Autonomic Effects Upon Stimulation:

Name the Cholinergic and Adrenergic Responses as well as the specific receptor.

1) Eye: Pupil, IOP, Accomidation

2) Lung

3) HR

4) Heart Contraction

5) Blood Vessels: skeletal and others

6) GI: longitudinal and sphincter

7) Bladder: body and sphincter

8) Liver: glycogenolysis

9) Pancreas: Insulin

9) Kidney: Renin

**Pneumonics:

PACH: parasym=cholinergic:

patch up your body when you rest: rest and digest

SAD: sympathetic=adrenergic:

it is sad to fight: fight or flight

1) Eye

Chol (M): myosis, decr IOP, Near Vision Accom

Adren (a1): mydriasis, incr IOP, far vision accom

2) Lung

Chol (M): bronchoconstrictor

Adren (B2): bronchodilator

3) HR

Chol (M): bradycardia/- chronotropy (decr HR)

Adren (B1): tachycardia/+ chronotropy (incr HR)

4) Heart Contraction

Chol (M): - inotropy (decr contractions)

Adren (B1): + inotropy (incr contractions)

5) Blood Vessels

BVs to skeletal muscle...

Chol (M): dilate

Adren (B2): dialate

Peripheral BVs...

Chol (M): dilate

Adren (a1): constrict

6) GI

Chol (M): contract long & relax sphincter...makes you poop!

Adren: (B2) relax longitundinal muscles & (a1) contract sphincter...constipation.

7) Bladder

Chol (M): contract body & relax sphincter...you urinate.

Adren: (B2) relax body & (a1) contract sphincter...anuria.

8) Liver

Chol (M): NO EFFECT

Adren (B2): incr glycogenolysis (incr bld glucose)

9)Pancreas: Insulin

Chol (M): NO EFFECT

Adren: (B2) insulin release, (a2) decr insulin release

**Insulin release lowers blood glucose**

10) Kidney: Renin Raises BP

Chol (M): NO EFFECT

Adren (B1): increase renin release

Which ANS sytem corresponds to the following phrases?

1) "fight or flight" : list characteristics of this response and the specific receptors.

2) "rest and digest".

1) SYMPATHETIC:

sAD=ADrenergic

it is sad to fight

fight or flight

• Dilates pupils and relaxes the lens, allowing more light to enter the eye. (a1)
• Dilates bronchioles of the lung, which allows for greater alveolar oxygen exchange. (b2)
• Increases heart rate and the contractility of myocytes, thereby providing a mechanism for the enhanced blood flow to skeletal muscles (heart b1).
• Kidney releases renin (b1), which increases BP.
• Vasodialator (b2) to skeletal muscles, lungs, heart.  Vasoconstrictor (a1) to skin and GI to move all blood inward to more important organs.
• Constricts all sphincters (a1), inhibits bladder and GI smooth muscle contraction (b2) to prevent urination and defecation.

2) Parasympathetic

paCH=CHolinergic

pach things up when you rest

Rest and digest

Dx Chemistry.

1) What are the 4 chemical classes of drugs and their relative absorptions (eg - best route of administration)? 

*Which chemical class composes the majority of drugs?

**What chemical class is most dangerous?

***Which are always unionized/ionized?

****Which dx is never absorped via p.o.?

2) What are 2 requirements for a dx to pass through cell membrane?

3) State the reactins of acids/bases in acidic/basic medias.

1)

a) Weak Base.  *Majority of drugs.* 

(BOH) <-> (B+) + (OH-)

p.o.: Absorbed in lower GI b/c pH increases.

b) Weak Acid.

(HA) <-> (H+) + (A-)

p.o.: Absorbed in stomach b/c of HCl acidic environment.

c) Neutral.

***ALWAYS UNIONIZED = **danger b/c of ability to pass through any cell membrane in body (e.g.: alcohol).

d) Charged.

***ALWAYS IONIZED = ****must administer parenterally.

2) Pass through membrane: unionized & liquified.

3) Base in basic media=unionized.

     Acid in acid media=unionized.

    Mix matched=ionized

The action of the drug on body.

1) Name

2) Explain efficacy

3) explain affinity

1) Pharmacodynamics.

Dx-->tissue-->receptor (macromolecule)=

Dx-Receptor Complex (DRC)

2) DRC formaton creates a stimulating RESPONSE=agonist.

3) DRC has NO RESPONSE, but functions just by competitively blocking receptor site=antagonist.

Agonistic Drug responses:

1) Therapeutic

2) Adverse: cause?

3) Hypersensitivity: requirements, commonly elicited after what administration, response stages, 1st sign.

4) Idiosyncratic

5) Lethal: which drugs elicit this reponse?

1) Therapeutic: desired response

2) Adverse: diffusion of dx to elicit undesired responses in untargetted areas.

3) Hypersensitivity Rxn: involves dx reaction with antibody (eg PCN).  Prior dx exposure required.  Often familial. 1st sign= rash.

Most common after parenteral administration.

