Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
129 Cards in this Set
- Front
- Back
|
Ion Channels
=To INHIBIT depolarization, what could you do? |
1) Block Na Channels
=decreased Na conductance 2) Block Ca Channels =decreased Ca conductance 3) Open K Channels =Increased K conductance 4) Open Cl Channels =Increased Cl conductance |
|
|
Drugs Acting Through SODIUM Channels
|
1) Nicotinic Type I Receptors
2) Nicotinic Type II Receptors 3) Na Channels of Cardiac Fast Fibers 4) Na Channels in the CNS 5) Na channels in sensory nerve fibers 6) Na channels coupled to 5HT3 receptors in the CTZ |
|
|
Nicotinic Type I Receptors
|
=Autonomic Ganglia
Agonists: =ACh + nicotine =ENHANCE Na conductancce Antagonists: =Trimethaphan + hexamethonium ="Ganglionic Blocking Drugs" |
|
|
Nicotinic Type II Receptors
|
**Skeletal muscle motor endplate
Agonists: =ACh, nicotine, + succinylcholine =Enhance Na conductance Antagonists: =d-tubocurarine (d-tc), pancuronium, Mg++ =i.e. the -curiums and -roniums |
|
|
Sodium Channels of Cardiac Fast Fibers
|
**Atria + ventricles
Class IA Drugs: =procainamide =disopyramide =quinidine Class IB Drugs: =Lidocaine --> ONLY affects VENTRICLES! |
|
|
Sodium Channels in the CNS
|
**The antiepileptic drugs:
=phenytoin =carbamazepine =valproate =inhibit the spread of electrical signals by prolonging the state of inactivation of the Na channel |
|
|
Sodium channels in sensory nerve fibers
|
**The cationic form of LOCAL anesthetic drugs (=cocaine, procaine, lidocaine) will BLOCK Na conductance by binding to a site in the channel on the AXOPLASMIC side (=i.e. inside cell)
|
|
|
Sodium Channels Coupled to 5-HT3 Receptors in the CTZ
|
=induce n/v
**Blocked by ondansetron! |
|
|
Calcium Channel Blockers
|
1) Nifedipine
2) Diltiazem 3) Verapamil **Block L-TYPE Ca channels in the HEART + vascular smooth muscle |
|
|
Ca channels in the SM of GI tract are blocked by:
|
1) Al
2) Fe 3) Diltiazem 4) Verapamil |
|
|
Ca channels in the SM of the uterus are blocked by:
|
Mg
|
|
|
T-type Ca channels in the CNS are blocked by:
|
ethosuximide
|
|
|
What blocks glutamate stimulation of NMDA type Ca receptors?
|
**Ketamine + phencyclidine (="angel dust") BLOCK NMDA receptors and PREVENT the excitatory effects of glutamate -->
Causes "dissociative" anesthesia + hallucinations **FELBAMATE prevents seizures by blocking NMDA receptors |
|
|
What blocks internal Ca channels of the SR?
|
**DANTROLENE
=prevents the release of "trigger" Ca **i.e. Dantrolene is the DOC for treatment of: =neuroleptic malignant syndrome =anesthesia-induced malignant hyperthermia |
|
|
What else can Dantrolene be used for?
|
**Prevent spasticity caused by neuro. diseases
**Causes GENERALIZED muscle weakness however--i.e. it relaxes ALL skeletal muscle NOT just the spastic muscle |
|
|
Drugs acting through POTASSIUM Channels:
|
Hyperpolarization = Inhibition
|
|
|
Muscarinic receptors at the SA node are coupled to a K-channel via a G-protin
|
Agonists:
=ACh =Pilocarpine =AChase inhibitors --> i.e. indirectly through increased ACh Antagonists: =atropine =pancuronium =quinidine =TCAs =older antihistamines--like diphenhydramine |
|
|
5-HT1A recectprs in the CNS
|
BUSPIRONE is a partial agonist = ANTI-ANXIETY
|
|
|
Vascular SM
|
1) Arterial Vasodilators
=hydralazine =minoxidil =diazoxide **All will activate ATP-modulated K-channels --> hyperpolarization = relaxation = vasodilation |
|
|
Class IA
|
Class IA:
=procainamide =disopyramide =quinidine **ALL will prolong repolarization (=APD + ERP increased) **ONLY quinidine actually widens the QRS and increases the QT interval |
|
|
Class IB
|
=Lidocaine
**Accelerates REPOLARIZATION =APD decreased |
|
|
Effects of Amiodarone + Sotalol
|
**Delay ventricular repolarization via block of K+ channels
=Increased APD, ERP, and Q-T interval |
|
|
What does Terfenadine do?
