Week 8 Flashcards
What is anxiety associated with?
- Threatening situations (medical procedures involve huge amount of uncertainty)
- Thoughts of threatening situations
List what patients are anxious about?
- Anaesthesia/unconscious
- Waking during surgery
- Pain (e.g post-operative)
- Life-threatening procedures
- Post-operative outcome
- Possibility of disfigurement
- Threat of severe illness
- Outcome of test results
- Unfamiliarity of surroundings
- Physical restriction
- Loss of independence
- Being away from home
What does Kiecolt-Glaser et al. Psychological influences on surgical recovery say?
Pre-operative anxiety effects outcomes of recovery
What are patients who experience high anxiety pre-operatively more likely to have?
- More pain post-operatively
- Use more analgesic
- Stay in hospital longer
- More complications
- Anxiety & depression after surgery
What does Kiecolt-Glaser et al. Psychological influences on surgical recovery say regarding “Communication”?
Anxious patients are less likely to understand the info they are told
What does Kiecolt-Glaser et al. Psychological influences on surgical recovery say regarding “Adherence”?
Patients with anxiety are less likely to be compliant with coughing & breathing exercises (reduce likelihood of pneumonia), getting out of bed & moving around (reduce phlebitis & enhance wound healing)
What does Kiecolt-Glaser et al. Psychological influences on surgical recovery say regarding “Pain Management”?
Pre-surgery anxiety & stress can influence the type & amount of anaesthetic
How can we help patients who have anxiety?
- Increase sense of control
- Procedural info
- Behavioural instruction
- Cognitive coping
- Sensory info
- Modelling
- Counselling
What are the benefits of procedural info & behavioural instruction according to Classic study by Egbert et al. (1964)?
- Patients were discharged from hospital on average 2.7 days earlier
- Required half as much pain medication as patients receiving usual care
Describe the 4 parts to the Langer, EJ, Janis, IL & Wolfer, JA. (1975) Journal of Experimental Social Psychology experiment?
- Teaching cognitive coping
- Procedural prep info
- Cognitive coping + procedural prep info
- Control group
What are the 3 positive effects of cognitive coping?
- Less analgesics
- Trend for early discharge (not statistically sign)
- Able to cope with discomfort better
Describe the 4 parts to the Kulik, JA & Mahler, HI. (1989) Personality & Social Psychology Bulletin experiment?
- Room with another pre-op patients, same surgery
- Room with another pre-op patient, different surgery
- Room with a post-op patient, same surgery
- Room with a post-op patient, different surgery
What are the 3 positive effects of having a room with post-op patient from same/different surgeries?
- Released more quickly
- Less anxious post-op
- More ambulatory post-op (movement)
Describe anxiety & non-surgical procedures?
- Can be just as anxiety-provoking & distressing
- Techniques used for surgery patients can also be beneficial to prepare patients for non- surgical procedures
What 2 ways can you prepare a patients for endoscopy?
- Procedural & sensory info- describing endoscopy procedure & sensations to expect
- Behavioural instructions- teaching how to breathe & swallow to facilitate throat anaesthetisation & tube passage
What does the 2 methods to prepare a patient for endoscopy do?
- Sensory information reduced distress
- Combination of coping information & behavioural instructions reduced distress & reduced time required for tube passage
Describe how cancer patients may experience anxiety around non-surgical procedures?
- Drug induced nausea & vomiting
- Repeated chemotherapy treatments, may also experience Anticipatory Nausea & Vomiting (ANV) before chemotherapy
- ANV may lead to discontinuing treatment
What are 3 ways to prepare a patient for a non-surgical procedure?
- Systematic desensitisation
- Information provision
- Relaxation training
What is a “Monitors” coping style?
Copes by seeking out detailed info
What is a “Blunters” coping style?
Copes by using avoidance to minimise the situation
According to a study on Women undergoing gyne exam, what happens when monitors are given little info & blunders are given a lot of info?
React negatively to the amount of info the received as evidence by their continued high pulse rates after the exam
According to a study on Women undergoing gyne exam, what happens who monitors are given more info & blunders are given low info?
Reacted more positively as evidenced by their reduction in pulse rates after the exam
What are the 2 explanations for how psychological preparation promotes recovery?
- Psychological prep –> Reduces stress –> Reduce sympathetic arousal –> Improves immunological & endocrine responses
- Preparations –> Reduced frequency & extent of maladaptive behaviours that unprepared patient can engage in (not doing breathing exercises)
What are the problems with Barbiturate drugs?
- Dependence
- Addiction
- Misuse due to highs
- Narrow therapeutic index
What 2 things are Barbiturates still used for?
- IV induction agents
2. Anti-convulsants
What are the 5 different classes of drugs for anxiolytics & sedatives?
- Antidepressants
- Benzodiazepines
- Z-drugs
- B-blockers
- Other ie. Melatonin, Sedating antihistamine
Describe Benzodiazepine drugs?
- Serendipity (librium)
- Highly lipophilic
- Well absorbed orally
- Highly protein bound (95%)
- Hepatic metabolism
- Active metabolites
- Excreted as glucoronide conjugate
What are the 5 major effects of Benzodiazepines?
- Anxiolytic- reduce anxiety (α2 & α3 )
- Hypnotic- induce sleep (α1)
- Reduce muscle tone
- Anterograde amnesia (pros&cons)
- Anticonvulsant effect
How do you administer Benzodiazepines?
- Orally or intravenously
- Not advised to be given intramuscular
What are the 2 categories of Benzodiazepines?
- Short acting- Lorazepam, Temazepam (t1/2 8-12hrs)
3. Long acting- Diazepam (t1/2 20-100hrs)
Describe the GABAa receptors?
- Pentameric
- Central ion channel pore (Chloride)
- 18 possible subunits
- 30 forms of receptor
- Some subunits location specific
- Anaesthetics & benzos allosterically activate the receptor
- Increase frequency of opening
What is sedation mediated via?
GABAa with α1 subunit
What is anxiolysis mediated via?
GABAa with α2 & α3 subunits
What is Flumazenil?
Competitive benzodiazepine antagonist
Describe Flumazenil drug?
- Short half life compared with benzodiazepines
- May precipitate agitation & seizures
- IV 100mcg increments
What are the side effects of Flumazenil?
Nausea & vomiting
Where do Z-drugs act?
Benzodiazepine receptors (very similar pharmacodynamic profile)
Give 3 examples of Z drugs?
