Palliative care

Question 1

verifying and certifying death (how, when nurses can, 3 things that death certificate needed for, 7 reasons to refer/discuss with coroner)

Answer 1

death verification: 5 minutes
- Pupillary response to light 30/30
- Carotid pulses 60/60
- Breath sounds - 15/15/15/15
- anterior and axilla L & R
- Heart sounds - all 4 areas 15/15/15/15
“Fixed dilated pupils, absent carotid pulses,
absent BS and HS. Death verified”.

registered nurses may verify death in specific circumstances (predictable ie long illness in care home)

death certification: Only by a doctor
- Enables family to:
register death
arrange funeral
settle the estate
Doctor who attended patient during last illness
- Knows cause of death
- Seen patient within 14 days of death (COVID 28d)
- (COVID not seen <28d but seen after death)
- Discuss with / refer to Coroner if:
cause of death uncertain
compulsory reasons for Coroner: police custody, SIDS, alcohol/drug/poison, suicide, industrial/transport/domestic accidents, not seen by doctor within 14 days

1 = causing the death
2 = contributing to but not causing the death
Underlying cause of death
A) 1a Bronchopneumonia
1b Carcinoma of bronchus
or
1a Myocardial infarction
1b
1c
2 Hypertension. Type 2 Diabetes

If a serious communicable disease has
contributed to the cause of death, you must record this on the death certificate

Question 2

emesis physiology (CTZ where and how senses blood, 5 things that have receptors there (inc what may be in final common pathway), 2 receptor types in vestibular system, how pharyngeal irritation is transmitted, how GI mucosa irritation is transmitted, how higher level causes are transmitted; 3 types of output in emesis, 5 steps of emesis (inc which parts of GI tract contract), 2 things from SNS response)

Answer 2

Receptors on the floor of the fourth ventricle of the brain represent a chemoreceptor trigger zone, known as the area postrema, stimulation of which can lead to vomiting. The area postrema is a circumventricular organ and as such lies outside the blood–brain barrier; it can therefore be stimulated by blood-borne drugs that can stimulate vomiting or inhibit it

The chemoreceptor trigger zone at the base of the fourth ventricle has numerous dopamine D2 receptors, serotonin 5-HT3 receptors, opioid receptors, acetylcholine receptors, and receptors for substance P. Stimulation of different receptors are involved in different pathways leading to emesis, in the final common pathway substance P appears involved.

The vestibular system, which sends information to the brain via cranial nerve VIII (vestibulocochlear nerve), plays a major role in motion sickness, and is rich in muscarinic receptors and histamine H1 receptors

The cranial nerve X (vagus nerve) is activated when the pharynx is irritated, leading to a gag reflex.

The vagal and enteric nervous system inputs transmit information regarding the state of the gastrointestinal system. Irritation of the GI mucosa by chemotherapy, radiation, distention, or acute infectious gastroenteritis activates the 5-HT3 receptors of these inputs (cell death leads to 5HT release from ECL cells)

The CNS mediates vomiting that arises from psychiatric disorders and stress from higher brain centers

The vomiting act encompasses three types of outputs initiated by the chemoreceptor trigger zone: Motor, parasympathetic nervous system (PNS), and sympathetic nervous system (SNS). They are as follows:
Increased salivation to protect tooth enamel from stomach acids. This is part of the PNS output.
The body takes a deep breath to avoid aspirating vomit.
Retroperistalsis starts from the middle of the small intestine and sweeps up digestive tract contents into the stomach, through the relaxed pyloric sphincter.
Intrathoracic pressure lowers (by inspiration against a closed glottis), coupled with an increase in abdominal pressure as the abdominal muscles contract, propels stomach contents into the esophagus as the lower esophageal sphincter relaxes. The stomach itself does not contract in the process of vomiting except for at the angular notch, nor is there any retroperistalsis in the esophagus (depending on the source that you read).
Vomiting is ordinarily preceded by retching.
Vomiting also initiates an SNS response causing both sweating and increased heart rate.

Question 3

summary of vomit centre inputs (6 primary afferent inputs, what they input to)

Answer 3

six primary afferent pathways involved in stimulating vomiting as follows:

The chemoreceptor trigger zone (CTZ) (metabolics, toxins, chemo, post-op)
The vagal mucosal pathway in the gastrointestinal system
Visceral pain (heart, testes etc - along vagal pathway too)
Neuronal pathways from vestibular system
Sensation in the pharynx
Higher pathways from cerebral cortex/limbic system (pain, anxiety, disgust etc)

these all input to vomiting centre which isn’t discrete place but scattered collection of neurons involved in decision to vomit, primarily in medulla

Question 4

anti-emetic pharmacology (5 classes, including the 3 subclasses within one group, 4 that don’t prolong QT)

Answer 4

antimuscarinics: hyoscine (atropine not used as would cause too much tachycardia); long duration of action, esp on vestibular system, however beware hallucinations and disinhibition

dopamine antags: prochlorperazine, levomepromazine (both these two broad spectrum with action on all these receptor subtypes - means they should work against most causes of nausea, and tend to last a long time), haloperidol (short acting so suitable for eg day case as antiemetic and sedative effect will wear off) domperidone, metoclopramide (these last two narrower spectrum for D2r and so less antichol/antihist s/e, but this also means dont have the antichol antimotility effect so promote gastric motility instead)

antihistamines: cyclizine, promtheazine

steroids: dexamethasone

5HT3 antags: ondansetron

many of these drugs will have some action on multiple of the above receptors

note almost all prolong QT interval except hyoscine, dexamethasone, cyclizine and prochlorperazine

Question 5

6 indications for specific anti-emetics (what pathway/what to use for vertigo, toxin, visceral/enteric, migraine, post-op, biochem)

Answer 5

Vertigo-related nausea, as well as motion sickness, are mediated by the acetylcholine and histamine systems of the vestibular apparatus, and therefore respond well to the anticholinergic and antihistamine antiemetics

Toxin-related nausea, such as nausea related to chemotherapy, can target the chemoreceptor trigger zone directly; 5-HT3 antagonists then interfere with serotonergic neurotransmission between the CTZ and the central pattern generator, preventing this sort of “central” nausea and vomiting

Visceral nausea from intestinal sources appears to be mediated mainly by serotonergic neurotransmission, and is therefore most responsive to 5-HT3 antagonists.

Migraine-related nausea seems to respond best to dopamine antagonists such as metoclopramide

Post-operative nausea and vomiting seems to be related to the direct effects of anaesthetic agents on the chemoreceptor trigger zone, because 5-HT3 antagonists seem to be effective in controlling it

biochem (ie uremia, liver failure) haloperidol is good

Question 6

post-op nausea and vomiting (5 risk factors + 3 in kids, prophylaxis is low, mod, high risk; usual prophylactic options then 2 egs of rescue therapies)

Answer 6

risk factors: duration of anaesthesia, use of volatile anaesthetics/NO, post-op opioids, previous episodes of PONV or motion sickness, certain kinds of surgery

Children are more at risk for PONV/POV
when they are older than 3 years, subjected to certain surgeries—namely tonsillectomy and eye surgeries, or are postpubertal females + as above; if low risk no proph, if 1-2 risk factors then 5HT3 antag or dex (can be IV during procedure), if 3 or more then both of above (IV during procedure)

so ondansetron is usual prophylactic, then rescue therapy if n&v by adding antiemetic from diff class eg haloperidol, promethazine

Question 7

some detail on metoclopramide (prokinesis, duration, source of other 2 s/e) and ondansetron (clearance, duration, what it doesn’t work on, 3 s/e)

Answer 7

metoclop prokinesis come from some muscarinic activity and get increased LOS tone (and maybe oesoph peristalsis), increased gastric emptying, and increased peristalsis of SI

metoclop duration is 1-2hrs

risk of dystonic reaction, especially with children under 10, and risk of galactorrhoea both linked to central anti D2r effect

ondansetron clearance almost entirely hepatic, duration of effect about 4-8 hours, doesn’t work on vertigo nausea as narrow spectrum binding; can cause constipation, headache (worsens migraines often), and prolongs QT

Question 8

emesis pharmacology (5HT3 agents indications and 5 s/e, DARr indications, 3 antihistamine indications and 4egs, 2 antichol egs)

Answer 8

5-HT3 receptor antagonists block serotonin receptors in the central nervous system and gastrointestinal tract. As such, they can be used to treat post-operative and cytotoxic drug nausea & vomiting. However, they can also cause constipation or diarrhea, dry mouth, headache, long QT, and fatigue - eg ondansetron

Dopamine antagonists act on the brainstem and are used to treat nausea and vomiting associated with cancer, radiation sickness, opioids, cytotoxic drugs and general anaesthetics. Side effects include muscle spasms and restlessness - eg domperidone, olanzapine, haloperidol, prochlorperazine, chlorpromazine, metoclopramide

Antihistamines (H1 histamine receptor antagonists) are effective in many conditions, including motion sickness, morning sickness in pregnancy, and to combat opioid nausea. H1 receptors in central areas include area postrema and vomiting center in the vestibular nucleus. Also, many of the antihistamines listed here also block muscarinic acetylcholine receptors - eg cyclizine, mirtazapine, promethazine, diphenhydramine (benadryl)

anticholinergics - hyoscine, atropine

dexamethasone is another good option

Question 9

N&V management (biochem, bowel obstruction with and w/o colic, 2 for raised ICP, 2 for movement related; then indication, mechanism, s/e for metoclop, haloper, cyclizine, levo, ondan, dex; what route to use?)

