Km is inversely related to…
the affinity of the enzyme for its substrate.
Vmax is directly proportional to…
the enzyme concentration.
Most enzymatic reactions follow…
a hyperbolic curve (follow Michaelis-Menten kinetics); however, enzymatic reactions that exhibit a sigmoid curve usually indicate cooperative kinetics (ex. hemoglobin).
On a Lineweaver-Burk plot, increased y-intercept means…
On a Lineweaver-Burk plot, the further to the right the x-intercept…
the greater the Km and the lower the affinity.
Slope of a Lineweaver Burk-plot =
x-intercept of Lineweaver-Burk plot =
y-intercept of Lineweaver-Burk plot =
On a Lineweaver-Burk plot, competitive inhibitors…
cross each other competitively, whereas noncompetitive inhibitors do not.
Inhibitors that resemble substrate
Competitive (both reversible and irreversible)
Inhibitor that is overcome by increased substrate
reversible, competitive inhibitors
Competitors that bind the active site
competitive, both reversible and irreversible
Effect of competitors on Vmax
Competitive reversible: unchanged Competitive irreversible: decreased Noncompetitive: decreased
Effect of competitiors on Km
Competitive reversible: increased Competitive irreversible: unchanged Noncompetitive: unchanged
Pharmacodynamics of competitors
Competitive reversible: decreased potency Competitive irreversible: decreased efficacy Noncompetitive: decreased efficacy
the effects of the body on the drug (absorption, distribution, metabolism, excretion)
the effects of the drug on the body (receptor binding, drug efficacy/potency, toxicity)
Bioavailability (F) is the…
fraction of administered drug that reaches the systemic circulation unchanged.
For an IV dose, F =
100%. Orally, F typically is <100% due to incomplete absorption and first-pass metabolism.
The volume of distribution (Vd) is the…
theoretical volume occupied by teh total absorbed drug amount at the plasma concentration.
The apparent volume of distribution of plasma protein boudn drugs can be altered by…
liver and kidney disease becasue decreased protein binding will increase Vd.
(amount of drug in the body)/(plasma drug concentration)
Vd is usually low if the drug is in the…
blood. Drug types include large, charged molecules that are plasma protein bound.
Vd is medium if the drug is in the…
ECF. Drug types include small hydrophilic molecules.
Vd is large if the drug is in…
all tissues including fat. Drug types include small lipophilic molecules, especially if bound to tissue protein.
Half-life (t1/2) is the…
time required to change the amoun tof drug in the body by 1/2 during elimination (or constant infusion).
To reach steady state, a drug infused at a constant rate takes…
4-5 half lives.
(.693 x Vd)/CL
Clearance (CL) is the…
volume of plasma cleared of drug per unit time. It may be impaired by defects in cardiac, hepatic or renal function.
(rate of elimination of drug)/(plasma drug concentration) = Vd x Ke
Loading dose =
(Cp x Vd)/F
Maintenance dose =
(Cp x CL x tau)/F
In renal or liver disease, maintenance dose…
decreases and loading dose is usually unchanged.
Time to steady state primarily depends on…
t1/2 and is independent of dose and dosing frequency.
Zero order elimination is when…
the rate of elimination is constant regardless of Cp. (capacity-limited elimination) (it is a constant AMOUNT of drug eliminated per unit time)
In zero order elimination, with time, Cp decreases…
Examples of drugs with zero order elimination
Phenytoin Ethanol Aspirin
First order elimination is…
when the rate of elimination is directly proportional to the drug concentration. (flow-dependent elimination) (a constant FRACTION of drug is eliminated per unit time)
In first order elimination, with time, Cp decreases…
Ionized drug species are…
trapped in the urine and cleared quickly. Netural forms can be reabsorbed.
Examples of weak acids
Phenobarbital, Methotrexate, aspirin (overdose should be treated with bicarbonate)
Weak acids become..
trapped in basic environments.
Example of weak base
Amphetamines (overdose should be treated with ammonium chloride)
Weak bases become…
trapped in acidic environments.
