Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

ACEM viva > neuro pharmacology > Flashcards

neuro pharmacology Flashcards

1
Q

. Cholinergic Pharmacology: Atropine
What is the MOA of atropine?

A

● A competitive, reversible muscarinic ACh receptor antagonist
● Anticholinergic activity
● Equipotent at M1, M2, M3 receptors. Minimal effects at nicotinic receptors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Describe the pharmacokinetics of atropine

A

● Administration: IV, oral, topical, nebulized/inhaled
● Distribution: wide Vd including into the CNS
● Metabolism & excretion: Half life of 2 hours, 60% is excreted unchanged via the
kidneys. 40% undergoes phase I and phase II metabolism and is then renally
excreted

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Describe the organ effects of atropine

A

● Eye - mydriasis and cycloplegia
● CNS - delirium, decreased tremor in parlinsons
● CVS - tachycardia (dose dependent, some small doses can cause initial
bradycardia)
● Resp - bronchodilation and decreased secretions
● GIT - decreased saliva, decreased gastric acid secretion, decreased mucin
production, delayed gastric emptying, decreased gut motility and resulting
increased transit time
● Urinary - relaxes ureteric and bladder wall smooth muscle, urine retention
● Skin - decreased sweating

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What is atropine used for clinically?

A

● Treatment of symptomatic bradycardia or other bradyarrhythmias - especially if
vagally mediated,
● Used in ophthalmology for inducing mydriasis
● Occasionally used as an adjunct in RSI for paediatrics
● Drying of secretions in cholinergic exposure or in palliative care
● Travellers diarrhoea

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Describe the effects of atropine poisoning.

A

● Agitation and delirium (Mad as a hatter)
● Raised temp (hot as Hades)
● Blurred vision/mydriasis (Blind as a bat)
● Flushed skin (red as a beet)
● Dry mouth (Dry as a bone)
● Tachycardia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

A 40 yr old man develops a dystonic reaction following a metoclopramide
injection. How does metoclopramide cause this dystonic reaction?

A

Metoclopramide is a dopamine antagonist and causes an imbalance in the
anticholinergic/dopamine transmission in the basal ganglia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

You treat this dystonic reaction with benztropine. What is the mechanism of
action?

A

Benztropine is a centrally acting antimuscarinic agent.
Blocks the muscarinic cholinergic receptors, to reduce the imbalance in the signalling
that causes the dystonic reaction

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Indirectly acting cholinomimetics (Acetylcholinesterase inhibitors)
What is the MOA of indirectly acting cholinomimetics

A

● These inhibit the acetylcholinesterase enzyme thereby increasing the
concentration of ACh in the vicinity of cholinoreceptors.
● Action on both nicotinic and muscarinic receptors.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What types of agents are there of Acetylcholinesterase inhibitors)

A

● Reversible - neostigmine, physostigmine, pyridostigmine
● Irreversible - organophosphates and insecticides

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What are the cardiovascular effects of these drugs?

A

● Both sympathetic and parasympathetic ganglia can be activated
● Parasympathetic effects generally predominate - bradycardia, decreased CO,
decreased contractility and no major change in BP
● Overdose may cause a tachycardia and hypotension

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Adrenergic Pharmacology: Adrenaline
Your patient has an allergic reaction that requires adrenaline
Describe the pharmacokinetics of adrenaline

A

● Administration: IM, IV, subcut, nebulised. Poor oral absorption.
● Distribution: Crosses the placenta but does not cross blood brain barrier. 50%
protein bound. Onset of action in seconds, duration of 2 mins.
● Metabolism: terminated by metabolism in sympathetic nerve terminals by COMT
and MAO. Circulating adrenaline metabolised by COMT.
● Elimination: metabolites excreted in the urine.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What are the pharmacodynamic effects of adrenaline?

A

Equal effects at alpha and beta receptors
● Alpha = vasoconstriction
● B1= positive inotropic and chronotropic effects
● B2= smooth muscle relaxation in airways and skeletal muscle

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Describe the effects of adrenaline on other organs besides the heart

A

● Respiratory - bronchodilation
● Eyes - pupil dilation, decreased IOP and production of aqueous humour
● Gastric smooth muscle - relaxation
● Genitourinary - bladder smooth muscle relaxation
● Liver - enhanced glycolysis
● Increased production of sweat at apocrine glands

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What are some undesired complications of an adrenaline infusion?