Answer 9

Biochemical causes
Haloperidol

Bowel obstruction
Metoclopramide* (if no colic)
Hysocine butylbromide (if colic)

Raised ICP
Cyclizine*
Dexamethasone

Movement-related
Cyclizine*
Prochlorperazine

Metoclopramide
Indication: GI obstruction without colic (functional/partial mechanical)
Mechanism: D2 antagonist, 5HT4 agonist
Adverse effects: colic, diarrhoea, extra-pyramidal symptoms

Haloperidol
Indications: chemical causes including opioids, renal failure
Mechanism: D2 antagonist
Adverse effects: drowsiness, extra-pyramidal symptoms

Cyclizine
Indications: raised ICP, motion-induced
Mechanism: antihistaminic, antimuscarinic
Adverse effects: constipation, dry mouth, confusion; note that IV cyclizine can cause a high which can lead to addiction - if concerned a pt may be addicted or drug seeking you can give IV cyclizine in 100mL of D5% or normal saline over 15 minutes, which preserves the anti-emetic effect while reducing the high

Levomepromazine
Indications: unknown or multiple causes, anxiety-related
Mechanism: broad spectrum, multiple receptors
Adverse effects: sedation

Ondansetron
Indications: damage to bowel
Mechanism: 5HT3 antagonist
Adverse effects: constipation, headache

Dexamethasone
Indications: raised intracranial pressure, GI obstruction
Mechanism: unclear, reduced inflammation
Adverse effects: hyperglycaemia, disturbed sleep

subcut/IM/IV routes as n&v reduces absorption, oral is only prophylaxis

Question 10

6 classes of laxative and 4 classes of prokinetics; 4 s/e of bulk formers and 3 of osmotic laxatives, role of 5HT in gut including major receptor

Answer 10

Bulk-forming laxatives which increase the mass of stool (eg. isphagula; help to prevent constipation more than fixing once established)
Osmotic laxatives which increase the water content of stool by altering the osmotic gradient across the bowel wall (eg. lactulose, macrogol (aka laxido/movicol)
Lubricants which aid the passage of stool mechanically (eg. microlax and paraffin)
Stool softeners which act mainly on surface tension to increase the penetration of water and fat into stool (eg. bisacodyl and docusate; help to avoid constipation but don’t help much once constipated)
Stimulants which directly affect the myenteric nervous system (eg. senna and picosulfate, should be taken at night and then takes a number of hours to work with BO in the morning; can get tolerance long term)
Secretagogues which increase the secretion of water or mucus into the gut to alter stool consistency (eg. linaclotide and lubiprostone)

prokinetics
5-HT agonists such as cisapride and tegaserod
Motilin agonists such as macrolides
Cholinergic agents such as neostigmine (metoclop has some muscarinic effect too)
Opioid antagonists such as naxolone

s/e bulk formers: Abdominal distension due to metabolism by gut bacti, obstruction (if not enough water), delayed absorption of drugs/nutrients; rely on gut motility so not good if gut ischaemic, inflamed, infected etc

s/e osmotic laxatives: bloating, electrolyte/fluid depletion, malnutrition (an reduced PO med absorption); need good flui intake otherwise will result in dehydration, and can take up to 3 days to work

role of serotonin in gut: 90% of the serotonin in the body is synthesised by mucosal enterochromaffin cells, is NT for mediating peristalsis, and 5HT4r agonism stimulates peristalsis

Question 11

constipation/obstruction management - palliative - 3 options if functional or partial mechanical w/o colic, 2x options if complete or partial with colic)

Answer 11

a) Functional MBO or b) partial mechanical without colic
Metoclopramide
Stool softeners (+ consider stimulants in functional BO)

a) Complete mechanical MBO or b) partial mechanical with colic (spasms, pain etc, non-operable)
Morphine sulphate
Hyoscine butylbromide

Question 12

approach to constipation (med selection, 2 ix, 3 other things to check, 3 tier mx (6 things in last stage), ileus sx/ix/mx)

Answer 12

remember bulk forming and stool softening are not full laxatives, more useful for preventing constipation

if impacted use a glycerine or bisacodyl suppository for hyperosmotic effects, but only work if stool in rectum (PR might help prove this), work immediately as do phosphate enemas which work same as above

generally if constipated try BD macrogol and senna at night
if PR shows rectum impacted then enema/suppository from above + macrogol BD; if impacted higher up then disimpaction regime of macrogol if pt can take that much fluid -> needs 8 sachets of movicol

general approach to constipated pt:
U&Es and bone profile to correct and electrolyte contributing factors, r/v fluid status to ensure euvolaemia, check drug chart for exposure to opioids, anticholinergics, CCBs; senna and macrogol (2 sachets BD + senna 30mg), if not succeeding try a movicol challenge of 8 sachets +/- suppository, micro-enema, full enema; can give arachis oil enema overnight then phosphate next day if stools hard

if still constipated can try prokinetics, opioid antags; if still fails then manual disimpaction, neostigmine, gastrograffin etc

ileus: abdominal distension and bloating that is often a slow onset as opposed to the sudden onset usually seen with mechanical bowel obstruction. Pain is usually diffuse, persistent without peritoneal signs. Other common signs and symptoms include nausea and vomiting, as well as delayed or inability to pass flatus, and inability to tolerate oral diet. The patient is often distended and tympanic on physical exam with mild diffuse tenderness; need AXR/CT to r/o obstruction

in paralytic ileus make NBM, NGT on free drainage, check U&Es/bone profile, start IV fluids, correct dehydration + electrolytes, limit anti-motility meds as above, consider pro-kinetic medication

Question 13

naloxegol

Answer 13

a peripherally acting opioid antagonist that can be used to treat opioid induced constipation if resistant to more conventional laxatives

should be taken on an empty stomach at least two hours after the last meal, should discontinue regular laxatives before starting it

Question 14

Palliative care - secretions mx (conservative 3x steps, then 3x med options)

Answer 14

Conservative:
Avoiding fluid overload - particularly stopping IV or subcutaneous fluids
Educating the family that the patient is likely not troubled by secretions
Repositioning

Medical:
hyoscine hydrobromide or hyoscine butylbromide is generally used first-line

glycopyrronium bromide may also be used

Question 15

palliative haemorrhage control - 3 main cancers where it might happen for structural reason, a group where it might happen for other reasons, 3 meds that might contribute, 2 other things that inc risk; 2 steps if non-catastrophic, 2 steps if larger bleed, 2 options for just in case drugs)

Answer 15

tumour location
GI haemorrhage: haematemesis / PR bleed
Lung neoplasms: haemoptysis
Head & neck cancers - carotid involvement

• Haematological malignancies / low platelets
• NSAIDs / Steroids / Anticoagulants
• Liver failure
• Radiation necrosis

if non-catastrophic:
Local Measures
Direct pressure / pressure dressings
Adrenaline 1:1000 or TXA soaked gauze

Systemic Measures
Tranexamic acid 1g tds
Interventional radiology

catastrophic use just in case drugs
- Midazolam 10 - 20 mg IV / IM / SC / buccal
- Diazepam 10 - 20 mg Rectal

Question 16

management of minor bleeds (1 for skin inc fungating tumours, 2 pastes you can use, mouthwash if bleed there, what if nose, systemic med choice and when not, how to inc and when to stop, option for oesophageal bleeds, 5 options for haemoptysis, 3 options for GI bleeds)

Answer 16

skin (inc fungating tumors): direct pressure with gauze (can soak in adr 1:1000 or TXA 500mg:5ml), TXA soak can be left in situ with dressing over top; or can make paste from 4x 500mg TXA crushed up in paraffin cream then applied BD - or you can give a sucralfate paste (first line), and can make a TXA 5% solution to use as mouthwash QDS if bleeding in mouth; haemostatic dressings, nasal packs can be helpful

if bleeding not due to DIC can do TXA 1.5g then 1g TDS (inc’d to 1.5 TDS if not controlled), discontinued after bleeding stops; sucralfate mouth wash, PO (for oesophageal bleeds)

if haemoptysis lie on bleeding side (if known) to maximised ventilation for the other lung; treat pneumonia/PE if that could be causing and is appropriate to treat; cough suppressant, TXA; radiotherapy can control bleeding

GI bleeding PPI/H2Ra, TXA/sucralfate as above, consider vit K

Question 17

descending pathways and pain (4 systems pain is integrated with, descending systems located where, role of PAG, placebo effect inc somatotrophism)

Answer 17

pain is heavily modulated, allowing it to be integrated with other systems like skin sensation, attention, emotion and autonomics; descending systems located in periaqueductal grey (PAG) matter of mid brain, the raphe nuclei and other nuclei of the rostral medulla

PAG thought to control nociceptive gate in dorsal horn by integrating inputs from cortex, thalamus and hypothalamus; opioids produce antinociception by inhibiting GABAergic neurons in the PAG that disinhibit glutamatergic output neurons projecting to RVM OFF cells which inhibit nociception at the spinal level; other PAG neurons produce antinociception through direct GABA output to RVM which is inhibited by opioids, disinhibiting the OFF cells; Within the RVM, opioids inhibit ON cells and indirectly increase the activity of OFF cells through inhibition of GABAergic neurons projecting to OFF neurons from the PAG and release of excitatory neurotransmission from the PAG to OFF neurons as above; PAG neurons also directly influence activity of ON neurons in RVM via direct excitatory PAG neurons and inhib interneurons excited and inhibited by PAG neurons

