Key Things to memorise for PH4117 Flashcards
Despite a highly regulated environment around the development, supply and safe use of medicines in the UK, medicines mismanagement and drug misuse constitute a growing and significant population-wide concern with respect to patient health and well-being.
Explain what is meant by adverse drug reactions (ADRs) and medication errors, and their risk to patient health and wellbeing. Briefly explain the different routes by which medication safety incidents are reported and highlighted for corrective action in England and Wales.
Previous reporting of medication errors and other patient safety incidents were previously reported to the National Reporting and Learning System (NRLS), now replaced following NHS patient safety strategy review in 2019 (1). (PSSR)
For NHS England, ‘Learning from Patient Safety Events’ (LFPSE) is the now centralised NHS-wide digital platform for reporting patient safety events (1). The Patient Safety Incident Response (PSIRF) Framework was established for management of serious patient safety incidents (1). National patient safety alerts (NPSA) issued following clinical review, requiring national action (with compliance monitored via Care Quality Commission). (1)
For NHS Wales, parallel systems for local reporting of patient harm and near misses (via Once for Wales Concerns management system). (1) Nationally reported incidents (e.g., unexpected/avoidable deaths or serious harm, never events etc) reported to NHS Wales Delivery Unit. (1) Alerts and notices issued, with monitoring of compliance under remit of NHS Wales Delivery Unit. (1)
Adverse drug reactions (ADRs) – response to medicine that is noxious or unintended, resulting not only from authorised use at normal doses (1); but also from medication errors and uses outside of marketing authorisation, including misuse, off-label use and abuse of medicine (1). ADRs are reported by healthcare professionals or patients to the MHRA (UK Medicines and Healthcare Regulatory Agency) Yellow Card scheme (1). Following review, MHRA will then issue safety communications as required (1). These communications can take the form of regular drug safety updates, specific safety warnings; and alerts and product recall if appropriate (1)
Medication errors - Incident in which there has been an error in the process of prescribing, dispensing, preparing, administering, monitoring or providing medicines advice (1), regardless of whether any harm occurred (1).
Recent media coverage has highlighted the alarming global rise in cases of sepsis. It is now estimated that one in five deaths around the world is caused by the condition, with an estimated 49 million cases and 11 million deaths from sepsis each year. It is responsible for more deaths than breast, bowel and prostate cancer combined. Reports have highlighted the greatest burden of disease in low- and middle-income countries, however wealthier nations are also dealing with a growing sepsis caseload.
(a) Briefly outline what is meant by sepsis and discuss the possible causes for the increasing disease burden in recent years (8 marks).
(a) Definition of sepsis (2 marks) - the body’s extreme response to an infection (a life-threatening medical emergency). Sepsis happens when an infection you already have triggers an exaggerated immunological response / chain reaction throughout your body. Without timely treatment, sepsis can rapidly lead to tissue damage, organ failure, and death. [Must mention infection AND immune response to get 2 marks].
Reasons for increasing disease burden (up to 6 marks)
· More data from LMICs - majority of cases still occur in these countries (1 mark)
· LMIC – poorer access to clean water, good sanitation, vaccinations, and healthcare services (1 mark)
· Better recognition of the condition leads to increased number of diagnoses (1 mark)
· Improved recording of sepsis as cause of death (1 mark)
· Ever-growing problem of antimicrobial resistance (1 mark)
· More people living with a sub-optimal immune state e.g., ageing population, immunocompromised as result of other medical conditions (1 mark)
· Sepsis survivors have higher risk of contracting other infections within a few months of recovery, including COVID-19 (1 mark)
What are the symptoms that an adult patient would likely present with, to enable the diagnosis of sepsis (3 marks)? When recording a patients’ observations on a NEWS chart, what score should make you ‘think sepsis’?
(b) Likely symptoms (3 marks)
· Slurred speech (1/2 mark)
· Extreme shivering or muscle pain (1/2 mark)
· Passing no urine in a day (1/2 mark)
· Severe breathlessness (1/2 mark)
· Skin mottled or discoloured (1/2 mark)
· Patient feeling like they are going to die (1/2 mark)
NEWS score of ≥3 – think sepsis (1 mark)
Outline the current treatment protocol for sepsis (4 marks)
· Current treatment relies on the Sepsis 6 pathway (1 mark)
· Administer high flow oxygen if needed (1 mark)
· Give broad spectrum antibiotics (1 mark)
· Give iv fluids (1 mark)
· Provide vasopressors and /or other organ support as required (1 mark)
Certain population groups are more susceptible to developing sepsis. For the three groups below, explain why they are considered at-risk groups for developing the condition (4 marks).
