Acute Confusion Flashcards
What is delirium
Condition of acute brain failure - characterised by acute onset, fluctuating course, disorientation, reduced awareness of surroundings, and other disturbances
What is hyperactive delirium (20%)
Makes a person restless, agitated, aggressive
Increased confusion, hallucinations, sleep disturbance, less co-operative
What is hypoactive delirium (40%)
Makes a person withdrawn, quiet, sleep
Poor concentration, less aware, reduced mobility, reduced appetite
When should pharmacological interventions for delirium be used
should only be considered if all non-pharmacological interventions have failed
Treatments should be short term (<1 wk)
What drugs are used to treat delirium
Haloperiodol (do ECG first to check QTe interval)
Lorazepam (if antipsychotics contraindicated e..g. Parkinson’s)
Chlordiazepoxide usually used for alcohol withdrawal
What are anaethesias
render unconscious (propofol, etomidate)
What are sedatives
reduce anxiety (enzodiazepines, barbiturates)
What are analgesias
relief of pain (morphine, fentanyl, codeine, tramadol)
What is propofol
Anaesthetic induction, maintenance of anaesthesia, sedation ,anti-emesis
What is the mechanism of action of propofol
Enhances GABA-induced chloride currents (hyperpolarisation of post synaptic membrane) + inhibits NMDA glutamate receptors
Increases dopamine in nucleus accumbens (sense of well-being)
Decreases serotonin in area postrema (anti-emetic)
What are the effects of propofol
Neurological: loss of consciousness, seizure suppression, decrease ICP, decrease IOP/CPP, antiemesis
Resp: obtunds laryngeal reflexes, causes apnoea, decreases TV, increases RR
CV: decrease CO, SVR, BP. Baroreceptor reflex inhibition. Decrease O2 consumption
How is propofol metabolised
Oxidised and conjugated in liver (makes it more polar). Excreted by kidneys. Competitive inhibitor of CYP4A54, increases duration of action of midazolam.
What are barbiturates
Anxiolytic, anaesthetic induction, seizure suppression, sleeping aids
What is the mechanism of action of barbiturates
Low dose: positive allosteric modulator (enhances GABA-A receptor effect)
High dose: directly stimulates GABA-A receptors causing increased chloride current and hyperpolarisation
What are the effects of barbiturates
Neuro: loss of consciousness, decrease CMRO2, ICP, CBF, seizure suppression
Resp: decrease TV, RR. Causes apnoea, bronchoconstriction
CV: peripheral vasodilation, negative inotrope, increase HR, can prolong QT interval
How are barbiturates metabolised
Induce Cyt P450 enzymes. Much longer context sensitive half time than propofol
What is ketamine
Analgesia (acute), sedation (paeds), anaesthetic induction, bronchodilation
What is the mechanism of action of ketamine
Phencyclidine binds to NMDA (can potentiate pain) receptor (antagonist)
Racemic mixture of S and R ketamine (S isomer more potent)
Produces dissociative anaesthesia because px may not appear asleep
What are the effects of ketamine
Neuro: increase CMRO2, CBF, ICP, emergence reaction, vivid dreams, extracorporeal experiences, hallucinations
Resp: transient decrease in MV but rarely apnoea. Bronchial smooth muscle relaxant, increase salivation
CV: increase BP, HR, CO and myocardial O2 consumption. Increases sympathetic nervous system, can cause pulmonary hypertension
How is ketamine metabolised
Metabolised in liver to norketamine (less activity than ketamine) and hydroxynorketamine
Metabolites excreted in urine
Bioavailability orally less than intranasally
What is eomidate
GABA-A facilitation (lower dose of GABA required to activate receptor) - does not decrease BP
What are the effects of eomidates
Neuro: decrease CBF, CMRO2, CPP maintained, decrease ICP
What are benzodiazepines
Sedative, anticonvulsant, co-induction agent, sleeping aid
What is the mechanism of action of benzos
Bind to GABA-A receptor, enhance response to GABA
Midazolam (short acting) - rapid onset, hepatically metabolised by CYP system including active metabolite 1-hydroxymidazolam
Lorazepam and temazepam (intermediate) - conjugated in liver to inactive compounds
Diazepam (long acting)
Flunitrazepam (Rohpnol)
What are the effects of benzos
Neuro: anxiolysis, sedation, amnesia, anticonvulsant
Resp: decrease muscular tone in upper airway, response to increased CO2, hypoxic response (synergistic effect with opioids)
CV: decreased SVR leading to small drop in BP, preserved baroreceptor reflexes, CO maintained
What are the endocrine effects of eomidates
Endocrine: dose dependent inhibition of 11B-hydroxlase (cannot produce cortisol or aldosterone)
What is flumazenil
benzo receptor antagonist
Competitive antagonist
Short half-life- may get rebound effect of agonist
Rapid onset, 1-3 minutes
Can cause seizures in px on chronic benzos
What is dexemetomidine
Sedation, withdrawal, delirium, opioids sparing analgesia
Alpha-2 receptor agonist (brain/spinal cord)
Useful for awake craniectomy (sedation without resp depression)
How is dexemetomidien cleared
Almost complete biotransformation in liver with P450 system involvement
Clearance is impaired in liver failure but not renal impairment due to inactive metabolites
What are the effects of dexemeomidine
CNS - sedation, analgesia, enhances neurological blockage (epidural), decrease CBF
CVS - bradycardia, reduced CO, initial increase BP (peripheral alpha1 receptor agonism)
What are the ascending pain pathways
transmitting stimulus (C fibre is slow, A delta fast)
What is the main receptor of opioid binding
Mu
Agonist binding -> decreased release of NT + pain transmissions
What is morphine
