Pharmacology of the Peripheral Nervous System Flashcards
drugs that affect the ANS are used in what
- anesthesia and emergency medicine
- treatment of allergic reactions, cardiovascular disease, gastrointestinal/urologic disorders, asthma, psychiatric disorders, and glaucoma
adverse rxns to PNS drugs are due to
expression through interactions with receptors in the ANS
drugs that directly affect somatic responses at skeletal muscles are used when?
- during surgical procedures and in the ICU to limit movement
- in treatment of myasthenia gravis
see slides 2&3
see slides 2&3
where do neurohumoral transmissions occur
btwn nerve cells (across synapses) and btwn nerve cells and effectors cells (across neuroeffector junctions)
what are the 2 major neurotransmitters in the PNS
- Acetylcholine (ACh)
2. Norepinephrine (NE)
what are the steps in neurotransmission
- synthesis of neurotransmitter
- sotrage of neurotransmitter
- release of neurotransmitter
- receptor binding (recognition) of neurotransmitter
- inactivation of neurotransmitter
see slide 6
see slide 6
what type of neurotransmitter is acetylcholine
a cholinergic
where is acetylcholine stored
in synaptic vesicles via a proton antiporter
see slides 8-12
see slides 8-12
what are the adrenergic receptors
alpha1, alpha2 (3 subtupes each)
beta1, beta2, beta3
what are the cholinergic receptors
nicotinic receptors: Nn, Nm (sodium channels compromised of 5 subints)
muscarinic receptors: M1,M2,M3,M4,M5
where are alpha 1 receptors located
- vascular smooth m.
- pupillary radial m.
- genitourinary smooth m.
- sphincters
- pilomotor smooth m.
- sweat glands
what are the physiological responses of Alpha 1 receptors
Contraction (vasoconstriction; TPR) Contraction (dilates pupil) Contraction Contraction Contraction (erects hair) Secretion
where are alpha 2 receptors located
Some vascular smooth muscle Presynaptic (NE, some ACh nerves) Platelets Pancreas CNS
what are the physiological responses of Alpha 2 receptor
Contraction (vasoconstriction) Inhibits NT release Aggregation Inhibits insulin release Multiple sites ( sympathetic outflow)
see slides 14-21
see slides 14-21
what are the catecholamines
- epinephrine
- norepinephrine
- dopamine
what are the uses of Epinephrine
Anaphylaxis, Vasoconstrictor added to local anesthetics, topical hemostatic, cardiac rescue
what are the uses of norepinephrine
blood pressure support
what are the uses of dopamine
severe CHF; cardiogenic/septic shock
see slide 23
see slide 23
what are the types of Adrenergic Agonists
- direct
- indirect (amphetamine, tyramine)
- mixed (ephedrine)
the clinical effects of alpha receptor agonists are due to what
activation of alpha-adrenergic receptors in vascular smooth m.
