How can we help?

You can also find more resources in our Help Center.

116 terms

Pharmacology Exam 2 (Part 1)

Subject of cards are in this order: - Intro to Autonomic Pharmacology (Regan) (Note: I did not like how Regan went through this packet. He drew a lot of schemes on the board and I thought it was difficult to follow him with the packet. So I may not have done a good job summarizing the main points from this packet.) -Pharmacology of Cholinoceptor Agonists (Cherrington) -Cholinoceptor Blockers: Antimuscarinic Drugs (Cherrington) -Nicotinic receptor blockers: Ganglion and Neuromuscular Drugs (Cherr…
the cells of origin for the sympathetic nervous system are located where?
thoracic and lumbar cord (thoracolumbar)
one sympathetic preganglionic fiber innvervates about how many post-ganglionic fibers?
20 post-ganglionic fibers (polysnaptic)
all preganglionic neurons in the autonomic nervous system release what neurotransmitter?
Most postganglionic neurons in sympathetic nervous system release what neurotransmitter?
(exception are those innervating eccrine sweat glands which are cholinergic)
cells of origin for the parasympathetic nervous system are located where?
cranial and sacral cord (craniosacral)
one parasympathetic preganglionic fibers innrevates about how many postganglionic fibers?
1 postganglionic fiber
all postganglionic parasympathetic neurons release what neurotransmitter?
What is the main source of norepinephrine in the body?
Adrenal medulla.
acetylcholine acts on receptor on adrenal medulla
Does the somatic nervous system have intermediate ganglions?
No, neuron goes straight to the muscle.
Where are the cells of origin for the somatic nervous system?
throughout the spinal cord
Where are the cells of origin for the enteric nervous system located?
intramural plexuses (myenteric and submucosal) of the wall of the intestine

I think simply "in the walls of the intestine" is good enough
T or F: the enteric nervous system only receives input from the parasympathetic division.
F: receives input from both divisions of the autonomic nervous system
T or F: the neurons of the enteric nervous system utilize a variety of neurotransmitters
There are three main muscarainic cell receptor subtypes. Where are they located?
M1: nerves
M2: heart, nerves, smooth muscle
M3: glands, smooth muscle, endothelium
When M2 receptor is activated, does it result in an up regulation or down regulation of heart activity?
down regulation
The choline esters acetylcholine, methacholine, carbachol, and bethanechol are muscarinic agonists. Why is it that they have no CNS activity?
postively charged quaternary amine does not cross membranes
Of the choline esters (acetylcholine, methacholine, carbachol, bethanechol) which are not readily hydrolyzable so have a longer halflife?
Which are selective for muscarinic action (no nicotinic action)?
carbachol and bethanechol have negligble susceptibility to hydrolysis

methacholine and bethanechol are selective for muscarinic action
The cholinomimetic alkaloids discussed in class include muscarine, oxytremorine, arecoline, DMPP, pilocarpine, and nicotine. Are any of these selective for receptor sub-types?
Are any of the choline esters (acetylcholine, methacholine, carbachol, bethanechol) selective for muscarinic receptor subtypes?
The cholinomimetic alkaloids discussed in class include muscarine, oxytremorine, arecoline, DMPP, pilocarpine, and nicotine
Do any of these have CNS activity?
oxytremorine, nicotine and DMPP (dimethylphenylpiperazinium) do.
It does not explicitly say in the lecture that arecoline has central activity, but arecoline does.

Pilocarpine has some

Muscarine does not due to quaternary amine
do the cholinomimetic alkaloids muscarine and oxytremorine have chiefly nicotinic or muscarinic action?

What about nicotine and DMPP (dimethylphenylpiperazinium)?

do muscarinic effects on GI and urinary tracts increase or decrease tone, contraction and peristaltic activity (urination and defecation?

increase or decrease secretion of mucus, pepsin, and gastric acid?

