Analgesia, Anti-inflammatory, Anticoagulants Drugs Flashcards Preview

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Flashcards in Analgesia, Anti-inflammatory, Anticoagulants Drugs Deck (50)
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0
Q

What would prescribe some for

1) severe acute pain- e.g. Trauma ?
2) mild inflammatory pain?
3) Severe Chronic pain?

A

1) iv strong opioids
2) NSAIDS & weak opioids given orally
3) strong opioids given orally cs or epidural +\~pt controlled analgesic systems

1
Q

What approach is used when deciding on to start analgesia?

A
  • A progressive approach starting with SIMPLE ANALGEISA (e.g. NSAIDS) supplemented first by WEAK OPIOIDS and later STRONG OPIOIDS- “analgesic ladder”
2
Q

Name the 4 classes of analgesic drugs?

A
  • Opioids
  • NSAIDS
  • Centrally acting non opioids - paracetamol, amitripylline , carbamazepine
  • Local anaesthesics
3
Q

Name some strong and weak opioids ?

A
  • Strong- morphine, diamorphine, fentanyl , pethidine, buprenorphine
  • Weak- codeine, dihydrocodeine, dextropropoxyphene
4
Q

How do opioids work?

A
  • They MIMIC ENDOGENOUS OPIOID PEPTIDES by causing a PROLONGED ACTIVATION OF OPIOID RECEPTORS- usually mu (µ) receptors
  • these receptors are disrupted widely thruout the CNS most highly in areas involved in nociception such as dorsal horn of the spinal cord / thalamus
  • so facilitating the OPENING OF POTASSIUM CHANNELS ( causing HYPERPOLARIZATION) and CALCIUM CHANNELS ( inhibiting transmitter release) at the NEURONAL LEVEL, acting via G PROTEINS linked to ADENYLATE CYCLASE
5
Q

Where are opioid receptors concentrated?

A
  • Most highly in areas involved in NOCICIEPTION e.g. DORSAL HORN of the spinal cord and THALAMUS
6
Q

What are the clinical effects of opioids ?

A
  • Analgesia
  • Sedation
  • Euphoria
7
Q

What are the adverse effects of opioids ?

A
  • *Respiratory depression
    • removed with naxolone ( short acting) or naltrexone ( long acting)
  • * Nausea and Vomiting
    • due to stimulation of chemoreceptor trigger zone
  • *Constipation
    • require laxatives with strong opioids
  • *Tolerance and Dependance-
    • to strong opioids in addicts
  • * Postural Hypotension-
    • depression of vasomotor centre
  • *bilary spasm!
    • constriction of sphincter of Oddi- esp morphine
  • ***Pruritis due to histamine release **
  • Bronchoconstriction- due to histamine release
8
Q

What acts quicker morphine or diamorphine?

A
  • Diamorphine ( heroin) as more lipid soluble than morphine
  • Fentanyl can be given transdermally
  • Buprenorphine is effective given sublingually but associated with vomiting
9
Q

Give so examples of NSAIDS?

A
  • Salicylate acid derivates
    • aspirin
  • Propionic acid derivates-
    • ibuprofen, naproxen ( low incidence of side effects, first line in inflammatory arthropathies)
  • Miscellaneous -
    • diclofenac, Indomethacin
  • Selective cox2
      • celecoxib, rofecoxib ( few GI side defects but increased risk of cardiovascular morbidity / mortality)
  • Oxicams- piroxicam (long t1/2 but assoc with GI bleeding)
  • Pyrazolones- azapropazone- potent and high incidence se
10
Q

How do NSAIDS act?

A
  • All inhibit CYCLO- OXYGENASE (COX) -> INHIBITION OF PROSTAGLANDIN SYNTHESIS.
  • PG sensitize the nociceptive nerve endings to inflammatory mediators like histamine and bradykinine.
11
Q

What is cox1/2?

