Therapeutics Flashcards
1
Q
Why should amoxicillin and methotrexate never be prescribed together?
A
Because Amoxicillin reacts with methotrexate by increasing the plasma concentration of it, thereby increasing toxicity, blood disorders and bleeding.
2
Q
What class of drugs does penicillin belong to?
A
Beta-lactams
3
Q
What is the specific function of Pencillin at a cellular level?
A
Interferes with cell wall synthesis and is bactericidal
4
Q
What are the three main mechanisms of action of Penicillin?
A
- Inhibits cross-linking transpeptidase proteins
- Inactivates autolysin inhibitors causing bacterial suicide
- Rapidly divides bacteria
5
Q
What type of bacteria is penicillin most effective against?
A
Gram +ve cocci
6
Q
Why does penicillin act preferentially on rapidly diving bacteria?
A
Because it is within these bacteria that majority of cell wall synthesis takes place.
7
Q
What are the three different types of penicillin preparations?
A
- Pen G
- Pen V
- Procaine/ Benzathine Pencillin
8
Q
What type of pencillin preparation is described:
An injectable from of penicillin which is partly destroyed by gastric processes and has a low absorption.
A
Pen G
9
Q
What type of pencillin preparation is described:
Well absorbed, gastric acid stable, suitable for oral administration. Regarded as highly effective against dento-alveolar infections.
A
Pen V
10
Q
What type of pencillin preparation is described:
Used for long term prophylaxis and for the treatment of early and late latent syphilis.
A
Procaine/ Benzathine Penicillin
11
Q
According to the BNF, what are the dental indications for Pen V?
A
- oral infections
- acute sinusitis
- prevention of recurrent cellulitis (specialist use only)
12
Q
How common is penicillin hypersensitivity?
A
Occurs in 8% of the population
13
Q
What is the key clinical feature of penicillin hypersensitivity?
A
Maculopapular or urticarial rash
14
Q
What is the proportion of fatalities from penicillin reaction?
A
1:60,000
15
Q
What happened at a cellular level upon immediate reaction (type I) to penicillin?
A
Mast cell degradation and histamine release
16
Q
What can be consequences of (the less severe) delayed reaction (type II) to penicillin?
A
- blood dyscrasias (imbalance)
- haemolytic anaemia
- Leukoplenia
- thrombocytopenia
- aplastic anaemia
17
Q
Pencillin hypersensitivity can lead to other obscure autoimmune conditions. Name the 4 conditions.
A
- Eosinophilia
- Steven’s-Johnson syndrome
- Exfoliative dermatitis
- DRESS syndrome
18
Q
What is Stevens’ Johnsons syndrome?
A
“A rare condition arising from “over-reaction” of the immune system to a trigger such as a mild infection or a medicine”
This condition leads to blistering and peeling of the skin,eyes, mouth and throat.
19
Q
What is DRESS syndrome?
A
Drug Reaction with Eosinophilia and Systemic Symptoms.
Caused by medications which can result in a severe reaction. Involves extensive rash, fever, organ involvement etc.
20
Q
What is the cause of mortality in 10% of individuals with DRESS syndrome?
A
Visceral organ compromise
21
Q
What is one of the most severe form of Steven’s Johnson’s syndrome?
A
Toxic epidermal necrolisos
22
Q
Define, eosinophilia.
A
Elevation of total number of bloodstream eosinophils
23
Q
What are the 5 main risk factors for penicillin hypersensitivity?
A
- Multiple drug allergies
- Atopic disease
- Asthma
- Allergic rhinitis
- Nasal polyps
24
Q
In what two groups of individuals will risk of recurrent Pencillin reactions be higher?
A
- Those with repeated exposure to the allergen over short term
- Those who have a long retention of IgE
25
How long should we wait before re-prescribing Pencillin ideally to the same individual and why?
3 years, as serum IgE antibodies often are retained for 10-1000 days.
26
What should be completed when an adverse drug reaction (ADR) occurs?
Yellow card ADR reporting mechanism
27
What regulatory agency administers the yellow card ADR reporting scheme?
Medicines and Healthcare products Regulatory Agency (MHRA) records
28
What is the purpose of the yellow card ADR reporting scheme?
To provide an early warning that the safety of a product may require further investigation.
29
What is the dose, duration, frequency and route of pen V? Also, when should the dose be taken in relation to food?
Dose= 500mg
Interval = 6 hourly
Duration = 3-5 days
Route = oral
Should be take 30 minutes before or two hours after food
30
What are the three main mechanisms by which bacteria evades Pencillin?
1. Reduced drug binding to Penecillin protein PBP
2. Hydrolysis of the drug by beta lactamase enzymes (principle mechanism)
3. Development of tolerance by disabling their autolysin mechanism
31
Define, antagonism of drugs.
