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99 Cards in this Set

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Michaelis-Menton kinetics

Km - inversely related to affinity of enzyme for substrate
Vmax - directly proportional to enzyme concentration

Km - inversely related to affinity of enzyme for substrate


Vmax - directly proportional to enzyme concentration

Lineweaver-Burk plot

Inc. y-intercept, dec. Vmax
Inc. x-intercept (toward O), inc. Km

Inc. y-intercept, dec. Vmax


Inc. x-intercept (toward O), inc. Km

Competitive inhibitors, reversible



Resemble substrate:


Overcome by inc. [S]:


Bind active site:


Effect on Vmax:


Effect on Km:


Pharmacodynamics:

Competitive inhibitors, reversible



Resemble substrate: Yes


Overcome by inc. [S]: Yes


Bind active site: Yes


Effect on Vmax: Unchanged


Effect on Km: Increase


Pharmacodynamics: decrease potency

Competitive inhibitors, irreversible



Resemble substrate:


Overcome by inc. [S]:


Bind active site:


Effect on Vmax:


Effect on Km:


Pharmacodynamics:

Competitive inhibitors, irreversible



Resemble substrate: Yes


Overcome by inc. [S]: No


Bind active site: Yes


Effect on Vmax: Decrease


Effect on Km: Unchanged


Pharmacodynamics: Decrease efficacy

Noncompetitive inhibitors



Resemble substrate:


Overcome by inc. [S]:


Bind active site:


Effect on Vmax:


Effect on Km:


Pharmacodynamics:

Noncompetitive inhibitors



Resemble substrate: No


Overcome by inc. [S]: No


Bind active site: No


Effect on Vmax: Decrease


Effect on Km: Unchanged


Pharmacodynamics: Decrease efficacy

Enzyme inhibition graph

Bioavaliability

Fraction of drug reaching systemic circulation unchanged (F)

Bioavalibility: IV and Oral

IV: F = 100%



Oral: F <100% - incomplete absorption and first-pass metabolism

Volume of distribution (Vd)

Volume occupied by total amount of drug in body relative to its plasma concentration


 


 

Volume occupied by total amount of drug in body relative to its plasma concentration



Low Vd



Compartment:


Drug types:

Compartment: Blood



Drug types: Large/charged molecules; plasma protein bound



Apparent Vd of plasma protein-bound drugs can be altered by liver/kidney disease (dec. protein binding, inc. Vd)

Medium Vd



Compartment:


Drug types:

Medium Vd



Compartment: ECF



Drug types: small hydrophilic molecules

High Vd



Compartment:


Drug types:

High Vd



Compartment: All tissues including fat



Drug types: Small lipophilic molecules, especially if bound to tissue protein

Clearance (CL)

CL = Vd x Ke (elimination constant)


 


Decreased with cardiac, hepatic, renal problems

CL = Vd x Ke (elimination constant)



Decreased with cardiac, hepatic, renal problems

Half-life

Property of first-order elimination


 

Property of first-order elimination


More half-life info:



How many half-lives until drug infused at constant rate reaches steady-state?



How many half-lives until it reaches 90% of steady-state level?



Half-life chart: # half-lives and % remaining

Infused drug at constant rate takes 4-5 half-lives to reach steady state
 
Takes 3.3 half-lives to reach 90% of steady state level

Infused drug at constant rate takes 4-5 half-lives to reach steady state



Takes 3.3 half-lives to reach 90% of steady state level

Loading dose

Cp = target plasma [ ] at steady state


 


Unchanged by liver/renal disease

Cp = target plasma [ ] at steady state


Vd = distribution volume


F = bioavailability



Unchanged by liver/renal disease

Maintenance dose

Cp = target plasma [ ] at steady state


Tau = dosage interval (if not given continuously)


 


Decreased by liver/renal disease

Cp = target plasma [ ] at steady state


Tau = dosage interval (if not given continuously)


