Therapeutics Flashcards
Why should amoxicillin and methotrexate never be prescribed together?
Because Amoxicillin reacts with methotrexate by increasing the plasma concentration of it, thereby increasing toxicity, blood disorders and bleeding.
What class of drugs does penicillin belong to?
Beta-lactams
What is the specific function of Pencillin at a cellular level?
Interferes with cell wall synthesis and is bactericidal
What are the three main mechanisms of action of Penicillin?
- Inhibits cross-linking transpeptidase proteins
- Inactivates autolysin inhibitors causing bacterial suicide
- Rapidly divides bacteria
What type of bacteria is penicillin most effective against?
Gram +ve cocci
Why does penicillin act preferentially on rapidly diving bacteria?
Because it is within these bacteria that majority of cell wall synthesis takes place.
What are the three different types of penicillin preparations?
- Pen G
- Pen V
- Procaine/ Benzathine Pencillin
What type of pencillin preparation is described:
An injectable from of penicillin which is partly destroyed by gastric processes and has a low absorption.
Pen G
What type of pencillin preparation is described:
Well absorbed, gastric acid stable, suitable for oral administration. Regarded as highly effective against dento-alveolar infections.
Pen V
What type of pencillin preparation is described:
Used for long term prophylaxis and for the treatment of early and late latent syphilis.
Procaine/ Benzathine Penicillin
According to the BNF, what are the dental indications for Pen V?
- oral infections
- acute sinusitis
- prevention of recurrent cellulitis (specialist use only)
How common is penicillin hypersensitivity?
Occurs in 8% of the population
What is the key clinical feature of penicillin hypersensitivity?
Maculopapular or urticarial rash
What is the proportion of fatalities from penicillin reaction?
1:60,000
What happened at a cellular level upon immediate reaction (type I) to penicillin?
Mast cell degradation and histamine release
What can be consequences of (the less severe) delayed reaction (type II) to penicillin?
- blood dyscrasias (imbalance)
- haemolytic anaemia
- Leukoplenia
- thrombocytopenia
- aplastic anaemia
Pencillin hypersensitivity can lead to other obscure autoimmune conditions. Name the 4 conditions.
- Eosinophilia
- Steven’s-Johnson syndrome
- Exfoliative dermatitis
- DRESS syndrome
What is Stevens’ Johnsons syndrome?
“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.
What is DRESS syndrome?
Drug Reaction with Eosinophilia and Systemic Symptoms.
Caused by medications which can result in a severe reaction. Involves extensive rash, fever, organ involvement etc.
What is the cause of mortality in 10% of individuals with DRESS syndrome?
Visceral organ compromise
What is one of the most severe form of Steven’s Johnson’s syndrome?
Toxic epidermal necrolisos
Define, eosinophilia.
Elevation of total number of bloodstream eosinophils
What are the 5 main risk factors for penicillin hypersensitivity?
- Multiple drug allergies
- Atopic disease
- Asthma
- Allergic rhinitis
- Nasal polyps
In what two groups of individuals will risk of recurrent Pencillin reactions be higher?
- Those with repeated exposure to the allergen over short term
- Those who have a long retention of IgE
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.
What should be completed when an adverse drug reaction (ADR) occurs?
Yellow card ADR reporting mechanism
What regulatory agency administers the yellow card ADR reporting scheme?
Medicines and Healthcare products Regulatory Agency (MHRA) records
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.
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
What are the three main mechanisms by which bacteria evades Pencillin?
- Reduced drug binding to Penecillin protein PBP
- Hydrolysis of the drug by beta lactamase enzymes (principle mechanism)
- Development of tolerance by disabling their autolysin mechanism
Define, antagonism of drugs.
Where the administration of two drugs together results in neither of them working efficiently
What effects do NSAIDs/probenecid have on Penicillin?
Increases its half-life
How do methotrexate and pencillin interact?
Penicillin can reduce the excretion of methotrexate, increasing retention of methotrexate and Therefore increases toxicity of the drug.
What are the three main common unwanted side effects of penicillin?
- Diarrhoea
- Nausea
- Skin rash
What are three uncommon unwanted effects of penicillin?
- Vomiting
- Urticaria (hives) and pruritis (itchy skin)
- Arthralgia
Name 4 alternatives to penicillin if unwanted side effects were to occur?
- Metronidazole
- Clarithromycin
- Erythromycin
- Clindamycin
Name three drugs that interact with penicillin.