Where the administration of two drugs together results in neither of them working efficiently
32
What effects do NSAIDs/probenecid have on Penicillin?
Increases its half-life
33
How do methotrexate and pencillin interact?
Penicillin can reduce the excretion of methotrexate, increasing retention of methotrexate and Therefore increases toxicity of the drug.
34
What are the three main common unwanted side effects of penicillin?
1. Diarrhoea
2. Nausea
3. Skin rash
35
What are three uncommon unwanted effects of penicillin?
1. Vomiting
2. Urticaria (hives) and pruritis (itchy skin)
3. Arthralgia
36
Name 4 alternatives to penicillin if unwanted side effects were to occur?
1. Metronidazole
2. Clarithromycin
3. Erythromycin
4. Clindamycin
37
Name three drugs that interact with penicillin.
1. Warfarin
2. Methotrexate
3. Allopurinol
38
What is a rare unwanted side effect of penicillin to be extra cautionary about?
Potential for toxicity in severe renal failure
39
What is the half life of penicillin?
30 mins
40
What is the mechanism of action of Metronidazole?
Inhibits DNA replication
41
What type of bacteria is metronidazole selective towards?
Anaerobic bacteria
42
What is meant by metronidazole being “concentration dependant” in its killing mechanism?
It kills bacteria based on the peak concentration, so dosage of metronidazole has to be high enough for bacterial killing to be assured.
43
What is the half life of metronidazole?
8 hours
44
What side effect of metronidazole is due to elimination in the kidney?
Causes reddish/brown urine discolouration
45
Where is metronidazole metabolised and eliminated?
Metabolised in the liver and eliminated in the kidney
46
What group of patients need to avoid metronidazole?
1. Those with severe hepatic dysfunction
2. Pregnancy (especially first trimester)
3. Nursing mothers
47
What are the indications for using metronidazole?
1. When anaerobes are suspected
2. Acute necrotising gingivitis
3. Pericoronitis (with systemic involvement)
4. Dental abscess
5. Beta-lactamase producing anaerobes
6. Alternative to pencillin where there is hypersensitivity
48
What enzyme metabolises metronidazole in the liver?
CYP450
49
Give 2 examples of medications that act as enzyme inducers to reduce the half-life of metronidazole?
Phenytoin and phenobarbital
50
What medication decreases enzyme activity in the liver, resulting in a prolonged half-life of metronidazole?
Cimetidine
51
What affect is metronidazole reported to have on warfarin?
It potentiates the anticoagulant effect of warfarin leading to prolonged prothrombin time
52
What are the common adverse effects of metronidazole which would indicate the patient should cease taking the drug?
GI issues: includes nausea, vomiting, anorexia, diarrhoea, constipation, epigastric distress & abdominal cramping.
53
What are the two rarer adverse effects of metronidazole which would indicate the patient should immediately cease taking the drug?
1. Convulsive seizure
2. Peripheral neuropathy
54
What are adverse oral side effects of metronidazole. Name 5.
1. Taste disturbance (unpleasant, sharp/metallic)
2. Furred tongue
3. Glossitis
4. Stomatitis
5. Candida
55
Name 3 very rare adverse affects of metronidazole.
1. Blood dyscrasias
2. Temporary neutropenia (puts you at risk of severe infection)
3. Thrombocytopenia
56
Why should you never drink alcohol when talking metronidazole?
It has a similar interaction with alcohol as the drug disulfirim does. Can be violent reaction (vomiting).
57
For metronidazole, what is the:
Dose given
Interval between dosage
Duration of course
Route of administration
Does it have a loading dose?
Dose = 200-400mg
Interval = 8-12 hourly
Duration = 3-5 days
Route = oral
Loading dose = NO
58
What is the half-life of metronidazole?
8 hours
59
What is the mode of action of metronidazole?
DNA Inhibition
60
What group of antibiotics does clindamycin belong to?
Lincosamides
61
What type of bacteria tend to have resistance to clindamycin?
Aerobic gram -ve bacilli
62
What is the mechanism of action of clindamycin? (Which is similar to that of clarithromycin and erythromycin)
Inhibits protein synthesis by binding to 50s ribosomal subunit
63
What is a key notable feature of clindamycin?
It penetrates bone very well
64
What is a rare and potentially fatal side effect of clindamycin?
Pseudomembraneous colitis
65
What is GI disturbance due to clindamycin treated with?
Vancomycin or metronidazole
66
What other antibiotic should clindamycin never be prescribed alongside and why?
Erythromycin, antagonism causes each drug to be less effective.
67
What is the main contraindication of clindamycin?
Allergy
68
For clindamycin, what is the:
Dose
Interval between taking drug
Duration of course
Route of administration
Is there a required loading dose?
