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Antidiabetic Drugs
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Title: Antidiabetic Drugs
1
Lecture 14
- Chapter 46
- Antidiabetic Drugs
2
Antidiabetic Drugs
- Drugs used to control diabetes mellitus - a
chronic disease that affects carbohydrate
metabolism - 2 groups of antidiabetic agents Insulin oral
hypoglycemic agents - - Oral hypoglycemic agents synthetic
preparations that stimulate insulin release or
alter metabolic response to hyperglycemia - - Insulin a protein secreted from the beta
cells of the pancreas - necessary for carbo
metabolism an important role in protein fat
metabolism
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Antidiabetic Agents
- Diabetes Mellitus - A chronic disease resulting
from deficient glucose metabolism, caused by
insufficient insulin secretion from the beta
cells high blood sugar (hyperglycemia). 3
Ps - 1. Polyuria - inc. urine output
- 2. Polydipsia - inc. thirst
- 3. Polyphagia - inc. hunger
- 2 forms of diabetes
- 1. Insulin-dependent diabetes mellitus (IDDM)
or type I - was refereed to as juvenile-onset w/
no insulin secretion
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Antidiabetic Agents
- 2. Non-insulin-dependent diabetes mellitus
(NIDDM) or type II - was referred to as
maturity-onset or adult-onset diabetes w/ some
insulin secretion - Unknown how lack of insulin causes diabetes -
poss. infection, heredity - Insulin - Released from the beta cells of the
islets of Langerhans in the pancreas in response
to an increase in bld. glucose - - Promotes the uptake of glucose, amino acids,
fatty acids converts them to substances
stored in body cells
5
Antidiabetic Agents
- - Glucose is converted to glycogen for future
glucose needs in the liver muscle lowers bld.
glucose level (range for bld. glucose is 70 - 110
mg/dl) - bld. glucose gt 180 sugar in urine
diuretic effects polyuria - - Insulin can be animal (pork or beef), or
human (using DNA technology) - - Concentration of insulin is 100 U/ml,
insulin packaged in a 10 ml vial. For accurate
dosing, insulin can be given in insulin syringes
ONLY.
6
Antidiabetic Agents
- - Before using insulin, need to ensure well
mixed - always roll between hands - Do NOT Shake
Vial bubbles inaccurate dose - - insulin CANNOT be administered orally - GI
tract secretions destroy insulin structure - - Given subcutaneous at a 45 to 90 degree
angle - - Regular insulin ONLY can be given IV
- - Insulin sites need to be rotated to prevent
lipodystrophy (tissue atrophy or hypertrophy)
interferes w/ insulin absorption
7
Antidiabetic AgentsInsulin
- Types of Insulin's - 3 standard types
- 1. Rapid-acting - Regular insulin - clear soln
w/o added substances to prolong insulin action - Onset 1/2 to 1 h Peak 2 to 4 h Duration
6 to 8 h - 2. Intermediate-acting - NPH, Lente - contain
protamine (a protein that prolongs the action of
the insulin) - Onset 1 to 2 h Peak 6 to 12 h Duration
18 to 24 h - 3. Long-Acting - Ultralente - contain lg.
crystals which dissolve slowly to prolong
duration - Onset 4 to 8 h, Peak 14 to 20 h Duration
24 to 36 h
8
Antidiabetic AgentsInsulin
- Lispro Insulin (Humalog) - a new rapid acting
insulin approved in 1996 - Action 5 min. Duration 2 to 4 h - can be
administered 5 min. before meal time - Combination Insulin's - commercially premixed
- Humulin 70/30, Novolin 70/30, Humulin 50/50
- (70/30 70 NPH and 30 Reg)
- Reg can be mixed w/ NPH or Lente - Reg goes in
first in the syringe Clear to Cloudy
9
Antidiabetic AgentsInsulin
- SE adverse RXNS
- -Hypoglycemic - when more insulin is
administered than needed for glucose metabolism - - S S nervous, trembling, uncoordinated,
cold clammy, incoherent (drunk) - - Rx giving sugar orally or IV
- - Ketoacidosis - An inadequate amt. of insulin
inability to metabolize sugar fat catabolism
use of fatty acids (ketones) for energy - - S S Extreme thirst, polyria, fruity
breath odor - - Rx Insulin
10
Antidiabetic AgentsOral Agents
- Used by persons w/ NIDDM - should NOT be used by
persons w/ IDDM - NIDDM has some degree of insulin secretion by
pancreas - Several classes of oral hypoglycemic agents
- Sulfonylureas - First Second generation
- - Chemically related to sulfonamides, but lack
antibacterial activity - stimulate the beta cells
to secrete more insulin - - 1st generation divided into short,
intermediate long acting antidiabetics
11
Antidiabetic AgentsOral Agents