Stg 1: histamine release, urticaria

Stg 2: anaphylaxis: rash, SOB, BP drops, HR incr.

4) Idiosyncratic: unknown cause

5) Lethal: ALL DRUGS can kill...depends on dose.

The actions of the body on the drug.

1) Name

2) 4 components.

*4 Requirements of mov't across membrane.

*Cause of adv rxns.

1) Pharmacokinetics

2)

a) Absorption: mov't of drug across (lipid) membrane. *Dx must be lipid soluble, small (500-1000) unionized, & liquified.

b) distribution: *cause of adv rxns because drug goes to untargeted areas.

c) metabolism: chem conversion of compound into more H2O solube form (for excretion).

d) excretion: dx removed from body via urine, feces, sweat.

Dose response curves: state what it assesses, x/y axis labels, constants, and anything else.

1) Graded

2) Quantal. *thera index

3) Time Action

4) What is the effect plateau called?

1) Graded: Potency

x=dose, y=effect

Constant: time & subject

Two drugs are plotted.  Drug with more potency has more adverse effects.

[image]

2) Quantal: Safety

x=dose, y=unit

Constant=time & effect

Plots therapeutic and lethal dosages of a drug.  The greater distance between two curves, the safer the drug.

Therapeutic Index=LD50/ED50...greater #=safer drug.

[image]

[image]

3) Time Action: Onset, duration, peak.

x=time, y=effect

constant: unit

Plots onset, duration, and peak effect of the same drug given in different dosages.

greater dose=shorter onset, longer duration, greater peak effect.

[image]

4) Ceiling effect.

LD₅₀ / ED₅₀

greater #...safer drug.

p.o. adminisration

1) time for max absorption

2) Overdose Tx: Dx, time of action, complication of tx

1) 30-60 min

2) Ipecac to induce vomiting within 10-15 min.

Mallory Weiss: esophageal sphincter rips b/c it remains constricted during vomiting...Ouch.

Distribution of Dx.

1) Explain the concept and effects of free vs. bound drug.

2) Hypoalbuminemic pts (2 examples and effect)

3) steady state

4) #1 cause of adv effects in geriatrics??  Potential interacters.  Explain testing procedures..

1) Dx + Albumin -->Dx-Alb Complex (DAC)

Dx = free drug=effect on tissues

Albumin = plasma protein

DAC = bound dx= no effect on tissues

2) Hypoalb pts (geriatrics and alcoholics): have more free dx (stronger effect) in body because they have less alb for dx to bind.

3) steady state = (5)(t^1/2) = therapeutic response is greatest and level of dx in body in constant.

4) Older pt = more drugs they take.  Drugs compete for albumin.  A potential interactor has binding >90% and blocks other drugs from binding.

Blood test: yields tota dx conc

Saliva: yields ONLY free dx (schlemm filter).

Metabolism

1) Liver System vs. Blood System Kinetics

2) What could happen if you have an anatomical liver problem and you administer a drug that requires the liver system for metabolization?

3) Case Study: Riampin (anti-TB dx) and Oral Contraceptives: girls were becoming preggers.  Explain what happened.

1) Liver metabolizes with P450 isoenzyme system.  This sytem is slower than the plasma esterase enzyme in the blood which metabolizes ester drugs rapidly.

2) Liver disease=not sufficient #s of isoenzymes to metabolize dx...could lead to toxic levels of free dx in blood.

3) Oral contraceptives contain estrogen which is metabolized by P540 isoenzyme. Riampin increases P540 esoenzyme, metabolizing out all the estrogen, rendering the contraceptive ineffective

Elimination

1) Elimination Half Life and total elimination.

2) #1 elimination route: qualitative or quantitative?  Used to screen for what?

3) other elim routes.

1) Elim Half Life=time for conc of dx in body to drop by 50%.

Total elim=(5)(t^1/2)

2) Urine.  Qualitative.  Screen for compliance, drug abuse, and metabolites.

3) Biliary, rectal, lungs, saliva, sweat.

ANS - Autonomic/Involuntary Nervous System

1) neurons are mostly efferent or afferent?

2) state the route of the impulse.

3) All ANS pre-ganglionic neurons are...

4) All parasympathetic post-gang neurons are

5) all sympathetic post-gang neurons are.....except for.....which are......

6) What receptor is found on the ANS post-gang cell body?

7) What receptor is found on ANS Cholinergic organs?

8) what receptor is found on ANS adrenergic organs?  What receptor is found on adrenergic nerve ending and what does do?

9) what receptor is found on skeletal muscle (this is somatic system, not ANS)?

1) efferent (CNS -->periphery)

2) Impulse begins in CNS at pre-ganglionic neuronal body.  Conducts down neuron to synapse and then to post-gang cell body which resides outside of CNS.  Then transmission of impulse to receptors on organs.

3) cholinergic (ACh)

4) PACH: cholinergic (ACh)

5) SAD: adrenergic (NE) except salivary glands and piloerectus muscles which are cholinergic.

