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PHARM250 the Immune system Cheat Sheet by

Overview of the immune system drugs and there adverse side effects.

Fever - classes of medication

Acetam­inophen
Mech­anism of action: acts at hypoth­alamus to cause peripheral vasodi­lation, which enables sweating and allows body to rid excess heat
No anti-i­nfl­amm­atory action
Primary use: fever, mild to moderate pain, osteoa­rth­ritis
NSAID's
Same mechanism of action as acetam­inophen (for fever)
Because of acetam­ino­phen’s safety record (few drug intera­ctions and side effects), it is first-line for fever
NSAID could be more approp­riate if inflam­mation is also present (ibuprofen > ASA)
ASA is contra­ind­icated in children  Reye’s Syndrome (ASA + virus + fever in child)

Adverse effects

NSAID
nausea, dyspepsia, ulcer with long-term use, potential anti-p­latelet action, hypert­ension, increased risk of cardiac event with long-term use
Take with food
Caution in kidney disease, cardio­vas­cular disease, GI conditions
Cortic­ost­eroids
Acetom­inophen
very rare liver toxicity (max dose of 4g/24h­ours), avoid alcohol, interacts with warfarin
(but doesn’t ↑ bleeding on its own)
1st-Ge­ner­ation Antihi­sta­mines
Signif­icant sedation
2nd-Ge­ner­ation Antihi­sta­mines
Intranasal Cortic­ost­eroids
nasal irrita­tion, dryness and bleeding (epist­axis), bad taste, loss of smell
Decongestants
Phenylephrine, pseudo­eph­edrine
oral – hypert­ension, anxiety, insomnia;
intranasal – nasal irrita­tion, rebound conges­tion, rarely systemic effects
Penicillin
anaphy­laxis, diarrhea, nausea, vomiting, pain at injection site, superi­nfe­ctions, some (minor) drug intera­ctions
Cephal­osp­orins
Cefotaxime (3rd Gen.)
hypers­ens­iti­vity, rash, itching, anaphy­laxis, diarrhea, vomiting, nausea, pain at injection site, some (minor) drug interactions
Must be given IV or IM (not orally)
Tetrac­yclines
diarrhea, yeast infect­ions, nausea, vomiting, epi-ga­stric burning, yellow­-brown teeth discol­our­ation in young children (we don’t prescribe for kids), photos­ens­itivity
Can potent­ially interfere with oral contra­cep­tives (recommend backup method)
Higher chance of superi­nfe­ctions because it is broad-­spe­ctrum
Macrolides
Erythromycin
: signif­icant nausea, vomiting, diarrhea (take with food), some important drug intera­ctions
Warfarin, cyclos­porine, antico­nvu­lsants (all via CYP450 inhibition/induction)
Fidaxo­micin – new; for treatment of c. difficile; not absorbed, stays in GI tract nausea, consti­pation, vomiting
Aminoglycosides
Gentamicin
ototox­icity, nephro­tox­icity
Fluoro­qui­nolones
Cipro­flo­xacin
nausea, diarrhea (can take with food), photos­ens­itivity
Separate from minerals like calcium, iron, magnesium, aluminum (including supple­ments and antacids) by 2h
Serious adverse effects associated with fluoro­qui­nol­ones: Tendinitis or tendon rupture (1.3-5.6 in 10,000)
Cardiac arrhyt­hmias (15-57 in 100,000)
CNS effects  seizures, tremors, altered mental state
Peripheral neuropathy
Sulfon­amides
Sulfamethoxazole-Trimethoprim (SMZ-TMP, Septra®, Bactrim®, -DS)
nausea, vomiting, skin rashes, photos­ens­iti­vity, anemia, crystalluria
Drink lots of water to prevent crystalluria
Monitor for: painful urination, abdominal pain, blood in urine, fever
Carbap­enems
ertapenem, imipenem, meropenem
skin reactions, inflam­mation at injection site, diarrhea, nausea, vomiting
Clinda­mycin
High risk of superi­nfe­ction (GI)
Nitrof­ura­ntoin
Changes urine to orange colour
Must take with food
Metron­idazole
Disulfiram reaction – flushing, tachyc­ardia, shortness of breath, severe nausea & vomiting, throbbing headache, visual distur­bance, confusion, dizziness
Occurs ~ 5-10 minutes after intake, lasts 30 mins  several hours
Vancomycin
Ototox­icity and nephro­tox­icity
Linezolid
lactic acidosis, myelos­upp­ression (↓WBC and platel­ets), peripheral and optic neurop­athy, serotonin syndrome, diarrhea,
Major drug intera­ction with any seroto­nergic drug, may need to discon­tinue until course of treatment finished, also inhibits MAO
Rifampin (RMP)
Rashes, blood dyscra­sias, GI distur­bances, liver damage, nephro­tox­icity
Secretions coloured a reddis­h-o­range (sweat, urine, sputum, tears)
Amphot­ericin B
fever & chills during infusion, vomiting, headache, phlebitis, nephro­tox­icity, hypoka­lemia, ototox­icity
Azole Antifungals
fluconazole, itraco­nazole, ketoco­nazole, micona­zole, vorico­nazole
Rare hepato­tox­icity – avoid alcohol, watch for jaundice, monitor liver enzymes
Nystatin
Oral thrush – swish and swallow oral suspension four times daily (works topically) (needs Rx)
Classic Immuno­-su­ppr­essant
Increased risk of infect­ions, Increased risk of cancers such as lymphomas, cysts, and polyps
Frequency increases with intensity and duration of treatment, Kidney impair­ment, hepatic impair­ment, Hypert­ension, hyperlipidemia,
CNS: tremor, headache, skin prickling sensation,
GI: nausea, vomiting, abdominal pain, diarrhea, gingival hyperplasia,
MSK: Muscle cramps, myalgia
Endocrine: Menstrual distur­bances, gyneco­mastia, Hypert­ric­hosis (abnormal amount of hair growth over body), Fatigue
Chemot­herapy
short term
Nausea­/vo­miting, Diarrhea or consti­pation, Mucosi­tis­/st­oma­titis, Myelos­upp­res­sion, Hair growth altera­tions, Weight gain / weight loss, Taste altera­tions, Fatigue, Hepatic and renal changes, Cardiac function changes, Rash / skin changes / nail changes, High blood pressure
Long term
Infertility, Secondary malign­ancies, Heart failure, Osteop­orosis, Pulmonary fibrosis, Cataracts, Peripheral neurop­athy, Hearing loss, Fatigue, Endocrine abnorm­alities
 

