Neurology Flashcards
Muscarinic Receptors
Involved in parasympathetic nervous system
M1: Gq: CNS, enteric nervous system
M2: Gi: Heart, slows heart rate
M3: Gq: inreases exocrine gland secretions, increases gut peristalsis, increases bladder contraction, bronchoconstriction, increases pupillary sphincter muscle contraction, ciliary muscle contraction (accomodation)
Nicotinic Receptors
Found on neuromuscular junction.
Found on pre-gangilionic ANS.
Ionotropic and activated by nicotine as well as acetylcholine
Cocaine
Local Anesthetic
First anesthetic discovered, lead to synthesis of procaine
Inhibits NET, leading to increased concentration of NE at α adrenergic receptors and vasoconstriction, leading to decreased diffusion away from the target site
Thought to cause mental effects by blocking dopamine reuptake.
Causes sensitization to catecholamines, vasoconstriction, and mydriasis.
Lidocaine
Local Anesthetic
May produce dysphoria, euphoria, muscle twitching, and loss of consciousness.
Also causes tinnitus, dizziness, drowsiness.
Produces faster, more intense, longer-lasting, and extensive anesthesia than procaine.
Given with epinephrine (but not topically. Topically given with phenylephrine) Broken down and excreted in urine
Can be used to treat post-herpetic neuralgia
Bupivicaine
Local Anesthetic
A potent agent capable of producing prolonged anesthesia
Often used during labor or the postoperative period
Causes vasoconstriction (without epinephrine)
Can cause ventricular tachycardia and fibrillation (only one that does), meaning it is more cardiotoxic than lidocaine.
Local Anesthetics
the loss of sensation in a body part without the loss of consciousness or the impairment of central control of vital functions.
Bind reversibly to receptor sites within the pore of the Na+ channels in nerves and block ion movement. This leads to reversible inhibition of action potentials in both motor and sensory neurons when applied locally.
Typically contain hydrophilic (amines) and hydrophobic (aromatic) moieties that are separated by an intermediate ester or amide linkage. The pore blocked is hydrophobic (meaning the hydrophobic moiety is responsible) on the internal plasma membrane (must diffuse across membrane to have effect).
Diazepam
Spasmolytic Drug
Facilitates the action of GABA in the CNS through GABAA (it is a benzodiazepam).
It produces sedation at the doses required to reduce muscle tone.
It is somewhat effective in patients with cord transaction
Baclofen
Spasmolytic Drug
Activates the GABAB receptor, orally active, results in neuronal hyperpolarization.
May also reduce pain through inhibiting substance P release
Causes less sedation than diazepam, and drowsiness subsides after prolonged usage. Withdrawal has to be done slowly due to risk of seizures.
Baclofen does not leave the spinal cord readily, enabling higher potential doses.
Might be useful for reducing cravings in recovering alcoholics. Works on sensory and alpha motor neurons.
Tizanidine
Spasmolytic Drug
A congener of clonidine that is an α2-adrenoceptor agonist. It reduces spasticity at doses that cause fewer cardiovascular effects than clonidine or dexmedetomidine.
It inhibits nociceptive transmission in the spinal cord. Displays linear pharmacokinetics, and dosage requirements vary considerably among patients (must take into account renal or hepatic impairment).
Might also be used for treating of chronic migraine
Barbituates vs. Benzodiazepines
Benzodiazepines cause an increase in frequency of GABA channel openings, while barbiturates appear to increase the duration of GABA channel openings.
Barbiturates can also be GABA-mimetic at high concentrations.
Spasticity is characterized by an increase in tonic stretch reflexes and flexor muscle spasms. It is often associated with spinal injury, MS, cerebral palsy, and stroke. Drugs that modify this reflex arch may modulate excitatory or inhibitory synapses.
Bethanechol
Most widely used for the treatment of gastrointestinal problems, urinary problems, et c.
