Drugs and the PNS Flashcards
What are the receptors mediating sympathetic nerve activity ?
Uses adrenergic receptors, which respond to neurotransmitters like norepinephrine
- α1 is linked to Gq, IP3 and DAG formation is increased, activation causes vasoconstriction, increased peripheral resistance, and pupil dilation
- α2 is linked to Gi, reduction in cAMP formation, activation leads to inhibition of norepinephrine release, reducing sympathetic outflow
β receptors are linked to Gs (and increased cAMP formation)
- β1, activation increases heart rate (chronotropy), force of contraction (inotropy), and renin release
- β2, activation causes bronchodilation, vasodilation, and muscle relaxation
- β₃, activation promotes lipolysis and relaxation of the bladder detrusor muscle
What are the receptors mediating parasympathetic nerve activity ?
Uses cholinergic receptors, which respond to acetylcholine
Muscarinic receptors - G protein linked, M1-M5
M1, M3, M5 (Gq) → ↑ IP3 & DAG
M2, M4 (Gi) → ↓ cAMP
Nicotinic receptors - located in ganglia and the neuromuscular junction, these receptors are involved in transmitting the nerve signal from pre-ganglionic to post-ganglionic neurones
What are the subtypes of adrenergic receptors ?
Alpha-1 (α1): receptors are coupled to Gq proteins, leading to an increase in intracellular calcium (Ca²⁺) and causing smooth muscle contraction
Alpha-2 (α2): These are Gi-coupled receptors that inhibit adenylate cyclase activity, decreasing cAMP levels and reducing neurotransmitter release.
Beta-1 (β1): These receptors are Gs-coupled, leading to an increase in cAMP, which enhances heart rate and contractility.
Beta-2 (β2): Also Gs-coupled, these receptors lead to smooth muscle relaxation
Beta-3 (β3): Found mainly in adipose tissue, they stimulate lipolysis via Gs-mediated increases in cAMP.
What are the subtypes of cholinergic receptors ?
Muscarinic receptors
M1: Gq-coupled, leading to increased intracellular calcium, an increase in IP3 and DAG formation, function = Cognitive function, memory
M2: Gi-coupled, decreasing cAMP and slowing heart rate
M3: Gq-coupled, mediating smooth muscle contraction and gland secretion
M4 - Gi coupled, a reduction in cAMP formation, inhibits dopamine release
M5 - Gq coupled, an increase in IP3 and DAG formation, function = Modulates dopamine pathways, vasodilation
Nicotinic receptors:
- ligand gated ion channel
- Activation causes a rapid influx of Na⁺ (depolarization) → Excitation
- ionotropic
Explain what the terms ganglion, pre-ganglionic, and post-ganglionic refer to:
Ganglion - cluster of nerve cell bodies located outside the central nervous system (CNS), where synapses between preganglionic and postganglionic neurons occur
Pre-ganglionic - neurons that originate in the CNS and transmit signals to the ganglia. They release acetylcholine (ACh) to activate nicotinic receptors on postganglionic neurons
Post-ganglionic - neurons arise from the ganglia and extend to the target organs
Identify two ganglion-stimulating drugs that are clinically useful:
Nicotine: A potent ganglionic stimulant, acting on nicotinic receptors in both sympathetic and parasympathetic ganglia. Clinically, nicotine is used in smoking cessation therapies (e.g., nicotine patches).
Varenicline: A partial agonist at nicotinic receptors, used to help individuals quit smoking by reducing cravings and withdrawal symptoms
What are agonists ?
- drugs that activate receptors, mimicking the effect of the natural neurotransmitter
- enhance or stimulate the normal physiological response
- do not discriminate between sympathetic and parasympathetic ganglia
- effects are variable and complex
Muscarinic agonists:
- parasmypathetic activation
- Pilocarpine → Treats glaucoma by constricting pupils (↑ aqueous humour drainage)
- Bethanechol → Stimulates bladder & GI motility in cases of hypomotility
Adrenergic agonists:
- sympathetic activation
- Salbutamol (β2 agonist) → Bronchodilation (used in asthma)
- Dobutamine (β1 agonist) → Increases heart contractility (used in heart failure)
Explain why antagonists of the ganglion type of nicotinic receptor do not have any current clinical uses:
Ganglion nicotinic receptor antagonists (e.g., hexamethonium) inhibit neurotransmission at both sympathetic and parasympathetic ganglia
Leads to widespread autonomic blockade
This results in severe side effects such as hypotension, constipation, urinary retention, and dry mouth
The non-selectivity and the broad impact on autonomic functions make them impractical and dangerous for clinical use in modern medicine, so they are no longer used therapeutically
Describe the effects of agonists and antagonists of muscarinic receptors:
Alpha-1 agonists cause vasoconstriction, useful for raising blood pressure.
Alpha-1 antagonists are used to treat hypertension and benign prostatic hyperplasia (BPH).
Beta-1 agonists increase heart rate and contractility, useful in heart failure.
Beta-1 antagonists are used to treat hypertension, arrhythmias, and heart failure.
Beta-2 agonists induce bronchodilation, commonly used in asthma and COPD.
Beta-2 antagonists are not commonly used clinically, but non-selective beta-blockers can have side effects (e.g., bronchoconstriction)
What are antagonists ?
- drugs that block or inhibit receptors, preventing the natural neurotransmitter from binding and exerting its effect
- reduce or oppose the normal physiological response
- Effects more clearly defined
- removal of all autonomic activity
Muscarinic antagonists:
- mimic sympathetic activation by blocking parasympathetic activity
- Atropine → Increases heart rate (used in bradycardia), dilates pupils (for eye exams)
- Ipratropium → Relaxes bronchioles
Adrenergic antagonists:
- reduce sympathetic activity
- Propranolol (β1 & β2 blocker) → Lowers blood pressure & controls anxiety
- Prazosin (α1 blocker) → Lowers blood pressure by reducing vasoconstriction
Describe some parasympathetic effects:
acetylcholine (Ach) mediates the effects of parasympathetic nerve activation at the level of the tissue
Parasympathetic responses include bronchoconstriction, constriction of circular muscles to cause pupillary constriction, ciliary muscle contraction to adapt the eye for close up vision, thin saliva, increased GI secretion and motility, decreased heart rate and force of contraction, decreased blood pressure and urination
Describe some sympathetic effects:
sympathetic nerves which cause bronchodilation, pupillary dilation, ciliary muscle relaxation to prepare the eye for distant viewing, thick saliva, decreased GI motility and secretion, increased heart rate and force, vasoconstriction in the blood vessels of most viscera and increased blood pressure
