Dx @ the nicotinic type I receptors

agonists: ACh & nicotine

antagonist: trimethaphan, hexamethonium

Rx @ the nicotinic type II receptors

skeletal muscle motor endplate

Agonist: ACh, nicotine, succinylcholine

Antagonists: d-tubocurarine, pancuronium

Rx @ the Na+ channels of cardiac fast fibers (atria & ventricles)

Class IA: procainamide, quinidine

Class IB: lidocaine--only affects ventricles

Class III: amiodarone, dronedarone

Rx that act @ the Na+ channels of the CNS

antiepileptic: phenytoin, carbamazepine, valproate, & lamotrigine

Rx @ the Na+ channels in sensory nerve fibers

cocaine, procaine, lidocaine

What states of the Na+ channel (activated, resting, inactivated) do local anesthetics bind most avidly to

Activated and Inactivated states

Ca+ channel blockers at L-type channels in heart and vascular smooth muscle (VSM)

nifedipine, diltiazem & verapamil 

Al, Fe, diltiazem & verapami blooc Ca+ channels where? 

Smooth Muscle of GI tract

What blocks Ca channels in smooth muscle of uterus? 

Mg++

Blocks T-type Ca++ channels in CNS

ethosuximide

DOC for tx of neuroleptic malignant S/O and anesthesia induced hyperthermia

Dantrolen (a.k.a Dantrolene Sodium)

*causes generalized muscle weakness bc relaxes ALL skeletal muscle (vs Banclofen)

Muscarinic receptors @ SA node (couple to K-channel via G-protein)

agonist: ACh, pilocarpine, AChase inhibitors

antagonist: atropine, pancuronium, quinidine, TCA's, older antihistamines

MOA of atropine? 

antagonist of muscarinic receptors @ the SA node

Arterial Vasodilators

activated ATP-modulated K-channels=hyperpolarization=relaxation=vasodilation

Hydralazine, Minoxidil, Diazoxide

Class IA antiarrhythmic drugs

procainamide & quinidine 

*quinidine: widens QRS and incres. Q-T interval

Class IB

Lidocaine

*accelerates repolarization

Delayed ventricular repolarization via block of K+ channels, increased APD, ERP, & Q-T interval

S/E Torsades de Pointes

Amiodarone and Sotalol

"Resets the heart"

Opens K+ channels in the AV node to hyperpolarize and Stop ALL AV conduction

Adenosine

Insulin Secretion 

via closure of K+ channels-->depol-->Ca+ channels and whola!!! insulin secretion 

Tolbutamide, Chlorpropamide, Glypizide, Repaglinide

Inhibit Insulin Secretion

(tx for insulinoma, chronic hypoglycemia)

 opens K+ channels (repol)

Diazoxide

Acts on GABA-b receptors coupled to K+ channels in the CNS --> hyperpolarizes presynaptic terminals --> reduces NT glutamate onto alpha-motor neurons. 

muscle relaxant 

Baclofen 

Hyperpolize neurons via Mu receptors 

Opiates (morphine) 

Dopamine, Bromocriptine, & Pergolide act on which receptors? 

D2 receptors in the anterior pituitary 

MOA of clonidine 

alpha-2 receptors in the medulla to inhibit peripheral sympathetic outflow 

Increase FREQUENCY of GABA channel opening

BZs 

Increases DURATION of GABA channel opening 

Barbiturates

Increases GABA by increasing Glutamic Dehydrogenase and inhibiting GABA transaminase

Releases GABA from its neurons 

Gabapentin 

What class of drugs (acc. to MOA)

papaverine, dipyridamole, amrinone, milrinone

Phosphodiesterase inhibitors

(convert CGMP to 5'GMP)

*also include theophylline and aminophylline but I didn't include them bc it would give away the answer. 

Phosphodiesterase inhibitor --> bronchodilation --> tx of neonatal apnea

Theophylline, aminophylline

relaxation of s.m. in the corpus cavernosa = penile erection 

Papaverine 

decreased platelet aggregation when used w/ aspirin

dipyridamole 

increased cardiac dp/dt (tx of terminal CHF)

*used in ICU 

Amrinone and Milrinone

Nitrate Vasodilator (nitroglycerin) & Na+ nitroprusside

MOA? 

Converted to NO which activates guanyl cylclase: CGMP relaxes arterial/venous VSM and inhibits platelet aggregation. 

Sildenafil 

MOA? 

Causes erection by inhibiting the type V PDEase which degrades CGMP. 

Digoxin

MOA? 