What happens with toxic doses?
increase tone, contraction and peristaltic activity

increase secretion of mucus, pepsin, and gastric acid

nausea, vomiting, abdominal cramps occur with toxic doses
concerning muscarinic effects on the eye:
miosis or mydriasis?
contraction or relaxation of ciliary muscle lens?
decreased or increased intraocular pressure?

contraction of ciliary muscle of lens, lens becomes more convex, accomodation for near vision

decreased intraocular pressure due to increased aqueous humor outflow through the trabecular meshwork and canal of Schlemm. (This effect is believed to be mediated by contraction of the ciliary muscle)
concerning muscarinic effects on the cardiovascular system:
vasodilation or vasoconstriction?
tachycardia or bradycardia?
increased or decreased force of heart contraction?
what will happen to the heart and toxic doses?
M2 receptor is on the heart. Remember that agonism of M2 receptor results in down regulation of heart.

vasodilation and hypotension (direct effect on arterioles) and reflex tachycardia

bradycardia (negative chronotropic effect) - direct effect on heart

decreased force of heart contraction (negative inotropic effect)

cardiac arrest at toxic doses.

*NOTE: something I'm not sure about is what is the net effect on heart rate. As you can see we get bradycardia by directly effecting the M2 receptor on the heart, but also reflex tachycardia from the hypotension caused by vasodilation of arterioles. So I am not sure what the net effect on heart rate is as both of these processes happen simultaneously.
Why are muscarinic effects bad for asthma?
Increased secretion of exocrine glands. This leads to increased tracheobronchial secretions (as well as lacrimal, salivary, and sweat).

Increased bronchoconstriction.
At toxic doses of a muscarinic agonist, what effect can it have on skeletal muscle?
nictonic effect: skeletal muscle contraction and cramps
concerning indications of drugs that have muscarinic effects:
T or F: can be used to treat nonobstructive urinary retention and neurogenic atony of urinary bladder.

T or F: can be used to treat closed angle glaucoma

T or F: can be used to treat xerostomia (dry mouth)
T: can be used to treat urinary retention

F: can be used to treat wide angle (chronic simple) glaucoma, not closed angle.

T: can be used to treat dry mouth in cancer patients treated with radiation and occasionally in patients receiving tricyclic antidepressants.
Why are drugs that cause muscarinic effects contraindicated for...
peptic ulcer?
coronary insufficiency?
colorectal or bladder cancer?
kidneys stones?
peptic ulcer: increases gastric secretions, which is bad if you have an ulcer

asthma: causes bronchoconstriction, harder to breathe

coronary insufficiency: negative chronotropic (heart rate) and inotropic (strength of heart beat) effects

colorectal or bladder cancers: more likely to have a blockage with these conditions, so increasing GI motility can cause increased pressure

kidney stone: I believe the principle is the same as above
Concerning the mechanism of action of acetylcholine esterase:

What part of ACh is involved in the electrostatic bond made between ACh and the anionic site of AChE?

At the esteratic site, a weak bond is formed between what part of ACh and what amino acid in the esteratic site of AChE?

AChE is then acetylated and what is released for reabsorption by the presynaptic nerve?

Acetylated AChE then reacts with _____ to form acetic acid and regenerated enzyme.
an electrostatic bond is formed between the enzyme and the positive charge at the nitrogen atom

a weak bond is formed between the carbonyl carbon of ACh and the oxygen from a serine in the esteratic site of AChE

Once AChE is acetylated, choline is released for reabsorption by the presynaptic nerve.

Acetylated AChE then reacts with water to form acetic acid and the regenerated enzyme
"reversible" acetylcholinesterase inhibitors include physostigmine, neostigmine, pyridostigmine, carbaryl, and edrophonium.

They differ from ACh in that they form what kind of enzyme intermediate instead of an acetylated enzyme?
these have a carbamyl instead of the carbonyl that acetylcholine has, so
they form a carbamylated enzyme intermediate which undergoes slow hydrolysis

Upon further investigation, edrophonium does not have a carbamyl
AChE inactivation by organophosphates ("irreversible" inhibitors: echothiophate, parathion, malathion, sarin - tabun - VX - Binary GV) forms a strong covalent bond between the phosphorous atom of the inhibitor and what site of the enzyme?

What must happen in order for degradation of ACh to continue?
forms strong covalent bond between phosphorus atom of inhibitor and the esteratic site of the enzyme.

