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Flashcards in Pharmacology Deck (65)
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1
Q

What is an opioid?

A

Endogenous or synthetic substance that produces morphine life effects

2
Q

What are the main groups of synthetic analogues of opiods?

A
  1. Piperidines
  2. Methadone-like drugs
  3. Benzomorphans
  4. Thebaine derivatives
3
Q

Which receptors are responsible for most of the analgesic effects of opioids?

A

mu

4
Q

All types of opioid receptors are what type of receptors?

A

Gi/Go proteins

5
Q

Describe the effects of morphine

A
  1. Analgesia
  2. Euphoria and sedation
  3. Respiratory depression and suppression of cough
  4. Nausea/vomiting
  5. Pupillary construction
  6. Reduced GI motility
  7. Histamine release causing bronchoconstriction
  8. Hypotension
6
Q

Which opioid cause physical dependance?

A

u-receptor agonists

7
Q

What may relieve withdrawal symptoms?

A

Long acting u-receptor agonists such as methadone and buprenorphine

8
Q

Which opioids are less likely to cause dependance?

A

codeine, pentazocine, buprenorphine and tramdol

9
Q

Define pain

A

Unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage

10
Q

What are the main pain receptors?

A

Polymodal nociceptors

11
Q

Name some chemical stimuli of pain receptors

A

Bradykinin, protons, ATP and vanilloids

12
Q

Describe the fibres of pain pathways

A

Mostly non-myelinated C fibres whose endings respond to thermal, mechanical and chemical stimuli

13
Q

Through where do nociceptive neutrons run and where are their cell bodies?

A

Peripheral sensory nerves

Their cell bodies lie in the dorsal root ganglia or peripheral nerves just inside the spine

14
Q

Describe the myelination of nociceptive neurones

A

Lightly or non-myelinated

15
Q

Where do C fibres and some Aδ fibres terminate?

A

Laminae I and II (aka the substantia gelatinosa)

16
Q

What does the substantial gelatinosa contain a lot of?

A

Endogenous opioid receptors

17
Q

What neurotransmitters do the nociceptive afferent neurons release when they synapse in the dorsal horn?

A

Glutamate, substance P and ATP

18
Q

Where do pain signals travel up the spinal cord?

A

Contralateral white matter called the spinothalamic tract

19
Q

Describe some processes involved in modulation of pain transmission

A

Periaqueductal grey, endogenous opioid peptides

20
Q

Name the 3 types of endogenous opioid peptides

A
  1. Enkephalins
  2. Endorphins
  3. Dynorphins
21
Q

What is the gate control theory of pain?

A

Non-painful input closes the ‘gates’ to painful input, which prevents pain sensation from travelling to the CNS. Therefore, stimulation by non-noxious input is able to suppress pain

22
Q

Name the different types of opioid receptors

A

Delta, mu, kappa receptors

23
Q

What are the 2 types of cholinergic receptors?

A

Nicotinic nAChR and muscarinic mAChR subtypes

24
Q

Describe the nAChr and where it is found

A

Directly coupled to caption channels and mediate fast excitatory synaptic transmission at the neuromuscular junction, autonomic ganglia and various sites in the CNS

25
Q

Describe the mAChR and where they are found

A
  1. mAChRs are typical GPCRs with 5 molecular subtypes (M1-M5)
  2. M1,3&5 couple with Gq to activate the inositol pathway
  3. M2/4 act through Gi to inhibit adenylate cyclase and reduce cAMP
  4. mAChRs mediate acetylcholine effects at postganglioic parasympathetic synapses
26
Q

Where are the different muscarinic receptors found?

A

M1 - neural
M2 - cardiac
M3 - glandular/smooth muscle
M4/5 - mostly CNS

27
Q

Choline is acetylated to form ACh by which enzyme?

A

Choline acetyl transferase

28
Q

What is the source of acetyl groups?

A

Acetyl-coenzyme A

29
Q

How is Ach released from the vesicles into the synaptic space when an AP arrives at the pre-synaptic neuron?

A

Ca2+ mediated exocytosis

30
Q

What type of receptors are found at the neuromuscular junction?

A

Nicotinic

31
Q

How does a presynaptic action potential produce only 1 postsynaptic action potential?