- Zopiclone
- Zaleplon
- Zolpidem
What is the definition of Tolerance?
Physiological state characterized by decrease in effects of a drug with chronic administration
Describe the tolerance of Benzodiazepines?
Tolerance develops quickly for sedative effects & slowly for anxiolytic & anticonvulsant effects
What are the 4 mechanisms for tolerance?
- Neuro-adaptive process
- Desensitisation of inhibitory GABA receptors
- Sensitisation of (excitatory) NMDA receptors
- Adaptions on different time scale
When/How does drug dependence occur?
- Induces a rewarding experience
- Drug taking becomes compulsive
- Psychological/ Physical dependence
- Genetic factors
Describe the feelings of withdrawal?
- Increased anxiety, onset / exacerbation of depression
- Disturbed sleep
- Pain, stiffness, muscular aches
- Convulsions
What is withdrawal a result of?
Physical dependence (occur after relatively short courses of treatment)
What are Anxiolytics?
Medication/other intervention that inhibits anxiety
What are the clinical roles for sedative & anxiolytic agents/ when would you prescribe them?
- Enable uncomfortable diagnostic & therapeutic procedures to be carried out
- Management of acute alcohol withdrawal
- Other: anticonvulsant
What would you prescribe for management of acute alcohol withdrawal?
Chlordiazepoxide 1-2 week reducing regime
What is the CAGE questionnaire?
- Have you ever felt you should Cut down your drinking?
- Annoyed by other people criticizing?
- Felt Guilty about drinking?
- Taken a drink in morning to steady nerves or ease a hangover (Eye- opener)?
What are the symptoms of alcohol withdrawal?
- Insomnia / anxiety/ restlessness/ agitation
- Tremor
- Nausea & vomiting
- Sweating/Palpitations
- Hallucinations auditory /visual/tactile
- Seizures
What are 4 investigations suggestive of chronic alcohol consumption?
- Raised MCV
- Pancytopenia (alcohol induced bone marrow suppression)
- Folate deficiency
- Prolonged prothrombin time
Describe the timeline for symptoms of alcohol withdrawal?
- May start 8hrs after drop in alcohol levels
- Peak day 2
How do you manage insomnia?
- Assessment (pain/breathlessness)
- Good sleep hygiene
- Hypnotics reserved for acutely distressed
- Caution in elderly
Why is there caution in the elderly for using hypnotics?
- Confusion
- Falls
- Slower metabolism
What is sleep hygiene?
Aims to make people more aware of behavioural, environmental & temporal factors that may be detrimental or beneficial to sleep
What should you prescribe (if you must) for insomnia?
- Short acting Benzodiazepine or Z-drug
- Lowest effective dose for shortest time
- Inform patient no repeat prescriptions & explain why
How do you manage prolonged seizures?
- O2 if available
- Longer than 5 mins IV Lorazepam
- IV not available consider rectal Diazepam or intranasal / buccal Midazolam
What should you consider/exlude in prolonged seizures?
Hypoglycaemia
Describe the management of acute anxiety?
- Guided self help: reduce caffeine & alcohol, mantras, mindfulness, worrytime
- Cognitive behavioural therapy
Should you use benzodiazepines for acute anxiety in a primary care setting?
- NO, its inappropriate for “mild”
- Indicated for short-term relief of anxiety that is severe, disabling or causing patient unacceptable distress
Describe the effect of B-blockers for managing the somatic symptoms of anxiety?
- Helps with tachycardia,
palpitations, tremor, sweating - Usually Propranolol
What are the advantages of B-blockers?
- Non-sedative
- No dependence or abuse
What is Gabapentin & Pregabalin used for?
- NICE: consider pregabalin for generalised anxiety
- Used to manage chronic pain
- But misuse / abuse
What is Melatonin?
Naturally occurring hormone synthesized in pineal gland
What are the levels of people’s melatonin throughout the day?
High levels at night, low during day
What is Melatonin secreted in response to?
Input from retina
When is Melatonin drug used?
- Children with sleep disturbance
- Licensed for insomnia > 55yrs
What are the laws on driving (March 2015)?
- Offence to drive with certain drugs above specified levels in body, whether driving is impaired or not
- Taking drugs as directed & driving not impaired= NOT breaking the law
What 3 medications can affect driving?
- Benzodiazepine
- Opioids
- Amphetamines
What are the 3 main categories of harm?
- Physical Harm
- Dependence
- Social harms
What is Doxapram?
Short acting respiratory stimulant used in respiratory failure
In what 3 scenarios would you use Doxapram?
- Post-operative respiratory depression
- Acute respiratory failure
- Neonatal apnoea
Describe Strychnine convulsant drug?
- Poison
- Powerful convulsant
- Violent extensor spasms triggered by minor sensory stimuli
- Blocks glycine receptors
What does small doses of Strychnine drug cause?
Improvement in visual & auditory acuity
What do Hallucinogen drugs (psyhchotomimetic drugs) act on?
5-HT receptors & transporters
Give 4 examples of Hallucinogen drugs?
- LSD (D-lysergic acid diethylamine)
- Psilocybin
- Mescaline
- MDMA (Ecstasy)
What are the main pharmacological effect of Hallucinogens?
- Alter perception of sights & sounds
- Hallucinations (visual, auditory, tactile or olfactory)
- Sounds perceived as visions
- Thought processes illogical & disconnected
What are “bad trips”?
- Hallucinations can take on menacing quality
- Maybe accompanied by paranoid delusions
When can “flashbacks” occur due to hallucinogens?
Weeks or months later
When can a tolerance to Hallucinogen’s develop?
Quickly (plus cross-talk between drugs ie. LSD causes higher doses of MDMA needed for the same effects)
Describe the withdrawal of Hallucinogen’s?
No physical withdrawal syndrome, psychological effects i.e. “flashbacks & psychosis
What are the risks for Hallucinogen’s?
- Injury & accidental death whilst intoxicated
- Poisoning due to mistaken identity
- Adrenergic effects with LSD
- GI effects with Psilocybin
Describe Phencyclidine (PCP, “Angel Dust”) dissociative anaesthetic?
- Synthesised as possible IV general anaesthetic
- Disorientation & hallucinations
Describe the use of Ketamine?
Induction & maintenance of anaesthesia
What effects do Phencyclidine & Ketamine dissociative anaesthetics have?
