CNS

• Levodopa:

  • prodrug to dopamine
  • crosses the BBB and supplements the low endogenous levels of dopamine to treat Parkinson's symptoms
  • administered with peripheral dopa decarboxylase inhibitor - carbidopa - to prevent metabolism of levodopa until it has crossed into the CNS
• Pharmocokinetics of levodopa:

  • well-absorbed in GIT via aminoacid transport system
  • 80-90% bioavailability
  • Tmax of around 1 hour
• Extended-release of Levodopa:

  • Sinemet CR
  • oral tablet formulation with hydroxypropylcellulose and poly(vinyl acetate-crotonic acid) copolymer
  • useful for nocturnal immobility with end-of-dose deterioration
• Dispersible Levodopa formulations:

  • for patients who require a rapid onset of action - usually with morning akinesia
• Methylphenidate formulations:

  • used to control ADHD behaviours and is available in 18, 27, 36, and 54mg children doses
  • immediate release:
  • taken 2-3x a day
  • compliance and abuse issues
  • social stigma
  • extended-release:
  • single daily dose
  • better social acceptance
  • behaviour is less well controlled later in the day
• Osmotic drug delivery of methylphenidate:

  • CONCERTA
  • extended-release formulation to given ascending release later in the day to prevent tolerance

  
• Osmotic drug delivery of methylphenidate:

  • CONCERTA
  • extended-release formulation to given ascending release later in the day to prevent tolerance

  
• Challenge of brain tumour therapy:

  • glioblastoma is the most rapidly progressing brain cancer and is uniformly fatal
  • the chemo treatment carmustine has a short half-life, is extremely toxic, and injections require crossing the BBB
• Carmustine delivery for glioblastoma:

  • uses a biodegrable poly(anhydride) wafer implant at the brain tumour site - local delivery
  • the monomer is hydrophobic so there is slow penetration into the bulk wafer so it degrades by surface erosion from soluble acids - prolonged delivery
• Features of the blood brain barrier:

  • an extreme lipid barrier
  • few intercellular pores
  • numerous tight junctions
  • surrounded by glial cells
• Effect of meningitis on the BBB:

  • the BBB is less effective
  • means antibiotics which do not normally pass through the BBB can be given like benzylpenicillin
• Difference between domperidone and metoclopramide:

  • both are antiemetic drugs by antagonising dopamine receptors
  • domperidone doesn't cross the BBB
  • metoclopramide does cross the BBB and can cause drug-induced Parkinson's
• Two compartment distribution - propofol (general anaesthetic)

  • rapid entry into the brain as it is highly lipid-soluble used to induce unconsciousness
  • has to be replaced with a maintenance anaesthetic as redistribution to other tissues removes anaesthetic effect
• Zero-order kinetics:

  • most drugs show first order when rate of elimination is proportional to drug conc
  • for some drugs like phenytoin, the enzymes become saturated so it is no longer proportional
• $Loading dose =$$Css x Vd$

  $Maintenance dose =$$Vmax x Css / Km +$$Css =$$S x Fx Dose /interval$
• Antiepileptic drugs in pregnancy

  • Phenytoin and carbamazepine (less risk):
  • carniofacial abnormalities
  • hypoplasia
  • growth and mental deficiency
  • Valporate
  • neural tube defects
  • severe learning difficulties
• Counselling with antiepileptics in pregnancy:

  • continuation or planned discontinuation is preferred
  • carbamazepine is preferred with 5mg folic acid
  • lamotrigine is first choice to avoid teratogenic drugs but the pharmokinetics in preganacy make it difficult to use
• Antidepressants in pregancy:

  • SSRIs especially citalopram and sertraline is associated with cardiac septal defects and the risk is increased in the first trimester
  • can possible use TCAs if the benefit outweighs the risk
• Health-associated problems with opioid addiction:

  • infections like cellulitis, septicaemia, and pulmonary problems
  • blood-bourne viruses like hep B and HIV
  • dental issues from difficulty accessing services and freq consumption of sugary drinks
• How pharmacies reduce blood-bourne viruses in opioid addicts:

  • needle exchange
  • safe sex promotion
  • screenings
• Advice around dental issues in opioid issues:

  • drink water or use sugar-free gum after methadone
  • good oral hygiene
  • avoid sugary drinks
• Mental health and Substance abuse:

  • Depression 
  • Self-treatment of depression
  • This can lead to worsening symptoms with short highs and then drops
  • Schizophrenia 
  • individuals who use cannabis regularly have an increased risk of developing schizophrenia
  • Drug-induced psychosis is often the reason for hospital admissions but can be resolved by the excretion of the drug
• Types of stigma:

  • Stereotype (people with severe mental illness are dangerous)
  • Prejudice (associated negative reaction with the stereotype)
  • Discrimination (behavioural response like avoidance, withholding support)
• Effect of stigma:

