Flashcards in Drugs Deck (68)
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1
Describe the mechanism of action of NSAIDs
Block production of prostaglanding by blocking COX conversion of arachidonic acid to PGG2
2
Compare COX 1 and 2
- COX1: constitutive, always present, maintain turnover cells, required for life
- COX2: inducible, active in response to inflammatory stimulus, invoke production of PGs that are not usually there (PGE2)
3
Where are COX1 found?
- Intestines
- Platelets
- Stomach
- Kidney
4
Where are COX2 found?
- Macrophages
- Leukocytes
- Fibroblasts
- Endothelial cells
5
Outline some equine specific problems with NSAIDs
- Thrombophlebitis wih pheynbutazone if have perivascular injection
- Prescription of phenylbutazone only done when this can be entered into passport immediately
6
Give examples of suggested equine specific effects of NSAIDs that have
Inhibit:
- Inflammation
- Pyrexia
- Oedema
- Endotoxaemia
- Ileus
- Adhesion formation (tenuous evidence)
- Thrombosis
7
Discuss the effect of NSAIDs on wound healing
- Some compromise to healing
- However pain has more significant impact on wound healing so administration of NSAIDs still positive
8
Outline the pharmacokinetics of NSAIDs
- Hepatic metabolism and renal excretion
- High protein binding, low vol of distribution
- Significant individual variation in response and susceptibility to toxicity
- Effects often outlive the plasma half life
9
Compare the risks of NSAIDs in ponies and horses
Ponies more susceptible to phenylbutazone toxicity than horses
10
Explain the adverse effects of NSAIDs regarding the kidney
- Reduce renal blood flow as this is mediated by prostaglandins in the medulla
- Hypotension + NSAID = renal damage
- Some concern regarding pre/peri-operative use bu several NSAIDs licensed for this
11
Explain the adverse effects of NSAIDs regarding the GI system
- Prostaglandins cytoprotective in the GIT
- GI side effects most common with chronic use
- Direct irritation and PG inhibition are the cause of these signs
- Some require administration with food, others on empty stomach
12
List the serious GI side effects of NSAIDs
- Vomiting (small animals)
- Colic
- Inappetance
- Diarrhoea
- Protein losing enteropathy (PLE), secondary anaemia
- Ulceration
- Death
13
Explain the role of prostaglandins in the GIT
- Cytoprotective
- Decrease volume, acidity and pepsin content in the stomach
- Stimulate bicarbonate secretion
- Promote mucosal blood flow and repair and turnover of cells
14
Compare the adverse effects of NSAIDs on the GI system of young and adult hoses
- Young: more susceptible to gastric ulceration
- Adults: more susceptible to right dorsal colitis
15
Describe the long term adaptation of the GI system to NSAID use
- Increased mucosal blood flow
- Increased mucosa cell regeneration
- Decreased inflammatory cell infiltrate
- From 14 days
16
Explain the role of enterohepatic recycling in the GI safety of NSAIDs
- Excretion into intestine from bile
- Leads to repeated exposure of the duodenum to the drug
- Directly correlates to toxicity
17
Give examples of ways in which the GI safety of NSAIDs can be improved
- Protective strategy
- Sucralfate sucrose (aluminium sulphate)
- H2 agonists
- Protein pump inhibitors
- Newer coxibs
- Different formulation of NSAIDs sometimes tolerated better by different individuals
18
How does hepatotoxicity occur as a consequence of NSAID use?
Type I and type III reactions
19
List the adverse effects of NSAID use in cats
- Hyperthermia
- Respiratory alkalosis
- Metabolic acidosis
- Methaemoglobinaemia
- Haemorrhagic gastro-enteritis
- Renal failure
- Hepatic injury
20
Which NSAID is particularly dangerous in cats?