- Resemble other psychotomimetic drugs
- Analgesic
- Stereotyped motor behaviour like Amphetamine
- Can give “bad trip” as LSD
What are both Phencyclidine & Ketamine?
NMDA receptor antagonists
Describe the tolerance of dissociative anaesthetics?
Rapid over regular, repeated doses
Describe the dependence of dissociative anaesthetics?
- Physical & psychological
- Withdrawal
syndromes with PCP
Describe the risks of dissociative anaesthetics?
- Accidents/loss of control/automatic behaviour
- PCP: hyperthermia, convulsions
- Ketamine: overdose with heart attack/respiratory failure (rare)
What is Cannabis (cannabis sativa, indica)?
- Psychotomimetic drug
- Tetrahydrocannabinol (THC) & 11-hydroxy-THC
Give 5 examples of psychomotor stimulants?
- Amphetamine (speed)
- Dextroamphetamine
- Methylamphetamine (crystal meth)
- Methylphenidate (ritolen)
- 3,4-methylenedioxymethamphetamine (MDMA)
What are the main effects of psychomotor stimulants?
- Locomotor stimulation
- Euphoria & excitement
- Insomnia
- Anorexia (diminishes with continued use)
- Stereotypic behaviour (chronicuse)
What are the behavioural effect of Amphetamine probably due to?
Release of dopamine rather than noradrenaline
Describe the effects of Amphetamine?
- Become confident, hyperactive & talkative
- Sex drive enhanced
- Fatigue (both physical & mental) reduced
- Doesn’t enhance mental performance, just ability to concentrate for longer
Describe the mode of action of Amphetamines?
- Competitive inhibitors of monoamine uptake (noradrenaline, dopamine)
- Inhibit MAO at high concentrations
- Cause NET to work in “reverse”
What are the 3 dopamine pathways in the brain & what do they do?
- Nigrostriatal- Motor control
- Mesolimbic & Mesocortical- behavioural effects
- Tuberohypophyseal system- endocrine function
What are the 2 noradrenaline pathways in the brain & what do they do?
- Locus coeruleus- wakefulness, alterness
2. Medulla/hypothalamus- Blood pressure regulation
What are the 2 serotonin pathways in the brain & what do they do?
- Locus coeruleus- sensory signals
2. Raphe nuclei- sleep, wakefulness, mood
Describe the tolerance of Amphetamines?
Rapid tolerance to euphoric & anorexic effects, slowly for other effects
Describe the dependance of Amphetamines?
Moderate dependence potential due to euphoria
Describe “Amphetamine psychosis”?
- If taken repeatedly over a few days
- Almost indistinguishable from acute schizophrenic attack
- Stereotypic behaviour
- After cessation, period of deep sleep
What can the subject feel after cessation of Amphetamines?
Lethargic, depressed, anxious & often very hungry
What are the risks of Amphetamines?
- Vascular accidents (tachycardias, arrhythmias, ↑ BP)
- Cerebral convulsions & coma
- Excitation syndrome (hyperthermia/tachycardia)
- Anorexia
- Chronic paranoid psychosis
- Cognitive impairment
- Personality/mood
What is Khat (Catha edulis)?
- Psychomotor stimulant
- Contains cathinone, an amphetamine-like stimulant
What is Nicotine (Nicotiana tabacum)?
Psychomotor stimulant
Where does Cocaine comes from?
Leaves of South American shrub, Erythroxylum Coca
What is Cocaine?
Potent inhibitor of catecholamine uptake into nerve terminals (esp. dopamine)
What are the effects of Cocaine (which resemble Amphetamines)?
- Euphoria (related to ↓ dopamine & 5-HT reuptake)
- Alertness & wakefulness
- Increased confidence & strength
- Increased sexual feelings
- Indifference to concerns/cares
How can cocaine be administered?
- Readily absorbed by many routes
- Nasal damages the mucosa & septum
- Free-base form (‘crack’) can be smoked
Describe the tolerance of cocaine?
Occurs rapidly
Describe the dependance of cocaine?
- Physical dependence mild
- Strong psychological
dependence occurs
What are the ACUTE risks of cocaine?
- Cardiovascular (↑BP, tachycardia, ventricular fibrillation, heart attack, respiratory arrest, stroke)
- Muscle spasms, tremor
- Hyperthermia
- Seizures, headaches, excited delirium
What are the CHRONIC risks of cocaine?
- Heart attacks (furring of coronary arteries)
- Malnutrition & weight loss
- Decreased libido & impotence
- Personality/mood
- “Toxic syndrome”
What is “toxic syndrome” from chronic cocaine similar to?
Acute paranoid schizophrenia
What contains Methylxanthines?
Tea, coffee, cocoa
What are the main 2 Methylxanthines?
- Caffeine
2. Theophylline
Describe the effects of Caffeine & Theophylline (Methylxanthines)?
- Mild CNS stimulants
- Diuretics
- Cardiac muscle stimulants
- Smooth muscle relaxants (esp. bronchial)
What are the main psychological effects of Methylxanthines?
Reduce fatigue & improve mental performance without any euphoria
Methylxanthines develop what to a small extent?
Tolerance & habituation
What can Theophylline be used for clinically?
Bronchodilator in severe asthma attacks
What do all endocrine glands NOT have?
Ducts
What is an endocrine secretion?
Hormones diffuse directly into capillaries to act on distant target organs
What is a paracrine secretion?
Hormones secreted & act more locally
What is a autocrine secretion?
Hormones which act on themselves
Endocrine glands are very ______?
Vascular (fenestrated capillaries)
Describe the 3 different locations of endocrine glands?
- Discrete organs (thyroid, pituitary, adrenals)
- Associated with other tissues (pancreas)
- Scattered within complex organs (ovary, kidney, gut)
List the major endocrine glands?
- Pineal
- Hypothalamus
- Pituitary
- Thyroid
- Parathyroid
- Thymus
- Adrenal
- Pancreas
- Ovary
- Testis
What are the 3 factors controlling hormone release from endocrine glands?
- Humoral
- Neural
- Hormonal
What are the hormones in the hypothalamus-pituitary axis?
Endocrine & Neuroendocrine hormones
What are the hormones in the adrenal cortex/medulla?
- Glucocorticoids
- Mineralocorticoids
- Catecholamines
What are the hormones in the thyroid?
- Thyroid hormones
- Calcitonin
What is the hormone in the parathyroids?
