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Pre-reg exam > N&V > Flashcards

N&V Flashcards

1
Q

Anti-emetics

D2-receptor antagonist (metoclopramide)

Common indications

A
  1. Prophylaxis and treatment of N&V in a wide range of conditions, but particularly in the context of reduced gut motility
  2. NB- Domperidone does not cross BBB so can be used in PD patients
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2
Q

Anti-emetics

D2-receptor antagonist (metoclopramide)

MOA

A
  • N&V are triggered by a variety of factors, including gut irritation, drugs, motion and vestibular disorders, as well as high stimuli (sights, smell emtions)
  • The various pathways converge on the vomiting centre int he medulla, the solitary tract nucleus (which is innervated by the vagus nerve), the vestibular system and higher neurological centres
  • Dopamine, acting via D2 receptors, is relevant in 2 respects
  • First, the D2 receptor is the main recpeotr in the CTZ, which is the area responsible for sensing emetogenic substances in the blood (e.g. drugs)
  • Second, DA is an important neurotransmitter in the gut, where it promotes relaxation of the stomach and lower oesophageal sphincter and inhibits gastroduodenal co-ordination
  • Drugs that block D2 therefore have a prokinetic effect- promote gastric emptying- which contributes to anti-emetic
  • They are effective in N&V due to CTZ stimulation (e.g. due to drugs) and reduced gut motility (e.g. opioids)
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3
Q

D2-receptor antagonist (metoclopramide)

Important adverse effects

A
  • Diarrhoea is probably the most common side effect of blocking D2
  • Extra-pyramidal side effects (movement abnormalities) via the same mechanism as antipsychotics
  • In the context of short-term treatment for nausea and vomiting, this is likely to take the form of an acute dystonic reaction (oculogyric crisis)
  • Domperidone tends not to cause EPSE because it does not cross BBB (NB- CTZ is largely outside the BBB)
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4
Q

D2-receptor antagonist (metoclopramide)

Warnings

A
  • EPSE are more common in children and young adults so it should be avoided in these groups
  • As both have pro-kinetic effects, they are contraindicated in GI obstruction and perforation
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5
Q

D2-receptor antagonist (metoclopramide)

Interactions

A
  • Increased risk of EPSE when taken with antipsychotics
  • It should not be combined with dopaminergic agents for parkinsons disease, as it will antagonise their effects
  • Domperidone is not subject to these interactions
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6
Q

Histamine H1-receptor antagonist

Common indications

A
  • Prophylaxis and treatment of N&V, particularly in the context of motion sickness or vertigo
    *
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7
Q

Histamine H1-receptor antagonist

MOA

A
  • N&V are triggered by a variety of factors, including gut irritation, drugs, motion and vestibular disorders as well as higher stimuli (sight, smell, emotions)
  • The various pathways converge on the vomiting centre of the medulla, which receives impulses from the CTZ, the solitary tract nucleus (which is innervated by the vagus nerve), the vestibular system and higher neurological centres
  • Histamine (H1) and ACh (Muscarinic) receptors predominate in the vomiting centre and in its communication with the vestibular system
  • Drugs such as cyclizine block both of the receptors
  • This makes them useful treatments for N&V in a wide range of conditions (e.g. drug induced, post-operative, radiotherapy), but most particularly with motion and vertigo
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8
Q

Histamine H1-receptor antagonist

Adverse effects

A
  • The most common adverse effect is drowsiness
  • Cyclizine is the least sedating drug in this class and is therefore usually preferred
  • Due to their anticholinergic effects they may cause dry throat and mouth
  • This is usually undesirable, but in patients with copious mucosal secretions it may be beneficial
  • After IV injection they may cause transient tachycardia, which the patient may notic as palpitations
  • Along with their central anticholic effects
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9
Q

Histamine H1-receptor antagonist

Warnings

A
  • Hepatic encephalopathy
  • They should also be avoided in patients susceptible to anticholinergic side effects such as those with prostatic hypertrophy (who may develop urinary retention)
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10
Q

Histamine H1-receptor antagonist

Interactions

A
  • Sedation may be greater when combined with other sedative drugs (e.g. BZ, opioids)
  • Anti-cholinergic effects may be more pronounced in patients taking ipratropium or tiotropium
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11
Q

Histamine H1-receptor antagonist

Cyclizine, cinnarizine, promethazine

Prescription

A
  • Cyclizine 50mg 8H PRNV
  • It may be given PO, IV, IM with no dose adjustment
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12
Q

Phenothiazines

Prochlorperazine, Chlorpromazine

MOA

A
  1. Prophylaxis of N&V in a wide range of conditions particularly when due to vertigo. Howeverm due to their side effect profile, others are usually preffered
  2. Psychotic disorders such as schizophrenia, where they are used as a first-generation (typical) antipsychotic
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13
Q

Phenothiazines

Prochlorperazine, Chlorpromazine

MOA

A
  • N&V are triggered by a variety of factors including gut irritation, drugs, motion and vestibular disorders, as well as higher stimuli (Sight, smell, emotion)
  • The various pathways converge on a vomiting centre in the medulla, which receives input from the CTZ, STN, vestibular centre and higher neurological centres
  • The antiemetic properties of phenothiazines arise from blockade of various receptors, including dopamine D2 receptors in the CTZ and gut and to a lesser extent H1 and M1 in vomiting and vestibular system
  • This makes them effective for nausea and vomiting in a wide range of situations, including chemotherapy, radiotherapy and vertigo
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14
Q