- Warfarin
- Methotrexate
- Allopurinol
What is a rare unwanted side effect of penicillin to be extra cautionary about?
Potential for toxicity in severe renal failure
What is the half life of penicillin?
30 mins
What is the mechanism of action of Metronidazole?
Inhibits DNA replication
What type of bacteria is metronidazole selective towards?
Anaerobic bacteria
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.
What is the half life of metronidazole?
8 hours
What side effect of metronidazole is due to elimination in the kidney?
Causes reddish/brown urine discolouration
Where is metronidazole metabolised and eliminated?
Metabolised in the liver and eliminated in the kidney
What group of patients need to avoid metronidazole?
- Those with severe hepatic dysfunction
- Pregnancy (especially first trimester)
- Nursing mothers
What are the indications for using metronidazole?
- When anaerobes are suspected
- Acute necrotising gingivitis
- Pericoronitis (with systemic involvement)
- Dental abscess
- Beta-lactamase producing anaerobes
- Alternative to pencillin where there is hypersensitivity
What enzyme metabolises metronidazole in the liver?
CYP450
Give 2 examples of medications that act as enzyme inducers to reduce the half-life of metronidazole?
Phenytoin and phenobarbital
What medication decreases enzyme activity in the liver, resulting in a prolonged half-life of metronidazole?
Cimetidine
What affect is metronidazole reported to have on warfarin?
It potentiates the anticoagulant effect of warfarin leading to prolonged prothrombin time
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.
What are the two rarer adverse effects of metronidazole which would indicate the patient should immediately cease taking the drug?
- Convulsive seizure
- Peripheral neuropathy
What are adverse oral side effects of metronidazole. Name 5.
- Taste disturbance (unpleasant, sharp/metallic)
- Furred tongue
- Glossitis
- Stomatitis
- Candida
Name 3 very rare adverse affects of metronidazole.
- Blood dyscrasias
- Temporary neutropenia (puts you at risk of severe infection)
- Thrombocytopenia
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).
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
What is the half-life of metronidazole?
8 hours
What is the mode of action of metronidazole?
DNA Inhibition
What group of antibiotics does clindamycin belong to?
Lincosamides
What type of bacteria tend to have resistance to clindamycin?
Aerobic gram -ve bacilli
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
What is a key notable feature of clindamycin?
It penetrates bone very well
What is a rare and potentially fatal side effect of clindamycin?
Pseudomembraneous colitis
What is GI disturbance due to clindamycin treated with?
Vancomycin or metronidazole
What other antibiotic should clindamycin never be prescribed alongside and why?
Erythromycin, antagonism causes each drug to be less effective.
What is the main contraindication of clindamycin?
Allergy
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
When should clindamycin be ceased immediately?
If patient has symptom of diarrhoea
With what drug is there a theoretical interaction with clindamycin?
Neuromuscular blocking agents
What is the half life of clindamycin?
3 hours
Is paracetemol believed to have more of a central our peripheral affect?
Peripheral
What are the 3 main indications of taking paracetamol?
- First line for dental pain
- Inflammatory conditions
- Where NSAIDs cant be taken
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
How many grams of paracetamol can lead to acute liver damage?
10-15g
How many grams of paractemol is fatal?
25g
What is the treatment for overdose of paracetemol?
Activated charcoal or acetylcysteine IV (oral methionine)
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
What is the therapeutic activity of aspirin?
- Anti-pyrexic
- Anti-platelet/thrombotic
- Anti-inflammatory
- Analgesic (mild/moderate)
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)
What is the mechanism of action of NSAIDs?
COX isoenzyme inhibition
What two compounds in aspirin are involved in its regulatory functions?
PGE2 (prostaglandin) and TXA (thromboxane)
Aspirin affects COX activity, what type of COX activity is it selective over- COX-1 or COX-2?
COX-1
What are the indications for aspirin?
- Acute pain
- Dental pain
- Rheumatic fever
- RA or other inflammatory diseases
- Fever
- ACS/ischemic stroke
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.
What is the half life of aspirin?
20-30 minutes
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.
What are the contraindications of taking aspirin? Name 5.
- AERD- aspirin-exacerbated respiratory disease
- Renal issues (3x increase of renal failure)
- GI issues
- Gout (increases uric acid levels)
- Poor glycemic control
Etc.
In higher doses, particularly over 5 grams a day, what can aspirin cause?
Hypoglycaemia
In higher doses, >10 grams a day, what can aspirin cause?