- - tolbutamide (Orinase) - short Tolazamide
(Tolinase) - intermediate Chlorpropamide
(Diabinese) - long - - Action - Stimulate beta cells to secrete
insulin - - Use NIDDM
- - SE - similar to insulin - hypoglycemic rxn
w/o adequate food intake - - DI - ASA, anticoagulant, anticonvulsants,
sulfonamides, some NSAIDs can inc. action of
sulfonylureas an insulin rxn
12
Antidiabetic AgentsOral Agents
- Nonsulfonylurease Newer drugs
- Biguanides Metformin (Glucophage)
- - Decreases hepatic production of glucose from
stored glycogen diminishes the inc. in serum
glucose after a meal - - Dec. the absorption of glucose from the
small intestine - - Evidence it inc. insulin receptor
sensitivity - - Does not produce hypo or hyperglycemia
- - SE - N V, anorexia, abd cramping, gas
- - Can be combined w/ a sulfonylurea insulin
13
Antidiabetic AgentsOral Agents
- Alpha-Glucosidase Inhibitor Acarbose (Precose)
- - Action - inhibits the digestive enzyme in
sm. intestine responsible for release of glucose
from the complex carbohydrates (CHO) in the diet - - By inhibiting alpha glucosidase (enzyme) -
the CHO cannot be absorbed they pass into the
lg. intestine - - does not cause a hypoglycemic rxn
- - Use - for clients who do not achieve results
on diet alone
14
Antidiabetic AgentsOral Agents
- Thiazolidinediones Troglitazone (Rezulin) -
unrelated to other antidiabetic drugs - - Action - Decrease insulin resistance, helps
muscle cells respond to insulin use glucose
more effectively - - May be used w/ sulfonylurea, metformin, or
insulin - - May cause serious hepatic toxicity - Not
used in England - Rapaglinide (Prandin) - classification unknown -
Newest - - For use alone or w/ metfromin - short acting
- - Action - similar to sulfonylureas, but does
not cause hypoglycemia
15
Antidiabetic AgentsOral Agents
- Hyperglycemic Drugs - Glucagon
- - Action - A hyperglycemic hormone secreted by
the alpha cells of the islets of Langerhans -
Inc. bld sugar by stimulating glycogenolysis
(breakdown of glycogen to glucose) in the liver -
protects body cells - - Use - Insulin-induced hypoglycemia when
other methods not available or not working - - Clients prone to hypoglycemia should keep in
home family members taught how to use - - Begins to work in 5 to 20 min.
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Antidiabetic AgentsOral Agents
- Diazoxide (Proglycem) - chemically related to
thiazide diuretics - - Action - Inc. bld sugar by inhibiting
insulin release from the beta cells stimulating
release of epi (adrenalin from the adrenal
medulla - - Use - Chronic hypoglycemia caused by
hyperinsulinism d/t islet cell Ca or hyperplasia - - Not used to Rx hypoglycemic rxns
- - Parenteral form (Hyperstat) used for
malignant HTN - - Oral diazoxide usually does not cause
hypotension
17
Chapter 33
- Anticancer Drugs
18
Anticancer Drugs
- In the US, cancer is the 2nd cause of death
(heart dx - 1st) - Results from the alterations in DNA w/in the cell
- Use of anticancer drugs include - cure, control,
palliative - Chemo may be used as sole Rx of Ca or in
conjunction w/ radiation surgery - Cell-Cycle Nonspecific Specific - Anticancer
drugs cause Ca cell death by interfering w/ Ca
cell replication - - Interferes w/ either all phases or a specific
phase of the cell cycle (pg. 575, fig. VII-I)
19
Anticancer Drugs
- - Cell-cycle nonspecific (CCNS) act on any
phase during the cell cycle - - kill the cell during the dividing resting
phase of cell cycle alkylating drugs, antitumor
antibiotics, hormones - - Cell-cycle specific (CCS) act on a specific
phase of the cell cycle - - effective against rapidly growing Ca cells
antimetabolites, vica alkaloids, antitumor
antibiotics - Growth fraction doubling time are two factors
that play a major role in the Ca cell response to
the anticancer drug
20
Anticancer Drugs
- - Anticancer drugs are more effective against
the Ca cells having a high growth fraction -
leukemias some lymphomas - - Ca of the breast colon melanomas low
growth fraction poor response to
antineoplastics - - small early forming Ca cells fast-growing
tumors respond well to anticancer drugs - Drug Rx for early dx higher cure rate than late
stages - Solid tumors low growth fraction less
sensitive to drugs
21
Anticancer Drugs
- Higher doses of drugs result in better
tumoricidal (killing) effects - Ca growth usually faster in earlier stages. As
tumor grows bld supply dec growth rate dec.