This complex is virtually irreversible thus for practical purposes de novo synthesis of AChE must occur before degradation of ACh takes place
Pralidoxime (Protoam or 2-PAM) is a cholinesterase reactivator and is used to treat organophosphate poisoning.
Does it have a strong nucleophilic or electrophilic group that competes with AChE for the phosphorous group of the inhibitor?

Why must protopam be given within 24-36 hours of poisoning?
strong nucleophilic group competes with AChE for phosphorous group of the inhibitor

The enzyme becomes resistant to antidotal effects due to "aging"
T or F: effects of cholinesterase inhibitors are essentially the same as direct-acting muscarinic agonists, therefore they have similar indications and contraindications

Some differences though...
More pronounced nicotinic effects especially on skeletal muscle.
Treatment of myasthenia gravis to improve muscle strength (nicotinic effects)
diagnosis of myasthenia gravis
Alzheimer's disease (tacrine, donepezil) to improve memory and cognition
What is the first sign of toxicity for cholinesterase inhibitors?
tunnel vision

fasciculations may be a side effect and turgid paralysis (depolarizing blockade) at toxic doses
Atropine and scopaoamine are natural alkaloids that are muscarinic antagonists.

Which of these two has more profound CNS effect and can be absorbed in GI and skin?
Tertiary amine blockers pirenzepine and dicyclomine are used for...
(hint: two GI related thangs)
used for peptic disease and hypermotility

also "occasional ocular use or when oral route of exposure for CNS activity is desirable"
(that's what it said verbatim in the packet. Is it just me or does that sentence sound weird?)
Compared to the tertiary amine blockers (cholinoceptor blockers )(pirenzapine and dicyclomine), how are quaternary amine blockers (propantheline and glycopyrrolate) different?

How are they similar?

What determines dose and toxicity of quaternary amine blockers?
quaternary amine blockeres have peripheral effects only, NO CNS activity

Like tertiary amine blockers, they are used for GI and peptic diseases.

renal function/disease determines dose and toxicity
MOA of muscarinic antagonists?
blocks action of cholinomimetics at muscarinic receptors
Competes for the receptor binding site

basically it sits on the receptor and gets in the way of ACh
concerning cholinoceptor blocker's effects on CNS:

between atropine and scopolamine, which has more pronounced drowsiness and can cause amnesia?

Why can cholinoceptor blockers be used to treat the tremor of Parkinson's disease?
Scopolamine causes more pronounced drowsiness and amnesia
Atropine: minimal stimulant with slower sedative effect

Tremor is caused by an excess of cholinergic activity, so by blocking the cholinoceptor we can treat the tremor.

Other effects: decreased concentration and memory. Sedation, excitation, ataxia, hallucinations, coma
concerning cholinoceptor blocker's effects on the eye:

topical atropine results in...?

good or bad for glaucoma?

what happens to near vision?

increased or decreased lacrimation?
topical atropine results in dilation (mydriasis). Extremely slow elimination in the eye

Bad for glaucoma. increases intraocular pressure.

ciliary muscle can no longer accommodate, so loss of near vision

decreased lacrimation
concerning cholinoceptor blocker's cardiovascular effects:

These effects are dose dependent. What happens with moderate to high doses? What about low doses?
remember that M2 receptor agonism results in down regulation of the heart.

Moderate to high doses block M2 receptors of the heart, blocking the "slowing" effect resulting in tachycardia.

Low doses may block the M1 autoreceptors on vagal postganglionic fibers which limit normal ACh release, resulting in initial bradycardia.
concerning cholinoceptor blocker's respiratory effects:

Cherrington: "ACh causes a lot of fluid and a lot of gunk"
Are cholinoceptor blocking drugs good for asthmatics?
causes some bronchodilation and reduction in secretion.

Note: not as effective as beta-adrenoceptor stimulants, but still these drugs can be used for asthma.

also used prior to inhalant anesthetics to reduce tracheal secretions
concerning cholinoceptor blocker's GI effects:

Why is it patients on these drugs have difficulty swallowing and digesting?
ACh stimulates salivating and gastric secretion, so blocking ACh receptors reverses that, decreasing motility and secretion.

