDs, some patientsdeive benefit from one and not from another.

Uses of NSAIDs:

1. Treatment of acute or chronic conditions where pain andinflammation are present. Research continues into theirpotential for colorectal cancer, and treatment of otherconditions such as cancer and cardiovascular disease.

2. NSAIDs are generally indicated for the symptomatic relief ofthe following conditions:

1) Rheumatoid arthritis.

2) Osteoarthritis.

3) Inflammatory arthropathies as ankylosing spondylitis.

4) Acute gout.

5) Dysmenorrhea.

6) Metastatic bone pain.

7) Headache and migraine.

8) Postoperative pain.

9) Mild to moderate pain due to inflammation and tissueinjury.


15/29

10) Pyrexia.

11) Renal colic.

12) Aspirin, the only NSAID able to irreversibly inhibit COX-1, is also indicated for inhibition of platelet aggregation; anindication useful in the management of arterial thrombosis andprevention of adverse CV events.

Pharmacokinetics of NSAIDs:

1) Most NSAIDs are weak acids and they are absorbed wellfrom the stomach and intestinal mucosa.

2) They are highly protein-bound in the plasma usually toalbumin, so that their Vd typically approximates to plamavolume.

3) Most NSAIDs are metabolized in the liver by oxidation andconjugation to inactive metabolites which are excreted in theurine. Some drugs are patially excreted in bile.

4) Metabolism of NSAIDs may be abnormal in certain diseasestates, and accumulation may occur even with normal dosage.

5) Ibuprofen and Diclofenac have short half-lives (2-3 hours).Some NSAIDs (oxicams) have very long half-lives (20-60hours).


16/29

Adverse Effects:

1) The main ADRs associated with the use of NSAIDs relate todirect and indirect irritation of GIT. NSAIDs cause a dualeffect on the GIT- the acidic molecules directly irritate thegastric mucosa; and inhibition of COX-1 reduces the levels ofprotective prostaglandins.

2. Common gastrointestinal ADrs include* Nausea and vomiting.* Dyspepsia.* Gastric ulceration and bleeding.* Diarrhea.

3. Risk of ulceration increases with duration of therapy, andwith higher doses. It is possible to minimize Gi ADRs by usingthe lowest effective dose for the shortest period of time.

4) Indomethacin, ketoprofen and piroxicam appear to have thehighest GI ADRs. Indomethacin, ketoprofen and piroxicamappear to have the highest prevalence of GI ADRs, whileibuprofen (lower doses) and diclofenac appear to have lowerrates.

5) Certain NSAIDs as aspirin have been marketed in enteric-coated formulations to reduce the incidence of GI ADRs.

6) GI ADRs can be reduced by suppressing acid production by

concomitant use of a proton pump inhibitor as omeprazole orPG analogue as misoprostol, however, misoprostol may beassociated with diarrhea. These techniques prove to beexpensive for maintenance therapy.

7) High incidence of renal ADRs are present probably due tochanges in renal blood flow ordinarily mediated by PGs, andaffected by NSAIDs


17/29

Common effects include salt and fluid retention andhypertension.

8) These agents may cause renal impairment, especially incombination with other nephrotoxic agents.

9) Renal failure is a risk if the paient is concomitantly takingan ACE inhibitor and a diuretic (triple whammy effect).

10) In rare instances, NSAIDs may cause more severe renalconditions as:* Interstitial nephritis.* Nephrotic syndrome.* Acute renal failure.* Acute tubular necrosis.

11) Photosensitivity is commonly an adverse effect of manyNSAIDs. These drugs may produce inflammation incombination with exposure to sunlight.. (Benoxaprofen waswithdrawn due to its hepatotoxicity, also was the mostphotoactive NSAID

12) During pregnancy:* Not recommended during pregnancy especially during thethird trimester Why?- They may cause premature closure of the fetal ductusarteriosus and renal ADRs in the fetus.- They are linked with premature birth.

- Aspirin, however, is used together with heparin in pregnantwomen with antiphospholipid antibodies.- Incontrast, paracetamol is safe during pregnancy.13) Doses of NSAIDs should be taken as prescribed due to riskof hepatotoxicity with overdoses.

14) Other common ADRs include raised liver enzymesheadache and dizziness.


18/29

15) Uncommon ADRs include heart failure, hyperkalemia,confusion, bronchospasm, rash. Ibuprofen may also rarelycause irritable bowel syndrome symptoms.

16) Most NSAIDs penetrate poorly into the CNS. However,COX enzymes are expressed in some areas of the CNS meaningthat even limioted penetration may cause adverse effects suchas somnolence and dizziness.