A
  • Cyclo-OXYGENASE exists as a CONSTITUTIVE ISOFORM
  • cox1 in most tissues where it has a house keeping function.
  • Yet at sites of INFLAMMATION Cox2 is stimulated by cytokines.
12
Q

How do NSAIDS exhibit their an-inflammatory action?

A
  • By inhibition of COX2
13
Q

What problems does inhibition of cox1 by NSAIDS do?

A
  • Results in gastrointestinal damage-
    • dyspepsia , gastritis, nausea
    • -as a result of loss of the gastroprotective effects of prostaglandins E2 ( PGE2) and I 2( PGI2) which inhibit gastric acids secretion, increased blood flow thru the gastritis mucosa.
14
Q

What chemical disadvantage does aspirin have? How does it do this? What other actions does it have?

A
  • It is an IRREVERSIBLE INACTIVATOR OF COX By ACETYLATING a SERINE residue of the CONSTITUTIVE form of the enzyme
  • ANTIPLATELET effects-
    • inhibition of Platelet Aggregation
    • Used in prevention of COLORECTAL CANCER/ delaying Alzheimer’s disease
15
Q

What other clinical effects do NSAIDS have? How do they do these things?

A
  • Analgesics
    • via inhibition of PG, which sensitize nocipetive nerve endings to inflammation
  • ANTI-INFLAMMATORY
    • via inhibition of prostaglandins -> less vasodilation and oedema
  • ANTIPYREXIAL-
    • by **inhibition of endogenous pyrogen IL-1 **which acts via PG to elevate the hypothalamic set point for temperature control to fever.
  • ** NSAIDS are reversible non selective competitve inhibitors of COX
16
Q

What are the side effects of NSAIDS ?

A
  • GI- Dyspepsia, nausea, gastritis
    • inhibition of COX1 due to loss of protective prostaglandins E2 and I2 which inhibit gastric acid secretion, increasing blood thru the gastric mucosa, cytoprotective action
  • RENAL
    • prostaglandins are involved in renal blood flow and NA/ h20 excretion.
    • pt with cirrhosis, cardiac failure -increase in angiotension 2/ catecholamines-> inhibiting renal PG synthesis -> sodium retention! reduced blood flow- reversible renal insufficiency
  • LUNG- bronchospasm in aspirin sensitive asthma, nasal polyposis
  • MINOR- rash, urticaria, photosensitivity rxns
17
Q

What is paracetamol ? How does it act?

A
  • ACETAMINOPHEN
  • A WEAK INHIBITOR OF SYNTHESIS OF PROSTAGLANDIN
  • via the production of reactive metabolites by the peroxidase function of COX 2 which could deplete gluthione, a cofactor of enzymes such as PGE synthase
  • Central action via descending serotonergic pathways
18
Q

What mode of actions do paracetamol have?

A
  • ANTIPYREXIAL
  • ANALGESIC
  • Weak antiinflammatory
  • well absorbed orally
  • doesn’t cause gastric irriation
19
Q

What side effects are there of paracetamol?

A
  • ANALGESIC- associated NEPHROPATHY
    • may occur follwoing long term high doses of paracetmol
  • HEPATOTOXICITY in OVERDOSE-
    • potentially fatal liver damage by saturation of the normal conjugating enzymes causing drug to be converted by mixed function oxidises to N-acetyl-p- benzoquinone imine. If it is not inactivated by conjugation with glutathione it reacts with cell proteins -> hepatic necrosis :(
20
Q

Name some type of local anaesthetics?

A
  • ESTERS- COCAINE, PROCAINE
  • AMIDES- Lignocaine, buprivacaine, prilocaine
21
Q

What is the action of local anaesthetics?

A
  • They BLOCK the **ACTION POTENTIAL INITIATION and PROPAGATION in NEURONS **By physically PLUGGING THE TRANSMEMBRANE PORE OF NA CHANNELS
22
Q

Describe the local anaesthetic molecules?

Why is this Important in their role?