drugs more effective against sm. tumors w/
sufficient bld supply - Cancer Chemotherapy - tumor cells are similar to
normal cells in that it is difficult for antiCa
drugs to be selective in killing tumor cells
not normal cells - - Drug protocol therapy too long doses too
high toxic - - Eliminating every Ca cell difficult (1
mill. cells could remain w/o symptoms - ??? on
continuing Ca therapy
22
Anticancer Drugs
- Drug Resistance - tumor resistance can develop
against an antiCa drug d/t drug used infrequently
or the tumors location limits the effectiveness - - Brain tumors respond poorly (BBB)
- Combination Chemotherapy - Single-agent drug
therapy seldom used - - Combo of drugs to enhance tumoricidal
effects - - CCS CCNS are often combined to max. cell
deaths - - dec. drug resistance, shorten intensify
drug effect - - inc. destruction of Ca cells, dec. drug
toxicity - several drugs lower doses less
injury to normal cells
23
Anticancer Drugs
- Alkylating Drugs - one of the largest groups of
Ca drugs - - Kill cells by forming cross-links on DNA
strands - - Belong to the CCNS category affect all
phases of the cell cycle - effective against many
types of cancers acute chronic leukemias,
lymphomas, mult. myeloma, solid tumors (breast,
ovaries, uterus, lungs) - - Classified into 4 groups Nitrogen mustards
(Cyclophosphamide), nitrosoureas (Carmustine),
alkyl sulfonates (Busulfan), alkylating-like
drugs (Cisplatin)
24
Anticancer Drugs
- Cyclophosphamide (Cytoxan) - Nitrogen mustard
- - Action - Inhibition of protein synthesis
through interference w/ DNA replication by
alkylation of DNA - - Use - Hodgkins dx, solid tumors
- - SE - bone marrow suppression , alopecia, N
V, diarrhea, wt. loss, hematuria (maintain
adequate hydration), impotence, sterility - - An early antiCa drugs, can be administered PO
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Anticancer Drugs
- Antimetabolites - Oldest group
- - Resemble natural metabolites - disrupt the
metabolic processes some of the agents inhibit
enzyme synthesis - - CCS (5-FU, floxuridine - also CCNS)
- - Subdivided into folic acid (folate)
antagonists (Methotrexate) - also used as an
immunosuppressant following organ transplant -
substitutes for folic acid, needed for the
synthesis of proteins DNA pyrimidine analogues
(5-fluorouracil) purine analogues
(6-mercaptopurine)
26
Anticancer Drugs
- Flurouracil (Adrucil, 5-FU, Efudex) - IV
- - Action - CCS, blocks the enzyme action
necessary for DNA RNA synthesis - - low therapeutic index
- - alone or w/ other drugs, can cross BBB
- - Use - Ca of breast, cervix, colon, ovary,
stomach, pancreas - - SE - N, V, diarrhea, alopecia, rash, bone
marrow suppression, stomatitis (inflammation of
oral mucosa)
27
Anticancer Drugs
- Antitumor Antibiotics - (Bleomycin, dactinomycin,
daunorubicin, doxorubicin) - inhibit protein
RNA synthesis bind DNA causing fragmentation - - Classified as CCNS (except for bleomycin)
- - Drugs differ from each other are used for
diff. Cas - Doxorubicin (Adriamycin) - IV
- - Action - Inhibits DNA RNA synthesis
- - Use - W/ other agents for Ca of breast,
ovaries, lung, bladder, leukemias, lymphomas - - SE - Similar to general adverse rxns to
antineoplastics
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Anticancer Drugs
- - Capable of causing vesication - blistering of
tissue if drug leaks out into surrounding
interstitial tissue - rxn ranges from painful,
reddened swelling to deep necrotic lesion needing
debridement skin grafts - - Drug is a deep red color - urine will be red
1 - 2 days after administration - - Can cause cardiotoxicity
- Mitotic Inhibitors (Vinca Alkaloids) - block cell
division at M phase of cell cycle (Vincristine,
Vinblastine, Vinorelbine tartrate) - CCS
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Anticancer Drugs
- - Single drugs or in combo therapy
- - SE - leukopenia, alopecia, stomatitis, N,V,
neurotoxicity - Hormones Hormone Antagonisits - Used in combo
therapy for Rx of various Ca. - - 2 major actions 1) Agonists that inhibit
tumor cell growth - estrogen, progestins,
androgens, adrenocorticosteroids 2) Antagonists
that compete w/ endogenous hormone -
aminoglutethimide, tamoxifen - Corticosteroids (glucocorticoids) classified as
antiinflammatory agents - suppressing the
inflammatory process that occurs w/ tissue
involvement
30
Anticancer Drugs
- - Hormones also suppress leukicytes is
effective in controlling leukemia lymphoma - - Used w/ other drugs as part of an
antineoplastic regimen - MOPP (oncovin,
procarbazine prednisone) - Hodgkins disease - - Prednisone frequently prescribed -
inexpensive cortisone derivative - - Dexamethasone hydrocortisone - IM or IV -
can decrease cerebral edema caused by a brain
tumor
31
Anticancer Drugs
- Tamoxifen (Nolvadex) -
- - Action - exact neoplastic action unknown,
acts as an estrogen antagonist - - Use - Breast cancer in women and men
- - SE - Adverse rxns usually minor well
tolerated - Miscellaneous Agents - antineoplastic drugs whose
MOA does not place them in a category. Used in
combo w/ other Ca drugs to Rx a variety of solid
tumors hematologic malignancies - pactitaxel
(Taxol), docetaxel (Taxotere), pentostatin
(Nipent), etoposide (VP-16)
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