Pharm Flashcards
Describe a michaelis menten kinetics curve including Km, Vmax, and the significance of them (what they determine/depend on).
It is a hyperbolic curve with velocity on the y axis and substrat conc. on the x axis.
V max is the maximum velocity that can be reached (when all the enzymes are saturated with enzyme).
It is proportional to the enzyme conc.
Km is the subs. conc. at 1/2Vmax.
It is inversely related to the affinity of the enzyme for its substrate.
Describe a lineweaver burk plot including what the y intercept and x intercept and slope are and what they signify.
A straight line with 1/V on the y axis and 1/S on the x axis.
Y intercept is 1/Vmax so the higher that the y intercept is, the lower the v max is.
X intercept is 1/-Km so the further to the right it is (less negative) the greater Km is and thus the lower the affinity.
Compare and contrast comp. inh (revers), comp. inh. (irrev), and non comp inh. according to whether they resemble substrate, are overcome by incr. in substrate, bind active sit, how they effect Vmax, how they effect Km, and how they effect potency/efficacy.
COMP INH, REVER
resemble substrate: Yes overcome by incr. in substrate: Yes bind active site: Yes how they effect Vmax: None how they effect Km: Decr how they effect potency/efficacy: decr. potency
COMP INH, IRREVER
resemble substrate: yes overcome by incr. in substrate: no bind active site: yes how they effect Vmax: decr how they effect Km: none how they effect potency/efficacy: decr. efficacy
NON COMP INH
resemble substrate: no overcome by incr. in substrate: no bind active site: no how they effect Vmax: decr how they effect Km: none how they effect potency/efficacy: decr. efficacy
What is the bioavailability? What is it IV? Oral? Why?
Fraction of administered drug reaching systemic circ. unchanged.
For IV=100%
Oral < 100%, incomplete absorption, first pass metabolism
What is Vd? How can the Vd of plasma protein bound drugs be altered? How is it calculated? What compartment does a low Vd drug enter? What types of drugs are they? Medium? High?
Theoretical volume occupied by the total amount of drug in the body relative to its plasma conc.
They can be altered by liver and kidney disease (decr. protein binding leads to incr. Vd)
Vd=(amount of drug in the body)/(plasma drug concentration)
Low: Blood; large/charged molecules, plasma protein bound
Medium: ECF, small hydrophilic molecules
High: all tissues including fat; small lipophilic molecules, especially if bound to tissue protein
What is clearance? What might iimpair it? What are two equations for it?
Volume of plasma cleared of drug per unit time.
May be impaired with defects in cardiac, hepatic, and renal function
CL=rate of elimination/plasma drug concentration
CL=Vd x Ke (elimination constant)
What is the half life? How many half lives til steady state? Til 90% of steady state? How is halflife calculated?
Time required to change the amount of drug in the body by 1/2 during elimination (or constant infusion).
4-5 half lives til steady state
3.3 half lives to reach 90%
t1/2= (.693 x Vd)/CL
How is loading dose calculated? How is maintenance dose calculated? How do they change in renal or liver disease? How do they determine tie to steady state?
Loading dose=(target plasma conc. at steady state x Vd)/F
Maintenance dose=(target plasma conc. x CL x dosage interval)/F
In renal or liver disease, maintenance dose will change but loading dose will not
Time to steady state depends on half life, not the loading or maintenance dose
What is zero order elimination? What are some examples?
Rate of elimination is constant regardless of the amount of substrate (constant amount of drug eliminated per unit time)
Decreases linearly
Phenytoin, ethanol, aspirin (PEA=a pea is round like a 0)
What is first order elimination?
Rate is proportional to drug concentration (constant fraction of drug eliminated per unit time)
Decreases exponentially
Explain how ion trapping works? What are some weak acids? How can they be trapped in basic environments? What are some weak bases? How can they be trapped in acidic environments?
Ionized species are trapped in urine and cleared quickly. Neutral forms are reabsorbed. By making something ionic, you can eliminate it quickly.
WA: Phenobarbital, methotrexate, aspirin, TCAs
Treat overdose with bicarb
WB: Amphetamines
Treat overdose with ammonium chloride
What reactions occur in phase I drug metabolism? Where? What are the results? What reactions occur in phase two drug metabolism? Results? What do geriatric patients lose? What is a genetic condition that can decr. rate of metabolism? Clinical effects?