what are the clinical effects of alpha receptor agonists
- peripheral vascular resistance is increased
- blood pressure is maintained or elevated
- useful in some patients with hypotension or shock - also are used topically as nasal decongestants
what are the direct acting Alpha-1 Selective agonists
- Phenylephrine
- methoxamine
- several “azoline” derivaties
what are mixed acting Alpha-1 Selective agonists
Metaraminol
what is the therapeutic use of alpha-2 selective agonists
- used for the treatment of hypertension (topically in opthalmology)
- capacity to lower BP results from activation of alpha2- receptors in the CV control centers of the CNS which suppress the outflow of sympathetic nervous system activity form the brain
what are the adverse effects of alpha-2 selective agonists
dry mouth and sedation
name 3 alpha-2 selective agonists
- Clonidine
- Guanfacine, Guanabenz
- Methyldopa (prodrug)
what is the therapeutic use of Beta Receptor Agonists
- treatment of bronchoconstriction in pts with asthma or chronic obstructive pulmonary disease
- occasionally used for cardiac stimulation
name 2 nonselective Beta Agonists
- isoproterenol
2. Epinephrine (also activates alpha receptors)
what causes the adverse effects of Beta adrenergic agonists
- stimulation of cardiac Beta-1 receptors
- drugs with preferential affinity for Beta-2 receptors compared with Beta-1 receptors have been developed
what are the selective Beta-2 agonists
Metaproterenol Terbutaline Albuterol, Pributerol, Fenoterol Bitolterol (prodrug) Salmeterol (long acting) Formoterol (long acting)
what are the adverse effects of Beta Agonists
Tachycardia, skeletal muscle tremor, restlessness, apprehension and anxiety, increased plasma glucose, decreased plasma K+
see slide 32
see slide 32
name a noncompetitive, nonselective alpha blocker
Phenoxybenzamine
name 2 competitive, nonselective alpha blocker
Phentolamine; Tolazoline
name 5 competitive selective alpha1 blockers
Prazosin, Terazosin, Doxazosin, Alfusozin, Tamsulosin (α1A)
what are the adverse effects of alpha blockers
- Decrease in peripheral resistance; mean blood pressure
- Increase in heart rate and cardiac output (mediated by baroreceptor reflex; less with alpha1 selective blocking agents)
- Improve urine flow in prostatic hypertrophy
what are the adverse effects if alpha blocker (continued)
Postural hypotension Tachycardia Nasal stuffiness Weight gain Psychomotor slowing in some individuals Inhibition of, or retrograde, ejaculation Epinephrine “reversal”.
what are the clinical uses of alpha blockers
Hypertension
Benign prostatic hypertrophy; urinary flow obstruction
Local vasoconstrictor excess (eg, vasoconstrictor + local anesthetic)
Pheochromacytoma (temporary symptomatic control)
how do Beta blockers differ
- in their relative affinity for beta receptors subtypes and pharmacokinetics
- some beta blockers are weak partial agonists of the beta receptors (intrinsic sympathomimetic activity)
- some retain a degree of local anesthetic-like (so-call membrane stabilizing) effect
see slide 39
see slide 39
what are the side effects of beta blockers
- decreased HR
- lower BP
- enhance cardiac efficiency (improve the balance btwn cardiac oxygen supply and demand)
- antiarrhythmic effects
- lower intraocular pressure
- bronchoconstriction
- metabolic effects
- exacerbate symptoms of PVD
- CNS effects (fatigue, sleep, disturbances, depression)
what are the antiarrhythmic effects of beta blockers
- depress SA node
- decrease ectopic pacemaker activity
- slow atrial and AV node refractory pd
what are the metabolic effects of beta blockers
- inhibit lipolysis
- delay recovery from, and mask symptoms of hypoglycaemia
what are the clinical uses of beta blockers
Hypertension
Supraventricular and ventricular arrhythmias
Angina pectoris
Hypertropic obstructive cardiomyopathy
Post-myocardial infarction (early phase treatment and prophylaxis)
Certain patients with congestive heart failure
Signs and symptoms of hyperthyroidism
Prophylaxis of migraine
Treatment of glaucoma
Social phobia; performance anxiety
Alcohol withdrawal; patients with akathisia
see lecture h/o
see lecture h/o
see slide 44
see slide 44
how is ACh synthesized
choline + acetyl CoA –> Acetylcholine + CoA-SH
where is ACh stored
in storage vesicles
release of ACh is blocked by what
botulinum toxin; stimulated by spider venom