It is a muscarinic agonist that activates M1-M3. Causes increased secretion and smooth muscle contraction.
Used for postoperative ileus, neurogenic ileus, and urinary retention.
Pilocarpine
Potent stimulator of sweat, tears, saliva.
Used for Open-angle (contracts ciliary muscle) and closed angle glaucoma (activates pupillary sphincter).
Resistant to AChE
Carbachol
Used for glaucoma, pupillary contraction, and relief of intraocular pressure.
“Carb-on copy of a-cetyl-chol-ine.”
Edrophonium
A simple alcohol bearing a quaternary ammonium group that is a reversible cholinesterase inhibitor (no covalent bond formed between esterase).
Can be used to diagnose Myasthenia gravis, ileus, arrhythmias.
Physostigmine
Used to treat anticholinergic overdose, like atropine overdose.
It crosses the blood-brain barrier and increases native Ach levels by inhibiting AChE with a stronger bond than Edrophonium
DUMBBELSS
Diarrhea,
Urination,
Miosis,
Bronchospasm,
Bradycardia,
Excitation of skeletal muscle and CNS,
Lacrimation,
Sweating,
Salivation.
Often accompanies organophosphate poisoning.
Echothiophate
An organic derivative of phosphoric acid that is a cholinesterase inhibitor and therefore an indirect choline agonist.
It is not highly lipid-soluble (whereas most organophosphates are).
It is of clinical value because it retains the very long duration of action of other organophosphates but is more stable in aqueous solution.
Used to treat Glaucoma
These types of drugs actually phosphorylate the esterase “Aging” strengthens the phosphate-enzyme bond, but this bond can be reversed if treated before aging occurs with pralidoxime
Malathion
An insecticide.
Quite lipid soluble.
A thiophosphate prodrug that are inactive; it is converted to a phosphate derivative in animals and plants and are used as insecticides.
Atropine
Found in the plant Atropa belladonna, deadly nightshade and jimson weed
Causes a reversible blockade of cholinomimetic actions at muscarinic receptors (can be overcome by increased concentrations of acetylcholine).
Tissues most sensitive are the salivary, bronchial, and sweat glands (acid secretion by stomach is least sensitive)
Hits M1-M3
First drug to treat Parkinson Disease (by affecting acetylcholinergic neurons in the putamen.)
Atropine
Causes tachycardia (by blocking muscaranic effects of parasympathetic) but does not greatly affect the ventricles.
Can be used to dilate the eye, but is not recommended unless cycloplegia or prolonged action is required.
Used to treat Amanita poisoning
More toxic in children than adults “dry as a bone, blind as a bat, red as a beet, mad as a hatter”
Scopolamine
More profound CNS effects; induces drowsiness at recommended doses and amnesia in sensitive individuals.
In high doses and cause coma.
Often used to prevent or reverse vestibular disturbances (cures seasickness)
Pralidoxime
Used to reverse the phosphorylation of cholinesterase by organophosphates.
It is most effective in regenerating the cholinesterase associated with skeletal muscle neuromuscular junctions.
It is a quaternary amine, and is therefore unable to enter the CNS.
It is not recommended for reversible inhibition due to carbamate inhibitors.
Amphetamine
Similar to ephedrine, but it more readily enters the central nervous system.
Its actions are mediated through the release of norepinephrine and, to some extent, dopamine
It blocks NET from taking up norepinephrine as well as causes the reverse reaction (extrusion of norepinephrine).
Used to treat narcolepsy, obesity, ADD
Ephedrine
Indirect general agonist (ß1 and ß2) releases stored catecholamines.
Used for nasal decongestion, urinary incontinence, hypotension
Clonidine
Direct acting sympathomimetic
α2 selective agonist that has an ability to devrease blood pressure through actions in the CNS even though direct application to a blood vessel may cause vasoconstriction.
Useful for treating hypertension.