A

● General - anxiety, tremor, nausea, pallor, vomiting
● Heart and circulation - palpitations and arrhythmias, myocardial ischaemia, HTN
● Metabolic - hyperglycaemia, lactic acidosis, hypokalemia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Your patient is hypotensive. A noradrenaline infusion is commenced.
What receptors does noradrenaline act on?

A

● Predominantly alpha 1 → vascular smooth muscle constriction
● Also some alpha 2 activity (presynaptic) which exerts negative feedback on
noradrenaline release
● There is some effect on beta 1 and 2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

How does noradrenaline increase the blood pressure?

A

● Increase is in both systolic and diastolic blood pressure
● Alpha 1 activity → vasoconstriction → increased total peripheral resistance →
increased diastolic blood pressure
● Beta 1 activity → increased myocardial contractility → increased systolic BP

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

How does norad affect the heart rate?

A

● Beta 1 activity causes an increased heart rate.
● However, the compensatory baroreceptor reflex causes a decrease in HR.
● Overall, there is a minimal change in HR

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

You are treating a patient with neurogenic shock and decide to use metaraminol.
What is the MOA of metaraminol?

A

Direct alpha 1 agonist - though there is some indirect effect via increased noradrenaline
release

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What are its effects on the cardiovascular system of metaraminol?

A

● Vaso and arterio constriction in vascular beds
● Arterioconstriction causes an increase in BP
● Direct cardiac effects are less important
● HR slows due to vagal feedback
● CO is mostly unchanged

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What role do sympathomimetics play in the management of shock?

A

Temporising measures only, used whilst other treatments are instituted i.e. antibiotics,
fluid replacement
Useful in conditions where there is ‘failure’ of the sympathetic NS i.e. in a spinal injury or
in anaesthesia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What classes of local anaesthetic are used in ED?

A

● Aminoamides -(two i’s) Lignocaine, bupivicaine, prilocaine.

● Aminoesters - (single i) Procaine, Benzocaine, Tetracaine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Describe the mechanism of action of lignocaine

A

● Sodium channel blocker.
● Class 1B antiarrhythmic.
● Local anaesthetic.
● Blocks voltage gated sodium channels without altering the resting membrane
potential.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What is the maximum safe dose of lignocaine for local anaesthesia?

A

● Without adrenaline 3mg/kg
● With adrenaline 7mg/kg

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What factors affect absorption of lignocaine after local infiltration?

A

● Dose
● Site of injection
● Drug-tissue binding
● Blood flow through the tissue
● Use of adrenaline

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

What are the toxic effects of lignocaine?

A

● CNS
○ Early: perioral or tongue numbness, metallic taste
○ Moderate: nystagmus, tinnitus, muscle twitching, nausea, vomiting
○ Severe: seizures, sedation

● CVS
○ Arrhythmias i.e. bradycardia, conduction blocks
○ Hypotension
○ Worsening of CCF
○ Cardiovascular collapse

● GIT
○ Vomiting, anorexia, nausea

● Haem:
○ Methaemoglobinaemia (most often associated with prilocaine)

● Allergy
○ Rare but not impossible

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Explain the solubility characteristics of nitrous oxide

A

● Low solubility in the blood so reaches arterial tension rapidly.
● Rapid equilibrium in the brain and fast onset of action and fast recovery

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

What is the MOA of nitrous?

A

Multiple actions
● Modulates GABA-A receptors
● Increases dynorphin release
● NMDA agonist

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

What are the organ effects of nitrous oxide?

A

● CNS: analgesia, amnesia, increased cerebral blood flow
● Renal: decreased GFR, increased renal vascular resistance
● CVS: dose dependent myocardial depression
● Resp: reduced response to carbon dioxide ad hypoxia
● GI: Nausea and vomiting

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

Please describe the pharmacokinetics of propofol

A

● Administration: IV only - as a bolus or an infusion
● Distribution: Rapid onset and recovery is driven by redistribution of the drug from
the brain to other areas. Distribution half life is 2-4 minutes, elimination half life up
to 25 mins,
● Metabolism: rapidly metabolised in the liver.
● Elimination: Excreted in the urine as inactive metabolites.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

What are the indications for propofol?

A

Induction agent, maintenance of anaesthesia, procedural sedation.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

What properties of propofol make it suitable for procedural sedation?