Selective COX inhibitors:1) COX-1 regulates many normal physiological processes. One

of these is in the stomach lining, where PGs serve a protectiverole, preventing the stomach mucosa from being eroded by itsown acid.

2) When non-selective COX-1/COX-2 inhibitors such asaspirin, ibuprofen and naproxen lowers stomach PGs levels,these protective effects are lost and ulcers of the stomach orduodenum and internal bleeding can result.

3) COX-2 is an enzyme facultatively expressed ininflammation, and it is inhibition of COX-2 that produces thedesirable effects of NSAIDs.

4) Oxicams, meloxicam was considered relatively selectiveCOX-2 inhibitor while Coxibs are true COX-2 selectiveinhibitors as celecoxib, rofecoxib, valdecoxib.

5) Controversies with COX-2 inhibitors: the clinical datashowed no significant difference in ADRs with celecoxib whencompared with diclofenac.

6) Inhibition of COX-3 could represent a primary centralmechanism by which these drugs decrease pain and possiblyfever as in case of paracetamol.

END OF THE LECTURE


19/29

VI. OPIOID ANALGESICS

Opium: an extract from the juice of the unripe seed capsulesof papaver somniferum (opium poppy.(

Opiate: a drug with close structural similarity to morphine.

Opioid: any substance that produce morphine-like effects.

Narcotic:

1.In the past applied to any drug that produces drowsiness,analgesia and a detached feeling.

2.For a number of years, used to refer to morphine-likeanalgesics

3.In the legal sense, narcotic is any drug included underFederal Narcotic Laws.


20/29

What are opioid receptors?

1.Include Mu, Kappa, Delta and Sigma receptors

2.Exert inhibitory modulation of synaptic transmission inboth the CNS and the mysenteric plexus.

3.Often found on presynaptic nerve terminals, where theiraction results in a decreased release of a large number ofneurotransmitters.

4.They are coupled to an inhibitory guanine nucleotidebinding protein (Gi protein.(

5.Main transduction mechanisms of all these receptors are:

A) Opening of ligand-gated K+ channels on postsynapticneurons.B) Blockade of voltage-gated Ca++ channels on presynapticnerve terminalsC) Inhibition of adenylyl cyclase activity.


21/29

TYPES OF OPIOID RECEPTORS & THEIR LIGANDS

EXOGENOUSLIGANDS

ENDOGENOUSLIGANDS

RECEPTORTYPE

MorphineB-endorphinMu receptors(Mu1, Mu2(

EthylketociclazocineDynorphin AKappa receptors(K1 and K3(

EtorphineMet-enkephalinDelta receptors,Delta1 and 2

N-allyl-normetazocine.

?Sigma receptors

PHARMACOLOGICAL CLASSIFICATION OF OPIOIDSAND OPIOD ANTAGONISTS:

DRUGCLASSMORPHINE, CODEINE,

HEROINAGONISTS

PENTAZOCINEPARTIAL AGONISTSBUTORPHANOLMIXED AGONISTS-

ANTAGONISTSNALOXONE,

NALTREXONEANTAGONISTS


22/29

ORGAN SYSTEM EFFECETS OF MORPHINE:

1.CNS EFFECTS:

1.Analgesia.

2.Euophoria.

3.Sedation.

4.Excitatory CNS effects.

5.Poikilothermia

6.Respiratory depression.

7.Cough suppression.

8.Miosis.

9.Nausea and vomiting

.


23/29

2.PERIPHERAL EFFECTS:

A) GIT EFFECTS:

1.Decreased peristalsis.

2.Decreased secretions.

3.Increased tone of smooth muscle.

B) CV EFFECTS:1.Vasodilation.

2.Inhibition of baroreceptor reflexes.

C) OTHER SYSTEMS:

1.Increased tone of detrusor and sphincter of the urinarybladder.

2.Decreased release of CRF and GnRH


24/29

ANALGESIC EFFECT OF MORPHINE

1.All types of pain (superficial and deep, somatic andvisceral) can be effectively relieved by opioids.

2.The relief of pain is relatively selective (other sensorymodalities are not affected by usual therapeutic doses.

3.Continuous dull pain is relieved more effectively thansharp, shooting, intermittent pain.

4.Nociceptive pain (pain transmitted over intact neuralpathways) is effectively relieved.

5.Neuropathic pain (pain caused by damage of neuralstructures) often respond poorly to opioids.

6.Opioids exert the analgesic effect by lowering of painperception (the pain threshold is raised) and but moderateeffects on pain threshold.

7.Another component of the analgesic effect is the allay ofsuffering and discomfort associated with pain perception.

8.Mechanisms of analgesic effect of morphine:

A) Inhibition of release of excitatory neurotransmitters,including substance P, from the terminals of afferent nerves

in spinal cord.