· A woman who is pregnant or who has delivered / lost a baby in the last 6 weeks.
· A child younger than 1 or a person over the age of 65.
· Someone with diabetes.
Pregnancy or post-partum: caesarean section (surgery), ruptured membranes (once waters break, risk of infection increases), infection following vaginal delivery, mastitis (1/2 mark for any of these up to 1 mark).
Extremes of age: very young have an under-developed immune system (1/2 mark) and may not have yet received full schedule of vaccinations (1/2 mark). Older people are thought to suffer from immune senescence (less efficient immune system) (1/2 mark), more likely to be suffering from chronic illness that increases risk of infection (e.g., COPD, diabetes, renal disease) (1/2 mark) (maximum mark = 2).
Diabetes: wounds / cuts are less likely to heal efficiently, immune abnormalities reported in diabetic patient, less efficient at fighting infections (1/2 mark for any of these up to 1 mark).
Early intervention with intravenous antibiotics is vital in cases of suspected or confirmed cases of sepsis. Briefly discuss the factors surrounding the choice of antibiotics and reasons for IV dosing as the preferred delivery route (5 marks)
Choice of antibiotics (3 marks), from:
· Microbiological diagnosis (lab or PoC).
· Initially broad spectrum as don’t want to delay treatment but should narrow as results become available.
· Nature of infection (site, likely organism, resistance patterns).
· Patient factors (allergies, renal/hepatic function, pregnancy, immunosuppressed).
Reasons for iv (2 marks)
· Decreased gastric and s/c absorption.
· Rapid onset of action – direct delivery by iv.
What key points should be considered in an expert witness case?
- Side effects relevant to the case
- Recency of the drug use, e.g. SSRI recently started, means increased risk of side effects such as depressive thoughts, suicidal thoughts etc.
- Quantity of medication taken and comparison to the recommended single dose and daily dose
- Benzodiazepine short-term - usually 2-4 weeks
If they have taken other substances such as alcohol - Things to note with alcohol:
- Over recommended 14 units?
- How long since ingestion (half life 4 - 5 hours) and time of incident.
- side effects of alcohol: increased sedation, Violence, including homicide, suicide, sexual assault, Increased risk of falls, and anxiety. (all generally increase with higher consumption)
- Combined sedative effect with their medication? - depressant effect of both drugs on the CNS
- Do they have alcohol tolerance? (regular drinker?) - 14 units would still be excessive
What extra information is useful for an expert witness case ?
- Blood levels of alcohol and drug taken as only have their word to go on for consumption. With this information could work out how much of each was in his system at time of incident (2 marks).
- Breathalyser results to rule out the involvement of alcohol (2 marks).
OR - Information on drinking habits (regular drinker or not) needed to draw conclusions on tolerance and likely state of intoxication at time of incident (2 marks).
OR - Information on height, weight and food consumption needed as these affect alcohol intoxication (2 marks).
- If not mentioned - Need information on how long he had been taking medication to establish if they knew it could make them sleepy (2 marks)
- If not mentioned, does the person have other medical conditions or take any other over-the-counter or prescribed medication as these could have influenced how they felt (2 marks)
- if not mentioned, the prescribed dosage of the medication to work out the tolerance
When would you deprescribe medication?
Pain medication, antidepressants, blood pressure, inhalers, tamsulosin, contraception, laxatives etc
- Pain medications (paracetamol and oramorph and fentanyl): continue to control pain throughout patient journey. Acceptable to state paracetamol and morphine up until patient can no longer swallow then switch to subcutaneous. Also, acceptable to say fentanyl continued until rapidly changing pain requirements then switch to subcutaneous.
- Sertraline: Should NOT be stopped until patient can no longer take medications orally. Patient should still be actively treated for depression.
- Donepezil: Should NOT be stopped until patient can no longer take medications orally. Patient should still be actively treated for dementia. Acceptable to state that should not be stopped because of potential withdrawal effects (hallucinations, symptom deterioration).
- Tamsulosin: Should NOT be stopped until patient can no longer take medications orally. Patient should still be actively treated for urinary retention.
- Salbutamol and beclomethasone: context dependent, award mark if reasonable rationale provided, EITHER: Should NOT be deprescribed and should be continued with help of a spacer (or nebuliser) if necessary for as long as possible to control symptoms. OR: could justify stopping if patient is poorly adherent.
- Ramipril – context dependent, award mark if reasonable rationale provided. EITHER: Do NOT stop until patient becomes bed bound and natural blood pressure will decrease towards later stages of end of life. OR: Appropriate to stop at that point but not whilst high blood pressure is still present.
