ORAL SURGERY – PHARMACOLOGY & THERAPEUTICS Flashcards
1
Q
Which receptors pick up pain superficially on our surfaces?
A
Nociceptors
2
Q
Which nerve fibres detect the pain stimuli?
A
A-delta and C-fibres
a delta faster - myelinated
c - non myelinated
3
Q
What limits the long-term use of NSAIDS’s?
A
Renal, Gastric and Cardiac complications
4
Q
Complete the WHO analgesic ladder?
1
2
3
4
A
- Pain: simple analgesics (non-opioid)
- Pain: simple analgesics + NSAID’s
- Pain persisting or increasing: weak opioids
- Pain persisting or increasing: + strong opioid morphine +/- adjuvant
5
Q
Aspirin has 4 therapeutic activity what are they?
A
- Anti-pyrexic
- Anti-platlet/thrombotic
- Anti-inflammatory
- Analgesic-mild/moderate
6
Q
What is the mechanism of action for aspirin?
A
Aspirin works as a COX inhibitor (cox 1,2,3) .
7
Q
What are the 7 functions of aspirin?
A
- Regulate BP
- Renal effects
- Inflammatory response
- Duration and intensity of pain
- Fever
- Gastric effects
- Inhibits platelet aggregation and thrombosis
8
Q
Aspirin has a greater inhibition of cox 1 or cox 2?
A
Cox 1 (x100)
9
Q
Which COX induces inflammatory sites?
A
COX-2
10
Q
Which COX induces stomach, kidney, intestines, platelets, endothelium?
A
COX-1
11
Q
What are the indications for Aspirin?
A
- Acute pain
- Dental pain
- Rheumatic fever
- Rheumatoid arthritis
- Other inflammatory disease
- Fever
- Acute coronary syndrome/ischemic stroke
- Anti-thrombotic
12
Q
How quickly is aspirin absorbed?
A
5-16 mins
13
Q
What is the half life of aspirin?
A
20-30 mins
14
Q
Why is aspirin avoided in pregnancy?
A
Because it crosses the placenta
15
Q
What are the contradictions for aspirin?
A
- Gastrointestinal
- Respiratory – AERD (What is aspirin-exacerbated respiratory disease)
- Renal (3x increase renal failure)
- Pregnancy
- Gout (increase in uric acid)
- Skin reactions
16
Q
Prostaglandin inhibition comes as a result of taking aspirin through the COX 1 route. One of the side effects of long-term use of aspirin is ulcerogenesis, how does this effect the intestines?
A
The long-term use of aspirin results in the inhibition of prostaglandins.
Prostaglandins are responsible for mucus production. Taking aspirin reduces the amount of mucus that is produced, which in turn increases the acid production in the intestines. It increases the cell permeability for H+. this over time increases the development of ulcers.
17
Q
What is the standard adult dose for aspirin?
A
Aspirin 300-900mg 4-6 hourly, maximum of 4g daily (preferably with food)
18
Q
What is the standard adult dose for Ibuprofen?
A
oral 400mg TDS max 2.4g/day
19
Q
What is the standard adult dose for diclofenac?
A
Oral 50mg TDS max 150mg/day
20
Q
Aspirin is NOT advised for some groups without medical advice, who are these groups?
A
- Children under 16
- Asthmatics
- Women in the last trimester of pregnancy
- Heavy alcohol drinkers
- People with bleeding disorders
21
Q
Why can’t/shouldn’t heavy alcohol drinkers take aspirin?
A
Mixing aspirin and alcohol can result in certain types of gastrointestinal distress. Aspirin can cause nausea and vomiting when mixed with alcohol. The combination can also cause or worsen ulcers, heartburn, or stomach upset.
22
Q
Acetylsalicylic acid is known as?
A
Aspirin
23
Q
What is antipyretic?
A
An antipyretic is a substance that reduces fever. Antipyretics cause the hypothalamus to override a prostaglandin-induced increase in temperature. The body then works to lower the temperature, which results in a reduction in fever.
24
Q
Is aspirin a NSAID?
A
Yes
25
Is prostaglandin an inflammatory mediator?
Yes
26
Prostaglandins bind to which receptors?
Prostanoid receptor.
27
What can arachidonic acid be converted to in the event of cell damage or illness?
Arachidonic acid can be converted to prostaglandin H2, which then converts to prostaglandin E2.
28
What is the function of prostaglandin E2?
Initiate fever, cause pain and inflammation.
29
Which enzymes are responsible for the conversion of arachidonic acid into prostaglandin?
Cyclo-oxygenase 1 and Cyclo-oxygenase 2 (Cox-1, Cox-2).
30
Why is Cox-1 always active in the body?
To maintain homeostasis
31
Which Cox is active during stress, injury, and trauma?