Reduction, oxidation, and hydrolysis with cytochrome p-450
Slightly polar, water soluble molecules (often active)
Conjugation (glucoronidaiton, acetylation, sulfation)
Very polar, inactive metabolites (excreted in urine)
Geriatric patients have GAS (phase I lost first)
Slow acetylators have decr. rate of metabolism which may lead to incr. side effects.
Compare and contrast efficacy and potency.
Efficacy is the maximal effect a drug can produce. It is represented by Vmax. It is unrelated to potency. Partial agonists have less efficacy than full agonists
Potency is the amount of drug needed for a given effect. It depends on Km. Left shifting mean increased potency. Unrelated to efficacy
What are dose response curves? How do comp. antag. affect dose response curves? How does the dose response curve of a partial agonist compare to that of a full?
Dose on x axis, perecent of maximal effect of y axis
Comp. antagonist: shifts curve right (decr. potency). No change in efficacy.
Non comp. antag: Shifts curve down (decr. efficacy).
Partial agonist: Lower maximal effect (decr. efficancy).
What is the therapeutic index? How is it calculated? What are some drugs with low TI values? What does this mean? What is the therapeutic window?
Measurement of drug safety
TD50/ED50=median toxic dose/Median effective dose
Digoxin, lithium, theophylline, and warfarin
Window: measure of clinical drug effectiveness for a patient.
Describe the presympathetic and postsympathetic nerve terminals in the autonomic pathways from the CNS to the parasympathetic pathway to cardiac and smooth muscle, gland cells, and nerve terminals? The symp. pathway to sweat glands? The symp pathway to cardiac and smooth muscle, gland cells, and nerve terminals? The symp. pathway to renal vasculature and smooth muscle? The somatic pathway to skeletal muscle? The symp. pathway to adrenal medulla?
Parasymp=long presynaptic, short postsynaptic
Symp: short presynaptic, long postsynaptic
Para: Nicotinic cholinergic then muscarinic
Symp sweat glands: Nicotinic then muscarinic
symp cardiac, etc: nicotinic then alpha/beta receptors
symp renal: nicotinic then D1
symp adrenal: nicotinic then epi/NE
somatic: nicotinic only (no ganglion)
What is the difference between nicotinic and muscarinic receptors?
Nico: ligand gated Na/K channels
Musc: G protein coupled receptors that use second messengers
What are the major functions of alpha 1, alpha 2, beta 1, and beta 2 receptors? What g protein class do they use?
alpha 1 (Gq): incr. vasc smooth muscle contraction, incr. pupillary dilator muscle contraction (mydriasis), incr. intestinal and bladder sphincter muscle contraction
alpha 2 (Gi): Decr. symp outflow, decr. insulin release, decr. lipolysis, incr. platelet aggregation, decr. aqueous humor production
beta 1 (Gs): Incr. heart rate/contractility, incr. renin release, incr. lipolysis
beta 2 (Gs): Vasodilation, bronchodilation, incr. lipolysis, incr. insulin release, decr. uterine tone (tocolysis), ciliary muscle relaxation (look far away), incr. aqueous humor production
Qiss
What are the major functions of M1, M2, and M3 receptors? What G protein class do they use?
M1 (Gq): CNS, enteric nervous system
M2 (Gi): Decr. heart rate and contractility of atria (incr. av node refractory period)
M3 (Gq): incr. exocrine gland secrections (lacrimal, salivary, gastric acid), incr. gut peristalsis, incr. bladder contraction, bronchoconstriction, incr. pupillary sphincter muscle contraction (miosis), ciliary muscle contraction (accomodation)
qiq
What are the major functions of D1, D2, H1, H2, V1, V2 receptors? What G protein class do they use?
D1 (Gs): Relaxes renal vascular smooth muscle
D2 (Gi): Modulates transmitter release, especially in brain
H1 (Gq): Incr. nasal and bronchila mucus production, incr. vasc. permeability, contraction of bronchioles, pruritus, pain
H2 (Gs): Incr. gastric acid secretion
V1 (Gq): Incr. vasc. smooth muscle contraction
V2 (Gs): Incr. H20 perm. and reabsorption in collecting tubules of kidney (V2 is found in the 2 kidneys)
What is the pathway of Gq receptors? Which receptors are Gq receptors?
Phospholipase C converts PIP2 to DAG and IP3
DAG forms protein kinase C
IP3 releases Ca from the SR
These actions lead to smooth muscle contraction
HAVe 1 M&M
H1, A1, V1, M1, M3
What is the pathway of Gs receptors? Which ones are Gsreceptors? Same questions for Gi receptors?