  • Fear and exclusion
  • Authoritarianism 
  • People with severe mental illness are irresponsible and so life decisions should be made by others 
  • Benevolence
  • People with severe mental illness are childlike and need to be cared for 
  • Labelling of patients 
  • Trivialisation of MH terms 
• Stigma in healthcare:

  • People with MH problems die younger - 10yr life expectancy gap
  • People with severe mental illness and learning disabilities have worse outcomes 
  • Diagnostic overshadowing 
  • Less likely to be diagnosed 
  • Less likely to be treated as vigorously 
  • Those with MH problems who develop physical problems are less likely to receive a diagnosis and treatment
• Diagnosis of mental health conditions:

  • No simple test
  • Asking the patient about the initial diagnosis and whether their medication is working 
  • Mental state exam
  • Appearance
  • Behaviour
  • Speech
  • Mood 
  • Thoughts
  • Perception
  • Cognition
  • Insight
• General rules of communication woth MH patients:

  • Adapt conversation to the level of the audience
  • Listen to the patient 
  • Try to avoid jargon and loaded terms
  • Find out what the patient wants and expects
  • Be aware of biases
  • Remember that patients feel stigma too
• How to communicate with patients that have specific MH conditions:

  • Depression
  • Some severe depression may need considerably longer to answer questions 
  • Don’t try to fill the gaps
  • Psychosis
  • A person may talk about unusual things or respond in a way that is unexpected
  • Content can be bizarre
  • Don’t collude or dismiss their reality
  • Suicide
  • Avoid terms like “committing” - use their choice of words
  • Have the conversation 
  • Talking about suicide doesn’t make it more likely to happen
  • Find out about their support system and get them involved with the patient’s permission
• Main principles of the Mental Capacity Act:

  • A person must be assumed to have capacity unless a lack of capacity has already been established
  • A person must not be assumed to be unable to make a decision unless all practicable steps have been taken and are unsuccessful
  • A person should not be assumed to be unable to make a decision just because they make an unwise decision
  • Before any act or decision is made, it must be considered if the outcome could be effectively achieved in a less restrictive way to the rights and freedom of action of the person
• Best interest:

  • No judgement should be made based on the age, appearance, condition, or their behaviour
  • Consider if the person will regain capacity and if the decision can wait for that time 
  • Involve the patient as much as reasonably possible 
  • No decision can be made if there is a motivation to end the patient’s life
  • Consider the person’s past and present wishes, beliefs, and values
  • Take in account views of carer, LPAs, or anymore appointed by the court
• Assessing capacity:

  • A person lacks capacity if at that time they are unable to make a decision for themselves due to an impairment/disturbance to mind/brain functioning 
  • A person cannot be deemed to lack capacity based solely on their age, conditions, appearance, or behaviours
  • Capacity ac doesn’t apply to anyone under 16
  • Deemed to lack capacity if they are unable to do the following
  • Understand the information relevant to the decision
  • Retain that information
  • Use that information as part of the decision-making process
  • Communicate their decision
• Next of kin:

  • person's closest living relative
  • most common person to be nominated as power of Attorney
• Power of attorney:

  • Can be predecided
  • Can make decisions if given permission or the person lacks capacity
  • Decisions in regard to health, welfare, money, and property
  • Can restrict POA to only certain aspects 
  • Short-term POA: property management while away
  • Long-term POA: make ongoing decisions about health when they lack capacity
• Advanced directive v Advanced statement

  • Advanced directive 
  • Document which can outline any treatments you wish to refuse in the future 
  • Clearly outlined
  • E.g. refuse CPR but agree to active treatment with antibiotics 
  • Advanced statement 
  • A written document which states all your preferences including beliefs and wishes about your care
  • E.g. Jehovah’s Witnesses accept medical care but do not believe in receiving blood products
• Informal admission:

  • When the patients are voluntarily hospitalised
  • Consent to treatment 
  • Cannot be detained legally - allowed to leave whenever they wish
  • If they require detainment for treatment and wish to leave, then a mental health act assessment needs to take place
• Section 136:

  • person appears to police as suffering from a mental illness in immediate need of care and are a risk to themselves or others
  • the person is transferred/kept in a place of safety for 24hrs
• MH Act assessment:

  • all practitioners must agree that detention is necessary and to the level of section
  • requires 2 doctors and an approved MH practitioner
• Section 2:

  • valid for 28 days
  • person must be suffering from a mental disorder and require detaiment
  • and is a risk to themselves or others
• Section 3:

  • valid for 6 months
  • requires 2 registered clinical practitioners
  • is suffering from a mental disorder and requires hospitalisation for treatment
  • and is a risk to themselves or others
  • and treatment cannot be provided unless there are detained and an appropriate treatment is available
• 3-month rule:

  • Treatment for mental illness can only be enforced for 3 months from the first section (2 or 3) date 
  • Following the 3 months, patients require:
  • Patient consents to treatment (T2 form)
  • Urgent treatment (section 62 form)
  • Second opinion appointed doctor if the patient is unable to consent/refuse (T3 form)