Drugs MT II Flashcards
Autonomic nervous system
Parasympathetic nervous system
Receptor and subtype
- ACh R is a Na channel -> if activated ⇒ Na influx ⇒ Depolarisation
- Muscarinic ACh R is a G-protein-coupled R -> if ACh is bound ⇒ G-protein cascade is activated.
- There are 5 subtypes, but mainly focus on M1, M2, M3
Autonomic nervous system
Parasympathetic nervous system
M1 and M3
M1,M3
- Stomach and glands,
- bronchial SM,
- eye ciliary muscle (cause miosis)
Indirectly cause vasodilation via NO
Autonomic nervous system
Parasympathetic nervous system
M2
○ M2
■ Heart
Autonomic nervous system
Parasympathetic nervous system
○ Symptoms: “Sludge”
○ Symptoms: “Sludge”
Salivation
Lacrimation
Urination
Digestion
GI irritation
Emesis
Others: bradycardia, bronchoconstriction, miosis
Autonomic nervous system
Parasympathetic nervous system
parasympathomimetics
= cholinergic drugs
● Drugs that act on the parasympathetic NS
Parasympathomimetics = cholinergic drugs
● Drugs that act on the parasympathetic NS
● Pharmacological effects acts on:
○ Eye:
○ Cardiovascular system:
○ GI-tract:
○ Respiratory tract:
○ Urinary tract:
Parasympathomimetics = cholinergic drugs
● Drugs that act on the parasympathetic NS
● Pharmacological effects EYE
- Constrict iris sphincter muscle ⇒ Constricting pupil will ↓ intraocular pressure (useful in glaucoma)
- Keratoconjunctivitis sicca (KCS) -> dry eye disease (autoimmune disease)
- Parasympathomimetics ⇒ ↑ lacrimal secretion (symptomatic treatment)
- Causative treatment -> immunosuppressants (e.g. cyclosporine, pimecrolimus)
Parasympathomimetics = cholinergic drugs
● Drugs that act on the parasympathetic NS
● Pharmacological effects - Cardiovascular system
- Negative chronotropic effects (bradycardia)
- ∅ inotropic effect (∅ contractibility effect)
- Vasodilation via NO (indirect)
Parasympathomimetics = cholinergic drugs
● Drugs that act on the parasympathetic NS
● Pharmacological effects: GI-tract:
- SM constriction
- Glandular hyperfunction (↑ secretion)
- Vomiting, diarrhoea
Parasympathomimetics = cholinergic drugs
● Drugs that act on the parasympathetic NS
● Pharmacological effects: GI-tract: Respiratory tract:
- Bronchoconstriction (must be careful in patients with asthma)
- ↑ bronchial secretion
Parasympathomimetics = cholinergic drugs
● Drugs that act on the parasympathetic NS
● Pharmacological effects: Urinary tract:
- Bladder contraction
- Sphincter relaxation
● Direct parasympathomimetics
○ Bind to ACh Rs
- Acetylcholine (ACh)
- Carbachol
- Pilocarpine
- Bethanechol
- Methacholine
● Direct parasympathomimetics
Acetylcholine (ACh)
● Direct parasympathomimetics
- Non-specific (N and M-ACh Rs)
- Non-selective
- Cannot be used therapeutically because of very short half-life
● Direct parasympathomimetics
CARBACHOL
● Direct parasympathomimetics
Old and obsolete
Non-specific to M-ACh Rs
Local administration only
Indications:
● Used to treat glaucoma (eye drops, obsolete drug)
● In uterus to treat metritis (intrauterine tablet)
● Direct parasympathomimetics
PILOCARPINE
● Direct parasympathomimetics
Natural alkaloid
Side effects are mild after administration
Indications:
● Glaucoma (miosis can be seen within 15 min)
● Keratoconjunctivitis sicca (KCS)
● Direct parasympathomimetics
BETHANECHOL
● Direct parasympathomimetics
Human
M-ACh R specific (less side effects)
Starts up bowel movement after surgery
Induce urination
● Direct parasympathomimetics
METHACHOLINE
● Direct parasympathomimetics
Human
M-ACh specific
Application is rare (theoretically it’s useful for atrial fibrillation, but practically it is not)
Indications:
● Ergot toxicosis, which leads to serious vasoconstriction ⇒ brain damage
Indirect parasympathomimetics
○ ACh esterase enzyme inhibition
⇒ ↓ ACh degradation ⇒ ↑ [ACh]
○ Contains a carboxylic acid group which binds to esteratic site and inactivates it for 1-6 hrs (i.e. ACh cannot bind and be down by ACh esterase enzyme)
○ Organophosphates
○ Physostigmine
○ Neostigmine
○ Pyridostigmine
○ Edrophonium
Indirect parasympathomimetics
ORGANOPHOSPHATES
Irreversible binding! ⇒ excess ACh TOXICOSIS
First sign
⇒ parasympathomimetic effect (salivation, emesis, diarrhoea etc)
Severe ⇒ tremors, convulsions, seizures
⇒ ↑ body temperature ⇒ death
Effects:
● Salivation
● Diarrhoea
● emesis
● Convulsions
● Tremors
Antidote:
-
Atropine
- Tropane alkaloid
- ↑ dose => ↑ symptoms (can cross BBB => hallucinations, coma)
- Dose: 0.01-0.02mg/kg IM/IV (narrow TI)
-
Pralidoxime
- AChE activator
- Works only shortly after organophosphate administration. If given later, it’ll have no effect (timing = important!)
Indirect parasympathomimetics
PHYSOSTIGMINE
- Tertiary N -> can cross BBB => small TI
- Lipophilic
- Topically -> eye drops, however, tolerance can occur!
- Can be used in case of atropine poisoning
Indirect parasympathomimetics
NEOSTIGMINE
- Quaternary N -> ∅ cross BBB
- ∅ Po (absorption = very bad)
- IV, IM
- Eye drop -> treatment of glaucoma (tolerance can occur!)
Indications:
- Myasthenia gravis (an autoimmune disease that destroys ACh Rs)
Effects:
- Suspends action of nondepolarizing muscle relaxants because they’re competitive antagonists of this R
- Restores function of SKM
- ↑ intestinal motility
- Induces emesis
Indirect parasympathomimetics
PYRIDOSTIGMINE
Quaternary N (∅ crossing BBB)
Po (F= 3-8%)
Indications:
- Myasthenia gravis
↑ intestinal motility
Indirect parasympathomimetics
EDROPHONIUM
- Competitive inhibition in neuromuscular junction -> action is suspended by diffusion
- Short DOA -> 5-15 min
- Used in diagnosis of myasthenia gravis (Tensilon test)
Parasympatholytics = anticholinergic drugs
- Muscarinic R antagonist
- Atropine
Parasympatholytics = anticholinergic drugs
- Tropane alkaloid
- Dose: 0.01-0.02mg/kg
