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Pharmacology: USMLE Step 1 Flash Cards by Seetal K Dhaliwal H. S
Pharmacology: USMLE Step 1 Flash Cards by Seetal K Dhaliwal H. S
PHARMACOLOGY
USMLE Step 1 Flash cards by Seetal K Dhaliwal H. S
by Seetal K Dhaliwal H. S
Section I
Pharmacokinetics:
Competitive inhibitors
Resemble substrate YES
Non-competitive inhibitors
NO
Overcome by [S]
Bind active site Effect on Vmax Effect on Km
YES
YES Unchanged
NO
NO Unchanged
Pharmacodynamics
potency
efficacy
Vd:
Drugs with low Vd distribute in blood; medium Vd in extracellular space or body water; high Vd distribute in tissues. A drug infused at a constant rate reaches ~94% steady state after 4 t1/2 (FIRST ORDER ELIMINATION):
# of half-lives 1
50%
t1/2:
2
75%
3
87.5%
4
93.75%
by Seetal K Dhaliwal H. S
concentration
Pharmacokinetics:
4
Loading dose:
Maintenance dose:
In patients with renal or hepatic disorder, the loading dose remains unchanged although the maintenance dose is .
Metabolism of drug:
Phase 1 (reduction, oxidation, hydrolysis) usually yields slight polar, water-soluble metabolites (often still active). CYP450. Geriatric patients lose phase 1 first. Phase 2 (acetylation, glucuronidation, sulfation) usually yields very polar, inactive metabolites (renally excreted). Conjugation phase. Zero order constant amount of drug eliminated per unit time. Phenytoin, Ethanol & Aspirin (high dose). First order constant fraction of drug eliminated per unit time. Rate of elimination is proportional to drug concentration. by Seetal K Dhaliwal H. S
Elimination of drugs:
Vd = Volume of distribution
k = elimination constant
Vd = D/C0 t1/2 = 0.7/k CL = k x Vd t1/2 = 0.7 x Vd/CL
t1/2 = half-life
CL = Clearance Css = steady state concentration LD = Loading Dose
by Seetal K Dhaliwal H. S
Section II
by Seetal K Dhaliwal H. S
ACh receptors:
Nicotinic ACh receptors are ligand-gated Na+/K+ channels; NN (found in autonomic ganglia) and NM (found in NMJ) subtypes.
Muscarinic ACh receptors are G-protein-coupled receptors that act through 2nd messengers; 5 subtypes: M1, M2, M3, M4 and M5.
by Seetal K Dhaliwal H. S
1
2 M1
s
s q
Para sympathetic
M2
M3 D1
i
q s
D2
H1 H2
i
q s
V1
V2
q
s
Cholinomimetic agents:
Drug - Direct Agonists Bethanechol Postoperative & neurogenic ileus & urinary retention Glaucoma, pupillary contraction, & release of IOP Potent simulator of sweat, tears, Contracts cilliary muscle of saliva eyes (open angle), pupillary sphincter (narrow angle); resistant to AChE. Challenge test for diagnosis of asthma Stimulates muscarinic receptors in airway when inhaled. Activates bowel & bladder smooth muscle; resistant to AChE. Clinical applications Action
10
Carbachol
Pilocarpine
Methacholine
by Seetal K Dhaliwal H. S
Cholinomimetic agents:
Drug
- Indirect Agonists (anti-cholinesterases)
11
Clinical applications
Action
Neostigmine
Postoperative & neurogenic ileus & urinary retention, myasthenia gravis, reversal of NMJ block (post-operative) Myasthenia gravis (longacting). Doesnt cross BBB. Diagnosing myasthenia gravis extremely short acting). If
+MG, symptoms disappear, if ACh overdose, symptoms get worse.
endogenous ACh; no CNS penetration. NEO CNS = NO CNS penetration. endogenous ACh; strength. endogenous ACh.
Pyridostigmine Edrophonium
Physostigmine Echothiophate
12
Caused by parathion & other organophosphates. Irreversible inhibitors. DUMBBELSS symptoms: Diarrhea, Urination, Miosis, Bradycardia, Bronchospasm, Excitation of skeletal muscle, Lacrimation, Sweating, Salivation (also abdominal cramps). Antidote ATROPINE (muscarinic antagonist) plus PRALIDOXIME (used to regenerate active cholinesterase).
pupil dilation (mydriasis), cycloplegia, airway secretions, acid secretion, motility, urgency & cystitis. Blocks SLUD: Salivation, Lacrimation, Urination & Diarrhea. Toxicity: body temperature, rapid pulse, dry mouth, dry flushed skin, cycloplegia, constipation, disorientation. Can cause acute angle-closure glaucoma in elderly, urinary retention in men with prostatic hyperplasia, & hyperthermia in infants. HOT as a HARE, DRY as a BONE, RED as a BEET, BLIND as a BAT, MAD as a HATTER.