Parathyroid hormone (PTH)
What are the hormones in the pancreas?
- Insulin
- Glucagon
- Pancreatic polypeptide
- Somatostatin
What are the hormones in the gastrointestinal tract?
- CCK, GIP, GLP 1&2
- Glicentin, Gastrin
- Bombesin
- Secretin, VIP
- Substance P
- Guanylins
What is the hormone in the pineal gland?
Melatonin
What is the hormone in the thymus?
Thymopoietin
What are the hormone in the gonads (testes/ovaries)?
- Sex steriods
- Inhibins
- Activins
What are the hormones in the heart?
- Natriuretic peptides
- ANP
- BNP
What are the hormone in the liver?
- Insulin-like growth factors
- Leptin
- Angiotensinogen
What are the hormones in the kidney?
- Erythropoietin
- Renin
What is the hormone in adipose tissue?
Leptin
Describe the location of the pituitary?
- Enclosed by bony
sella turcica of sphenoid - Enclosed superiorly by diaphragma sellae
- Related to cavernous sinus
- Lies posterior to optic chiasma & sphenoid sinus
Describe the 2 glands of the pituitary (hypophysis)?
- POSTERIOR pituitary- post lobe, neurohypophysis, pituitary stalk
- ANTERIOR pituitary- ant lobe, adenohypophysis, pars anterior (distalis), pars tuberalis (PT), pars intermedia
What is Pars intermedia of the pituitary derived from?
Rathke’s pouch
Describe the Pars intermedia of the pituitary gland?
- Poorly developed
- Between anterior & posterior lobes of
pituitary - May contain colloid-filled, epithelial lined follicles
What may be a connection of pars intermedia function?
Numerous basophilic cells, maybe connection with secretion of melanocyte stimulating hormone MSH
Describe the embryonic development of the anterior pituitary?
- Up-growth of epithelium from oral cavity (Rathke’s pouch)
2. Rathke’s pouch loses contact with oral cavity
Describe the embryonic development of the posterior pituitary?
Down-growth from the brain (infundibulum)
How can craniopharyngiomas develop?
Slow growing tumours may develop along track of Rathke’s pouch
Describe the staining of the different secretory cells of the anterior pituitary?
- Chromophils take up the stain & have 2 types- (A) Acidophils 65% GH & prolactin (B) Basophils 35%
- Chromophobes don’t stain (C)
List the neurohormones controlling the secretions from the anterior pituitary?
- Thyrotropin-releasing hormone
- Corticotropin-releasing hormone
- Growth hormone-releasing hormone
- Somatotropin-releasing hormone
- Somatostatin/Growth hormone release-inhibiting
- Gonadotropin-releasing hormone
- Follicle-stimulating hormone releasing hormone
- Luteinising hormone releasing hormone
- Prolactin releasing factor, TRH
- Prolactin release inhibiting factor, Dopamine
List the neurohormones released from the posterior pituitary?
- Vasopressin (VP)
- Anti-diuretic peptide (ADH)
- Oxytocin (OT)
What are the primary actions if trophic hormones?
On other endocrine glands
List the trophic hormones of the anterior pituitary?
- Thyrotropin/ Thyroid-stimulating hormone (TSH)
- Corticotropin/ Adrenocorticotropic hormone (ACTH)
- Gonadotropins: Luteinising Hormone (LH) & Follicle-stimulating hormone (FSH)
List the hormones of the anterior pituitary acting on peripheral target cells?
- Somatotropin / Growth hormone (GH)
- Prolactin (PL)
- α, β & γ Melanotropin / Melanocyte-stimulating hormone (MSH)
Describe the 3 steps to controlling growth hormone release?
- Neurosecretory cells in arcuate nucleus secrete GHRH that reaches somatotrophs via hypophyseal portal blood supply
- Periventricular cells release somatostatin which inhibits GH
- GHRH causes somatotrophs to synthesise & release GH
How does IGF-1 inhibit growth hormone (GH)?
- Indirectly by increasing secreting of somatostatin from nuclei in the periventricular region
- Indirectly by suppressing GHRH release from arcuate nucleus in hypothalamus
- Directly by suppressing somatotrophs
What does Growth hormone (GH) inhibit and stimulate?
- Inhibits own secretion via “short-loop” feedback on somatotrophs
- Stimulates secreting of IGF-1 from peripheral target tissue
What does growth hormone secretion control?
Circadian rhythms
What are the 4 physiological actions of Growth Hormone (GH)?
- Increased cartilage formation & skeletal growth
- Increased protein synthesis, cell growth & proliferation
- Increased lipolysis
- Increase blood glucose & other anti-insulin effects
What are the physiological consequences of Growth Hormone (GH)?
- Increased linear growth & lean body mass
- Vital for normal post-natal development & rapid growth through puberty
- Maintenance of protein synthesis & tissue functions in adult
What can growth hormone (GH) deficiency cause?
Dwarfism in children due to predictable effects on linear bone growth & decreased availability of lipids & glucose for energy
How can Dwarfism be treated?
With human growth hormone
What can growth hormone excess (acromegaly) often be due to?
Pituitary adenoma
What can growth hormone excess before puberty cause?
Gigantism due to excess stimulation of epiphyseal plates
What can growth hormone excess after puberty cause?
- Periosteal bone growth causing larger hand, jaw & foot size
- Soft tissue growth –> large tongue & coarsening of facial features
- Insulin resistance & glucose intolerance
What can growth hormone excess be treated with?
Synthetic long-acting somatostatins (Octreotide) with varying success
List the physical signs of gigantism/acromegaly?
- Swelling of soft tissue
- Skin tags (wart-like growths)
- Muscle weakness/fatigue
- Skin changes, including thickening, oiliness, acne
- Hirsutism (abnormal/unusual hair growth)
List the other symptoms of gigantism/acromegaly?
- Arthralgia (pain in joints) (75%)
- Amenorrhea in women (72%)
- Hyperhidrosis (excessive perspiration) (64%)
- Sleep apnea (60%)
- Headaches (55%)
- Paresthesia/ carpel tunnel syndrome (40%)
- Loss of libido or impotence (36%)
- Hypertension (28%)
- Thyroid disorders (goiter) (21%)
- Visual field defects (19%)
Where are Vasopressin (AVP) / Antidiuretic Hormone (ADH) synthesised?
