Pharm Flashcards
Competitive inhibitor Reversible
Resemble substrate, bind at active site Overcome by increase substrate Vmax: unchanged Km: increased decrease potency
Competitive inhibitor Irreversible
Resemble substrate, bind at active site NOT overcome by increase substrate Vmax: decreased Km: unchanged decrease efficacy
Noncompetitive inhibitor
Resemble substrate, DOES NOT bind at active site NOT overcome by increase substrate Vmax: decreased Km: unchanged decrease efficacy
Bioavailability
Fraction of administered drug reaching systemic circulation unchanged.
IV= 100%
F= AUC oral/ AUC IV
Volume of distribution
Theoretical volume occupied by the total amount of drug in the body relative to its plasma concentration.
Can be altered by liver and kidney disease (high Vd)
Vd= amount of drug in body / plasma concentration
Low –> intravascular
Medium –> ECF
High –> all tissues
Clearance
The time required to change the amount of drug in the body by 1/2 during elimination
First order- t1/2 = (.7*Vd) / CL
Loading dose
Cp*Vd/F
Maintenance dose
(Cp * CL *dosage interval) / F
Zero Order elimination
rate of elimination is constant regardless of Cp
Cp decreased linearly with time
Phenytoin, Ethanol, Aspirin
First order elimination
Directly proportional to drug concentration
Most drugs
Efficacy
Maximal effect a drug can produce
Vmax
Potency
Amount of drug needed for a given effect.
EC50
Competitive antagonist
Decrease potency
No change in efficacy
Can be overcome by increase agonist concentration
Noncompetitive antagonist
No change in potency
Decrease efficacy
Cannot be overcome by increase agonist concentration
Partial agonist
Independent of potency
Efficacy decreases
Therapeutic index
Measure of drug safety
TD50/ ED50
Safe drugs have high therapeutic index
Bladder control
Sympathetics: increase urinary retention
Parasympathetics: increase urine voiding
Urgency incontinence Meds
Muscarinic antagonists (-M3 --> relax detrusor M --> decrease overactivity) Oxybutynin Sympathomimetics (+B3 --> relax detrusor muscle --> increase bladder capacity) Miragegron
Urinary Retention meds
Muscarinic agonist (+M3 –> contract detrusor –> increase bladder emptying) Bethanechol
BPH meds
a1 blockers (-a1 --> relax smooth muscle --> decrease urinary obstruction) Tamsulosin
a1
Gq
increase vascular smooth muscle contraction, Mydriasis, increase intestinal and bladder sphincter muscle contraction
a2
Gi
decrease sympathetics, decrease insulin, decrease lipolysis, increase platelet aggregation, decrease aqueous humor production
B1
Gs
increase HR, contractility, renin, lipolysis
B2
Gs
vasodilation, bronchodilation, increase lipolysis, insulin, glycogenolysis, decrease uterine tone, increase aqueous humor production, increase cellular K+ intake
M1
Gq
mediates higher cognitive functions
Stimulate enteric nervous system
M2
Gi
decrease HR and contractility of atria
M3
Gq
increase exocrine gland secretions, increase gut peristalsis, increase bladder contraction, bronchoconstriction, miosis, ciliary M contraction, increase insulin, endothelium mediated vasodilation
D1
Gs
relax renal vascular smooth M, activate direct pathway of striatum
D2
Gi
modulate transmitter release in brain, inhibits indirect pathway of the striatum
H1
Gq
increase nasal and bronchial mucus production, increase vascular permeability, bronchoconstriction, pruritus, pain
H2
Gs
increase gastric acid secretion
V1
Gq
increase vascular smooth muscle contraction
V2
Gs
increase H2O permeability and reabsorption via up-regulating Aquaporin 2 in collecting tubules, increase release of vWF
Chilinomimetic agents
Watch for COPD, asthma and peptic ulcer
Bethanechol
activate bladder smooth muscle, resistant to AChE
Used for urinary retention
Carchachol
ACh but resistant to AChE
constricts pupil and relieves intraocular pressure in open angle glaucoma
Methacholine
stimulate M receptors in airway when inhaled
challenge test for asthma Dx
Pilocarpine
contract ciliary muscle of eye, pupillary sphincter