OFF cells decrease nociception and provide analgesia and ON cells are active during periods of enhanced nociception such as secondary hyperalgesia, opioid tolerance, and morphine withdrawal; PAG coordinates the inverse firing pattern of these two cell classes, and PAG also projects to Neutral cells that release serotonin to modulate nociception

placebo analgesia (non-analgesic gives analgesia) when subject told it’s a painkiller; naloxone intravenous infusion abolished placebo response suggesting it is mediated by one of endogenous opioid systems

argument that spatial specific organisation retained by endogenous opioid systems and indeed rats found to have somatotropic PAG, stimulating different areas producing analgesia in different cutaneous regions

Question 18

morphine dosing (how long does MST and oramorph last, starting in opioid naive, weak opioid pts, how much more potent is subcut morphine and diamorphine compared to oral morphine, oral morphine vs codeine/tramadol, how to prescribe CSCI, 2 other things to prescribe with opioid) neuropathic pain (3 step option, which is easier to swallow), bone pain (2 things, s/e of 1), if all else not working with an opioid what is option, which is safe in renal failure, oxycodone vs morphine

Answer 18

modified release MST lasts for 12 hours, immediate release oramorph lasts 4 hours
start oramorph 2.5mg 4-hrly and PRN, unless on weak opioid in which case convert to morphine
work out 24 hour dose, divide by 2 to get MST dose; oramorph 1/6th 24th hour dose for breakthrough (so goes up if MST goes up)

diamorphine subcut is 3x more potent than oral morphine, morphine subcut is 2x more powerful than oral morphine; prescribe prn dose 1/6 too
morphine is 10x more potent than codeine, tramadol

prescribe CSCI as 24 hour subcut infusion

remember also to prescribe stimulant laxatives (as opioid reduce motility), haloperidol if theyre feeling nauseated

neuro: gaba/pregab or ami, then gaba/pregab and ami, then maybe methadone; note pregab smaller and easier to swallow than gaba

bone pain: NSAIDs, bisphosphonates (may get osteonecrosis of the jaw)

if all else not working, can try switching to different strong opioid eg oxycodone, fentanyl
fentanyl is safe in renal failure
oxycodone is 2x more potent than morphine, otherwise works like morphine including IR and MR versions

Question 19

pharmacology of opioids (3 classes, absorption and bioavailability, lipid vs hydro solubility, what being more lipid soluble leads to, metabolised how, morphine vs fentanyl (duration inc why different, metabolism difference)

Answer 19

natural: codeine, morphine
semi-synthetic: oxycodone, hydrocodone, buprenorphine
synthetic: alfentanil, fentanyl, tramadol

opioids are well absorbed from an enteric form, and undergo significant first-pass metabolism to yield low-ish bioavailability

generally weak bases with a pKa close to 8. This means that at physiological pH many of them will have a substantial fraction of the drug present in a lipid-soluble form

High lipid solubility is associated with high analgesic efficacy. This makes sense, as it would be directly related to the rate of penetration through the blood brain barrier; likewise gives more rapid time of onset; however also means lower duration of action as cleared from CNS more quickly too

metabolised by liver and then excreted by kidneys

fentanyl vs morphine: morphine has longer duration of action as less lipid soluble, and the rapid clearance of fentanyl is more likely to lead to withdrawal; morphine metabolised by liver to active metabolites which accumulate in renal failure, whereas fentanyl is metabolised into inactive metabolites

Question 20

opioid receptor (what type of receptor are these, 3 main natural ligands, 2 ionic effects and physiological consequence of their activation, 4 main subtypes inc what each is responsible for, x3 locations of main subtype, x2 mechanism of analgesia, central physiology of natural endorphins, mechanism of resp depressionx2 , mechanism of constipation x2, 7 other s/e)

Answer 20

GPCRs

natural ligands are endorphins, dynorphins and encephalins

By activating, they increase potassium conductance and decrease calcium conductance - hyperpol membranes and reduce NT release, thus reducing synaptic transmission

four main types: μ, κ, δ and the NOP receptors

μ-opioid receptors are responsible for much of the analgesia, but also for the respiratory depression, constipation and cardiovascular effects
δ-opioid receptors seem to be involved in respiratory depression, constipation and mood
κ-opioid receptors are implicated in the sedation and confusion seen with opioid use
NOP receptors seem to have an anti-analgesic, pronociceptive effect

μ-opioid receptors, which are probably the most important clinically, are located all over the CNS, but particularly in the following key areas:

dorsal horn of the spinal cord: μ-receptors are present presynaptically on primary afferent neurons (where they have an inhibitory influence on neurotransmission)
Periaqueductal grey matter: This part of the brainstem sends descending efferents which act to inhibit nociceptive transmission in afferent fibres; μ-receptors remove some of the GABA-ergic inhibitory tone which regulates this descending inhibition
Also rostral ventromedulla, another key site of descending neuromodulators where PAG neurons synapse onto descending fibres

Mechanism of opioid-induced analgesia is by two main effects:

Spinal μ-receptor effect:
Presynaptic inhibition of neurotransmitter (glutamate) release from primary nociceptive afferent neurons
Thus, decreased transmission of nociceptive signals to the dorsal horn neurons
Midbrain μ-receptor effect:
Inhibition of GABA-ergic input into the periaqueductal grey matter
Thus, decreased inhibition of descending efferent regulatory fibres which project from the periaqueductal grey matter to the dorsal horn
Thus, increased descending inhibition of dorsal horn neurons.

This is also the mechanism of action of endogenous endorphin substances, which also bind to the same receptors. Their physiological role is also related to pain, and satiety, sexual arousal, goal-oriented incentive selection and maternal behaviour. They appear to be released by the pituitary gland in response to pain and injury, which suggests some sort of “natural analgesic” role

resp depression
Brainstem μ-receptor effect:
The target is the pre-Bötzinger complex in the ventrolateral medulla (aka resp pacemaker), opioids decrease the rate of firing
Opioids decrease the sensitivity of the medullary chemoreceptors to hypoxia and hypercapnia
This blunts the normal response to hypoventilation

δ- and κ-opioid receptors are expressed in the enteric nervous system; opioids produce direct activation of smooth muscle cells, leading to:
Constant tonic contraction of smooth muscle
Inhibition of normal intestinal secretions
Inhibition of peristalsis

other s/e
Bradycardia and ablation of cardiac reflexes
​​​​​​Histamine release and vasodilation
Nausea as direct result of action on area postrema
Sedation
Cough suppression is mediated by the inhibitory effect of opioids on the medullary controllers responsible for the mechanism of the cough reflex.
Miosis due to direct action on EWN in midbrain
Hallucinations

Question 21

analgesia in renal impairment (4 times when eGFR less accurate, 2 opioids to avoid and 2 to use inc best in stage 4/5 CKD, topical NSAIDs use, neuropathic agent use)

Answer 21

Be aware that estimates of GFR are less accurate in the presence of low protein states, cachexia, oedema, and acute renal failure

Morphine is problematic in patients with reduced renal function due to the risk of accumulation of active metabolites and therefore is generally avoided.
Pethidine should not be used due to the risk of seizures from accumulation of norpethidine. Oxycodone is a reasonable first line strong opioid, but it is partly renally excreted so there is some prolongation of the half-life so doses should be reduced in patients with severe renal impairment

Prolonged release oxycodone can be used in patients with mild to moderate CKD but may be more problematic in patients with stage 4-5 CKD.
Transdermal fentanyl or buprenorphine are not renally excreted and should be considered. The lowest possible dose should be used initially unless the patient is already established on other opioids, in which case dose conversion can be undertaken as usual

Topical NSAIDs can be effective for localised pain and are generally safe to use over a limited surface area in CKD patients.

gabapentin/pregabalin are renally excreted and will need closer monitoring for s/e; TCAs can be used at normal dose as not renally excreted

Question 22

opioid tolerant patients (2 problems, who might have this (dose and time usually whe you get, what to do with them inc 6 things you could use)

Answer 22

need more consideration:
pain scores often higher and more difficult to control
risk of withdrawal

may be on opioids long term for cancer pain or chronic non-cancer pain; problem mainly with >120mg/d for >3mo, likely to have been on them for years
so maintain the background opioid equiv theyre on (eg if they take oral morphine convert their normal dose into iv morphine/some other opioid)
then optimise non-opioid management: NSAIDs, paracetamol, local anaesthetics, ketamine, gabapentinoids, maybe iv lidocaine

Question 23

opioid induced hyperalgesia - what it is and when to suspect, why it happens x2, what you need to diff from x2, prevention and mx x3

Answer 23

occurs when opioids paradoxically enhance pain; should be suspected with worsening widespread pain in the absence of a novel injury coupled with: exacerbation of pain with a higher opioid dose or analgesic improvement with a lower opioid dose

largely believed that OIH is due to dysfunctional facilitation of descending nociceptive pathways of the spinal cord by the rostral ventral medulla; peripherally, opioid receptor activity results in hyperalgesia priming of prostaglandin

need to differentiate from opioid tolerance and central pain wind-up

Non-opioid analgesics can assist with opioid dose reduction and may play a role in OIH prevention.
Treatment of OIH requires tapering opioids and use of alternative pain management techniques. Ketamine can be used, and buprenorphine or methadone are good for longer-term as have some anti NMDAr activity

Question 24

ultra-rapid metabolisers - 2 meds, enzyme, how many ppl, what happens; how many are slow metabolisers and what do they need

Answer 24

if take codeine or tramadol

CYP2D6 haplotype resulting in fast metabolism of above drugs, giving increased active form

up to 10% of ppl, and they’re at inc’d risk of s/e even at low doses; also up to 10% may be slow metabolisers, and need higher doses for effect