6) Nicotinic I (post-gang cell body)

7) muscarinic (cholinergic)

8) a1, b1, b2, b3 (all on adren organs).  a2 (on adren nerve ending) reuptakes NE.

9) Nictonic II (skeletal muscle)

Describe the synthesis and breakdown of...

1) ACh

2) NE

1) Acetate + Choline -> ACh ->metabolized by ACh-ase (endogenous source) OR plasma esterase (exogenous source) -> choline is recycled back into nerve and acetate enters bloodstream.

2) tyrosine ->dopa -> dopamine -> vesicled NE...from here there are 3 options....

a) extracellular metab of NE by COMT

b) NE reuptake by a2 --> intracellular metab by MAO

c) bind to receptors a1, b1, b2, b3 on organs.

Adrenergic Receptors.

1) Generally, b2 stimulation....

2) Generally, a1 stimulation...

3) b1 is concerned with what organs?

1)b2 stim:  dilates/relaxes muscle

(eg. brochodilation, skel BV dilation, mydriasis by relaxing sphincter around pupil, longitudinal GI m. relaxer, bladder smooth muscle relaxer).

2) a1 stim: constrict/contracts muscle

(eg. peripheral BV constrict, pupil sphincter contricts=myosis, GI/GU sphincter contriction)

3) b1 stim: heart (+inotropy & +chronotropy), kidney (release renin=incr BP).

Adrenergic Agonists

1) What is the class? What do they do?

2) Define: direct acting

3) Define: Indirect acting.  Give dx name and clinical use.

4) Define: Mixed Acting.  Give the two classes of drugs that are in this category.

Adrenergic Agonists:

1) Sympathomimetics: mimic the flight or fight response.

2) Direct: Work on receptor site by stimulation

3) Indirect: release NE at nerve ending.  Tyramine: no clinical use.

4) Mixed acting: stimulate receptors AND release NE.  Ephedrines and Amphetamines.

Epinephrine:

1) Class (name the other 5 drugs in this class).

2) MOA

3) Therapeutic Uses (7)...effect on system

4) Adv Effects (1)

5) Can it cross blood/brain barrier?

1) Class: DIRECT Adrenergic Agonist (Sympathomimetic)

(along with Norepinephrine, Isoproterenol, Dobutamine, Dopamine, Albuterol)

2) MOA: non-selective alpha- & beta- stimulator

3) Therapeutic Uses...effect on system:

• Anaphylaxis, Epitaxis, nasal congestion, local anesthesia, shock...a1 peripheral vasocontriction.
• Cardiac Arrest...b1: +inotropy, +chronotropy, incr BP (kidney releases renin).
• Asthma...b2 bronchodilation.

4) Adv Effects: ventricular arrythmia (b1).

5) Can't cross blood/brain barrier b/c H₂O soluble.

Norepinephrine:

1) Class (name the other 5 drugs in this class).

2) MOA

3) Therapeutic Uses (5)...effect on system

4)Adv Effects

5) HR & BP effects

1) Class: DIRECT adrenergic agonist (symphathomimetic)

(along with epinephrine, isoproterenol, dobutamine, dopamine, albuterol).

2) MOA: non-selective alpha-stimulator (a1,a2).

3) Therapeutic Uses...effect on system

• Anaphylaxis, nasal congestion*, epitaxis**, shock, local anesthesia...a1 peripheral vasocontriction.
• *decongestion only temporary
• **may cause ischemia

4)**may cause ischemia of the nose if used for epitaxis.

5) HR (o/decr) & BP (incr: a1).

Isoproterenol:

1) Class (name the other 5 drugs in this class).

2) MOA

3) Therapeutic Uses (2)...effect on system

4) BP effect

1) Class: DIRECT adrenergic agonist (sympathomimetic)

(along with epinephrin, norepinephrine, dobutamine, dopamine, albuterol).

2) MOA: non-selective beta-stimulator (b1,b2)

3) Therapeutic Uses (2)...effect on system

• Cardiac Arrest...b1: +chronotropy, +inotropy
• Asthma...b2 bronchodilation

4) BP effect:

b2: dilates skeletal BVs     (incr BP)

b1: kidney releases renin  (decr BP)

net BP: o

Dobutamine:

1) Class (name the other 5 drugs in this class).

2) MOA

3) affects what organ?

1) Class: DIRECT adrenergic agonist (Sympathomimetic)

(along with epinephrine, norepinephrine, isoproterenol, dopamine, albuterol).

2) MOA: selective beta-1 stimulator

3) affects what systems?

Heart (+inotropy, +chronotropy)

Kidney (Renin increases BP)

Dopamine:

1) Class (name the other 5 drugs in this class).

