Brainscape's Knowledge GenomeTM

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


See full index

Karan - MBBS Year 1: Gastrointestinal Week 1 > Clinical Pharmacology of Hyoscine hydrobromide, D2, H1, 5HT3 and NK1 Antagonists > Flashcards

Clinical Pharmacology of Hyoscine hydrobromide, D2, H1, 5HT3 and NK1 Antagonists Flashcards

1
Q

(a) What is reflux?

(b) When do acid reflux symptoms become known as GERD?

(c) What can lead to acid reflux?

A
  • Flow of fluid through vessel in opposite direction to normal
  • When symptoms occur more than twice a week
  • Failure of LES to close - acid from stomach moves up into oesophagus
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What lifestyle modifications can be introduced to improve symptoms leading to emesis?

A
  • Reduction in caffeine, alcohol, smoking and obesity - relax oesophageal sphincter
  • Avoid late evening meals
  • Allow time for stomach emptying before lying supine
  • Pharmacological treatment usually initiated with antacids and alginates
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What are the rules behind prescribing anti-emetics?

A
  • Only prescribe anti-emetics when the cause of vomiting is known
  • When prescribing the choice of drug is dependent on the aetiology of the vomiting
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What are the clinical indications of use for anti-emetics treating nausea due to vertigo and motion sickness?

A
  • VERTIGO - H1 receptor inverse agonist: cyclizine (no sedation) or promethazine (if sedation required)
  • NAUSEA - Antimuscarinic: hyoscine hydrobromide, H1 receptor inverse agonist: cyclizine (no sedation) or promethazine (if sedation required)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

How would you treat nausea due to pregnancy?

A
  • Usually mild in the first trimester. However, on rare occasions if vomiting is severe short-term treatment with:
  • H1 receptor inverse agonist promethazine or a D2 antagonist prochlorperazine or metoclopramide
  • If symptoms do not settle in 24 to 48 hours then specialist opinion should be sought.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

How would you treat nausea due to post-operative procedures?

A
  • Depends on type and duration of surgery, risk factors
  • 5HT3 antagonists, dexamethasone, prochlorperazine, cyclizine
  • High risk: use a combination of 2 with different MOAs
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

How would you treat nausea due to migraines?

A
  • D2 antagonist prochlorperazine or metoclopramide
  • Metoclopramide should not be used regularly due to extrapyramidal symptoms
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

How would you treat nausea due to cancer therapy? PART 1

A
  • For those at low risk pre-treatment with dexamethasone or lorazepam
  • For those at high risk pre- treatment with dexamethasone, aprepitant and 5HT3 receptor antagonist
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

How would you treat nausea due to cancer therapy? PART 2

A
  • Low risk– moderate emetogenic: D2 receptor antagonist: Domperidone, Haloperidol, Metoclopramide,
  • Moderate risk- severe emetogenic:
  • Before therapy: NK1 antagonist Aprepitant usually administered with 5HT3 receptor antagonist Ondansetron, and Dexamethasone (91% efficacy)
  • Metoclopramide, Dexamethasone and lorazepam (63% efficacy)

Preventing emetic episodes in first 24hrs after cisplatin administration

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

How do muscarinic receptors lead to vomiting?

A
  • Stimulation of muscarinic receptors in GI tract increases secretion and motility
  • Activation ofM1receptors in the vestibular nuclei, the nucleus of the solitary tract and the vomitingcenter triggers nausea and vomiting reflex
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

How do muscarinic receptor antagonists work?

A
  • Hyoscine blocks M1 receptors in the vestibular nuclei, the nucleus ofthe solitary tract and the vomiting center
  • Useful for motion sickness and to dry secretions before surgery
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What are the major side effects of hyoscine?

A
  • Dry mouth
  • Constipation
  • Blurred vision
  • Difficulty passing urine
  • Tachycardia
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What are the two forms hyoscine comes in?

A
  • Hyoscine butylbromide cannot cross the BBB - prescribed to reduce spasms of the GI tract used to treat IBS
  • Hyoscine hydrobromide can cross BBB - reduce nausea and vomiting
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

How is hyoscine administered?

A

Oral or transdermal patch

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

Give examples of D2 receptor antagonists and their clinical indications of use.

A
  • Domperidone, metoclopramide and prochlorperazaine
  • Used for nausea and vomiting, dysmotility dyspepsia and gastro-oesophageal reflux
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What are the effects of D2 antagonists and why are they considered prokinetic?

A
  • Increase GI motilitythroughout the entire GI tract, therefore considered to beprokinetic
  • Enhanced gastric emptying
  • Reduction in the volume of acid available to reflux
  • Increased lower oesophageal sphincter basal tone
16
Q

What is the general mechanism of action of D2 receptor antagonists?