Question 25

opioid conversions (codeine, tramadol, oxycodone, SC/IV of morphine, diamorphine to PO morphine, oxycodone to PO oxycodone, alfentanil to diamorphine; 3x to consider oxy/alfent, what to do if dose of morph/oxy requires large volume and why, breakthroughs when on a patch and when to up CSCI, opioids to avoid/use in CKD, what to use in CSCI if GFR <15, how to do breakthroughs for above driver (inc how to calculate the breakthrough dose in this instance), what to avoid in hepatic impairment, what to do if converting from one strong opioid to another, and if converting from less sedating to more (inc what counts as less/more)

Answer 25

for oral morphine generally use oramorph 10mg/5ml

oral codeine or tramadol x10 gets you morphine
oxycodone is 1.5-2x stronger than morphine (just divide morphine dose by 2)

SC/IV morphine is 2x stronger than oral morphine
SC/IV diamorphine is 3x stronger than oral morphine
SC oxycodone is 2x stronger than oral oxycodone
SC alfentanil is 10x stronger than SC diamorphine

Use an alternative sc opioid e.g. alfentanil or oxycodone in patients with
o poor renal function,
o morphine intolerance
o where morphine is contraindicated

If volume of subcutaneous morphine or oxycodone becomes an issue at larger doses, consider changing to diamorphine or alfentanil - diamorphine has greater solubility, can give higher dose in same volume (or same dose in smaller volume)

when on patch prescribe some SC PRN and up syringe driver if >2/3x PRNs needed in 24 hours, after you’ve checked what the PRN was for (eg not if pre-care)

Renal failure/impairment GFR<30mL/min:
Morphine/Diamorphine metabolites accumulate and should be avoided.
 Fentanyl patch if pain is stable.
 Oxycodone orally or by infusion if mild renal impairment
 If patient is dying & on a fentanyl or buprenorphine patch top up with appropriate sc oxycodone or
alfentanil dose & if necessary, add into syringe driver as per renal guidance
 If GFR<15mL/min and unable to tolerate oxycodone use alfentanil sc

when on alfentanil use sc fentanyl for breakthrough - use 1/8th instead of 1/6th 24hr dose, and alfentanil to fentanyl conversion is to divide by 5 - so divide alfentanil dose by 40 to find fentanyl breakthrough dose

in hepatic impairment avoid oxycodone and reduce dose of the others

At higher doses consider a reduction in the dose when converting from one strong opioid to another as there is a risk of toxicity - it is safer to start lower and titrate up as needed; Consider a 30-50% dose reduction when converting from a less sedating to a more sedating opioid eg fentanyl to morphine, oxycodone or diamorphine

Question 26

oramorph vs zomorph (half life for morphine once absorbed, how often to give both forms, conversion, how to help zomorph be given to ppl with swallowing problems, morphine doses for dyspnoea/acute pulm oedema)

Answer 26

half life is 2-4hrs for morphine in the body; oramorph is rapid release so should be given every 4 hours, whereas zomorph is slow release and should be given every 12 hours

zomorph is slow release oral morphine, and the mg to mg conversion from oramorph is that they are the same ie no change needed
zomorph can be sprinkled onto semi-solid foods like yoghurt to be swallowed by people with swallowing problems

for dyspnoea you can start with 5mg PO every 4 hours and titrate as needed, for pulmonary oedema you can infuse at 2mg/min - likely only done by specialists, works by reducing preload

Question 27

transdermal opioids - useful when x2, contras x2 inc why, who to use with caution in, can you cut patches?, which to choose for opioid naive pt?, how long does it take to reach effective dose and how long to wait before titrating, what might you need to reduce when switching to fentanyl?, how long are plasma levels raised after patch removal and so how long to wait after taking patch off to switch to alternative route

Answer 27

Useful in stable pain or when oral route is difficult
* Contraindicated for acute pain and in severe uncontrolled pain requiring rapid dose titration, due to their long elimination half-life
* Use with caution in patients with cachexia as absorption may be unpredictable, so conversion charts may not apply
* Cutting matrix patches is not recommended. Reservoir patches should never be cut

For opioid naïve patients, the lowest strength buprenophine patch (BuTrans 5mcg/hr) may be appropriate

Takes at least 12hrs to reach effective plasma conc - wait at least 72hrs before titrating dose

Fentanyl is not as constipating as other opioids so laxatives may need to be reduced

Plasma levels of TD drugs remain raised for at least 24 hours after removal of patch – remove patch for at least 12 hours prior to switching to alternative drug routes

Question 28

buprenorphine and fentanyl patch indication and when not to use it, what caveat is there when converting to a patch (in terms of dosing), lowest dose butrans patch and morphine equiv. 7 other patch strengths and how often to change them; fentanyl patch lowest strength and morphine equiv, how often to change, 4 other strengths inc morphine equiv of strongest; can you shower and 3 things to avoid, when else to r/v dose; what med means cant use patch,if converting MST to patch when to put the patch on, likewise for if giving instant release, when to start b/g opioid if switching from a patch

Answer 28

for stable chronic pain, moderate intensity or higher, example might be abdo pain due to cancer (rather than obstruction), esp if oral route compromised; not for EOLC - SC/CSCI is preferred route; note also that below patch to opioid conversion is the mid-range, in diff ppl will be a bit higher or lower

5 microgram/hour buprenorphine patch is equivalent to about 12mg of oral morphine in 24 hours; 5/10/15/20mcg/hr patches changed once a week, 35, 52.5, 70 mcg/hr change every 3-4 days; note buprenorphine is a partial agonist

fentanyl patch lowest dose is 12mcg/hr, equiv of morphine 30mg/24hr; usually changed every 72 hours (48hrly if end of dose failure occurs, but needs 72hrs to reach steady state so don’t titrate dose/freq daily); other fentanyl patch strengths: 25, 50, 75, 100 (equiv of 240 morph in 24 hrs)

Showering is possible as the patches are waterproof, but patients should avoid soaking in a hot bath, sauna or sunbathing. If the patient has a persistent temperature of 39◦C or above, the patch dose may need reviewed

Can’t use if MAOIs used in past 2 weeks; if stopping MST then start patch at same time last dose given, if using instant release then continue giving for 12 hours after patch put on; if switching from patch to another route then ensure PRN prescribed, stop patch, start new maintenance form 12hrs later

Question 29

incident pain (what it is, how long prior to give rescue meds and 2 things beside IR opioid you can give, requirement to give fentanyl lolly and how to give)

Answer 29

Pain associated with an incident e.g. movement, swallowing, defaecating, coughing, dressing changes,
weight-bearing

Manage precipitating factors
* Rescue medication of IR opioid at least 30 minutes prior to incident
* Consider NSAIDs/ adjuvants
* Consider SL / buccal / nasal fentanyl preparations

Sublingual / Buccal / Nasal fentanyls inc fentanyl lollies aka fentanyl lozenge: for Incident Pain
* Patient must be taking a minimum of 60mg morphine/24 hours PO (or equivalent) for
at least one week

Give at least 15 minutes prior to an incident likely to cause pain
* Dose is not related to background opioid dose
* Drugs are not interchangeable
* Start at lowest dose and titrate up to effective level - eg 200mcg lozenge

Question 30

liver capsule pain (how it feels, 3x poss causes, 3mx)

Answer 30

Sharp, stabbing, right upper quadrant or right shoulder tip

causes: Liver metastases, immunotherapy,
other liver disease

NSAIDs * Dexamethasone 8mg od PO/SC for 5 days then assess benefit and stop if no improvement * Some may be considered for surgical resection

Question 31

muscle spasm pain - 5 mx strategies, mechanism of baclofen (+ its half life and clearance)

Answer 31

simple measures to try inc heat pad, massage

myofascial pain at a single point could benefit from transcut electrical stim

if widespread consider diazepam or baclofen TDS - starting at lower doses and increasing

baclofen is an agonist at the beta subunit of GABAr acting in the spinal cord to reduce the release of excitatory neurotransmitters in the pre-synaptic neurons and stimulate inhibitory neuronal signals in the post-synaptic neurons with resultant relief of spasticity; 2-6hr half life, mostly cleared by kidneys

Question 32

smooth muscle spasm pain (how it feels, 4 main systems affected, 2mx for bowel, 4mx for bladder spasm)

Answer 32

Crampy, colicky, intermittent pain

Bowel/Bladder/Biliary/ureter:
Constipation, bowel obstruction,
ureteric obstruction, bladder spasm

Treat constipation if present
* Review medication as prokinetic drugs (metoclopramide, domperidone) may be the cause of the smooth muscle spasm
* Use an anticholinergic for relief of pain although this may worsen constipation; other side effects including dry mouth.
o Hyoscine Butylbromide: oral absorption is poor: give 20mg PRN SC or 60- 120mg/24hr CSCI

For bladder spasm, exclude UTI: consider, oxybutynin SR, tolterodine, amitriptyline

Question 33

pain wind-up (link to NMDAr) and ketamine (mechanism, common routes given, metabolism, 3 uses, where less effective, 9 s/e and what might reverse)

