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242 Cards in this Set

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Define concussion.
Altered consciousness as a result of closed head injury. No parenchymal, CT, or MRI abnormalities. Includes confusion, amnesia, LOC, vacant stare, delayed verbal and motor responses, slow to answer questions or follow instructions, attention deficit, disorientation, altered speech, incoordination, exaggerated emotionality, memory deficits. Higher levels of glutamate. Brain becomes hyperglycolytic and hypermetabolic.
Define contusion.
Brain bruise as a result of sudden head deceleration causing the brain to impact bony prominences. May result in lingering neurological symptoms.
What is a contrecoup injury?
A contrecoup injury is injury to the brain under the point of impact as well as opposite the impact because of head returning to starting position.
Why are patients who have fallen off a motorcycle at high speeds usually rendered comatose in spite of no visible injury by imaging?

What are the pathologic hallmarks of this condition?
Diffuse axonal injury (microscopic tearing of axons) due to extreme torque on the brain occurs.

Retraction balls, microglial scars, small hemorrhagic foci
What is a linear fracture?

What is the clinical significance if this occurs in the skull?
A crack without displacement of bones.

For the skull to crack the trauma was likely great enough to damage the brain itself. The position is also important because it might cross the middle meningeal artery.
What is a comminuted fracture?
It is a shattered bone. It is difficult surgically because the surgeon must put all of the pieces back together correctly for proper healing.
What problems might a depressed skull fracture cause?
Hemorrhage, seizure, infection, laceration causing deficit
What is a compound fracture?

What site of infection is of concern?
A bone fracture with lacerated skin above it. High risk for infection.

Infection of the bone
What are the criteria for elevating a depressed fracture?

What is the exception to these criteria?
1. Depression greater than skull thickness
2. Deficit related to underlying brain injury
3. CSF leak
4. Compound fracture

Depressed piece of bone pressing on a dural sinus
What are the clinical hallmarks of basilar skull fractures?
Raccoon eyes
Battle sign
Leakage of spinal fluid out nose
Deficits in CN VII and VIII
What are two strong vital sign predictors of poor outcome after traumatic brain injury?
1. Prehospital hypotension
2. Prehospital hypoxia
What is the Monro-Kellie hypothesis?
The intracranial volume is composed of blood, brain, and CSF. If one increases, another must decrease or else ICP will rise.
What is the cerebral perfusion pressure? Why is it significant?
CPP=MAP-ICP

It is significant because if ICP increases, MAP must increase as well in order to maintain perfusion of the brain and avoid ischemic injury.
What are the two types of cerebral edema?
1. Cytotoxic edema- intracellular
2. Vasogenic edema- interstitial
What is Cushing's Triad?
It is the trio of symptoms present with unrestrained increases in ICP

1. HTN
2. Bradycardia
3. Respiratory irregularity
What are the three pharmacologic methods of reducing brain volume?
1. Mannitol
2. Hypertonic saline
3. Lasix
What is the effect on the brain of barbiturates?
Drastically slowed metabolism -> decreased ICP -> medical coma
Describe the basic structure of catecholamines.
Benzene ring with two adjacent hydroxyl groups and an amino group
From what substance are catecholamines synthesized?
Tyrosine
Name the intermediates between phenylalanine and epinephrine.
Phenylalanine -> Tyrosine -> Dopa
-> Dopamine -> Norepinephrine -> Epinephrine
What enzyme is mutated in PKU?
Phenylalanine hydroxylase
What is produced when tyrosine decarboxylase acts on tyrosine?
Tyramine
What is the rate-limiting step in catecholamine synthesis?

What type of poisoning leads to inhibition of this enzyme?
Tyrosine -> L-Dopa by tyrosine hydroxylase

Lead
How is tyrosine hydroxylase regulated?
Short term: Phosphorylation (activation)

Long term: Transcriptional regulation
What process is increased by amphetamines?
Conversion of L-Dopa to dopamine
What enzyme converts norepinephrine to epinephrine?
Phenylethylamine-N-methyl transferase
Name two inhibitors of MAO-B and describe the effect of this inhibition.
1. 1-deprenyl
2. Nicotine

Increase 1/2 life of dopamine
What molecule is an indicator of dopamine activity in the CNS?

Norephinephrine activity?
Homovanillic acid

MHPG
What area of the brain is associated with the dopamine rush of drugs or addiction?
Nucleus accumbens
What is the main pharmacologic effect of cocaine?
Inhibition of norepinephrine transporter (for reuptake of norepinephrine)
What is a contaminant of Demerol? What is the effect of this contaminant?
MPTP

Parkinson-like syndrome, due to death of dopaminergic neurons
What are the physiologic effects of stimulation of alpha-1 adrenergic receptors?
Vasoconstriction
Mydriasis

Alpha-1a agonism relaxes the bladder
What is the cellular effect of alpha-2 adrenergic receptors?
Inhibition of norepinephrine release

Inhibition of release of other neurotransmitter- alpha-2 is called a heteroceptor
What are the physiologic effects of beta-1 receptor activation?
SA node: Tachycardia, positive chronotropic effect (increased heart rate)
AV node: faster conduction
Atria: positive ionotropic effect (increased force of contraction)
Ventricle: positive ionotropic effect
What are the physiological effects of beta-2 receptor activation?
Arteriolar dilation (by skeletal muscle)
Bronchodilation
What receptors are found in skeletal muscle vascular beds?