B) Inhibition of nociceptive transmission in lateralspinothalamic tract.

C) Activation of descending aminergic bulbospinal pathwayswhich exert inhibitory effects on the processing ofnociceptive information in the spinal cord.


25/29

PSYCOLOGICAL EFFECTS OF OPIOIDS

1.A foggy, unreal feeling of being detached from things(mainly things that cause distress.(

2.Euophoria (a pleasant, relaxed, dreaming state) which ismore common when opiods are given to a patient with painor to addict

3.Dysphoria (a feeling of general malaise with difficulty ofmentation and apathy) which is more common when opioidsare given for the first time to a normal, pain-free person.

4.A "Kick" or "thrill" (a sensation in the lower abdomensimilar in quality to sexual orgasm) when given to an addictby rapid IV injection.

5.A period of sedation and tranquility ("on the nod") whichfollows the "kick" and lasts about one hour.

6.Decreased drives such as hunger, thirst and libido.

7.Dose-dependent sedation (decreased physical activity) anddrowsiness.

8.Very high doses of opioids can cause unconsciousness.


26/29

RESPIRATORY EFFECTS OF MORPHINE:1.All phases of respiratory activity are depressed (rate,

minute volume and tidal exchanges.(

2.Respiratory depression is detectable even at subanalgesicdoses and is dose-dependent.

3.The main mechanisms of respiratory depression:

A) Reduce the sensitivity of the respiratory centers (inbrainstem) to P CO2.

B) Depress the centers in the pons and in the medulla(pneumotaxic and apneustic centers) that regulate therhythmicity of breathing.

4.Depression of cough reflex partly due to depression ofcough center

5.Bronchoconstriction with large doses.

CARDIOVASCULAR EFFECTS OF MORPHINE:1.Arteriolar and venous dilation.

2.The mechanisms of vascular dilation include:A) Histamine release (the main mechanism.(B) Depression of vasomotor system (slight.(

C) Hypercapnia due to respiratory depression (with largedoses.(

3.Depression of baroreceptor breflexes.

4.Slight decrease in heart rate.


27/29

5.All the above mentioned effects can induce orthostatichypotension. CV effects are not prominent in normalindividuals.

GASTROINTESTINAL EFFECTS OF MORPHINE:

1.Marked increase in tone of smooth muscle (sphincteraland non-sphincteral.(

2.Marked increase in amplitude of nonpropulsive

contractions but marked decrease in amplitude ofpropulsive contractions.

3.Decrease in gastric, pancreaticm, biliary, intestinalsecretions

4.Nausea and vomiting.

TOLERANCE TO THE EFFECTS OF MORPHINE

1.The rate of tolerance development depends on the patternof opioid use.

2.Tolerance does not develop to all effects of opioids.

3.There is a high degree of cross-tolerance among opioidsacting on the same receptor type but no cross-toleranceamong opioids acting on different receptors.

4.Tolerance is mainly functional (or cellular) in nature.

5.Minimal or no tolerance developed to miosis, constipation,convulsions and antagonist actions.


28/29

MORPHINE PHARMACOKINETICS:1.Oral bioavailability is 25% due to large first-pass effect.

2.Rectal bioavailability may be higher.

3.Intramuscular bioavailability is 95%

4.Bound to plasma proteins (35%.(

5.Distributed mainly in kidneys, liver and lungs.

6.90%is conjugated with glucuronic acid mainly in the liverand gut wall to form morphine-3-glucuronide (inactive) and

morphine-6-glucuronide (active.(

7.10%excreted by the kidney and trace amounts by sweat,saliva and milk.

8.Half-life of morphine is 2 hours and morphine-6-glucuronide is 3.

DIFFERENCES BETWEEN MORPHINE AND OTHEROPIOIDS

Various opioids may differ from morphine in:

1.Potency

2.Pattern of effects.

3.Duration of analgesia.

4.Clinical efficacy.

5.Oral bioavailability.

6.Abuse liability


29/29

THERAPEUTIC USES OF MORPHINE

1.Acute pain due to trauma, burns, surgery, labor, colic,acute pancreatitis and myocardial ischemia.

2.Chronic pain due to terminal illness and cancer.(

3.Acute pulmonary edema.

4.Cough when it is non-productive and disturbing.

5.Diarrhea when it is exhausting and dehydrating.

6.Applications in anesthesia:A) Premedication before anesthesia.B) Primary component in anesthetic regimen in certainsurgical procedures.C) As regional analgesic when given into the epidural space.

7.Opioid resistant pains include:A) Neuropathic pains as post-herpetic neuralgia.B) Skeletal muscle spasm.C) tension headache.D) Increased intracranial pressure.

END OF THE LECTURE

analgesic-antipyretic drugs 343

Documents