A

Rapid onset and offset

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

What is the usual induction dose of propofol?

A

1-2.5mg/kg in adults, 2.5- 3.5mg/kg in kids

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

What are the clinical effects of propofol?

A

● Anaesthesia/sedation (no analgesia)
● Transient apnoea
● Decreased blood pressure
● Anti-emetic properties

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

What are the adverse effects of propofol?

A

Related to the system effects

● Hypotension from vaso and veno dilation and the negative inotropic effect
● Apnoea - dose related central depression of respiratory drive
● Pain on injection
● Allergy/anaphylaxis
● Propofol infusion syndrome (a metabolic acidosis)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

How can these adverse effects be minimised for propofol

A

● Titration of small doses
● Not using opiates or benzos concurrently
● Using an IV fluid bolus
● Reduce dose in elderly or those with poor cardiovascular reserve

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

. Ketamine
Describe the pharmacodynamics of ketamine

A

● NMDA receptor antagonist
● Inhibits reuptake of catecholamines and serotonin
● Potent short acting sedative, amnestic, analgesic and anaesthetic agent

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

What are the pharmacokinetics of ketamine?

A

● Absorption: Highly lipid soluble, so rapid onset
● Distribution: Effect is terminated by redistribution to inactive tissue sites. Low
protein binding.
● Metabolism: Metabolised in the liver via cytochrome P450 enzymes to inactive
metabolites
● Elimination: metabolites are excreted in the urine

38
Q

What are the system effects of ketamine?

A

● CNS: dissociative anaesthesia, profound analgesia. Cerebral vasodilation.
Potential anticonvulsant properties.
● CVS: hemodynamically stable, increases HR, BP, CO and myocardial oxygen
consumption
● Respiratory: Maintains airway reflexes, minimal respiratory depression,
bronchodilator effects. Can cause lacrimation and laryngospasm in children,
● Ocular: nystagmus

39
Q

What are the adverse effects of ketamine?

A

● Related to the system effects
● CNS- emergence phenomenon, dysphoria, hallucinations
● GI - nausea, vomiting
● Respiratory - laryngospasm, increased salivation

40
Q

Aside from procedural sedation, what are some other indications for ketamine?

A

● Induction agent
● Bronchodilator effect in asthma
● Acute behavioural disturbance

41
Q

What is an appropriate IV dose for induction or sedation for ketamine?

A

1-2mg/kg

42
Q

What are the main differences between ketamine and propofol?

A

● Propofol causes a marked decrease in peripheral BP, whereas ketamine is
hemodynamically stable on induction
● Ketamine has a slower recovery and is associated with emergence phenomena

43
Q

Thiopentone (included only to illustrate what to do if you get a question that you
don’t really know the answer to but you vaguely know the drug)
What are the pharmacokinetics?

A

● IV bolus
● Rapidly crosses BBB
● Highly lipid soluble
● Redistributes to muscle and fat
● Metabolised in the liver
● Excreted by the kidney

44
Q

What are the advantages of thiopentone?

A

Rapid onset, amnesic, reduction in ICP, anticonvulsant properties

45
Q

What are the adverse effects of thiopentone?

A

Drops BP, SV, CO due to myocardial depressant effect and increased capacitance
Apnoea

46
Q

Neuromuscular blockers: Suxamethonium
What is the MOA of sux?

A

Depolarizing neuromuscular blocker - 2 acetylcholine molecules linked end to end
2 phases

● Phase I (depolarising)
○ Reacts with nicotinic receptor to open the channel
○ Depolarises the motor endplate with spread to adjacent membranes
○ Causes fasciculation

● Phase II (desensitising)
○ Continued or repeated exposure to sux
○ End plate depolarisation increases
○ Membrane repolarizes but cannot be depolarised because it is now
desensitised
○ Means it is unresponsive to subsequent impulses
○ Causes a flaccid paralysis

47
Q

What are the pharmacokinetics of suxamethonium?

A

● Administration: IV
● Distribution: rapid onset (30-60 seconds) short duration (2-8 minutes)
● Metabolism: Hydrolysed rapidly by plasma pseudocholinesterase

48
Q

What are the adverse effects of sux?

A

● Muscle pain from fasciculations
● Bradycardia (with repeated doses)
● Release of K+, especially in burns, trauma
● Raised IOP and raised ICP
● Risk of malignant hyperthermia
● Risk of prolonged paralysis in cases of reduced or abnormal cholinesterase

49
Q

Rocuronium
What is the MOA of rocuronium?

