PHAR 736 Final Exam Structures Flashcards Preview

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Flashcards in PHAR 736 Final Exam Structures Deck (31)
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1
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Acetylcholine

2
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Muscarine

3
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Nicotine

4
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Physostigmine | Reversible AChE Inhibitor

Plant Natural product - used in 1877 for Glaucoma

Carbamoylated intermediate 10^10 fold more stable to hydrolysis than acetylated intermediate | AChE half-life for regeneration 3-5 minutes

5
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Neostigmine Bromide | Reversible AChE Inhibitor

Two Important Gruops: Quaternary ammonium, dimethylcarbamate

Half-life for regeneration 30-60 minutes

Used for Myasthenia Gravis

6
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Edrophonium Chloride | Reversible AChE Inhibitor

No group to transfer to active site serine | Can’t covalently modify the active site

Important groups: Quaternary ammonium

Short duration of action | often used to diagnose Myasthenia Gravis

7
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Donepezil | Non-covalent Reversible AChE | Alzheimer’s

Structure Importance: Two aromatic rings bind aromatic residues in AChE channel giving more affinity; structure developed base on crystal structue of AChE

Good AChE selectivity over BuChE

T1/2 greater than 70 hours | Once daily dosing | O-demethyl active metabolite (from 2D6 and 3A4) | significant aount excreted unchanged

8
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Rivastigmine | Reversible AChE Inhibitor | Alzheimer’s

Structure: Carbamate group (covalent modifier), S-enantiomer active

Lacks selectivity for AChE over BuChE

T1/2 = 1.5 hr | Extended, 10 hour duration of action | Dosed BID or QD as transdermal patch

9
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Galantamine | Non-covalent modifier | Isolated from daffodils | Alzheimer’s

Features help provide affinity for AChE | Some selectivity for AChE over BuChE

T1/2 = 7 hours | Dosed BID or QD as an ER formulation

10
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Huperzine A | Natural product form Chinese Club Moss | Reversible, non-covalent modifier | AChE Inihibitor

Structure: Primary amine that can be protonated | Aromatic ring

Considered a natraceutical | Unregulated in dietary and herbal supplements | Has pharmacological properties

11
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Echothiophate Iodide | Organophosphate | Irreversible AChE Inhibitor

Has thiocholine group

Phosphorylated-Serine (Di-ethyl) intermediate has half-life of regeneration of 8 hours | Aging can occur and results in resistance to hydrolysis and inactivation of AChE

Limited to use in eye for glaucoma and other conditions | Effects last days to weeks

12
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Sarin | Nerve Gas | Irreversible AChE Inhibitor

Bulkier group than O-Et

Slow regneration | Significant aging

13
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Malathion | Pro-drug Pesticide | Irreversible AChE inhibitor

Used to treat lice

Metabolism: Oxidized (slow in humans and insects) to Malaoxon, an effective AChE inhibitor, followed by breakdown with phosphatases (occuring slowly in insects); Plasma-carboxyesterases break cleave to inactive product fast in mammals

14
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Pralidoxime Chloride | AChE Reactivator

Aromatic ring and (+) charge give high selectivity for AChE | Hydroxylamine-like nucleophil needed to access modified serine

Can’t reactivate aged enzymes

15
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Verenicline | Nicotinic Partial Agonist | Full agonist at a7 containing receptors

16
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Cytisine

Plant natural product from Cytisus sp. | Used in Eastern Europe for Smoking Cessation

17
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SuccinylCholine | Depolarizing Neuromuscular Blocking Agent (all are symmetrical or dimer-like molecule)

Causes muscle paralysis | Rapid onset (1 minute) short duration (10 minutes)

Rapid hydrolysis by BuChE and plasma cholinesterases

Undesirable Side Effects: Hyperkalemia

18
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Tubocurarine | Non-depolarizing, competitive antagonist and Neuromuscular Blocking Agent

Plant natural product component of Curare

Contains Benzyl-isoquinolones

Long duration (80-120 minutes) | SEs include histamine release

19
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Cisatracurium Besylate | Nondepolarizing neuromuscular blocking agent

Protons alpha to carbonyl slightly acici, leading to easier deprotonation for the elimination reaction | 1R-cis 1’R-cis most effective enantiomer of original product, Atracurium

Intermediate duration (30-40 minutes) | No histamine release

Main route of inactivation is non-enzymatic Hofmann elimination | Some ester hydrolysis

20
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Pancuronium Bromide | Nondepolarizing Neuromuscular Blocking Agent (Ammonio Steroid)

Steroid backbone provides spacing between positive nitrogens

Long duration of action (2-3 hours) | Has 3-desacetyl metabolite, retaining some activity

21
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Vecuronium Bromide | Nondepolarizing Neuromuscular Blocking Agent (Amonnio Steroid)

Intermediate Duration (60-90 minutes) | Has 3-desacetyl metabolite

22
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Rocuronium Bromide | Nondepolarizing Neuromuscular Blocking Agent (Ammonio Steroid)

No 3-acetyl group | No active metabolites

23
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Sugammadex | SRBA (Selective Relaxant Binding Agent)

Positive charges on ammonio steroids (Rocuronium and Vecuronium) interact with negative charges lining the cavity of the cyclodextrin | Complex is excreted | Pancuronium has little affinity

24
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Dorzolamide | Carbonic Anhydrase Inhibitor

Designed to fit active site of Carbonic Anhydrase

Structure: Thiophene group; Aryl sulfonamide group (potential for hypersensitivity/sulfa reaction)

Used topically in the eye 2-3 times daily

25
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Brinzolamide | Carbonic Anhydrase Inhibitor

Structure: Thiophene group; Aryl sulfonamide group (potential for hypersensitivity/sulfa reaction)

Used topically in eye 2-3 times daily

26
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Prostaglandin F2a | Endogenous

Increases outflow of aqueous humor, lowering intraocular pressure

Limitations: Poor penetrance due to negatively charged carboxylate, Rapid metabolism (oxidized at C-15 hydroxy followed by further beta and omega oxidation)

27
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Latanoprost | Prostaglandin Analog Prodrug

Isopropyl ester and aromatic ring slow oxidation and increase penetrance into the eye

Long duration in eye with minimal side effects | T1/2 in plasma 17 minutes (beta oxidation)

28
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Latanoprostene bunod | Prostaglandin Analog | Dual-action Prodrug

Butanediolnitrate group cleaved to active | Latanoprost Acid + Nitric Oxide regulates IOP

29
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Travoprost | Prostaglandin Analog | Ester prodrug

Has trifluoromethyl

T1/2 in plasma (45 minutes)

30
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Bimatoprost | Prostaglandin Analog | Ethyl Amide Derivative (Prostamide)

Amide Prodrug

T1/2 Plasma (45 minutes)

31
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Tafluprost | Prostaglandin Analog | Isopropyl Ester Prodrug

Short Plasma T1/2 Due to Beta Oxidation

All prostaglandin analogs to treat glaucoma are dosed once daily