Other vascular beds?
Beta-2

Alpha-1 and Beta-2
What receptors are stimulated by phenylephrine?
Alpha-1
What receptors are stimulated by norepinephrine?
Alpha-1 and Beta-1
What receptors are stimulated by epinephrine?
Alpha-1, Beta-1 and Beta-2
What receptors are stimulated by isoproterenol?
Beta-1 and Beta-2
Where are D1 dopamine receptors found?
Renal, coronary, and cerebral vascular beds
Describe the differences between low and high dose use of dopamine.
Low doses of dopamine (or fenoldopam) will produce vasodilation. Useful for treating HTN.

Higher doses will engage beta and alpha-1 receptors, resulting in a positive inotropic effect. Useful for hypotensive crisis.
If a drug raises systolic blood pressure without raising diastolic, what is its effect on the arterioles?
No effect
What is the effect of a positive inotrope on pulse pressure?

Negative inotrope?
Increase

Decrease
What nerve mediates the cardiac reflex after increased blood pressure?
Vagus (ACh release), slow heart rate
What is the cardiac reflex after decreased blood pressure?
Sympathetic (adrenergic), increase heart rate
Do cardiac reflexes react to changes in mean blood pressure or pulse pressure?
Mean blood pressure
What receptor does phenylephrine antagonize? What physiologic action follows?
Alpha-1

Constriction of arterioles
-elevated diastolic and systolic
-compensatory decrease in HR
What are the three therapeutic uses of phenylephrine?
1. Nasal decongestion
2. Pressor agent in hypotensive states
3. Mydriasis
What receptors does norepinephrine act on? What is the physiologic effect?
Beta-1 and alpha-1

Positive inotropic effect, arteriole constriction, increased diastolic and pulse pressures. Heart rate is decreased because although beta-1 agonism increases the heart rate, it is mitigated by the vagal reflex.
What is the effect of atropine on the heart?
Heart rate goes up because the vagal reflex is disabled.
What receptors does epinephrine act on? What is the physiologic effect at moderate doses? at high doses?
Beta-1, Beta-2 and Alpha-1

Moderate doses: Stimulated heart rate, increased pulse pressure and systolic pressure, vasodilation in skeletal muscle + vasoconstriction elsewhere=decreased peripheral resistance -> decreased diastolic

High doses: increase in mean blood pressure and pulse pressure, vasoconstriction, bronchodilation
What receptors does isoproterenol act on? What is the physiologic effect?
Beta-1 and Beta-2

Arteriole dilation, decreased diastolic pressure, heart rate is driven up by sympathetic reflex and positive inotropic effect
What are the therapeutic uses of isoproterenol?
1. Stimulation of AV conduction
2. Bronchodilation
What is the physiologic effect of cocaine?
Sympathetic stimulation of the heart, mydriasis, elevated blood pressure, hyperthermia (typical of excessive increase of norepinephrine)
What is a clinical use of cocaine?
Hemostasis during nasal or throat surgery
What is the action of propranolol?

An effect of what drug will be mitigated by this? What specific effect?
Blocking of beta-1 receptor

Cocaine, propanolol will decrease the elevated heart rate
Is a light reflex present in the eyes of a cocaine user?
Yes
Cocaine potentiates the action of what neurotransmitter?
Norepinephrine
What are the cellular effects of amphetamines?
Blocking dopamine and norepinephrine reuptake and increasing their release. This action is accomplished by reversing the direction of dopamine and norepinephrine transporters.
What are the physiologic effects of amphetamines?
Arousal, euphoria, appetite suppression, restlessness, tremor, insomnia, anxiety
What is methylphenidate? What is it used for?
Methylphenidate is an amphetamine variant used to treat ADD.
What is tyramine?
Tyramine is an endogenously produced indirect sympathomimetic which is taken up by norepinephrine or dopamine transporters and then releases norepinephrine or dopamine from storage.
How is the action of tyramine blocked?
Deplete norepinephrine and dopamine stores (reserpine)

Inhibit dopamine and norepinephrine transporters (cocaine)
Where do direct sympathomimetics act?

Indirect?
Post-synaptic receptor

Pre-synaptic terminal
What are the physiologic effects of pseudoephedrine?
Vasoconstriction, inhibition of mucosal glands, HTN, cardiac arrhythmia
How can pharmacologic agents be used to determine whether a lesion is pre- or post-ganglionic?
If the lesion is pre-ganglionic, assume that the terminal is still functional. Cocaine can be administered to inhibit NET, so the pupil should respond by dilating.