Answer 33

NMDAr LTP is linked to development of severe acute pain and progression to chronic pain—by sustained facilitation of nociceptive transmission. At spinal level, NMDA receptor activation leads to development of central sensitization—an augmentation of nociceptive transmission towards higher brain centres. This is called wind-up pain and is also believed to play a role in development of opioid-induced hyperalgesia (OIH)

ketamine is an NMDAr antag and is generally given IV/IM/SC; metabolized by the liver to norketamine (with 20–30% analgesic activity of the parent compound) and inactive metabolites and is excreted in bile and urine

it reduces hyperalgesia and improves opioid responsiveness, reducing opioid requirement

good for post-surgical pain, is an option in cancer pain requiring large amounts of opioids or otherwise difficult to control, may be effective in central pain syndromes like fibromyalgia as well as headache, phantom limb etc; may be less effective at reducing opioid requirement in non-cancer chronic pain

s/e: dizziness, nausea, raised BP/HR/temp, visual or auditory hallucinations, dissociative feeling, paranoia, rigidity, delirium or sedation (BZDs can reverse the neurological problems sometimes)

Question 34

neuropathic pain relief (7 drugs inc mechanism)

Answer 34

SNRIs like duloxetine and TCAs like amitriptyline provide pain relief in neuropathic pain, presumably by descending inhib modulation from locus coeruleus via NA

gabapentin (GABA analogue developed as epilepsy drug) has no activity at GABAr, but can block neuropathic pain in some patients (not acute pain), appears to decrease PM CaV a2d1 subunit localisation (upregulated in some neuropathic pain to inc Ca current) thus gabapentin decreases CaV current density and decreases spinal NT release with pregabalin a successor with better pharmacokinetics

lidocaine acts by blocking NaVs, providing anaesthesia via local application by preventing spontaneous peripheral neuron discharge associated with neuropathic pain, carbamazepine and lamotrigine also NaV blockers used as anti-epileptics and neuropathic pain relief

Question 35

NSAIDs (how they inhib COX, why was COX2 selectivity thought to be better, how do you make a drug COX2 selective, common non-selective, which tend to be COX2 selective, negative aspect of COX2 selectivity (and how links to aspirin), commonest general NSAID risk and how to reduce, why give diclofenac PR)

Answer 35

most act by entering hydrophobic tunnel and reversibly blocking fatty acid entrance; hypothesis that only blocking COX2 would give benefits without side effects as COX1 constitutively expressed in stomach and kidneys, COX2 induced by inflam

COX2 has wider hydrophobic tunnel so drugs with bulky sulphur containing side group to only act on COX2; most NSAIDs (ibuprofen, naproxen) are non-selective as small and drugs ending in -coxib (celecoxib, parecoxib; also slightly diclofenac) tend to be COX2 selective
however COX2 selectivity increases thrombotic risk as COX1 make TXA2 which makes platelets clump so inhib (as by aspirin; also note ketorolac is v COX1 selective) makes clotting less likely, whereas COX2 makes more prostacylin which unsticks platelets so inhib here inc’s clotting; thus associated with myocardial risk thus reserve for those with chronic inflam (eg arthritis) who arent at risk of MI etc and when at high risk of GI bleeding (can still bleed with COX2 specific - maybe they interfere with previous ulcer healing)

most common side effect is gastric bleeding so chronic users, age 65+, or history of gastric ulceration high risk so co-administer with PPI (omeprazole) or PGE1 analogue misoprostol

giving diclofenac PR reduces effect on stomach so is preferred route to use when using for eg renal stones - otherwise will need PPI cover

Question 36

aspirin (mechanism, duration of action and why, what is formed by this process and what does it do, affect of its mechanism on platelets and endothelium and why duration of action matters, what else should you prescribe, anti-inflam action of aspirin due to what)

Answer 36

an NSAID that acetylates Ser530 to irreversibly inactive COX, hence long activity; when donating acetyl group, salicylate is formed which is reversible COX inhibitor though not likely to have therapeutic effect at this conc

platelets make TXA2 (aggregation/vasoconstriction) and endothelial cells mainly PGI2 (vasodilation/inhib aggregation), endothelial cells can replace acetylated COX1 but in platelets off for lifetime of 10 days

also lower risk of stomach ulcer but PPI still usually alongside

aspirin only weakly COX1 selective, so acts on COX2 to make it make 15R-HETE sterorisomer of 15S-HETE (turned into LXA4) so 5LO converts it to aspirin triggered lipoxin ATL which has similar function to LXA4 and may help contribute to anti-inflam action ie switches COX2 from prostaglandins to novel protective lipid mediators

Question 37

NSAID side effects - 4 main ones and effect of COX selectivity, salicylate overdose pathphys, biochem changes sequence, and sx + mx x2)

Answer 37

GI bleeding, renal insufficiency/nephropathy, stroke/MI (less vascular COX2 so less PGI2 - generally NSAIDs on spectrum of selectivity for COX1-neutral-COX2, with more favouring for COX2 meaning more CV risk, eg diclofenac prefers COX2 so big CV risk, aspirin COX1 so not, ibuprofen in middle so risks but milder than diclo) and bronchospasm

salicylate overdose:
resp centre stimulated (chemoreceptor sensitivity increased) giving resp alkalosis (bicarb and K excreted in urine to try and compensate), citric acid cycle suppressed and oxphos decoupled leading to inc’d anaerobic metabolism -> raised anion gap acidosis (ketones, lactate), O2 consumption increased (more hypervent) and thermogenesis leading to sweating, dehydration, hypokal, sets in; sodium bicarb to aklalinise urine helps trap salicylate in renal tubule, haemodialysis if severe
you’ll see n&v, tinnitus, tachypnoea, headaches, dizziness; damage to membranes can give pulm and cerebral oedema (hypovent -> resp failure)

Question 38

NSAIDs - COX2 selectivity risk/benefit, parecoxib is what (and licensed for what, what off-label use), ketorolac is what, used when x2, 3 reasons not to give and what you might prefer then)

Answer 38

selective COX-2 inhibitors have a lower propensity for gastrointestinal side-effects and complications at cost of higher MI/stroke risk

parecoxib is is an injectable selective COX-2 inhibiter licensed for post-surg pain, but can be used off label (make sure pt knows this) for palliative pain, especially bone pain due to mets

ketorolac is v COX1 selective; can be used when an NSAID is required but other routes than injectable are not available – or the pain is not responding to maximal doses of other NSAIDS; however, don’t give if history of bleeding problems of any sort or peptic ulcers, nor in asthmatics; in these cases prefer parecoxib

Question 39

paracetamol dosing with weight and 2 other times to dose reduce (plus reducing for IV)

Answer 39

> 50kg get 1g QDS 4g a day max
40-50kg get 500mg-1g TDS 3g a day max
<40kg get 500mg QDS 2g a day max

also reduce to 3g a day max if malnourished or alcoholic patients or patients with Child Pugh C cirrhosis (i.e. decompensated cirrhotic patients)

for IV paracetamol if <50kg do 15mg/kg up to max of 60mg/kg or 3g whichever is lower

Question 40

TENS - what it is, 3 contras, does it work?

Answer 40

uses electric current to activate nerves in order to decrease pain

Pregnancy, epilepsy, and pacemaker are all contraindications

overall divide across scientific literature regarding the efficacy of TENS application for particular types of pain or pain conditions; combining TENS with pharmacotherapy remains a worthwhile endeavour for interested patients willing to try the modality

Question 41

neurolytic blocks - what it is, 5 egs of block,

Answer 41

targeted destruction of a nerve or nerve plexus

Celiac plexus neurolytic blocks are frequently performed for visceral pain originating from upper abdominal malignancy, especially pancreatic cancer, also chronic pancreatitis; Superior hypogastric plexus neurolysis may be attempted for patients with pelvic visceral pain; trigeminal neuropathy may be alleviated with neurolysis of the trigeminal nerve; Intercostal nerve neurolysis can treat pain from fractured ribs, cancer metastasis, and post-thoracotomy pain; facetogenic and vertebral pain may be alleviated with neurolysis of the medial branch of the primary dorsal ramus

contras inc infection at site, inc’d bleeding risk

Question 42

specific chemo drug side effects (doxorubicin 1, bleomycin 2, vincristine 3 inc how you shouldnt give, cyclophos 2, cisplat 2, methotrex 5, thalid 3, docetax - gen)

Answer 42

doxorubicin - topoiso inhibitor, pancytopenia, hair loss, sore mouth, fatigue, hand-foot; dilated cardiomyopathy giving CHF; echo before (maybe during)
bleomycin - flu like symptoms, alopecia, raynauds, pulmonary fibrosis
vincristine - periph neurop (early symptom may be foot drop - avoid if FH of CMT), hyponat, constipation, alopecia; microtubule assembly inhib; dont give intrathec
cyclophos - alkylating agent so avoid in pregnancy, lactating; n&v, pancytopenia, haemorrhagic cystitis (micro or gross haematuria, maybe dysuria), very gonadotoxic; risk of myeloprolif malignancies and bladder/skin cancers inc AML
cisplatin - nephrotoxic so reduce dose if impaired kidney function; neurotoxic; ototoxic; severely emetogenic; hypomag/calc/kal; bone marrow suppression; carboplatin is alternative that isnt nephrotoxic so use if bad kidneys, but is more myelosuppressive so higher risk of neutro sepsis; for platinum drugs monitor FBCs, U&Es, audiometry
methotrexate - hepatotoxicity, ulcerative stomatitis, leukopenia, nausea, fatigue, pneumonitis or pulm fibrosis; teratogenic, dont have if trying for baby and either gender or while pregnant or breast feeding; tender/swollen gums; hair loss, anorexia, diarrhoea; nephotoxic (swollen hands etc); FBCs, LFTs, renal monitor initially every 1-2 weeks then every 2-3mo
thalidomide - excessive blood clots, teratogenic(dont take if can become pregnant or trying inc if man), periph neuro, SJS, liver damage
docetaxel - hair loss, pancytopenia, vomiting; is taxane that disrupts microtubs

Question 43

4AT

Answer 43

A score of 4 or more suggests delirium but is not diagnostic. In every case the diagnosis is reached by clinical judgement.