Phase I of drug metabolism includes…
reduction, oxidations, hydrolysis with cytochrome P-450 usually yields slightly plar, water-soluble metabolites (often still active).
Geriatric patients lose…
phase I first.
Phase II of drug metabolism includes…
conjugation (glucuronidation, acetylation, and sulfation) which usually yields very polar, inactive metabolites that are renally excreted.
Patients who are slow acetylators have…
greater side effects from certain drugs due to decreased rate of metabolism.
Efficacy is the..
maximal effect a drug can produce.
High-efficacy drug classes are…
analgesics, antibiotics, antihistamines and decongestants.
Potency is the…
amount of drug needed for a given effect. Increased potency has increased affinity for receptors.
High potency drug classes include…
chemo, antihypertensives, and lipid-lowering drugs.
Therapeutic index is a measure of…
drug safety. Safer drugs have higher TI values.
Examples of drugs with lower TI values include…
digoxin, lithium, theophylline and warfarin.
(TD50)/(ED50) = (median toxic dose)/(median effective dose)
The therapeutic window is the…
measure of clinical drug effectivenes for a pt.
The adrenal medulla and sweat glands are part of…
the sympathetic nervous system but are innervated by cholinergic fibers.
Botulinum toxin prevents release of…
NT at all cholinergic terminals.
Nicotinic ACh receptors are…
ligand gated Na+/K+ channels.
Subtypes of nicotinic receptors are…
N(N) - found in autonomic ganglia N(M) - found in NMJ
Muscarinic ACh receptors are…
G-protein coupled receptors that usually act through 2nd messengers. 5 subtypes (M1, M2, M3, M4 and M5).
alpha1 receptor G-protein class
alpha2 receptor G-protein class
beta1 and beta2 receptor G-protein class
alpha1 receptor major functions (3)
- increase vascular smooth muscle contraction 2. increase pupillary dilator muscle contraction 9mydriasis) 3. increase intestinal and bladder sphincter muscle contraction
alpha2 receptor major functions (4)
- decrease sympathetic outflow 2. decrease insulin release 3. decrease lipolysis 4. increase platelet aggregation
beta1 receptor major functions (4)
- increase hr 2. increase contractility 3. increase renin release 4. increase lipolysis
beta2 receptor major functions (9)
- vasodilation 2. bronchodilation 3. increase hr 4. increase contractility 5. increase lipolysis 6. increase insulin release 7. decrese uterine tone 8. ciliary muscle relaxation 9. increase aqueous humor production
alpha1 alpha2 beta1 beta2
M1 M2 M3
M1 and M3 G-protein class
M2 G-protein class
M1 receptor major functions
CNS, enteric nervous system
M2 receptor major functions
decrease hr and contractility of atria
M3 receptor major functions (6)
- increase exocrine gland secretions 2. increase gut peristalsis 3. increase bladder contraction 4. bronchoconstriction 5. increase pupillary sphincter muscle contraction (miosis) 6. ciliary muscle contraction (accommodation)
D1 receptor G-protein class
D2 receptor G-protein class
D1 receptor major function
relaxes renal vascular smooth muscle
D2 receptor major function
modulates transmitter releases, especially in the brain
H1 receptor G-protein class
H2 receptor G-protein class
H1 receptor major functions (5)
- increased nasal and bronchial mucus production 2. increased vascular permeability 3. contraction of bronchiles 4. pruritis 5. pain
H2 receptor major functions
increase gastric acid secretion
V1 (vasopressin) G-protein class
V2 (Vasopressin) G-protein class
V1 receptor major function
increase vascular smooth muscle contraction
V2 receptor major function
increase H2O permeability and reabsorption in the collecting tubules of the kidney
Gq proteins interact with…
Gs and Gi interact with..
Release of NE from a sympathetic nerve ending is modulated by…
NE itself, acting on presynaptic alpha2 autoreceptors, AngII and other substances.