If the lesion is post-ganglionic, then there will be no effect.
How does methyl dopa act?
Methyl dopa enters the adrenergic terminal and interacts with dopa decarboxylase, resulting in the production of methyl noradrenaline. Methyl noradrenaline binds more tightly than noradrenaline to the alpha-2 receptor, which prevents further noradrenaline release, decreasing blood pressure.
Name some side effects of methyl dopa.
Diarrhea
Ejaculation failure
Postural hypotension (decreased venous return, cardiac output, blood pressure)
How does clonidine act?
Clonidine is an alpha-2 receptor agonist, so it decreases norepinephrine release, decreasing blood pressure.
What is a paradoxical side effect of clonidine?
Bradycardia, due to imidazoline receptor binding
What happens when a patient stops taking clonidine abruptly?

Why does this happen?

How can this be treated?
Rebound HTN- may manifest as confusion and headaches

This happens because the alpha-1 receptor is upregulated in the absence of norepinephrine, so the system becomes super sensitive to sympathetic activity.

Alpha-1 blocker (HTN) and beta-1 blocker (HR)
How does guanethidine act?
It is pharmacologically inert but depletes adrenergic neurons of norepninephrine. It is taken up by norepinephrine transporter and is released upon sympathetic stimulation, in the place of norepinephrine. It results in a greater decrease in BP than clonidine or methyl dopa.
What are the adverse effects of guanethidine?
Similar to but more severe than clonidine and methyl dopa
Which sympatholytic agents can cross the BBB?
Clonidine and methyl dopa
What enzyme does metyrosine inhibit?
Tyrosine hydroxylase, thereby preventing dopa synthesis
What is pheochromocytoma?
An adrenal tumor that secretes large amounts of epinephrine and norepinephrine.
What is used to prevent norepinephrine release in pheochromocytoma?
Phentolamine

Metyrosine would also be useful
What is the relationship between pharmacological effect of sympathetic blockers and sympathetic tone?
When there is more sympathetic tone, the magnitude of the effect is greater. When there is less sympathetic tone, the effect is smaller.
What is the classic alpha-2 blocker?

What is its effect?
Yohimbine

Blocking inhibition, resulting in increased norepinephrine release.
Name two drugs that block both alpha-1 and alpha-2 receptors.

Name one that blocks only alpha-1 receptors.
1. Phentolamine (reversible/competitive)
2. Phenoxybenzamine (irreversible)

1. Prazosin
Which has a greater reflex tachycardia: phentolamine or prazosin?
Phentolamine because with prazosin, the alpha-2 receptor is not blocked so some norepinephrine is still released, resulting in a smaller increase in heart rate.
What are the clinical uses of alpha-1 blockers?
Prevention of NE necrosis
Essential HTN
Difficulty urinating
What are some side effects of alpha-1 blockers?
Miosis
Nasal congestion
Diarrhea
Sexual dysfunction
Postural hypotension
Light headedness
Reflex tachycardia
What are beta blockers used for?
Angina, chest pain, essential HTN, cardiac arrhythmias
Do alpha and beta blockers have any intrinsic activity?
No
What is the response of heart rate to the decrease in BP after a beta-1 blocker is administered?
No change
Name a drug that agonizes both beta-1 and beta-2 receptors.

Name a drug that agonizes beta-2 receptors mainly.
Isoproterenol

Albuterol
What is a therapeutic use of beta-2 agonists?

Adverse effect?
Bronchospasm of asthma

Cardiac stimulation
What are the desired and undesired actions of beta blockers?
Beta-1 blocking is the desired action and beta-2 blocking is undesired. Unfortunately, all beta blocking agents block beta-2.
What is a broad spectrum beta blocker?

What beta blocker is cardio-selective and prefers beta-1 to beta-2?

What beta blocker also has alpha-1 blocking action?
Propanolol

Atenolol

Labetolol
What is a major side effect of propanolol?
Asthma attack
Which beta blocker causes a greater increase in bronchiolar tone: propanolol or atenolol? Why?
Propanolol does because it binds beta-2 equally as well as it binds beta-1. Atenolol, on the other hand, has its primary effect on the heart because it has higher affinity for beta-1 than for beta-2 (pulmonary).
Describe the action of pindolol.
It has strong blocking action at beta-1 and beta-2 with weak agonist action at the same receptors. Pindolol displaces norepinephrine from beta-1 and beta-2 receptors and binds very tightly. It has slight agonist action on the receptors. This weak agonist effect is preferable to the action of norepinephrine.
What is the advantage of using pindolol in patients with some pulmonary conditions?
Because pindolol has a weak agonist effect on beta-2 receptors, the bronchioles are actually dilated with medication, instead of constricted as with other beta blockers.
Describe epinephrine reversal.
When high dose epinephrine is administered, the alpha-1 effect is greater than the beta-2 effect. However, if an alpha-1 blocker is administered, the alpha-1 effect will be lost and the beta-2 vasodilation will predominate, lowering the blood pressure.
What receptors are blocked by labetolol?
Alpha-1, beta-1, beta-2
Is the optic nerve located more laterally or medially?
Medial
What are the layers of the cornea?
1. Epithelium
2. Basement membrane
3. Stroma
4. Basement membrane
5. Endothelium monolayer
Where are stem cells found in the eye?
Limbus
What is the difference between the cornea and the sclera?
They are made of the same material, but the fiber arrangement and hydration levels are different such that the cornea is transparent and the sclera isn't.
What is the function of the conjunctiva?
Tear production, lubrication, vascularization
What are the components of the uvea?
Choroid
Iris
Ciliary process
What is the function of the choroid?