Gs activates adenylate cyclase leading to more cAMP
This activates protein kinase A
This leads to more calcium inflow in the heart and inhibition of myosin light chain kinase in smooth muscle
B1, B2, D1, H2, V2
Gi inhibits adenylate cyclase thus leading to less calcium inflow in heart and less inhib. of MLCK in SM
MAD 2s
M2, A2, D2
What type of drug is bethanacol? Clinical applications? Action?
Direct cholinnomimetic agonist
Postoperative ileus, neurogenic ileus, urinary retention
Activates bladder and bowel smooth muscle
“Bethany, call me to activate your bowels and bladder”
Resistant to AChE
What type of drug is carbachol? Clinical applications?
Direct cholinomimetic agonist
Constricts pupil and relieves intraocular pressure in glaucoma
What type of drug is methacholine? Clinical applications?
Direct cholinomimetic agonist
challenge test for diagnosis of asthma
What type of drug is pilocarpine? Clinical applications? Action?
Direct cholinomimetic agonist
Potent stimulator of seat, tears, and saliva
Open angle and closed angle glaucoma
Constracts ciliary muscle of eye (open angle glaucoma)
and pupilary sphincter (closed angle glaucoma)
resistant to AChE
“you cry, you drool, you sewat on your “pilo”
What kind of a drugs are donezipil, galantamine, and rivastigmine? Clinical use? Action?
Anticholinesterase
Alzheimers
Incr. ACh
What type of drug is edrophonium? Clinical applications? Action?
Anti AChE
Historically, diagnosis of myasthenia gravis (extremely short acting)
Incr. ACh
What type of drug is neostigmine? Clinical applications? CNS penetration?
Anti AChE
Postoperative and neurogenic ileus and urinary retention, myasthenia gravis, reversal of NMJ blockage
No CNS penetration
Incr. ACh
What type of drug is physostigmine? Clinical applications? Action? CNS penetration?
Anti AChE
Anticholinergic toxicity; crosses blood rain barrier
Incr. ACh
“Phyxes atropine overdose”
What type of drug is pyridostigmine? Clinical applications? Action? CNS penetration?
Anti AChE
Myasthenia gravis (long acting)
No CNS penetration
Incr. ACh
“rid of stiGMine” Gets rid of MG.
What should be watched for with all cholinomimetic agents? What causes cholinesterase inhibitor poisoning? Example? Where are these chemicals seen? What are the symptoms? What is the treatment?
Exacerbation of COPD, asthma, and peptic ulcers
Organophosphates (parathion), irreversibly inhibit AChE.
Found in insectisides (farmers)
DUMBBELSS
Diarrhea Urination Miosis Bronchospasm Bradycardia Excitation of skel muscle and CNS Lacrimation Sweating Salivation
Atropine (comp. inhib)
Pralidoxine (if given early, regenerates AChE)
What type of drugs are atropine, homatropine, and tropicamide? Clinical applications?
Muscarinic antagonists
Mydriasis and cycloplegia
What type of drug is Benztropine? Clinical applications?
Muscarinic antagonists
Parkinsons
Acute dystonia
“Park my Benz”
What type of drug is glycopyrrolate? Clinical applications?
Muscarinic antagonists
Parenteral: Pre op use to reduce airway secretions
Oral: Drooling, peptic ulcer
What type of drug is hyoscyamine and dicyclomine? Clinical applications?
Muscarinic antagonists
Antispasmodics for irritable bowel syndrome
What type of drug is ipratropium and tiotropium? Clinical applications?
Muscarinic antagonists
COPD, asthma
“I pray I can breath soon
What type of drug is oxybutynin, solifenacin, and tolterodine? Clinical applications?
Muscarinic antagonists
Reduce bladder spasms and urge incontinence
What type of drug is scopolamine? Clinical applications?
Muscarinic antagonists
Motion sickness (CNS)
What type of drug is atropine? Actions/location? Clinical applications? What is its toxicity like? What does Jimson weed result in?