Inflam­mation mediators

Histamines
Bradykinin
Leukot­rienes
Cytokines
Interl­eukins
Prosta­glandin

Inflam­mation classes of medication

Non-­ste­roidal anti-i­nfl­amm­ato­ries
NSA­ID
Inhibit cyclo-­oxy­genase (COX), which reduces prosta­glandin synthesis therefore inhibiting inflam­mation
Also have analgesic and antipy­retic properties
For mild to moderate inflam­mation
COX-1
– In all tissues, stomach lining (mucosa), involved in platelet aggreg­ation
COX-2
more specific for inflam­mation
Ibupr­ofen
mild to moderate inflam­mation, fever, mild to moderate pain, dysmen­orrhea, muscul­osk­eletal pain, arthritis
Corticosteroids
Mimic endogenous cortisol, attempting to bring body back to homeos­tasis after a fight-­or-­flight response
Anti-i­nfl­amm­atory and immuno-suppressive
For severe inflammation
Serious systemic adverse effects limit use to emerge­ncies and severe inflam­mation (multiple sclerosis, rheumatoid arthritis, auto-i­mmune diseases)
Local admini­str­ation, short-term use preferred whenever possible

Antibi­otics - Classes of medication

Peni­cil­lins
-cillin
Disrupt bacterial cell walls, Bactericidal
Penici­lli­n-b­inding protein: a protein only in bacterial cell walls that penicillin binds to which weakens the cell wall, allows fluid to enter and destroys the cell
Penici­llins contain a beta-l­actam ring in its structure necessary for activity
Many bacteria produce beta-l­act­amase (penic­ill­inase) that is a natural defense to penicillin – it breaks the beta-l­actam ring, leaving it ineffe­ctive therefore penicillin resistance
Amoxi­cillin + Clavulanic Acid (Amoxi­clav)
Clavulanic acid inhibits β–lact­amases (penic­ill­inases) of some microo­rga­nisms to allow amoxic­illin to be active against it
Synerg­istic relati­onship
Penic­illin G Potassium (Pen G)
Drug of choice against strept­ococci, pneumo­cocci, staphy­loc­occi, gonorrhea and syphilis (given IV or IM)
Ceph­alo­spo­rins
-ce(f)ph
Related to penici­llins (1st gen. also have beta-l­actam ring)
Also inhibit cell wall synthesis, Bactericidal
Classified according to “gener­ation” (1 - 4)
General Rules
1st generation not effective against bacteria producing beta-l­act­amase
More potent as go up in generation
Fewer simila­rities with penici­llins as go up in generation
Higher genera­tions reserved for known resistant infections
Cefot­axime (3rd Gen.)
Has broad-­spe­ctrum activity against gram-n­egative organisms; for serious infections of lower respir­atory tract, CNS, genito­urinary system, bones, blood, and joints
Tetr­acy­cli­nes
doxyc­ycline, minocy­cline, tetrac­ycline
-cycline
Inhibit bacterial protein synthesis, Bacteriostatic
Broad-­spe­ctrum (both gram-p­ositive and negative)
Usually given orally (PO)
Should not be given at the same time as iron, calcium, magnesium (ions bind to drug so it can’t absorb) – separate by 2h
Tetra­cyc­line
Used for Rocky Mountain spotted fever, h.pylori infect­ions, acne vulgaris, chlamydia
Macr­oli­des
azith­rom­ycin, clarit­hro­mycin, erythr­omycin, fidaxo­micin
-thro­mycin
Inhibit bacterial protein synthesis, Some are bacter­icidal, some bacteriostatic
No structural simila­rities to penicillin – zero chance of cross-­rea­ctivity
Eryth­rom­ycin
Used for upper and lower respir­atory tract infect­ions, whooping cough, diphth­eria, or for other infections in patients who cannot take penici­llins