Carprofen
21
Outline the dosing and frequency of administration of NSAIDs in cats
- Titrate to lowest effective dose
- Dose to lean/ideal body weight in obese animals
- Reduce dose but maintain frequency when titrating down
- Intermittent therapy i.e. 2-3 times a week rather than daily better than nothing
- Liquids more easily measured
22
Describe the screening recommended prior to commencing treatment with NSAIDs in cats
- Thorough history and physical examintion esp. looking at conditions that may impact on NSAID therapy e.g. blood pressure
- Blood biochem to asses renal and hepatic function
- Plasma proteins and haematocrit may be markers of GI bleeding and/or mucosal damage
- Abnormalities may not preclude NSAID use but must be evaluated and discussed with owner
23
List the NSAIDs licensed for systemic use in cats
- Caprofen (once only)
- Ketoprofen
- Meloxicam
- Robenacoxib
- Tolfenamic acid
- Acetylsalicyclic acid
24
Describe the suggested minimum monitoring parameters for long term NSAID use in cats
- History
- Full clinical exam
- Haematocri
- Urea, creatinine, ALT, ALP
- Specific gravity
- Dipstick biochem
25
Out;line guidelines for the safe use of NSAIDs in chronic MSK disease
- Ensure no hypovolaemia
- No concurrent administration of another NSAID or steroid
- No hepatic or renal insufficiency
- Regular (every 3-6 months) monitoring with serum biochem and haematology
26
Explain the risk of paracetamol use in cats
- OD and toxicity common
- Low feline capacity for glucoronidation of paracetamol, rely on sulfation
- When saturated, switches to P450 door detox, creates highly reactive metabolite NAPQI
- overwhelms glutathione availability and result is oxidative injury
27
For which species is paracetamol particularly useful?
- Dogs: adjunct in refractory long term arthritis
- Rodents/rabbits
- Pigs
28
Discuss the use of Mavacoxib
- 1 month duration in dogs
- Good for some owners
- No additional risk of problems in surgery over other NSAIDs
- May need to consider addition of gastroprotectants
29
Outline a therapeutic plan for the use of NSAIDs
- Initial course of NSAIDs, re-check 4 weeks later
- Improvement: continue and reassess q1-2 months
- Little or no improvement: check owner compliance
- Poor compliance: consider reason, consider different formulation
- Good compliance: switch to another NSAID while observing wash out period
- Improvement after switch: continue and reassess q1-2 months
- No/little improvement after switch: reassess diagnosis, consider individual variation, re-evaluate complementary techniques, consider additional of adjunct, seek referral
30
Outline other therapies other than NSAIDs used in the treatment of OA
- Exerise management
- Weight control and diet
- Modification to lifestyle e.g. ramps
- Hydrotherapy and physio
- Chrondroprotectives
- Joint replacement
- IRap (interleukin-1 receptor antagonist protein)
- Stem cell therapies
- Other "drugs": isoxsuprine hydrochloride, vegetable tablets, PLT
- Neutraceuticals
31
Discuss the use of NSAIDs vs opioids in the treatment of MSK pain
- NSAIDs good, if not better option for MSK pain, but less good for
- NSAIDs used more in horses as opioids can have severe side effects in horses
32
Outline the practical considerations for NSAIDs
- Non-scheduled but are POM-V
- Cheaper than opioids
- Little long term decrease in efficacy
- longer duration of action
- Side effects
- Complaince
- Co-morbidities
33
List the groups of antibiotics used for MSK disease
- Beta-lactams
- Aminoglycosides
- Tetracyclines
- Fluoroquinolones
- Sulfonamides
- Diaminopyrimidines (trimethoprim)
- Macrolides
- Phenicols
- Lincosamides
- Metronidazole
34
Which antibiotics used for MSK diseases have the highest priority?