|
**Blocks K+ channels AND delays repolarization in the VENTRICLES
=BUT, under normal conditions, terfenadine is completely metabolized by CYP450 to its active metabolite = FEXOFENADINE |
|
|
What can happen if you give the macrolide ERYTHROMYCIN w/ terfenadine?
|
**Erythromycin will INHIBIT the CYP450
=SO, terfenadine inhibits repolarization + can increase the QT interval enough to cause TORSADES DE POINTES (i.e. ventricular tachycardia) |
|
|
What else can cause torsades de pointes by partially inhibiting the K-repolarization current?
|
Cisapride
|
|
|
K+ Channels and the Pancreatic B-islet Cells:
|
**Orally active drugs:
=tolbutamide =chlorpropamide =glypizide are going to CLOSE K+ channels --> causing cell to DEPOLARIZE =depolarization will OPEN voltage-sensitive Ca channgels --> Ca flows in to activate PLC which INCREASES IP3 which then release MORE Ca from the SR =all this increased free intracellular Ca causes INSULIN SECRETION! |
|
|
What drug can open ATP-regulated K+ channels to PREVENT depolarization and thus insulin secretion??
|
Diazoxide
|
|
|
What other drugs inhibit insulin secretion by an unknown mechanism?
|
Thiazide diuretics
Furosemide |
|
|
GABA (B) Receptors are coupled to K+ Channels in the CNS:
|
Agonist:
=Baclofen |
|
|
How does Baclofen work?
|
=Baclofen enhances GABA-mediated K+ conductance --> HYPERPOLARIZES presynaptic terminals + thus REDUCES the release of the excitatory NT glutamate in teh spinal cord
|
|
|
What is Baclofen used for?
|
**Used to treat spasticity associated with:
=cerebral palsy =MS =stroke **Is as effective as BZ's BUT causes less sedation **ALSO causes less of a decrease in muscle strength than does dantrolene! |
|
|
What do opiates do?
|
HYPERPOLARIZE neurons via mu receptors
|
|
|
D2-receptors in the Anterior Pituitary
|
**Dopamine, bromocriptine, and pergolide can HYPERPOLARIZE cells to PREVENT prolactin release
note: in other parts of the brain, DA inhibits adenyl cyclase OR Ca conductance! |
|
|
alpha-2 adrenoceptors in the MEDULLA
|
**Clonidine HYPERPOLARIZES to inhibit peripheral sympathetic outflow
|
|
|
CHLORIDE CHANNELS:
|
1) GABA (A) Receptors
2) Glycine Receptors on Renshaw Cells |
|
|
GABA (A) Receptors
|
**Hyperpolarization = INHIBITION
|
|
|
What ENHANCES the effect of GABA (A)??
|
1) Ethanol
2) Propofol 3) Volatile anesthetic agents 4) Benzos =increased FREQUENCY of channel opening 5) Barbiturates =increased DURATION of channel opening |
|
|
How does VALPROATE increase GABA?
|
**Valproate increases GABA concentration by increasing glutamic acid dehydrogenase + INHIBITING GABA transaminase
|
|
|
What can release GABA from its neurons?
|
Gabapentin
|
|
|
Glycine Receptors on Renshaw Cells (=spinal interneurons)
|
**Glycine released from Renshaw cells INHIBITS alpha-motor neurons
**Strychnine blocks glycine receptors in the spinal cord =NO alpha-motor neuron inhibition --> CONVULSIONS |
|
|
cAMP Receptors
|
=receptors coupled to adenyl cyclase via a G-protein
Includes: =B1 adrenoceptors =B2 adrenoceptors =D1 dopamine receptors =H2 histamine receptors =PGI2 (prostacyclin) + PGE receptors =V2-AVP receptors =5-HT1 receptors |
|
|
B1-Adrenoceptors = in the HEART
|
**Heart:
=increase HR =increase contractility + impulse conduction =decrease APD + ERP |
|
|
B1-Adrenoceptors = in the ADIPOCYTE
|
=lipolysis --> INCREASED plasma free fatty acids
|
|
|
B1-Adrenoceptor = in the RENAL JG CELLS
|
=increased renin release
|
|
|
B2-Adrenoceptors = LUNGS
|
**i.e. BRONCHIAL SM
=relaxation = bronchodilation = increased FEV1 |
|
|
B2-Adrenoceptors = VSM
|
=relaxation
=vasodilation of arteries + veins |
|
|
B2-Adrenoceptors = UTERUS
|
=Relaxation
=inhibition of parturition |
|
|
B2-Adrenoceptors = LIVER
|
=glycogenolysis via protein kinase activation of phosphorylase A
|
|
|
B2-Adrenoceptors = MAST CELL
|
=decreased free intracellular Ca INHIBITS degranulation
|
|
|
D1-dopamine receptors
|
=vasodilation in the kidney
|
|
|
What bloccks D1-dopamine receptors?