Contraception - Not needed in palliative care as it wouldn’t be possible to deliver a healthy baby, so it can be stopped. Discuss with patient.
Laxative - Senna or lactulose - should be continued – patient will need laxative cover due to opioid analgesia
What medications are found in anticipatory medicines boxes and why?
- Cyclizine/metoclopramide (antiemetic) - nausea and vomiting
Cyclizine and metoclopramide not given together it cancels each other out
- Midazolam (Benzodiazepine)/ haloperidol (antipsychotic), usually given to treat agitation
levomepromazine (antipsychotic) - Severe agitation, nausea and vomiting
- Hysocine hydrobromide/Glycopyrronium (Antimuscarinics) - usually for chest secretions
morphine/diamorphine for pain
If a patient is buying medication online (suspected opioids), how should you advise them? (partner is concerned about them)
Non-judgemental approach, establish facts as far as possible before providing advice to try to minimise harm to patient (1)
Offer the opportunity for the patient to visit the pharmacy for advice directly [1], and the opportunity for medicines review and general check-up (pharmacy or GP surgery). [1]
Take a non-judgemental approach, establish facts as far as possible before providing advice to try to minimise harm to patient [1].
Highlight to customer the potential lack of reliability with respect to identity, purity, and dose (non-regulated supply chain), if purchased through certain online or other non-licensed (dealer) routes [1].
Suggest conversation with husband (ideally through pharmacy) to try to verify origin and reliability of online supply route [1]; supplemented by drug testing through local confidential and free drug testing service, e.g. Wedinos [1].
Sensitively encourage husband to seek medical check-up on physical and mental health, explaining dangers of combining two ‘depressant’ category drugs together (opioids and alcohol). [1]
Signpost to local drug and alcohol services (online information and in-person), again conversation with patient that there is nothing to be ashamed of [1].
What are key points to consider regarding DNAR?
One mark awarded for a definition of consent: the process of a fully informed patient giving permission for medical treatment without coercion.
One mark awarded for a definition of capacity: a patient is deemed to have capacity if they can fully understand the information given to them about the treatment.
One mark awarded for stating that if patient was deemed not to have capacity, then family would be required to sign the DNAR form (no marks awarded if the student assumes that patient would not have capacity due to dementia/illness).
One mark awarded for stating that if patient was deemed to have capacity, then he could sign the DNAR form.
Shouldn’t legally give opinion to patient.
- Ethically – The patient has ultimate control over her own life and therefore whilst considered to have capacity to make health decisions she can refuse to sign the form if she wishes regardless of the husbands wishes.
- Encouragement of family conversations and speaking to both the husband and wife together – advocating for the patient centred approach.
What are the general risks of surgery?
o Bleeding (haemorrhage)
o Shock
o Myocardial infarction (heart attack)
o Death
o Wound site pain
o Infection
o Deep vein thrombosis (DVT)/Pulmonary embolism (PE)
o Anaphylaxis (to peri-operative medicines like anaesthetic)
o Nausea and vomiting
o Urinary retention
Exam Question:
In a separate incident within your community pharmacy, a member of the public approaches and asks for advice. He explains that he has recently developed acne on his face and back and asks for advice on treatment.
You engage a conversation. The male explains there have also been issues with passing urine and heart rate “fluttering”.
The male looks to be around 35-40 years old, physically large with developed musculature, clearly a gym user!
What actions/advice would you take/give?
The indications are the male may be a steroid user [1]
It may be appropriate to clarify this – “are you using steroids?”. This question needs to be handled sensitively, as steroid use has been linked to increased loss of temper, aggression, and impatience. The conversation may be best undertaken in plain sight. [1]
Explain that steroid use is not a criminal offence, although supplying is. [1]
Referral to a needle exchange scheme may be appropriate – if this information is available in the pharmacy. [1]
Referral to a drug support scheme may be appropriate – if this information is available in the pharmacy. This needs to be handled sensitively – steroid users don’t consider themselves drug users. [1]
Further advice and links are available from the UK Anti-Doping (UKAD) or NHS website, or UKAD/WADA for anti-doping advice if a high-level sports performer (unlikely) [1]
Offer treatment for the acne (e.g. adapalene plus benzoyl peroxide, or similar). [1]
Offer advice/treatment for heart ‘fluttering’ (arrthythmias), e.g. beta blocker (such as esmolol hydrochloride) or calcium channel blocker (such as diltiazem hydrochloride). Or refer onwards for specialist assessment depending on severity of symptoms. (1)
What are common Pre-operative considerations?