Cox-2 (inflammatory)
32
Why is aspirin a non-specific NSAID?
Because it blocks both Cox-1 and Cox-2
33
In the event of an injury where you a bleeding, platelets work by forming a platelet plus to stop the bleeding. Arachidonic acid in platelets is converted to prostaglandin H2 through Cox-1. Prostaglandin H2 is then converted to what in PLATELETS?
Thromboxane A2 (this causes platelet aggregation).
34
COXIBS known as specific Cox inhibitor inhibits which Cox?
Cox-2
35
Aspirin, ibuprofen and naproxen are known as non-specific NSAIDS, meaning they influence both Cox1 and Cox2. What physiological effect do they have in the body?
They work as an antipyretic, analgesic and anti-inflammatory.
36
Cox-1 is normally active in the body and maintains homeostasis, particularly in the stomach and the kidneys. Why does inhibiting Cox-1 through the intake of aspirin have an affect on the stomach?
Cox-1 converts arachidonic acid in the stomach to prostaglandin H2, which then forms prostaglandin E2 and prostaglandin I2. These prostaglandins help reduce acid production in the stomach. So, by inhibiting Cox-1 in the stomach you are essentially allowing more acid to be produced in the stomach. Resulting in the long-term complications such as.
1. Dyspepsia
2. Nausea
3. Vomiting
4. Gastric ulceration
5. Haemorrhage
37
Cox-1 is normally active in the body and maintains homeostasis, particularly in the kidneys and the stomach. Why does inhibiting Cox-1 through the intake of aspirin influence the kidneys?
Cox-1 converts arachidonic acid in the stomach to prostaglandin H2, which then forms prostaglandin E2 and prostaglandin I2. In the kidneys prostaglandin E2 and Prostaglandin I2 help maintain renal blood flow. Taking aspirin can cause nephritis and kidney injury.
38
What are the 4 ANTS by aspirin?
1. Anticoagulant
2. Antihypertensives
3. Antidepressants
4. Anti-epileptics
5. NSAIDs
6. Thrombocytes
7. Steroids
39
There are hundreds of different types of antibiotics, but most of them can be classified into 6 groups. What are those groups.
1. Penicillin’s
2. Cephalosporins
3. Aminoglycosides
4. Tetracyclines
5. Macrolides
6. Fluoroquinolones
40
Antibiotics can be divided into two classes based on their mechanism of action that removes the bacteria, what are they?
1. Bactericidal – damaging the bacteria’s cell wall
2. Bacteriostatic – stalls bacterial cellular activity without directly causing bacterial death.
41
What type class does penicillin fall in to in reference to its structure?
Beta-lactam
42
Does penicillin work as a bactericidal or bacteriostatic?
Bactericidal affecting cell wall synthesis
43
Which class of bacteria has a thick peptidoglycan wall?
Gram positives
44
Which class of bacteria has an extra phospholipid bilayer outside of the cell wall?
Gram negative
45
Peptidoglycan walls in a bacteria is composed of chains of a amino sugars such as?
NAMS and NAGS
46
The NAMS and NAGS amino sugar chains are crosslinked together by which enzyme?
Transpeptidase enzyme.
47
Which protein does penicillin bind to in the cell membrane?
Penicillin binding protein, this activates the penicillin antibiotics.
48
What does the active penicillin antibiotics do to the peptidoglycan?
they bind and inactivate the transpeptidase enzymes, which results in the inactivation of the amino acids chains and the collapse of the cell wall.
49
Is penicillin a broad or narrow spectrum antibiotic?
Narrow spectrum
50
Penicillin is useless against organisms that produce what?
Beta lactamases
51
How is penicillin g administered?
Injection
52
Phenoxymethylpenicillin is known as what?
Penicillin v
53
What are the indications for penicillin g?
1. Reserved for severe infection (IV)
2. Oral route compromise (malabsorption syndrome or vomiting)
3. Recent penicillin or prophylaxis of Rh fever, alternative
54
Of the antibiotics which have the highest propensity for hypersensitivity reactions?
Penicillin and Beta lactams
55
What percentage of the population have a reaction to penicillin?
8%
56
What are the two common type of rash, experienced from an allergic reaction to penicillin V?
maculopapular or urticarial.
57
The following reactions are immediate or delayed reactions to penicillin v hypersensitivity?
1. Nausea/vomiting
2. Pruritis
3. Erythema/ urticaria/rash
4. Wheeze
5. Laryngeal oedema
6. Angiodema
7. Bronchospasm
8. Hypotension
9. Cardiovascular collapse
Immediate
58
The following reactions are immediate or delayed reactions to penicillin v hypersensitivity?
