Bethanecol

1.Drug Classification/MOA

2.Clinical Application

3.Actions

4. Caution

1.Direct muscarinic agonist

2. -postoperative/neurogenic ileus

-urinary retention

3. activates bowel and bladder smooth muscle

4. caution: COPD, asthma, peptic ulcers

Carbachol

1. Drug Classification/MOA

2. Clinical Applications

3. Special Notes

4. Caution

1. direct muscarinic agonist

2. -glaucoma

-pupillary contraction

-relief of intraocular pressure

3. CARBon copy of ACh

4. Caution: COPD, asthma, peptic ulcers

Pilocarpine

1. Drug Classification/MOA

2. Clinical applications

3. Action

4. Special notes

5. Caution

1. Direct muscarinic agonist

2. Glaucoma emergencies

-stimulates sweat, tears, saliva

3. contracts ciliary muscle of the eye

-contracts pupillary sphincter

4. resistant to AChE

5. caution: COPD, asthma, peptic ulcers

Neostigmine

1. drug classification/MOA

2. clinical application

3. Special Notes

4. Caution 

1. Anti-cholinesterase (indirect muscarinic agonist)

2.-reversal of paralytics post-op (NMJ block)

-post-op/neurogenic ileus

-urinary retention

-myasthenia gravis

3. NO CNS PENETRATION

4. Caution: COPD, asthma, peptic ulcers

Pyridostigmine

1. Drug class/MOA

2. clinical application

3. Special Notes

4. Caution

1. anti-AChE (indirect muscarinic agonist)

2. Myasthenia Gravis

3. -Long acting

-NO CNS PENETRATION

4. Caution: COPD, asthma, peptic ulcers 

Edrophonium

1. Drug Class/MOA

2. Clinical application

3. Special notes

4. Caution

1. Anti-AChE (indirect muscarinic agonist)

2. Diagnosis of myasthenia gravis

3.-Tensilon Test

-extremely short acting

4. Caution: COPD, asthma, peptic ulcers

Physostigmine

1. drug class/MOA

2. clinical applications

3. Special Notes

4. Caution

1. Anti-AChE (indirect muscarinic agonist)

2. -glaucoma

-atropine overdose

3. physostigmine phyxes atropine OD

4. caution: COPD, asthma, peptic ulcers

Organophosphate Poisoning

1. mechanism of action

2. symptoms

3. treatment

4. special notes

1. irreversible inhibitors of AChE

2. DUMBBELSS

diarrhea, urination, miosis, bronchospasm, bradycardia, excite skeletal muscle, lacrimation, sweating, salivation

3. Atropine (anti-muscarinic)

with Pralidoxime (regenerates AChE)

4. Farmers using insecticides (Parathion)

Atropine

1. MOA

2. Action

3.Toxicity

4. Cautions

1. muscarinic antagonist

2. dilates pupil, cycloplegia

decreases airway secretions

decrease gut motility

decrease bladder contraction

3. hyperthermia, tachycardia, xerostomia, dry flushed skin, constipation, delirium

4. Elderly- can cause narrow glaucoma

BPH- can cause urinary retention

Infants- hyperthermia

Benztropine

1. Drug Class/MOA

2. Organ system

3. Clinical Application

4. Special notes

1. muscarinic antagonist

2. CNS

3. Parkinson's Disease

4. Park my Benz

Scopolamine

1. Drug class/MOA

2. organ system  it affects

3. Clinical Applications

1. muscarinic antagonist

2. CNS

3. Motion sickness, end of life care

Ipratropium

1. Drug Class/MOA

2. Organ system it affects

3. Clinical Applications

4. Special notes

1. muscarinic antagonist

2. CNS

3. Asthma, COPD

4. IPray I can breathe soon.

Oxybutinin, Tolteridine, Trospium, Darifenacin/Solifenacin

1. MOA

2. Organ System it affects

3. Clinical Applications

1. muscarinic antagonist

2. genitourinary

3. urge incontinence/mild cystitis

Glycopyrrolate

1. MOA

2. Organ System it affects

3. Clinical Applications

1. muscarinic antagonist

2. genitourinary, respiratory

3. -anesthesiology- reduce airway secretions

-reduce urinary urgency

Methscopolamine, Propantheline

1. Drug Class/MOA

2. Organ System it Affects

3. Clinical Applications

1. muscarinic antagonist

2. Gastrointestinal

3. peptic ulcer treatment

Hexamethonium

1. Drug Class/MOA

2. Actions

3. Clinical Application

4. Toxicity

5. Special Notes

1. nicotinic receptor antagonist

2. blocks sympathetic and parasympathetic

(depends on tone of the organ)