Amin­ogl­yco­sides
amikacin, gentim­icin, strept­omycin, tobram­ycin
-mycin OR -micin
Inhibit bacterial protein synthesis and cause abnormal protein synthesis, Dose-d­epe­ndent bactericidal
Very effective, usually reserved for serious infections (like tuberc­ulosis) or when other antibi­otics have failed
Require therap­eutic drug monitoring – levels must be in specific range to be effective, but not toxic
Injection or topical
Genta­micin
Used for serious (life-­thr­eat­ening) infections or when other antibi­otics have failed (also topically as eye drops and creams­/oi­ntments – this would not require therap­eutic drug monito­ring)
Fluo­roq­uin­olo­nes
besif­lox­acin, ciprof­lox­acin, gatifl­oxocin, levofl­oxacin, moxifl­oxacin, norflo­xacin, ofloxacin
-flox­acin
Affect bacterial DNA synthesis, Bacter­icidal Most often used orally (also ear, eye)
Absorption is affected by minerals (calcium, iron, magnesium) and need to be separated (~2h)
Generally not used in children – affects cartilage develo­pment
Cipro­flo­xacin
Used commonly for respir­atory, urinary, ophtha­lmic, gastro­int­est­inal, and gyneco­logical infections – high usage in commun­ity­/ou­t-p­atient
Sulf­ona­mides
sulfa­cet­amide, sulfam­eth­oxa­zole, sulfap­yri­dine
Sulfa-
Suppress bacterial growth by inhibiting essential folic acid needed within the cell, Bacter­ios­tatic
Broad spectrum, older class  more resistance seen
Orally and topically (acne)
“Sulfa” is also a common “allergy”
Sulfa­met­hox­azo­le-­Tri­met­hoprim (SMZ-TMP, Septra®, Bactrim®, -DS)
Both drugs inhibit essential folic acid synthesis; work synerg­ist­ically (a pharma­cod­ynamic interaction)
Used to treat urinary tract infections
Carb­ape­nems
ertap­enem, imipenem, meropenem
-penem
Relatively new-ish
Contain beta-l­actam ring and inhibit cell wall synthesis (like penicillins)
The beta-l­actam ring is very resistant to destru­ction by penicillinase
Broad spectrum – and very effective; as a newer class, they are being reserved for resistant infections (like MRSA, etc.)
Miscel­laneous VIPs
Clind­amycin
protein synthesis inhibitor; bacter­ios­tatic
Used topically (acne), oral or IV for serious systemic infections
High risk of superi­nfe­ction (GI)
Nitro­fur­antoin
inhibits protein, RNA, DNA, and cell wall synthesis; bacter­icidal
Excreted unchanged through the kidney (no metabo­lism), therefore used only for urinary tract infections
Changes urine to orange colour
Must take with food
Metro­nid­azole
destroys bacterial DNA; bacter­icidal
For anaerobic bacteria
NO ALCOHOL USE (even small amounts present in cough syrup or mouthwash)
Vanco­mycin
inhibits cell wall synthesis; bacter­icidal (through different mechanism than aminoglycosides)
Reserved for severe infections that are resistant to anything else  usually only used in hospital (methi­cil­lin­-re­sistant staph. aureus - MRSA)
Injection or oral
If IV given too quickly  Red Man Syndrome (flushing, red face, hypote­nsion)  slow down infusion
Therap­eutic drug monitoring required (like aminog­lyc­osides)
Linez­olid
inhibits bacterial protein synthesis
Use to treat vancom­yci­n-r­esi­stant entero­coccus (VRE), pneumonia or skin infections caused by MRSA
i.e. Severe infections resistant to other antibi­otics
 