2) MOA

3) Therapeutic Uses...Eff on system

1) Class: DIRECT Adrenergic Agonist (Sympathomimetic) 

(along with epinephrine, norepinephrine, isoproterenol, dobutamine, albuterol)

2) MOA: selective beta-1 & alpha-1 stimulator

3) Therapeutic Uses...Eff on system:
-Cardiac Arrest...b1: +inotropy, +chronotropy, Renin

-Shock: a1: peripheral vasocontriction

Albuterol

1) Class (name the other 5 dx in this class)

2) MOA

3) Therapeutic Uses...Effect On System

1) DIRECT Adrenergic Agonist (Sympathomimetic)

(epinephrine, norepinephrine, isoproterenol, dobutamine, dopamine)

2) MOA: selective beta-2 stimulator

3) Therapeutic Uses...Effect On System

-Asthma...b2 bronchodilator

Tyramine

1) class

2) MAO

3) uses

1) Indirect Adrenergic Agonist (Sympathomimetic)

2) stimulates release of NE at nerve ending

3) no clinical use

Pseudophedrine

1) class

2) dx family

3) MAO

4) Use & duration 

1) class: Mixed acting adrenergic agonists (Sympathomimetic)

2) dx family: Ephedrines

3) MAO: stimulates receptors and stimulates the release of NE

4) Use & duration: Relieves nasal congestion for 2-4 hour...careful of rebound congestion.

Dx Family: Amphetamines

1) class

2) name the 3 drugs we learned in this family

3) MAO

4)Therapeutic Use...EOS

5) Adverse Rxns

6) Warnings 

1) class: Mixed Acting Adrenergic Agonists (Sympathomimetic)

2) in this family: Benzedine, Dextrodine, Methamphetamine

3) MAO: blocks NE reuptake and increases NE concentration in extra-neural space; also stimulates receptors; stimulates CNS

4)Therapeutic Use...EOS

-Nasal Congestion...a1 vasocontriction (2-3 hrs)*

-Narcolepsy

-Obestiy...incr BMR**

-...Causes Hyperactivity

5) Adverse Rxns

*Rebound Congestion

**Tolerance formed within 2-3wks

6) Warnings: ABUSE!  Compounds go to CNS and stimulate brain cells to create a high.  Tolerance can be formed within 2-3 wks.  DO NOT USE more than 3wks.

NE (non-selective alpha-stimulator) and Isoproterenol (nonselective beta-stimulator) are

Direct Acting Adrenergic Agonists.

NE: pulse pressure remains the same because systolic and diastolic rise together (no dx effect on heart).  Mean BP rises.

a1: incr BP (constrit peripheral BVs)

[image]

Isoproterenol: pulse pressure increases because systolic rises and diastolic decreases (because of beta effects on heart).  Mean BP remains the same.

b1: incr HR, contraction, sys BP

b2: decr diastolic BP (dilate skel BVs)

MOA: Selective a1 inhibitors:

1) Name three.

2) Class

3) Dx with longest duration

4) Therapeutic Uses (*which dx works best for each use?)

5) Adv Rxns

1) Prazosin, Terazosin, Doxazosin

2) Class: Adrenergic Agonists

3) Prazosin has longest duration

4) Therapeutic Uses...EOS

-HTN...inhibits a1 peripheral vasoconstriction

*prazosin best

-BPH...decr prostate size

*Doxazosin best

5) Syncope (*Prazosin is worst offender, advise pt to take before bed)

Prazosin, Terazosin, Doxazosin

1) Class

2) MAO

3) Therapeutic Uses

4) Adv Rxns

1) Adrenergic Antagonists

2) MAO: selective alpha-1-inhibitors

3) HTN (*prozosin), BPH (*Doxazosin)

4) Adv Rxn: Syncope (*especially prozosin)

Phentolamine

1) class

2) MAO

3) duration

4) Therapeutic Uses...EOS

5) Clinical Uses

6) Adv Rxns

1) class: Adrenergic Antagonist

2) MAO: non-selective alpha-inhibitor

3) duration: short

4) Therapeutic Uses...EOS

-HTN...inhibits a1 vasocontriction

5) Clinical Uses: OF NO CLINICAL VALUE

6) Adv Rxns: reflex tachycardia b/c inhibits a2 and NE release is uncontrolled...there is no a2 reuptake.

Phenoxybenzamine

1) class

2) MAO

3) duration

4) Therapeutic Uses...EOS

5) Clinical Uses

6) Adv Rxns

1) class: Adrenergic Antagonist

2) MAO: non-selective alpha-inhibitor

3) duration: long

4) Therapeutic Uses...EOS

-HTN...inhibits a1 vasocontriction

5) Clinical Uses: OF NO CLINICAL VALUE

6) Adv Rxns: reflex tachycardia b/c inhibits a2 and NE release is uncontrolled...there is no a2 reuptake.

Non-selective alpha-inhibitors:

1) name 2 drugs

2) class

3) Use

4) Adv Rxn

5) What is the difference between these 2 drugs?

1)Phentolamine & Phenozybenzamine

2) class: Adrenergic Antagonists

3) Use: OF NO CLINICAL VALUE. 

but, HTN...inhibits a1 peripheral vasocontriction

4) Adv Rxn: reflex tachycardia because NE release is uncontrolled because of a2 reuptake inhibition.  The NE then goes on to react on b1.