-decreased BP

-increased HR

-decreased CO

-dereased GI motility

-mydriatic pupils

-oliguria

3. experimental models to prevent vagal reflexes to BP change

4. severe orthostatic hypotension, blurry vision, constipation, sexual dysfunction

5. Put a hex on smokers to help them quit

Epinephrine

-class

-receptors 

-actions/applications

-special notes

-direct sympathomimetic

-alpha 1, 2 beta 1,2

(low doses- beta 2 high doses-alpha 1)

-Anaphylactic Shock, asthma, hypotension

- large dose + alpha blocker lowers BP (beta 2 effect unopposed by alpha) (caution in BPH patients)

Norepinephrine

-receptors

-applications

-special notes

direct sympathomimetic

-alpha 1, alpha 2 > beta 1

-Septic shock (hypotension)

-reflex bradtcardia

Isoproterenol

-receptors

-applications

-special notes

direct sympathomimetic

-beta 1= beta 2

-AV Block, lowers BP 

-rarely used clinically

-reflex tachycardia 

Dopamine

-receptors

-applications

-special notes

-direct sympathomimetic

-D1=D2 (inotropic, chronotropic on the heart) > Beta > Alpha

-Co administer with norepinephrine in septic shock to protect renal perfusion

- in vivo doesn't help kidney blood flow

Dobutamine

-receptors

-applications

direct sympathomimetic

-Beta 1 > Beta 2 (ino and chronotropic)

-heart failure, cardiac stress test ( increases O2 demand)

Phenylephrine

-receptors

-applications

direct sympathomimetic

-alpha 1 > alpha 2

-Nasal decongestion, epistaxis, causes mydriasis

Metaproterenol, Albuterol, Sametrerol

-receptors

-actions 

-applications

-special notes

Direct sympathomimetics

-Selective Beta 2 >> Beta 1

-relax bronchial, vascular smooth muscle

-Acute Asthma- metaproterenol, albuterol

-Asthma long term - salmeterol

-reflex tachycardia

Terbutaline, Ritodrine

-receptors

-Applications

direct sympathomimetics

-Beta 2

-Reduce premature uterine contractions

Amphetamine, Tyramine

-Drug class

-Actions

-Applications

-Indirect sympathomimetic

-Increases NE release at synapse

-Narcolepsy, ADD, obesity

Ephedrine

-Class

-MOA

-Applications

-indirect sympathomimetic

-Increases release of stored catecholamines

-Nasal decongestion, urinary incontinence, hypotension

Cocaine

-Class

-MOA

-Applications

-indirect sympathomimetic

-inhibits reuptake of NE at synapse

-Vasoconstriction (ENT) and local anesthetic

Clonidine,α-Methyldopa

Class

MOA

Applications

Special Notes

-sympathoplegic

α-2 agonists in CNS (stimulate autoreceptors)

-Hypertension-->renal dz and pregnancy

-frequent dosing, rebound hypertension if dose missed

Phenoxybenzamine, Phentolamine

-Drug class

-Application

-Special Notes

Non-selective Alpha blocker

-pheochromocytoma

-phenoxybenzamine is irreversible --> prophylaxis prior to resection of tumor

- orthostatic hypotension, reflex tachycardia

-if epinephrine given get drop in BP (unopposed B2 effect)

Prazosin, Terazosin, Doxazosin

Class

Applications

Toxicity

Special Note

-Selective Alpha 1 Blocker

-Hypertension, BPH-urinary retention

-First dose hypotension, dizziness, headache

-give first dose before bed

Tamsulosin

Class

Applications

-selective alpha 1 blocker prostate specific

-urinary retention in BPH for pts. w/o HTN

Mirtazapine

-Class

-Application

-Toxicity

selective Alpha 2 blocker

-depression, especially elderly

-sedation, hypercholesterolemia, orexigenic

Alpha 1 Receptor

-Major Functions

-G-Protein Class

Vasoconstriction

Mydriasis (contracts iris dilator m.)

Intestinal sphincter contraction

Bladder sphincter contraction

Uses Gq

(HAVe 1 M&M)

PLC-PIP2-IP3/DAG-PKC

Alpha 2 Receptor

Major Functions

Protein Class 

inhibitor of sympathetic outflow

vasodilation

decreases insulin release

Uses Gi

MAD 2's

(inhibits adenylyl cyclase->low cAMP, low PKA)

Beta 1 Receptor

Major functions

G protein class

Increase heart rate and contractility

increase renin release

increase lipolysis

Uses Gs

(Adenylyl cyclase-cAMP-PKA)

Beta 2 Receptor

Major functions

G Protein Class

Vasodilation

Bronchodilation

Uterine relaxation

Increases heart rate/contractility (reflexive)