F = bioavailability



Decreased by liver/renal disease

Zero-order elimination

Constant rate of elimination, regardless of Cp
- Constant amount eliminated with time
- Cp decreases linearly with time
- Capacity-limited elimination
 
Phenytoin, Ethanol, and Aspirin - PEA is shaped like 0

Constant rate of elimination, regardless of Cp


- Constant amount eliminated with time


- Cp decreases linearly with time


- Capacity-limited elimination



Phenytoin, Ethanol, and Aspirin - PEA is shaped like 0


First-order elimination

Elimination rate directly proportional to [drug]
- Constant fraction eliminated with time
- Cp decreases exponentially with time
- Flow dependent elimination

Elimination rate directly proportional to [drug]


- Constant fraction eliminated with time


- Cp decreases exponentially with time


- Flow dependent elimination

Trapped in urine/cleared in urine or reabsorbed?



Ionized species:


Neutral species:

Trapped in urine/cleared in urine or reabsorbed?



Ionized species: Trapped/cleared


Neutral species: Reabsorbed

Urine pH and drug elimination



Weak acids

Weak acids


- Trapped in basic environments


- Treat overdose with bicarbonate



RCOOH <=> RCOO- + H+


(Lipid soluble) (Trapped)



Ex: phenobarbital, methotrexate, aspirin, TCAs


Urine pH and drug elimination



Weak bases

Weak bases


- Trapped in acidic environments


- Treat overdose with ammonium chloride



RNH3+ <=> RNH2 + H+


(Trapped) (Lipid soluble)

Drug metabolism: Phase I

Reduction, oxidation, and hydrolysis with cytochrome P-450



Yields slightly polar, water-soluble metabolites


- May still be active



Lost by geriatrics first

Drug metabolism: Phase II

Conjugation (Glucuronidation, Acetylation, Sulfation)



Yields polar, inactive metabolites - renally secreted



Geriatric patients have GAS


Slow acetylators: dec. metabolism, inc. side effects

Efficacy

Max effect drug can produce
- Y-value = Vmax
- Inc y = inc Vmax = inc efficacy
- Unrelated to potency

Max effect drug can produce


- Y-value = Vmax


- Inc y = inc Vmax = inc efficacy


- Unrelated to potency

Potency

Amount of drug needed for a given effect
- Inc potency (dec EC50) = less drug needed
- X-value = EC50
- Left shift = dec EC50 = inc potency
- Unrelated to efficacy

Amount of drug needed for a given effect


- Inc potency (dec EC50) = less drug needed


- X-value = EC50


- Left shift = dec EC50 = inc potency


- Unrelated to efficacy

Competitive agonist



Shift curve?


Effect on potency or efficacy?


Overcome by increasing [S]?


Example

Competitive agonist
 
Shift curve right
Dec potency
Overcome by inc [S]
 
Flumazenil vs. diazapam (agonist) on GABA receptor

Competitive agonist



Shift curve right


Dec potency


Overcome by inc [S]



Flumazenil vs. diazapam (agonist) on GABA receptor

Noncompetitive agonist



Shift curve?


Effect on potency or efficacy?


Overcome by increasing [S]?


Example

Noncompetive agonist
 
Shift curve down
Dec efficacy
Not overcome by inc [S]
 
Phenoxybenzamine vs. norepinephine (agonist) on alpha-receptors

Noncompetive agonist



Shift curve down


Dec efficacy


Not overcome by inc [S]



Phenoxybenzamine vs. norepinephine (agonist) on alpha-receptors

Partial agonist



Shift curve?


Effect on potency or efficacy?


Overcome by increasing [S]?