A
  • AMPIPHILIC molecules with a HYDROPHOBIC AROMATIC GROUP LINKED by an ESTER or AMIDE bond to a BASIC AMINE GROUP.
  • Their activity is strongly pH DEPENDENT-
    • being INCREASED in ALKALINE pH - proportion of ionized molecules is LOW- allows them to penetrate the nerve sheath/ axon as the unionized form is more membrane permeant.
23
Q

What is the order of the nerves local anesthetic block first?

A
  • Small myelinated axons- NOCICIEPTION and sympathetic transmission in** A delta/C** fibres first
  • Unmeylinated axons
  • Large myelinated axons
24
Q

How can local anesthetic be given?

A
  • Direct infiltration
  • Intravenously
  • Nerve block
  • Spinal
  • Epidural
25
Q

What is the max dose of lignocaine , bupivicaine, Levobuvicaine and prilocaine that can be given to an adult?

A
  • Lignocaine 4mg/kg , w adrenaline 7mglkg (90-200mins)
  • Bupivicaine 2mg/kg , w adrenaline 3mg/kg (180-300 mins)
  • Levobupivicaine 2mg/kg , w ardrenaline 3mg/kg (180-300mins)
  • Prilocaine- 7mg/kg (w adrenaline 10mg/kg ( 60-90 mins)
  • To calculate the maximum recommended dose, the weight of the patient must be known.
  • A maximum dose of 4 mg/kg of lidocaine can be used per 90-200 minutes. In a 10 kg patient, this means that: 4 mg/kg x 10 kg = 40 mg total can be used. As 1% Lidocaine contains 10 mg of Lidocaine per mL, this means that we can use a total of 4 mL.
26
Q

How are the ester and AMIDE local anaesthetics broken down?

A
  • Esters- rapidly hydrolysed by plasma cholinesterase
  • Amides-metabolised in the liver
27
Q

What are the adverse effects of local anaesthetics?

A
  • CNS
    • agitation, confusion, tremors -> CONVULSIONS, RESPIRATORY DESPRESSION
  • CVS-
    • MYOCARDIAL DEPRESSION, VASODILATION-> HYPO BP
  • HYPERSENSITIVITY REACTIONS
28
Q

What are glucorticoids and name some examples?

A
  • a class of steriod hormones that bind to the glucocorticoid receptor ( present in every cell)
  • glucocorticoids are part of the feedback in the immune system to turn down immune activity ( inflammation)
  • Mild potent ( class I) - hydrocortisone
  • Moderately potent ( class 2)- triamcinolone
  • Potent ( class III)- methylprednisolone
  • very potent ( class iv)- betamethasone diproprionate
29
Q

What are the effects of glucocorticoids?

A
  • Anti-inflammatory
  • Immunosupressive
30
Q

How do glucocorticoids act?

A
  • Act on all phases of inflammatory response
  • interact with intracellular receptors forming steroid-receptor complexes that modify gene transcription at the DNA level-> induction or inhibition of protein synthesis
    • e.g. inhibition of genes for COX-2, phospholipase A2, cytokines such as IL
  • Glucocorticoids also directly depress monocyte/macrophage function, decrease T cell levels and directly inhibit lymphocyte transport to the site of antigenic stimulation and antibody production
31
Q

How can glucocorticoids be given?

A
  • Orally
  • topically
  • parentenally
32
Q

How are glucocorticoids carried in the blood?

A
  • Bound to corticosteriod binding globulin
  • enter cells by diffusion
  • metabolised in liver
33
Q

What are the effects of glucocorticoids?

A

“I WAS HOPPING MAD”

  • Infection
  • Wasting of muscles ( due to protein loss)
  • Adrenal insufficiency
  • Sugar disturbances ( hyperglycaemia/diabetes)
  • Hypotension
  • Osteoporosis
  • Peptic ulcer
  • Pancreatitis
  • Proximal myopathy ( due to protein loss)
  • Incidental ( moon facies/orange on a stick- central obesity, easy bruising, hirstism
  • Necrosis of femoral head
  • Glaucoma
  • MAD- psychological cahnges- europhia/depression/psychosis/emotional lability)
34
Q

When are anticoagulants used?