A

● A nondepolarizing neuromuscular blocker
● Competitive inhibitor of acetylcholine at the nicotinic receptors
● In large doses is can enter the pore of the ion channel and cause a stronger
block

50
Q

What are the pharmacokinetics of rocuronium?

A

● Absorption: Given as an IV bolus 1.2mg/kg, onset within 45-60seconds.
● Distribution: Rapid. Highly ionized, small Vd. Duration of 20-75 mins.
● Metabolised in the liver, short half life
● Eliminated in the urine

51
Q

How does suxamethonium differ from rocuronium?

A

● Duration of action of sux is much shorter (5-10 mins)
● Different side effect profile and contraindications
● Sux is a depolarizing NMB, whereas roc is a non depolarising
● Rocuronium has an antidote
● Suxamethonium metabolised in the plasma, roc in the liver

52
Q

Your patient is intoxicated.
What are the pharmacodynamic effects of ethanol?

A

● CNS: sedation, disinhibition, impaired judgement, impaired motor skills, ataxia,
slurred speech, coma, respiratory depression.
● CVS: decreased contractility
● Smooth muscle vasodilation = hypothermia

53
Q

Describe the pharmacokinetics of ethanol

A

● Absorption: rapidly absorbed from the GIT (water soluble)
● Distribution: Rapid, Vd is total body water
● Metabolism: mostly in the liver by alcohol dehydrogenase via zero order kinetics
● Excretion: Lungs, urine.

54
Q

What does zero order kinetics mean?

A

Elimination occurs at a constant rate, independent of the drug concentration

55
Q

What drugs have zero order kinetic metabolism?

A

Phenytoin, theophylline, warfarin, salicylate, heparin.

56
Q

What is the MOA of benzodiazepines?

A

Binds to components of the GABA- A receptor in neuronal membranes in the CNS.
This receptor is a chloride ion channel.
Benzodiazepines enhance GABAs effects without directly activating the channel.
This causes an increased frequency of channel opening.

57
Q

What are the organ level effects of diazepam?

A

● Sedation - calming effect, anxiolysis at low doses. Can also cause psychomotor
and cognitive depression, amnesia
● Hypnosis and anaesthesia at higher doses.
● Anticonvulsant effects
● Muscle relaxation
● Respiratory and cardiovascular depression - especially at high doses or in those
with CCF/chronic heart disease or in hypovolemic states

58
Q

What are the uses of diazepam in the ED?

A

● Anticonvulsant
● Sedation of an agitated patient
● Withdrawal states - alcohol, benzodiazepines
● Various toxidromes to prevent seizures

59
Q

Antiepileptics: Carbamazepine
What is the mechanism of action of carbamazepine?

A

● Sodium channel blockade
● Binds to those in an inactive state and stabilises them there
● Inhibits high frequency repetitive firing neurons - so no interference with baseline
or normal activity

60
Q

What are the pharmacokinetics of carbamazepine?

A

● 100% oral bioavailability
Peak levels 6-8 hours
● 70% protein bound
● Low clearance - 36 hour half life initially which decreases over time
● Induces its own metabolism via P450 enzyme effect so dose increase required in
the first few weeks of treatment

61
Q

What are the adverse effects of carbamazepine?

A

● Ataxia, diplopia
● Sedation at high doses
● Blood dyscrasias - aplastic anaemia, agranulocytosis
● Skin rash
● Drug interactions with other P450 metabolised drugs i.e. phenytoin

62
Q

Describe the pharmacokinetics of phenytoin

A

● Given oral or IV, High oral bioavailability, not well absorbed IM
● Peak serum concentration at 3-12 hours
● Highly plasma protein bound with moderate volume of distribution
● Metabolised in the liver to inactive metabolites and then renal excretion
● Elimination is dose dependent - lower concentrations is first order kinetics, but
enzymes become saturated at high concentrations and metabolism shifts to zero
order kinetics
● As a result, the half life is variable

63
Q

What is the MOA of phenytoin?

A

● Sodium channel blockade
● Prolongation of the inactive state of the Na channel
● Als o enhances GABA release
● These actions work to inhibit the generation of rapidly repetitive action potentials

64
Q

What is the rationale for using a loading dose of phenytoin?