What is a common pathology of the choroid?
Provide nutrition and oxygen to the posterior five layers of the retina.

Vasculature leaks in Age Related Macular Degeneration
What is the function of the ciliary body?
Production of aqueous humor
Accommodation of the lens
How is aqueous humor drained?

Name the disorder in which drainage is blocked.
Aqueous humor flows through the trabecular meshwork and into Schlemm's canal.

Glaucoma
What type of tissue surrounds the lens?
Epithelium
Where in the eye are cataracts found?
In the lens due to opacity of lens tissue
What are the ten layers of the retina?
1. Retinal pigment epithelium- monolayer in front of choroid, most metabolically active cells in body
2. Photoreceptor layer- rods and cones
3. External limiting membrane
4. Outer nuclear layer- nuclei of photoreceptors
5. Outer plexiform layer- synapse of photoreceptors with bipolar cells
6. Inner nuclear layer- cell bodies of bipolar cells
7. Inner plexiform layer- synapse of bipolar cells and retinal ganglion cells
8. Ganglion cell layer
9. Nerve fiber layer- Axons of retinal ganglion cells running to optic nerve
10. Inner limiting membrane

Mnemonic: Receiving perfect exams over other interns is good news indeed.
What is the macula?

What is a pathology of this area?
The macula is a 3-4 mm area of the retina with the highest concentration of cones

Age Related Macular Degeneration
How many cones to each retinal ganglion cell in the macula?
1
What is the fovea?
Central part of the macula

There is a dip with only cones in the center 0.5 mm, with no capillaries in the middle 0.3 mm.
Where does the optic tract end?
Lateral geniculate body (nucleus of the thalamus)
What structure is found posterior to the optic chiasm?
Infundibulum
What is neuron 1 in the central visual pathway?

Neuron 2?

Neuron 3?
1. Bipolar cell
2. Ganglion cell (axons form optic nerve)
3. Lateral geniculate body
Are the occipital lobes responsible for the ipsilateral halves of the visual field, or the contralateral halves?
Contralateral
Where in the PLIC does the visual pathway course?
Retrolentiform/most posterior part
What is the course of the optic radiations?
Through posterior parietal lobe or temporal lobe (Meyer's loop), surrounding posterior horn of lateral ventricle.
Which part of the visual field travels through the temporal lobe?

Parietal lobes?
Upper quadrants of the visual field

Lower quadrants of the visual field
What two pathways leave the visual association cortex?
What- goes to temporal visual association cortex

Where- goes to multimodal association cortex
Where is the macula represented in the visual cortex?
Most posteriorly in a disproportionately large area
What is effect of a lesion of the optic nerve?
Anopsia of ipsilateral eye
What is the effect of a lesion of the central optic chiasm?
Bitemporal hemianopsia
What is the effect of a lesion of the optic tract?
Contralateral homonymous hemianopsia
What is the effect of a lesion of the entire optic radiation?
Contralateral homonymous hemianopsia
What is the effect of a lesion of the Meyer's loop?
Superior (contralateral homonymous) quadrantanopsia
What is the effect of a lesion of the optic radiation going straight back to the occipital lobe?
Inferior (contralateral homonymous) quadrantanopsia
What is the effect of a lesion of the visual cortex?
Contralateral homonymous hemianopsia
What is the path of the pupillary light reflex?
Optic nerve - optic chiasm - optic tract - midbrain (superior colliculus) - pretectal area (pupillary reflex) - EW nucleus (some fibers ipsilateral, some cross via posterior commissure to contralateral) - CN III - ciliary ganglion - sphincter pupillae
What are the two ways that the pupillary light reflex becomes bilateral?
1. The nasal fibers will cross at the optic chiasm and go to the contralateral pretectal area.
2. After the pretectal area, some fibers cross via the posterior commissure to the contralateral EW nucleus.
What happens to the pupillary light reflex if the optic nerve, optic tract, or pretectal area are damaged?
?
What is the path of the accommodation reflex (near triad)?
Retina - optic nerve - optic chiasm - LGB - optic radiations - primary visual cortex - accomodation center (superior midbrain) - EW nu. and III motor nu. - CN III - ciliary ganglion - ciliary ganglion - sphincter pupilae and ciliary muscle

