Pharmacology: Drug emesis and GI motility Flashcards
What are the different routes of administration?
Sublingual
Oral
Rectal
What is nausea?
Nausea is a sensation of unease and discomfort in the upper stomach with
an involuntary urge to vomit. It may precede vomiting, but a person can have
nausea without vomiting.
When prolonged it is a debilitating symptom.
What causes nausea?
Motion sickness
Pregnancy
Disease (infection,migraine)
Drugs (opioids, digoxin, anti-cancer agents)
What are the high centres when vomiting occurs?
Hypothalamus
Cerebellum
Labyrinth
Area postrema
What is the Chemoreceptors trigger zine ( CTZ)?
An area of the medulla oblongata that receives inputs from blood-borne drugs or hormones, and communicates with other structures in the vomiting center (VC) to initiate vomiting.
What is emesis?
Action or process of vomiting
What are the neurotransmitters of emesis?
How?
Histamine (H1) Acetylcholine (M) Dopamine (D2) 5-hydroxytryptamine (5HT3) Neurokinin (NK1) (substance P)
Afferent nerves communicate with the CTZ which communicates with the VC and transfers signals to efferent nerves
What the antagonists for neurotransmitter that stimulate emesis?
Receptor antagonists of
acetylcholine (M) histamine (H1) dopamine (D2) serotonin (5HT3) neurokinin (NK1)
- Cholinergic muscarinic antagonistis
- Histamine antagonists
- Dopamine antagonists
- 5-hydroxytryptamjne (5-HT3) antagonists
- Neuroni in (NK 1) antagonists
What are cholinergic muscarinic antagonists?
Drugs and patches that Hyoscine hydrobromide To prevent NOT TREAT motion sickness
What are histamine antagonists?
Therapeutic use?
Drugs containing:
Cinnarizine
(+ calcium channel block)
Cyclizine
(+ muscarinic antagonism)
Promethazine - least side effects + used for sedation as well
(+ muscarinic antagonism)
Therapeutic use: motion sickness, stomach irritants
pregnancy (if severe, promethazine)
What are dopamine antagonists?
Selective antagonists:
Drugs containing Metoclopramide - central action in CTZ, peripheral increase motility - blockade of other CNS dopamine receptors results in fatigue, prolactin↑
Non selective antagonists
Drugs containing Phenothiazines (I.e. prochloroperazine)
Therapeutic activity: Antagonise dopamine (D2) receptor in CTZ
Additional mechanisms – antagonist for acetylcholine/histamine
Adverse effects - sedation, hypotension, tardive dyskinesia
What are the anatagonists for 5-Hydroxytryptamine (5-HT3)?
Drugs containing Ondansetron
Therapeutic activity:
Peripheral : Blocks effect of 5HT on visceral afferent fibres
CNS : Blocks effect of 5HT onto Chemoreceptor Trigger Zone
Therapeutic use:
vomiting post-operative and due to radiotherapy,
vomiting due to cytotoxic drugs including cisplatin (high emetic potential). Effective in all forms of emesis (acute, delayed, anticipatory)
Adverse effects
constipation, headache, flushing
Alternatives : granisetron, palonosetron
What are Neurokinin (NK1) Antagonists?
When are they used
Drug containing Aprepitant:
Effective in both acute and delayed emesis
Used in Vomiting more likely :-
50 years old↓, female, anxious, suffer from motion sickness,
repeated exposure to cytotoxic therapy.
Times of vomiting:
acute (<24h), delayed (>24h), anticipatory (lorazepam)
What are the 2 types of vomiting stimulus?
Vestibular: histamine & acetylcholine released
Visceral: dopamine f serotonin released
What are the three types of cytotoxic drugs (cancer drugs)?
Mildly Emetogenic : to apt rest use dopamine antagonists
Moderately emetogenic: to treat use dexamethasone or lorazepam
Highly emetogenicm (I.e. cisplatin )to treat use 5HT3 antagonists and neuroni in antagonists