A

● Need 4 half lives to reach steady state, which would take 5-6 days
● So to reach target concentration more rapidly, we use a loading dose.

65
Q

What are the risks associated with IV phenytoin administration?

A

● Hypotension and bradycardia with rapid infusion - can cause cardiovascular
collapse
● Local necrosis if there is extravasation
● Purple glove syndrome - black discoloration distal to the IV site

66
Q

What are the adverse effects of phenytoin use?

A

● Nystagmus and loss of smooth pursuits is normal with therapeutic levels and not
concerning
● Anyone with diplopia and ataxia needs a decrease in their dose
● Gingival hyperplasia and hirsutism can occur over long term use, as can
abnormal rashes, osteomalacia and low vitamin D
● Can cause foetal abnormalities if used in pregnant people
● Sedation, coma, cerebellar toxicity are associated with toxic levels.

67
Q

What is the mechanism of action of levetiracetam?

A

● Binds the the SV2A synaptic vessel protein
● Undergoes endocytosis and binds in the vesicle
● Prevents release of glutamate during increased frequency activity

68
Q

What are the pharmacokinetics of keppra?

A

● Given orally or IV, rapid oral absorption in just over an hour
● Low protein binding
● Half life 6-8 hours so BD dosing
● ⅔ excreted unchanged in the urine
● ⅓ is deaminated in the blood
● NO liver metabolism = minimal interactions when compared to other
antiepileptics

69
Q

What are the side effects of keppra

A

● Mild: somnolence, ataxia, dizziness
● Worse: behavioural and mood changes - aggression/anxiety

70
Q

What is the dose for status epilepticus of keppra

A

● Paeds - 40mg/kg IV/IO up to 3g
● Adults 60mg/kg IV/IO up to 4.5g

71
Q

Na Valproate
What is the mechanism of action of valproate

A

Unknown, could be action on GABA channels, Na channels or NMDA receptors
Works on a number of different epilepsy models and the clinical effect doesn’t seem to
be associated with serum drug levels.

72
Q

What are the adverse effects?

A

● Mild: Can cause nausea, vomiting, abdominal pain
● Severe: cerebral oedema and coma
● Hepatic toxicity including acute liver failure (more common in patients under 2 yrs
old)
● Thrombocytopaenia and bruising from bone marrow depression
● Neural tube defects if used during pregnancy
● Hyperammonaemia leading to sedation
● Lots of drug interactions - inhibits metabolism of several drug via inhibition of the
P450 enzyme system. Directly displaces phenytoin from plasma proteins,
increases levels of carbamazepine and decreases the clearance of lamotrigine.

73
Q

Antidepressants:SSRIs and serotonin syndrome
Describe the mechanism by which serotonin syndrome occurs

A

● Excessive stimulation of serotonin receptors in the CNS due to overdose of a
single drug or concurrent use of several drugs.
● Predictable rather than idiosyncratic.

74
Q

How do drugs cause excessive stimulation of serotonin receptors?

A

● Inhibition of serotonin metabolism - i.e. amphetamines, moclobemide
● Prevention of serotonin reuptake in nerve terminals - fluoxetine, sertraline,
venlafaxine, tramadol, TCAs
● Serotonin release or increased intake of serotonin precursors - tryptophan,
lithium

75
Q

What is the MOA of tricyclic antidepressants?

A

● Inhibition of serotonin and noradrenaline reuptake
● This increases the amount of serotonin and noradrenaline in certain parts of the
brain and spinal cord.
● Based on the monoamine hypothesis for depression, this leads to improved
mood and can alleviate neuropathic pain
● TCAs also block sodium channels, potassium channels, muscarinic (M1)
receptors, Histaminic (H1) receptors and postsynaptic alpha 1 adrenergic
receptors

76
Q

What are the pharmacokinetics of tricyclics?

A

● Well absorbed orally
● Bioavailability 40-50%
● Long half life
● High first pass metabolism
● High protein binding
● High lipid solubility
● Large volume of distribution
● Metabolised in the liver with active metabolites

77
Q

What clinical manifestations would be seen in an overdose of tricyclic
antidepressants?

A

Can be divided into important systems - cardiac, CNS, and then other anticholinergic
symptoms

Cardiac
● Tachycardia
● Hypotension (from alpha 1 blockade)
● ECG changes - prolonged PR, wide QRS (Na block) long QT (K block) VT, VF

CNS
● Drowsiness
● Delirium (from anticholinergic effects)
● Seizures
● Coma

Other Anticholinergic Effects
● Agitation
● Mydriasis
● Warm, dry, flushed skin
● Urinary retention
● Ileus

78
Q

How does the volume of distribution of TCAs influence their toxicity?