Dose =150-300mg
Interval = 6 hourly
Duration= 3-5 days
Route = oral
Loading dose = NO
69
When should clindamycin be ceased immediately?
If patient has symptom of diarrhoea
70
With what drug is there a theoretical interaction with clindamycin?
Neuromuscular blocking agents
71
What is the half life of clindamycin?
3 hours
72
Is paracetemol believed to have more of a central our peripheral affect?
Peripheral
73
What are the 3 main indications of taking paracetamol?
1. First line for dental pain
2. Inflammatory conditions
3. Where NSAIDs cant be taken
74
What are the drugs that interact with paracetemol and should always be remembered using the SCRAPPP anagram?
S- St John’s wort
C- Carbemazepine
R- Rifampicin
A- alcohol
P- Phenobarbital
P- phenytoin
P- Primidone
75
How many grams of paracetamol can lead to acute liver damage?
10-15g
76
How many grams of paractemol is fatal?
25g
77
What is the treatment for overdose of paracetemol?
Activated charcoal or acetylcysteine IV (oral methionine)
78
What are the contraindications of taking paracetamol?
- liver or kidney issues
- drink more than recommended amounts of alcohol (14 units)
- If weight is less than 50kg
79
What is the therapeutic activity of aspirin?
1. Anti-pyrexic
2. Anti-platelet/thrombotic
3. Anti-inflammatory
4. Analgesic (mild/moderate)
80
Why is it important aspirin should be swallowed and never allowed to dissolve in the mouth?
Secondary to its acidic nature it can lead to sloughing and ulceration in the mouth (essentially an acid burn)
81
What is the mechanism of action of NSAIDs?
COX isoenzyme inhibition
82
What two compounds in aspirin are involved in its regulatory functions?
PGE2 (prostaglandin) and TXA (thromboxane)
83
Aspirin affects COX activity, what type of COX activity is it selective over- COX-1 or COX-2?
COX-1
84
What are the indications for aspirin?
1. Acute pain
2. Dental pain
3. Rheumatic fever
4. RA or other inflammatory diseases
5. Fever
6. ACS/ischemic stroke
85
How does aspirin reduce fever?
Infection or inflammation results in release of cytokines which results in prostaglandins release from the hypothalamus which results in raised body temperature. Aspirin inhibits prostaglandins hence reduces fever.
86
What is the half life of aspirin?
20-30 minutes
87
Is aspirin safe to take in pregnancy or as a breastfeeding mother?
No, avoid, as evidence it crosses the placenta and is present in breast milk.
88
What are the contraindications of taking aspirin? Name 5.
1. AERD- aspirin-exacerbated respiratory disease
2. Renal issues (3x increase of renal failure)
3. GI issues
4. Gout (increases uric acid levels)
5. Poor glycemic control
Etc.
89
In higher doses, particularly over 5 grams a day, what can aspirin cause?
Hypoglycaemia
90
In higher doses, >10 grams a day, what can aspirin cause?
Glycogen depletion in the liver and hyperglycaemia
91
What can result from taking NSAIDs such as aspirin where prostoglandins production is reduced?
Ulcerogenesis
92
What effect does prostaglandin inhibition have on mucous secretion, bicarbonate secretion, and gastric acid production?
Prostaglandins are essential for mucous secretion. Prostaglandins mediate bicarbonate secretion and inhibit gastric acid production.
So, by inhibiting prostaglandins with NSAIDs this INCREASES gastric acid production. Mucous layer is rendered less hydrophobic due to acidic nature of NSAID.
93
How do prostaglandins influence gastric blood flow?
Prostaglandins influence gastric blood flow and increase cell permeability to H+ ions.
94
What medication should be given in conjunction with aspirin to those individuals at higher risk of gastric issues? And why?
Give a prostaglandin analog (e.g. Misoprostol) to reduce the risk of NSAIDs induced gastric ulcers by reducing secretion of gastric acid from parietal cells.
95
Below what age should aspirin never be administered?
Children under 16
96
Why should aspirin be avoided in children under 16?
Due to risk of Reye’s syndrome, a rare but serious condition that causes swelling in the liver and brain.
97
What is considered, in grams, an overdose of aspirin?
10-30g
98
What group of drugs cause principle interactions with aspirin? Use the AAAANTS anagram.
A- anticoagulants
A- antihypertensives
A- antidepressants
A- anti-epileptics
N- NSAID’s
T- thrombocytes
S- steroids
99
What can joint of administration of aspirin and warfarin lead to?
Fatal bleeding
100
Why can aspirin not be given alongside anti-epileptics?
Aspirin increases the effect of antiepileptics
101
When should NSAID’s be used with caution?
In patients who are:
1. Elderly
2. Have renal or hepatic insufficiency
3. IHD
102
In what groups of individuals should NSAIDs always be avoided?