A
  • Prophylaxis
  • tx of thromboembolism
35
Q

What are the different classes of anticoagulants?

A
  • Vitamin K antagonists
    • Warfarin
  • Inhibitors of thrombin
    • unfractionated heparin
    • low molecular weight heparins (LMWH)
      • enoxaparin/dalteparin
    • Fondaparinux
    • oral thrombin inhibitors
      • melgatran
36
Q

What is warfarin?

A
  • A coumarin derivative
  • with a similar structure to vitamin K
  • active orally
  • blocks vitamin K dependent Gamma carboxylation of glutamine residues on factors II, VII, IX, X -> modified factors known as PIVKA (proteins in vitamin K absence)
  • these modified factors cannot bind calcium and so inactive for coagulation
37
Q

How long does it take for warfarin to achieve it full anticogulant effect?

A
  • 2-3 days
  • as inactive factors replace active ones
38
Q

How is the effect of warfarin measured?

A
  • Prothrombin time
  • expressed as the internatinal normalised ratio (INR)
39
Q

What is the half life of warfarin?

A
  • 40 hrs
  • 5 days for INR to return to normal after cessation of tx
40
Q

How is warfarin metabolised?

A
  • by hepatic microsomal enzymes to inactive 7 hydroxywarfarin
41
Q

What are the adverse effects of warfarin?

A
  • Haemorrhage
    • in overdose - acutely reverse with clotting factors, if severe consider vitamin K
  • Drug reactions
    • induce- Barbiturates/ carbamazepine
    • Inhibit- ethanol/metronidazole
  • **Teratogenicity **
42
Q

What is heparin?

A
  • A naturally occuring glycosaminogylcan
  • vary molecular weight (5000-15000)
  • given by injection
    • subcutaneous/ IV
  • Short acting
43
Q

How does heparin work?

A
  • It forms a 1:1 complex with anti-thrombin III, a protease inhibitor that inactivates thrombin ( factor II)
  • also inactivates factor Xa
44
Q

How is heparin effects measured?

A
  • Activated partial thromboplastin time - APTT
  • heparin has short duration of action ( 4-6 hours)
45
Q

What does low molecular weight heparin inhibit?

A
  • LMWH anti-thrombin III complex inhibits factor Xa only
  • results in less bleeding
  • longer half life and so only single daily doses
  • given subcutaneously injection
  • doesn’t require monitoring
46
Q

What are the adverse effects of LMWH?

A
  • Haemorrhage
    • less with LMWH than heparin
    • stop in bad cases, give protamine sulphate
  • Allergic reaction
  • Heparin induced throbocytopenia ( HIT) - monitor platelets, less with LMWH cf heparin
  • Osteoporosis when used long term
  • Thrombosis- rare
47
Q

what is fondaparinux?

A
  • A pentasaccharide
  • inhibits factor Xa
  • Reduce thromboembolism more effectively than LMWH in hip/knee arthroplasty and fx of hip
  • Given 6h after surgery and at least 12h after removal of spinal/epidural catheter
48
Q

What is melagatran?

A
  • Newer direct oral thrombin inhibitor
  • wide therapeutic and safety window
  • lack of need for monitoring no reported interactions with drugs
49
Q

What is rivaroxiban?

A
  • An oral active direct factor Xa inhibitor
  • max asorbed from but
  • action is hours
  • effects last 8-12 hours but factor Xa activity does not return for 24 hrs so once daily dosing fine
  • Inhibition of Factor Xa interrupts the intrinsic and extrinsic pathway of the blood coagulation cascade, inhibiting both thrombin formation and development of thrombi.
  • Rivaroxaban does not inhibit thrombin (activated Factor II), and no effects on platelets have been demonstrated