Common important pre-operative considerations
- Appropriate pre-operative investigations
- Blood tests, imaging, specialist - Starvation
- 2,6 Rule or 2-4-6 Rule in children - Thromboprophylaxis
- always considered for hospital patients
- Medicinal: Low molecular weight heparins
- Mechanical: Stockings or mechanical stimulation - cause blood to circulate more quickly.
Antibiotic prophylaxis
- Antimicrobial stewardship
- How long do antibiotics need to be maintained for etc
What are potential sources of information required when thinking of supplying an emergency supply to a patient?
o NHS Choices, which will have information about the other pharmacy’s opening times
OR
NHS Find a Pharmacy
o The pharmacy’s Patient Medication Record (if any)
o The NHS Summary Care Record (consent must be sought to access this)
o The man’s GP (although noting that the GP surgery is likely to be closed)
o The Drug Action Team (or equivalent) responsible for the man’s drug misuse service (although noting that the office is likely to be closed)
Why do we need to supply anticipatory medication?
- Hard to get hold of medication fast and easily
- Make sure patients’ symptoms are properly treated
- It Saves loves ones from having to leave and find medication it’s there already
- Advanced planning
- Difficult to see patient suffer if there is a delay on medication
What do you think are the barriers to deprescribing?
- Limited time available and lack of clarity over whose ‘job’ it is to deprescribe.
- Possible concerns around stopping a medications that were initiated by a specialist.
- Uncertainty about the ongoing benefits of a medication.
- Concern over drug withdrawal effects and possible worsening of symptoms
- Uncertainty on the timing of deprescribing discussions when prognosis and goals of care may be unclear.
- Concern that the patient, family members, or healthcare professionals may see deprescribing as a sign of ‘giving up hope’.
- Unwillingness or reluctance from the patients to change their medications.
List five reasons to consider deprescribing in the palliative patient towards the end of life
- Reduced adverse events
- Prioritisation of the most essential medications
- Reduced tablet burden
- Reduced costs
- Enhanced quality of life.
Describe the symptoms of Opiate Toxicity
· Drowsiness
· Pin point pupils
· Twitching
· Respiratory depression
· Confusion
· Hallucinations (may not be obvious)
· Itch
· Nausea
What are Severe sepsis and septic shock defined as?
Severe Sepsis: sepsis with the dysfunction of one or more organ systems
Renal failure for example
Septic Shock: is the final stage where hypotension persists despite adequate fluid resuscitation
what is chronic pain?
An unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or potential tissue damage.
n Pain that persists or recurs for more than 3 months- pain after the normal healing process
what are the risk factors for a patient becoming infected whilst undergoing a surgical procedure?
surgical - inexperience, length of treatment, ineffective scrubbing technique
patient - extremes of body weight, smoking, diabetes
Why would i be suitably qualified as an expert witness ?
- Academic qualifications (1 mark): One of: 1st degree, MSc, Ph.D.
- Professional qualifications (1 mark): membership of GPhC and other professional bodies
- Work Experience (2 marks): Current job, years of experience, other relevant experience
- Expert witness experience (1 mark): Amount of experience as an expert witness
discuss which factors should be
assessed when formulating an end-of-life care plan
- Address the spiritual needs of the patient and the family
- The availability of anticipatory or just-in-case medications and the community administration chart to give the medications against
- Deprescribing unnecessary medications
- Understand and address the psychological needs of the patient (and family) (provide counselling etc)
- Understand the package of care required if necessary for the patient to go home
- Provide links to family support networks.
- Access to Macmillan nurses/palliative care teams
- Address the oral hygiene needs of the patient through their palliative care journey.
- Ensure a patient-centred approach to the patient’s end-of-life pathway.
- Communication of the care plan to the patient and the patient’s family. Sensitivity in communication, empathetic.
why are anticpatory boxes used in the later stages of palliative care?
- Access to medications out of hours.
- Prevent patient distress/ symptom control
- Prevent family having to travel to find medications, prevent family distress at watching patient in distress, not spending final moments with patient.
- Less stress and more useful for district nurse’s time.
- Allows a psychological safety net for patient when leaving hospital – they know medications are there ready for when they need them.
Compare and contrast the differences in approach towards the development and supply of new psychoactive substances (‘street’ drugs) and conventional medicinal products. Include in your answer discussion relating to quality control/quality assurance around drug efficacy and safety; drug purity, labelling and consumer information; dosing and frequency of consumption; and the risk of adverse effects on health and wellbeing.
QA/QC around efficacy and safety: NPS: little evidence of efficacy/safety testing within experimental models (in vitro/in vivo) prior to human consumption, user ‘experiences’ widely shared online (1). Medicines: a rigorous process of efficacy/safety testing in multiple experimental models (in vitro/ in vivo) according to medicine regulator mandates (1).
