By R. Boss. Massachusetts College of Pharmacy and Health Sciences.

Drug that decreases effects of methotrexate: (1) Leucovorin (citrovorum factor buy kamagra effervescent 100mg without a prescription best erectile dysfunction pump, folinic acid) Leucovorin antagonizes the toxic effects of methotrexate and is used as an antidote for high-dose methotrexate regimens or for overdose order kamagra effervescent 100mg mastercard erectile dysfunction quad mix. It must be given exactly at the specified time, before affected cells become too damaged to respond. Drugs that increase effects of vinca alkaloids: (1) Erythromycin increases vinblastine toxicity; itracona- These drugs probably inhibit metabolism of vinblastine and vin- zole increases vincristine toxicity cristine. What is the basis for the anticancer effects of hormones and antihormones? For which cytotoxic drugs are cytoprotective drugs avail- duced in the bone marrow. List at least one intervention to prevent or minimize each bone marrow depression is given. When red blood cells decrease, as ev- idenced by a hemoglobin of less than 9 g/dL, the patient will ex- perience anemia and fatigue. Principles of chemotherapy handwashing, avoiding contact with infected individuals), espe- and hormonal therapy. The importance of keeping appointments for monitoring Drug facts and comparisons. Louis: Facts and should be stressed so that blood products can be given if values Comparisons. New agents in gastrointestinal malignancies: diotoxicity, hepatotoxicity, nephrotoxicity, neurotoxicity)? Teach clients, family members, or caretakers influence drug therapy of eye disorders. Use correct techniques to administer ophthalmic scribed to protect and preserve eyesight. Assess for ocular effects of systemic drugs and systemic effects of ophthalmic drugs. Critical Thinking Scenario Jean Green, a 40-year-old accountant, has made an appointment to have her eyes examined because she has been having difficulty reading small print. When she arrives at the office, you explain that the examination will include using medications to dilate her eyes and a test for glaucoma. Which drugs are used to dilate the eyes for examination, and how they work. When the conjunctiva is irritated or certain emotions are experienced (eg, sadness), the The eye is the major sensory organ through which the per- lacrimal gland produces more fluid than the drainage son receives information about the external environment. The excess fluid overflows Extensive discussion of vision and ocular anatomy is beyond the eyelids and becomes tears. The sclera is a white, opaque, fibrous tis- • The eyelids and lacrimal system function to protect the sue that covers the posterior five sixths of the eyeball. The eyelid is a covering that acts as a barrier to the The cornea is a transparent, special connective tissue entry of foreign bodies, strong light, dust, and other po- that covers the anterior sixth of the eyeball. The canthi (singular, canthus) are blood vessels and connective tissue, continues forward the angles where the upper and lower eyelids meet. The iris is composed of pigmented The lacrimal system produces a fluid that constantly cells, the opening called the pupil, and muscles that moistens and cleanses the anterior surface of the eye- control the size of the pupil by contracting or dilating ball. The fluid drains through two small openings in the in response to stimuli. The retina is the innermost inner canthus and flows through the nasolacrimal duct layer of the eyeball. The most common type of glaucoma is called primary Light rays do not travel directly to the retina. Its etiology is unknown, but contribut- they are deflected in various directions according to the ing factors may include advanced age, a family history of density of the ocular structures through which they pass. In addition, the inci- is the area of the retina where ophthalmic blood vessels dence of glaucoma in African Americans is about three times and the optic nerve enter the eyeball. Closed-angle glau- • The structure and function of the eyeball are further in- coma is usually an acute situation requiring emergency fluenced by the lens, aqueous humor, and vitreous body. It may occur when pupils are dilated and the outflow The lens is an elastic, transparent structure; its function of aqueous humor is blocked. Darkness and drugs with anti- is to focus light rays to form images on the retina.

Hilton-Brown & Stalberg cheap kamagra effervescent 100 mg with visa erectile dysfunction gene therapy,˚ 1986;Semmler & Turker kamagra effervescent 100 mg with visa doctor for erectile dysfunction philippines,¨ 1994) and in abductor digiti minimi (Mazzocchio, Heteronymous monosynaptic Ia Rothwell & Rossi, 1995), the largest responses to Ia excitation in the lower limb input have not been found in low-threshold units. Pattern and strength of distribution Inhibitory mechanisms limiting the efficacy of the monosynaptic Ia input In striking contrast with data for the cat and baboon hindlimb (see pp. The constraints raised above, the conclusions advanced larger the maximal soleus H reflex at rest, the smaller below have generally been confirmed using more the tonic on-going presynaptic inhibition of Ia ter- than one method. Grey cells represent Contamination by oligosynaptic IPSPs muscle–nerve combinations with a statistically sig- nificantconnectioninhumans. This limitation could also based on the average size of the heteronymous peak contribute to the absence of a recordable H reflex relative to that of the homonymous peak, both in at rest in muscles, such as tibialis anterior, abduc- response to stimulation at 1 × MT. As expected, the tor pollicis brevis and ECR, though this would imply stronger the connection, the more frequently was it that the Ia/Ib balance was then shifted in favour of observed: e. In these muscles, the appearance of an trocnemius medialis to biceps femoris, five aster- Hreflex during a tonic voluntary contraction could isks) was observed in 21/21 (100%) units and was, involve depression of non-reciprocal group I inhibi- on average, 54% of the homonymous peak, whereas tion to the active motoneurone pool (see Chapter 6, the weakest connection (from the intrinsic plantar pp. Thresholds for α motor axons and Ia afferents Connections between close synergists operating Alternatively, if the threshold for motor axons was at the same joint closer to that of Ia afferents, the maximal H reflex would probably be smaller and the reflex more diffi- At knee level, strong connections exist between the cult to obtain and, with single motor units, the peak two heads of the quadriceps (vastus lateralis and 82 Monosynaptic Ia excitation Table 2. Monosynaptic heteronymous Ia excitation in the lower limb Columns: nerve stimulated: Sol (inferior soleus), GM (nerve to the gastrocnemius medialis), SP (superficial pero- neal), DP (deep peroneal), FN (femoral nerve), TN (tibial nerve at the ankle). Lines: motoneurone pools (MN) investigated with the PSTH method: Sol (soleus), GM (gastrocnemius medialis), Per Brev (peroneus brevis), TA (tibialis anterior), Q (quadriceps), Bi (biceps femoris), ST (semitendinosus). Grey cells indicate the existence of significantIaexcitationinhumans(crossedcellscorrespondtohomonymouspathways). Thenumberofasterisks indicates the average size of the heteronymous peak relative to the homonymous peak (both recorded using sti- mulationat1×MT):*<10%;**between10and20%;***between20and30%,****between30and40%;*****>40% (from Meunier, Pierrot-Deseilligny & Simonetta, 1993;Marque et al. Connections are compared to those described in the cat (cells with horizontal lines, Eccles, Eccles & Lundberg, 1957)andthebaboon(cellswithverticallines,Hongoetal. Withtheanimalexperiments,onlyconnections with a heteronymous EPSP >5% of the homonymous EPSP are shown. There is no Ia excitation from gastrocnemius medialis to soleus, There are bidirectional connections between soleus a finding confirmed using different techniques: the andperoneusbrevis(Fig. Organisation and pattern of connections 83 Transjoint connections exist between all Phylogenetic adaptations muscle–nerve combinations tested In Table 2. However, it should be emphasised that cat(cellswithhorizontallines,Eccles,Eccles&Lund- conclusions based on stimuli at 1 × MT underesti- berg, 1957) and the baboon (cells with vertical lines, matethestrengthoftheconnectionsbecause,asdis- Hongo et al. These connections are not confined to Connections between close synergists units in the low-threshold range investigated with Theabsenceofconnectionsbetweensomeclosesyn- the PSTH method. Many of the connections have ergists operating at the same joint in humans is pre- alsobeenobservedwithmethodsthatexplorealarge dictable because of their weakness in the baboon. Proximal-to- distal transjoint connections can be explored safely Themoststrikingdifferencesinvolvethepresenceof only from the femoral nerve, because it does not heteronymous connections that do not exist in the contain afferents from distal muscles. Because of cat or the baboon or, when they exist, are <5% of the the difficulty in stimulating the nerves to hamstrings homonymous Ia EPSP (e. Ia connections from tri- without encroaching upon afferents from foot and ceps surae onto quadriceps motoneurones, Edgley, leg muscles in the sciatic nerve (or of stimulating Jankowska&McCrea,1986;Hongoetal. Thus, the posterior tibial nerve without encroaching upon in human subjects, there are transjoint connections afferents from plantar foot muscles), it has not been between all muscle–nerve combinations tested. The possibletodeterminewhethertheconnectionsfrom functionalimplicationsofthesedifferencesinorgan- legmusclestohamstrings(andfromfoottoproximal isation of Ia connections are considered on pp. Projections to antagonists acting at another joint Aremarkable feature of these transjoint connections Heteronymous monosynaptic isthattheyoftenlinkamuscleorgroupofmusclesto Ia excitation in the upper limb a pair of antagonistic muscles operating at another joint, e. There is bidirectional, 84 Monosynaptic Ia excitation though asymmetrical, heteronymous Ia excitation Table 2. Electri- excitation in the upper limb cal stimuli at 1 × MT applied to the median nerve at elbow level often evoke monosynaptic Ia excitation ofFCUunits,whereassimilarstimulationoftheulnar nerve rarely evokes significant excitation of FCR units (Malmgren & Pierrot-Deseilligny, 1988). An asymmetry has also been demonstrated using per- cussion of the tendons of FCR and FCU (Chalmers & Bawa, 1997), but this was less marked, possibly due to spread of the mechanical stimulus. Weak ECU facilitation by ED Ia afferents has been observed consistently but, in contrast with forearm flexors, there is no evidence for heteronymous Ia excitation at a latency consistent with a monosynaptic linkage between ECR and ECU (Chalmers & Bawa, 1997).

Fixed-dose combination tablets (eg buy kamagra effervescent 100mg online erectile dysfunction and high blood pressure, Rifamate and with MDR-TB or suspected of having MDR-TB should Rifater) are recommended by some authorities order 100mg kamagra effervescent visa erectile dysfunction essential oils, because be designed in consultation with infectious disease they help to prevent the emergence of drug-resistant or- specialists. Treatment of MDR-TB requires concurrent adminis- of usual activities of daily living. Short-course regi- tration of more drugs (eg, 4 to 6), for a longer period mens, intermittent dosing (eg, 2 or 3 times weekly of time (eg, 2 years or longer), than for drug-susceptible rather than daily), and fixed-dose combinations of tuberculosis. The specific regimen is derived from cul- drugs (eg, Rifater or Rifamate) reduce the number of tures of infecting strains and susceptibility tests with pri- pills and the duration of therapy. It should include 2 or 3 drugs to which the With clients for whom English is not their primary isolate is sensitive and that the client has not taken language, it is desirable to have a health care worker before. The fluoroquinolones are not recommended for who speaks their language or who belongs to their eth- use in children. All drug therapy for suspected or known MDR-TB tively teach clients and others, elicit cooperation with should involve daily administration and DOT. HIV population, and costs many thousand dollars more than the treatment of drug-susceptible TB. Monitoring Antitubercular Drug Therapy Increasing Adherence to Antituberculosis There are two main methods of monitoring client responses Drug Therapy to treatment, clinical and laboratory. The current trend seems to be increasing clinical monitoring and decreasing laboratory Failure to complete treatment regimens is a major problem in monitoring. Identifying drug therapy and obtaining medical care (eg, hepato- and treating LTBI requires several steps, including adminis- toxicity). It also includes regular assessment by a tering and reading skin tests, obtaining medical evaluations health care provider. Clinical monitoring should be of infected persons, and initiating, monitoring, and complet- repeated at each monthly visit. Nonadherence is common in all of these as- sessed for signs of liver disease (eg, loss of appetite, pects. Numerous strategies have been proposed to increase nausea, vomiting, dark urine, jaundice, numbness or adherence, including: tingling of the hands and feet, fatigue, abdominal ten- 1. This may be es- derness, easy bruising or bleeding) at least monthly if pecially important with treatment of LTBI. Most peo- receiving INH alone or rifampin alone and at 2, 4, and ple are more motivated to take medications and schedule 8 weeks if receiving rifampin and pyrazinamide. In follow-up care when they have symptoms than when addition to detecting adverse effects, these ongoing they feel well and have no symptoms. The importance contacts are opportunities to reinforce teaching, as- of treatment for the future health of the individual, sess adherence with therapy since the last visit, and significant others, and the community must be em- observe for drug interactions. In addition, clients should be informed view form may be helpful in eliciting appropriate about common and potential adverse effects of drug information. Monitoring during therapy is indi- with inconvenient hours, long waiting times, and un- cated for patients who have abnormal baseline values supportive staff) may deter clients from being evalu- or other risk factors for liver disease and those who ated for a positive skin test, initiating treatment, or develop symptoms of liver damage. Some clinicians completing the prescribed treatment and follow-up recommend that INH be stopped for transaminase care. Individualizing treatment regimens, when possible, ciated with symptoms and five times the upper limit to increase client convenience and minimize disruption of normal if the patient is asymptomatic. CHAPTER 38 DRUGS FOR TUBERCULOSIS AND MYCOBACTERIUM AVIUM COMPLEX (MAC) DISEASE 571 Effects of Antitubercular are HIV-seronegative clients. The regimen may be longer if Drugs on Other Drugs the bacteriologic (eg, negative cultures) or clinical response (eg, improvement in symptoms) is slow or inadequate. Isoniazid (INH) increases risks of toxicity with several drugs, A major difficulty with treatment of TB in clients with apparently by inhibiting their metabolism and increasing HIV infection is that rifampin interacts with many protease their blood levels. These include acetaminophen, carba- inhibitors (PIs) and nonnucleoside reverse transcriptase in- mazepine, haloperidol, ketoconazole, phenytoin (effects of hibitors (NNRTIs). If the drugs are given concurrently, ri- fampin decreases blood levels and therapeutic effects of the rifampin are opposite to those of INH and tend to predomi- anti-HIV drugs. Rifabutin has fewer interactions and may be nate if both drugs are given with phenytoin), and vincristine. The PIs indinavir and nelfinavir and INH increases the risk of hepatotoxicity with most of these most of the NNRTIs can be used with rifabutin. Ritonavir drugs; concurrent use should be avoided when possible or (PI) and delavirdine (NNRTI) should not be used with ri- blood levels of the inhibited drug should be monitored.

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