A score of 1-3 suggests cognitive impairment and more detailed cognitive testing and informant history-taking may be indicated.

A score of 0 does not definitively exclude delirium

Score for alertness, then do AMT4 (age, DOB, place, year), score for attention, score for acute change

4AT SCORING OF PATIENTS UNABLE TO ENGAGE IN CONVERSATION: If the patient cannot engage with the tester and attempt the AMT4 or the Attention test, then they are rated ‘untestable’ and given a score for this. Untestable status on both of these items yields a score of 4, which suggests possible delirium.

So if a patient is unable to speak because of drowsiness the tester does not record that the patient is unable to be assessed (or UTA) on the 4AT. Instead, we encourage that the patient is scored as having abnormal alertness (Item 1) and also an untestable result on the cognitive testing items (Items 2 & 3)

Question 44

rockwood frailty scale

Answer 44

1 - very fit, among fittest for age, exercise regularly
2 - well, no active disease but only very occasional exercise
3 - managing well, medical sx controlled but not active beyond routine walking
4 - vulnerable, sx limit activities eg feel slower or more tired than used to, but not dependent on others for help
5 - mildly frail, need help with harder things like finances, transport, medications
6 - moderately frail, need help with eg stairs, housework, maybe bathing
7 - severely frail, completely dependent for care due to physical or cognitive reasons, but stable and not likely to die in next 6 months
8 - very severely frail, completely dependent and approaching end of life, wouldn’t recover from a minor illness
9 - terminally ill, with life expectancy <6 months regardless of how otherwise frail they are

Question 45

diabetes/BM control in palliative patients - target, approach for medication changes, approach for pt on steroids

Answer 45

target range 6-15mmol/L

T2DM - diet controlled or metformin only: stop monitoring BM

T2DM - other tablets or insulin: stop tablets, stop insulin only if on small dose with BM <10, keep monitoring BM twice a day, and if >20 give novorapid; if 2 or more corrections needed then start low dose basal insulin; if keeping insulin on then do once daily form of 25% less than previous total insulin and monitor BM BD or once a day with dinner, if BM <8 reduce insulin by 10-20% and if >20 increase by 10-20%

T1DM - continue once daily with dose reduction as above and adjustment based on OD/BD reading

steroids: 6-15 remains target (more lax than in non-EOL pts); increase morning insulin until pre-dinner BM in target range if T1DM or T2DM on insulin; if T2DM no insulin etc can start OD gliclazide 40mg and titrate up

Question 46

octreotide in palliative care (what it is, 4 hormones it counters, 5 things it does, how it is given and starting + usual + max doses, 7 s/e)

Answer 46

Octreotide is an analogue of somatostatin. Somatostatin blocks the secretion of several hormones including insulin, glucagon and gastrin, and vasoactive intestinal polypeptide.

It reduces splanchnic blood flow, portal blood flow, gastro-intestinal motility, gastro-intestinal secretions, and increases water and electrolyte absorption

can relieve sx from some gastro tumours
* Carcinoid tumours with features of carcinoid syndrome
* VIPomas
* Glucagonomas

also used for symptom control in:
* Neuro-endocrine tumours
* Intractable diarrhoea
* Intestinal obstruction
* Severe vomiting.

given via syringe driver; starting dose is 200-300 micrograms in 24 hours. The dose is titrated against response in 200-300 microgram increments. The usual dose is up to 600 micrograms daily, but occasionally doses up to 1500 micrograms can be used

it can cause hyperglycemia so careful if DM, on steroids etc

also may cause anorexia, nausea/vomiting, abdominal pain and bloating, flatulence, diarrhea, and steatorrhoea

Question 47

SPIKES model

Answer 47

model for breaking bad news

Setting - consider location, privacy, + whether family/friends are wanted there

Perception - patient’s current level of knowledge about their medical issue and what they think about their status on the road to recovery.

Invitation - ask your patient if they want to know the details of their condition or the treatment they might face

Knowledge - explain and provide info

Empathy - give space for pt to react, empathise with them

Strategy/summary - what will come next?

Question 48

palliative biomarkers - 7 top candidates (found in cancer pts)

Answer 48

lymphocyte count, white blood cell count, serum C-reactive protein, albumin, sodium, urea and alkaline phosphatase

in particular may see CRP, WCC, and lymphocytes going up; albumin goes down and is a good predictor on the scale of months but not weeks, hypernat suggests sooner death (dehydration driven) and hyponat less soon

Question 49

AKPS - stands for, 6 reference numbers

Answer 49

Australia-modified Karnofsky Performance Scale (AKPS)

100 is normal
80 is can do normal activites but sx of disease
40 in bed >50% of the time
20 bedbound
10 comatose
0 dead

Question 50

hiccups - 3 types, pathway, mx of acute, 2 (1:5) common causes of persistent and how to mx, 22 other causes of persistent, mx of persistent

Answer 50

acute, lasting less than 48 hours, persistent, lasting over 2 days, or intractable, lasting more than one month

afferents along PNS and SNS nerves to central nuclei in midbrain/brainstem, then efferent along phrenic nerve

Valsalva, breath holding, and breathing into a paper bag may be therapeutic in acute phase, and generally this is benign - increase the partial pressure of carbon dioxide or stimulate the vagus nerve

> 48 hours need to be concerned about serious causes
GERD is a common cause of persistent hiccups - antacids, PPIs to fix
Dexamethasone, benzodiazepines, opioids, chemotherapeutics, and anti-Parkinson medications - discontinue these, switch for alts where possible

MI, pericarditis, cavernomas, aneurysms (esp PICA), stroke, MS, neuro tumour, PD, seizure, syringomyelia, menigo/enceph, (neuro)TB, disease or procedure involving mediastinal structures or lungs (esp if irritate diaphragm), uremia, hypokal/calc/nat, subphrenic inflam, dyspepsia, oesophagitis, bowel obstruction, gastric distension, oesophageal cancer, somatisation or stress

metoclop (DA antag + empty stomach), GABA agonist baclofen or gabapentin, can give haloperidol; if can’t do those or not indicated then try levomepromazine; if meds don’t work can try acupuncture, can try phrenic nerve block

Question 51

dystonia - what it is, two main types, 3mx approaches

Answer 51

involuntary maintained contraction of agonist and antagonist muscles yielding abnormal posturing, twisting and repetitive movements

may assume a pattern of overextension or over-flexion of the hand, inversion of the foot, lateral flexion or retroflection of the head, torsion of the spine with arching and twisting of the back, forceful closure of the eyes, or a fixed grimace. It may come to an end when the body is in action and during sleep; worsened by stress, fatigue, anxiety, or lack of sleep

primary is linked to genetics and dystonia may be only sx; secondary caused by insult inc injury, drug, neuro disease

can try baclofen, benzos; local can get botulinum injection

Question 52

itching - 22 dd, 9 ix, 5mx

Answer 52

look for dermatitis, psoriasis etc; look for candida, lice, scabies, fungus
consider meds: opioids, SSRIs, ACEi, statins, chemo
consider jaundice, CKD, leukaemia, mycosis fungoides, thyroid disease, paraneoplastic, fe def, lymphoma, multiple myeloma, polycythemia, uremia

ix: FBC, LFTs, U&Es, bone profile, TFTs, glucose, ferritin, CRP, myeloma screen

treat cause if find one; apply emollient liberally; biliary stenting if cholestatic; phototherapy may help if uraemic, chlorphenamine

Question 53

itchiness

Answer 53

Risk factors include:
* Hepatic disease e.g. biliary obstruction
* Chronic renal failure
* Systemic opioid therapy
* Lymphoma
* Paraneoplastic phenomenon
* Immunotherapy
* Parasites, e.g. scabies, fleas
* Iron deficiency
* Skin diseases, e.g. eczema, psoriasis
* Graft versus host disease after allogenic bone marrow transplant

try to avoid provocative factors like sweating, rough clothing etc; treat cancers and other causes

break itch/scratch cycle through nail trimming, distraction techniques, emollient soap substitute, topical emollients for dry skin (remember risk of fire if paraffin based), aqueous cream, and can seek advice from dermatology

above important regardless of cause but also consider below:

cholestatic: stent, dex 8mg OD, sertraline second line (cholestyramine doesnt work if enterohepatic circulation completely blocked)
uraemia: gabapentin, sertraline second line
opioids: antihistamine eg loratadine, or opioid switch
heart failure: sertraline
other: check U&Es and LFTs, look for scabies, antihistamine if rash, sertraline as second line

Question 54

malignant hypercalc approach - first steps mx, prognosis, 3ix, 4 means of getting hypercalc, calcitonin, bisphos complications and who doesn’t respond as well, 4 other mx options

Answer 54

treat with Iv fluids, and can use bisphos per hypercalc protocol - eg zolendronate 4 mg IV

treatment resistant hypercalc has poor prognosis, may be <6 weeks

test for PTH, PTHrP, vit D levels

PTHrP acts on osteoblasts, leading to enhanced synthesis of RANKL, with subsequent activation of osteoclasts and bone resorption with calcium release into the bloodstream. Increased renal calcium reabsorption is another mechanism through which PTHrP leads to hypercalcemia
Osteolytic mets release Ca
Ectopic activity of 1-alpha-hydroxylase and the formation of 1,25-dihydroxycholecalciferol, common in lymphomas and in some ovarian germ cell tumors
Can get ectopic PTH production

calcitonin is a good bridge, as rapid action but tachyphylaxis after 48 hrs as r downreg’d, in severe hyperca can bridge while waiting for other therapies to work - eg bisphos takes 2-4 days to work

bisphos risk of AKI - need good renal function ideally; watch out for dyspepsia; osteonecrosis of the jaw is not typically a problem during acute management of hypercalcemia of malignancy - usually on mx for at least 4mo. It is important to mention that bisphosphonates are given once, and the dose should be repeated no earlier than 1-week after the administration of the first dose. Moreover, as mentioned above, patients with marked elevation of PTHrP may be more resistant to the hypocalcemic effects of bisphosphonates

denosumab is monoclonal antibody to RANKL, and works in pts refractory to bisphos; also not removed by kidneys but may still need to reduce dose as effects enhanced in renal disease; 120 mg subcutaneously, and the dose should be repeated no earlier than 1-week following the first administration, takes 2-4d to work; can also get osteonecrosis if on for several mo

if over-produce vit D then pred can help by reducing GIT absorption of Ca

cinacalcet good if raised PTH, as suppresses release from parathyroid glands

haemodialysis an option as a final resort but may not always be appropriate

Question 55

mental health act - non-emergency sections (x3)

Answer 55

Section 131 of the Mental Health Act is a section of the legislation which covers the informal admission of patients.