|
=D1-D2 receptor blockers like HALOPERIDOL
|
|
|
H2-Histamine Receptors
|
**relaxation of VSM
=DIRECT + through NO =causes VASODILATION **increased GASTRIC ACID secretion from oxynitic cells |
|
|
PGI2 + PGE Receptors
|
=relaxation of VSM --> vasodilation
=decreased platelet aggregation |
|
|
V2-AVP Receptors
|
**Located in the RENAL COLLECTING DUCT
=AVP (ADH) increases water reabsorption |
|
|
What can INHIBIT this process?
|
1) PGE's
2) atrial natriuretic factor 3) lithium 4) demeclocycline |
|
|
What can POTENTIATE the antidiurectic effect?
|
=chlopropramide
=carbamazepine |
|
|
5-HT1 Receptors
|
Relaxation of VSM causes SUSTAINED VASODILATION
|
|
|
What HORMONES can activate adenyl cyclases?
|
1) ACTH
2) FSH 3) LH 4) Glucagon 5) PTH |
|
|
What are the phosphodiesterase inhibitors?
|
1) Theophylline, aminophylline
2) Papaverine 3) Dipyridamole 4) Amrinone and milrinone |
|
|
Theophylline, Aminophylline
|
**Bronchodilation
=treatment of neonatal apnea |
|
|
Papaverine
|
=Relaxation of smooth muscle in the corpus cavernosa
=Penile ERECTION |
|
|
Dipyridamole
|
=decreased platelet aggregation when used w/ aspirin
|
|
|
Amrinone and Milrinone
|
=increased cardiac dp/dt
=i.e. treatment of terminal CHF |
|
|
Signal Transduction via cGMP:
|
**THINK antianginal drugs!!
=NO is produced tonically by the vascular endothelial cells =NO activates guanyl cyclase =cGMP relaxes arterial/venous VSM --> i.e. a kinase dephosphorylates the myosin light chains + THUS INHIBITS PLATELET AGGREGATION |
|
|
What drugs are converted to NO?
|
=Nitrate vasodilators (i.e. nitroglycerin)
=Na nitroprusside |
|
|
ANF
|
=also decreases BP by activation of guanyl cyclase and thus increases cGMP
|
|
|
Sildenafil
|
=causes erection by INHIBITING the Type V PDEase which degrades cGMP
|
|
|
IP3 and DAG
|
=IP3 releases Ca from the SR
=Ca then bings to calmodulin whicch then activates enzymes --> SM contraction or secretion |
|
|
Which receptors does this include?
|
1) Muscarinic Receptors
2) alpha-1 adrenoceptors 3) Ang II receptors on VSM 4) TXA2 receptors on VSM 5) V1-AVP receptors = VSM 6) H1 histamine receptors =Vascular endothelial cells =SM of bronchioles + GI tract 7) 5-HT2 receptors on VSM 8) PGE receptors =SM of uterus =GI tract |
|
|
Where are the muscarinic receptors located that use this IP3/DAG method?
|
=sphincter muscle of iris
=SM of bronchioles =bronchial glands =SM of GI tract + GB =detrusor muscle of urinary bladder =pancreatic acini and alpha-islet cells (glucagon) =salivary glands =lacrimal glands =nasopharyngeal glands |
|
|
What can INHIBIT the recycling of PIP2 and THUS interrupt the IP3 signaling pathway?
|
Lithium
|
|
|
Normal process of Ca entry into cardiac cells:
|
=Depolarization allows Ca to move into the cardiac cell via L-type (=voltage-sensitive) Ca channels
=SOME of this Ca is pumped into the SR--additional Ca is extruded by a Na-Ca antiporter which uses the HIGH outside/LOW inside Na to move Ca out against its concentration gradient **This outside/inside Na gradient is maintained by the membrane Na-K-ATPase |
|
|
SO, what would a drug like digoxin do?