Neurosecretory cells within the supra-optic nucleus (SON) & paraventricular nucleus (PVN)
What 3 things cause ADH release?
- Increased blood osmolality (osmoreceptors in brain)
- Decrease blood volume
- Renin/ angiotensin/ aldosterone system (RAAS)
What does ADH release do?
- Recruitment of
AQP water channels - Water retention (kidney collecting tubule)
What can a deficiency in hypothalamic neurohypophysial hormones cause?
Diabetes Insipidus (polyuria, polydispia)
What 2 things can cause a deficiency in hypothalamic neurohypophysial hormone?
- Cranial- 30% tumours, 30% trauma or disease induced, 30% familial disorders of NS cells
- Nephrogenic- sex-linked genetic defect in collecting tubule
What produces Oxytocin?
Hypothalamic neurones in paraventricular & supraoptic nuclei
Describe Oxytocin?
- Bound to glycoproteins
- Carried in axons to posterior pituitary
- Stored in vesicles in expanded ends of axons
What is Oxytocin release (neurosecretion) controlled by?
Directly by nervous impulses from hypothalamus
Describe the 4 steps to the hypothalamic control of milk production & ejection & roles of Prolactin & Oxytocin?
- Stimulus from suckling
- Neurons from spinal cord inhibit dopamine release from arcuate nucleus, prolactin increases –> milk
- Neurons from spinal cord stimulate oxytocin
- Neurons from spinal cord inhibit neurons in arcuate nucleus & preoptic area causing fall in GnHR which inhibits ovarian cycle
What does dopamine usually inhibit?
Lactotrophs in anterior pituitary which stops prolactin release
Where is the pineal gland location?
Midline in posterior part of the roof of the 3rd ventricle
What do pinealocytes have connections to?
Neural connections with hypothalamus
Describe the functions of the pineal gland?
- Darkness secretes melatonin (from tryptophan)
- Regulates circadian rhythms (melatonin hypnotic effect)
- Regulates reproductive processes, onset of puberty
- Aging & regulation of immune system
- Accumulates calcium phosphate with time, ‘brain sand’
What is a benign neoplasia?
Not invasive but its expanding and can still cause damage
What are the 3 commonest primary tumours which metastasise to the brain?
- Breast
- Melanoma
- Lung
What are the 3 other primary tumours which metastasise to the brain?
- Kidney
- Gut/gastric/colorectum
- Lymphoma/leukaemia
Describe the effects of metastatic brain tumours?
- None
- Space occupying lesions: fits, raised intracranial pressure, headaches, drowsiness, behavioural changes
- Haemorrhage
What does brain tumours do?
Skull can’t expand so it can destroy brain tissue or force it down the vertebral canal
What are the 3 types of lung cancer which can metastasise to the brain?
- Small cell (aggressive)
- Squamous
- Adenocarcinoma
What is the normal intracranial anatomy?
- Brain
- Linings ie. arachnoid membrane
- Pituitary
- Peripheral nerve elements: VIII cranial nerve
What does the brain (cerebrum) contain?
- Neurons
- Astrocytes
- Microglia
- Oligodendroglia
- Choroid plexus
- Ependyma
What is the characteristic of the commonest malignant tumour?
Its metastatic
What is the commonest intracranial primary neoplasm?
Meningioma ~1/3
What is the commonest primary neoplasms on a malignant spectrum?
Gliomas ~2/3
What is the commonest intracranial peripheral nerve tumour?
Acoustic Schwannoma (acoustic neuroma) <10%
Describe Meningiomas?
- Sporadic
- Post-irradiation (radiation)
- Part of NF2
Describe the location/growth of a Meningioma?
- Sites of arachnoid
- Well demarcated
- Slowly growing
- Not invasive, but erosive & compressive
What are the effects of Meningiomas?
- Fits
- Drowsiness
- Headaches
- Raised intracranial pressure
How can you treat meningiomas?
Surgical removal
What are most Glioma’s derived from?
Astrocytes
What are the 5 common Glioma’s (most common 1st)?
- Astrocytes (most common)
- Oligodendroglioma
- Ependymoma
- Choroid plexus tumours
- Medulloblastoma & PNET
Describe Astrocytoma (glioma)?
- None completely benign, always degree of malignancy
- Grading informs prognosis & treatment
Describe the WHO grading system for Astrocytoma’s?
I- localised
II- diffuse
III- anaplastic astrocytoma
IV- glioblastoma multiforme
What does PNET stand for?
Primitive neuroectodermal tumours
What are the 3 different types of peripheral nerve tumours?
- Neural- neuroblastoma, ganglioneuroma
- Schwannoma or Neurofibroma
- Cranial nerve VIII- acoustic nerve
Describe a Schwannoma & how it presents clinically?
- Lump within nerve
- Benign & not invasive
- Cause pain due to nerve compression
- Surgically remove it
Describe a Neurofibroma & how it presents clinically?
- Mixed between the nerve fibres
- Benign
- Difficult to surgically remove without sacrificing the nerve
Describe Neurofibromatosis 1 (NF-1)?
- Autosomal dominant
- 50% spontaneous
- White spots due to melanin disturbance
- Hard to remove
What are the different Neurofibromatosis 1 (NF-2)?
- MISME: Multiple Inherited Schwannomas, Meningiomas & Ependymomas
- Bilateral acoustic Schwannoma
- Merlin NF2
What is general anaesthesia?
Reversible, drug induced loss of consciousness, usually to allow a surgical procedure to be performed
What are intravenous induction agents?
Agents which will
induce loss of consciousness in one arm brain circulation time
Give 3 examples of commonly used anaesthetic agents (drugs)?
- Propofol
- Thiopentone
- Etomidate
What is an inhalation anaesthetic agent?
- Gas/vapour delivered to patient via breathing circuit
- May be used to induce anaesthesia (children)
- More commonly used to maintain anaesthesia
Give 4 examples of inhalation anaesthetic agents?
- Nitrous oxide
- Isoflurane
- Sevoflurane
- Desflurane
What is Entonox?
50 nitrous: 50 oxygen
When might you use Entonox?
- Analgesic
- Labour
- Trauma
How were anaesthetics initially thought to work?
Due to lipid solubility
What does MAC stand for?
Minimum alveolar concentration
What is MAC?
- Measure of potency of an anaesthetic
- More lipid soluble = more potent = lower MAC
What are the more blood soluble anaesthetics?
Slower onset
How are anaesthetics now thought to work via?