Resistant to AChE
can cross BBB
used to stimulate sweat, tears and saliva (Sjogrens, open and closed angle glaucoma)
Donepezil, rivastigmine, galantamine
increase ACh
Alzheimers
Edrophonium
increase ACh
diagnose MG
Neostigmine
increase ACh
No CNS penetration
postop and neurogenic ileus and urinary retentions, MG, reversal of NMJ blockade
Physostigmine
increase ACh
Cross BBB
Antidote for anticholinergic tox
Pyridostigmine
increase ACh
increase muscle strength
used with glycopyrrolate, hysocyamine or propantheline to control side effects
used for MG (long lasting)
Muscarinic anti AChE poisoning
Diarrhea Urination Miosis Bronchospasm Brady Emesis Lacrimation Sweating Salivation REVERSED BY ATROPINE
Nicotinic anti AChE poisoning
neuromuscular blockade
REVERSED BY PRALIDOXIME
CNS effects AChE poisoning
Respiratory depression, lethargy, seizures, coma
Produce mydriasis and cycoplegia
Atropine Homatropine, tropicamide
Parkinson Disease Acute Dystonia
Benzotropine trihexyphenidyl
Parenteral: preop use to reduce airway secretion
Oral: drooling, peptic ulcer
Glycopyrrolate
Antispasmodics for IBS
Hyoscyamine
Dicyclomine
COPD, asthma
ipratropiu
tiotropium
Reduce bladder spasms and urge urinary incontinence (overactive bladder)
Oxybutynin
Solifenacin
tolterodine
Motion sickness
Scopolamine
Adverse effects of Atropine use
increase body temp, increase HR, dry mouth, flushed skin, cyclopegia, constipation, disorientation
Albuterol, salmeterol, terbutaline
B2>B1 increase heart rate Albuterol for acute COPD/asthma Salmeterol for long term COPD/ asthma Terbutaline for bronchospasm in asthma and tocolysis
Dobutamine
B1>B2, a
increase HR and CO
used in HF, cardiogenic shock, cardiac stress test
Dopamine
D1=D2>B>a
increase BP, HR and CO
used in unstable brady, HF, shock
Epinephrine
B>a
increase BP, HR and CO
used for anaphylaxis, asthma, open angle glaucoma
Fenoldopam
D1
decrease BP, increase HR and CO
post op HTN, vasodilator. Promote natiuresis
Isoproterenol
B1=B2
decrease BP, increase HR and CO
Midodrine
a1
increase BP, decrease HR
used in autonomic insufficiency and postural hypotension
Mirabegron
B3
used in urinary urgency or incontinence or overactive bladder
Norepinephrine
a1>a2>B1
increase BP and HR
used in.hypotension, septic shock
Phenylephrine
a1>a2
increase BP decrease HR
used in hypotension, ocular procedures, rhinitis, ischemic priapism
Amphetamine
indirect agonist, reuptake inhibitor, release catecholamine stores
used in narcolepsy, obesity, ADHD
Cocaine
indirect agonist, reuptake inhibitor
causes vasoconstriction and local anesthesia
If given B blockers –> extreme hypertension
Ephedrine
indirect agonist, releases catecholamine stores
used in nasal decongestion, urinary incontinence, hypotension
NE vs isoproterenol
NE causes reflex brady due to a1 effects
isoproterenol causes vasodilation and increased HR
Clonidine, guanfacine
a2 agonist
Used in hypertensive urgency, ADHD, Tourette syndrome, symptom control in opioid withdrawal
Adverse: CNS depression, brady, hypotension, respiratory depression, miosis, rebound HTN with abrupt cessation
a methyldopa
a2 agonist
used in HTN in pregnancy
Adverse: direct Coombs hemolysis, drug indcled lupus, hyperprolactinemia
Tizanidine
a2 agonist
used for relief of spasticity
Adverse: hypotenion, weakness, xerostomia
Phenoxybenzamine
Irreversible a blocker
Pheochromocytoma to prevent catecholamine crisis
adverse: orthostatic hypotension, reflex tachy
Phentolamine
reversible a blocker
given to patients on MAO inhibitors who eat tyramine containing foods for severe cocaine induced hypertension
adverse: orthostatic hypotension, reflex tachy
Prozasoin, terazosin, doxazosin, tamsulosin
a1 blockers
used in urinary symptoms of BPH, PTSD hypertension
adverse: 1st does, orthostatic hypotension, dizzy, HA
Mirtazapine
a2 blocker
used in depression
adverse: sedation, increase serum cholesterol, increase appetite
B blockers on angina pectoris
decrease HR and contractility –> low O2 consumption
Glaucoma
