Usmle Step 1: Pharmacology

Front 1

Enzyme Kinetics

(Km, Vmax, types of inhibitors)

Back 1

- Km: [S] required to achieve 50% of Vmax; reflects the affinity of the enzyme for the substrate (low Km = high affinity)

- Vmax: velocity achieved as [S] approaches infinity (with constant [E])

- Competitive inhibitors: bind E thereby increasing Km (decreasing E-S affinity)
- Noncompetitive inhibitors: bind ES thereby decreasing Vmax
- Uncompetitive inhibitors: bind both E and ES thereby increasing Km and decreasing Vmax

Front 2

Pharmacokinetics

(Vd, CL, t1/2)

Back 2

- Vd: volume of distribution = (amount of drug in the body)/(plasma drug concentration)
- Drugs with: low Vd distribute in blood; medium Vd distribute in extracellular space or body water; high Vd distribute in tissues

- CL: (rate of drug elimination)/(plasma drug concentration) = Vd x Ke

- t1/2: time required to change the amount of drug in the body by 1/2 during elimination (or infusion)
- t1/2 = 0.7Vd/CL

Front 3

Dosage Calculations

(Loading dose, Maintenance dose)

Back 3

- Loading dose = CpVd/F
- Maintenance dose = CpCL/F

- Cp: target plasm concentration
- F: bioavailability (= 1 when drug given IV)

Front 4

Elimination of drugs

(0 order, 1st order)

Back 4

- Zero-order elimination: rate of elimination is constant (regardless of concentration); phenytoin, ethanol and aspirin are all zero-order at high/toxic concentrations

- First-order elimination: rate of elimination is proportional to drug concentration

Front 5

Urine pH and drug elimination

Back 5

- ionized species get trapped

- weak acids: trapped in basic environments; treat overdose w/ biocarbonate
- weak bases: trapped in acidic environment; treat overdose w/ ammonium chloride

Front 6

Phase I vs. Phase II metabolism

Back 6

- Phase I: reduction, oxidation, hydrolysis (cytochrome-p450; usually yields slightly polar, water-soluble metabolites (often still active)

- Phase II: acetylation, glucuronidation, sulfation (conjugation); usually yields very polar, inactive metabolites (renally excreted)

Front 7

Pharmacodynamics

(partial and full agonists)

Back 7

- a partial agonist has lower maximal efficacy than a full agonist
- potency is independent

- efficacy: percent of maximal efficacy achieved by a given dose
- potency: dose required to achieve a specific efficacy

Front 8

Therapeutic index

Back 8

- TI = LD50/ED50 (TILE)

- LD50: median toxic dose
- ED50: median effective dose

- safer drugs have higher TI values

Front 9

ACh Receptors

Back 9

- Nicotinic ACh receptors are ligand-gated Na/K channels

- Muscarinic ACh receptors are GPCRs that act through 2nd messangers

Front 10

Bethanechol

Back 10

- direct cholinergic agonist
- used to treat postoperative and neurogenic ileus and urinary retention
- activates bowel and bladder smooth muscle
- resistant to AChE

- Beth Anne, Call me if you want to active your Bowels and Bladder

Front 11

Pilocarpine

Back 11

- direct cholinergic agonist
- potent stimulated of sweat, tears, saliva
- contracts ciliary muscle of eye, pupillary sphincter
- resistant to AChE

- PILE on the sweat and tears

Front 12

Neostigmine

Back 12

- indirect cholinergic agonist
- used for postoperative and neurogenic ileus and urinary retention, myasthenia gravis, reversal of NMJ blockade (postoperative)
- increases endogenous ACh
- no CNS penetration

Front 13

Physostagmine

Back 13

- indirect cholinergic agonist
- used to treat glaucoma and atropine oversdoes
- increases endogenous ACh

- PHYS is for EYES (how shitty is that)

Front 14

Cholinesterase inhibitor poisoning

Back 14

- syptoms include: diarrhea, urination, miosis, bronchospasm, bradycardia, excitation of skeletal muscle and CNS, lacrimation, sweating and salivation (also abdominal cramping)
- antidote: atropine (muscarinic antagonist) plus pralidoxime (chemical antagonist used to regenerate active cholinesterase)

- DUMBBELSS

Front 15

Atropine

Back 15

- muscarinic antagonist
- works on the eye
- produces mydriasis and cycloplegia

Front 16

Scopolamine

Back 16

- muscarinic antagonist
- works on CNS
- used for motion sickness

Front 17

Epinephrine

Back 17

- alpha-agonist
- decreases aqueous humor synthesis due to vasoconstriction
- used to treat glaucoma

Front 18

Atropine

Back 18

- muscarinic antagonist

- pupillary dilation, cycloplegia
- decreased bronchial secretions
- decreased stomach acid secretion
- decreased gut motility
- decreased bladder urgency in cystitis

- blocks DUMBBELSS

toxicity
- increased body temp, rapid pulse, dry mouth, dry/flushed skin, cycloplegia, constipation, disorientation

Front 19

Hexamethonium

Back 19

- nicotinic antagonist
- ganglionic blocker

- used to prevent vagal reflex response to changes in blood pressure

- toxicity: severe orthostatic hypotension, blurred vision, constipation, sexual dysfunction

Front 20

Epinephrine

Back 20

- agonist of α1, α2, β1, β2, low doses selective for β1
- selective for beta-1 at low doses

- used to treat anaphylaxis, open angle glaucoma, asthma, hypotension

Front 21

Norepinephrine

Back 21

- agonist of α1, α2 > β1

- used to treat hypotension
- but decreases renal perfusion

Front 22

Isoproterenol

Back 22

- agonist of β1 = β2

- used as an AV block

Front 23

Dopamine

Back 23

- agonist of D1 = D2 > β > α, inotropic and chronotropic

- used to treat shock (↑ renal perfusion), heart failure

Front 24

Dobutamine

Back 24

- agonist of β1 > β2, inotropic but not chronotropic

- used to treat shock, heart failure and in cardiac stress testing

Front 25

Phenylephrine

Back 25

- agonist of α1 > α2

- used to cause pupillary dilation, vasoconstriction, nasal decongestion

Front 26

Terbutaline

Back 26

- agonist of β2 > β1

- used to reduce premature uterine contractions

Front 27

Ritodrine

Back 27

- agonist of β2

- reduces premature uterine contractions

Front 28

Ephedrine

Back 28

- indirect general sympathetic agonist; releases stored catecholamines

- used to treat narcolepsy, obesity, attention deficit disorder

Front 29

Cocaine

Back 29

- indirect general sympathetic agonist; releases stored catecholamines

- causes nasal decongestion, urinary incontinence, hypotension

Front 30

Clondine

Back 30

- centrally acting α2-agonist, ↓ central adrenergic outflow

- used to treat hypertension, especially with renal disease (no ↓ in blood flow to kidney)

- are you sure this isnt an antagonist?

Front 31

α-methyldopa

Back 31

- centrally acting α2-agonist, ↓ central adrenergic outflow

- used to treat hypertension, especially with renal disease (no ↓ in blood flow to kidney)

- are you sure this isnt an antagonist?