Pharmacology and Therapeutics Flashcards

(37 cards)

1
Q

Explain the difference between pre and post ganglions

A

Preganglionic - The cell bodies are in the CNS

They are myelinated

The fibres release Ach –> which act on nicotinic receptors

Postganglionic - Cell body is in the autonomic ganglion

These are unmyelinated

The synapse is close to the target organ…..except for the adrenal medulla… which has no postganglionic fibre!!

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2
Q

Explain how ipratropium works

A

This is a muscarinic antagonist of both M2 and M3 receptors

This prevents the stimulations of M2 and M3, and in turn prevents the negative feedback loop that can occur when Ach builds up due to not binding to the M3 receptor

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3
Q

What is Wernicke-Korsakoff’s syndrome caused by?

A

Thiamine deficiency, normally caused by alcohol abuse

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4
Q

What will blocking H3 receptors do?

And what drug is used to exploit this?

A

This will increase the release of histamine

Ciproxifan is an inverse agonist, which will increase the histamine production, and increase wakefullness

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5
Q

Explain how Antibiotic-Associated Diarrhoea (AID) can occur

A

Broad spectrum antibiotics can disrupt the natural gut flora

Toxins produced from C.difficile can also cause an inflammatory response –> leading to diarrhoea

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6
Q

What are the 3 divisions of the autonomic nervous system (ANS)?

A

Sympathetic

Parasympathetic

Enteric

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7
Q

How do you treat hepatic encephalopathy?

A

Reduce toxin production, and improve toxin excretion

Lactulose is good for reducing the nitrogen load in the gut (by binding to ammonia)

Antibiotics can be used to decrease ammonia forming bacteria

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8
Q

What is the mucus barrier used for in the stomach?

A

It is an alkaline barrier that protects the stomach lining from acid and pepsin

The mucus is secreted by surface mucous epithelial cells

This is all done under hormonal control

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9
Q

Where is histamine most commonly found?

A

Tissue mast granule cells

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10
Q

What are the key things to avoid when treating liver disease?

A

Drugs which cause…

Sedation –> as may worsen encephalopathy

GI Ulceration –> Due to possibility of bleeding as potentially a loss of clotting factors

Constipation –> As we need to get rid of toxins

Have a narrow therpeutic index

Are hepato/nephrotoxic

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11
Q

What makes up the enteric branch of the ANS?

And what neurotransmitters are used in it?

A

Myenteric and Submucosal plexuses

Acetylcholine (Ach)

Noradrenaline (NA)

Non-Adrenergic Non-Cholinergic (NANC)

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12
Q

What are the 4 different types of laxatives?

And how do they work?

A

Bulk Forming - These increase the size and fluid of the stools

Stool Softening - Reduce the surface tension, and increase the fluid content of the stools

Osmotic - Increases the volume and retention of intraluminal fluid

Stimulant - Increases peristalsis and water/electrolyte secretion by the mucosa

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13
Q

Muscarininc poisioning causes what kind of response?

A

Excessive parasympathetic responses

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14
Q

What is diarrhoea?

A

The abnormal passage of loose/liquid stools more than 3x daily….. or volume that is greater than 200g per day

Acute - Less than 14 days

Persistant - Longer than 14 days

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15
Q

Describe the 4 mechanisms of diarrhoea

A

Osmotic - Fluid and secondary ions are drawn into the lumen

Secretory - When fluid and electrolyte balance is unregulated

  • This type will persist despite fasting

Inflammatory - Defective absorption of fluid and electrolytes

  • Caused by the destruction of the mucosa….and associated with blood loss (dysentery)

Abnormal Motility - There is an increased motility, and so full absorption cannot take place

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16
Q

Define Constipation

And what is primary/secondary constipation?

A

When the frequency of bowel movements are less than three times a week

Primary - Chronic constipation without a known cause

Secondary - Constipation that is caused by a drug, or medical condition (not natural)

17
Q

Whats the main difference between M1/3/5 and M2/4 receptors?

A

M1/3/5 - Gq coupled

These increase IP3 and Ca2+ concentration

M2/4 - Gi coupled

Decrease cAMP and Ca2+ concentration, whilst increasing [K+]

18
Q

What role do Enterochromaffin Cells (ECL) play in the secretion of gastric acid?