Transmitter ligand gated ion channels, principally via GABAa receptor
What are IV anaesthetics mediated by?
GABA β3 subunit
What are IV hangovers mediated by?
GABA β2 subunit
What do Etomidate, Propofol & Barbiturates work on & what does this result in?
Excite GABAa receptors –> Decrease consciousness movement
What does volatile anaesthetics work on & what does this result in?
Excite GABAa receptors, Inhibit Sodium channels, Excite Potassium channels –> decrease consciousness movement
What does Nitrous oxide & Xenon work on & what does this result in?
Excite Potassium channels & Inhibit NMDA receptors –> decrease consciousness movement
What does Ketamine (dissociative anaesthetic) work on & what does this result in?
Inhibits NMDA receptors –> decrease consciousness movement
What is the main place anaesthetics target?
Thalamus
How does waking up from anaesthetic work?
When stopping administeration concentration in brain decreases & becomes redistributed to the rest of the body –> Waking up!
What is the main learning points regarding anaesthetics?
Virtually all anaesthetic agents (exception-ketamine) will to a greater/ lesser effect have a negative inotropic effect on heart & reduce systemic vascular resistance
What can any drug causing loss of consciousness lead to?
Obstruction of the airway/ respiratory depression
What does respiratory depression tend to be with IV agents?
Fall in respiratory rate
What does respiratory depression tend to be with inhalation agents?
Fall in tidal volume
What do we want an ideal anaesthetic agent to do?
- Act rapidly
- Pleasant
- Cheap to manufacture
- Stable (soda lime)
- Analgesic effect
- Amnesic effect
- Minimal “hangover”
What do we NOT want anaesthetic agents to do?
- Irritant on veins/ airways
- Emetic
- Minimal effects on other systems (breathing, cardiovascular)
- Produce toxic metabolites
- Cause histamine release / anaphylaxis
What anaesthetic agents are painful on injection?
Propofol & Etomidate
What is “balanced anaesthesia”?
Selection of drugs & techniques bearing in mind-
- Health & requests of patient
- Properties of drugs
- Requirements of surgery to minimise patient risk & maximise patient safety & comfort
What type of traumatic stressors can cause PTSD to develop?
- Threaten life or well-being
- Overwhelm coping abilities
- Challenge the assumptions that people make about the World
Describe the historic of “Railway spine” in the 19th century after Industrial Revolution?
- Physical disorders in healthy & apparently uninjured railway accident victims.
- Result from molecular changes in spinal cord
- Horror of experiencing railway accident was part or all of the syndrome
Describe the historic of “Shell shock” in World war I?
- Believed that concussion of artillery shells cause CNS damage
- Not explain cases of shock/distress among those who were not exposed to exploding shells
List the diverse populations which are possible to find cases of PTSD?
- Family & relationship abuse
- Exposure to pathogens (HIV)
- Assaults
- Motor vehicle accidents
- Natural disasters
- Human caused disasters
- Exposure to noxious agents (chernobyl)
What are the evidence rates (%) of 3 different PTSD events?
- Rape: 80%
- Witnessing/experiencing someone’s tragic death: 30%
- Motor vehicle accidents with injury: 23%
Why is it important to examine long-term experience in PTSD cases?
PTSD symptoms subside in many people other time & symptoms wax & wane
What are the 4 symptoms of PTSD according to NICE CG26 p7?
- Re-experiencing symptoms
- Avoidance of reminders of the trauma
- Hyperarousal
- Emotional numbing
Describe re-experiencing symptoms associated with PTSD?
- Through intrusive thoughts, flashbacks/ nightmares
- Flashbacks feel ‘real’
- Images described as if being in a film of the incident
- At 1st, may feel actually ‘in’ the film but perspective change to observer as they recover
Describe the avoidance symptoms associated with PTSD?
- Avoidance of thoughts, feelings, people, places, & activities related to event
- Difficulty remembering important aspects of event
Describe the persistent feelings of over-arousal associated with PTSD?
- Irritability, anger
- Being easily startled/ hyper-vigilant
- Insomnia
- Difficulty concentrating
Describe emotional numbing associated with PTSD?
- Lack of ability to experience feelings
- Feeling detached from other people
- Giving up previously significant activities
- Amnesia for significant parts of the event
Evidence shows that what 6 feelings go with PTSD (Brewin & Holmes)?
- Guilt
- Shame
- Sadness
- Betrayal
- Humiliation
- Anger
Describe the onset of symptoms for PTSD?
Can develop immediately, in some (<15%) the onset of symptoms may be delayed
What do some PTSD sufferers do?
May NOT seek help for months/years despite considerable distress
How is assessment of PTSD challenging?
Many people avoid talking about their problems when presenting with associated complaints
What are the 2 predictors of PTSD?
- Characteristics of event
2. Characteristics of person
Describe the PTSD predictor- characteristics of the event?
- Stressors of human origin more likely to cause PTSD than natural disasters
- How deliberate human-caused stressors are judged to be, also important
What are 4 vulnerability factors of the person which may makes them more prone to develop PTSD?
- Childhood trauma
- Early separation from parents
- Pre-existing depression / anxiety
- Family history of anxiety
What are the 6 additional vulnerability factors for PTSD according to NICE clinical knowledge summaries?
- Previous trauma
- History of psychiatric illness
- Gender
- Younger & older age
- Lower SES / minority status
- Lower educational status
What may be the case for vulnerability pre-existing factors?
May only predict PTSD in extreme cases
What are other 5 psychological factors associated with how severe the impact of a stressor may be & how likely PTSD is to develop?
- Personal impact of event
- Extent of perceived control over future threats
- How one is prepared to deal with a stressor
- One’s beliefs & assumptions about trauma
- Social support
What are majority of adults exposed to?
At least 1 potentially traumatic event in their lifetime, only a small subset of exposed adults develop PTSD
What is Resilience?
Adult capacity to maintain healthy psychological & physical functioning
Describe the 3 characteristics of resilient people?
- Process flexible adaptation to challenges
- Sense of continuity in their beliefs about themselves/ lives
- Retain ability to regenerate positive experiences
Describe the physiology of PTSD?
- Shows higher levels of catecholamine compared to without PTSD
- Lower levels of cortisol which may interfere with body’s ability to restore itself fully after trauma & related to increased rate of physical illness in trauma survivors
What is the physiology of PTSD similar to?