Musc. antag
Incr. pupil dilation/cycloplegia Decr. airway secretions Decr. acid secretion in stomach Decr. motility in gut Decr. urgency in cystitis
Treats bradycardia
Opthalmic applications
Blocks DUMBBLSS (not CNS or skel. muscle=nicotinic)
Toxicity:
Incr. body temp (decr. sweating) rapid pulse dry mouth dry, flushed skin cycloplegia constipation disorientation
HOT as a hare DRY as a bone RED as a beet BLIND as a bat MAD as a hatter
Acute angle closure glaucoma in elderly (mydriasis)
urinary retention in men with prostatic hyperplasia
hyperthermia in infants
Jimson Weed leads to gardner’s pupil (mydriasis due to plant alkaloids)
What is the mechanism of tetrodotoxin? Where is it found? Symptoms? Treatment?
Very potent: binds fast voltage gated Na channels and prevents depolarization
Pufferfish
Nausea, diarrhea, paresthesias, weakness, dizziness, loss of reflexes
Supportive
Where is ciguatoxin found? Mechanism? What is the presentation like?Specific symptoms?
Reef fish
Opens Na channels causing depolarization
Similar to cholinergic poisoning
Temperature related dysthesias are a specific finding
Supportive
What causes scombroid poisoning? Mechanism? How is it misdiagnosed? Symptoms? Teratment?
Dark meat fish improperly stored at warm temp.
Bacterial histidine decarboxyl. converts histadine to histamine which isn’t degraded by cooking.
Misdiagnosed as allergy to fish
Acute onset burning sensation of the mouth, flushing of face, erythema, urticaria, pruritus, headache
Anaphylaxis like presenation is possible
Antihistamines
Possible antianaphylactics
What type of drug is albuterol? What is their effect? Clinical applications?
Direct sympathomimetics
beta 2 > beta 1
Acute asthma
What type of drug is dobutamine? What is their effect? Clinical applications?
Direct sympathomimetics
beta 1 > beta 2
alpha
Heart failure (inotropic > chronotropic) Cardiac stress testing
What type of drug are dopamine? What is their effect? Clinical applications?
Direct sympathomimetics
D1=D2 > beta > alpha
unstable bradycardia
HF
Shock
Inotropic and chronotropic alpha effects predominate at high doses.
What type of drug are epinephrine? What is their effect? Clinical applications?
Direct sympathomimetics
Beta > alpha
Anaphylaxis
asthma
open angle glaucoma
Alpha effects predominate at high doses
What type of drug are isoproterenol? What is their effect? Clinical applications?
Direct sympathomimetics
Beta 1 = beta 2
electrophysiologic eval. of tachyarrythmias
Can worsen ischemia
What type of drug are NE? What is their effect? Clinical applications?
Direct sympathomimetics
alpha 1 > alpha 2 > beta 1
hypotension (but decr. renal perfusion)
What type of drug are Phenylephrine? What is their effect? Clinical applications?
Direct sympathomimetics
alpha 1 > alpha 2
hypotensin (vasoconstrictor) ocular procedures (mydriatic) rhinitis (decongestant)
What type of drug is salmeterol? Effect? Clinical application?
Direct sympathomimetic
Beta 2 > beta 1
Long term asthma or COPD control
What type of drug is amphetamine? Mechanism? Application?
Indirect sympathomimetic
Indirect general agonist
Reuptake inhibitor
Releases stored catecholamines
Narcolepsy
Obesity
ADHD
What type of drug is cocaine? Mechanism? Application? What shouldn’t be given in case of intoxication? Why?
Indirect sympathomimetic
Indirect general agonist
reuptake inhibitor
Vasoconstriction and local anesthesia
Never give beta blocker in intoxication b/c it can lead to unopposed alpha 1 activation and extreme hypertension
What type of drug is ephedrine? Mechanism? Application?
Indirect sympathomimetic
Indirect general agonist
Releases stored catecholamines
Nasal congestion
Urinary incontinence
Hypotension
Describe what happens to blood pressure as a result of NE administration vs. isoproteronol admin.
NE incr. systolic and diastolic BP (alpha 1) which leads to incr. MAP leading to reflex bradycardia
Isoproteronol causes beta 2 mediated vasodilation leading to decr. in MAP and incr. in heart rate through reflex and Beta 1
What type of drug is clonidine? Clinical applications? Waht is Toxicity like?
sympatholytic (alpha 2 agonist)
Hypertensive urgency; does not decr. renal blood flow
ADHD
Tourette Syndrome
CNS Depression bradycardia hypotension resp. depression miosis
What type of drug is alpha methyl dopa? Clinical applications? Waht is Toxicity like?
sympatholytic (alpha 2 agonist)
Hypertension in pregnancy
Direct coombs + hemolysis
SLE like syndrome
What type of drug is phenoxybenzamine? Clinical applications?
