Step 1 - Pharm 1

denniskwinn's version from 2015-04-25 16:12


Question Answer
Kmreflects the affinity of the enzyme for its substrate. ↓Km, ↑ affinity
Vmaxdirectly proportional to the enzyme concentration.
Competitive inhibitorsresemble substrate, bind the active site, can be overcome by increased substrate, no change of Vmax, increases Km and decreases potency
Noncompetitive inhibitorsdo not resemble substrate, can not be overcome by increasing substrate concentration, does not bind active site, reduces Vmax, doesn’t change Km, decreases efficacy
Volume of distribution (Vd)relates the amount of drug in the body to the plasma concentration. Vd of plasma protein-bound drugs can be altered by liver and kidney disease = amount of drug in the body/plasma drug concentration
Low Vd drugs(4-8L) distribute in blood
Medium Vd drugsdistribute in extracellular space or body water
High Vd drugs greater than body weight - distributes in tissues
Clearance (CL)Relates the rate of elimination to plasma concentration = rate of elimination of drug / plasma drug concentration = Vd x Ke (elimination constant)
Half life (T(1/2))The time required to change the amount of drug in the body by 1/2 during elimination (or during a constant infusion) - A drug infused at a constant rate reaches about 94% of steady state at 4 half lives
Loading doseTarget concentration x Volume of distribution / bioavailability
Maintenance dose = Target concentration x Clearance/bioavailability
Dosing patients with renal/hepatic impairmentLoading dose remains the same, maintenance dose will decrease
Zero order eliminationRate of eliminalion is constant regardless of C (i.e. constant amount of drug eliminated per unit time). Cp ↓ linearly with time. Examples of drugs-Phenytoin, Ethanol, and Aspirin (at high or toxic concentrations).
First-order eliminationRate of elimination is proportional to the drug concentration (i.e. Constant fraction of drug eliminated per unit time) - Cp ↓ exponentially with time
Weak acid drugsget trapped in basic environments - treat overdose with bicarbonate - examples: phenobarbitol, methotrexate, TCAs, aspirin
Weak base drugsGet trapped in acidic environments - treat overdose w/ ammonium chloride - examples: amphetamines
Phase I metabolism(reduction, oxidation, hydrolysis) usually yields slightly polar, water-soluble metabolites (often still active) - done by cytochrome p-450 (lost first by geriatric patients)
Phase II metabolism(acetylation, glucuronidation, sulfation) - usually yields very polar, inactive metabolites (renally excreted) - conjugation
Efficacymaximal effect a drug can produce
Potencyamount of drug needed for a give effect
Competetive antagonistshifts curve to the right - decreasing potency, increasing EC 50
Noncompetetive antagonistshifts agonist curve downward - decreasing maximal efficacy
Partial agonistlower maximal efficacy as full agonist - potency is an independent factor
Therapeutic indexmedian lethal dose / median effective dose - - safer drugs have higher TI values
Nicotinic ACh receptorsligand-gated a+/K+ channels; 1 N (found in autonomic ganglia) and NM (found in neuromuscular junction) subtypes.
Muscarinic ACh receptorsG-protein-coupled receptor that act through 2nd messengers; 5 subtypes: MI, M2> M3> M4> and M5·
Alpha 1 receptor funcitonsG protein q class - ↑ vascular smooth muscle contraction, ↑ pupillary dilator muscle, contraction (mydriasis), ↑ intestinal and bladder sphincter, muscle contraction
Alpha 2 receptor functionsGprotein I class - ↓ sympathetic outflow, ↓insulin release
Beta 1 receptor functionsGprotein s class - ↑HR,↑contractility,↑renin,↑lipolysis
Beta 2 receptor functionsGprotein s class - Vasodilation, bronchodilation, ↑HR, ↑contractility, ↑lipolysis,↑insulin release,↓uterine tone
M1 receptor functionsGprotein q class - CNS, enteric nervous system
M2 receptor functionsGprotein I class - ↓ heart rate and contractility of atria
Sympathetic receptorsalpha 1, alpha 2, beta 1, beta 2
Parasympathetic receptorsM1, M2, M3
M3 receptor functionsGprotein q class - ↑exocrine gland secretions (e.g., sweat, gastric acid), ↑ gut peristalsis, ↑ bladder contraction, bronchoconstriction, ↑ pupillary sphincter muscle contraction (miosis), cilial muscle contraction (accommodation)
D1 receptor functionsGprotein s class - relaxes renal vascular smooth muscle
D2 receptor functionsGprotein I class - modulates transmitter release, especially in the brain
H1 receptor functionsGprotein q class -nasal and bronchial mucus production, contraction of bronchioles, pruritis and pain
H2 receptor functionsGprotein s class - ↑ gastric acid secretion
V1 receptor functionsGprotein q class - ↑ vascular smooth muscle contraction
V2 receptor functionsGprotein s class - ↑ H2O permeability and reabsorption in CT of kidney
Gprotein receptor families for receptorsQISS and QIQ till you’re SIQ of SQS (sex).
Q family mode of actionreceptor activated for phospholipase C to PIP2 to IP3 and DAG - IPD increases Ca, DAG increases Protein kinase C (HAVe 1 M&M)
S family mode of actionreceptor to adenylyl cyclase activating cAMP to activate protein kinase A
I family mode of actionreceptor to adenylyl cyclase lowering cAMP and lowering protein kinase A (mad 2s)
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Question Answer
Bethanechol applicationsPostoperative and neurogenic ileus and urinary retention
Bethanechol actionActivates bowel and bladder smooth muscle - resistant to AChE.
Carbachol applicationsGlaucoma, pupillary contraction, release of intraocular pressure
Pilocarpine applicationsPotent stimulator of sweat, tears, saliva
Pilocarpine actionContracts ciliary muscle of eye (open angle), pupillary sphincter (narrow angle)- resistant to AChE, PILE on the sweat and tears
Methacholine applicationsChallenge test for diagnosis of asthma
Methacholine actionStimulates muscarinic receptors in airway when inhaled.
Cholemimetic direct agonistsBethanechol, Carbachol, Pilocarpine, Methacholine
Cholemimetic indirect agonists (anticholinesterases)Neostigamine, Pyridostigmine, Edrophonium, Physostigmine, Echothiophate,
Neostigmine applicationsPostoperative and neurogenic ileus and urinary retention, myasthenia gravis, reversal of NM junction blockade (postop)
Neostigmine actions↑ endogenous ACh; no CNS penetration -
Pyridostigmine applicationsMyasthenia gravis (long acting); does not penetrate CNS
Pyridostigmine actions↑ endogenous ACh, ↑ strength
Edrophonium applicationsDiagnosis of myasthenia gravis (extremely short acting)
Edrophonium actions ↑ endogenous ACh
Physostigmine applicationsGlaucoma (crosses BBB) and atropine overdose
Physostigmine actions↑ endogenous ACh
Echothiophate applicationsGlaucoma
Echothiophate actions↑ endogenous ACh
Cholinesterase inhibitor poisoningDUMBBELSS - Diarrhea, Urination, Miosis, Bronchospasm, Bradycardia, Excitation of skeletal muscle and CNS, Lacrimation, Sweating, Salivation (also abdominal cramping)
Cholinesterase inhibitor poisoning antidoteAtropine (muscarinic antagonist) plus pralidoxime (chemical antagonist used to regenerate active cholinesterase)