Sedation is a potential side effect
Produces symptoms of dry mouth
Tertbutaline
ß2 selective agonist
Relaxes the pregnant uterus. It has been used to suppress premature labor. The goal is to defer labor long enough to allow adequate maturation of the fetus.
Pseudoephedrine
Mixed-acting sympathomimetic
One of the four ephedrine enantiomers.
It used to be used as a nasal decongestant but now it is more controlled due to its use for making methamphetamines.
Phenylephrine
Used to dilate the eye via α1 receptors.
This can also increase the outflow of aqueous humor from the eye and can be used clinically to reduce intraocular pressure.
Alpha agonist
Isoproterenol
Direct acting sympathomimetic
A nonselective beta agonist. It activates both ß1 and ß2.
The net effect is to maintain or slightly increase systolic pressure and to lower diastolic pressure, so that mean blood pressure is decreased.
Has little effect on α receptors. Has positive chronotropic and inotropic actions and is a potent vasodilator.These lead to a marked increase in cardiac output associated with a fall in diastolic and mean arterial pressure and a lesser decrease or slight increase in systolic pressure
Benztropine
Anti-muscarinic used to treat Parkinson’s
Affects aspiny acetylcholine secreting neurons of the putamen
Aspiny neurons preferentially activate the indirect (inhibitory) pathway
IFNß1a & IFNß1b
MS treatment
For relapsing/remitting attacks
Suppresses the movement of T-cells into the CNS, as well as their proliferation
Shifts cytokine profile from pro-inflammatory to anti-inflammatory
Glatiramer acetate
MS Treatment
For relapsing/remitting attacks
Random-sequence polypeptide made up of alanine, lysine, glutamate and tyrosine directly binds to MHC II DR molecules
Induces CD4+ T cells to secrete Th2 cytokines
Cyclophosphamide
Alkylating agent used to treat MS by suppressing the immune system.
Used in patientsthat are refractory to immunomodulators.
Mitoxantrone
A DNA intercalater used to treat MS.
Methylprednisolone
Steroid used for MS.
given for relief during acute attacks in a pulsatile fashion (1g/day i.v. for 3-5 days)
non-specific therapy maintains function and quality of life
L-Dopa: MOA
Served as the precursor to dopamine that was able to be transported through the blood brain barrier (unlike dopamine).
It is used by the substantia nigra.
It was metabolized by both MAOs, COMTs, and amino acid decarboxylases
L-Dopa: GI Side Effects
Gastrointestinal Nausea and vomiting secondary to stimulation of D2 receptors in the area postrema
Usually transient and not a problem if co-administered with carbidopa to prevent peripheral metabolism
L-Dopa: Cardiovascular Side Effects
Cardiovascular Tachyarrhythmias secondary to increased peripheral catecholamine formation-less common if taken with carbidopa
Postural hypotension from failure to appropriately release NE due to activation of inhibitory D2 receptors on noradrenergic terminals…or.. Hypertension since high levels of DA can also stimulate a adrenergic receptors in the periphery
Carbidopa
A peripheral decarboxylase inhibitor used with L-Dopa for treatment of Parkinson’s.
It is never used as a monotherapy
L-Dopa Contraindications
Psychosis
Closed-angle glaucoma
Melanoma
Avoid Vitamin B6
Non-selective MAO inhibitors
Dopamine Agonists
Did not require presence of substantia nigra cells.
Directly activated dopamine receptors in putamen and caudate.
Work as monotherapy
Pramipexole: A D3 agonist
Ropinorole: a D2 agonist
Apomorphine: A D4 agonist
Apomorphine
A D4 dopamine agonist that is used as rescue therapy for Parkinson’s disease.
Highly emetogenic. Used as a last ditch effort
Selegeline
An MAO-B inhibitor
Inhibits dopamine breakdown in the CNS Early symptomatic relief for Parkinson’s disease.
