This document discusses various methods for treating postoperative pain, including pharmacological, non-pharmacological, and anticoagulant options. Pharmacological methods include acetaminophen, NSAIDs, opioids, local anesthetic infiltration, peripheral nerve blocks, PCA, and epidurals. Non-pharmacological options involve ice/heat therapy, physical therapy, and relaxation techniques. Common anticoagulants described are warfarin, heparin, low molecular weight heparins, fondaparinux, and direct thrombin inhibitors. Adverse effects, monitoring, and considerations for different anticoagulants are also summarized.

1. Orthopaedic
Pharmacology
DR MUHAMMAD BASIT ALI

2. Methods to Treat Post
Operative Pain
Pharmacologic
01
Procedures
02
Non-Pharmacologic
03
• ACETAMIPHEN,NSAIDS,OPIOIDES
• LA infiltration at incision site
Regional anesthesia
• Peripheral nerve blocks
• PCA
• Epidural
• ICE AND HEAT THERAPY
• PHYSICAL THERAPY
• RELAXATION TECHNIQUES

3. ANTICOAGULANT
S
• Vitamin K
antagonists:
• Warfarin
• Heparin and
derivative
substances:
• Unfractionated
heparin
• Low-molecular
weight heparin
(enoxaparin,
dalteparin)
• Fondaparinux.
• Direct thrombin
inhibitors:
• Dabigatran
• Apixaban
• Rivaroxaban)

4. WARFARIN
• Structure similar to vitamin K
• Forms MODIFIED factors called protein in vitamin k (PIVKA)
• It takes 2–3 days to achieve its full anticoagulant effect
• Monitored with the prothrombin time (INR)
• Effects on factor 2, 7, 9, 10 mainly affecting the extrinsic pathway
• Long half-life (around 40 H) - takes 5 days for INR to become normal
• Metabolized by hepatic microsomal enzymes to inactive 7- hydroxy warfarin.
• Hemorrhage: In overdose that
can be reversed acutely with
• Clotting factor
concentrates or fresh
frozen plasma
• If severe, intravenous
vitamin K can also be
considered
• Drug interactions:
• Drugs that induce
coagulation (e.g.
barbiturates,
carbamazepine)
• Drugs that inhibit
coagulation (e.g. ethanol,
metronidazole)
• Teratogenicity:
• Absolute contraindication
in pregnancy.

5. Site Of Action Of
Anticoagulants

6. Heparin is a glycosaminoglycan of varying molecular weight (5000–15,000
Daltons).
It forms complex WITH antithrombin III, a protease inhibitor that inactivates
thrombin when bound to heparin.
The heparin– antithrombin III complex also inactivates factor Xa (among
others).
If given intravenously it needs MONITORING with the activated partial
thromboplastin time (APTT).
short duration of action (4–6 h).
LMWHs are defined as heparin salts having an average molecular weight
of less than 8000 Daltons.
LMWH–antithrombin III complex inhibits factor Xa only, thereby preventing
thrombin synthesis
Longer half-lives and therefore require only single daily dosing.
Prophylactic doses do not require monitoring.
HEPARIN AND DERIVATIVES

7. Haemorrhage:
There is less hemorrhage with LMWHs than with heparin.
Bleeding with heparin can normally be controlled by stopping its
administration, but in severe cases protamine sulphate may be required.
Heparin-induced thrombocytopenia (HIT) is caused when heparin–PF4–
IgG immune complex binds to platelets causing
platelet activation, which accelerates coagulation reactions and generates
thrombin.
Osteoporosis: when used long term.
Allergic reaction, bruising at the injection site.
HEPARIN AND DERIVATIVES
ADVERSE EFFECTS

8. • Reduce venous thromboembolism more effectively than LMWHs in hip
and knee arthroplasty and fractures of the hip.
• Reduced risk of HIT
• Given at 6h post op or 12h post removel of epidural cathetar.
• Use of LMWHs may need to be monitored closely in patients at
extremes of weight or inpatients with renal dysfunction.
• An anti-factor Xa assay may be useful for monitoring LMWH
anticoagulation.
HEPARIN AND DERIVATIVES
FONDAPARINUX(ARIXTRA)

9. HEPARIN AND DERIVATIVES
DIRECT THROMBIN INHIBITORS
• They Act as anticoagulants by competitively and directly
inhibiting the enzyme thrombin
• Often taken orally
• They do not Requires monitoring and have no reported
significant drug interactions.
• A phase III study, comparing dabigatran with enoxaparin
have equal efficacy in preventing thrombosis, with a
similar risk profile.
• Dabigatran has been authorized for use as
thromboprophylaxis following hip and knee arthroplasty.
ADVEESE EFFECTS
Haemorrhage (similar to LMWHs but less than warfarin)
Gastritis
Hypersensitivity, rash

10. DMARDS
Disease-Modifying
Antirheumatic Drugs
MODIFY DISEASE AND SLOW ITS
PROGRESSION

11. Examples
METHOTREXATE
LEFLUNOMIDE
TUMOR NECROSIS FACTOR @
SULFASALAZIN
E
INTRAMUSCULAR GOLD

12. DMARDS Methotrexate
• Antimetabolite
• inhibits the metabolism of folic acid
• inhibits dihydrofolate reductase (DHFR)
• it also inhibits enzymes involved in purine
metabolism
• it stops T-cell activation and suppression of
intercellular adhesion molecule expression by T-
cells
Leflunomide
• antimetabolite and inhibits
dihydroorotate dehydrogenase an
enzyme involved in pyrimidine synthesis.
• directly supress T cells
Sulfasalazine
• 5-ASA scavenges the toxic oxygen
metabolites produced by neutrophils
thereby retarding disease activity
Sodium aurothiomalate
• effect in 3 months IM inj
• inhibit macrophage activation.
TNF-α
• interfere with the inflammatory cascade
• binds to TNF-α receptors
• Adalimumab is a human-sequence
antibody that binds specifically to TNF-α
• infliximab is a chimeric monoclonal
antibody that binds to TNF-α.

13. ADVERSE EFFECTS
Common – rash, ulcerative stomatitis, nausea, abdominal
pain, diarrhoea,Dizziness.
Folic acid supplements may help prevent some of the minor
sideeffects.
Rare – leucopenia and predisposition to infection, pulmonary fibrosis, hepatic,
renal and bone marrow toxicity, necessitating regular blood monitoring.

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