M1 selective blockers (Pirenzipine) reduce acid without many side effects.
T or F: scopolamine (cholinceptor blocker) can be used for motion sickness
heavy sedation is limiting
dimenhydrinate (dramamine) is preferable
T or F: cholinoceptor blockers are useful in ophthalmologic exams because of miosis and ciliary paralysis
causes mydriasis and ciliary paralysis
T or F: amnesia associated with scopalamine can be beneficial
beneficial in obstetrics (woman forget's childbirth)
T or F: Concerning using cholinoceptor blockers for cholinergic poisoning: There are methods to reverse nicotinic effects of AChE inhibitors.
packet: "NO method to reverse nicotinic effects of AChE inhibitors- both block transmission"
T or F: quaternary amines (cholinoceptor blockers) are used to block muscarinic effects of cholinergic poisoning - CNS and peripheral
tertiary amines are used to block muscarinic effects -CNS and peripheral

quaternary amines are charged so do not have access to CNS
Does pralidoxime enter the CNS?

It is used for organophosphate poisoning, can it be used with carbamate (physostigmine, pyridostigmine, neostigmine) poisoning?
No and no.
Why are cholinoceptor blockers contraindicated for...
elderly and cardiac tachyarrythmias?
use in patients with glaucoma?
gastric ulcer?
cholinoceptor blockers cause tachycardia

increases intraocular pressure

due to slower gastric emptying, patients with gastric ulcer have increased symptoms. H2 antagonists are preferred.
T or F: Nicotinic acetylcholine receptors are channels.
composed of 5 subunits arranged to form a transmembrane pore
What are the two types of nicotinic receptors?
Nm: muscle type, end plate receptor located on skeletal muscle and neuromuscular junction
Nn: neuronal type, ganglion receptor. located on postganglionic cell body, dendrites
(not sure how important this is to know)
How many mV is the resting potential of the membrane?
How mnay mV is the action potential of the membrane?
resting potential: -70mV
action potential: -50mV
Binding of acetylcholine to the nicotinic acetylcholine receptor results in what?
opening of the channel, resulting in flow of ions down the gradient, depolarizing the membrane
Ganglion blockers are nicotinic receptor blockers are drugs that look like acetylcholine
T or F: these drugs have no CNS effects
Mecamylamine and others cause extreme sedation, tremor and mental aberrations
Ganglion blockers are nicotinic receptor blockers:
What effect do they have on vascular resistance and venous return?
Effect on blood pressure?
Vasoconstriction signal is blocked.
Vascular resistance and venous return decreased.
Acute decrease in blood pressure (used to treat hypertensive emergencies)

Note: most definitely not the preferred treatment
Ganglion blockers are nicotinic receptor blockers:
T or F: they are used frequently clinically
F: Use has been abondoned
Cherrington "these are useless"

More selective autonomic blockers makes ganglion blockers obsolete

Because effector cell receptors are blocked in multiple tissues types, autonomic derugs effects are exaggerated or opposite.
What is the difference between depolarizing and nondepolarizing muscle blockade?
depolarizing: opens the nicotinic acetylcholine receptor/channel and keeps it open.

nondepolarizing: kepps the nicotinic acetylcholine receptor/channel closed
T or F concerning nondepolarizing pharmacokinetics:
- all neuromuscular blockers are charged and polar
- are orally bioavailable
-distribution is almost exclusive to plasma
T: all neuromuscular (at least the ones I see in the packet) have quaternary amines
F: these are always administered IV, not orally bioavailable. T: Distribution is almost exclusive to plasma
concerning nondepolarizing pharmacokinetics:
there are 3 ways these drugs are inactivated: excretion by kidney, inactivation by plasma cholinesterases, steroid nondepolarizing drugs hydroxylated in the liver to less active metabolites by CYP450.

Rank these three in terms of speed of inactivation
kidney: slow
plasma cholinesterases: fast
liver: intermediate (biliary excretion is responsible for the short half-life of steroid drugs. Not sure how important that is to know, but it was on the slide)
T or F: In class we discussed two kinds of nondepolarizing neuromuscular blockers, nondepolarizing isoquinoline drugs and nondepolarizing steroid drugs

nondepolarizing isoquinoline drugs include tubocurarine and atracurium
nondepolarizing steroid drugs include pancuronium and vecuronium

Cherrington didn't seem to stress these drugs individually, but rather seemed to focus on nondepolarizing neuromuscular blockers as a whole, so I'm not how important this designation is.
Atracurium is an isoquinoline derivative nondepolarizing neuromuscular blocker and is mainly inactivated by spontaneous breakdown.