1. Pregnant Individuals
2. Asthmatic individuals
3. Anti-coagulated individuals
4. Individuals taking methotrexate
103
What is the daily dosage for a standard adult taking aspirin?
300-900mg 4-6 hourly (max 4g daily)
104
What is the daily dosage for a standard adult taking ibuprofen?
400mg three times a day (max 2.4g daily)
105
What is the daily dosage for a standard adult taking diclofenac?
50mg three times a day (max 150mg/day)
106
What medication should be prescribed with NSAIDs to reduce NSAIDs-induced GI adverse events?
Proton pump inhibitors
107
What does inhibition of COX-2 by NSAIDs cause?
Decreases the synthesis of prostaglandins Involved in mediating inflammation, pain, fever and swelling.
108
What does inhibition of COX-1 by NSAIDs cause?
Some of the side effects of NSAIDs including GI ulceration
109
What is another name for aspirin?
Acetylsalicyclic acid
110
Is the affect of aspirin on COX pathway reversible or irreversible?
Irreversible, it blunts platelets entire lifespan.
111
What drug is considered the most potent type of opiate?
Morphine
112
What type of pain does morphine treat?
Acute severe pain-continuous dull
113
What are the common side effects of taking morphine?
Drowsiness, sedation & euphoria
114
Why is nausea and vomiting sometimes and unwanted effect of taking morphine?
Due to direct stimulation of chemoreceptors in the medulla this causes feeling of nausea and the need to vomit.
115
What are unwanted side effects of morphine? List 6.
1. Nausea and vomiting
2. Urticaria/pruritis
3. Respiratory depression
4. Constipation
5. Eye signs (miosis)
6. Confusion in the elderly
116
Define miosis.
Refers to having small or constricted (pin-point) pupils in the eye.
117
Morphine delays absorption of other drugs. For this reason, what should be prescribed alongside it?
A laxative
118
What are contraindications of taking morphine?
1. Dependence if used in long term
2. Ulcerative colitis
3. Suspected head injury (morphine can mask signs and symptoms of this)
4. Acute alcoholism
5. Reduced respiratory function (acute asthma etc)
6. Hepatic and renal insufficiency
7. Hypersensitivity
8. Previous history of overdose
119
What are 5 signs that an individual has overdosed on morphine?
1. Seem asleep
2. Low RR
3. Low BP
4. Miosis of eyes
5. Cold and clammy skin with flaccid skeletal muscle
120
How would morphine overdose be managed?
Administration of opioid antagonist (e.g. naloxone) and help to maintain airways.
121
What type of drug is codeine/dihydrocodeine?
Naturally occurring oral opioid
122
What drugs make up cocodamol?
Codeine and paracetemol
123
What drugs make up Codydramol?
Dihydrocodeine and paracetamol
124
On a dose per dose basis how does the potency of codeine compare to morphine?
Codeine has about 8-10% the potency of morphine
125
What is meant by ‘ultrametabolisers” who take codeine? and why are these individuals considered ‘ultrametabolisers’?
These individuals don’t feel that codeine works as an analgesic but still experience side effects of codeine intake.
These individual are considered ultrametabolisers as they lack the enzyme CYP450 2D6.
126
What component of codeine acts as the analgesic and is metabolised in the liver?
Morphine
127
What are side effects of codeine use?
1. Constipation
2. Nausea
3. Drowsiness
4. Confusion
5. Feeling dizzy/vertigo
6. Dry mouth
7. Headaches
8. Constipation (with longer term use)
128
What are contraindications of codeine use?
1. Hypotension
2. Symptoms of GI disturbance
3. Pregnancy or breastfeeding
129
What is the standard adult dose of codeine? What is the max dose in 24 hours?
30-60mg 4-6 hourly. Max dose in 24 hours is 240mg.
130
What are the indications to take codeine/dihydrocodeine?
1. Mild to moderate pain
2. Post-operative pain
3. As an opiate adjunct
4. As an antitussive (inhibits cough)
5. Anti-diarrhoreal
131
Intake of what group of medications is contraindicated when using codeine?
NSAIDs
132
What medications principally interact with codeine and should be avoided in conjunction with one another?
1. Alcohol
2. Antihistamines
3. Anxiolytics (panic disorder treatment) & Hypnotics
4. Antipsychotics
133
What effect does taking alcohol and codeine together have?
Enhances hypotensive effect
134
What effect does taking antihistamine and codeine together have?
Sedative effect
135
How is analgesia efficacy expressed?
As the NNT = the number of patients who need to receive the active drug for one to achieve at least 50% relief of pain compared with placebo over a 4-6 hour treatment period.
136
Do more effective drugs have a low or high NNT?
Low NNT - of just over 2. (Means for every 2 patients, 1 will get at least 50% pain relief from the drug)