5) What is the difference between these 2 drugs?  Phentolamine is shorter acting.  Phenozybenzamine is longer acting.

Reserpine

1) class

2) MAO

3) Therapeutic Uses

4) Adv Rxn (why?)

1) class: Adrenergic Antagonist

2) MOA: adrenergic Neuronal Blocker (deplete NE inside nerve ending, NE metabolize by MAO enzyme).

3) Therapeutic Uses: HTN

4) Adv Rxn: Depression and Suicide b/c dx crosses blood/brain barrier.

Diarrhea

Atenolol

1) class

2) MOA

3) Ther Use...EOS.

4) What type of pts is this good for?  Why?

1) class: adrenergic antagonists

2) MOA: selective beta-1-inhibitor (beta blocker, think Heart!)

3) Ther Use...EOS

-#1 dx for HTN (b/c q.i.d. dosage)...no renin release.

4) What type of pts is this good for?  Asthmatics and diabetics b/c NO b2 bronchocontriction or b2 change in glucose levels.

What is the #1 drug used for HTN?

1) Class and MAO

2) Why #1?

3) What adv rxns are NOT present?  What pts is this good for?

Atenolol.

1) Adrenergic Antagonist: Selective b1 blocker.

2) q.i.d

3) Asthmatic and Diabetic Pts don't have b2 bronchoconstriction and blood-glucose effects.

Propranol

1) class

2) MOA

3) Ther Uses (3)...EOS

4) Adv rxns

1) class: adrenergic antagonist

2) MOA: non-selective beta-blocker

3) Ther Uses...EOS

-HTN...no renin release (b1 inhibition)

-ANGINA...(-) inotropy (b1 inhibition)

Hyperthyroidism...(-) chronotropy (b1 inhibition)

4) Adv rxns: b2 inhibitory effects...

bronchoconstriction, incr glucose, cold extremities

Timolol

1) class

2) MOA

3) Ther Use (administration?)...EOS

4) Adv rxns

1) class: adrenergic antagonist

2) MOA: non-selective beta-blocker

3) Ther Use (opthalmic drops)

-glaucoma...decr IOP

4) Adv rxns: none, b/c localized

Beta Stimulation vs. Blocking

1) Heart

2) Kidney

3) Lungs

4) BVs

5) Pancreas

6) Liver

7) GI

8) GU

9) Fat Tissue

             Receptor     Stimulation              Blocking

1) Heart          b1      pos inotropy/chronotropy        neg inotropy/chrono

2) Kidney        b1      Renin (incr BP)                      no renin (decr BP)

3) Lungs         b2      bronchodilation                      bronchoconstriction

4) BV (skel)    b2     vasodilation                            vasocontriction

5) Pancreas     b2    incr insulin (decr gluc)              decr ins (incr gluc)

6) Liver          b2    incr glycogenolysis (incr gluc)     decr glycogenolysis (decr gluc)

7) GI             b2     longitudinal m. relax                 longitudinal muscle contracts

8) GU             b2    body relax                               body contracts

9) Fat Tissue  b3     incr triglyc breakdown             decr triglyc breakdown

                             decr chol                                decr LDL, incr Chol

What effect do adrenergic blockers/antagonists have on blood sugar levels? 

Can you use adrenergic blockers on DM pts?

Effect on blood-glucose levels varies from pt to pt because of opposing effects of pancreas and liver.

Pancreas: decr insulin release (incr glucose)

Liver: decr glycogenolysis (decr glucose)

In DM pts, just monitor blood-glucose levels if pt is on adrenergic blockers.

Cholinergic Agonists

1) aka and function

2) Direct Acting.  Name the receptors that these drugs could work on.

3) Indirect Acting.  Kinetics

1) Parasympathomimetic. Stimulate rest and digest action.

2) act on receptor sites:

-on post-ganglionic cell bodies = nicotinic I

-on parasym post-gang organs=muscarinic

-on somatic skeletal muscles=nicotinic II

3) inhibit acetyl-cholinase enzyme (which increases ACh in synapse).  Very fast acting and reversable...continuously releases and binds to enzymes.

Acetyl Choline

1) Class

2) MOA

3) Chemistry, Kinetics, Metabolization

4) EOS: pupil, secretions, lung, heart, BV, BP, GI, GU

5) Ther Uses

6) Adv Rxns

1) Class: Cholinergic Agonist (parasympathomimetic)

2) MOA: Direct Acting: Non-Selective Cholinergic Stimulator.

3) Chemistry, Kinetics, Metabolization: ester N+ (IM), short duration, metabolized by plasma esterase.

4) EOS: myosis, incr secretions, bronchocontriction, [(-chronotropy, -inotropy, vasodilation)=decr BP], diuresis, diarrhea.