Increases lipolysis and insulin release

Uses Gs

(Adenylyl cyclase-cAMP-PKA)

M1 Receptor

Major Functions

G Protein Class

CNS-arousal, memory

Enteric Nervous system- ECL cells-histamine

Uses Gq

HAVe 1 M&M

PLC-PIP2-IP3/DAG-PKC

M2 Receptor

Major functions

G protein class

Decrease heart rate and contractility (atria)

Uses Gi

(MAD 2's)

(Inhibits adenylyl cyclase- low cAMP- low PKA)

M3 Receptor

Major functions

G Protein Class

Exocrine glands- increase secretion

Gut secretions and peristalsis

Bladder contraction

Bronchoconstriction

Miosis (contracts iris constrictor m.)

Accommodation (contracts ciliary m.)

Uses Gq

HAVe 1 M&M

(PLC-PIP2-IP3/DAG-PKC)

D1 Receptor

Major Functions

G Protein Class

Renal vasodilation

Uses Gs

Adenylyl Cyclase- cAMP-PKA

D2 Receptor

Major Functions

G Protein Class

Modulates neurotransmitter release in brain

Uses Gi

MAD 2's

(inhibits adenylyl cyclase- low cAMP, low PKA)

H1 Receptor

Major functions

G Protein Class

Respiratory mucus production

Bronchiolar constriction

Pruritus

Pain

Allergies!

Uses Gq

(HAVe 1 M&M)

(PLC-PIP2-IP3/DAG-PKC)

H2 Receptor

Major functions

G Protein Class

Increases gastric acid secretion from parietal cells 

Uses Gs

(Adenylyl Cyclase-cAMP-PKA)

V1

Major functions

GProtein Class

vascoconstriction

Uses Gq

(HAVe 1 M&M)

PLC-PIP2-IP3/DAG-PKC 

V2

Major Functions

GProtein Class

Urine concentration/H20 resorption

(expression of resorption channels in collecting tubules of kidney)

(AQP2, NKCC2)

Uses Gs

Adenylyl cyclase- cAMP-PKA

Nadolol

Propranolol

Pindolol

Timolol

-Drug Class

-What's special about timoilol? Propranolol?

Non Selective Beta Blockers

(Block B1 and B2 equally)

-Timolol: Glaucoma (decreases secretion aqueous humor)

-Propranolol: SVT- class II antiarrhythmic

                      slows AV conduction velocity

Acetbutolol

Betaxolol

Esmolol

Atenolol

Metoprolol

Drug Class

Patient population

What's special about metoprolol? Esmolol?

Selective Beta 1 Blockers

A BEAM of Beta 1 Blockers

-Patients with comorbid pulmonary dz.

-Metoprolol reduces mortality after MI

-Esmolol: SVT short acting, IV, Class II antiarrhythmi

Slows AV conduction velocity

Carvedilol

Labetalol

Drug Class

What's special about carvedilol?

Non-Selective Alpha and Beta Blockers

Carvedilol reduces post-MI mortality

Beta Blockers

Applications

Toxicity

Specific Contraindications

App:

Hypertension: DOC for aortic dissection

Angina

Post-MI (metoprolol and carvedilol)

SVT (propranolol and esmolol)

Chronic/Stable CHF

Glaucoma (timolol)

TOX:

Impotence

Asthma exacerbation (use ABEAM of B1 selectives )

Bradycardia, AV block, CHF

CNS-sedation, altered sleep

Contraindications: Cocaine (unopposed alpha 1)

acebutolol, betaxolol, esmolol atenolol, metoprolol, propranolol, timolol, pindolol, labetolol

Volume of Distribution

Formula

Values and spaces

Vd = amt. drug in body

    Conc. in plasma

Low Vd- blood

Med Vd- ECF

High- all tissues (lipids)

Clearance

Formula

CL= V_d (0.7)

  t_1/2

(rate of elimination/plasma concentration)

Half Life

Formula

Steady States

t_1/2=0.7 (V_d)

CL

4 half lives- 93.75%

(of Css reached OR eliminated from the body)

Loading Dose

Formula

Special Situations

LD=C_p x V_d

              F

Affected by volume of distribution

Not altered by renal or liver disease

Bioavailability usually 1

Maintenance Dose

Formula

Special situations

 MD=C_p x CL

               F

Altered in renal or liver disease

Bioavailability usually 1

A substrate concentration; reflects enzyme affinity for substrate

Higher Km, lower affinity 

[S] at 1/2V_max

Increased by competitive inhibitors

Relates to potency of a drug

Max rate of enzyme activity- saturation

Proportional to enzyme concentration

Lowered by non-competitive inhibitors

Related to a drug's efficacy