F5. Pharmacology, neurotransmission

Question 1

What drugs block the Na+ channels, blocking AP generation?

Answer 1

Lidocaine (local anaesthetic)
Lamotrigine (antiepileptic)
-prevents excitation of both pre- and postsynaptic cells

Question 2

Describe Lidocaine

Answer 2

Blocks the pore of the Na+ channel after opening, preventing passage of ions

Question 3

Describe how inhibition of synthetic enzymes depletes transmitter?

Answer 3

-Methyl-DOPA is a false substrate for DOPA decarboxylase, competing for enzyme catalytic site
-build up of inert product and depletion of transmitter
-Methyl-dopamine cannot be converted to noradrenaline
-L-DOPA can be used as a therapy in Parkinson’s disease
ONE NOTE

Question 4

Describe how inhibition of vesicle transporter prevents loading

Answer 4

Reserpine blocks NA uptake (and other monoamines)
-vesicles fail to load
ONE NOTE

Question 5

What drugs interfere with vesicle release

Answer 5

-Calcium triggers vesicle fusion and transmitter release
-Conotoxin blocks calcium channels
-Botulinum toxin (Botox) degrades vesicle release machinery
ONE NOTE

Question 6

What are the mechanisms of antagonism of ionotropic receptors

Answer 6

occupy NT binding site, prevent channel opening, or block the open pore
ONE NOTE

Question 7

what are metabotropic receptors

Answer 7

membrane G protein coupled receptors on the target cell

Question 8

Describe antagonism of metabotropic receptors

Answer 8

-Antagonists of metabotropic receptors prevent target cells from responding to released NT
-Occupy binding site or inhibit G protein activation
-Receptor antagonists are common drugs

Question 9

Describe how drugs can interfere with NT clearance

Answer 9

-Inhibition of transporters or degradation enzymes prolongs activation of postsynaptic cell
-Amitriptyline inhibits NA uptake (reuptake)
-Neostigmine blocks acetylcholinesterase

Question 10

Describe autonomic pharmacology

Answer 10

-Drugs sometimes aimed at correcting defects in the ANS itself
-Primary or secondary autonomic dysfunction
-Diabetic neuropathy
-More commonly: exploiting the ANS to correct for other problems:
Hypertension
Asthma
Incontinence
Etc. etc.

Question 11

Common antagonists?

Answer 11

Tropicamide (mAChR blocker)
Atenolol (bR blocker)
Tamsulosin (aR blocker)

Question 12

Common agonists

Answer 12

Salbutamol (bR agonist)
Pilocarpine (mAChR agonist)
Nicotine (nAChR agonist)

Question 13

Describe antagonists for B-adrenoreceptors (b-blockers)

Answer 13

-Atenolol, propranolol, acebutolol
-Indications:
Hypertension, angina, arrythmias
-Contra-indications:
Asthma, bradycardia, severe peripheral arterial disease, etc. (selectivity and not exclusivity)
-Side effects:
Bronchospasm, GI disturbances, hypotension, bradycardia, visual disturbances, headache, dizziness, etc. etc

Question 14

B-blocker effects (general)?

Answer 14

-Counteracts sympathetic input
-Reduce cardiac output
-Risk of pulmonary side effects ONE NOTE

Question 15

What are antimuscarinics? provide examples

Answer 15

Antagonists for muscarinic acetylcholine receptors
e.g Hyoscine, atropine, oxybutynin

Question 16

Describe indications, contraindication and side effects of antimuscarinics

Answer 16

-Indications:
Premedicants to dry bronchial and salivary secretions,
bradycardia, GI disorders, urinary incontinence, ophthalmology
-Contra-indications:
Glaucoma, myasthenia gravis, urinary retention
-Side effects:
Dry mouth, blurred vision, constipation, tachycardia, palpitation, arrythmias

Question 17

Describe antimuscarinic effects (general)

Answer 17

-Counteracts parasympathetic input
-Inhibits glandular secretion
-Blocks smooth muscle contraction
ONE NOTE

Question 18

What are clinical signs of defects in the autonomic control?

Answer 18

-Pupil dilation:
Mydriasis (pupil dilation)
Miosis (pupil constriction)
Light reflex
-Heart beat rate:
Bradycardia (decreased rate)
Tachycardia (increased rate)
-Sweating/salivary outflow:
Profuse sweating
Dry mouth

Question 19

Why is drug action on the ANS so tricky?

Answer 19

-dozens of b blockers that act on similar targets
-high chance of side effects as high chance of hitting on target (at wrong place) or hitting wrong target