Increases dp/dt of myocytes by partially blocking the Na+/K+ ATPase -->outside/inside Na+ gradient decrs.--> less Ca+ is extruded and stored in SR --> the next depol results in greater release of Ca+ from SR

Blocks Na+:K+:2CL- symporter in ascending limb of Henle's loop 

Furosemide & Ethacrynic Acid

blocks  Na+:Cl- symporter in renal DT

Thiazide diuretic dx

blocks

1) Na+ channels in principal cells of LDT/CD

2) H+ ion secretion from LDT/CD

Amiloride and Triamterene 

Decreases H+ secretion in renal PT and DT by inhibiting CA

Acetazolamide

Increased deposition of fibrillar collagen in the extracellular matrix of the heart. 

Aldosterone

*incrsd. basolateral ATPase, Na+ channels and Es (enzymes) for oxidative phosphorylation (ATP) in LDT/CD. 

MOA of glucocorticoids= cortisone, hydrocortisone, prednisone, prednisolone

• incrsd gene transcription for lipocortin [inhibits PLA2], IkB [inhibits NFkB], enzymes for gluconeogenesis. 
• decrsd genes trancript for COX-2, IL-1, IL-6 in monocytes & macrophages, gene for NFkB, and E's for glycogen storage

Block ATP binding site of the IkappaK kinase

-->prevents phosphorylation and subsequent dissociation of the inhibitory IkappaB from NFkB

--> block expression of inflammatory mediators

NSAIDs

Stanozolol

Androgen Steroid NOT a Beta-blocker

Tx hereditary Angioedema: peripheral edema, abdominal pain and pot. fatal laryngeal edema)

Increased erythropoesis and hepatic synthesis of C1 esterase inhibitor of complement

Androgens

Increases hepatic protein synthesis=transcortin (CBG), TBG, angiotensinogen, transferrin, fibrinogen, and clotting factors 2, 7, 9, 10

Estrogens

Paclitaxel and Docetaxel 

Cause the phosphorylation of the antiapoptosis gene Bcl-2

Blocks binding of the ATP site of the tyrosine kinase in Chronic Myelogenous leukemia 

Imatinib

Bortezomib

Trastuzumab

Cetuximab

**dx w/ underrepresented letters of the alphabet :) 

1) inhibits 26S proteasome --> NFkB not released

2) blocks EGFR by HER1/neu (ErbB-2) in breast CAs

3) blocks HER1 (ErbB-1) EGFR in colorectal CAs 

Plasma Pseudocholinesterase Deficiency 

NMB by SuccCholine last hrs instead of minutes

Case: Procedure where pt given SuccCholine & pt does not start breathing in nl amount of time

Aspiring Hypersensitivity in pts w/ nasal polyps

Aspiring and NSAIDs

*block PG synthesis --> shunts all arachidonic acid to leukotriene synthesis --> rhinoconjuctivitis, angioedema, urticaria. 

Hemolytic Anemia produced by primaquine, isoniazid, sulfonamides, nitrofurantoin, or eating fava beans

Glucose-6-phosphate dehydrogenase deficiency

Someone taking malaria meds (primaquine)

or antibiotics (sulfonamides) or ate fava beans develops hemolytic anemia, what do they have? 

Glucose-6-phosphate dehydrogenase deficiency

SHIP drugs 

sulfapyridine: hemolytic & aplastic anemia, hep 

hydralazine: SLE like S/O

isoniazid: hep damage, peripheral neuropathy

Procainamide: SLE like S/O

Pt takes volatile anesthetic + SuccCholine --> massive release of Ca+ = masseter muscle spasm

Malignant hyperthermia 

*incrsd BP, HR, muscle contraction w/ hyperthermia, lactic acidosis, and cardiac dysrhythmias

Tx of Malignant hyperthermia 

Dantrolene Sodium 

*prevents release of Ca from the SR

Rapid blockade of central DA receptors w/ the typical antipsychotic dx like haroperidol 

Neuroleptic Malignant S/O

* severe Parkinson's dx w/ catatonia=EPS, stupor, hyperthermia, incsd CPK, myoglobinuria, ARF

tx of Neuroleptic Malignant S/O

Dantrolene Sodium (stops contraction) + bromocriptine (a D2 receptor agonist) 

Favorite Inducers of CYP450

phenobarbital, phenytoin, carbamazepine, nicotine, and chronic EtOH consumption

Inhibitors of CYP450

erythromycin, cimetidine, ketoconazole

Question w/ inhibitor of CYP450 and decreased clearance of Ca+ channel blocker 

Grapefruit juice 

Rx to increased clearance of acidic drugs by making urine alkaline

Sodium Bicarbonate

Acetazolamide

Make urine acidic to increase clearance of basic drugs 

Ammonium Chloride