Direct ACh agonists (4)
- Bethanechol 2. Carbachol 3. Pilocarpine 4. Methacholine
activate bowel and bladder smooth muscle; resistant to AChE
Use of Bethanechol
postoperative ileus, neurogenic ileus and urinary retention
carbon copy of acetylcholine
Use of Carbachol
-glaucoma -pupillary constriction -relief of intraocular pressure
contracts ciliary muscle of eye, pupillary sphincter; resistant to AChE
Use of Pilocarpine
-potent stimulator of tears, sweat and saliva -open and closed angle glaucoma
stimulates muscarinic receptors in the airway when inhaled
challenge test for asthma diagnosis
Indirect agonists of ACh (anticholinesterases) (5ish)
- Neostigmine 2. Pyridostigmine 3. Physostigmine 4. Donepezil, Rivastigmine, Galantamine 5. Edrophonium (they all increase endogenous ACh)
Use of Neostigmine
-postoperative and neurogenic ileus and urinary retention, myasthenia gravis, reversal of NMJ blockade
Use of Pyridostigmine
myasthenia gravis (long acting) (does not penetrate CNS)
Use of Donepezil, Rivastigmine, Galantamine
Use of Edrophonium
Dx of myastenia gravis (historically) *Myasthenia gravis now diagnosed by anti-AChR Ab
With all cholinomimetic agents, watch for..
exacerbation of COPD, asthma, and peptic ulcers.
Cholinesterase inhibitor poisoning is often due to..
organophosphates such as parathion that irreversibly inhibit AChE. Organophosphates are components of incesticides so this poisoning is usually seen in farmers.
Cholinesterase inhibitor poisoning causes…
diarrhea, urination, miosis, bronchospasm, bradycardia, excitation of skeletal muscle and CNS, lacrimation, sweating and salivation.
Antidote for cholinesterase inhibitor poisoning
atropine (competitive inhibitor) + pralidoxime (regenerates AChE)
Atropine, homatropine and tropicamide are…
muscarinic antagonists that work on the eye to produce mydriasis and cycloplegia.
Benztropine is a…
muscarinic antagonist that works on the CNS for parkinson disease.
Scopolamine is a…
muscarinic antagonist that works on the CNS for motion sickness.
Ipratropium and tiotropium are…
muscarinic antagonists that work on the respiratory system for COPD and asthma.
Oxybutynin, darifenacin adn solifenacin are…
muscarinic antagonists that work on the GU system to reduce urgency in mild cystitis and reduce bladder spasms. Also: tolterodine, fesoterdine, trospium
Glycopyrrolate is a…
muscarinic antagonist that works on the GI and respiratory systems to reduce airway secretions, drooling and peptic ulcers.
bradycardia and ophthalmic problems.
Atropine actions (5)
- increase pupil dilation and cycloplegia 2. decreases airway secretions 3. decreses stomach acid secretions 4. decreases gut motility 5. decreses urgency in cystitis
increased body temp, rapid pulse, dry mouth and skin, cycloplegia, constipation, disorientation
Atropine toxicity can cause…
acute angle-closure glaucoma in the elderly, urinary retention in men with prostatic hyperplasia and hyperthermia in infants.
Epinephrine works on…
mainly beta receptors to treat anapylaxis, open angle glaucoma, astham, hypotention. (the alpha effects predominate at high doses)
Norepinephrine works mainly on…
alpha1 receptor to treat hypotension (but it decreases renal perfusion).
Isoproterenol works on..
beta 1 and beta 2 equally for electrophysiologic evaluationof tachyarrhythmias. It can worsen ischemia.
unstable bradycardia, heart failure, shock (it has inotropic and chronotropic alpha effects at very high doses)
Dobutamine works on…
beta 1 and alpha receptors to treat heart failure and for cardiac stress testing.
Phenlyephrine works on..
alpha1 receptors mainly to treat hypotension, for ocular procedures (mydriatic) and rhinitis.
Albuterol, Salmeterol and Terbutaline work on…
beta2 more than beta1.
Amphetamine is an…
indirect general sympathomimetic agonist, reuptake inhibitor and also releases stored catecholamines.