A

TCAs have a large Vd and tissue concentrations are high, especially in well perfused
organs such as the brain and the heart

79
Q

What therapies for TCA toxicity might reduce their tissue distribution?

A

Alkalinisation - bicarb or hyperventilation
Increases plasma protein binding of the free drug, removing it from the tissues and
reducing its toxicity

80
Q

Describe the pharmacokinetics of lithium

A

● Oral administration, rapid and near complete absorption. Peak concentrations at
1-2 hours but complete by 6-8 hours.
● Volume of distribution is in total body water - very slow distribution from extra to
intracellular compartments
● No protein binding
● No metabolism
● Excreted unchanged in the urine - 20% of the creatinine clearance
● Plasma half life is 20 hours

81
Q

What factors may influence lithium excretion?

A

● Renal function - slowing down of the GFR = more time in the PCT for
reabsorption
● Water and sodium status - lithium can be reabsorbed in place of sodium in
water/sodium depleted states
● Drug interactions that reduce or enhance clearance
● Serum concentration to begin with

82
Q

What are some drug interactions with lithium?

A

● Thiazide diuretics - cause a reduction in lithium clearance
● Newer NSAIDs also reduce clearance
● Osmotic or loop diuretics actually increase clearance

83
Q

What are the toxic effects of lithium?

A

● Neuro: tremor, ataxia, dysarthria, confusion
● Thyroid: reversible hypothyroidism
● Renal: polyuria, polydipsia via nephrogenic diabetes insipidus
● CVS: oedema
● Pregnancy: category D, causes Ebstein’s anomaly (a congenital cardiac
malformation)

84
Q

How do you assess and treat lithium toxicity?

A

● Measure lithium levels (10-12 hours after the last dose)
● Treatment is supportive, dialysis

85
Q

By what route can olanzapine be administered?

A

Oral (tablet or wafer), parenteral with short acting IM or long acting depot injection

86
Q

What is the predominant mechanism of action of atypical antipsychotic
medication?

A

● Serotonin receptor antagonism
● There is also a weaker effect on dopamine receptor antagonism (D2)

87
Q

What are the adverse effects of atypical antipsychotics?

A

● Sedation
● Extrapyramidal reactions - less common that with the typical antipsychotics
● Tardive dyskinesia, akathisia
● Antimuscarinic effects - dry mouth, urinary retentions
● Orthostatic hypotension
● Weight gain
● Hyperglycaemia
● Hyperprolactinaemia
● Agranulocytosis (seen with clozapine)
● Neuroleptic malignant syndrome

88
Q

Why is levodopa used in combination with carbidopa?

A

● Carbidopa is a peripheral dopa decarboxylase inhibitor
● Because it doesn’t penetrate the BBB, it reduces the peripheral metabolism of
levodopa which leads to increased half life and more dopa being available to
enter the CNS to exert its effects

89
Q

What are the adverse effects of levodopa?

A

● GIT: anorexia, nausea, vomiting is common due to stimulation of the emetic
centre in the brainstem
● CVS: arrhythmias due to increased peripheral formation of catecholamines
● Dyskinesias: can occur in 80% of people receiving this treatment long term
● Behavioural change: depression, anxiety, agitation, insomnia, nightmares
● Other miscellaneous: gout, abnormalities to taste and smell, abnormal LFTs

90
Q

How does sumatriptan work in the treatment of migraine?

A

● Migraine thought to arise secondary to vasodilation of cerebral meningeal blood
vessels
● Triptans are selective agonists for 5HT-1 receptors found on these vessels
● Cause vasoconstriction, preventing symptoms

91
Q

What are the pharmacokinetics of triptans?

A

● Bioavailability is low or varied (10-70%)
● So given subcut or intranasal more often than orally
● Half life is 2-3 hours so frequent daily dosing

92
Q

What are the pros and cons of sumatriptan use?

A

● Pros: only usually mild side effects (tingling, weakness) usually very effective
● Cons: contraindicated in patients with IHD due to coronary spasm risk, short
duration of effect so requires multiple dosing. Very expensive.

ACEM viva (25 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions