What do you do to inhibit depolarization?

Cl, K, Na, Ca channels

         - block sodium channels = decreased sodium conductance

         - block calcium channels = decreased calcium conductance

         - open potassium channels = increased potassium conductance

         - open chloride channels = increased chloride conductance

nicotinic type I receptors = autonomic ganglia

Name the agonists and antagonists:

agonists = ACh and nicotine (enhance Na conductance)

   antagonists  (ganglionic blocking drugs) = trimethaphan, hexamethonium

nicotinic type II receptors = skeletal muscle motor endplate

Name the agonists and antagonists:

agonists = ACh, nicotine, succinylcholine = enhance Na conductance

         antagonists = d-tubocurarine (d-tc), pancuronium, Mg++ = the -curiums and

         -roniums

sodium channels of cardiac fast fibers = atria, ventricles

Name the class 1A, 1B, III drugs

class IA drugs = procainamide, quinidine

         class IB drugs = lidocaine - only affects ventricles

         class III drugs = amiodarone, dronedarone

How do valproate & lamotrigine inhibit the spread of electrical signals?

by prolonging the state of inactivation of the sodium channel

How do cocaine, procaine, and lidocaine block sensory nerve firing?

the cationic form of local anesthetic drugs blocks Na⁺  conductance by binding to asite in the channel on the axoplasmic side (inside cell)

Sodium channels coupled to 5-HT₃ receptors in CTZ = induce nausea/emesis

Which drugs block L-type channels

         in heart and vascular smooth muscle (VSM)?

nifedipine, diltiazem & verapamil

Ca⁺⁺  channels in SM of GI tract blocked by?

Al, Fe, diltiazem and verapamil

T-type Ca⁺⁺ channels in CNS blocked by?

ethosuximide

What blocks NMDA receptors and prevent the

         excitatory effects of glutamate to cause “dissociative” anesthesia and

                        hallucinations? 

What is the DOC for tx of neuroleptic malignant syndrome and anesthesiainduced malignant hyperthermia (hyperpyrexia)?

dantrolene-- MOA - Internal Ca⁺⁺  channels of SR blocked

Muscarinic receptors at the SA node - coupled to a K-channel via a G-protein

agonists and antagonists?

agonists = ACh, pilocarpine, AChase inhibitors (indirect through increased ACh)

antagonists = atropine et al., pancuronium, quinidine, TCA’s, older antihistamineslike diphenhydramine

What drug is a partial agonist at 5-HT_1A-receptors in the CNS?

buspirone- for antianxiety

Which drugs?

Vascular smooth muscle - arterial vasodilators

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

hydralazine, minoxidil, diazoxide

Fast cardiac fibers - antiarrhythmic drugs

Class IA

Class IB

Class IA: procainamide & quinidine slow K⁺ conductance and thus prolong repolarization (APD & ERP increased); only quinidine actually widens theQRS and ­ the Q-T interval

Class IB = lidocaine accelerates repolarization (APD decreased)

Which drugs?

delay ventricular repolarization via block of K⁺ channels;

         APD, ERP and Q-T interval increase.  The prolongation of repolarization can cause

         torsades de pointes = polymorphic ventricular tachycardia

Amiodarone and sotalol

Which drug?

opens potassium channels in the AV node to hyperpolarize and stop all

                        AV conduction           

Which drugs?

pancreatic b-islet cells

close K⁺-channels causing the cell to depolarize; depolarization opens voltage-

         sensitive Ca⁺⁺ channels; Ca⁺⁺ flows in to activate PLC which increases IP₃ which

         release more Ca⁺⁺  from the SR; increased free intracellular Ca⁺⁺ causes insulin

         secretion

tolbutamide, chlorpropamide, glypizide, repaglinide

Which drug?

opens ATP-regulated K⁺-channels to prevent depolarization and thus

                        inhibit insulin secretion. Used to decreases insulin release from insulinomas

Diazoxide

Which drug?

GABA_B-receptors coupled to K⁺-channels in the CNS; agonist

enhances GABA-mediated K⁺ conductance to hyperpolarize presynaptic

Ia fiber terminals and thus reduce the release of the excitatory NT glutamate onto a-motor neurons. 

tx spasticity ass w cerebral palsy, multiple

                        sclerosis and stroke. 

Which drug?

         - in the spinal cord tizanidine stimulates presynaptica₂-adrenoceptors on Ia fiber

           terminals to prevent the release of glutamate onto a-motor neurons.  

           also hyperpolarizes a-motor neurons via stimulation of a₂-adrenoceptors.  These two actions decrease spasticity.

Which drugs?

GABA_A-receptors = hyperpolarization = inhibition

ethanol, propofol, volatile anesthetic agents, BZ’s (increased frequency of channel opening) and barbiturates (increased duration of channel opening)

Which drugs?

V₂-AVP receptors (renal collecting duct) = AVP (ADH) increases water reabsorption. This cyclase inhibited by PGE’s, atrial natriuretic factor, ______, ______. 

Antidiuretic effect of AVP potentiated by _____, _______.

lithium and demeclocycline

chlopropramide and carbamazepine

Which drugs?

- increases gene transcription for lipocortin (inhibits PLA2), IKB (the inhibitor of nuclear factor kappa-B (NFKB) and enzymes (E's) for gluconeogenesis

         ¯ transcription of genes for COX-2; IL-1 & IL-6 in monocytes & macrophages; 

            gene for NFKB, and E’s for glycogen storage (except glycogen synthetase)

glucocorticoids = cortisone, hydrocortisone, prednisone, prednisolone

Which drugs?

block the ATP binding site of the I_KK kinase.  This prevents the

         phosphorylation and subsequent dissociation of the inhibitory I_KB from NFKB: thisaction prevents the increased expression of the genes which code for many inflammatory mediators.

NSAID’s

Which type of drug?

increased hepatic protein synthesis = transcortin (CBG), thyroxine-

         binding globulin (TBG), angiotensinogen (renin substrate), transferrin, fibrinogenand clotting factors 2, 7, 9 and 10.

Which drug?

precipitate an anaphylactic-like reactions in patients with nasal polyps.  Blockade of PG synthesis by the

shunts all the arachidonic acid to leukotriene synthesis ®  LT's causerhinoconjunctivitis, angioedema and urticaria.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency = hemolytic anemia is produced by___, ____, ___, and ___.

primaquine, isoniazid, sulfonamides, nitrofurantoin

Hydralazine

Procainamide

What causes

Malignant hyperthermia (hyperpyrexia) = a gene defect prevents Ca⁺⁺ from being sequestered correctly in the sarcoplasmic reticulum (SR) of skeletal muscle.

      -  anesthesia with a volatile anesthetic agent (e.g., halothane) plus the administration

         of succinylcholine causes the massive release of Ca⁺⁺ = masseter muscle spasm

      -  S/S = ­ BP, HR, & muscle contraction w hyperthermia,  lactic acidosis and cardiac dysrhythmias

How do you treat it?

Causes- halothane and succinylcholine

Treatment- Dantrolene

What causes

Neuroleptic malignant syndrome - etiology NOT related to malignant hyperthermia

      = produced by rapid blockade of central DA receptors with the typical antipsychotic.

-  S/S = resembles severe Parkinson's dx w catatonia = EPS, stupor, hyperthermia,­ CPK, myoglobinuria,

What do you treat it with?

Cause- haloperidol

Treatment- Dantrolene + Bromocriptine (D2 agonist)

inducers of CYP450

phenobarbital, phenytoin, carbamazepine, nicotine

      and chronic EtOH consumption.

inhibitors of CYP450

erythromycin, cimetidine and ketoconazole.  Thetime is ripe for them to ask about grapefruit juice as an inhibitor of CYP450: the question will probably involve decreased clearance of a calcium channel blocker

Which drug?

diagnosis of myasthenia gravis (MG)

   - to differentiate between “myasthenic” and “cholinergic” crisis in patients tx w neostigmine

   - used w atropine in reversal of neuromuscular blockade (NMB) caused bynon-depolarizing drugs (d-tc, pancuronium)

edophonium

Which drug?

- tx of MG (always used w atropine to prevent indirect muscarinic S/E’s)

   - used w glycopyrrolate in reversal of NMB caused by non-depolarizing drugs.

Symptoms of organophosphate (malathion, parathion, isofluophate (DFP)) poisoning:

How do you treat it?

bradycardia, lacrimation, salivation, diaphoresis, miosis, blurred vision, dyspnea, pulmonary edema, bowel cramping, involuntary urination, skeletal muscle fasciculations (N₂)

Treatment:

atropine and pralidoxime (2-PAM) (regenerates phosphorylated

   AChase)Carboxylesterases in humans degrade organophosphates and prevent our death.

Scopolamine, dimenhydrinate, meclizine

trihexyphenidyl, benztropine, diphenhydramine

solifenacin, tolterodine

Which drug:

nauseas and vomiting, poison ivy and oak

DOC for fundoscopic exam

tropicamide

DOC for determination of refractive error

Cyclopentolate

DOCs for tx of pain in anterior uveitis, keratitis and choroiditid

atropine and scopolamine

Which drug?

1) non-competitive blockade of NE, Epi, DA, 5-HT uptake₁ in the CNS

2) blocks uptake₁ in peripheral sympathetic neurons - potentiates effects of NE and Epi, but not isoproterenol (ISO)

3) Euphoria via release of DA in nucleus accumbens

4) local anesthetic effect via blockade of Na⁺ channels in sensory neurons

5) toxic doses/OD = dilated pupils, euphoria, hallucinations, excitation, halo vision, itchy skin, ­ BP/HR, convulsions - difficult to distinguish from amphetamin toxicity/OD

6) withdrawal syndrome = sleepiness, depression, anhedonia

cocaine

MAO inhibitors

phenelzine, tranylcypromine

selegiline – selectively inhibits MAO-B to prevent breakdown of DA in CNS

Which drugs?

1)  MOA:  negative chronotropic & inotropic effects decreases the rate-pressure product

     (HR x SBP);  also decrease cardiac afterload (= decreased DBP)

2)  net effect is decreased cardiac oxygen demand

3)  prolongation of diastole improves diastolic perfusion of the endocardium

b-blockers = atenolol, metoprolol, propranolol, timolol

Which drugs?

1)  MOA: NO donors which selectively venodilate; venodilation ¯ venous return to

     decrease LV wall tension during diastole and systole

2)  net effect: decreased cardiac oxygen demand

3)  decreased wall tension during diastole improves diastolic perfusion of the

     endocardium

4)  have to give NTG sublinguallly to prevent high first-pass metabolism

5)  drug tolerance is a big problem

6)  S/E = headache

nitrates = nitroglycerin (NTG)  a.k.a. glyceryl trinitrate, isosorbide mono- and dinitrate

Which worm drugs?

ganglionic nicotinic cholinergic agonists = muscular tetany

pyrantel pamoate             

levamisole

Which worm drug?

binding toglutamate-gated Cl^- channels (found only ininvertebrates  such as helminths, insects and ectoparasites)increases Cl^- conductance:  hyperpolarization causestonic paralysis of musculature

ivermectin

DOC for

Trematodes (flukes) = Schistosoma

patient passes tape worm segments (proglottids) - most likely Taenia saginata (beef

     tapeworm) or a patient who likes to eat sushi passes tapeworm segments - most likely to be Diphyllobothrium latum (fish tapeworm) - treat with?

niclosamide or

     praziquantel

     Fish tapeworm causes megaloblastic anemia because the worm takes up all the

     vitamin B₁₂ in the gut

     Always worry that patient may have Taenia solium, pork tapeworm, which may

produce cysticercosis (larval cysts) in the brain, orbit, muscles, liver and lungs.

Tx cysticercosis w albendazole

Praziquantel is DOC if identity of the type of tapeworm is uncertain

   Baby w anal itching (pruritis) and a postive “cellophane tape” test = pinworm

                        infestation - tx w___ or ____

mebendazole

or pyrantel pamoate

Pt w mixed infestation = cestode (tapeworm) + trematode (fluke. Tx w ___

praziquantel

Which drug?

DOC for Giardia, Trichomonas and C. dificile infections

1.  active against anaerobic protozoa and bacteria

2.  MOA: bacterial and protozoal ferrodoxins reduce metronidazole to an active

     nitroderivative that inhibits DNA replication and causes mutations

3.  Tx of protozoa Giardia lamblia (beaver fever, campers fever), Trichomonas

     vaginalis (trichomoniasis), Entamoeba histolytica (amebiasis).

4.  Tx of obligate anerobic bacteria Bacteroides spp  and Clostridium dificile (pseudomembraneous colitis)

5.  S/E = inhibits aldehyde dehydrogenase to cause a disulfiram-like reaction w EtOH

     ingestion = headache, n/v, flushing: teratogenic       

DOC for tx of PCP (Pneumocystis jiroveci

                        pneumonia) in patients w AIDS.
Positive silver stain. ____

2nd drug for PCP____

Trim sulfa

Pentamide

Which drug?

does not cross the blood-brain barrier

1.  MOA: binds to ergosterol in fungal membranes to form pores which increases the

     permeability of the fungal membrane, cells lose ions and macromolecules; enhances

    penetration of other antifungal drugs such as flucytosine

2.  Resistance from decreased membrane ergosterol or altered structure of ergosterol

3.  The old DOC for Coccidioides immitis and Aspergillus infections

4.  Also effective against Candida.

5.  clinical usefulness is limited by its nephrotoxicity (plasma creatinine rises)

   - histological damage to renal tubules w cell necrosis

   - renal tubular acidosis (a defect of renal function that produces systemic acidosis

     because  bicarbonate ion cannot be reabsorbed in the PT or DT).