5) Ther Uses: Not used clinically, too short duration

6) Adv Rxns: SOB, hypotension

Bethanocol

1) Class

2) MOA

3) Chemistry, Kinetics, Metabolization

4) EOS: pupil, secretions, lung, heart, BV, BP, GI, GU

5) Ther Uses

6) Adv Rxns

1) Class: Cholinergic Agonist (parasympathomimetic)

2) MOA: Direct Acting: Selective Muscarinic Stimulator

3) Chemistry, Kinetics, Metabolization: ester N+ (IM), more resistance to cholinesterase=long duration.

4) EOS (same as ACh): myosis, incr secretions, bronchocontriction, [(-chronotropy, -inotropy, vasodilation)=decr BP], diuresis, diarrhea.

5) Therap Uses: makes post-op pts urinate (Atropine is given pre-op to stop secretions)

6) Adv Rxns: SOB, hypotension

Pilocarpine

1) Class

2) MOA

3) Chemistry, Administration, Metabolization

4) EOS (2)

5) Ther Uses

6) Adv Rxns

1) Cholinergic Agonist

2) Direct Acting

3) tertiary-uncharged, administer via po or opthalmic drops, long duration

4) STRONG stimulation of salivary glands, decr IOP w/ opthalmic administration.

5) glaucoma

6) spared adv rxn because given by eye drops

Neostigmine

1) Class

2) MOA

3) Chemistry, Reversability, Kinetics

4) EOS

5) Therap Uses and Administration

6) Adv Rxns

1)REVERSABLE Indirect Cholinergic Agonist

2) inhibits plasma esterase and ACh-ase, this causes high cholinergic activity.

3) N+, reversable enzyme inhibitor with short duration(3-6hrs)

4) same as ACh + stimulates skeletal muscle

5) Tx for myastenia gravis to activate limp skeletal muscle.  IM 2-3 times/day.

6) Cardiovascular effects: SOB, hypotension

Physostigmine

1) Class

2) MOA: which enzyme does it inhibit more?

3) Chemistry

5) Therap Use

1) REVERSABLE Indirect Cholinergic Agonist

2) stronger enzyme inhibitor of plasma esterase than ACh-ase

3) tertiary uncharged

4) reverse hallucinogenic effects of mushrooms (reverses cholinergic blockers)

Edrophonium

1) Class

2) Kinetics

3) Chemistry

5) Therap Use

1) REVERSABLE Indirect Cholinergic Agonist

2) Fast acting/short duration

3) N+

4) Used to dx myastenia gravis.  Inject and if you see a response in 3-4 minutes, you have mg.  Continue treatment 2-3x/day IM with neostigmine.

Isoflurophate

1) Class

2) MOA

3) Chemistry

5) Use and Anecdote

1) IRREVERSABLE indirect cholinergic agonist

2) inhibit plasma esterase by chemically attaching to the enzyme

3) N+

4) Used in herbicides and WAR gases...anecdote is pralidoxine(IM) (2-pam-chloride) which chemically rips off isoflurophate from plasma esterase.

Cholinergic Antagonist:

1) MOA

2) 3 classes

1) inhibit muscarinic sites on organs, nicotinic I sites on post-ganglionic cell neuronal bodies, OR nicotinic II sites skeletal muscle.

2) Antimuscarinic Agents, Ganglionic Blockers, Neuromuscular Blockers

Atropine

1) Class

2) MOA

3) Chemistry and kinetics

4) EOS: pupil, saliva, HR (normal, tachy, and brady pt), BV, GI, GU

6) Uses

7) Adv rxns

8) Derivatives (2) used by opthamologists

1) Class: Cholinergic Antagonist: Antimuscarinic Agents

2) MOA: competitive muscarinic inhibitor

3) Chemistry and kinetics: uncharged, long duration (12-24 hrs)

4) EOS: mydriasis, xerostoma, HR (norm pt=nothing/slt incr; tachy pt= decr; brady pt=incr), no effect of BV, NO peeing/pooping.

6) Therap Use: asthma (emergency situation), cardiac arrest, pre-op (decr secretions w/o cardiac effects), cold preparations

7) Adv rxns: #1=xerostoma, urine retention/constipation, blurred visions (b/c mydriasis), goes to CNS=hallucinations with high dose (tx with physostamine)

8) Opthalamic Derivatives: Homoatropine/Mydriatic: used to dilate pupil, short acting.

Scopolamine

1) Class

2) MOA

3) Chemistry and kinetics

4) EOS: pupil, saliva, HR (normal, tachy, and brady pt), BV, GI, GU

6) Uses

7) Adv rxns

8) Derivatives (2) used by opthamologists

1) Class: Cholinergic Antagonist: Antimuscarinic Agents

2) MOA: competitive muscarinic inhibitor

3) Chemistry and kinetics: uncharged, long duration (12-24 hrs)

4) EOS: mydriasis, xerostoma, HR (norm pt=nothing/slt incr; tachy pt= decr; brady pt=incr), no effect of BV, NO peeing/pooping.

6) Therap Use: #1 for motion sickness.  OB/GYN: decrease secretions and sediates a delivering mama.

7) Adv rxns:  less xerostoma than atropine.