Laudanosine (a metabolite of atracurium) has a long halfe life and crosses the blood brain barrier. Is this is a good thing or a bad thing?
Bad, this causes problems
Laudanosine accumulation during surgery causes a 30% increased anesthetic requirement and may cause seizures.

Cisatracurium (another isoquinoline nondepolarizing neuromuscular blocker) forms less laudanosine and releases less histamine
T or F: There is only one clinically relevant drug that is of the depolarizing neuromuscular blocker class
T: succinylcholine
T or F: the structure of succinylcholine is two acetylcholines attached tail to tail
not sure how important that is to know, but he said it and I wrote it down.
T or F: succinylcholine (the depolarizing neuromuscular blocker) does not undergo hydrolysis of plasma cholinesterase in plasma and liver
F: succinylcholine undergoes rapid hydrolysis by plasma cholinesterase in plasma and liver ((half life is about 8 minutes)

But there can be large individual variability of plasma cholinesterase so half life may vary largely
T or F: when using succinylcholine (depolarizing neuromuscular blocker) all muscles fire at maximum. This is called turgid paralysis.
T or F:
nondepolarizing neuromuscular blockers have a noncompetitive interaction with acetylcholine at the nicotinic receptor site
F: nondepolarizing neuromuscular blockers compete with acetylcholine at the nicotinic receptor site
T or F: nondepolarizng neuromuscular blockade is surmountable
T:it can be overcome by having more acetylcholine than blocker
Neostigmine (AChE inhibitor) can be used to overcome blockade
T or F: succinylcholine binding and activity is much longer than acetylcholine
Concerning the neuromuscular blocker depolarizing mechanism:

Succinylcholine opens channel and depolarization spreads through entire muscle. Membrane potential is exhausted leading to turgied, then flaccid paralysis.

Will membrane potential reestablish despite continued exposure to succinylcholine.?
Yes, membrane channels eventually refuse to open despite presence of ACh or succinylcholine

The membrane is not easily depolarized again and the channels remain closed for a prolonged time, so we get characteristics similar to a non-depolarized blockade.

The mechanism for this is not understood
concerning nondepolarizing neuromuscular blockers:
T or F: early muscle weakness occurs and finally turgid paralysis
F: early muscle weakness and flaccid paralysis
concerning nondepolarizing neuromuscular blockers:
T or F: large muscles (diaphragm) are more resistant and recover faster
"Transient muscle fasciculations begin on the chest and abdomen"
Is this fact true for nondepolarizing or depolarizing neuromuscular blockers?

"Arms legs and neck are quickly paralyzed, voice and fast are last"
Is this fact true for nondepolarizing or depolarizing neuromuscular blockers?
depolarizing for both
T or F neuromuscular blockers do not have any cardiovascular effects

many drugs cause interference by acting at autonomic ganglia, cardiac muscarinic receptors or causing histamine release

Tubocurarine and others produce hypotension by histamine release
Pancuronium (M2 block) - increased heart rate and output
Succinylcholine stimulates all autonomic cholinoceptors - nicotinic and both symp, and parasymp. muscarinic in SA node
There are some effects that occur only with depolarizing block and not nondepolarizing block:

what is the effect on potassium?
hyperkalemia: potassium release can be sufficient enough to cause cardiac arrest

intraocular pressure builds from 1-4 min, subsidies after 5 min
Cherrington: "Oh my eyes!"

increase in intragastric pressure: possible vomiting (emesis) in muscular patients

muscle pain - muscle damage caused by uncontrolled fasciculations
Neuromuscular blockers have drug interactions with...
local anesthetics

What are the interactions they have with each?
aneshetics: augment nondepolarizing neuromuscular blockade, so you need less neuromuscular blocker

antibiotics: aminoglycosides enhance blockade of calcium channels (so I believe to you need less neuromuscular blocker)

local anesthetics: large doses block neuromuscular transmission, requires lower neuromuscular block (require less neuromuscular blocker)