Glycogen depletion in the liver and hyperglycaemia
What can result from taking NSAIDs such as aspirin where prostoglandins production is reduced?
Ulcerogenesis
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.
How do prostaglandins influence gastric blood flow?
Prostaglandins influence gastric blood flow and increase cell permeability to H+ ions.
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.
Below what age should aspirin never be administered?
Children under 16
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.
What is considered, in grams, an overdose of aspirin?
10-30g
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
What can joint of administration of aspirin and warfarin lead to?
Fatal bleeding
Why can aspirin not be given alongside anti-epileptics?
Aspirin increases the effect of antiepileptics
When should NSAID’s be used with caution?
In patients who are:
1. Elderly
2. Have renal or hepatic insufficiency
3. IHD
In what groups of individuals should NSAIDs always be avoided?
- Pregnant Individuals
- Asthmatic individuals
- Anti-coagulated individuals
- Individuals taking methotrexate
What is the daily dosage for a standard adult taking aspirin?
300-900mg 4-6 hourly (max 4g daily)
What is the daily dosage for a standard adult taking ibuprofen?
400mg three times a day (max 2.4g daily)
What is the daily dosage for a standard adult taking diclofenac?
50mg three times a day (max 150mg/day)
What medication should be prescribed with NSAIDs to reduce NSAIDs-induced GI adverse events?
Proton pump inhibitors
What does inhibition of COX-2 by NSAIDs cause?
Decreases the synthesis of prostaglandins Involved in mediating inflammation, pain, fever and swelling.
What does inhibition of COX-1 by NSAIDs cause?
Some of the side effects of NSAIDs including GI ulceration
What is another name for aspirin?
Acetylsalicyclic acid
Is the affect of aspirin on COX pathway reversible or irreversible?
Irreversible, it blunts platelets entire lifespan.
What drug is considered the most potent type of opiate?
Morphine
What type of pain does morphine treat?
Acute severe pain-continuous dull
What are the common side effects of taking morphine?
Drowsiness, sedation & euphoria
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.
What are unwanted side effects of morphine? List 6.
- Nausea and vomiting
- Urticaria/pruritis
- Respiratory depression
- Constipation
- Eye signs (miosis)
- Confusion in the elderly
Define miosis.
Refers to having small or constricted (pin-point) pupils in the eye.
Morphine delays absorption of other drugs. For this reason, what should be prescribed alongside it?
A laxative
What are contraindications of taking morphine?
- Dependence if used in long term
- Ulcerative colitis
- Suspected head injury (morphine can mask signs and symptoms of this)
- Acute alcoholism
- Reduced respiratory function (acute asthma etc)
- Hepatic and renal insufficiency
- Hypersensitivity
- Previous history of overdose
What are 5 signs that an individual has overdosed on morphine?
- Seem asleep
- Low RR
- Low BP
- Miosis of eyes
- Cold and clammy skin with flaccid skeletal muscle
How would morphine overdose be managed?
Administration of opioid antagonist (e.g. naloxone) and help to maintain airways.
What type of drug is codeine/dihydrocodeine?
Naturally occurring oral opioid
What drugs make up cocodamol?
Codeine and paracetemol
What drugs make up Codydramol?
Dihydrocodeine and paracetamol
On a dose per dose basis how does the potency of codeine compare to morphine?
Codeine has about 8-10% the potency of morphine
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.
What component of codeine acts as the analgesic and is metabolised in the liver?
Morphine
What are side effects of codeine use?
- Constipation
- Nausea
- Drowsiness
- Confusion
- Feeling dizzy/vertigo
- Dry mouth
- Headaches
- Constipation (with longer term use)
What are contraindications of codeine use?
- Hypotension
- Symptoms of GI disturbance
- Pregnancy or breastfeeding
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.
What are the indications to take codeine/dihydrocodeine?
- Mild to moderate pain
- Post-operative pain
- As an opiate adjunct
- As an antitussive (inhibits cough)
- Anti-diarrhoreal
Intake of what group of medications is contraindicated when using codeine?
NSAIDs
What medications principally interact with codeine and should be avoided in conjunction with one another?
- Alcohol
- Antihistamines
- Anxiolytics (panic disorder treatment) & Hypnotics
- Antipsychotics
What effect does taking alcohol and codeine together have?
Enhances hypotensive effect
What effect does taking antihistamine and codeine together have?
Sedative effect
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.
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)