   - hyperchloremic metabolic acidosis

6.  renal toxicity can be avoided by giving mannitol to induce a high rate of urinary flow

DOC for Aspergillis

DOC for Coccidioides immitis

fluconazole - crosses blood-brain barrier

DOC for cryptococcal meningitis in AIDS patient

= fluconazole (the -conazoles cross the

   blood-brain barrier)

Which drug?

MOA: inhibits fungal CYP450 which prevents the demethylation of lanosterol to ergosterol, so blocks cell wall synthesis

Ketoconazole

why is ketoconazole contraindicated in a patient receiving tx w amphotericin B?

because ketoconazole will PREVENT the antifungal MOA of amphotericin B

Which drug is selectively toxic to fungi because mammalian cells are unable to catalyze its deamination?

flucytosine

patient w gonorrhea - tx w penicillin for 8 weeks - patient returns with similar

     symptoms but no diplococci in urine (no longer has gonorrhea) - patient has Chlamydia infection

- tx w doxycycline unless patient is a PG female, then tx w azithromycin

patient has Streptococcus infection and is allergic to PCNs

tx w erythromycin or

     another macrolide (azithromycin, clarithromycin)

Patient w AIDS develops infection w Pneumocystis carinii

tx patient with clindamycin - patient develops pseudomembranous colitis –

                        caused by Clostridium dificile

- tx w oral metronidazole (or oral vancomycin)

Bacteriostatic Drugs

macrolides = erythromycin

clindamycin

tetratcyclines = doxycycline

chloramphenicol

spectinomycin

Protein synthesis inhibitors = buy AT 30, CELL at 50

A= aminoglycosides (cidal) + spectinomycin (static) – use for penicillin-resistant

T = tetracyclines (static)                                                gonorrhea                                                                    

C = chloramphenicol (static)

E = erythromyicn (static)

L = Lincomycin (static)

L = cLindamycin (static)

DOC for partial seizures

ethosuximide

DOC for tonic-clonic seizures

Phenytoin

diazepam i.v. is DOC, if ineffective, tx w fosphenytoin i.v

schizophrenic patient w depression

tx w SSRI like fluoxetine

depressed pat w hypotension

SSRI like fluoxetine

Depressed patient being tx w antidepressant suffers from sedation and hypotension

  could be MAOI or TCA since both cause sleepiness and hypotension, but pick TCA bx

     TCA’s cause greater orthostatic hypotension than do MAOI’s

small child w nocturnal enuresis -

tx w TCA for atropine-like effect in urinary bladder

Which NT involved in OCD?

= 5-HT; tx for OCD = clomipramine or SSRI (e.g.,

     fluoxetine)

depresssed patient w CHF tx w digoxin is given TCA

  = inverts or flattens T-wave,

     slows conduction in fast fibers so QRS widens

OD with imipramine

¯ BP from alpha-blockade; ­ HR from ¯ BP and anticholinergic effects +

     direct cardiac toxicity = AV block ­ Q-T interval, QRS widens = failure of cardiac conduction

serotonin syndrome

= results from excessive stimulation of central 5-HT receptors = ­ BP, HR

    and respiration; increased muscle activity (muscle twitching, shivering, myoclonus) causing

             hyperthermia and sweating; pupillary dilation; confusion, agitation, hallucinations

  MAOI + TCA

= hyperpyrexia, convulsions, coma, death

patient being treated for Giardia + some other infection (e.g., bacterial)      

    develops n/v and headache after drinking wine. Which drug causes this rx? =

metronidazole.

: tx of female w acute pain from gallstones w morphine causes greater pain. Why?

Morphine contracts smooth muscle of gall bladder

female on methadone has emergent surgery and is tx w butorphanol; patient

              experiences S/S of opiate withdrawal.  Why? 

Butorphanol is a partial agonist at mu

     receptors.  The partial agonists pentazocine, nalbuphine and buprenorphine can also cause

              S/S of opiate withdrawal in a patient taking methadone.

which opiate does not cause a dose-related inhibition of respiration

= the partial

              agonists pentazocine, butorphanol and nalbuphine

newborn baby has respiratory depression bx mom received

an opiate during

     labor

patient with MI tx with morphine, why? 

Chest & arm pain ­ the activity of the

     sympathetic nervous system which constricts arterioles and venules to increase preload and

     afterload.  The damaged heart cannot pump the increased venous return, especially in the

     face of an increase in afterload.  Morphine acts centrally to decrease pain and to decrease

     sympathetic outflow.  Decreased activity of the SNS decreases preload and afterload and

     improves CO.  the analgesic effects of morphine also make the patient more comfortable.