Drug purity, labelling, consumer information: NPS: little control of drug purity, common to see drug mixtures or agents ‘cut’ with cheap bulking agents. Poor and inadequate labelling is common, even mislabelling; and consumer misinformation or sparse information on consumption (1). Medicines: rigour in bulk synthesis and formulation to GMP/GLP standards, including stability and impurity profiling (1).
Dosing/frequency of consumption: NPS: Dosing and dosing frequency is largely guesswork based on anecdotal online information or users’ experimentation; slow onset of psychoactive effect or too high starting dose increases likelihood of overdose with potential for long-term major organ toxicity or injury through accident (1). Medicines: rigorous dose range experiments in animal models prior to establishing a cautious efficacious starting dose for the patient (1).
Risk of adverse effects on health and wellbeing: NPS: Taking psychoactive substances of unknown toxicity, manufactured with poor quality control and often in combinations, heightens risk of overdose and consumer harm, as well as risk of dependency/addiction (1). Medicines: side effects alerts monitored closely during clinical development and beyond, with reporting to regulatory authorities (e.g. yellow card scheme in UK) (1).
c) Outline the pros and cons of developing a drug as a single enantiomer from a patient and regulatory standpoint
Pros of single enantiomer: Biological target is chiral, so one enantiomer expected to be more active than the other – optimise efficacy for an enantiomerically pure compound (1). ‘Inactive’ isomer might also present additional toxicity to patient (1). Cons of single enantiomer: Likely to be more expensive to synthesise and/or purify in single enantiomer form (1). If other enantiomer is equally efficacious and safe, why waste time and money developing single stereoisomer compound (1). Note drug regulator makes ultimate decision based on preclinical/clinical data (1).
f) In the US, where the initial drug approval was obtained via the FDA, the cost of sotorasib is around US$17,900 (around £13,600) per patient per month. Sotorasib is currently protected by compound patent filings, with an expected US expiry date in 2038. Given that the US drug price far exceeds the cost of drug manufacture, formulation and distribution, outline reasons for the high drug price, and the pros and cons of such a high price point. Include in your answer consideration of how a commercial focus for drug development and product pricing might impact on availability of sotorasib to patients from low and middle-income countries.
(f) High cost of research and development over many years of pre-clinical and clinical development (including cost of drug failures) (2). Need to recoup development costs whilst drug on patent (max 16 yrs exclusivity in US) (1). Once patent expires, generic competition on open market leads to dramatic fall in price of drug (1). Pros – incentivising large future investment in new innovative therapeutic products with improved patient outcomes versus standard of care within disease sub-types (1). Cons – exclusion of patients with unmet medical need on the basis of the ability to pay (either via healthcare provider or individually), disadvantaging LMICs (2).
[other potential mark for recognising that non-US countries like UK/NHS negotiate with manufacturers to make patented drugs available at lower price as a bulk purchaser (1)]
(b) Briefly compare and contrast the quality assurance processes associated with the development and production of recreational stimulants such as BMPEA, and therapeutic medicinal products approved by regulators such as the U.K. Medicines and Healthcare products Regulatory Agency (MHRA)
Often developed over many years by user experimentation; lack of scientific rigour
(anecdotal evidence/reports) on determination of psychoactive properties and toxicological
side effects (2 marks).
Characterised by inter-batch variability (at least lack of control) over identity, purity, stability
and side effect profile (2 marks).
Regulated therapeutic products:
Development takes years of pre-clinical (GLP studies)/clinical profiling on patient groups -
full efficacy and safety profiling to ensure product outperforms current market standards
within disease setting (2 marks).
Validated (GMP) scaled-up method of API manufacture, with consistent purity/impurity
profile and predictable stability (2 marks)
black triangle drugs what does the triangle indicate and when is it assigned?
Report all suspected ADRs for new drugs(marked ▼) - even if not serious
The black triangle indicates a medicine is being intensively monitored.
-new drugs
-new combinations of drugs
-novel routes or delivery systems for drugs
-significant new indications for drugs
aids to help medicine taking
Multicompartment aids
Pill crusher
Blister popper
Tablet cutter
Pill timers/alarms
Eye drop holders
why is polypharmacy a concern?
More medicines, more potential for adverse effects
Some adverse effects can lead to hospital admission
Drug interactions especially with complex medicines
Drug drug interactions
Drug disease interactions
Relationship between polypharmacy and frailty
Increased risk of falls
Complicated medicine regimes can cause adherence problems
Increased cost of medicines