Stress response
Describe the relationship of PTSD & medical conditions?
- Onset of illness can be stressful- MI, stroke etc.
- Diagnosis of a life-threatening disease- heart failure, HIV, cancer
- Prolonged treatment or unpleasant medical procedures
What is Psychological debriefing?
- Talking through trauma in a structured way with counsellor soon after trauma
- Usually single session
Describe how Psychological debriefing may be ineffective in preventing PTSD or actually increase the risk of the disorder?
- Secondary traumatisation
- Medicalising normal distress
- May prevent potentially protective responses of denial & distancing
What does NICE guidelines state for Psychological debriefing being used as prevention for PTSD?
Psychological debriefing should NOT be routine practice when delivering services
What are the NICE guidelines CG26 for treating PTSD where symptoms have been present for more than 3months?
- Trauma-focused psychological treatment: CBT or eye movement desentisation & reprocessing
- Non-trauma focused interventions: relaxation or non-directive therapy, don’t address traumatic memories (not routinely offered with chronic PTSD)
What is PTSD?
An anxiety disorder as a response to experiencing a traumatic event
What are the ocular defence mechanisms?
- Eyelids
- Lacrimal system
- Conjunctiva
- Cornea
- Blood-ocular barrier
What are the bacterial conjunctivitis 3 common conditions?
- Haemophilus influenzae
- Streptococcus pneumoniae
- Moraxella spp.
What are the 5 bacterial conjunctivitis in neonatal?
- Neisseria gonorrhoeae
- Escherichia coli
- Staphylococcus aureus
- Haemophilus influenza
- Chlamydia trachomatis
What is the HAI bacterial conjunctivitis?
Pseudomonas aeruginosa
What are the clinical features of bacterial conjunctivitis?
- Hyperaemic red conjunctivae
- Mucopurulent discharge
What samples would you take for bacterial conjunctivitis?
- Conjunctival swabs
- Corneal scrapings
What lab diagnosis would you do for bacterial conjunctivitis?
Culture & NAAT
What 3 local antibiotics can you give to treat bacterial conjunctivitis?
- Fusidic acid
- Tetracycline
- Chloramphenicol
Describe Adenovirus infections?
- Purulent conjunctivitis
- Enlargement of ipsilateral periauricular lymph node
- Possible corneal involvement
(punctate keratitis, subepithelial inflammatory infiltration)
What should you avoid when treating Adenovirus infections?
Topical steroids
Describe Varicella Zoster Virus (VZV) Infections?
- Shingles
- Ophthalmic dermatome of 5th cranial nerve
What are 4 the clinical features of Varicella Zoster Virus (VZV) Infections?
- Skin lesions
- Anterior uveitis
- Ocular perforation
- Retinal involvement
Describe Shingles?
- Chronic disease ~25%
- Very painful (post-herpetic neuralgia)
What is the antiviral treatment for Shingles & Herpes Simplex Virus?
Aciclovir
What is the treatment for severe inflammation in Shingles?
Topical steroids
How would you prevent the primary infection of Shingles?
Live attenuated vaccine
What is the most common infectious cause of blindness in developed world?
Herpes Simplex Virus (HSV) Infections
What are the 4 clinical features of Herpes Simplex Virus (HSV) Infections?
- Ulcerative blepharitis
- Follicular conjunctivitis
- Regional lymphadenopathy
- Corneal involvement (not unusual)
When may Herpes Simplex Virus relapses occur?
~4 years
Describe a dendritic ulcer associated with Herpes Simplex Virus?
(marker of infection)
- Inflammation in deeper tissue
- Keratitis
- Corneal oedema
- Opacity
What should you avoid in treatment of Herpes Simplex Virus?
Steroids
What happens when there is repeated scarring in Herpes Simplex Virus?
Corneal grafting
Describe Onchocerciasis (River Blindness)?
- Caused by parasite Onchocerca volvulus
- Transmitted by blackfly
Where especially is Onchocerciasis (River Blindness) a public health problem?
West Africa
What is the international control programme for Onchocerciasis (River Blindness)?
- Mass treatment of whole populations
- Invermectin & Doxycyline
Describe Trachomatis?
- Chlamydia trachomatis
- Chronic keratoconjunctivitis
- Largely confined to tropics
Describe the 4 symptoms of Trachomatis, which occur 3-10d post-infection?
- Lacrimation
- Mucopurulent discharge
- Conjuntival involvement
- Follicular hypertrophy
What is the treatment for Trachomatis?
Oral macrolides i.e. Azithromycin
Describe the ocular manifestations of AIDS?
- Cotton wool spots
- Infarction of retinal nerve fibre layer
- Cytomegalovirus infection late in course of HIV disease
What is the antiviral treatment for AIDS?
IV Ganciclovir
What does Endophthalmitis develop after (4)?
- Ocular operation
- Trauma
- Inoculation of foreign body
- Complication of systemic infection
What are the bacterial causes of Endophthalmitis treated with?
Systemic antibiotics & early vitrectomy
What are the 4 common (>50%) normal microbiota of the respiratory tract?
- Bacteroides spp.
- Candida albicans
- Oral Streptococci
- Haemophilus influenzae
What are the 3 occasional (<10%) normal microbiota of the respiratory tract?
- Streptococcus pyogenes
- Streptococcus pneumoniae
- Neisseria meningitidis
What are the 4 latent state normal microbiota of the respiratory tract tissues?
- Herpes simplex virus type I (HSV) 2. Epstein-Barr virus (EBV)
- Cytomegalovirus (CMV)
- Mycobacterium tuberculosis
What are the 5 respiratory tract host defences?
- Saliva
- Mucus
- Cilia (muco-ciliary escalator/elevator) 4. Nasal secretions
- Antimicrobial peptides
What is the common cold also known as?
Acute Coryza
What is the transmission of the common cold (Acute Coryza)?
- Aerosol
2. Virus-contaminated hands
What are the 5 causative agents for the common cold?
- 40% Rhinoviruses
- 30% Coronaviruses
- Coxsackie virus A
- Echovirus
- Parainfluenza virus
What seasons does the common cold arise (Acute Coryza)?
Early autumn & mid / late spring
List the clinical features of the common cold (Acute Coryza)?
- Tiredness
- Slight pyrexia
- Malaise
- Sore nose & pharynx
- Profuse, watery nasal discharge becoming mucopurulent
- Sneezing in early stages
- Secondary bacterial infection in minority
What are the 6 VIRAL causative agents for Acute Pharyngitis & Tonsillitis?
