Pharmacology of Agents acting on the peripheral nervous system
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What does sympathomimetic mean?
mimic the effect of NA
What does sympatholytic mean?
block the effect of NA
what does parasympathomimetic mean?
mimic the effect of ACh
what does parasymptholytic mean?
block the effect of ACh
what does Ganglionic Blockade mean?
block nicotinic ACh receptors
What are the 5 types of enzymes that work on NE
- Tyrosine hydoxylase (TH)
- (AAAD) aromatic L-amino acid decarboxylase
- Dopamine beta hydroxylase (DBH)
- Coatechol O methyl transferase (COMT)
- Monoamine oxidase (MAO)
what are the ways that drugs can enhance or mimick noradrenergic transmission?
- 1. facilitate release
- 2. inhibit metabolism
- 3. block reuptake
- 4. Receptor agonists
What kind of feedback mechanism does NE/NA do?
negative feedback through alpha 2 receptors
three types of adrenergic agonists
direct acting and indirect acting and mixed acting
2 types of direct acting agonists
4 types of indirect acting agonists
- releasing agents
- uptake inhibitor
- MOA inhibitors
- COMT inhibitors
How do indirect acting drugs work?
drug enhances release of norepinephrine from vesicles
how do mixed acting drugs work?
drug acts both directly and indirectly
How do direct acting drugs work
drug directly activates receptor
therapeutic applications of sympathomimetics
- Cardiovascular (hyportension local anesthesia nypertension)
- Anaphylactic Shock (intramuscular injection of adrenaline,antihistamines and glucocorticoids as secondary medication to stabilize the patient)
- pulmonary (asthma)
- Opthalmology (phenylephrine)
- Nasal congestion (phenylephrine for vasoconstrictor)
- OB/CYN applications (terbutaline for relaxing pregnant uterus, Drug abuse)
what is the treatment for asthma
Beta adrenergic agonists
Adversive effects of indirect sympatholytics
- orthostatic hypotension
- nasal congestion
- increased GI activity
what does Guanethidine do?
inhibits vesicular release
what does reserpine do?
treatment of hypertension
Disulfiram does what?
prevents conversion of DA to NA used to treat alcoholism
Therapeutic application of Beta Blockers
- hypertension,ischemic heart,cardiac arrythmias
Adverse effects of beta blockers
- heart failure in patients with cardiac disease
- increased airway resistance (asthma)
- fatiue and depression
- rebound hypertension
- augmented hypoglycemia
3 Therapeutic applications of alpha adrenergic antagonists
- 1.pheochromocytoma = tumor of the adrenal medulla, releasing adrenaline and noradrenaline (phentolamine, phenoxybenzamine)
- 2. Chronic Hypertension = prazosin and related compounds
- 3. Benign Prostatic Hyperplasia = effective in reducting smooth muscle tone of prostate and urinary bladder for improving urinary flow (prazosin and phenoxybenzamine)
4 adversive effects of alpha adrenergic antagonists
- 1. orthostatic hypotension
- 2. Tachycardia
- 3. Nasal Congestion
- 4.Sodium and water retention
3 drugs that enhance the cholinergic transmission
- nicotinic agonists
- muscarinic agonists
- cholinesterase inhibitors
what do choleric stimulants do?
increase acetylcholine concentration and lifetime by inhibiting degradation and act by binding AChE active site (reversible or long lasting)
what is physostigmine?
a reversible cholinesterase inhibitor and indirectly stimulates both nicotinic and muscarinic acetylcholine receptors
what is an irreversible AChE inhibitor called?
types of direct acting parasympthomimetics
Clinical applications of direct acting parasympathomimetics
ophthalmic (glaucoma) and reflux disease
types of indirect parasympathomimetics
- physostigmine (Glaucoma)
- edrophonium (Myathenia gravis)
- tacrine (Alzheimers)
- echothiopate (glaucoma)
- sarin (chemical warfare)
- parathion (pesticide)
What is myasthenia gravis?
autoimmune process that causes production of antibodies that decreases the # of functional nicotinic receptors on the posjunctional end plates
- maintenance of vital signs
- atropine parenterally
- rescue of AChE activity with hydroxyl amines
4 classes of parasympatholytics
- receptor antagonists
- inhibitors of release
- inhibitors of vesicle storage
- inhibitors of choline transport
effects of muscarinic antagonists
- decreased salivary bronchialand sweat secretion
- CNS effects of mascarinic inhibition (restlessness, delirium excitation, hallucination)
- GI and Bladder atony
- Mydriasis and Cycloplegia
Uses of Atropine
- to treat heart block, Bradycardia
- To treat cholinesterase inhibitors
- Anti-diarrheal agent
- to product mydriasis in refraction error testing
what is scopolamine?
competitive muscuranic receptor antagonist
what receptors does scopolamine work on?
M1> M2 and M3
what does scopolamine do?
reduces nausea and prevents sea sickness through a transdermal patch
what are the 2 types of nicotinic receptor blockers?
neuromuscular blockers and ganglionic blocking drugs
What are 2 types of neuromuscular blockers
nondepolarizing and depolarizing
what do non depolarizing Nm blockers do?
block Nm receptors to prevent depolarization of muscle membrane and muscle contraction
what is the antidote to non-depolarizing antagonists?
neostigmine is used to reverse the effects of non-depolarizing agents
what do depolarizing muscular nicotinic blockers (Succinylcholine) do?
- stimulates the Nicotinic receptor similar to ACh but does not go away(metabolized) thus it continuously occupies the receptors causing a persistent depolarization = flaccid paralysis of muscle
- it is used in very short procedures
side effects of succinylcholine
succinylcholine is metabolized rapidly by plasma pseudocholinesterase and some people do not have this enzyme so they can accumulate toxic doses of this drug.
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