or

Retina - optic nerve - optic chiasm - LGB - optic radiations - primary visual cortex - accomodation center (superior midbrain) - EW nu. and III motor nu. - CN III - medial rectus
What are the three changes that happen with the accommodation reflex?
1. Adduction
2. Lens becomes convex
3. Pupil contracts
What is Argyle Robertson Pupil?
The accomodation reflex is present but the pupillary reflex is absent. This is a sign of tertiary syphilis. The lesion is believed to be in the pretectal area.
Describe the pathology of ARMD.
Drusen deposits, senescence and dysfunction of RPE, vision loss due to photoreceptor damage secondary to RPE dysfunction
Which type of ARMD is more common: wet or dry?
Dry (90%) of cases
Describe dry ARMD.
-RPE senescence
-Drusen accumulation between RPE and Bruch's membrane
-RPE atrophy and pigment clumping (Geographic Atrophy)
What are the treatments for dry ARMD?

Wet ARMD?
Follow with Amsler grid
Antioxidant vitamins
In the works: human embryonic stem cell transplant

Photodynamic therapy
Anti-VEGF drugs
Describe wet ARMD.
-starts as early dry ARMD
-neovascularization from choroid into subretinal space
-fluid leakage and hemorrhage
What are the risk factors for ARMD?
-Age
-Family hx
-CV risk factors
-Oxidative damage
-Chronic inflammation
-Complement Factor H polymorphisms
What are the signs and sx of ARMD?
1. Blurry vision
2. Image distortion
3. Central scotoma
4. Difficulty reading- use of magnifying glass
5. Difficulty driving
Describe glaucoma.
Increased IOP resulting in damage to ganglion cell axons, leading to optic atrophy and peripheral visual field loss. This occurs due to inadequate drainage of the anterior chamber.
In what group of people is glaucoma the most common cause of blindness?
African Americans
What is normal IOP?
22 mmHg
What are the two major types of glaucoma? Which is more common?
Primary open angle glaucoma- chronic problem, late diagnosis shows visual field loss, 95% of cases

Acute closed angle glaucoma- iris occludes Schlemm's canal, people with shallow anterior chamber are predisposed
What are the presenting signs and symptoms of POAG?

ACAG?
Late:
1. Visual field loss
2. Blurry vision
3. Halos around lights (due to corneal edema)

1. Nausea
2. Vomiting
3. Intense pain
How is POAG managed?
1. Observation of IOP (3-6 mo.)
2. Visual field exam (6-12 mo.)
3. Gonioscopy and optic nerve exam
4. Trabeculoplasty
5. Trabeculectomy
6. Glaucoma drainage implant
How is ACAG managed?
1. Constrict the pupil
2. Hyperosmotic agents (glycerol, mannitol)
3. Peripheral laser iridectomy
Describe the pathology of cataract.
-Lens opacities impeding vision
-Can be caused by UVB exposure
-Result from systemic diseases
What are the two major types of cataracts?
1. Cortical degeneration: opacities radiate in from periphery due to swelling and liquefaction of young cortical fiber cells

2. Nuclear sclerosis: opacity in center of lens, with discoloration due to deterioration of older cortical fiber cells
What are the presenting symptoms of cataracts?
1. Blurry vision
2. Glare
3. Monocular diplopia
4. Myopia
5. Second sight (no longer need reading glasses)
How are cataracts managed?
Elective cataract extraction and insertion of intraocular lens.

Dilation for those for whom surgery isn't appropriate.
What are the two types of diabetic retinopathy?
1. Proliferative: neovascularization extending into the vitreous and bleeding, exudates, retinal detachment, hemorrhage

2. Non-proliferative: early stage, venous dilation, A/V nicking, microaneurysms resulting in dot-blot appearance of retina, macular edema
What are the presenting symptoms of diabetic retinopathy?
Blurry vision, floaters, visual field loss, poor night vision
How is diabetic retinopathy managed?
1. Blood glucose control
2. DM monitoring
3. Monitoring of co-existing conditions
4. Yearly retinal exam
5. Photocoagulation
6. Surgical vitrectomy
What is the effect on the eye of phentolamine?
Constricted pupil
What are the two classes of drugs that will produce miosis?
Parasympathomimetic (pilocarpine)
Alpha-1 blocker (phentolamine)
What are the two classes of drugs that will produce mydriasis?
Muscarinic blocker (atropine)
Alpha-1 agonist (phenylephrine)
What would be the effect of alpha-1 blockers or agonists on accomodation?
Nothing because it is entirely under PSP control.
What is cycloplegia?
Paralysis of the ciliary muscle resulting in loss of near accomodation
What would be the effect of muscarinic blockers or agonists on accomodation?
Blocker: ciliary muscle would be relaxed, therefore near vision would be blurred but far vision would be okay

Agonist: ciliary muscle would be contracted, therefore far vision would be blurred but near vision would be okay
Is the pupillary light reflex under sympathetic or PSP control?
PSP
Will a patient with Horner's syndrome be able to accomodate?