Examples

Acts on same site as full agonist but with lower max effect (dec efficacy)
- Potency is an independent variable
 
Buprenorphine vs. morphine (full agonist) at opioid mu-receptors

Acts on same site as full agonist but with lower max effect (dec efficacy)


- Potency is an independent variable



Buprenorphine vs. morphine (full agonist) at opioid mu-receptors

Therapeutic index

TD50/ED50 = median toxic dose/median effective dose
 
Safe drugs: high TI
Low TI: Digoxin, lithium, theophylline, warfarin
LD50 (lethal) often replaces TD50 in animal studies

TD50/ED50 = median toxic dose/median effective dose



Safe drugs: high TI


Low TI: Digoxin, lithium, theophylline, warfarin


LD50 (lethal) often replaces TD50 in animal studies

Adrenal medulla and sweat glands are part of sympathetic nervous system but are innervated by cholinergic fibers



Botulinum toxin prevents release of ACh at cholinergic terminals

ACh receptors



Nicotinic


Muscarinic

NAChR: ligand-gated Na+/K+ channels


- Nn (autonomic ganglia) and Nm (neuromuscular junction)



MAChR: G-protein-coupled recptors


- Act through second messengers


- 5 subtypes: M1through M5

G-protein-linked 2nd messenger mnemonic

Qiss and qiq until you're siq of sqs



alpha (1, 2) beta (1, 2) m (1,2,3) d (1,2) h (1,2) v (1,2)

Alpha receptors

Sympathetic



Alpha 1 - q


Inc: vascular smooth muscle contraction, pupillary dilator muscle contraction (mydriasis), intestinal and bladder sphincter contraction



Alpha 2 - i


Dec: sympathetic outflow, insulin release, lipolysis, aqueous humor production


Inc: platelet aggregation

Beta receptors

Sympathetic



Beta 1 - s


Inc: HR, contractility, renin release, lipolysis



Beta 2 - s


Inc: vasodilation, bronchodilation, lipolysis, insulin release, aqueous humor production


Dec: uterine tone (tocolysis), ciliary muscle tone

Muscarinic receptors

Parasympathetic



M1 - q


CNA, enteric nervous system



M2 - i


Dec: HR and atrial contractility



M3 - q


Inc: exocrine gland secretions (lacrimal, salivary, gastric acid), gut peristalsis, bladder contraction, bronchoconstriction, pupillary sphincter contraction (miosis, ciliary muscle contraction (accommodation)



Dopamine receptors

D1 - s


Relaxes renal vascular smooth muscle



D2 - i


Modulates transmitter release, especially in brain

Histamine receptors

H1 - q


Inc: nasal bronchial mucus production, vascular permeability, contraction of bronchioles, pruritus, pain



H2 - s


Inc gastric acid secretion

Vasopressin receptors

V1 - q


Inc vascular smooth muscle contraction



V2 - s


Inc H2O permeability and reabsorption in collecting tubules of kidney


V2 is found in 2 kidneys

What receptors use phospholipase C, protein kinase C, and Ca2+ in their pathways?

H1, A1, V1, M1, M3 (Gq)



All Gq receptors follow this pathway

What receptors use adenylyl cyclase, ATP, cAMP, and protein kinase A in their pathways?

B1, B2, D1, H2, V2 (Gs)



M2, A2, D2 (Gi)


MAD 2's



All Gs and Gi receptors follow this pathway

Sea otters sleep holding paws so they don't drift apart at night



Just wanted to include all the images. Sorry this is small on phones.

Release of norepi from a sympathetic nerve ending is modulated by norepi itself, acting on presynaptic alpha-2 autoreceptors



Just wanted to include all the images. Sorry this is small on phones.

Bethanechol



Category:


Clinical application:


Action:


Category: cholinomimetic - direct agonist



Clinical application: postop ilius, neurogenic ileus, urinary retention



Action: activates bowel and bladder smooth muscle; resistant to AChE

Carbachol



Category:


Clinical application:


Action:

Category: cholinomimetic - direct agonist



Clinical application: constricts pupil, relieves intraocular pressure in glaucoma



Action: carbon copy of acetylcholine

Methacholine



Category:


Clinical application:


Action:

Category: cholinomimetic - direct agonist



Clinical application: Challenge test for asthma diagnosis



Action: methacholine stimulates muscarinic receptors of airways

Pilocarpine



Category:


Clinical application:


Action:

Category: cholinomimetic - direct agonist



Clinical application: potent stimulator of sweat, tears, and saliva; open- and closed-angle glaucoma



Action: Contracts ciliary eye muscles (open-angle), pupillary sphincter (closed-angle); resistant to AChE


"You cry, drool, and sweat on your pillow"

Donepezil, galantamine, rivastigmine



Category:


Clinical application:


Action:

Category: cholinomimetic - indirect agonist (anticholinesterase)



Clinical application: Alzheimer disease



Action: inc ACh

Edrophonium



Category:


Clinical application:


Action:

Category: cholinomimetic - indirect agonist (anticholinesterase)



Clinical application: historically used to dx myasthenia gravis (very short acting), but now MG diagnosed by anti-AChR Ab test



Action: inc ACh

Neostigmine



Category:


Clinical application:


Action:

Category: cholinomimetic - indirect agonist (anticholinesterase)



Clinical application: Postop and neurogenic ileus and urinary retention, myasthenia gravis, reversal of neuromuscular junction blockade (postop)



Action: inc ACh


Neo CNS = no CNS penetration

Physostigmine



Category:


Clinical application:


Action:

Category: cholinomimetic - indirect agonist (anticholinesterase)



Clinical application: ACh toxicity; crosses blood-brain-barrier (CNS)



Action: inc ACh


Physostigmine phyxes atropine overdose

Pyridostigmine



Category:


Clinical application:


Action:

Category: cholinomimetic - indirect agonist (anticholinesterase)



Clinical application: Myasthenia gravis (long acting); doesn't penetrate CNS



Action: inc ACh; inc muscle strength


Pyridostigmine gets rid of myasthenia gravis

Potential side-effect of cholinomimetics to watch for

Cholinomimetics can cause exacerbation of COPD, asthma, and peptic ulcers

Cholinesterase inhibitor poisoning

Due to organophosphates that irreversibly inhibit AChE


Antidote: atropine (competitive inhibitor) + pralidoxime (regenerates AChE if given early)



DUMBBELSS


diarrhea, urination, miosis, bronchospasm, bradycardia, excitation of skeletal muscle and CNS, lacrimation, sweating, salivation

Atropine, homatropine, tropicamide



Category:


Organ systems:


Clinical application:


Category: muscarinic antagonist



Organ systems: Eye



Clinical applications: produce mydriasis and cycloplegia

Benztropine



Category:


Organ systems:


Clinical application:

Category: muscarinic antagonist



Organ systems: CNS



Clinical applications: Parkinson disease (park my Benz); acute dystonia

Glycopyrrolate



Category:


Organ systems:


Clinical application:

Category: muscarinic antagonist



Organ systems: GI, respiratory



Clinical applications:


Parenteral: preoperatively to reduce airway secretions


Oral: drooling, peptic ulcer


Hyoscyamine, dicyclomine



Category:


Organ systems:


Clinical application:

Category: muscarinic antagonist



Organ systems: GI



Clinical applications: antispasmodic for irritable bowel syndrome

Ipratropium, tiotropium



Category:


Organ systems:


Clinical application:

Category: muscarinic antagonist



Organ systems: respiratory



Clinical applications: COPD, asthma


I pray I can breathe soon!

Oxybutynin, solifenacin, tolterodine



Category:


Organ systems:


Clinical application:

Category: muscarinic antagonist



Organ systems: genitourinary



Clinical applications: reduce bladder spasms and urge urinary incontinence (overactive bladder)

Scopolamine



Category:


Organ systems:


Clinical application:

Category: muscarinic antagonist



Organ systems: CNS



Clinical applications: motion sickness

Albuterol, salmeterol



Category:


Receptors effected:


Clinical application:

Category: Sympatheticomimetic



Receptors effected: B2 > B1



Clinical application: Albuterol for acute asthma, salmeterol for long-term asthma or COPD

Dobutamine



Category:


Receptors effected:


Clinical application:

Category: Sympatheticomimetic



Receptors effected: B1 > B2, A



Clinical application: heart failure (inotropic > chronotropic), cardiac stress testing

Dopamine



Category:


Receptors effected:


Clinical application:

Category: Sympatheticomimetic



Receptors effected: D1 = D2 > B > A



Clinical application: unstable bradycardia, HF, shock


- Inotropic and chronotropic alpha effects predominate at high doses

Epinephrine



Category:


Receptors effected:


Clinical application:

Category: Sympatheticomimetic



Receptors effected: B > A



Clinical application: anaphylaxis, asthma, open-angle glaucoma


- Alpha effects predominate at high doses


- Significantly stronger effect at beta 2 receptor than norepi

Isoprotenrenol



Category:


Receptors effected:


Clinical application:

Category: Sympatheticomimetic



Receptors effected: B1 = B2



Clinical application: electrophysiologic evaluation of tachyarrhythmias


- Can worse ischemia

Norepinephrine



Category:


Receptors effected:


Clinical application:

Category: Sympatheticomimetic



Receptors effected: A1 > A2 > B1



Clinical application: hypotension (but dec renal perfusion)


- Weaker effect on beta 2 receptor than epi

Phenylephrine



Category:


Receptors effected:


Clinical application:

Category: Sympatheticomimetic



Receptors effected: A1 > A2



Clinical application: hypotension (vasoconstriction), ocular procedures (mydriatic), rhinitis (decongestant)

Amphetamine



Category:


Mechanism:


Clinical application:

Category: Indirect sympatheticomimetic



Mechanism: indirect general agonist, reuptake inhibitor, also releases stored catecholamines



Clinical application: narcolepsy, obesity, ADHD

Cocaine



Category:


Mechanism:


Symptoms:

Category: Indirect sympatheticomimetic



Mechanism: indirect general agonist, reuptake inhibitor



Symptoms: causes vasoconstriction and local anesthesia



Never give beta-blockers if cocaine intox suspected (can lead to unopposed alpha 1 activation and extreme HTN)

Ephedrine



Category:


Mechanism:


Clinical application:

Category: Indirect sympatheticomimetic



Mechanism: indirect general agonist, reuptake inhibitor, releases stored catecholamines



Clinical application: nasal decongestion, urinary incontinence, hypotension

Norepinephrine vs. isoproterenol

Norepinephrine inc􏰀 BP (alpha 1) but dec HR b/c inc 􏰂􏰀mean arterial pressure causes reflex bradycardia



Isoproterenol has little alpha effect but causes vasodilation (beta 2), resulting in dec 􏰁MAP and􏰀 inc HR through beta 1 and reflex activity

Clonidine



Category:


Applications:


Toxicity:

Category: Sympatholytic (alpha 2 agonist)



Applications: hypertensive urgency (limited situations); doesn't decrease renal blood flow


ADHD, Tourette syndrome



Toxicity: CNS depression, bradycardia, hypotension, respiratory depression, miosis

Alpha-methyldopa



Category:


Applications:


Toxicity:

Category: Sympatholytic (alpha 2 agonist)



Applications: HTN in pregnancy



Toxicity: direct Coombs positive hemolysis, SLE-like syndrome

Non-selective alpha blockers



Applications:


Side effects:

Phenoxybenzamine (irreversible)


Applications: pheochromocytoma (preoperative) to prevent catecholamine (hypertensive) crisis



Phentolamine (reversible)


Applications: give to patients on MAO inhibitors who eat tyramine-containing foods



Side effects: orthostatic hypotension, reflex tachycardia


Alpha 1 selective blockers



Examples:


Applications:


Side effects:

Examples: prazosin, terazosin, dexazosin, tamsulosin (all end in -osin)



Applications: urinary symptoms of BPH, PTSD (prazosin), HTN (except tamsulosin)



Side effects: 1st-dose orthostatic hypotension, dizziness, headache

Alpha 2 selective blockers



Applications:


Side effects:

Mirtazapine



Applications: depression



Side-effects: inc serum cholesterol and appetite

Effect on blood pressure of alpha-blockade of epinephrine vs. phenylephrine

Epinephrine


Initial response: increase BP (alpha response)


After alpha-block: decrease BP below normal (beta response)



Phenylephrine


Initial response: increase BP (alpha response)


After alpha-block: BP back to normal (not decreased like epi b/c it has no beta action)

Beta-blocker application and effects

Angina pectoris: dec HR and contractility, dec O2 consumption


MI: decrease mortality


SVT (metoprolol, esmolol): dec AV conduction velocity (class II antiarrhythmic)


HTN: dec cardiac output, dec renin secretion (beta 1 receptor blockade on JGA cells)


Heart failure: dec mortality in chronic HF


Glaucoma (timolol): dec secretion of aqueous humor

Beta-blocker toxicity

Impotence


Heart issues (bradycardia, AV block, HF)


CNS issues (seizures, sedation, sleep alterations)


Dyslipidemia (metoprolol)


Asthma/COPD exacerbations



Don't give with cocaine (unopposed alpha - HTN)



Still give to diabetics - don't worry about hypoglycemia b/c benefits outweigh risks

Beta 1 selective antagonists

Acebutolol, (partial agonist), atenolol, betaxolol, esmolol, metoprolol



Selective antagonists mostly go from A to M


Beta 1 with 1st 1/2 of alphabet

Non-selective beta antagonists

Nadolol, pindolol (partial agonist), propranolol, timolol



Non-selective antagonists mostly go from N to Z


Beta 2 with the 2nd 1/2 of the alphabet

Non-selective alpha and beta antagnoists

Carvedilol and labetalol



Non-selective alpha and beta antagonists have modified endings (-ilol and -atol instead of -olol)

Nebivolol - what's special about it?

Combines cardiac-selective beta 1 blockade with stimulation of beta 3 receptors, activating nitric oxide synthase in vasculature

Study the list of specific antidotes and drug reactions from page 257 to 260 in First Aid 2015.

It is too long of a list for flashcards. Sorry :(

Drugs that cause.....



Vasospasm

Cocaine, sumatriptan, ergot alkaloids

Drugs that cause.....



Cutaneous flushing

Vancomycin, adenosine, niacin, Ca2+ channel blockers



Vanc

Drugs that cause.....



Dilated cardiomyopathy

Anthacyclines (doxorubicin, daunorubicin)



Prevent with dexrazoxane

Drugs that cause.....



Torsades de pointes

Class II (solatol) and class IA (quinidine) antiarrhymics, macrolide antibiotics, antipsychotics, TCAs

Drugs that cause.....



Adrenocortical insufficiency

HPA surpression secondary to glucocorticoid withdrawal

Drugs that cause.....



Hot flashes

Tamoxifen, clomiphene

Drugs that cause.....



Hyperglycemia

Tacrolimus, protease inhibitors, niacin, HCTZ, corticosteroids



Taking pills necessitates having blood checked

Drugs that cause.....



Hypothyroidism

Lithium, amiodarone, sulfonamides

Drugs that cause.....



Acute cholestatic hepatitis, jaundice

Erythromycin

Drugs that cause.....



Diarrhea

Metformin, erythromycin, colchicine, orlistat, acarbose



Might excite colon on accident

Drugs that cause.....



Focal to massive hepatic necrosis

Halothane, amanita phalloides (death cap mushroom), valproic acid, acetaminophen



Liver HAVAc

Drugs that cause.....



Hepatitis

Rifampin, isoniazid, pyrazinamide, statins, fibrates

Drugs that cause.....



Pancreatitis

Didanosine, corticosteroids, alcohol, valproic acid, azathioprine, diuretics (furosemide, HCTZ)



Drugs causing a violent abdominal distress

Drugs that cause.....



Pseudomembranous colitis

Clindamycin, ampicillin, cephalosporins



Antibiotics predispose to superinfection by resistant C. difficile