Analgesia, palliation, perioperative
Can be given, oral, subcut, IV, intrathecal ,transdermal
Metabolised in liver (glucorinated)
Active metabolite (morphine 6 - glucuronide) - potent + longer lived
Excreted via urine
Low lipid solubility - slow BBB penetration and slow onset
What are the effects of morphine
Neuro: sedation, analgesia, euphoria, cough suppression
Morphine stimulates CTZ (nausea, vomiting)
Edinger Westphal nucleus of III nerve - constriction of pupil
Resp: resp suppression and increased ventilator response to CO2
CV: vasomotor centre suppression, morphine can stimulate vagal centre (bradycardia), histamine release (vasodilatation)
Other: constipation (GI receptors), pruritis (histamine release)
What is fentanyl
Synthetic opioid 80-100x more potent than morphine Few CV effects Less histamine release High lipid solubility, enters brain rapidly and produces peak analgesia in 5 minutes after IV Short duration of action (30-40 minutes) Transdermal fentanyl now available
What does fentanyl target
Mu+delta
What is codine
50% analgesia potency compared to morphine
Given orally
Pro-drug>active metabolites (only works by metabolism in the liver)
Metabolised by CPY2D6. Caution in ultra-rapid metabolisers. Lack of efficacy in poor metabolisers. Susceptible to drug-drug interactions
Risk to neonates (and breast feeding mother if rapid metaboliser)
What is tramadol
Atypical opioid (analogue of codeine) Targets mu receptors + NA/5HT reuptake inhibition Has active metabolite 1/10 potency of oral morphine Safer cardio-resp profile Risk of serotonin syndrome
What is naloxone
Competitive opioid receptor antagonist
Different route IV (2 mins onset), IM (5 mins onset), nasal
Short half life
What is TIVA
Propofol + remifentanil infusion IV Avoids conventional anaesthetic gases Improved CV profile Less nausea and vomiting Improved tube tolerance
What is remifentanil
Potent mu receptor agonist Ultra-short acting drug Rapid onset (1.3 minutes) Rapid offset (metabolised by specific non tissue esterase)
What is remifentanil used for
Sedation in ICU, PCA in obstetrics, pain relief during surgery, total intravenous anaesthesia
What are the signs of alcohol withdrawal
Increase pulse and BP Sweating Shaking Agitation May be confused Hallucinating - tactile, auditory, visual May develop seizures Does not have to be BAC 0.00mg/l Use the CIWA-Ar to assess
What does alcohol do
Alcohol potentiates GABA as well as directly opening channel at high does
GABA is main inhibitory NT in the brain
What does chronic drinking cause
fewer and less responsive GABA-A receptors
Alcohol is also an NMDA antagonist - inhibits CA2+ influx through NMDA glutamate receptors - reducing neuronal excitation
Chronic alcohol leads to receptor up-regulation - associated with impaired memory
What is alcohol withrawl
Alcohol withdrawal results from sudden removal of alcohol in the presence of glutamate/GABA imbalance
Increased excitation of glutamate NMDA receptor
Decreased inhition of GABA-ergic activity
Leads to Ca2+ influx í neuronal hyperexcitablilty, seizures, cell death
What is Wernicke-Korsakoff syndrome
(cerebral thymine deficiency) - alcohol inhibits thymine absorption and inhibits thymine storage. When px stops drinking, thymine reserves are depleted -> acute confusion state ->Irreversible brain damage and amnesia
What are the signs of Wernicke-Korsakoff syndrome
Classic triad of ophthalmoplegia, ataxia, and confusion
Ask do you miss meals or suffer from pins and needles in hands or feet
What is GHB/GBL
GHB is a GABA analogue -> can be metabolised to GABA
What are the effects of GHB
Acute effects: Euphoria Increased sexual arousal, stamina and pleasure Reduce negative self-esteem Altered perception of time Impaired memory Salivation Slouching and unsteadiness Loss of consciousness Bradycardia, hypotension Respiratory depression Death
What is the mechanism of action of GHB
Binds to GABA-B receptors and specific receptors
Effect is to decrease GABA release
GHB binds to presynaptic GHB receptors
Effect is to decrease GABA release
In high conc, binds to post-synaptic GABA-B receptors - inhibit post synaptic neuron
What does GHB withdrawal cuase
Anxiety, agitation, sweating, shaking, increased HR and BP, visual and auditory hallucinations
Quicker onset than alcohol, fewer seizures and more DTs
How to detox GHB
Use CIWA
Add benzodiazepines
Initially 20 mg diazepam then reassess every couple of hours
If not controlled, add baclofen
How do opiods affect resp drive
Suppress resp via action on regions in the medulla and pons which control ventilation
Central control of resp occurs in the brainstem and medulla
Chemoreceptors detect pO2 and pCO2 which usually stimulates resp drive
There are mu opioid receptors in both resp centres in the brainstem and medulla and in chemoreceptors
Stimulation of these receptors slows resp
What is the treatment for opioid OD
Give 400 mcg naloxone injection into outer thigh or upper arm muscle
Naloxone:
Antagonist
Competes with opioids for binding sites, blocking their action
Naloxone has high affinity for the mu opioid receptor
Rapidly redistributed from brain
Half-life is 60-90 minutes
Too much can send px into acute opioid withdrawal
What is SCRA
G protein coupled receptors - CB1 (brain) and CB2 (immune system) Widely distributed in the brain Endocannabinoids - anandamide and 2-AG Rewards Learning and memory
How is SCRA withdrawal treated
Cardiac monitoring U&Es, LFTs, CK Fluids Benzodiazepines Anti-emetics Antipsychotics - safe - no reports of increased seizures Get liaison psychiatry involved