This means that patients can be admitted for care and treatment without formal restrictions, and they are free to leave at any time.
To be admitted under section 131, patients must meet the following criteria:
The patient must have capacity
The patient must consent to the admission

Section 2 of the Mental Health Act is used for compulsory detention for assessment.

A person can be detained under section 2 only if both of the following apply:
The person suffers from a mental disorder that warrants detention in hospital for assessment for at least a limited period.
The person ought to be detained in the interests of their own health or safety or the protection of others.
The maximum period a person can be detained for assessment is 28 days, which cannot be renewed.

The application for admission can be made by an approved mental health professional (AMHP) or the nearest relative. This application must be supported by two doctors, one of which must be an approved section 12 doctor.

Section 3 of the Mental Health Act is used for compulsory detention for treatment.

A person can be detained under section 3 only if all the following apply:
The person suffers from a mental disorder of a nature or degree that makes it appropriate for them to receive treatment in hospital.
It is necessary for the health or safety of the person or the protection of others, that the person should receive treatment which cannot otherwise be provided unless the patient is detained.
Appropriate medical treatment is available for them.
The maximum period a person can be detained under this section is 6 months, which can be renewed.

The application for admission can be made by an AMHP or the nearest relative. The nearest relative can oppose this and/or request it is rescinded (unlike section 2).

This application must be supported by two doctors, one of which must be an approved section 12 doctor

Question 56

mental health act - emergency sections

Answer 56

Section 4 of the Mental Health Act is used for admission for assessment in cases of emergency.

It is primarily used in outpatient services when it is not possible to wait for a section 2 to be arranged. An application can be made by an AMHP or nearest relative and only requires the support of one doctor.
This section allows patients to be detained for a maximum of 72 hours, after which it is often changed to a section 2

Section 5(2) is an emergency order where an inpatient who is a voluntary patient in hospital can be detained for up to 72 hours for a mental health act assessment.
Only one doctor (usually the one in charge of the patient’s care) is required to make an application for this section
Section 5(2) cannot be used in an Accident and Emergency Department. However if a patient has been allocated a hospital bed and is occupying that bed he or she is an “in-patient” for the purposes of section 5(2)

Section 5(4) patient can be detained by a nurse for up to 6 hours to allow further assessment by medical staff.

The application can be made by a nurse if:

The patient is suffering from a mental disorder to such a degree that it is necessary for their health or safety or the protection of others, that they are immediately restrained from leaving hospital.
It is not feasible or practical for a clinician to be immediately available to detain the patient under Section 5(2)

Question 57

mental health act - other sections

Answer 57

Section 135 is a court order that allows police officers to enter private property, by force, to remove a person suffering from a mental health disorder and place them in a place of safety (usually an Emergency Department or police station) if there is reasonable cause to suspect that they:

Have been ill-treated or neglected
Is unable to care for themselves and are living alone
The patient can be detained under this court order for up to 72 hours

Section 136 allows police officers to detain someone suspected of suffering from a mental health disorder, from a public place to a place of safety without a warrant, for up to 24 hours to allow them to be assessed by a medical practitioner

Question 58

insomnia - something helpful to assess, 5dd, managing short (3) and long term (3) + melatonin

Answer 58

a sleep diary kept over 2 weeks can be helpful - time when to be and up, night time waking, sleep quality

consider OSA, circadian rhythm disorders (inc shift work), restless leg syndrome, narcolepsy, parasomnias

short-term: manage mental health problems, sleep hygiene regime, if these measures fail but likely to resolve soon (eg sleep due to short term stressor or other cause that will be fixed) then do 3-7 day course of z-drug
if not likely to resolve soon then CBT for insomnia, and longer course of hypnotic (but not more than 2-4 weeks as tolerance and dependence can dev and you can get withdrawal), if not improving after eg 4 weeks consider referral to specialist sleep services

if >55yo then can give MR melatonin, initially 3 weeks then up to 10 if response; does inc risk of falls; metabolised by liver so in liver failure may accumulate and cause excessive drowsiness; it may be safe for 6-12mo or more but show diminishing effects, so intermittent dosing might be good idea; if taking for >13 weeks can try 2-4 weeks without and restart if sleep gets worse again

melatonin is also used in kids with certain indications (cerebral palsy, ADHD etc)

Question 59

cough

Answer 59

Consider reversible causes where possible

Non-drug measures
* Positioning
* Chest physiotherapy and optimise cough technique

Drug therapies
Consider the type of cough:
* wet / dry cough
* patient able to cough effectively /unable to cough effectively
o Mucolytics – if wet and patient able to cough effectively
Ø Nebulised saline 2.5-5mls prn to qds
Ø Carbocisteine 1.5-2.25g PO daily in divided doses
o Cough suppressants (anti-tussives) – if dry cough, or if patient unable to cough
effectively
Ø Simple linctus
Ø Opioids - Codeine linctus 5-10mls qds PO or
- immediate release morphine 1-2.5mg 4 hourly PO and titrate according to effect

Question 60

mouth problems

Answer 60

Lack of good quality saliva: sugar free gum, sips of water, saliva substitutes eg biotene gel or xerotin spray, can give pilocarpine tablets or drops

candidiasis: ensure good saliva flow using above, Nystatin oral suspension 3 - 5ml qds
buccal then swallowed. Treat for at least
7 days or Fluconazole 50mg od PO for 7 days. Less effective in xerostomia

aphthous ulcers: local steroid eg hydrocortisone

Question 61

restlessness

Answer 61

may be referred to as terminal agitation

causes
Physical discomfort – unrelieved pain, distended bladder or rectum, inability to move,
insomnia, uncomfortable bed, breathlessness
* Drugs – opioid toxicity (especially in renal, liver impairment) hyoscine hydrobromide
(paradoxical agitation), dopamine antagonists (akathisia), steroids
* Infection
* Raised intracranial pressure
* Biochemical abnormalities – hypercalcaemia, uraemia, hypoxia
* Psychological/spiritual distress

address above causes where possible first
If there are hallucinations or frank delirium
o Haloperidol, olanzapine, risperidone and quetiapine
- or levomepromazine

If symptoms are intractable, may need to add:
o Diazepam 2mg bd or 5mg nocte PO
o Midazolam 2.5-5mg prn SC or in a driver

Question 62

delirium or restlessness antipsychotics and benzos

Answer 62

If paranoid, deluded, agitated or hallucinating AND distressed (inc also hypoactive delirium)

Haloperidol 0.5-3mg od PO/SC
Repeat after 2hr if
necessary
Olanzapine† 2.5-5mg nocte PO
Risperidone† 0.25mg-1mg nocte
Quetiapine† 25-300mg PO
Levomepromazine† 6.25-25mg nocte or
bd PO/SC

levo is more sedative than the others’ the other 4 are equally effective, haloperidol usually first line unless congen long QT or on multiple other meds that prolong QT interval

all of the above 5 should be avoided in PD and dementia with lewy bodies due to D2 antag

benzos: loraz, diaz, midaz; may worsen delirium
Preferred choice in:
o Alcohol and drug withdrawal
o Parkinson’s disease
o Lewy body dementia
* Add to antipsychotics for acute distress and
to control dangerous behaviour

Question 63

insomnia

Answer 63

nocturia? fear or anxiety vs trouble actually getting to sleep?
Drugs – stimulants (caffeine etc.), steroids (worse if given later than 2pm), diuretics,
opioids (vivid dreams, hallucinations), fluoxetine, propranolol (nightmares)
* Drug withdrawal – alcohol, benzodiazepines, barbiturates

manage above where possible inc changing drug times or types

Establish good sleep hygiene (e.g. a consistent bed time ritual)
* Encourage relaxation techniques

Zopiclone 3.75-7.5mg PO, zolpidem 5-10mg PO have fewer residual effects than benzos; benzos can be used if more anxiety than just trouble getting off to sleep

also consider melatonin2mg 1-2hr before bedtime PO starting dose with maximum dose of 10mg daily
TCA can help ensure better sleep throughout the night (vs just helping with getting off to sleep); also consider mirtazapine if low mood or appetite problems

Hypnotics may increase risk of falls and nocturnal confusion, especially in the elderly - advise them to ask for nurses via call bell instead of just walking to the toilet

o Use low dose Haloperidol evening or at bedtime if any evidence of delirium overnight