A

ACh is hydrolysed within about 1ms by acetylcholinesterase

32
Q

Name some muscarinic agonists and their uses

A
  1. Acetylcholine carbachol
  2. Methacholine
  3. Muscarine and pilocarpine
  4. Mainly used for glaucoma
33
Q

Name some muscarinic antagonists and their uses

A
  1. Atropine
  2. Hyoscine
  3. Ipratropium and pirenzepine
  4. Sinus bradycardia
  5. Prevention of motion sickness
  6. Asthma or COPD
34
Q

Name some nicotinic agonists and their uses

A
  1. Nicotine
  2. Carbachol
  3. No real therapeutic use except for aiding stopping cigarette smoking
  4. NB succinylcholine is an agonist although behaves like an antagonist
35
Q

Name some nicotinic antagonists and their uses

A
  1. Hexamethonium
  2. Tubocurarine
  3. Treat hypertension
  4. Relax skeletal muscles during surgery
36
Q

Name a non-depolarising neuromuscular-blocking agent

A
  1. Tubocurarine
  2. Pancuronium
  3. Atracurium
37
Q

Name a depolarising neuromuscular blocking agent

A

Suxamethonium

38
Q

What are 2 main forms of cholinesterase?

A
  1. Acetylcholinesterase AChE

2. Butyrylcholinesterase BuChE

39
Q

Give 2 examples of cholinesterase inhibitors

A
  1. Neostigmine

2. Physosyigmine

40
Q

Describe the symptoms you would get in a cholinergic crisis

A

Diarrhoea, urination, muscle weakness, bradycardia, bronchorrhoea, emesis, lacrimation, salivating/sweating

41
Q

Describe the symptoms you would get in an anticholinergic crisis

A

High body temperature, mydriasis, dry mouth, dry eyes, decreased sweat, flushed, delirium

42
Q

How does a presynaptic action potential produce only one postsynaptic action potential?

A

ACh is hydrolysed within about 1ms by acetylcholinesterase

43
Q

Define pharmacokinetics

A

What the body does to the drug

44
Q

How do rugs cross lipid membranes?

A
  1. Passive diffusional transfer

2. Carrier mediated transfer

45
Q

What does ADME stand for?

A

Absorption, Distribution, Metabolism, Excretion

46
Q

What determines the rate of passive diffusional transfer of a drug across membranes?

A

Lipid solubility

47
Q

What kind of drugs does albumin bind?

A

Mainly acidic drugs

48
Q

Describe some factors absorption of a drug from the gut depends on

A

Gastrointestinal motility, gastrointestinal pH, particle size, physiochemical interaction with gut contents

49
Q

Define bioavailability

A

Fraction of an ingested dose of a drug that gains access to the systemic circulation

50
Q

Why might bioavailability be low?

A

Absorption is incomplete, or because the drug is metabolised in the gut wall over liver before reaching the systemic circulation

51
Q

In drug metabolism, what does phase 2 involve?

A

Oxidation, reduction and hydrolysis

52
Q

In drug metabolism, what does phase 2 involve?

A

Conjugation of a reactive group

53
Q

Can drugs cross the filtration barrier at the glomerulus of the kidney?

A

Yes, unless highly bound to plasma proteins

54
Q

Which drugs aren’t efficiently excreted in the urine and why?

A

Lipid soluble drugs are passively reabsorbed by diffusion

55
Q

Which drugs are actively secreted into the renal tubule and thus more rapidly excreted?

A

Weak acids and bases

56
Q

What fundamental parameter describes the elimination of a drug?

A

Total clearance

57
Q

How is rate of elimination worked out?

A

Total clearance multiples by the plasma concentration

58
Q

What are the 3 main stages of drug development?

A
  1. Drug discovery
  2. Preclinical development
  3. Clinical development
59
Q

What processes are involved in the drug discovery part of drug development?

A

Candidate molecules are chosen on the basis of their pharmacological properties

60
Q

What processes are involved in the preclinical development part of drug development?

A

Wide range of non-human studies (eg toxicity testing, pharmacokinetic analysis and formulation)

61
Q

What processes are involved in the clinical development part of drug development?

A

The selected compound is tested for efficacy, side effects and potential dangers in volunteers and patients

62
Q

What happens during lead finding?

A

High throughput screening using assays or in silico (computer prediction models) - end up with around 100 potential candidates

63
Q

What happens during lead optimization?

A

Candidates are tested on wider range of assays to determine things like selectivity and metabolic stability - identifies one or more candidates for further development

64
Q

What are the 4 main parts to pre-clinical development?

A
  1. Safety pharmacology (test the drug doesn’t cause arrhythmias, ataxia, bronchoconstriction)
  2. Toxicology (finding out lethal dose, post-mortems of animals to look at histology)
  3. Pharmacokinetic testing (ADME)
  4. Chemical development - can the drug me made on a large scale?
65
Q

What are the stages of clincal development?

A

Phase 1 - small group (20-80) healthy volunteers to check things like tolerability, dangerous effects, pharmacokinetic properties etc
Phase 2 - 100-300 patients to test for efficacy and establish dose
Phase 3 - double-blind RCT on thousands of patients to compare new drug with already available ones
Phase 4: Post-marketing surveillance to monitor long-term use