Nicotine

1) Class

2) MOA

3) Chemistry

4) Clinical Use

5) Effect on Smokers

Nicotine

1) Class: Cholinergic Antagonist: Ganglionic Blockers

2) MOA: stimulates AND inhibits ganglionic nicotinic receptors.

3) Chemistry: N+

4) Clinical Use: Not used clinically

5) Effect on Smokers: long term smokers have less stimulatory effects.

Mecamylamine

1) Class

2) MOA

3) Chemistry

4) Clinical Use and Past Use (why is past use not currently used?)

1) Class: Cholinergic Antagonist: Ganglionic Blockers

2) MOA: inhibits nicotinic ganglia

3) Chemistry: uncharged

4) Clinical Use and Past Use (why is past use not currently used?): not clinically used today.  Past use for HTN tx - had too many adv effects.

Tubocuarine

1) Class

2) MOA.  What is a common name that describes its MOA?

3) Chemistry, Metabolization, Kinetics

4) Clinical Use and Past Use

5) Adv rxns

1) Class: Cholinergic Antagonist: Neuromuscular blockers

2) MOA: somatic blockers of nicotinic II receptors on skeletal muscles...¨muscle relaxers¨

3) Chemistry, Metabolization, Kinetics: N+, metabolized slowly by liver, long duration.

4) Current Use and Past Use: not currently used; past uses for anesthesia and monkey paralyzing blowdarts

5) Adv rxns: respiratory arrest

Mevacurium

1) Class

2) MOA.  What is a common name that describes its MOA?

3) Chemistry, Metabolization (spd relative to what drug?), Kinetics

4) Uses

5) Adv rxns

1) Class: Cholinergic Antagonist: Neuromuscular Blockers

2) MOA: somatic blocker of nicotinic II receptors on skeletal muscle...¨muscle relaxers¨

3) Chemistry, Metabolization (spd relative to what drug?), Kinetics: N+, metabized by liver quicker than tubocuarine, shorter duration relative to tubocuarine.

4) Use: mercy killings

5) Adv rxns: respiratory arrest

Succenylcholine

1) Class

2) MOA.

3) Chemistry, Metabolization , Kinetics (spd relative to what drugs?)

4) Uses

5) Adv rxns

6) As the pt's medical provider, what should you test for before giving your pt this dx?

1) Class: Cholinergic Antagonists: Neuromuscular Blockers

2) MOA: stimulates, THEN blocks somatic nicotinic II receptors on skeletal muscles. ¨Muscle Relaxers¨

3) Chemistry, Metabolization, Kinetics: N+, metabolized by plasma esterases (super quickly!), very fast duration in comparison to tubocuarine & mevacurium.

4) Uses:

-short duration anesthesia

-shock therapy (prevents jerky mov't that come with shocks).

5) Adv rxns: respiratory arrest.

6) Test for function & conc of plasma esterases before giving this drug.

Is this chart applicable (maybe a little???)) 

(From google images)

Name 6 Direct (stimulates certain receptor sites) Adrenergic Agonists.

State Which Receptor Sites Each Stimulates.

questions about above drugs:

a) Which dx is best to treat asthma?

b) Which dx has no effect on pulse pressure but raises mean BP?

c) Which dx increases pulse pressure and has no effect on mean BP?

d) Which drug may cause ischemia of the nose if used for tx of epitaxis?

e) All of these drugs have a terrible adv rxn EXCEPT for 2 drugs...what is the rxn and what is the exception dx?

1) Epinephrine: a1 a2 b1 b2

2) Norepinephrine: a1 a2

3) Isoproterenol: b1 b2

4) Dobutamine: b1

5) Dopamine: a1 b1

6) Albuterol: b2

____________________________

a) Which dx is best to treat asthma? Albuterol

b) Which dx has no effect on pulse pressure but raises mean BP?  Norepinephrine

c) Which dx increases pulse pressure but has no effect on mean BP? Isoproterenol.

d) Which drug may cause ischemia of the nose if used for tx of epitaxis? Norepinephrine

e) All of these drugs have a terrible adv rxn EXCEPT for 2 drugs...what is the rxn and what is the exception dx?

ventricular arrythmia (b1). 

Norepinephrine is a non-selective alpha-stimulator.

Albuterol is a selective b2-stimulator and doesn't have this rxn.

Name an Indirect Acting Adrenergic Agonist.

What does indirect acting mean?

Tyramine (not clinically used)

Stimulates the release of NE at nerve ending.

1-2) Name 4 Mixed Acting Adrenergic Agonists

(make sure to specify which family of drugs each is in).

3) What does mixed acting mean?

4) What are 4 therapeutic Uses of these drugs?

5) What are 3 adv rxns relating to CNS, decongestion, and weight loss?

1) Ephedrine Family: Pseudophedrine

2) Amphetamine Family:

Benzedrine, Dextrodrine, Methamphetamine.

3) Mixed Acting: Stimulates release of NE at nerve ending & stimulates receptors.

4) Nasal Congestion*, Narcolepsy, Obesity** , Hyperactivity

5) abuse (CNS stimulator), *rebound congestion (only lasts 2-3 hrs), **(tolerance within 2-3 wks).