Have a light reflex?

What will the pupil look like?
Yes

Yes

These are under PSP control

Pupil will be constricted.
What agent is used to dilate eyes by the ophthamologist for a standard exam? Why is this used?

What might the ophthamologist use to constrict the patient's pupil after the exam?
Tropicamide, because the duration of action of atropine is several days, rather than hours.

Pilocarpine
Why is physostigmine used in the eye rather than neostigmine?
Physostigmine is a tertiary amine and neostigmine is a quarternary amine. Tertiary amines are lipid soluble and cross membranes better, so physostigmine is preferred.
What is a side effect of ophthamologic use of irreversible ChE inhibitors?
Cataract formation
What pharmacologic agents can be used to treat Acute Closed Angle Glaucoma?
Pilocarpine
Physostigmine
What pharmacologic agents can be used to treat POAG? What is their mechanism of action?
Parasympathomimetics: increase outflow by contracting ciliary muscle and increasing porosity of trabecular network

Carbonic anhydrase inhibitors (dorsolamide): decrease bicarbonate production, decreasing aqueous production

Beta blockers (timolol, betaxolol): inhibit aqueous formation- betaxolol is preferred to minimize bronchoconstriction

Prostaglandin analog (latanoprost): increases uveoscleral outflow of aqueous

Alpha-2 agonist (aproclonidine): decreases aqueous formation and facilitates uveoscleral drainage by unknown mechanisms

Marijuana: decreases IOP by unknown mechanisms
How can systemic side effects of opthamologic pharmacologics be minimized?
Block the lacrimal duct after administration of the drug to prevent drainage to the rest of the body.
Why isn't propanolol used for glaucoma treatment?
It has a local anesthetic effect with dulls the blink reflex, so the eye is left unprotected.
What is a side effect of ophthamologic use of latanoprost?
Iris pigmentation, and eyelash growth and thickening
Where is the area of the highest visual acuity?
Macula
Describe the process by which photoreceptor cells transmit a signal.
In its resting state, a photoreceptor cell is depolarized with open calcium channels, allowing calcium entry. In this state, glutamate is released.
Light causes a drop in cGMP, proportional to the amount of light, resulting in calcium channel closure and graded hyperpolarization. Glutamate release is proportionally suppressed.
How are photons sensed?
11-cis retinal (vitamin A derivative) is combined with opsin to produce rhodopsin in the RPE cells. When 11-cis retinal is hit by a photon, it is converted to all-trans retinal, changing the conformation of rhodopsin. Rhodopsin activates transducin with GTP, which will result in hydrolysis of cGMP.
What type of receptor is rhodopsin?
GPCR
How do photoreceptor cells reset after sensing light?
The decreased intracellular calcium level stimulates cGMP formation so the calcium channels will reopen. Protein kinase and arrestin deactivate rhodopsin. All-trans retinal will be sent back to the RPE to be isomerized to 11-cis retinal.
What cell type is necessary for the cycle of visual signal transduction?
RPE, because it isomerizes all-trans retinal to 11-cis retinal.
Which type of photoreceptors are more light-sensitive?
Rods
Besides isomerization of retinal, name two functions of the RPE.
Phagocytosis of outer segments of photoreceptors every morning. Secretion of growth factors.
Mutations in which proteins can cause blindness? Name the corresponding disease.
1. Rhodopsin- retinitis pigmentosa
2. GRK and arrestin- Oguchi's disease/congenital stationary night blindness
3. Transducin- Nougaret's congenital stationary night blindness
4. Phosphodiesterase- retinitis pigmentosa
5. Guanylate cyclase- Leber's congenital amaurosis
How do receptor fields allow us to see edges?
Firing rate differences between ganglion cells are exaggerated at edges.
Why is red/green color blindness so common in males?
There is a high degree of homology between the red and green cone genes and they are located near one another on the X chromosome. During homologous recombination, both copies of one gene may be left on one copy of the chromosome, leaving the other copy without one of the genes.
What is the precursor for serotonin?
Tryptophan
Describe the biosynthesis of serotonin.
Tryptophan hydroxylase produces 5-hydroxy-tryptophan from tryptophan. This is then decarboxylated, forming serotonin.
How is serotonin metabolized?
MAO converts serotonin to an aldehyde. This is acted on by aldehyde dehydrogenase to form 5-HIAA, which is measured as an indication of serotonergic activity.