Also: nondepolarizing drugs given before succinylcholine (depolarizing) helps decrease pain - increases required dose.
Note about above: I'm not sure how that works or what "increases required dose" means.
Disease and aging as effects on neuromuscular blockade and how the patient reacts to neuromuscular drugs. What is the effect of the following on neuromucsular blockade and drugs?

myasthenia gravis
burn victims
elderly patients
myasthenia gravis augments neuromsucular blockade

burn victims are refractory to non-depolarizing drugs (potassium danger: too much potassium leaving, hyperkalemia leads to heart problems)

decreased clearance in elderly causes prolonged effects
Nondepolarizing neuromuscular blockade is surmountable and can be reversed. What drug can we use to sufficiently increase ACh concentrations to overcome neuromuscular blockade?
Neostigmine (carbamate AChE) increase presynaptic ACh levels by inhibiting AChE

neostigmine is more effective than edrophonium at reversing blockade (not sure how important this is to know)
T or F: neuromuscular blockers cannot be used in respiratory failure

cannot be used for short term elimination of convulsions from epilepsy or anesthetic toxicity
F for both
neuromuscular blockers can be used for ventilation in respiratory failure. Eliminates inefficient breathing and allows for easier ventilation without resistance

Can be used for short term elimination of convulsions from epilepsy or anesthetic toxicity. Only treats muscular convulsion, does not cause CNS to treat the cause of convulsions though.
Muscle has a feedback mechanism that is way of recruiting all parts of the muscle. As muscle fires it sends two signals that circulate through the spinal column.

One signal says "fire more" and the other signal says "stop inhibiting my firing."

What is this called?
stretch reflex
Your brain controls fine motor skills by inhibiting what?
inhibiting the stretch reflex
What is the job of the internuncial neuron?
To stop the signal from the muscle to "fire more" and to "stop inhibiting firing"
Diazepam is a benzodiazepine antispasticity drug. It increases ___-mediated inhibition of the excitatory neuron.
increases GABA-mediated inhibtion of the excitatory neuron. It facilitates GABAa receptor activation at spinal cord.

Facilitates inhibtion from the internuncial neuron.

(The above is really 3 ways to say the same thing. The first two are from the slides, the third is one I cam up with on my own to help organize my thoughts)
T or F
Diazepam (an antispasticity drug) is a GABA analogue.

Causes heavy sedation at required doses.

Causes withdrawal symptoms, so taper off slowly
F: not a GABA analogue, it allosterically activates the GABAa receptor.


Baclofen is an orally active GABAb mimetic antispastic drug that reduces the release of excitatory transmitters by causing hypopolarization or hyperpolarization?

Does baclofen cause more or less sedation than diazepam?

T or F: no need to withdraw slowly

less sedation than diazepam

F: sudden discontinuation can result in seizures, confusion, and rebound muscle hyperactivity
Tizanidine is an antispastic drug that is a strong agonist of the alpha 2 adrenoceptor and increases both pre and post synaptic inhibition at the spinal cord.

T or F
This drug causes drowsiness.
This drug has huge interindividual variability.
T for both
causes about as much drowsiness as baclofen (so less drowsiness than diazepam)

He did not go into detail with this drug, so I do not understand how being a strong alpha 2 agonist helps with spasticity (mechanism).
Dantrolene is an antispastic drug. It blocks the release of calcium from sarcoplasmic reticulum. What result does this have on the muscle?

Do you get sedation with this drug?
release of calcium for the sarcoplasmic reticulum is required for contraction, so it makes it so that the muscle can not work fully.
You get muscle weakness

You get sedation, but not to the extent of diazepam, baclofen, or tizanidine
Botulinum Toxin A (Botox) cleaves SNAP-25 protein. What effect does this have on ACh?
SNAP-25 is required for the release of ACh so your muscles don't work very well.
It takes 2-6 months to grow new neuromuscular endplate from axon sprouting, so it's like having less nerves for 2-6 months.