Amphetamine is used to…
treat narcolepsy, obesity, ADHD.
Ephedrine is an..
indirect general sympathomimetic agonist that als releases stored catecholamines.
Ephedrine is used for…
nasal decongestion, urinary incontinence, and hypotension.
Cocaine is an…
indirect general sympathomimetic agonist and reuptake inhibitors.
vasoconstriction and local anesthesia.
Never give beta-blockers if cocaine intoxication is suggested because….
it can lead to unopposed alpha1 activation and extreme HTN.
NE causes an increase in…
systolic and diastolic pressures as a result of alpha1-mediated vasoconstriction. This leads to increased mean arterial pressure which leads to bradycardia.
Isoproterenol has little alpha effect but causes…
Beta2 mediated vasodilation resulting in decreased mean arterial pressure adn increased HR through beta1 and reflex activity.
Clonidine is an…
alpha2-agonist (a sympatholytic).
Clonidine is used for…
hypertensive urgency (does not decrease renal blood flow); ADHD; severe pain
CNS depression bradycardia hypotension respiratory depression small pupil size
alpha-methyldopa is an…
alpha2-agonist (a sympatholytic).
Alpha-methyldopa is used for…
HTN in pregnancy.
Toxicity of alpha-methyldopa
direct coombs + hemolytic anemia SLE-like syndrome
Phenoxybenzamine is an…
irreversible alpha blocker (nonselective).
Phenoxybenzamine is used to treat…
pheochromocytoma to prevent catecholamine crisis.
Toxicity of Phenoxybenzamine
orthostatic hypotension, reflex tachycardia
Phentolamine is a…
reversible alpha-blocker (nonselective).
Phentolamine is given to pts on…
MAO inhibitors who eat tyramine containing foods.
alpha1-selective blockers (4)
- Prazosin 2. Terazosin 3. Doxazosin 4. Tamsulosin
Use of Prazosin, Terazosin, Doxazosin, and Tamsulosin
urinary symptoms of BPH PTSD (prazosin) HTN (except tamsulosin)
Toxicity of Prazosin, Terazosin, Doxazosin, and Tamsulosin
orthostatic hypotension, dizziness, HA
Mirtazapine is an…
alpha2 sective blocker used for depression.
- Metoprolol 2. Acebutolol 3. Betaxolol 4. Carvedilol 5. Esmolol 6. Atenolol 7. Nadolol 8. Timolol 9. Pindolol 10. Labetolol
Beta-blocker indications (6)
- angina 2. MI 3. SVT 4. HTN 5. CHF 6. Glaucoma
Beta-blockers are used for angina because…
they decrease HR and contractility resulting in decreased O2 consumption.
Beta-blockers are used for MI because they…
decrease mortality. (Metoprolol, Carvedilol and Bisoprolol)
Beta-blockers are used for SVT because they…
decrease AV conduction velocity. (Metoprolol and Esmolol)
Beta-blockers are used for HTN bc they…
decrease CO, decrease renin secretion (due to beta1 blockade on JGA cells)
Beta-blockers are used for CHF because they…
slow the progression of chronic failure.
Beta-blockers are used for glaucoma because they…
decrease secretion of aqueous humor. (timolol)
Toxicity of Beta-blockers includes…
impotence CV adverse effects CNS adverse effects dyslipidemia (metoprolol) exacerbation of asthma/COPD
Beta1-selective antagonists (5)
- Acebutolol (partial agonist) 2. Atenolol 3. Betaxolol 4. Esmolol 5. Metoprolol
Nonselective beta antagonists
- Nadolol 2. Pindolol (partial agonist) 3. Propranolol 4. Timolol
Nonselective alpha and beta antagonists
Carvedilol and Labetalol
cardiac selective beta1-adrenergic blockade with stimulation of beta3 receptors, which activate NO synthase in the vasculature.