Allergies- Classes of Medication

Anti­his­tam­ines
1st-Ge­ner­ation Antihi­sta­mines
Block H1 receptors
Shorter acting, cause more drowsi­ness, and work faster than 2nd Generation
Used mostly to treat allergic response
Diphe­nhy­dra­mine and chlor­phe­nir­amine most common
Have antich­oli­nergic effects
Signif­icant sedation – some use as a sleep aid
2nd-Ge­ner­ation Antihi­sta­mines
Cetirizine (React­ine®), loratidine (Clari­tin®), deslor­atidine (Aerius®), fexofe­nadine (Alleg­ra®)

Cetirizine (React­ine®), loratidine (Clari­tin®), deslor­atidine (Aerius®), fexofe­nadine (Alleg­ra®)
Intr­anasal Cortic­ost­ero­ids
To reduce inflam­mation in nasal mucous membranes, and local immunosuppression
Used daily to prevent symptoms
Can take up to 2 weeks for full effect
Local admini­str­ation prevents systemic side effects
Deco­nge­sta­nts
Phenylephrine, pseudo­eph­edrine
Sympat­hom­imetics – stimulants – cause vasoco­nst­riction and reduction of mucous production
For immediate relief of nasal congestion – oral or intranasal
Short term-use only – rebound congestion if longer than 3-5 days (intra­nasal)
Drugs for Anaphy­laxis
Epinep­hrine
Stimulates both α and β adrenergic receptors {{nl} Via α–rece­ptors: counters the high vascular permea­bility that occurs during anaphy­laxis that leads to loss of intrav­ascular fluid and hypote­nsion
Via β–rece­ptors: causes bronchial smooth muscle relaxation and relieves bronch­ospasm, dyspnea, and wheezing
Also alleviates pruritus, urticaria, and angioedema

Anti-f­ungals - Classes of medication

Amph­ote­ricin B
Binds to fungal cell membranes, making them leaky, Given IV
Azole Antifu­ngals
fluconazole, itraco­nazole, ketoco­nazole, micona­zole, vorico­nazole
Alter fungal cell membranes by depleting ergosterol
Used orally, topically, injection; flucon­azole available OTC
Safer than amphot­ericin B
Most often for vaginal candid­iasis, athlete’s foot, or thrush
metronidazole is NOT an azole antifungal
Misc­ell­ane­ous
Ciclo­pirox
topical med used for fungal nail or scalp infections (nail polish or shampoo)
Terbi­nafine
oral med for fungal nail infections
Nystatin
cream available without prescr­iption for many topical fungal infections (ringworm, diaper rash)