Question 64

fungating wounds

Answer 64

• Identify location, size, nature of ulcer - these affect choice of dressing and fixation
• Check amount of devitalised tissue in ulcer - affects need for cleansing and
  debridement
• Condition of surrounding skin - if skin is macerated, protective barrier or film may be
  needed
• Consider potential for serious complications, haemorrhage, vessel/airway
  obstruction and plan accordingly

treat any secondary infections

early discussion with TVN

dress wounds, give analgesia (topical morphine may be sufficient otherwise systemic +/- neuropathic agents), breakthrough analgesia for dressing changes, if bleeding can consider TXA, topical adrenaline, cautery, malodour can get charcoal dressing, consider crisis bleed midaz

Question 65

hypersalivation mx

Answer 65

commonly seen in patients on antispychotics

least systemic s/e: sublingual atropine
next best: hyoscine patch
next best: oral hyoscine

Question 66

lymphoedema

Answer 66

Treatment is aimed at improvement and control, as cure is not possible

Skin care - emollients, monitor for breaks
* Manual lymphatic drainage (massage)
* Compression - compression then special hosiery, needs specialist input
* Exercise - move around limb to promote muscle pump

Corticosteroids may help to reduce lymphadenopathy but may increase fluid
retention. Give dexamethasone 8mg od PO with omeprazole 20mg od PO for one
week. If effective reduce in 2mg increments per week to the minimum effective
dose. If ineffective taper to zero

Lymphoedema hampers leukocyte surveillance resulting in localized
immunocompromise
* Use antibiotics as per local cellulitis guidelines but treat for longer (e.g. 14 days from the time of clinical response)

If first line antibiotics ineffective at 48 hours, substitute second line oral treatment

Question 67

steroid use in pall care

Answer 67

• Prescribe as a single, or two, morning doses to avoid sleep disturbance
• Give a 5 - 7 day trial as assess effect
  o if there is no benefit - stop
  o If benefit achieved - reduce to lowest effective dose and then review regularly
• Stop if ineffective or when benefit lost (see below)
• Check blood sugars weekly if on 8mg dexamethasone or more

if SSRI or NSAID also prescribed consider if you can stop them, if you can’t will need PPI (ideally will be on anyway)

Dose needs increasing (up to double) when used together with hepatic enzyme
inducers e.g. phenytoin or carbamazepine which reduce its effectiveness through more
rapid metabolism

Can withdraw immediately if less than 3 weeks treatment and less than 4 mg/day
dexamethasone or 30mg/day prednisolone
* Otherwise tail off by 2mg every 3/5/7 days

2mg dex ~ 15mg pred ~ 50mg hydrocort

s/e
Early: oral thrush, hyperglycaemia, heartburn, sleep disturbance, mania
* Late: proximal myopathy, skin atrophy, bruising, depression, face & body shape
changes
* Change in mood is common, in addition to depression; mania, delirium and psychosis
can occu

Question 68

endocannabinoid system - receptor level

Answer 68

Endogenous cannabinoids are endogenous lipids that engage cannabinoid receptors; precursors are present in lipid membranes, then on GPCR activation or cell depol they are cleaved and released into extracellular space

effects of endocannabinoids are primarily mediated by CB1 and CB2 cannabinoid receptors, though some also bind to PPAR and TRP receptors; they are both GPCRs coupled to Gi and Go; their activation inhibits adenylyl cyclases and certain voltage dependent calcium channels and activates several MAP kinases and inwardly rectifying potassium channels, with some variation depending on the particular type of cell

CB1r abundant in CNS, mostly on axon terminals and pre-terminal axon segments; Cortical and hippocampal CB1 receptors are particularly enriched on cholecystokinin (CCK) positive interneurons (low threshold spiking interneurons) and also widely on glut neurons, and medium spiny neurons in both the dorsal and ventral striatum, esp direct pathway axons in globus pallidus; they are also found on peripheral nerves inc autonomics

CB2 primarily on microglia and vascular elements, but is on some neurons esp when injured; also commonly on immune cells

endocannabinoids mainly function as retrograde messenger and contribute to synaptic plasticity, including depolarisation induced inhibition/excitation (transient suppression of inhibitory/excitatory input onto a neuron following its strong activation, lasting seconds, affecting both GABA/glu and also neuropeptides like CCK);

Metabotropic induced suppression of inhibition (or excitation) is another form where postsynaptic Gq GPCR activation (eg mGluRs, orexinA, CCKa leads to PLC producing an endocan which diffuses to suppress presynaptic firing, and as PLC is Ca senstive this can be coincidence detector for Gq signalling and postsynaptic depol

they also contribute to LTD and slow self inhibition (interneurons produce endocan during intense firing

Question 69

endocannabinoid system - function

Answer 69

have a role in memory extinction and hippocampal neurogenesis

hypothalamic neurons may tonically produce endocannabinoids that work to tightly regulate hunger with amount of endocannabinoids produced inversely correlated with the amount of leptin in the blood, so CB1r signalling increases appetite, as well as increasing dopamine signalling in NA; it is also linked to regulation of metabolic activity and insulin sensitivity

stress: habituation of the stress-induced HPA axis via 2-AG prevents excessive secretion of glucocorticoids to non-threatening stimuli, the increase of basal corticosterone secretion resulting from decreased anandamide allows for a facilitated response of the HPA axis to novel stimuli; also linked to anxiety processing in the brain, anxiolytic or anxiogenic depending on if excitatory or inhibitory neurons inhibited

via TRP channels it has role in thermoregulation, contributing to vasodilation; increases sleep (more adenosine, REM deprivation gives inc’d CB1r expression), possibly circadian with levels higher at night

also one of the key systems in pain: like opioids, cannabinoids produce centrally-mediated analgesia by activating a descending pathway which includes PAG and its projection to downstream RVM neurons, which in turn send inhibitory projections to the dorsal horn of the spinal cord; receptor activation on presynaptic GABAergic terminals reduces the probability of neurotransmitter release thus dis-inhibiting the PAG-RVM-dorsal horn antinociceptive pathway; cannabinoids produce analgesia through the dis-inhibition of PAG glutamatergic projecting neurons that results in the stimulation of RVM OFF cells and inhibition of the ON cells

weaker effect than that produced by opioids, however sitmulating some parts of the PAG produces analgesia which opioid antagonists doesn’t block but CB1r antags does

Question 70

acute dystonic reactions

Answer 70

involuntary contractions of muscles of the extremities, face, neck, abdomen, pelvis, or larynx in either sustained or intermittent patterns that lead to abnormal movements or postures; may also see psychiatric symptoms such as agitation and anxiety, psychosis, depression

occur after taking any dopamine receptor-blocking agents due to dopaminergic-cholinergic imbalance in the basal ganglia. Reactions usually occur shortly after the initiation of an offending agent or an increased dose of a possible offending agent

in pall care likely following metoclopramide, possibly ondansetron, haloperidol (and all antipsychotics - 2nd gen are less likely); can also see with carbamazepine, lamotrigine, gabapentin, oxcarbazepine, SSRIs, and rarely other drugs

oculogyric is most well known, but also torticolic, buccolingual (trismus, dysarthria, tongue protrusion), tortipelvic, opisthotonic (arching back), laryngeal (dysphonia, stridor) crises and pseudomacroglossia (tongue feels big and like it’s protruding even though it isn’t any bigger)

diphenhydramine (benadryl) should treat (stat IV then oral for a couple of days); if resists this then give a benzo (loraz); may need to give O2 and even intubate depending on where the contraction is

these conditions can also be seen in hereditary and sporadic movement disorders including disorders of dopamine metabolism, parkinsonism (inc wilsons), focal brain lesions etc

Question 71

serotonin syndrome and neuroleptic malignant syndrome

Answer 71

serotonin syndrome develops rapidly after exposure to the precipitating drug

may range from barely perceptible tremors to life-threatening hyperthermia and shock. Signs and symptoms include agitation, anxiety, restlessness, disorientation, diaphoresis, hyperthermia often >40deg, tachycardia, hypertension, nausea, vomiting, tremor, muscle rigidity, hyperreflexia, myoclonus, dilated pupils, ocular clonus, dry mucous membranes, flushed skin, increased bowel sounds, and a bilateral Babinski sign. Clonus and hyperreflexia are particularly common. Neuromuscular findings tend to be more pronounced in the lower extremities

cool, IVF, benzos to sedate

usually results after having multiple drugs with 5HT activity: SSRIs, tramadol, metoclop, TCAs, MAOIs (note includes linezolid), MDMA, cocaine, tryptophan

NMS develops within hours/days/weeks of antipsychotic drug exposure (1st and 2nd gen but esp 1st inc haloperidol); abruptly stopping doapminergic agents like l-DOPA can also trigger; fever, muscle rigidity (dysphagia), confusion/coma, tachycardia, hypertension, diaphoresis, tremor; note lack of GI sx, hyperrflexia, clonus compared to 5HT syndrome and hyporeflexia (lead pipe rigidity), pupils also are normal and CK is more likely to be raised

aggressive hydration (CK release -> rhabdo), bromocriptine and/or dantrolene

Question 72

tardive dyskinesia and akathisia

Answer 72

TD: involuntary repetitive body movements, which may include grimacing, sticking out the tongue or smacking the lips; may also see chorea and athetosis; often after long term antipsych or metoclop use (months-years of use)

akathisia: inability to remain still +/- sense of unease; compulsion to move, often repetitive; may look like continuous fidgeting; appears soon after starting or changing dose; antipsychs, metoclop, SSRIs, SNRIs; change medication, and if needed start mirtazapine or propranolol