N-acetylcysteine (replenishes glutathione)
AChE inhibitors, organophosphates antidote
Atropine followed by Pralidoxime
NH4Cl (acidifies urine)
Antimuscarinic, anticholinergic agent antidotes
Physostigmine salicylate, control hyperthermia
100% O2, hyperbaric O2
Copper, arsenic, gold (antidote)
nitrite + thiosulfate + hydroxocobalamin
Anti-dig Fab fragments
EDTA, dimercaprol, succimer, penicillamine
Mercury, arsenic, gold antidote
Methanol, polyethylene glycol (antifreeze) antidote
Methylene blue, vitamin C
NaHCO3 (alkalinize urine), dialysis
NaHCO3 (plasma alkalinization)
tPA, streptokinase, urokinase antidote
vitamin K, plasma
Coronary vasospasm can be caused by…
cocaine, sumatriptan and ergot alkaloids
Cutaneous flushing can be caused by…
vancomycin, adenosine, niacin, and calcium channel blockers
Dilated cardiomyopathy can be caused by…
doxorubicin and danorubicin
Torsades de pointes can be caused by
class III (sotalol) and class IA (quinidine) antiarrhythmics, macrolides, antipsychotics and TCAs
Adrenocortical insufficiency is caused by…
HPA suppression secondary to glucocorticoid withdrawal.
Hot flashes can be caused by…
tamoxifen and clomiphene.
Hyperglycemia can be caused by..
tacrolimus, protease inhibitors, niacin, HCTZ, beta-blockers and corticosteroids.
Hypothyroidism can be caused by…
lithium, amiodarone, and sulfonamides.
Acute cholestatic hepatitis and jaundice can be caused by…
Diarrhea can be caused by…
Metformin, Erythromycin, Colchicine, Orlistat and Acarbose.
Focal to massive hepatic necrosis can be caused by…
halothane, amanita phalloides, valproic acid, and acetaminophen.
Pancreatitis can be caused by…
didanosine, corticosteroids, alcohol, valproic acid, azathioprine, and diuretics
Pseudomembranous colitis can be caused by…
clindamycin, ampicillin and cephalosporins
Agranulocytosis can be caused by…
dapsone, clozapine, carbamazepine, colchicine, methimazole, NSAIDs, and PTU
Aplastic anemia can be caused by…
carbamazepine, methimazole, NSAIDs, benzene, chloramphenicol and PTU
Direct Coombs-positive hemolytic anemia can be caused by…
methyldopa and penicillin
Gray baby syndrome can be caused by…
Hemolysis in G6PD deficiency can be caused by…
INH, Sulfonamides, Dapsone, Primaquine, Aspirin, Ibuprofen and Nitrofurantoin.
Megaloblastic anemia can be caused by…
phenytoin, methotrexate and sulfa drugs.
Thrombocytopenia can be caused by…
heparin and cimetidine.
Fat redistribution is caused by…
protease inhibitors and glucocorticoids.
Gingival hyperplasia is caused by…
phenytoin, verapamil, cyclosporine and nifedipine.
Hyperuricemia (gout) can be caused by…
pyrazinamide, thiazides, furosemide, niacin and cyclosporine.
Myopathy can be caused by…
fibrates, niacin, cochicine, hydroxychloroquine, IFN-alpha, penicillamine, statins, and glucocorticoids.
Osteoporosis can be caused by..
corticosteroids and heparin.
Photosensitivity can be caused by…
sulfonamides, amiodarone, tetracyclines, and 5-FU.
Rash (Stevens-Johnson syndrome) is caused by…
Anti-epileptic drugs (ethosuxamide, carbamazepine, lamotrigine, phenytoin, phenobarbital), Allopurinol, sulfa drugs and penicillin.
SLE-like syndrome is caused by…
sulfa drugs, hydralzine, INH, procainamide, phenytoin and etanercept.
Tendonitis, tendon rupture and cartilage damage is caused by…
Cinchonism is caused by…
quinidine and quinine.
Parkinson-like syndrome is caused by…
antipsychotics (esp. typicals), Reserpine and Metoclopramide.