Adrenergic Antagonists

1) Name 3 selective a1-inhibitors. *Note the longest acting.

2) Name 2 non-selective alpha-inhibitors. *Longer acting?

3) Name 1 adrenergic Neuronal Inhibitor (what does this mean?)

4) Name 1 selective b1-inhibitor.

5) Name 2 non-selective beta-inhibitors.

Questions About Above Drugs:

a) What dx is best for treating BPH?

b) Which dx is #1 for treating HTN? Why?

c) What drug causes bad syncope?

d) Which two drugs have no clinical value? Which is reversible/irreversible?

e) Which drug is used to treat glaucoma?

f) Which drug crosses blood/brain barrier?  What adv effect is caused by this crossing?

g) Which dx causes adv rxns of incr glucose, bronchocontriction, insomia, & cold extremities? What are the drug's therapeutic uses?

1) Selective a1-inhibitors:

*prazosin, terazosin, doxazosin

2) Non-selective alpha-inhibitors:

Phentolamine, *phenoxybenzamine

3) Adrenergic Neuronal Inhibitor

(deplete NE inside nerve ending-metabolized by MAO):

Reserpine

4) Selective b1-inhibitor:

Atenolol

5) Non-selective beta-inhibitors:

Propranol, Timolol

Questions About Above Drugs:

a) What dx is best for treating BPH? Doxazosin

b) Which dx is #1 for treating HTN? Why? Atenolol b/c only q.i.d.

c) What drug causes bad syncope? Prazosin

d) Which two drugs have no clinical value? Which is reversible/irreversible? Phentolamine (reversible), Phenoxybenzamine (irreversible).

e) Which drug is used to treat glaucoma? Timolol

f) Which drug crosses blood/brain barrier?  What adv effect is caused by this crossing? Reserpine.  Depression, Suicide.

g) Which dx causes adv rxns of incr glucose, bronchocontriction, insomia, & cold extremities? Propranol...used for tx of HTN, Angina, Hyperthyroidism.

Cholinergic Agonists.

1) Name 3 Direct Cholinergic Agonists. Where do they act?

2) Name 4 Indirect Cholinergic Agonists. Where do they act? Which 1 dx is irreversible?

Questions:

a) Which dx is used for glaucoma?

b) Which dx is not used clinically because too short of duration?

c) which drug is used to make myastinia gravis dx (duration)?  After + dx, which dx is used to treat it (dosage)?

d) Which dx is used as a war gas?  What is the anecdote (not on this list?)

e) which dx reverses hallucinogenic effects of mushrooms?

f) Which drug is given to post-op pts to reverse the effects of atropine?

1) Direct Chol Agonists: stimulate muscarinic receptor.

Acetylcholine, Bethanocol, Pilocarpine.

2)

Indirect Chol Agonists (reversible): inhibit ACh-ase.

Neostigmine, Physostigmine, Edrophonium

Indirect Chol Agonist (irreversible): inhibit plasma-esterase...Isoflurophate.

Questions:

a) Which dx is used for glaucoma? Pilocarpine.

b) Which dx is not used clinically because too short of duration? Acetylcholine.

c) which drug is used to make myastinia gravis dx? Edrophonium (3-4min). After + dx, which dx is used to treat it (dosage)? Neostigmine (IM 2-3 times/day).

d) Which dx is used as a war gas?  Isoflurophate. What is the anecdote? Pralidoxine.

e) which dx reverses hallucinogenic effects of mushrooms? Physostigmine.

f) Which drug is given to post-op pts to reverse the effects of atropine? Bethanocol.

Cholinergic Antagonists.

1) Name 2 antimuscarinic agents.

2) Name 2 ganglionic blockers.  What is their antagonistic action?

3) Name 3 Neuromuscular blockers.  What is their antagonistic action?  What is another name?

Questions About the Above Drugs:

a) #1 tx for motion sickness.

b) #1 adverse rxn for atropine.

c) to reduce secretions in delivering mothers.

d) which dx used in shock therapy to prevent jerky movements?

e) what dx stim & inhibits ganglia?

f) which is the only NM blocker is metabolized by plasma esterase?

1) Antimuscarinics: Competitive musc inhibitors.

Atropine, Scopolamine

2) Ganglionic blockers: inhibit nicotinic I receptors.

Nicotine, Mecamylamine

3) Neuromuscular blockers: inhibit somatic nicotinic II receptors on skeletal muscle. ¨Muscle Relaxers¨

Tubocuarine, Mevacurium, Succenylcholine.

Questions About the Above Drugs:

a) #1 tx for motion sickness. Scopolamine

b) #1 adverse rxn for atropine. Xerostoma

c) to reduce secretions in delivering mothers. scopolamine

d) which dx used in shock therapy to prevent jerky movements? Succenylcholine

e) what dx stim & inhibits ganglia? Nicotine

f) which is the only NM blocker is metabolized by plasma esterase? Succenylcholine