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Year 2 - Musculoskeletal (DP) > Pharmacology > Flashcards

Flashcards in Pharmacology Deck (81):
1

Where are motor neurone cell bodies located?

Grey matter:
- Inner spinal cord
- Surface of brain

2

Are motor neurones myelinated?

Yes

3

Are motor neurone branches supplying individual muscle fibres myelinated?

No

4

What does each branch of a motor neurone divide into? What is the function of this?

Terminal bouton:
- Forms a chemical synapse at NMJ
- Releases ACh

5

Where do synaptic vesicles move to in the terminal bouton to release ACh?

Active zones

6

What part of the muscle fibre receives the incoming ACh?

End-plate

7

What happens to the sarcolemma in the end-plate?

Thrown into folds:
- Nicotinic ACh receptors at junctional folds

8

Describe briefly an overview of synaptic transmission

1. Choline + AcetylCoA = ACh
2. ACh storage
3. ACh release upon Calcium influx
4. Receptor activation
5. ACh inactivation by acetylcholinesterase
6. Re-uptake of choline and acetylCoA

9

How is choline transported into the pre-synaptic nerve?

Via choline transporter:
- Symported with sodium

10

Where dose the AcetylCoA come from for ACh formation?

Mitochondria

11

Where is ACh synthesised and what enzyme catalyses it?

Cytosol
Choline acetyltransferase

12

What happens when an action potential arrives at the pre-synapse?

1. Depolarisation
2. Opening of voltage-gated calcium channels
3. Calcium influx

13

What happens after calcium influx?

ACh-containing vesicles exocytose into cleft at active zones

14

What is the structure of the nicotinic ACh receptor?

Pentamer of glycoprotein subunits:
- [(Alpha1)2, Beta1, Delta, Epsilon]

15

What is the epsilon subunit in embryonic muscle nicotinic ACh receptors?

A Gamma subunit

16

What does the nicotinic ACh receptor surround?

Central, cation sensitive pore:
- Five M2 helices

17

What is the conformation of the pore in:
1. Absence of ACh
2. The binding of one ACh
3. The binding of two ACh
4. The binding of three ACh

1. Closed
2. Closed
3. Open
4. Not possible

18

Which one of the following values is the rough true value for the permeability ratio of the nicotinic ACh pore to potassium and sodium (PK+/PNa+):
A) 0.7
B) 0.9
C) 1.1
D) 1.4
E) 2.3

C) 1.1
They have roughly the same permeability

19

What ions move in/out of the pore in the sarcolemma?

Sodium in
Potassium out

20

At resting potential, which effect is the greatest; the sodium driving force or the potassium driving force and what does this result in?

Sodium driving force since sodium in > potassium out:
- Depolarisation -> End Plate Potention (e.p.p.)

21

How do we describe the amount of ACh contained in a vesicle?

A quantum

22

What do we call the electrical response on the sarcolemma upon exposure to one quantum of ACh?

Miniature e.p.p.

23

What dose the term 'Electrotonic repsonse' mean?

Many m.e.p.p. sum to produce the e.p.p

24

What does the End Plate Potential need to be greater than to trigger an 'all-or-nothing' AP to be generated?

Threshold

25

What happens when threshold is reached?

Voltage-activated sodium channels open up along the sarcolemma resulting in contraction along the muscle

26

Why do we need sodium channels along the length of the muscle fibre?

To allow AP propagation

27

What feature of the sarcolemma does the AP enter that is in close proximity to the sarcoplasmic reticulum?

Transverse (T) Tubules

28

What does the AP trigger when it gets close to the SR?

Calcium release

29

When calcium is released from inside the SR into the cell what happens?

It interacts with troponin on myofibrils -> Contraction

30

What does acetylcholinesterase hydrolyse ACh into?

Choline and acetate

31

True or false; Acetylcholinesterase is so efficient that some ACh is hydrolysed even before it binds to receptors?

True

32

What is the alternate name for Neuromyotonia?