Seizures are caused by…
INH (B6 deficiency), Bupropion, Imipenem/Cilastatin, Tramadol, Enflurane and Metoclopromide.
Tardive dyskinease is caused by…
Antipsychotics (esp. typicals) and Metoclopramide.
Diabetes insipidus can be caused by…
lithium and demeclocycline.
Fanconi syndrome can be caused by…
Hemorrhagic cystitis can be caused by…
cyclophosphamide and Ifosfamide. This side effect can be prevented by co-administering with Mesna.
Interstitial nephritis can be casued by…
methicillin, NSAIDs, and furosemide.
SIADH can be caused by…
carbamazepine, cyclophosphamide and SSRIs.
Dry cough can be caused by…
Pulmonary fibrosis can be caused by…
bleomycin, amiodarone, busulfan, and methotrexate.
Antimuscarinic rxns can be caused by…
atropine, TCAs, H1-blockers and antipsychotics.
Disulfiram-like reaction can be caused by…
metronidazole, cephalosporins, griseofulvin, procarbazine, and 1st gen sulfonylureas.
Nephrotoxicity/Ototoxicity can be caused by…
aminoglycosides, vancomycin, loop diuretics and cisplatin.
CYP450 Inducers (9)
- Chronic alcohol use 2. Modafinil 3. St. John’s wort 4. Phenytoin 5. Phenobarbital 6. Nevirapine 7. Rifampin 8. Griseofulvin 9. Carbamazepine (Chronic alcoholic Mona Steals Phen-Phen and Never Refuses Greasy Carbs)
CYP450s Substrates (8)
- Anti-epileptics 2. Antidepressants 3. Antipsychotics 4. Anesthetics 5. Theophylline 6. Warfarin 7. Statins 8. OCPs (Always, Always, Always, Always Think When Starting Others)
CYP450 Inhibitors (12)
- Acute alcohol abuse 2. Gemfibrozil 3. Ciprofloxacin 4. Isoniazid 5. Grapefruit juice 6. Quinidine 7. Amiodarone 8. Ketoconazole 9. Macrolides 10. Sulfonamides 11. Cimetidine 12. Ritonavir (A cute Gentleman “Cipped” Iced Grapefruit juice Quickly And Kept Munching on Soft Cinammon Rolls)
Sulfa drugs (8)
- Probenecid 2. Furosemide 3. Acetazolamide 4. Celecoxib 5. Thiazides 6. Sulfonamide antibiotics 7. Sulfasalazine 8. Sulfonylureas (Popular FACTSSS)
Pts who take sulfa drugs who have sulfa allergies may develop…
fever, UTIs, Stevens-Johnson syndrome, hemolytic anemia, thrombocytopenia, agranulocytosis and urticaria.
erogsterol synthesis inhibitor Ex. ketoconazole
antiparasitic/antihelmintic ex. Mebendazole
peptidoglycan synthesis inhibitor (ex. ampicillin)
protein syntehsis inhibitor (tetracycline)
neuraminidase inhibitor (oseltamivir)
protease inhibitor (ritonavir)
DNA polymerase inhibitor (acyclovir)
macrolide antibiotic (azithromycin)
inhalational general anesthetic (halothane)
typical antipsychotic (thioridazine)
local anesthetic (lidocaine)
5HT-1B/1D agonists (sumatriptan)
cholinergic agonist (bethanechol/carbachol)
-curium or -curonium
non-deplarizing paralytic (atracurium or vecuronium)
AChE inhibitor (neostigmine)
PDE-5 inhibitor (sildenafil)
dihydropyridine CCB (amlodipine)
ACE inhibitor (captopril)
Angiotensin II receptor blocker (Losartan)
HMG-CoA reductase inhibitor (Atorvastatin)
PPAR-gamma activator (Rosiglitazone)
proton pump inhibitor (omeprazole)
prostaglandin analog (latanoprost)
pituitary hormone (somatotropin)
chimeric monoclonal Ab (basiliximab)
humanized monoclonal Ab (Daclizumab)