Pharmacology

Question 1

describe the structure of the alpha motor neurone

Answer 1

it is myelinated

cell bodies are located in the spinal cord and brainstem

Question 2

what happens to the alpha motor neurone as it nears the muscle?

Answer 2

it divides into unmyelinated branches which end in a terminal bouton (NMJ)

Question 3

synaptic vesicles containing ACh in the NMJ are located where?

Answer 3

active zones

Question 4

where are nAChR located?

Answer 4

junctional folds that face active zones

Question 5

pre-synaptic processes

Answer 5

• choline is transported into the terminal by choline transporter (symport with Na+)
• ACh is synthesised in the cytosol with acetyl coenzyme A by choline acetyltransferase
• ACh is concentrated in vesicles by vesicular ACh transporter
• AP causes depolarisation and Ca2+ enters and causes vesicles in active zones to undergo exocytosis
• ACh diffuses into the synaptic cleft and activates nAChR in endplate region

Question 6

post-synaptic processes

Answer 6

• two ACh molecules activate each nAChR (pentamers of glycoprotein subunits surrounding central cation pore with a gate that only opens when ACh binds)
• channel is equally permeable to Na+ and K+, but does not conduct anions
• when the gate is open Na+ influxes at a faster rate than K+ effluxes
• causes simultaneous opening of many nAChR

Question 7

what terminates ACh

Answer 7

hydrolysis by acetylcholinesterase (enzymes associated with the endplate membrane).

Question 8

five examples of the clinical relevance of the NMJ

Answer 8

neuromyotonia 
Lambert-Eaton Myasthenia Syndrome
Myasthenia gravis
botulinum toxin
curare-like compounds

Question 9

describe neuromyotonia

Answer 9

autoantibodies to K+ channels leading to excitability

Question 10

presentation of neuromyotonia

Answer 10

cramps
stiffness
slow relaxation
twitches

Question 11

management of neuromyotonia

Answer 11

carbamazepine and phenytoin block Na+ channels

Question 12

describe Lambert-Eaton myasthenic syndrome

Answer 12

autoantibodies to Ca2+ channels leading to reduced Ca2+ entry

Question 13

presentation of LEMS (small cell lung carcinoma association)

Answer 13

muscle weakness

Question 14

management of LEMS

Answer 14

anticholinesterases e.g. pyridostigmine

K+ channel blockers e.g. 3,4-diaminopyridine

Question 15

describe myasthenia gravis

Answer 15

progressive muscle weakness during periods of activity, eye and eyelids

autoantibodies against nAChR in endplate region reducing functional challenges and AP

Question 16

management of myasthenia gravis

Answer 16

anticholinesterases e.g. edrophonium

immunosuppressants e.g. azathioprine

Question 17

describe botulinum toxin

Answer 17

exotoxin that irreversibly inhibits ACh release. it modifies proteins involved in vesicles preventing exocytosis (used in botox)

Question 18

role of curare-like compounds (muscle relaxant)

Answer 18

competitive antagonist of ACh

Question 19

three classes of drugs involved in inflammatory arthritis management

Answer 19

• NSAIDs
• DMARDs
• biologics

Question 20

examples of NSAIDs used in inflammatory arthritis management

Answer 20

ibuprofen
naproxen
diclofenac

Question 21

describe NSAIDs

Answer 21

anti-inflammatory with analgesic properties

Question 22

indications for NSAIDs

Answer 22

inflammatory arthritis
mechanical MSK pain
pleuritic/pericardial pain

Question 23

adverse of NSAIDs

Answer 23

peptic ulceration

increased risk of cardiovascular problems

Question 24

when should DMARDs be started in inflammatory arthritis?

Answer 24

within 3 months of symptom onset
slow onset (weeks-months)

Question 25

examples of DMARDs

Answer 25

- methotrexate - leflunomide - sulfasalazine - hydroxycholorquine - others e.g. sodium aurothiomalate and penicillamine

Question 26

what is methotrexate used in?

Answer 26

RA psoriatic arthritis CT disease vasculitis

Question 27

adverse of methotrexate

Answer 27

``` leukopenia thrombocytopenia cirrhosis pneumonitis rash/mouth ulcers nausea diarrhoea teratogenic- stop 3 months before conception need FBC and LFTs monitoring ```

Question 28

what is often used in combination with methotrexate?

Answer 28

sulfasalazine

Question 29

adverse of sulfasalazine

Answer 29

``` nausea mouth ulcers low sperm count hepatitis monitoring of FBC and LFTs required ```

Question 30

what is hydroxychloroquine used in?

Answer 30

all connective tissue diseases

Question 31

describe biologics

Answer 31

they are drugs designed to target specific aspects of the immune system

Question 32

what scoring system is used to determine the need for biologics?

Answer 32

DAS28

Question 33

examples of biologics

Answer 33

anti-TNF e.g. infliximab, adalimumab, etanercept rituximab (B cells) tocilizumab (IL-6) secukinimab (IL-17)

Question 34

when is anti-TNF used?

Answer 34

RA psoriatic arthritis ankylosing spondylitis

Question 35

adverse of anti-TNF

Answer 35

risk of infection (TB) malignancy (skin) contradicted in pulmonary fibrosis and HF

Question 36

acute management of gout

Answer 36

colchicine (diarrhoea) NSAIDs steroids

Question 37

prophylaxis of gout

Answer 37

allopurinol (xanthine oxidase inhibitor reducing uric acid levels) febuxostat (used in those who cannot tolerate allopurinol) uricosurics