(verbatim from slide "inhibits neurotransmitter release from neuromuscular junction." I feel like "from" is kind of confusing...)
Does botulinum toxin A (botox) cause sedation?
No sedation for CNS effect
Cyclobenzaprine, carisoprodol, orphenadrine, metaxalone, methocarbamol, chlorzoxazone are used for what kind of muscle condition/
acute local muscle spasm (caused by local trauma or strain, may inlolve local nerve damage or inappropriate nerve stimulation, but does not involve any contribution by the CNS, unlike spasticity)
these can be giving to specific muscles locally

(not sure how important these are to know, he really didn't go into detail, he just listed these drugs and said they did this.

There's also a slide on page 48 of his handout that says "others." He basically skipped over that slide due to lack of time. Not sure if we're responsible for them)
Of these acute local muscle spasm drugs, when of these are most effective for acute local muscle spasm?


also causes high sedation and confusion

Has no effect in upper motor neuron syndrome (typical spasticity)
The upper motorneuron syndrome resulting from lesions to brain or spinal cord that result in hyperexcitability of the stretch reflex is called?
What is the difference between the GABAa and GABAb receptors?
GABAa are ligand gated chloride channels
GABAb are G-protein coupled receptors
What is the difference between the vitreous humor or aqueous humor?
vitreous humor is behind the lens and is thick and gel-like and gives eyeball structure.

aqueous humor is more watery and is in front of the lens
The muscles of the iris include the outer radial muscle and the inner circular muscle.

contraction of which muscle results in miosis?
contraction of which muscle results in mydriasis?

Which action is sympathetic and which action is parasympathetic?

Neurontransmitters and receptors involved?
parasympathetic stimulation (ACh acting on M3 receptor on muscle) results in contraction of sphincter muscle (I guess that's another name for the inner circular muscle...?) results in miosis

sympathetic stimulation (NE acting on alpha 1 receptor on muscle) results in contraction of outer radial muscle causing mydriasis
The ciliary body is a muscle that goes around the lens (in front of the lens) and is continuous with the iris.

What is the relationship between the ciliary body and lens and distance vision vs near vision?
Distance vision: dominant sympathetic tone, ciliary body relaxed, zonules tight, lens relatively flat (less focusing power)

near vision: parasympathetic activation, ciliary muscle contracted, zonules relaxed, more rounded lens (more focusing power)
What is it that produces aqueous humor?
aqueous humor is made by the ciliary body
wikipedia definition: the process by which the vertebrate eye changes optical power to maintain a clear image or focus on an object as its distance varies.

What is the term that describes this?
There are two outflow pathways for the aqueous humor. What are they and which one is responsible for 90% of aqueous humor outflow?
trabecular meshwork (90%)
uveoscleral (10)
healthy intraocular pressure (IOP) is between 14-20 mmHg and helps keep the eye structurally sound.

T or F changes in pressure in the front of the eye does not effect the rest of the eye
changes in aqueous humor formation (by the ciliary body) or outflow (mostly at trabecular meshwork) are felt by the whole eye.
Liquids are not compressible, so any increase in pressure in the front of the eye is communicated to the whole eye
any IOP >20 mmHg increases risk of glaucoma. High IOP is not glaucoma, glaucoma is loss of vision due to IOP.
What is it that gets damaged that leads to vision loss and eventual blindless if left untreated?
Optic nerve damage
There are two primary types of glaucoma wide-angle/open angle/chronic simple and narrow-angle/closed/acute congestive.
The angle refers to the angle between the iris and cornea.

Which one is most common?
Which one is painful?
Which one is rapid and an emergency?
Which one is slow and progressive?
Which one is exacerbated by dilation?
wide-angle is most common

closed angle is painful

closed angle is rapid and an emergency

wide-angle is slow and progressive

closed angle is exacerbated by dilation (A lot of drugs have potential to dilate the iris muscarinic blockers and anticholinergics increase risk of glaucoma)
What are the three mechanisms used to treat glaucoma?
increase outflow through trabecular meshwork

increase uveoscleral outflow

decrease aqueous formation by the ciliary body
Latanoprost, bimatoprost, unoprostone, and travoprost are prostaglandin F2alpha analogs used to treat glaucoma.

Which of the 3 mechanisms used to treat glaucoma does these drugs use?