Anti-V­irals -Classes of medication

HIV
Because of antire­tro­viral drugs, HIV patients are able to live sympto­m-free for much longer with very low counts of the retrovirus
Antire­tro­viral drugs block the HIV replic­ation cycle
HAART – highly active antire­tro­viral therapy
Goal is to reduce plasma HIV to its lowest possible level - HIV still remains in the lymph nodes
Blood and lymph are separate rivers that cross occasi­onally
Use different classes of antire­tro­virals at same time to reduce resistance
Each class ‘attacks’ different step of replic­ation cycle
Herpes Infect­ions
HSV1: oral cold sores
HSV2: genital ulcera­tions
Zoster: shingles (due to previous varice­lla­-zoster infection)
Acycl­ovir, famcic­lovir, valacy­clovir
Mostly controlled by oral therapy of antivirals – taken at first sign of outbreak, continued for short term
These antivirals prevent viral DNA synthesis
Very well tolerated – take with food
Over the Counter medica­tions for Herpes
Lipac­tin® - heparin + zinc
can reduce pain, may speed healing
Mechanism does not match pathop­hys­iology
Abreva® - docosanol
prevents viral entry into cells, stops spread if caught early (can reduce duration of cold sore by ~1 day)
Infl­uenza
Amanta­dine, and neuram­inidase inhibitors (oselt­amivir and zanamivir)
BEST PROTECTION = VACCIN­ATION
Antiviral drugs may decrease severity of symptoms of influenza and may shorten symptom time by a couple days IF taken within first 48 hours
Generally used only in patients at high risk of compli­cations from influenza

Immuno­sup­pre­ssion - Classes of Medication

Calc­ineurin Inhibitors
Cyclo­spo­rine, tacrol­imus, pimecr­olimus (topical)
“Classic” immuno­-su­ppr­essants used for transp­lants (or topically for psoriasis)
Disrupt T-cell function by binding to calcin­eurin
They are not specific – suppress the ENTIRE immune system  patient is very suscep­tible to any other infection
Extensive monitoring for detailed WBC counts and signs of infection (see slide on monito­ring)
Cort­ico­ste­roids
Anti-i­nfl­amm­atory and immuno­sup­pre­ssant activity
Often used to control exacer­bations of condition such as asthma, rheumatoid arthritis, MS, etc.
Pulse therapy (very high doses, gradual taper) to minimize side effects
Many, many side effects
Biol­ogics
medica­tions produced using biological processes in living organisms such as yeast and bacteria
Have active pharma­ceu­tical ingred­ients that cannot reasonably be synthe­sized by chemical means (too complicated)
Are complex, large molecules derived from living sources and produced through a number of intricate steps
Biologics can be immuno­sup­pre­ssant or immuno­sti­mulant (very specif­ically) or replace a substance that is missing (insulin)
Vaccines, Blood products, Hormones & growth factors, Enzymes Gene therapy, Cancer treatments
Chem­oth­erapy
Cytotoxic drugs
tradit­ional; interfere with or damage DNA, causing apoptosis (progr­ammed cell death)
Hormonal therapy
not cytotoxic; effects mediated through hormonal receptors (depri­vation) – for hormon­e-r­esp­onsive cancer (breast, prostate, etc.)
Immun­oth­erapy
monoclonal antibo­dies, vaccines; non-sp­eci­fically boost immune system to help eradicate cancer (inter­feron alfa)
Targeted agents
monoclonal antibo­dies, tyrosi­ne-­kinase inhibitors (TKIs); the future of treatment – to target cancer cells only

Tuberc­ulosis medica­tions

Rifampin (RMP)
Most potent anti-TB drug available
Good bacter­icidal activity, prevents acquired drug resistance and is very important in preventing relapse
Current doses are based on studies performed in the 1960s, when the lowest effective dose was used because of the high cost of the drug; concerns now that dose is too low -> current trials -> dosing recomm­end­ations may change
               
 

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