|
=Digoxin partially blocks the Na-K-ATPase --> SO, the outside/inside Na gradient is DECREASED
=THUS, less Ca is extruded by the Na-Ca exchange =this excess Ca in the cell is stored in the SR =AND, the next depolarization results in an even GREATER release of Ca from the SR |
|
|
What drug can inhibit the gastric H+-K+ ATPase (=proton pump)??
|
Omeprazole
|
|
|
What drug can block the Na/K/2Cl symporter in the ascending limb of Henle's Loop??
|
=Furosemide
=Ethacrynic acid |
|
|
What can block the Na/Cl symporter in the renal DT?
|
=thiazide diuretic drugs
|
|
|
What can block Na channels in the principal cells of the LDT/CD??
|
=Amiloride
=Triamterene |
|
|
What can block H+ ion secretion in renal PT and DT?
|
=decreased by ACETAZOLAMIDE bc it inhibits CA
|
|
|
What blocks H+ ion secretion from the LDT/CD??
|
**Bloccked by:
=Amiloride =Triamterene |
|
|
Changes in DNA Transcription:
|
=i.e. what causes INCREASED vs. DECREASED gene transcription?
|
|
|
Thyroxine
|
=INCREASED B-receptors + mitochondrial enzymes for oxidative phosphorylation (=ATP)
|
|
|
Aldosterone
|
=INCREASES basolateral ATPase, Na channels, + enzymes for oxidative phosphorylation in the LDT/CD
=INCREASED deposition of fibrillar collagen in the extracellular matrix of the heart |
|
|
Glucocorticoids
=1st--what are the glucocorticoids? |
=Cortisone
=Hydrocortisone =Prednisone =Prednisolone =Beclomethasone =Triamcinolone |
|
|
What do they do??
|
1) Increased transcription of the genes for:
=lipocortin via inhibiting phospholipase A2 =the inhibitor of NFKB =enzymes for gluconeogenesis 2) Decreased transcription of genes for: =COX-2 =IL-1 and IL-6 in monocytes + macrophages =Gene for NFKB =Enzymes for glycogen storage (EXCEPT for glycogen synthetase) |
|
|
Cyclosporine
|
=DECREASED transcription of the gene for IL-2 in helper T-cells
|
|
|
Androgens
|
=INCREASED erythropoesis and hepatic synthesis of C1-esterase inhibitor of complement
|
|
|
Estrogens
|
**Increased hepatic protein synthesis:
=increased transcortin (CBG) =increased thyroxine-binding globulin (TBG) =increased angiotensinogen (=renin substrate) =increased transferrin =increased fibrinogen and clotting factors 2, 7, 9, + 10 |
|
|
NSAIDs
|
=Prevent the activation of nuclear factor kappa-B
=this action PREVENTS the increased expression of the genes that code for many inflammatory mediators |
|
|
What is a Scatchard Plot?
|
=Measures the affinity of a ligand for a receptor
**Slope: = -1/KD = AFFINITY **Number of receptors per mg of protein: = Bmax = X-intercept |
|
|
Idiosyncratic Drug Reactions
|
=They usually have a GENETIC BASIS
|
|
|
What if you have a Plasma Pseudocholinesterase Deficiency?
|
=the NMB caused by succinylcholine lasts HOURS instead of minutes!
|
|
|
Barbituates in OLDER patients:
|
=cause EXCITATION + ANXIETY instead of sedation
|
|
|
OLDER ANTIHISTAMINES (=i.e. diphenhydramine) in young children OR older patients:
|
=Cause excitation instead of sedation
|
|
|
Patients w/ Nasal Polyps
|
=Aspirin + other NSAIDs precipitate an anaphylactic-like reaction (=i.e. aspirin hypersensitiviy) in patients w/ nasal polypos
**i.e. blocckade of PG synthesis by the NSAID shunts all the arachidonic acid to leukotriene synthesis --> LTs cause: =rhinoconjunctivitis =angioedema =uticaria |
|
|
G6PD-Deficiency
|
**Can cause HEMOLYTIC ANEMIA when taking:
=primaquine =isoniazid =sulfonamides =nitrofurantoin =eating fava beans |
|
|
SLOW ACETYLATORS
|
**i.e. SHIP Drugs will exhibit toxicity in slow acetylators:
1) Sulfapyridine (=contained in the drug Sulfasalazine) =hemolytic + aplastic anemia =hepatic damage 2) Hydralazine =SLE-like syndrome 3) Isoniazid =hepatic damage =peripheral neuropathhy 4) Procainamide =SLE-like syndrome |
|
|
What can we treat the peripheral neuropathy found in slow acetylators taking ISONIAZID with?