There are two drugs of the ones listed that are most important/widely used. Which are they?
increases uveoscleral outflow

latanoprost (most widely used)
bimatoprost (I remember Regan saying this drug was important)

Other notes: good efficacy, few side effects, can be combined with other drugs, may cuase hypertrichosis (growth of eyelash) and increase iridial pigmentation

(I'm not sure how important those other notes are)
Pilocarpine and carbachol are cholinergic (muscarinic) agonists that can be used to treat glaucoma.

Which of the 3 mechanisms used to treat glaucoma do these drugs use?
increase trabecular outflow

"prinicpal features": oldest, effective, but now largely replaced by newer agents
requires multiple daily dosing
constricts pupillary sphincter = miosis = poor vision in low light
contracts ciliary muscle = myopia (nearsightedness) and blurred vision due to accommodation
(not sure how important all those are to know)
Physostigmine (short acting) and echothiophate (long acting) are cholinesterase inhibitors that can be used to treat glaucoma.

Which of the 3 mechanismsused to treat glaucoma do these drugs use?
Similar to muscarinic agonists, increases trabecular outflow

"principal features": same features as muscarinic cholinergic agonists but more pronounced
high incidence of cataracts with chronic use
rarely used
Timolol, (non-selective) also levobunolol, carteolol, metipranolol

betaxolol (beta 1 selective)

These drugs are beta adrenergic antagonists that can be used to treat glaucoma.

Which of the 3 mechanisms used to treat glaucoma do these drugs use?
decrease aqueous humor formation (sympathomimetics increase aqueous humor formation so blocking the receptor decreases aqueous humor formation)

Principal features: good efficacy and widely used, can be combined with other drugs, possible systemic side effects include bronchoconstriction, bradycardia, hypotension,
Lung disease and diabetes possible contraindications

I believe Regan said timolol is most important drug in this class
Brimonidine and apraclonidine are alpha 2 adrenergic agonists that can be used to treat glaucoma.

Which of the 3 mechanisms used to treat glaucoma do these drugs use?
decrease aqueous humor formation (target presynaptic alpha 2 receptor, decrease norepinephrine so decrease aqueous humor production)

"principal features": similar effectiveness to PGF2alpha analogs (latanoprost, bimatoprost) and beta blockers (timolol). can be combined with other drugs. Possible systemic side effects such as sedation, hypotension. Dry mouth, altered taste. May be "neuroprotective"
acetazolamide (oral), dorzolamide (topical), brinzolamide (topical) are inhibitors of carbonic anhydrase that can be used to treat glaucoma.

Which of the 3 mechanisms used to treat glaucoma do these drugs use?
decrease aqueous humor formation

carbonic anhydrase is a very important enzyme is responsible for maintaining aqueous humor formation, so inhibiting it decreases aqueous humor formation.

Principal features:
side effects of oral administration greatly limit use of acetazolamide
topical agents can be used alone, but more often in combination with PGF2alpha analogs (latanoprost, bimatoprost) and beta blockers (timolol)
acetazolamide used for altitude sickness
Marijuana for glaucoma
Is it good for glaucoma treatment?
can lower IOP but effects only last 3 hours or it kinda sucks
T or F: variability in drug response is only due to genetic factors
F: age, sex, race, disease state, drug-drug interaction, and environment are other factors
Which of the CYPs has the largest phenotypic variability?
20-25% metabolized at least partially by CYP2D6
A poor metabolizer is treated with standard doses of metoprolol. What is the drug's effect on the patient?
ineffective? excessive?

What about an ultrarapid metabolizer?
Metoprolol is inactivated by CYP2D6, so the drug will have an excessive drug effect with a poor metabolizer

ineffective/inadequate therapeutic response for ultrametabolizer
a poor metabolizer is treated with standard doses of codeine. What is the drugs effect on the patient? ineffective? excessive?

what about an ultrarapid metabolizer
Codeine is metabolized to CYP2D6 to morphine.

Will have an ineffective/inadequate response in poor metabolizer

Will have excessive response in ultrarapid metabolizer
What is the difference between pharmacogenomics and pharmacogenetics?
Pharmacogenetics is monogenic, focusing on a single gene and its relation to drug response.

Pharmacogenetics is polygenic, focusing on multiple genes and their relation to drug response. A genome wide approach
For Dr. Tong's packet I would just go through his T or F questions that made.
I figure, no use in me making questions since he already did.