Question Answer
Muscaranic antagonistsAtropine (homatropine, benztropine), scopolamine, Ipratropium, Oxybutinin, glycopyrrolate, Methscopolamine, pirenzepine, propantheline
Atropine, homatropine, tropicamide usein the eye - produces mydriasis and cycloplegia
Benztropine usein CNS - parkinsons
Scopolamine useCNS - motion sickness
Ipratropium useRespiratory - Asthma, COPD (I pray I can breathe soon)
Oxybutynin, glycopyrrolate useGU - reduces urgency in mild cystitis and reduce bladder spasms
Atropine effect in eye↑ pupil dilation, cycloplegia
Atropine airway effect↓ secretions
Atropine stomach effect↓ acid secretion
Atropine Gut effect↓ motility
Atropine bladder effect↓ urgency in cystitis
Atropine toxicity ↑ body temperature, rapid pulse, dry mouth, dry, flushed skin, cycloplegia, constipations, disorientation = Hot as a hare, dry as a bone, red as a beet, blind as a bat, mad as a hatter. . . Also can cause acute angle-closure glaucoma in elderly, urinary retention in men with prostatic hyperplasia and hyperthermia in infants


Question Answer
Hexamethonium useNicotinic antagonist - ganglionic blocker - used in experimental models to prevent vagal reflex responses to changes in BP - not used clinically
Hexamethonium toxicitySevere orthostatic hypotension, blurred vision, constipation, sexual dysfunction


Question Answer
Direct sympathomimeticsEpinepherine, NE, Isoproterenol, Dopamine, Dobutamine, Phenylephrine, Metaproterenol (albuterol and salmeterol, terbutaline), Ritodrine,
Epinepherine selectivityalpha1,alpha2, beta1, beta2 - low dose selective for beta1
Epinepherine applicationsAnaphylaxis, glaucoma (open angle), asthma, hypotension
NE selectivityalpha 1, alpha 2 > beta 1
NE applicationsHypotension (but ↓ renal perfusion
Isoproterenol selectivityB1=B2 (only b)
Isoproterenol applicationsAV block (rare)
Dopamine selectivityD1=D2 > beta > alpha, inotropic and chronotropic
Dopamine applicationsShock (↑renal perfusion), heart failure
Dobutamine selectivityBeta1 > Beta 2 , inotropic but not chronotropic
Dobutamine applicationsShock, heart failure, cardiac stress testing
Phenylephrine selectivityalpha 1 > alpha 2
Phenylephrine applicationsPupillary dilation, vasoconstriction, nasal decongestion
Metaproterenol, albuterol, salmeterol, terbutaline selectivityselective beta 2 agonist (Beta 2 > Beta 1)
Metaproterenol, albuterol, salmeterol, terbutaline usesMAST - M and A for acute asthma, S for long term treatment, T to reduce premature uterine contractions
Ritodrine selectivityBeta 2
Ritodrine applicationReduces premature uterine contractions
Indirect sympathomimeticsAmphetamine, Ephedrine, Cocaine
Amphetamine actionIndirect general agonist - releases stored catecholamines
Amphetamine clinical usesNarcolepsy, obesity, ADHD
Ephedrine actionIndirect general agonist, releases stored catecholamines
Ephedrine clinical useNasal decongestion, urinary incontinence, hypotension
Cocaine actionIndirect general agonist, uptake inhibitor
Cocaine clinical usecauses vasoconstriction and local anesthesia
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