by Seetal K Dhaliwal H. S
Muscarinic antagonist:
13
Atropine, homatropine, tropicamide EYE produces mydriasis & cycloplegia. Benztropine CNS Used in Parkinson disease (PARK my BENZ). Scopolamine CNS Anti-motion Sickness. Ipratropium bromide Respiratory used in Asthma & COPD. Oxybutynin, glycopyrrolate Genitourinary used to reduce urgency in mild cystitis & reduce bladder spasms.
Methscopolamine, pirenzepine, propantheline Gastrointestinal peptic ulcer treatment.
Ganglion blocker. Used in experimental models to prevent vagal reflex responses to changes in blood pressure e.g., prevents reflex bradycardia caused by NE. Toxicity: Severe orthostatic hypotension, blurred vision, constipation, sexual dysfunction. Put a HEX on smokers (nicotine) to help them quit.
by Seetal K Dhaliwal H. S
Direct - Sympatomimetics:
14
1,2,1,2; low doses selective for 1. 1, 2 > 1 1 = 2 (isolated to ) D1 = D2 > > , inotropic & chronotropic 1 > 2 , inotropic but NOT chronotropic 1 > 2
Used in anaphylaxis, glaucoma (openangle), asthma, hypotension. Used in hypotension but renal perfusion. Used in AV block (rare) Used in shock (to renal perfusion), heart failure. Used in shock, heart failure, cardiac stress testing (if treadmill cannot use) Used to dilate pupil, as a vasoconstrictor & nasal decongestant.
MAST: Metaproterenol & Albuterol for acute asthma, Salmeterol long-term tx, Terbutaline to reduce premature uterine contractions.
Reduces premature uterine contractions
by Seetal K Dhaliwal H. S
15
Amphetamine indirect general agonist; releases stored catecholamines used in Narcolepsy, obesity, attention deficit disorder (ADHD). Ephedrine indirect general agonist; releases stored catecholamines used in nasal decongestion, urinary incontinence, hypotension.
Cocaine indirect general agonist; uptake inhibitor causes vasoconstriction & used as local anesthesia.
Celecoxib, Furosemide, Probenecid, Thiazides, TMP-SMX, Sulfasalazine, Sulfonylureas, Sumatriptan. Patients with sulfa allergy may develop fever, pruritic rash, SJS, hemolytic anemia, thrombocytopenia, agranulocytosis, & urticaria (hives). Symptoms range from mild to life-threatening.
by Seetal K Dhaliwal H. S
16
Application
Toxicity
Pheochromocytoma Orthostatic hypotension, reflex (use tachycardia phenoxybenzamine before removing tumor)
1 selective (-zosin) Prazosin, terazosin, Hypertension, urinary doxazosin. retention in BPH. 2 selective Mirtazepine
Depression
17
Effect Cardiac output, renin secretion (due to -receptor block on JGA cells) HR & contractility, resulting in O2 consumption. -blockers, mortality AV conduction velocity (class II antiarrhythmics) Slows progression of chronic failure
Toxicity: Impotence, exacerbation of asthma, CVS effects (bradycardia, AV block, CHF), CNS effects (sedation, sleep alterations); USE WITH CAUTION IN DIABETICS (masks hyperglycemia) Selectivity: Nonselective antagonist Propanolol, Timolol, Nadolol, Pindolol & Labetolol. 1-selective antagonists (1>2) Acebutolol (partial), Betaxolol, Esmolol (short acting), Atenolol, Metoprolol (A BEAM of 1 blockers). Nonselective & antagonists Carvedilol, Labetolol. Partial -Agonist Pindolol, Acebutolol by Seetal K Dhaliwal H. S
-agonist Epinephrine outflow of aqueous humor Mydriasis, stinging, do not use in closed-angle glaucoma
Brimonidine
-blockers Timolol, betaxolol, carteolol
Diuretics
Acetazolamide Cholinomimetics Pilocarpine, carbachol, physostigmine, echothiophate
outflow of aqueous humor (echothiophate, physostigmine); contract cilliary muscle & open trabecular meshwork (pilocarpine, carbachol); use pilocarpine in emergencies very effective at opening canal of Schlemm.
Miosis, cyclospasm
Prostaglandin
Latanoprost (PGF2) outflow of aqueous humor Darkens color of iris (browning)
by Seetal K Dhaliwal H. S