Non selective alpha blocker
pheochromocytoma (operatively) to prevent catecholamine crisis
What type of drug is phentolamine? Clinical applications?
non select alpha blocker
Give to pts. on MAOIs who eat tyramine containing food
orthostatic hypertension
Reflex tachycardia
What type of drug is , terazosin, doxazosin? Clinical applications? Sx?
Alpha 1 selective blockers (2)
urinary symptoms of BPH
Hypertension
1st dose orthostatic hypotension
dizziness
headache
What type of drug is mirtazapine? Clinical applications?
Alpha 2 selective alpha blocker
Depression
Sedation
Incr. serum cholesterol
Incr. appetite
What type of drug is prazosin? Clinical applications? sx?
Alpha 1 selective blockers
urinary symptoms of BPH
PTSD
Hypertension
1st dose orthostatic hypotension
dizziness
headache
What type of drug is tamsulosin? Clinical applications? sx?
Alpha 1 selective blockers
urinary symptoms of BPH
1st dose orthostatic hypotension
dizziness
headache
What are the clinical applications of beta blockers and how do they accomplish them (mechanism)? Which are used for certain applications? Toxicity? Certain beta blockers associated with the toxicity?
Angina: decr. HR and contractility leading to decr. O2 consumption
MI: Decr. mortality (metoprolol, carvedilol, bisoprolol)
SVT: Decr. AV conduction velocity (class II antiarryth) (Metoprolol, esmolol)
Hypertension: Decr. CO, Decr. renin secretion (Beta 1 receptor blockade on JGA cells)
HF: Decr. mortality
Glaucoma: Decr. secretion of aqu. humor (timolol)
What is the selectivity of acebutolol, atenolol, betaxolol, esmolol, and metoprolol?
Beta 1 selective antagonists (B1 with first half of alphabet=First letter begins with A-M)
What is the selectivity of nadolol, pindolol, propranolol, and timolol?
Non selective beta antagonists (N to Z first letter)
What makes pindolol and acebutolol unique in their selectivity?
Partial beta agonists
What is the selectivity of carvedilol and labetalol?
non selective alpha and beta antagonists
Modified suffix (-olol)
What is the selectivity/ mechanism of nebivolol?
cardiac selective beta 1 blockade
stimulation of beta 3 leading to NO synthase in vasculature
Antidotes for:
acetaminophen: AChe Inhibitors, organophosphates: Amphetamines Antimuscarinic/anticholinergic: Benzodiazepines: Beta blockers: CO: Copper, arsenic, gold: Cyanide: Digitalis (digoxin): Heparin: Iron: Lead: Mercury, arsenic, gold: methanol/ethylene glycol (antifreeze): Methemoglobin: Opiods: Salicylates: TCAs: tPA, streptokinase, urokinase: Warfarin:
acetaminophen: N-acetylcysteine (replenishes glutathione)
AChe Inhibitors, organophosphates: Atropine > pralidoxime
Amphetamines: NH4Cl (acidify urine)
Antimuscarinic/anticholinergic: Physostigmine salicylate, control hyperthermia
Benzodiazepines: Flumazenil
Beta blockers: glucagon
CO: 100% O2, hyperbaric O2
Copper, arsenic, gold: penicillamine
Cyanide: nitrate + thiosulfate, hydroxocobalamin
Digitalis (digoxin): Anti dig Fab fragments
Heparin: Protamine sulfate
Iron: Deferoxamine, deferasirox
Lead: EDTA, dimercaprol, succimer, penicillamine
Mercury, arsenic, gold: Dimeraprol (BAL), succimer
methanol/ethylene glycol (antifreeze): Fomepizole > ethanol, dialysis
Methemoglobin: methylene blue, vitamin C
Opiods: naloxone, naltrexone
Salicylates: NAHCo3 (alkalinize urine), dialysis
TCAs: NaHCO3 (plasma alkalinize)
tPA, streptokinase, urokinase: Aminocaproic acid
Warfarin: Vitamin K (delayed) FFP (immediate)
What drugs cause coronary vasospasm? Cutaneous flushing? Dilated Cardiomyopathy? Torsades de Pointes?
What do these groups of drugs cause?
Cocaine, sumatriptan, ergot elkaloids
Vancomycin, adenosine, niacin, Ca channel blockers
Anthracyclines (doxorubicin, daunorubicin); prevent with dexrazoxane
Class III and Class IA antiarrythmics, macrolides, antipsychotics, TCAs
