USMLE - Pharm Part 1

v = (Vmax[S])/(Km + [S])
Vmax directly proportional to enzyme concentration
Km inversely related to the affinity of the enzyme for its substrate
At 1/2 Vmax, Km=[S]
Hyperbolic

Enzymes that show cooperative kinetics (hemoglobin) have sigmoid curves

1/V

1/[S]

Km/Vmax

1/Vmax. As y-intercept ↑, Vmax ↓

-1/Km. As x-intercept moves further to the right, ↑Km (lower affinity)

Vmax stays the same as Km moves closer to the right. ↑Km (lower affinity)
y-intercept increases (↓Vmax) but Km (x-intercept) stays the same

Resemble substrate

Overcome by ↑[S]

Binds active site

Vmax unchanged

Km ↑

↓ potency

NonCompetitive Inhibitors

Resemblance to substrate

Over come by ↑[S]

Bind active site

Effect on Vmax

Effect on Km

Pharmacodynamics

F
Fraction of administered dose that reaches systemic circulation unchanged
IV dose

Vd
Theoretical fluid volume required to maintain the total absorbed drug amount at plasma concentration
Vd of plasma-protein bound drugs can be altered by liver and kidney disease (↓ protein binding, ↑ Vd)
(Amount of drug in body)/(plasma drug concentration)

4-8L
Blood
Large/charged molecules; plasma protein bound

ECF
Small hydrophilic molecules

All tissues
Small lipophilic molecules, especially if bound to tissue protein

4 to 5

First Order Elimination (.7Vd)/CL

CL
Relates rate of elimination to the plasma concentration
Impaired with defect in cardiac, hepatic, or renal function
(Rate of elimination)/(Plasma drug concentration) = Vd x Ke (elimination constant)

Cp x (Vd/F)

Cp = target plasma concentration

Cp x (CL/F)

Cp = target plasma concentration

Loading dose remains the same
Maintenance dose ↓

Half life
Independent of dosing frequency or size

Rate of elimination is constant regardless of Cp. Constant amount of drug eliminated per unit time
“PEA looks like a 0”
Phenytoin, EtOH, Aspirin (at high concentrations)

Rate of elimination is directly proportional to the drug concentration. Constant fraction of drug eliminated per unit time
Cp ↓ exponentially with time
Flow-Dependent Elimination

Ionized species trapped in the urine and cleared quickly. Neutral forms can be reabsorbed
Trapped in basic environments so treat OD with bicarb. Phenobarbital, Methotrexate, Aspirin
Trapped in acidic environments. Treat OD with Ammonium chloride. Amphetamines

RedOx or hydrolysis
Cytochrome P450
Usually yields slightly polar water soluble metabolites (often still active)
Lost in geriatric pts

"GAS"

Conjugation (Glucuronidation, Acetylation, Sulfation)

Very polar inactive metabolites

Renally excreted

Slow acetylators

Maximal effect a drug can produce
Analgesics, Antibiotics, Decongestants

Amount of drug needed for a given effect
↑ potency --> ↑ receptor affinity
Chemotherapeutic drugs, AntiHTN, AntiLipid

Shifts curve to Right

Potency ↓

No change in efficacy

↑ [agonist]

Diazepam and Flumazenil @ GABA Receptor

Shifts curve down
Efficacy ↓
Cannot be overcome by ↑ [agonist]
NE and Phenoxybenzamine @ α receptors

Acts at same site as full agonist but with reduced maximal effect

Left shift at low concentrations but then levels off sooner and at lower concentration

Variable

Efficacy ↓

Buprenorphine @ μ

Measure of drug safety
"TILE"
(Median Lethal dose)/(Median Effective dose)
Safer drugs have high TI
Low TI: Digoxin, Li, Theophylline, Warfarin

Measure of clinical drug safety
Range of minimum effective dose to minimum toxic dose
Safe drugs have large TW

NaHCO3 (alkalinize urine), Dialysis

NH4Cl (acidify urine)

