pharmacology midterm

• erectile dysfunction
• e.g. sildenafil

nAchR agonist, mAchR agonist

choline ester: major hydrolysis by AchE

initiates local depolarization at synaptic region via ligand-gated ion channels

taken up into synaptic terminal

blocks release of Ach via proteases

blocks Ca release from SR

used to counteract malignant hyperthermia caused by succinylcholine excess

partial agonist of nAchR

i.e. depolarizing blocker

first activates, then desensitizes

AchE inhibitor

non-covalent, rapidly reversible

half-life: ~few minutes (i.e. short acting)

used as diagnostic for myasthenia gravis

blocks choline uptake

depletes Ach

organic phosphate --> AchE inhibitor

covalent, irreversible binding

competitive antagonist of AchR

metabolized by pChE

~15 min duration

AchE inhibitor

carbamate ester

covalent, reversible

half-life ~0.5 -- couple hours

used to counteract d-turbocararine and other nAchR antagonists

AchE inhibitor

carbamate ester

covalent, reversible binding

half-life ~0.5 -- couple hours

used to counteract nAchR antagonists

normally reactivates AchE that has been phosphorylated

cannot reactivate "aged" phosphorylated AchE

partial agonist of AchR

i.e. depolarizing blocker

first activates, then desensitizes

hydrolyzed by pChE

can lead to malignant hyperthermia in predisposed: treat with dantrolene

competitive antagonist of AchR

~40 min duration

nAchR inhibitor

nAchR inhibitor

nAchR agonist

nAchR agonist

major mAchR agonist in GI, urinary; NO nAchR activity

choline ester: NOT hydrolyzed by ChE

used as GI stimulant

major nAchR agonist, major mAchR agonist in GI, urinary (not CV)

choline ester: NOT hydrolyzed by ChE

sympathomimetic

mostly mAchR agonist, slight nAchR agonist

choline ester: slight hydrolysis by AchE

used as diagnostic for airway hyperreactivity

mAchR agonist (alkaloid)

parasympathomimetic

mAchR agonist (alkaloid)

parasympathomimetic

• used to treat:
• glaucoma
• dry mouth

mAchR inhibitor (tertiary)

• biphasic dose response:
• low dose: increases PNS flow from CNS
• low dose: acts preferentially on presynaptic mAchR, causes more release of Ach onto heart mAchR, which causes decresed heart rate

high dose: blocks mAchR on terminal and heart, causes increased heart rate

• uses:
• block vasodilation, but little effect on BP alone

selective M3 mAchR agonist

• uses:
• xerostomia
• Sjorgren's syndrome

fewer side effects than pilocarpine

mAchR inhibitor (quaternary)

not lipid soluble (vs. atropine), poorly absorbed into general circulation

• uses:
• inhaled for bronchodilation without inhibiting ciliary clearance of mucous
• asthma, COPD
• sometimes combined with beta2-agonists

selectively activates mAchR (M1) in SNS ganglia

• uses:
• increases BP by stimulating SNS modulatory pathway

mAchR inhibitor (quaternary)

selectively blocks mAchR (M1) in SNS ganglia

mAchR inhibitor (tertiary)

selective M3 mAchR inhibitor (quaternary)

• uses:
• inhaled bronchodilator
• COPD

selective H2 receptor agonist

• uses:
• diagnostic for Zollinger-Elson syndrome

1st generation H1 receptor inhibitors

anti-allergenic

• common:
• dimenhydrinate (dramamine)
• diphenhydramine (benedryl)

major sedation

1st generation H1 receptor inhibitor

common: hyroxyzine (highly sedative)

non-OTC: potential for abuse

• uses:
• motion sickness
• anxiety

highly selective H1 antagonism

common GI side effects, moderate sedation

moderate sedation

H1 antagonists

pheniramine derivatives

• common:
• brompheniramine (dimetapp)

OTC: allergy, common cold, rhinitis

slight sedation

H1 antagonist

common: promethazine (phenergan)

strong sedation

• non-OTC:
• pre-operative anesthetic
• alpha-adrenergic blockade
• used for severe motion sickness

1st generation piperidine

• uses:
• anti-serotonin effect
• used for adolescent migraine
• used for Cushing's syndrome

lead compound for 2nd generation H1 antagonists

• common:
• loratadine (claritin)
• fexofenadine (allegra)
• zyrtec

• drugs of choice for allergy
• highly selective for H1 receptor
• non-sedating

• complications:
• lethal ventricular arrhythmias

used to reduce gastric acid secretions

• common:
• ranitidine (zantac)
• famotidine (pepcid)

stimulant, nootropic effects

treat neurodegeneration, obesity, sleep disorders, etc.

none currently used clinically

current drugs of choice for GA disorder

• common:
• omeprazole (prilosec)
• pantoprazole (protium)

• common:
• sucralfate
• prostaglandin analogs
• bismuth compunds

B2-adrenergic agonist

indirect sympathomimetic

B1-adrenergic agonist

• increases contractile force of heart
• little effect on HR and TPR

mixed-acting sympathomimetic

more potent at B2 than a1

uses: treat anaphylatic shock, cardiac stimulation, relaxation of GI/bronchi

dopaine D1 receptor agonist

emergency managment of HTN

stimulates B1 and B2 adrengergic receptors

strongly stimulate B-adr and a1-adr

stimulates a1-adr

B2-adrenergic agonist

B2-adrenergic agonist

B2-adrenergic agonist

indirect sympathomimetic

selective B1 beta-blocker

selective B2 beta-blocker

non-selective beta-blocker AND a1-blocker

selective B1 beta-blocker

non-selective beta-blocker AND a1-blocker

selective B1 beta-blocker

non-selective B-adrenergic inhibitor

covalent, nonselective alpha-adrenergic inhibitor

noncovalent, non-selective alpha-adrenergic inhibitor

selective a1 alpha-adrenergic inhibitor

non-selective B-adrenergic inhibitor

non-selective B-adrenergic inhibitor

selective a2 alpha-adrenergic inhibitor