Isaac's Syndrome

33

What are the symptoms of neuromyotonia?

Cramps
Stiffness
Myotonia - Slow relaxation
Fasciculations

34

What is the pathogenesis of the acquired form of neuromyotonia?

1. Autoantibodies against voltage-gates K+ channels in motor neurone
2. Cell cannot be brought back to resting potential
3. Hyperexcitability

35

How is neuromyotonia treated?

Anticonvulsants:
- Carbamazepine
- Phenytoin
> Block Na+ channels
> May potentiate GABA

36

This syndrome is a rare cause of muscle weakness in the limbs that is associated with small cell lung cancer.

Lambert-Eaton Myasthenic Syndrome (LEMS)

37

What is the origin of LEMS?

Autoimmune related:
1. AutoAbs against voltage-gated calcium channels in motor neurone terminal
2. Reduced calcium entry during depolarisation
3. Reduced ACh release

38

How is LEMS treated?

Anticholinesterases:
- Pyridostigmine
Potassium channel blockers:
- 3,4-diaminipyridine
(Both increase [ACh} in cleft)

39

A patient presents with muscle weakness especially during exercise. They have also noticed that their eyelid is drooping and they have difficulty moving their eyes.

Myasthenia gravis

40

What is the pathogenesis of Myasthenia Gravis?

Autoimmune:
1. AutoAbs against nicotinic ACh receptors in endplate
2. Reduced number of functional channels
3. Reduced amplitude of e.p.p.

41

How can myasthenia gravis be treated?

Anticholinesterases:
- Edrophonium (For diagnosis)
- Pyridostigmine
Immunosuppressants:
- Azathioprine

42

What type of toxin is botulinum toxin?

Exotosin

43

How does the botulinum toxin work?

1. Enzymatically modifies vesicle docking proteins
2. Prevents ACh exocytosis
3. Irreversibly inhibits ACh release

44

True or false; Anticholinesterases are highly effective in treating botulinum toxicity?

False!

45

When can botulinum toxin be used clinically?

IM injections:
- Dystonia treatment (squint)
- Reduces wrinkling

46

How do vecuronium and atracurium work? Where are they used and why?

Action:
1. Competitive antagonists of nicotinic ACh receptors
2. Reduce e.p.p. to below threshold
Use:
- In surgery
- Induce reversible muscle paralysis

47

True or false; Paracetamol has a lot of anti-inflammatory action?

False

48

What NSAID reduces the risk of peptic ulcers and how?

Celecoxib:
- Targets cyclooxygenase-2 (COX-2 Inhibitor)
> Responsible for pain
- No COX-1 action -> Reduced peptic ulcer risk

49

If prescribing an NSAID for pain relief in arthritis what must you co-prescribe?

A PPI

50

What NSAID should be avoided in the patient has cardiovascular (IHD/CHF/PAD/CVA/Uncontrolled Hypertension) risk factors?

Diclofenac
(And high dose [>2400mg daily] Ibuprofen)

51

What two NSAIDs are 'safest' to prescribe?

Ibuprofen
Naproxen

52

What is step 1 of the WHO analgesia ladder?

Non-opioid:
- Paracetamol
- Aspirin
- NSAID
+/- Adjuvant

53

What is step 2 of the WHO analgesia ladder?

Weak opioid:
- Codeine/Dihydrocodeine/Tramadol
+/- Non-opioid
+/- Adjuvant

54

What is step 3 of the WHO analgesia ladder?

Strong opioid:
- Morphine/Diamorphine/Fentanyl/Oxycodone
+/- Non-opioid
+/- Adjuvant

55

What are the indications to prescribe a DMARD?

1. Active inflammation were benefit > risk
2. Almost all new-onset RA -> Start within 3 months
3. If steroid dose needs reduced

56

What is methotrexate?

A folate antagonist

57

What are the side effects of methotrexate?

Leukopaenia/Thrombocytopaenia
Hepatitis + cirrhosis
Pneumonitis
Rash/Mouth ulcers
Nausea/Diarrhoea
Teratogenic:
- Stop in M and F >= 3 months before pregnancy

58

What are the side effects of sulfasalazine?