A

They secrete histamine when stimulated by G cells

This histamine then binds to H2 receptors on parietral cells….. which secretes H+

19
Q

Histamine will bind to H receptors… but what type of receptors are these??

20
Q

How does the rotavirus/norovirus cause diarrhoea?

A

They decrease the Na+ absorption, and so more water moves into the lumen via osmosis

21
Q

Explain the peripheral stimuli of vomiting

A

The ingestion of poisions and toxins will cause ECL cells to release 5HT (serotonin) onto vagal afferent sensory neurone

This stimulates 5HT receptors, which have a neuro-endocrine function…..which stimulates higher order centres such as the chemoreceptor trigger zone (area postrema)

22
Q

What drugs are muscarininc antagonists (parasympatholytics)?

A

Atropine

Hyoscine

Darifenacin

Ipratropium

Tiotropium

23
Q

Explain the central stimuli of vomiting

A

The vomiting (emetic) centre is located in the medulla oblongata…. this receives input from…..

Cerebral cortex

Chemoreceptor trigger zone (outside of the BBB)

Vestibular system

24
Q

What activation does what in terms of vomiting?

A

Somatic motor nerves - Cause muscular contraction, and close the glottis/pharynx

Parasympathetic - Retroperistalsis, opeining of pyloric and oesophageal sphincters

Sympathetic - Sweating, palpations and a racing heart

25
How do H3 receptors work?
They reduce the release of histamine, and so drug that inhibit these will increase histamine release...and so also alertness These receptors have a high basal activity....so inverse agonists are the best drugs to use
26
What are the two main pathways of **H+ secretion** And what is the role of **somatastatin**?
G cells secrete gastrin, stimulating ECL cells to release histamine --\> which acts on parietal cells Enteric neurones detect when more H+ is needed....and so stimulate Acetylcholine release from the neurones, which binds to parietal cells **Somatastatin** inhibits acid secretion, by negatively feedbacking to the G cells, ECL cells and parietal cells when acid levels are high in the stomach
27
What are the **3 stages** of liver disease?
Hepatitis Fibrosis Cirrhosis
28
Explain how **M3 selective antagonists** work And how is the most common?
They antagonise the M3 receptor.... but the negatvie feedback loop is maintained inside of the nerve So Ach is still produced....but its effect is suppressed **Tiotropium**
29
Why do many treatments for diarrhoea like dioralyte have **high glucose contents**?
This is because the idea is to **absorb Na+** from the lumen, but this requires glucose for the **coupled transporter**
30
What is the difference between **muscarinic** and **nicotinic** receptors?
**Muscarinic** - Ligand gates ion channels **Nicotinic** - GPCRs
31
What is the combined antibiotic **treatment** used for **H.pylori**?
Amoxicillin Metronidazole Clarithromycin
32
What are the **ALARMS** symptoms for GERD?
**A**naemia **L**oss of weight **A**norexia **R**ecent onset of progressive symptoms **M**elana / Haematemesis **S**wallowing difficulties
33
How is **Pirenzipine** useful in the treatment of peptic ulcers?
Pirenzipine is a **M1 antagonist**, which prevents the binding of Ach from activating the G cell This then prevents gastrin from being produced.... but the other pathway is still possible So this isn't perfect
34
How is **H+ secreted** from Parential cells?
Carbonic acid is formed from carbonic anhydrase The bicarbonate is antiported out of the cell, bringing Cl- in Proton pump pushes H+ into the cell, with K+ coming back K+ levels are maintained in the stomach by a symport with Cl-
35
What is the **Triple Response**, when talking about histamine?
**Flush** - Local vasodialation that is caused by binding to H1 receptors --\> which releases Nitric Oxide (causing the vasodialation) **Wheal** - Endothelial cells contract, causing an increase in vascular permeability **Flare** - Histamine binds to H1 receptors, activating sensory nerves NKA also acts as a positive feedback loop --\> increasing the amount of histamine that is present
36
What are **Parasympathomimetic** and **Parasympatholytic** drugs?
- mimetic = Muscarinic agonist - lytic = Muscarinic antagonist Inhibitors of parasympathomimetic drugs have an indirect effect of muscarinic receptors
37
Where are H4 receptors found?
White blood cells So the presence of histamine will increase the inflammatory response