Alternatively, it can be acetylated and methylated to form melatonin.
Which serotonin receptor is not a GPCR?
5-HT3, which is a receptor Na ionophore.
There is a higher frequency of intron 7 A218C in what illness?
Manic depression
Where does LSD act?
Serotonergic receptors
Low levels of 5-HIAA are associated with what?
Agressive, criminal and suicidal tendencies
What receptor does ecstasy act on? What is a possible adverse effect of ecstasy use?
5-HT, by an indirect mechanism. Causes loss of serotonergic neurons.
Where in the brain is histamine produced?
Tuberomammillary nucleus of the hypothalamus
What is the metabolic fate of histamine?
Methylation, followed by oxidation and then acetylation
What is the precursor to histamine?
Histidine
What are the major functions of each of the four histamine receptors?
1. H-1: bronchoconstriction
2. H-2: regulate adenylate cyclase, antagonists block gastric acid secretion
3. H-3: Autoreceptors
4. H-4: Present on leukocytes
What does histamine do in the hypothalamus?
Alter food and water intake, and thermoregulation
Why do psychotropic and antipsychotic medications cause sedation?
They are H1 receptor antagonists.
Long-term use of antagonists of what neurotransmitter receptors may contribute to Alzheimer's?
H-1
What neurological conditions are associated with GABA?
Epilepsy, schizophrenia, tardive dyskinesia, Huntington's
What are the two major locations of GABA?
Purkinje cells, spinal cord
What enzyme converts glutamate to GABA?
GAD

This is the regulatory enzyme in GABA formation.
What type of receptor is GABA receptor?
A: Chloride channel, closed by GABA binding

B: Use second messengers to monitor GABA concentration
What receptor does benzodiazepam act on? What is an antagonist of this receptor?
GABA-A

Bicuculline (convulsant)
Name a non-competitive GABA-A receptor antagonist. What is it used for?
Picrotoxin

Antidote for barbiturate poisoning
What do low levels of alcohol do to GABA receptors?

What is the connection between valium and alcohol use?
Increase activity.

People react similarly to the two, likely due to GABA-A receptor composition.
What is gamma hydroxybutyrate?
It is a breakdown product of GABA. It is available on the street as liquid ecstasy. Toxicity includes coma, seizures, vomiting, respiratory depression, and amnesia.
Name two antagonists of glycine receptor.
Strychnine: plant alkaloid, competitive antagonist, convulsant

Picrotoxin: non-competitive inhibitor, antidote for barbiturate poisoning
What is the major function of glycine?
It is the major inhibitory transmitter in the brain stem and spinal cord, acting predominantly with short axon interneurons.
What causes Human Startle Disease?
Single base mutation in glycine receptor, resulting in 100-fold decrease in glycine affinity.
How do benzodiazepines act?
They bind the GABA receptor and potentiate existing signaling.
How are benzodiazepines metabolized?
Oxidation and glucoronidation in the liver for renal excretion.

Some of these metabolites are active benzodiazepines.
What are benzodiazepines used for?
Sedation, muscle relaxation, sleep induction, anti-anxiety, adjunctive in anesthesia, control of jet lag
What are some of the side effects of benzodiazepines?
Psychomotor and respiratory depression, loss of self-control, anterograde amnesia
What is the antidote for benzodiazepine overdose?
Flumazone
Why aren't benzodiazepines generally prescribed for long periods of time?
Tolerance leading to dependence
What are some specific indications for benzodiazepines?
Situational anxiety/adjustment disorder

Generalized anxiety disorder
Can benzodiazepines be stopped abruptly?
No, they should be tapered. Those with longer half-lives may be stopped faster.
What drug blocks both serotonin and norepinephrine reuptake?
Venlafaxine
Where and how do 5-HT1a and 5-HT1b receptors act?
They are both inhibitory autoreceptors on the pre-synaptic neuron. 1a is on the cell body and 1b is at the terminal.
What types of anxiety are SSRIs useful for? What is the drawback and how do you get around it?
General Anxiety Disorder, Panic Disorder, Social Phobia

Take 3-4 weeks to act, so benzodiazepines can be used in the meantime. This drawback is thought to be a result of the excess serotonin in the synapse acting on the 5-HT1a/b receptors.
What is the first line of treatment for PTSD?

What are good adjunctive agents?
SSRIs, peroxitine and sertraline in particular

Antiadrenergics, clonidine and propranolol
What is the only therapy for obsessive-compulsive disorder?
SSRIs like imiprimine, venlafaxine.

This is effective about 50% of the time.
What can be used to treat stage fright?
Beta blockers
What is buspirone?
It is a partial 5-HT1a agonist, which should downregulate serotonin release. It is thought to work by downregulating this receptor, causing more serotonin release. It is an anxiolytic, although the patient does not notice the same improvement that others do.
Where does strychnine act?
Glycine receptor (gated chloride channel)- antagonist

In the spinal cord
What is the effect of strychnine?
What is its primary use?
General excitation of the CNS due to disinhibition. Results in hyperreflexia.

No clinical use- used as a pesticide
What are the toxic effects of strychnine?