Can be used as a monotherapy, but also prolongs the effects of L-Dopa
Has methamphetamine breakdown products
Rasagiline
An MAO-B inhibitor
Inhibits dopamine breakdown in the CNS
Early symptomatic relief for Parkinson’s disease.
Can be used as a monotherapy, but also prolongs the effects of L-Dopa
More potent than Selegeline
Tolcapone
A COMT inhibitor used in treating Parkinson’s disease
Used along with L-Dopa.
Has both peripheral and CNS distribution.
It is associated with acute liver failure
Entacapone
A COMT inhibitor used in treating Parkinson’s disease
Used along with L-Dopa.
Has only peripheral distribution and is not associated with liver failure
Amantidine
Anti-viral with some Parkinson’s activity.
Benefits short lived but effective
Diphenhydramine
Anti-muscarinic used to treat Parkinson’s
Trihexphenidyl
Anti-muscarinic used to treat Parkinson’s
Tetrabenazine
VMAT2 inhibitor used to treat Huntington’s.
It prevents loading of dopamine into vesicles.
This lessens excitatory effects of the substantia nigra pars compacta
Reserpine
VMAT2 inhibitor used to treat Huntington’s.
It prevents loading of dopamine into vesicles.
This lessens excitatory effects of the substantia nigra pars compacta
Not used as frequently as Tetrabenazine
Riluzole
Only treatment for ALS
Prevents glutamate release
Prolongs life 2-3 months
Penicillin G
Treatment for N. meningitidis
MOA: interferes with cell wall synthesis
MOR: can be hydrolized by penicillinase, but resistance to Neisseria meningitidis is infrequent
Cefotaxime
3rd generation cephalosporin
Treatment for N. meningitidis
Good alternative to Pen G due to ability to penetrate CNS
MOA: interferes with cell wall synthesis
MOR: hydrolysis of the b-lactam ring by b-lactamase
Chloramphenicol
Treatment for N. meningitidis
Alternative for those with severe b-lactam allergy
Can cause dose dependent pancytopenia, or an idiopathic aplastic anemia
MOA: inhibits microbial protein synthesis
MOR: inactivation by bacterial acetyltransferases
Ampicillin
Bacterial meningitis in immunocompromised patients is usually due to L. monocytogenes
Not for the treatment of bacterial meningitis due to N. meningitides due to high levels of resistance
MOA: inhibition of bacterial cell wall synthesis
MOR: destruction by b-lactamase
Rifampin
Prophylactic for N. meningitidis
Used to treat the carrier state and those who may have been exposed to the organism.
Also used to treat M. leprae
MAO: inhibits microbial RNA synthesis via inhibition of DNA-dependent RNA polymerase
MOR: mutations in the target
Dapsone
Used to treat M. leprae
MOA: inhibits RNA synthesis
Clofazimine
Used to treat M. leprae
MOA to be determined
Eflornithine
Used to treat the early and late stages of T. brucei Gambiense
MOA: inhibits ornithine decarboxylase
Penetrates CNS
Pentamidine
Treats T. brucei Gambiense early stage only
Can also be used to treat Acanthamoeba
Suramin
Treats early stages of both T. brucei Gambiense and Rhodesiense
It is slow acting
Melarsoprol
Treats the late stage of both T. brucei Gambiense and Rhodesiense
Benznidazole
Used to treat T. cruzi
Trypanocidal due to generation of nitrogen radicals
Benznidazole is usually preferred due to less toxic side effects
Side effects are common: hypersensitivity, nausea, vomiting, weakness, headache, psychic disturbances
Nifurtimox
Used to treat T. cruzi
Trypanocidal due to generation of nitrogen radicals
Nifurtimox may also be given in conjunction with eflornithine to treat T. brucei infections
Side effects are common: hypersensitivity, nausea, vomiting, weakness, headache, psychic disturbances
Phenoxybenzamine
An alpha1 and 2 inhibitor, more selective for alpha1.
It is irreversible, and forms covalent bonds with the receptors.