Phenothiazines

Adverse effects

A
  • Drowsiness and postural hypotension are common with phenothiazines
  • EPSE- arise from D2-antagonism
  • In the short term they will likely manifest as acute dystonic reaction such as oculogyric crisis
  • Longer-term treatment (which is more likely when they are used as an antipsychotic
  • Other EPSEs: Tardative dyskinaesia may occur
  • QT prolongation
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15
Q

Phenothiazine

Warnings

A
  • Due to the sedative effect and potential hepatotoxicity, these drugs should be avoided in patients with severe liver disease
  • They should also be avoided in patients susceptible to anticholinergic side effects such as prostatic hypertrophy (who may develop urinary retention)
  • Doses should be reduced in the elderly
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16
Q

Phenothiazines

Interactions

A
  • Drugs that prolong QT interval (Anti-psychotics, amiodarone, cipro, macrolides, qunine, SSRI)
  • Drugs that cause EPSE (Metoclopramide)
17
Q

Phenothiazine

Prescription, Comms and monitoring

A
  • For N&V 20mg PO or 12.5mg IM to settle attack then 10mg 12H maintenance
  • Schizophrenia- 12.5mg BD for 7 days then titrate to maintenance 75-100mg daily
  • Explain you may need multiple anti-sickness medication
  • Discuss drowsiness, dizziness on standing and movement abnormalities
18
Q

Serotonin 5-HT3 receptor antagonist

Common indication

A
  • Prophylaxis and treatment of N&V, particularly in the context of general anaesthesia and chemotherapy
19
Q

5HT3 antagonist

MOA

A
  • Nausea and vomiting are triggered by a variety of factors, including gut irritation, drugs, motion and vestibular disorders, as well as higher stimuli (sights, smells, emotions).
  • The various pathways converge on a ‘vomiting centre’ in the medulla, which receives inputs from the CTZ + STN (which is innervated by the vagus nerve), the vestibular system and higher neurological centres.
  • There is a high density of 5HT3-R in CTZ, which are responsible for sensing emetogenic substances in the blood (e.g. drugs)
  • Serotonin is a key transmitter released in the gut in response to emetogenic stimuli
  • Acting on 5-HT3-R, it stimulates the vagus nerve, which activates the STN
  • 5HT3 antagonists are effective against N&V due to CTZ stimulation (e.g. drugs) and visceral stimuli (GI infection, radiotherapy) but not motion sickness
20
Q

5HT3 antagonist

Adverse effects

A
  • Constipation
  • Diarrhoea
  • Headaches
21
Q

5HT3 antagonist

Warnings

A
  • There is a small risk that 5-HT3 antagonism may prolong QT interval, although this is usually evident only at high doses (>16mg). BUT should still be avoided in patients with prolonged QT
22
Q

Ondansetron

Interactions

A
  • Drugs that prolong QT interval
23
Q

1st gen antipsychotics (Typical)

Haloperidol, chlorpromazine, prochlorperazine

common indications

A
  1. Urgent treatment of severe psychomotor agitation that is causing dangerous or violent behaviour, or to calm patients to permit assessment
  2. Schizophrenia- particularly metabolic side effects of 2nd gen are likely to be problematic
  3. Bipolar disorders- particularly in acute episodes of mania or hypomania
  4. N&V- particularly palliative setting
24
Q

Typical antipsychotics

MOA

A
  • Block post-synpatic D2 receptors
  • There are 3 main dopaminergic pathways in the central nervous system
  • The Mesolimbic mesocortical pathway (midbrain, frontal cortex and limbic system). D2 blockage in this part results in antipsychotic effect
  • Nigrostriatal pathway (substantia nigra, corpus striatum and basal ganglia). Results in EPSEs
  • Tuberohypophyseal path (hypothalamus, pituitary_
  • CTZ have D2 receptors and there blockage results in anti-emetic effect
  • All antipsychotics are sedative which can be useful for agitation
25
Q

Typical side effects

Adverse effects

A
  • EPSE- movement abnormalities that arise from D2 blockade in nigrostriatal path- are the main drawback of 1st gen anti-psychotics
  • Acute dystonic reactions are involuntary parkinsonian movements (occur in early treatment)
  • Akathisia- inner restlessness (occur in early treatment)
  • Neuroleptic malignant syndrome- rare but life threatening side effect characterised by rigidity, confusion, autonomic dysregulation and pyrexia (occur in early treatment)
  • Tardative dyskinesia- pointless, involuntary movements (lip smacking) and may not resolve on stopping treatment (late in treatment)
  • Other effects: Drowsy, QT prolongation, ED, gynaecomastia, galactorrhoea
26
Q

Typical side effects

Warnings + interactions

A
  • Elderly patients are particulalry sensitive to antipsychotics so start lower
  • Antipsychotics should be avoided in dementia, as they increase the risk of death and stroke
  • Should be avoided in parkinsons due to EPSEs
  • Interactions: drugs that increase QT
27
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28
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Pre-reg exam (113 decks)

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