How is this treated?
Tonic extension of body and limbs, respiratory impairment, tetanic convulsions, postictal depression and hypoxia

1. Administer central depressants to control convulsions
2. Respiratory support
3. Lavage with charcoal, KMnO4, tannin
Describe the mechanism of action, effects, clinical use, and toxicity of picrotoxin.
Mechanism: Blockade of GABA receptor chloride channels (esp. in brain)

Effects: CNS excitation due to disinhibition

Clinical use: Treatment of CNS depressant OD (not used anymore)

Toxicity: Uncoordinated tonic-clonic convulsions with coma and death. Treat by the same methods as strychnine.
Describe the mechanism of action, effects, clinical use, and toxicity of pentylenetetrazole/metrazole.
Mechanism: Blockade of GABA receptor chloride channels (esp. in brain)

Effects: CNS excitation due to disinhibition

Clinical use: Activation of EEG during seizure disorder diagnosis and for anticonvulsant drug screening.

Toxicity: Uncoordinated tonic-clonic convulsions with coma and death. Treat by the same methods as strychnine.
Name the three major xanthines.

What is their general mechanism of action?
1. Caffeine
2. Theophylline
3. Theobromine

Blockade of adenosine receptor causing elevation of intracellular calcium. This has a stimulant effect.
What are the effects of xanthines?
Alertness, reduction of drowsiness and fatigue. Bronchial smooth muscle relaxation, increase in gastric acid secretion. Diuresis.
High doses will produce nervousness, insomnia, tremors, nausea, emesis increased heart rate, increased blood pressure and hyperesthesia.
Very high doses will produce convulsions, especially with theophylline.
What are the clinical uses of xanthines?
Theophylline: bronchodilator in asthma
Others: treatment of apnea in premature infants, additive in headach and migraine prescriptions
Describe xanthine toxicity.
This is very rare but includes excitement progressing to delirium, emesis, convulsions, tachycardia, arrhythmias, premature ventricular contractions. Treated with diazepam with barbiturates or anticonvulsants and lavage.
What are the three major types of amphetamines?
1. Benzedrine: racemic mixture of L and D isomers
2. Dexedrine: D isomer
3. Methamphetamine/methedrine: amphetamine derivative with potent CNS stimulation and fewer side effects
Describe the mechanism of action of amphetamines.

How are they metabolized?
Mechanism: Stimulate dopamine and norepinephrine release and block reuptake

Low dose: norepinephrine-specific
High dose: striatal dopamine (motor)
Higher dose: mesolimbic dopamine and serotonin (psychosis and hallucination)

They are not metabolized by MAO or CMT. At high concentrations the are methylated or hydroxylated, but these metabolites are still hallucinogenic.
What class of drugs does amphetamine fit into? What are its effects?
Sympathomimetic

1. Euphoria
2. Hyperactivity
3. Insomnia, prevention of narcolepsy
4. Anorexia
5. Medullary respiratory center stimulation
6. Psychosis (with chronic use)
7. Increased BP, reflex bradycardia, some arrhythmia
What are the three major clinical uses of amphetamines?
1. Narcolepsy
2. ADHD
3. Obesity
What are the toxic effects of amphetamine?

How can these toxic effects be treated?
Acute: Nervousness, hyperactivity, insomnia, tremor, sweating, anorexia, euphoria, convulsion, coma, fatigue, depression, rebound sleep, angina, HTN, arrhythmias, circulatory failure

Chronic: psychosis, motor stereotypy, necrotizing arteritis, addiction

Treatment: Dopamine receptor antagonist, alpha-adrenergic antagonist, sodium nitroprusside, ammonium chloride (to acidify urine and increase elimination rate)
What are two stimulant drugs that act similarly to amphetamine and are used to treat ADHD?
1. Methylphenidate/Ritalin
2. Pemoline
What are two ephedrine derivatives used to treat nasal congestion?
1. Phenylephrine
2. Pseudoephedrine
Describe the mechanism of action and effects of nicotine.
Mechanism of action: Acts at alpha-4/beta-2 and alpha-7 nicotinic receptors in the CNS. It increases dopamine release in the nucleus accumbens, resulting in euphoria. Stimulant action is attributed to norepinephrine and epinephrine release. It may desensitize nicotinic receptors, resulting in a depressive effect.

Effects: Alertness, euphoria, muscle relaxation, appetite reduction, biphasic sympathomimetic effect, GI motility, biphasic salivary response, cause inappropriate gene expression in hypothalamus of developing fetus
What are some clinical uses of nicotine?

Name three toxic effects.

How is toxicity treated?
1. Alzheimer's
2. Self-medication in schizophrenia and Parkinsonism

Toxicity:
1. Tremor and convulsions
2. CNS depression and respiratory failure
3. Emesis

Treatment: Vomiting, activated charcoal, respiratory support
Name two pharmaceuticals that can help in quitting smoking.
1. Clonidine
2. Bupropion