|
Pyridoxal phosphate = VITAMIN B6
|
|
|
What is the basis of Malignant Hyperthermia (Hyperpyrexia?)
|
=Gene defect prevents Ca from being sequestered correctly in the SR of skeletal muscle
|
|
|
What can cause it?
|
=Anesthesia w/ a volatile anesthetic agent (=i.e. Halothane) PLUS the administration of SUCCINYLCHOINE causes the massive release of Ca
=masseter muscle spasm |
|
|
Symptoms and Signs:
|
=Increased BP
=Increased HR =Muscle contractions =Hyperthermia Also see: =lactic acidosis =cardiac dysrhythmias |
|
|
Treatment?
|
DANTROLENE SODIUM
=prevents the release of Ca from the SR |
|
|
What is the etiology of Neuroleptic Malignant Syndrome?
|
=NOT RELATED TO malignant hyperthermia!
=Produced by a rapid blockade of central DA receptors w/ the typical antipsychotic drugs like HALOPERIDOL |
|
|
Symptoms/Signs:
|
**Resembles severe Parkinson's Disease w/ Catatonia
=EPS =Stupor =Hyperthermia =Increased CPK --> ARF =Myoglobinuria |
|
|
Treatment?
|
Dantrolene Sodium + Bromocriptine (=a D2-receptor agonist)
|
|
|
Abbreviations:
|
Vd = Volume of Distribution
|
|
|
Vd
|
Cl = Clearance
|
|
|
Cp
|
Cp = Plasma concentration
|
|
|
Cpss
|
Cpss = Plasma [ ] at steady state
|
|
|
Cpo
|
Cpo = estimated plasma concentration at zero time
|
|
|
Xo
|
Dose (mg)
|
|
|
XL
|
Loading dose
**Depends ONLY on the Vd |
|
|
XM
|
Maintenance Dose
**Depends ONLY on the Cl |
|
|
F
|
Bioavailability
=ONLY used w/ p.o. treatment **When given IV, F = 1.0 |
|
|
t1/2
|
Elimination half-life
|
|
|
k
|
fractional rate of elimination
|
|
|
rate in
|
=dosing rate
|
|
|
rate out
|
=elimination rate
|
|
|
Cpo =
|
Cpo = (Xo x F) / Vd
|
|
|
XL =
|
XL = (Cp x Vd) / F
|
|
|
k =
|
k = 0.7 / t1/2
|
|
|
t1/2 =
|
Vd/Cl
|
|
|
Cl =
|
Cl = rate out/Cp
|
|
|
AT Cpss =
|
rate in = rate out
|
|
|
What drugs INDUCE CYP450??
|
1) Phenobarbital
2) Phenytoin 3) Carbamazepine 4) Nicotine 5) Chronic EtOH consumption |
|
|
What drugs INHIBIT CYP450?
|
1) Erythromycin
2) Ketoconazole **Note: =the time is right for them to ask about grapefruit juice as an inhibitor of CYP450 =the question will probably involve decreased clearance of a calcium channel blocker |
|
|
How can the renal clearance of ACIDIC drugs (=aspirin) be INCREASED?
|
=by making the urine ALKALINE
i.e. via administration of: 1) Sodium bicarbonate 2) Carbonic anhydrase inhibitor (=i.e. acetazolamide) **The LOWER pKa of the acidic drug = the GREATER the increase in renal clearance when the urine is made alkaline! |
|
|
How can the renal clearance of BASIC drugs (=i.e. amphetamines) be incrased?
|
**By making the urine ACIDIC via administration of ammonium chloride
**The higher the pKa of the basic drug, the GREATER the increase in renal clearance when the urine is made acidic |
|
|
Which drug exerts a pharmacologic effect--free or bound?
|
ONLY FREE
|
|
|
What is the effect of decreased plasma protein concentration?
|
=Decreased plasma protein concentration (=albumin) INCREASES the fraction of free drug in plasma
|