Atropine, Pralidoxime

Physostigmine Salicylate and Control Hyperthermia

Glucagon

"stay "KALM"
| Normalize K, Anti dig Fab Fragment, Lidocaine, Mg

DeFEroxamine, deFErasirox

EDTA, Dimercaprol, Succimer, Penicillamine

Dimercaprol, Succimer

Penicillamine

Nitrite + Thiosulfate, Hydroxocobalamin

Methylene Blue, VitC

100% O2, Hyperbaric O2

Fomepizole, EtOH, Dialysis

Naloxone, Naltrexone

Flumazenil

NaHCO3 (plasma alkalinization)

Protamine Sulfate

VitK, Fresh Frozen Plasma

Aminocaproic Acid

β blockers

Cocaine, Sumatriptan, Ergot Alkaloids

"VANC"
| Vancomycin, Adenosine, Niacin, Ca channel blockers

Doxorubicin (Adriamycin), Daunorubicin

Class III (Sotalol) and Class IA (Quinidine)

"Agranulocytosis Could Certainly Cause Pretty Major Damage"

| Clozapine, Carbamazepine, Colchicine, Propylthiouracil, Methimazole, Dapsone

Chloramphenicol, Benzene, NSAIDs, Propylthiouracil, Methimazole

MethyDOPA, Penicillin

Chloramphenicol

"Hemolysis IS PAIN"

| Isoniazid, Sulfonamides, Primaquine, Aspirin, Ibuprofen, Nitrofurantoin

"Having a blast with PMS"

| Phenytoin, Methotrexate, Sulfa drugs"

OCP (estrogen)

ACEI

"BLAB"

| Bleomycin, Amiodarone, Busulfan

Erythromycin

"Liver HAVAc"

| Halothane, Amanita Phalloides, Valproic Acid, Acetaminophen

INH

Clindamycin and Ampicillin

Steroids

"Some Drugs Create Awkward Enormous Knockers"

| Spironolactone, Digitalis, Cimetidine, Alcohol, Estrogen, Ketoconazole

Tamoxifen, Clomiphene

Niacin, Tacrolimus, Protease Inhibitors, HCTZ, Corticosteroids

Li, Amiodarone, Sulfonamides

Steroids, Protease Inhibitors

Phenytoin, Verapamil

Furosemide, Thiazides, Niacin, Cyclosporine

"Fish N CHIPS Give you myopathies"

| Fibrates, Niacin, Colchicine, Hydroxychloroquine, IFNα, Penacillamine, Statins, Glucocorticoids

Glucocorticoids, Heparin

"SAT for a photo"

| Sulfonamides, Amiodarone, Tetracycline

"bad rash for a PEC SLAPP"

| Penicillin, Ethosuximide, Carbamazepine, Sulfa drugs, Lamotrigine, Allopurinol, Phenytoin, Phenobarbital

"HIPP"

| Hydralazine, INH, Procainamide, Phenytoin

Tetracyclines

Fluoroquinolones

Li, Demeclocycline

Expired Tetracycline

Cyclophosphamide, Ifosfamide

| Prevented by Mesna

Methicillin, NSAIDs, Furosemide

Carbamazepine, Cyclophosphamide

Quinidine, Quinine

Antipsychotics, Reserpine, Metoclopramide

"during seizures I BITE My tongue"

| Isoniazid, Bupropion, Imepenem/cilastatin, Tramadol, Enflurane, Metoclopramide

Antipsychotics

Atropine, TCAs, H1 blockers, Neuroleptics

Metronidazole, Cephalosporins, Procarbazine, 1st gen Sulfonylureas

Aminoglycosides, Vancomycin, Loop Diuretics, Cisplatin

"Momma Barb Steals Phen-phen and Refuses Greasy Carbs Chronically"

Modafinil, Barbiturates, St John's wort, Phenytoin, Rifampin, Griseofulvin, Carbamazepine, Chronic EtOH

"MAGIC RACKS in GQ"

Macrolides, Amiodarone, Grapefruit juice, Isoniazid, Cimetidine, Ritonavir, Acute EtOH abuse, Ciprofloxacin, Ketoconazole, Sulfonamides, Gemfibrozil, Quinidine

"Popular FACTSSS"

| Probenecid, Furosemide, Acetazolamide, Celecoxib, Thiazides, Sulfonamide Antibiotics, Sulfasalazine, Sulfonylureas

Fever, UTI, Pruritic rash, Stevens-Johnson Syndrome, Hemolytic Anemia, Thrombocytopenia, Agranulocytosis, Urticaria

Antifungal