- 3rd and 4th gen cephalosporins
- Fluoroquinolones
- Macrolides
35
State whether beta-lactams are bacteriocidal/static and time/concentration dependent
- Bacteriocidal
- Time dependent
36
State whether aminoglycosides are bacteriocidal/static and time/concentration dependent
- Bacteriocidal
- Concentration dependent
37
State whether Tetracyclines are bacteriocidal/static and time/concentration dependent
- Bacteriostatic
- Time dependent
38
State whether fluoroquinolones are bacteriocidal/static and time/concentration dependent
- Bacteriocidal
- Concentraton dependent
39
State whether sulfonamides are bacteriocidal/static and time/concentration dependent
- Bacteriostatic
- Time dependent
40
State whether trimethoprim is bacteriocidal/static and time/concentration dependent
- Bacteriostatic
- Time dependent
41
State whether metronidazole is bacteriocidal/static and time/concentration dependent
- Bacteriocidal
- Concentration dependent
42
What is the mechanism of action of beta-lactams? Give examples
- Interfere with cell wall synthesis
- Examples: penicillins, cephalosporins, amoxyclav, vancomycin
43
What is the mechanism of action of aminoglycosides? Give examples
- Act on 50s and 30s ribosome subunits to interfere with protein synthesis
- Amikacin, gentaycin, tobramycin, neomycin, streptomycin, kanamycin
44
What is the mechanism of action of amphenicols? Give examples
- Act on 50s subunit to interfere with protein synthesis
- Chloramphenicol, florfenicol
45
What is the mechanism of action of macrolides? Give examples
- Act on 50s subunit to interfere with protein synthesis
- Erythromycin
- Acythromycin
46
What is the mechanism of action of lincosamides? Give examples
- Act on 50s subunit to interfere with protein synthesis
- Lincomycin, clindamycin, pirlimycin
47
What is the mechanism of action of sulphonamides? Give examples
- Act on 30s subunits to interfere with protein synthesis, interfere with metabolic pathways
- Sulfamethoxazole
48
What is the mechanism of action of dyaminopyrimidines? Give examples
- Act on 30s subunits to interfere with protein synthesis, interfere with metabolic pathways
- Trimethoprim, pyremethamine
49
Which antibiotics are DNA synthesis inhibitors? State how
- Fluroquinolones (DNA gyrase inhibitors)
- Metronidazole (free radical disruption of bacterial DNA)
50
Which antibiotics are RNA synthesis inhibitors? State how
Rifamycin only - inhibit DNA dependent RNA synthesis
51
Which antibiotics are cell membrane inhibiting?
- Polymyxin B
- Bacitracin
52
What is the difference in use between time dependent and concentration dependent antibiotics?
- Concentration: only needs to be given SID (usually)
- Time: frequent admin, 2/3/4 times a day
53
Give examples of antagonistic antibiotic combinations?
- Bacteriostatic + bacteriocidal usually antagonistic
- Chloramphenicol + beta lactams
- Tetracycline + quinolones
- Erythromycin + aminoglycosides
54
List the key side effects of penicillins
- Anaphylaxis
- Cardiac arrythmias
- Transient hypotension
- Autoimmune haemolytic anaemia
55
List the key side effects of aminoglycosides
- Nephrotoxic
- Neuromuscular blockade
- Ototoxic
56
List the key side effects of metronidazole
- Inappetance/anorexia
- Enterocolitis
57
List the key side effects of tetracyclines
- Nephrotoxic
- Gastric ulceration
- Erupting teeth and urine discolouration
58
List the key side effects of chloramphenicol
Reversible aplastic anaemia (humans)
59
List the key side effects of fluoroquinolones
Oral ulceration
60
List the key side effects of TMPS
Enterocolitis
61
What are the contraindications for TMPS?
- Pus (natural source of PABA)
- Gestation (blocks folic acid production)
- Bioavailability decreased by feed
- Sudden death when used with IV alpha 2
62
What are the contraindications for use of fluoroquinolones?
<3yo - causes cartilage disorder
63
What are the contraindications for use of tetracyclines?
IM administration (high risk of necrotic reaction)
64
Which antibiotics are concentrated in urine?
- Fluroquinolones
- Aminoglycosides
- Beta-lactams
- Sulfonamides/potentiated sulfonamides
65
Which antibiotics are concentrated in leukocytes?
- Clindamycin
- Erythromycin
- Fluoroquinolones
- Rifampicin
66
Which antibiotics will always cross the BBB?
- Chloramphenicol
- Doxycycline minocycyline
- Fluoroquinolones
- Metronidazole
- Rifampicin
- Sulphonamides/trimethoprim
67
Which antibiotics will cross the BBB when there is inflammation?
- Penicillins
- Some cephalosporins (ceftriaxone, ceftazidime, cefotaxime)
- Vancomycin
68