1. Vesicular
2. Maculo-papular
3. Bullous
4. Urticarial
5. Scarlatiniform
delayed
59
What are the risk factors for developing hypersensitivity to penicillin v?
1. Multiple drug allergies
2. Atopic disease
3. Asthma
4. Allergic rhinitis nasal polyps
60
When an adverse drug reaction occurs, it is important to complete the?
Yellow card reporting mechanism.
61
What is the dose/duration/frequency/route for penicillin v?
1. Dose – 500mg
2. Interval – 6 hourly
3. Duration – 3-5 days
4. Route – oral
5. Loading dose – yes
6. Food? – fasting
62
What is the dose/duration/frequency/route for penicillin G
1. Dose – 1.2g
2. Interval – 6 hourly
3. Duration – 3-5 days
4. Route – IV
5. Loading dose – no
63
What are the 3 evasion mechanisms of penicillin v?
1. Reduced drug binding to penicillin binding protein PBP (altering configuration)
2. Hydrolysis of the drug by beta lactamase enzymes (this is the principal mechanism in most species)
3. Development of a tolerance by disabling their autolysis mechanism (penicillin becomes bacteriostatic instead of bacteriocidal)
64
Rapidly dividing bacteria are most affected by bacteriostatic or bacteriocidal antibiotic?
Bacteriocidal. Something to do with them dividing there cell walls and the antibiotic works by breaking these new forming walls. Meh
65
How to NSAIDs increase the half life of penicillin?
They reduce the renal excretion
66
What are the common/uncommon side effects of penicillin?
1. Diarrhoea
2. Nausea
3. Skin rash
Uncommon
1. Vomiting
2. Urticaria & pruritis
3. Arthralgia
67
What are the alternatives to penicillin if you have an allergy to it?
1. Metronidazole
2. Clarithromycin
3. Erythromycin
4. Clindamycin
68
what are the indications for prescribing penicillin v?
oral dental infections
69
what is penicillin mechanism of action?
Cell wall inhibitor
70
what is the half life of penicillin?
30 mins
71
What is metronidazole’s mechanism of action?
Inhibition of DNA replication
72
Which antibiotic penetrates all cells equally?
Metronidazole (enzymatic reduction/oxidoreductase)
73
Is metronidazole a bactericidal or bacteriostatic?
Bactericidal
74
What is the spectrum of metronidazole spectrum of activity?
1. Obligate anaerobes
2. Gram-ve pathogens (anaerobes)
3. Clostridium (c.diff)
4. Fusobacterium spp
5. Prevotella
6. Peptostreptococcus
75
What is the killing mechanism for metronidazole?
Concentration dependent
76
What is the oral absorption rate of metronidazole?
Nearly 100 percent
77
What is the half life of metronidazole?
8 hours
78
What is the peak serum time for metronidazole?
60-120 mins
79
Which trimester is metronidazole to be avoided?
1st trimester
80
How many metabolites of metronidazole is there and where is it metabolised in?
5 active metabolites and metabolised in the kidney.
81
Metabolism of metronidazole is severely reduced in what patients?
Patients with severe hepatic function.
82
What are the indications for metronidazole?
1. Oro-dental infections
2. Anaerobes suspected
3. Acute necrotizing forms of gingivitis
4. Pericoronitis (with systemic involvement)
5. Dental abscess
6. Beta-lctamase producing anaerobes
7. Alternative to penicillin allergy
83
Which enzyme pathway metabolises metronidazole?
Cytochrome P450 pathway
84
The cytochrome P450 pathway increases the production of what for the reduction of the half life of metronidazole?
Phenobarbital and phenytoin.
85
What are the main adverse effects of metronidazole?
1. Gastrointestinal
2. Nausea
3. Vomiting
4. Anorexia
5. Diarrhoea
6. Epigastric distress
7. Abdominal cramping
8. Constipation
86
What are the rare adverse effects of metronidazole?
1. Convulsive seizure
2. Peripheral neuropathy (paraesthesia extremities)
3. Also: dizziness, vertigo, incoordination, ataxia, irritability, depression, weakness and insomnia
4. Prolonged or intensive
87
What are the main oral adverse effects of metronidazole?
1. Unpleasant taste (varied)
2. Sharp/metallic
3. Taste disturbances
4. Furred tongue
5. Glossitis
6. Stomatitis
7. Candida
88
What are the rare reversible adverse effects of metronidazole on blood?
1. Blood dyscrasias (any blood related disease)
2. Temporary neutropenia
3. Thrombocytopenia (deficiency of platelets in the blood.)
89
What is the main mechanism method of resistance to metronidazole?
Chromosomal/plasmid mediated – reduction in the oxidoreductase
90
What structural similarity does metronidazole have?
Tetraethylthiuram disulfide (drug taken for alcoholics) bad reaction.