Timolol
decrease aqueous humor production
Heart Failure
Bisoprolol, Carvedilol, Metoprolol
decrease mortality
B blockers of HTN
decrease CO, decrease renin secretion
Hyperthyroidism
Propanolol
symptom control
B blockers on Hypertrophic cardiomyopathy
decrease HR –> increase filling time, relieve obstruction
B blockers for MI
decrease O2 demand, decrease mortality
Supraventricular tachy
metoprolol, esmolol
decrease AV conduction velocity
Variceal bleeding
Nadolol, propanolol, carvedilol
decrease hepatic venous pressure gradient and portal HTN
Adverse for B blockers
ED, cardiovascular, CNS, dyslipidemia and asthma/COPD exacerbation
B blocker B1>B2
acebutolol, atenolol, betaxolol, bisoprolol, esmolol, metoprolol
Nonselective B blockers
nadolol, propanolol, timolol, pindolol
Nonselective a and B antagonists
carvedilol, labetolol
Theophylline
Nonspecific PDE inhibitor
decrease cAMP hydrolysis –> increase cAMP –> bronchial smooth muscle relaxation –> dilation
used in COPD/ asthma
adverse: cardiotox, ab pain, neurotox
PDE5 inhibitors
-fil
decrease hydrolysis of cGMP –> increases cGMP –> increase smooth muscle relaxation by enhancing NO activity –> pulmonary vasodilation and increase blood blow to corpus cavernosum
used in erectile dysfunction, pulm HTN, BPH
adverse: flushing, HA, dyspepsia, hypotension in patients taking nitrites
PDE4 inhibitors
roflumilast
increase cAMP in neutrophils, granulocytes, bronchial epithelium
used in severe COPD
adverse: ab pain, weight loss, mental disorders
PDE3 inhibitors
Mirinone
in cardiomyocytes increase cAMP –> Ca influx –> increase ionotropy and chronotropy
in vascular smooth M increase cAMP –> MLCK inhibition –> vasodilation –> decrease preload and afterload
used in acute decompensated HF with cardiogenic shock
adverse: tachy, ventricular arrhythmias, hypotension
Platelet inhibitors PDE inhibitor
Cilostazol, Dipyridamole
increase cAMP –> inhibit platelet aggregation
used in intermittent claudication, stroke or TIA prevention, cardiac stress test, prevent coronary stent restenosis
Adverse: nausea, HA, facial flushing, hypotension, ab pain
Histamine Scromboid poisoning
Eating spoiled dark meat fish
Bacterial histidine decarboxylase converts histidine to histamine
Anaphylaxis symptoms
Treat with antihistamines, albuterol and epi if needed
Tetrodotoxin
puffer fish
bind to VGNaC in nerve tissues preventing depolarization
Nausea diarrhea, paresthesias, weakness, dizzy, loss of refelxes
Ciguatoxin
reef fish
open Na channels cause depolarization
Nausea, vomiting, diarrhea, perioral numbness, reversal of hot and cold sensations, brady, heart block, hypotension
Beers criteria
Dont give elderly a blockers anticholinergics, antidepressant, antihistamines or opioids benzos NSAIDs PPIs
Treat acetaminophen poisoing
NAC –> replenish glutathione
Treat AChE inhibitors, organophosphate
Atropine > pralidoxime
Antimuscarininc, anticholinergic tox
physiostigmine
Arsenic tox
Dimercaprol, succimer
Benzo tox
flumazenil
B blocker tox
atropine, glucagon, saline
CO tox
100% O2, hyperbaric O2
Copper tox
penicillamine, trientine
CN tox
Hydroxocobalamin, nitrates + sodium thiosulfate
Digitalis tox
Digoxin Ab fragments
Heparin tox
protamine sulfate
Iron tox
deferoxamine, deferasirox, deferiprone
Lead tox
EDTA, dimercaprol, succimer, penicillamine
Mercury tox
dimercaprol, succimer
Methanol tox (antifreeze)
fomepizole > ethanol, dialysis
methoglobin tox
methylene blue, vit C
opioid tox
naloxone
Salicylates tox
NaHCO3
TCA tox
NaHCO3
Warfarin tox
vitamin K, PCC/FFP
Drugs that cause coronary vasospasm
Cocaine, amphetamines, sumatriptan, ergot alkaloids
Drugs that cause cutaneous flushing
vancomycin, adenosine, Niacin, CCB, echinocandins, Nitrates
Red man syndrome via vancomycin. Tx with diphenhydramine
Drugs that cause dilated cardiomyopathy
Doxorubicin and Daunorubicin
treat with dexrazoxane
Drugs that cause Torsades
Class 1A and III antiarrhythmics antibiotics (macrolides) antipsychotics antidepressants antiemetics