- Epstein-Barr virus
- Cytomegalovirus
- Herpes simplex virus type I
- Rhinovirus
- Coronavirus
- Adenovirus
What are the 3 BACTERIAL causative agents for Acute Pharyngitis & Tonsillitis?
- Streptococcus pyogenes
- Haemophilus influenzae
- Corynebacterium diphtheriae
Describe Cytomegalovirus (CMV)?
- Transmission in body secretions & organ transplants
- Usually asymptomatic or mild
- Can reactivate & cause disease when cell-mediated immunity compromised
What 3 things can be used to treat Cytomegalovirus (CMV)?
- Ganciclovir
- Foscarnet
- Cidofovir
What is another name for Epstein-Barr Virus (EBV)?
Glandular fever
What does Epstein-Barr Virus (EBV) do?
Replicates in B lymphocytes
List the clinical features of What does Epstein-Barr Virus (EBV)?
- Fever, Headache - Malaise
- Sore throat
- Anorexia
- Palatal petechiae
- Cervical lymphadenopathy - Splenomegaly
- Mild hepatitis
What are the ORAL clinical features of Epstein-Barr Virus (EBV)?
- Swollen tonsils & uvula
- Petechiae on the soft palate
- White exudate
What is the treatment for Glandular fever (EBV)?
- NOT with antibiotics (ampicillin & amoxycillin)!
- Contact sports/ heavy lifting avoided during 1st month of illness & until splenomegaly has resolved
What are the 3 possible complications of Glandular fever (EBV)?
- Burkitt’s lymphoma
- Nasopharyngeal carcinoma
- Guillain-Barré syndrome
What is Tonsillitis caused by?
Streptococcus pyogenes
What are the 4 clinical features of Tonsillitis?
- Fever
- Pain in throat
- Enlargement of tonsils
- Tonsillar lymphadenopathy
What treatment is Tonsillitis susceptible to?
Penicillin
increasing resistance to erythromycin & tetracycline
What are the 5 complications of Streptococcus pyogenes?
1. Scarlet Fever (erythrogenic toxin from S. pyogenes) 2. Peritonsillar abscess 3. Otitis media / sinusitis 4. Rheumatic heart disease 5. Glomerulonephritis
What is parotitis caused by?
Mumps virus
List the clinical features of Parotitis?
- Fever, Malaise
- Headache
- Anorexia
- Trismus
- Severe pain & swelling of parotid gland(s)
What are the 2 primary sites of replication for Parotitis?
- URT
2. Eye
What are the 3 forms of treatment for Parotitis?
- Mouth care
- Nutritional
- Analgesia
What are the 2 forms of prevention for Parotitis?
- Active immunisation
2. Measles-Mumps-Rubella (MMR) vaccine
What are the complications of Parotitis?
- CNS involvement
- Epididymo-orchitis (~30% infected after puberty)
What is Acute Epiglottitis caused by?
Haemophilus influenzae
Describe the prevalence of Acute Epiglottitis?
- Nasopharynx of 75% healthy people
- 88% reduction in England & Wales since Hib vaccine in 1992
List the clinical features of Acute Epiglottitis?
- High fever
- Massive oedema of epiglottis
- Severe airflow obstruction –> breathing difficulties
- Bacteraemia
Describe the diagnosis of Acute Epiglottitis?
- Do NOT examine throat/ take swabs as this will precipitate complete obstruction of airway
- Blood cultures to isolate H. influenzae
What are the 3 possible treatments for Acute Epiglottitis?
- Life-threatening emergency
- Urgent endotracheal intubation
- IV antibiotics (ceftriaxone or chloramphenicol)
What causes Diptheria?
Corynebacterium diphtheriae
Describe Diphtheria infection?
- Usually childhood disease
- Colonises pharynx, larynx & nose (rarely skin & genital)
- Transmission aerosol
List the clinical features of Diphtheria?
- Sore throat
- Fever
- Formation of pseudomembrane
- Lymphadenopathy
- Oedema of anterior cervical tissue (bull-neck)
Describe the diagnosis of Diptheria?
Clinical grounds as therapy is usually urgently required
Describe the 3 possible treatments of Diptheria?
- Anti-toxin therapy intramuscularly
- Concurrent antibiotics (penicillin or erythromycin)
- Strict isolation
Describe the 2 prevention techniques for Diptheria?
- Childhood immunisation with toxoid vaccine
2. Booster doses if travelling to endemic areas if >10 years have elapsed since primary vaccination
What are 4 possible viral origins of Laryngitis & Tracheitis?
- Parainfluenza
- Respiratory Syncytial
- Influenza
- Adenovirus
What are the clinical features of Laryngitis & Tracheitis in adults?
- Hoarseness
- Retrosternal pain
What are the clinical features of Laryngitis & Tracheitis in children?
- Dry cough
- Inspiratory stridor (croup)
Describe Otitis & Sinusitis?
- Blockage of eustachian tube/ sinuses
- Mucosal swelling prevents muco-ciliary clearance of infection
- Exacerbated by local accumulation of inflammatory bacterial products
What are the 5 main causative agents for Otitis & Sinusitis?
- Respiratory syncytial virus (RSV)
- Mumps virus
- Streptococcus pneumoniae
- Haemophilus influenzae
- Bacteroides fragilis
Describe the prevalence of Otitis Media?
- Most common in infants & small children
- 50% viral origin, mainly Respiratory Syncytial Virus (RSV)
List the clinical features of Otitis Media?
- Fever
- Diarrhoea & vomiting
- Bulging ear drum & dilated vessels
- Fluid in middle ear (“glue ear”)
What can Otitis Media lead to?
- Chronic suppurative otitis media
- Hearing difficulties & delayed learning development
What 3 bugs is Otitis Externa favoured by?
- Staphylococcus aureus
- Candida albicans
- Pseudomonas aeruginosa
What is the treatment of Otitis Externa?
Antibiotic ear drops containing Polymyxin
Acute Sinusitis aetiology & pathology is similar to what?
Otitis media
What are the 2 clinical features of Acute Sinusitis?
- Facial pain
2. Localised tenderness
What is the treatment for Acute Sinusitis?
- Ampicillin
- Amoxycillin
- Oral Cephalosporins (esp. with β-lactamase-producing organisms)