A

Inhibition of dopamine binding at dopamine D2 receptors (Gi GPCR)

17
Q

What are the major side effects of D2 receptor antagonists?

A
  • Parkinsonism, tardive dyskinesia(sometimes irreversible) and dystonia in 25% of patients given high doses and 5% of patients given long-term therapy
  • Avoid long-term use (esp. in the elderly)
  • Drowsiness, or nervousness, agitation and anxiety in 10-20% of patients
  • Increased pituitary prolactin release(impotence, galactorrhea, menstrual disorders)
18
Q

Describe pharmacokinetics of D2 receptor antagonists.

A
  • Metoclopramidecrosses the BBB, and therefore also has CNS actions; domperidonedoes not cross as easily so less CNS effects
  • Metoclopramide: used recreationallydue to increased absorption when co-administered with pill/powder based orally administeredrecreational drugs
19
Q

Describe when 5HT3 antagonists are used.

A
  • Primary agents for prevention and treatment of chemotherapy-induced nausea and vomiting
  • Most effective in preventing acute phase (<24 hours after chemotherapy) if given 30 minutes prior to antineoplastic drugs
  • Not particularly effective during delayed phase (2-5 days after chemotherapy) also used for postop and post-radiation nausea and vomiting
20
Q

Outline the mechanism of action of 5HT3 antagonists and where they act.

A
  • Selective blockade of peripheral5HT3receptors on intestinal vagal afferents
  • CNS actions at both the CTZ and vomiting center
21
Q

Outline the side effects of 5HT3 antagonists.

A
  • Transient mild headache
  • Dizziness
  • Constipation
  • Prolongation of QT interval - especially dolasetron e.g avoid in patients with cardiac pathology
22
Q

Describe the pharmacokinetics of 5HT3 antagonists. PART 1

A
  • Can be administered as a single dose prior to chemotherapy (either oral or IV)
  • Slow IV administration
  • Longer duration of action so great for chemotherapy induced emesis
23
Q

Describe the pharmacokinetics of 5HT3 antagonists. PART 2

A
  • Extensively metabolised by the liver to an active metabolite
  • Dose adjustments required in hepatic insufficiency
  • Urinary excretion via the kidney
24
Q

Describe the clinical indications of use for H1 receptor inverse agonists e.g cyclizine.

A
  • Main use in motion sickness to control the symptomsof nauseas and vomiting
  • Also used for vestibular disturbances: Labrinythitis and meniéres disease
25
Q

Describe the context behind the mechanism of action of H1 receptor inverse agonists.

A
  • Anti-histamine - inverse agonists NOT ANTAGONISTS
  • H1 receptor has 2 states
    active and inactive
  • The inverse agonist binds preferentially to the inactive form to reduce receptor activity
26
Q

Describe the major side effects of H1 receptor inverse agonists

A
  • Drowsiness due to prominent CNS depressive effects
  • Avoid activities such as driving and hazardous work until patient has seen how much they are affected
  • Prolong the QT interval mechanism
  • Anticholinergic effects e.g dry mouth, urinary retention, dry eyes and pupil dilation
27
Q

Describe pharmacokinetics of H1 receptor inverse agonists.

A
  • Well absorbed from GI tract - Reach peak plasma concentration in 2-3 hours
  • Distributed throughout peripheral tissues and CNS
  • Metabolised by liver - induce CYP450 enzymes so may affect metabolism of other drugs
  • Dose adjustment required in severe liver disease
  • Safe to use in children and pregnancy
28
Q

Describe when NK1 antagonists e.g aprepitant are used.

A
  • Used in adults and children
  • Prevent nausea and vomiting caused by cancer chemotherapy with moderate or high emetogenic outcomes
  • In adults only: pre-med for surgery
29
Q

Describe the general mechanism of action of NK1 antagonists.

A
  • Preventative only - will not treat nausea or vomitingthat you already have.
  • Antagonist of the NK1 receptor
  • Substance P cannot bind
30
Q

Describe side effects and pharmacokinetics of NK1 antagonists.

A
  • Side effects are fatigue and constipation
  • Administered orally with addition dexamethasone and a ‘setron’
  • Metabolised by CYP3A4 enzymes
  • Dose adjustments required in hepatic insufficiency
  • Induces CYP3A4 - can shorten warfarin half life
31
Q

Describe when dexamethasone can be used.

A
  • Initially used in children for tonsillectomy and adults for labyrinth disorders
  • It was found that the nausea and vomiting rates dropped markedly with use
32
Q

Describe how dexamethasone is used.

A
  • Now used as a mainstay post operatively
  • 24-48 hours only short use
  • Be cautious in those with diabetes as it can induce increased glucose in the blood

Karan - MBBS Year 1: Gastrointestinal Week 1 (6 decks)

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