91
What is the chemical responsible for hangovers?
Acetaldehyde this is also experienced in metronidazole.
92
What is the dosage for metronidazole?
200mg – 400mg
93
What is the interval for metronidazole?
8-12 hourly
94
What is the duration for metronidazole?
3-5 days
95
What is the route for metronidazole?
Oral
96
Do you need a loading dose for metronidazole?
No
97
What are the two interactions you want to avoid with metronidazole?
Alcohol and warfarin
98
Clindamycin derives from which antibiotic?
Lincomycin
99
What is the spectrum of activity for clindamycin?
1. G +ve / G-ve bacteria
2. Penicillinase staph.
3. Bacterioides
4. Prevotella
5. Porphyromonas, veilonella
6. Peptostrep, actinomyces
7. Eubacteria and clostridium
100
What is the mechanism of action for clindamycin?
Inhibits protein synthesis by binding on the 50sribosomal subunit
101
Is clindamycin bacteriostatic or bactericidal?
Its mechanism of action is dependant on its concentrations, it is bactericidal at higher concentrations, bacteriostatic at lower.
102
What is the oral absorption of clindamycin?
90%
103
What is the half life of clindamycin?
3 hours
104
Where is clindamycin metabolised?
Liver
105
Is clindamycin affected by food?
No
106
How quickly can clindamycin reach peak serum time?
45-60
107
Can clindamycin penetrate to the bone?
Yes
108
Can clindamycin penetrate the CSF?
No
109
What are the unwanted affects of clindamycin?
1. Nausea/vomiting
2. Abdominal pain
3. Oesophagitis
4. Glossitis
5. Stomatitis
6. Allergy
7. Myelosuppression (reversible)
8. Metallic taste
9. Maculopapular rash
110
What drugs significantly slow down absorption for clindamycin?
Anti-diarrhoeal drugs
111
Clindamycin is regarded as a second line antibiotic drug, what are the indications for it?
1. Oro-facial infections
2. Penicillin allergy
3. Refractory to penicillin(s)/metronidazole.
4. Beta lactam resistance
112
What are the contraindications for clindamycin?
1. Allergy
2. Clindamycin should not be used routinely
3. No more effective than penicillin
4. Cross resistance with erythromycin-resistant bacteria
113
What is the dose for clindamycin?
150-300mg
114
What is the interval for clindamycin?
6 hourly
115
How long would you expect to take clindamycin for?
3-5 days
116
What is the route for clindamycin?
Oral
117
Do you need a loading dose for clindamycin?
No
118
If you have diarrhoea whilst on clindamycin what should you do?
Cease immediately.
119
What is acetaminophen?
Paracetamol
120
The mode of action for paracetamol is quite vague, however there is strong evidence that paracetamol affects which COX pathway
COX-3.
121
According to the WHO analgesic ladder, paracetamol is considered a what?
A first line analgesic, used for acute and chronic, mild to moderate pain. Also, an antipyretic.
122
What affects does paracetamol have on platelet aggregation?
No effects
123
What are positive negative effects that paracetamol has?
1. Fewer adverse drug reaction
2. Little effect respiratory
3. Little effect cardiovascular
4. Little or no gastric irritation
5. No relevant impact on uric acid excretion
124
What are the indications for paracetamol?
1. First line for dental pain
2. Non inflammatory conditions - where NSAIDs are contraindicated (asthmatics, gastric ulceration)
125
What are the 3 methos of taking paracetamol?
1. Tablet
2. Suppository
3. Iv
126
What is the half life of paracetamol?
4-8 hours
127
What is the peak plasma for paracetamol?
60 mins
128
Where is the primary transformation of paracetamol?
Liver
129
What are the contraindications/side effects for paracetamol?
1. Blood dyscrasias (thrombocyte-, neuro, -leuco-penia)
2. Hepatotoxicity
3. Liver disease, alcohol, malnutrition, dehydration
130
What is the dosage for paracetamol?
Standard adult dose: 10-15mg/Kg every 4-6 hours to a daily maximum of 4 grams (500mg = 1 tablet)
131
What are the side effects of paracetamol – systematic review?
1. Increased mortality
2. Cardiovascular adverse events
3. Gastrointestinal adverse effects
4. Renal impairment
132
What are the special considerations for paracetamol?
1. Overdose and toxicity
2. Toxic dose (20-30 tablets)
3. Acute liver damage – 10-15g (8g)
4. 25g fatal
5. Maximal liver damage 3-4 days post ingestion
6. Urgent hospital transfer
7. Treatment for overdose – activated charcoal, acetylcysteine IV – 10-32 hours
133
What is the function of inactivating glutathione?
It binds to the toxic metabolite NAPQI, of paracetamol, and inactivates it making it nontoxic.
134