Nausea
Rash/Mouth ulcers
Neutropaenia
Reversible oligozoospermia
Orange urine

59

What is a very rare side effect of hydroxychloroquine (HCQ)?

Retinopathy

60

What are the side effects of sodium aurothiomalate (gold) and penicillamine?

Bone marrow suppression
Glomerulonephritis
Rash/Mouth ulcers

61

Give some examples of anti-TNFs and their administration route

Subcutaneous:
- Etanercept
- Adalimumab
- Certolizumab
IV:
- Infliximab

62

True or false; DMARD and Anti-TNF co-prescription increases their efficacies? Explain why

True
Steroids -> Immunosuppress -> Prevent Abs against Anti-TNFs

63

What is the 1st line treatment for RA?

Methotrexate + One other DMARD + Short-term steroids

64

What do you do if the 1st line treatment for RA fails?

Try a different combination of two DMARDs (usually still including methotrexate)

65

What is the 2nd line treatment for RA? (Assuming two DMARDs gives inadequate response)

Methotrexate + Anti-TNF (usually Certolizumab in Tayside)

66

When can an Anti-TNF be prescribed?

1. If >= 2 standard DMARDs fail to control disease
2. If a patients DAS28 score is >5.1, on two occasions, three months apart. This includes:
- Counting tender joints
- Counting swollen joints
- Check CRP
- Ask patient to rate severity (0-100)

67

What is the 3rd line treatment for RA?

Methotrexate + Tocilizumab (Tayside)/Rituximab

68

How does rituximab work?

Monoclonal Ab against CD20/B cells

69

What are side effects of Anti-TNFs?

Major infection risk:
- TB reactivation -> Anti-TNF breaks down granulomas
Malignancy
Contraindications:
- Pulmonary fibrosis
- CHF

70

How does tocilizumab work?

Inhibits IL-6

71

What other biologic therapies are available and how do they work?

Abatacept:
- CTLA-4 Ig
- Blocks full T cell activation
Ustekinumab:
- Inhibits IL-12 + IL-23

72

For each of the following drugs, state what conditions they can be used to treat:
1. Anti-TNFs
2. Rituximab
3. Tocilizumab
4. Abatacept
5. Ustekinumab

1. RA, PA, AS
2. RA, CTDs
3. RA
4. RA
5. PA
(PA = Psoriatic Arthritis)
(AS = Ankylosing Spondylitis)
(CTDs = Connective Tissue Disorders)

73

What are the treatment options for acute gout?

1st - NSAIDs
2nd - Colchicine (Diarrhoea and vomiting)
3rd - Steroids

74

How can we lower urate and prevent gout?

Xanthine oxidase inhibitors:
- Allopurinol
- Febuxostat
Uricosurics

75

What are side effects of allopurinol?

(Vasculitic) Rash
Azathioprine interaction
Marrow aplasia (rare)

76

When is febuxostat used instead of allopurinol?

- If allopurinol isn't tolerated
- If a patient has renal impairment (GFR

77

What can febuxostat worsen?

IHD

78

Give some examples of uricosurics

Probenecid
Sulphinpyrazone
Azapropazone
Benzbromarone

79

What are common indications for steroids?

CTDs
PMR/GCA
Vasculitis
RA

80

Which of the following is not a metabolic effect of steroids:
- Salt and water retention
- Increased lipolysis
- Increased gluconeogenesis
- Increased hepatic glycogen deposition
- Increased protein breakdown
- Increased calcium absorption

Increased calcium absorption
(Steroids can reduce calcium absorption hence long term use being associated with oestoporosis)

81

Common side effects of steroids

Weight gain:
- Centripetal obesity
- Muscle wasting
Skin atrophy
Osteoporosis
Diabetes
Hypertension
Cataract and Glaucoma
Fluid retention
Adrenal + Immune suppression
Femoral head AVN