what are the natural alkaloids
- Muscarine
- Pilocarpine
- Nicotinic
what is Muscarine isolated from
from the mushroom Amanita muscaria
where does muscarine act
almost exclusively at muscarinic receptors
where is Pilocarpine isolated from
chief alkaloid obtaiined from the leaflets of S/A shrubs
what is the MOA of Pilocarpine
acts on muscarinic agonist
what is the therapeutic use of Pilocarpine
- is a MIOTIC agent in the treatment of glaucoma and in the treatment of xerostomia
- sweat and salivary glands are extremely sensitive to the drug
what type of receptors are nicotinic receptors
ligand-gated ion channels
activation of nicotinic receptors cause what
- a rapid increase in cellular permeability to Na+ and Ca++
- depolarization and excitation
what are the 2 agents of Nictonic
- nicotine
- lobeline
what are synthetic congeners
chemically related to ACh
- undergo slower rate of hydrolysis
- clinical uses limited to muscarinic effects of bladder and GI-tract
what effects do acetylcholinesterase inhibitors cause
-accumulation of Ach at all cholinergic synapses
what is the therapeutic use of acetylcholinesterase inhibitors
- myasthenia gravis
- glucoma
- paralytic ileus
- atony of the urinary bladder
- Alzheimer’s disease
- as pesticides and chemical warfare agents
acetylcholinesterase can reverse the paralysis of
competitive NM blockers and reduce symptoms of atropine-like toxicity
what are the side effects of acetylcholinesterase inhibitors
- intoxication manifest as an intense cholinergic response (“cholinergic crisis”)
- effects also exerted on skeletal m. and CNS
what are the different classification of AChE inhibitors
competitive reversible
alternate substrates; slowly reversible
irreversible (organophophates)
what are the effects of AChE inhibitors on eye
miosis; blurred vision; spasm of accommodation
what are the effects of AChE inhibitors on the GI
salivation; increased secretions; increased tone and motility; urination; vomiting; diarrhea
effects of the AChE inhibitors on respiratory tract
- increased bronchial secretions; watery
nasal discharge; bronchoconstriction; weakness or paralysis of respiratory muscles
what are the effects of AChE inhibitors on the cardiovascular system
- bradycardia; decreased cardiac output; hypotension; atrial flutter
what are the effects of AChE inhibitors on the CNS
tremor; anxiety; restlessness; convulsions; coma
what are the effects of AChE inhibitors on skeletal muscle
fasciculation; increased force of
muscle contraction followed by weakness; muscle paralysis due to depolarizing-type neuromuscular blockade
which AChE inhibitors are used to treat Alzheimer’s Disease
Tacrine (reversible)
Donepezil (reversible)
Rivastigmine (carbamate)
Galantamine (reversible)
what is the function of antimuscarinic such as atropine
-reduces the effect of ACh at muscarinic sites
see slide 55
see slide 55
what are muscarinic receptor antagonists
-are drugs (organic esters) that inhibit the actions of Ach on autonomic cholinergic nerves and on smooth m. cells that lack parasympathetic innervation
what drugs are classificed as belladonna alkaloids
atropine and scopolamine
what is the MOA of muscarinic receptor antagonists
-are competitive antagonists of muscarinic agonists competing for a common binding site on the receptor
what are the effects of atropine at low doses
Slight cardiac slowing followed by slight increases in heart rate, decreased salivation, inhibition of sweating. At moderate does dryness of mouth is pronounced with tachycardia, mydriasis, and cycloplegia
what are the effects of atropine at high doses
Reduced tone and motility in GI tract; decrease in vagus stimulated gastric, pancreatic, intestinal and biliary secretions; urinary retention
what are the side effects of atropine
Pulse rapid and weak; iris obliterated; vision very blurred; skin is flushed, hot, and dry; ataxia, restlessness, excitement, hallucinations, delirium, coma
what are the clinical uses of muscarinic blockers
Reduce GI tone/motility and bladder voiding Ocular exams Anesthesia ( ↓ vagal influences) Reverse sinus bradycardia Motion sickness Treat acute mushroom; AChE(-) poisoning Adjunct in Parkinson’s disease Adjunct in bronchial asthma (“tropiums”)
what are the limited clinical use of ganglionic blocking agents
controlled hypotension; “bloodless” surgical field
