Pharmacology Final, Diabetic Medications And Neurodegenerative Disease Drugs

Front 1

What are the four types of pancreatic cells?

Back 1

Alpha - Produce glucagon
Beta - Produce Insulin, Amylin
Delta - Produce somatostatin - inhibitor of secretory cells
F - Pancreatic Polypeptides

Front 2

What are the causes of Diabetes Mellitus?

Back 2

Impaired insulin secretion, or inappropriate function of glucagon

Inappropriate hepatic gluconeogenesis and glucose release

Insulin insensitivity

Front 3

This type of diabetes has selective beta cell destruction. It is subdivided into immune mediated and idiopathic DM. This type of diabetes makes up 5-10% of diabetic population.

Back 3

Type 1 Diabetes

Front 4

What happens in a severe form of Diabetes Mellitus 1?

Back 4

Catabolic state, severe form-ketoacidosis

Front 5

What is the Rx for Type I diabetes?

Back 5

Insulin Injections, Pancreas Transplant

Front 6

What are the details of type II diabetes?

Back 6

Tissue resistance to the actions of insulin combined with decreasing insulin secretion.

Insulin is produced by Beta cells but inadequate to overcome resistance resulting in increase of blood glucose and subsequently affecting fat metabolism. Insulin production sufficient to avoid ketoacidosis.

Front 7

Ketoacidosis is not likely in type II diabetes, but it may occur as a resutl of what two things?

Back 7

Stress (Infection), or medication that enhances insulin resistance (corticosteroids)

Front 8

In type II diabetes, dehydration in untreated people can lead to what?

Back 8

Nonketotic hyperosmolar coma = levels of glucose 6-20 times increased in blood.

Front 9

What is the Rx for diabetes mellitus type II?

Back 9

Treatment escalates over time.

Dietary control, weight loss

Monotherapy: 2nd generation sulfonylureas

30% of patients benefit from insulin therapy.

Commonly failure within five years, drug combinations (insulin action + insulin release)

Oral Agent and Insulin

Front 10

What is considered to be Type 4 Diabetes Mellitus?

Back 10

Gestational Diabetes Mellitus

Front 11

What are the two risks associated with gestational diabetes, and how is gestational diabetes treated?

Back 11

1. Indicates risk for Type II diabetes later in life.

2. 30% increase in fetal abnormalities

Rx = Insulin, a-glucosidase inhibitors only.

Front 12

What are the diagnostic criteria for diabetes?

Back 12

Two or more of the following more than 24 hours apart.

1. Fasting Blood Sugar >126mg/dL on 2 occasions

2. Symptoms of DM + random glucose > 200mg/dL

3. Blood Glucose > 200mg/dL two hours after ingesting 75mg of oral dextrose.

4. Uriinanalysis positive for glucose and acetone (ketone body), elevated HbA1C

Front 13

Within the insulin chain, what are the numbered designations for the different insulins?

Back 13

Insulin Lispro - Lys28, Pro29

Insulin Aspart - Asp28

Insulin Glargine - 31arg, 32arg

Procine, and Bovine Insulins - 30Als

Front 14

When is insulin released?

Back 14

Released at low basal rate and much higher stimulated rate.

Front 15

What are stimulants of glucose?

Back 15

Glucose, Mannose, Leu, Arg. hormones (glucagon-like polypeptide-1), vagal activity.

Front 16

Where is insulin degraded?

What is the half life of circulating insulin?

Back 16

In the liver (60%) and in the kidney (40%)

The half life of circulating insulin is 3-5 minutes.

Front 17

What are the three insulins that act as rapid acting insulins?

Back 17

Insulin Lispro
Insulin Aspart
Insulin Glulisine

Front 18

What are the benefits of using rapid acting insulin?

Back 18

Advantage over human insulin - Low propensity to self associate and form dimers.

Binding to the receptor, circulating half life, and immunogenicity similar to human insulin

Lowest variability of absorption, recommended in insulin pumps

Front 19

What are the details of rapid acting insulin?

Onset?
Peak?
Duration?

Back 19

Rapid onset and early peak better mimic physiologic prandial insulin secretion.

Onset = 5 minutes
Peak = 1 hour
Duration = 3-4 hours, decreased risk of postmeal hypoglycemia

Front 20

What are the short acting insulins?

Back 20

Regular Insulin (Humulin, Novolin, Velosulin)

Front 21

What are the details of short acting insulin?

Back 21

Can be given IV in ketoacidosis, post up when insulin requirement is changing rapidly.

Self aggregates - dimers stabilize around Zn and form hexamers resulting in three rates of absorption.

Front 22

What is the onset, peak and duration of short acting insulin?

Back 22

Onset = 30 minutes
Peak = 2-3 hours
Duration = 5-7 hours

Front 23

Which short acting insulin contains P04 buffers - decreased aggregation - recommended for infusion pumps?

Back 23

Velosulin

Front 24

What is the Intermediate acting insulins?

Back 24

NPH - Neutral Protamine Hagerdorn, or Isophane Insulin

Front 25

What do you not use NPH with?

Back 25

Rapid acting Insulin

Front 26

What are the details of NPH?

Back 26

Protamine is a mixture of arginine rich peptides that form complex with insulin

After subcutaneous inejection, proteolytic enzymes degrade protamine allowing insulin absorption

Front 27

What is the onset and duration of intermediate acting insulins?

Back 27

Onset = 2-5 hours
Duration = 4-12

NOTE: This is dependent on dose

Front 28

What are the long acting insulins?

Back 28

Glargine and Detemir

Front 29

What are the details about Glargine?

Back 29

It is ultra long acting and "peakless" designed to provide background insulin replacement.

Soluble in acidic: (pH4) but precipitates in neutral pH allowing individual insulin molecules to slowly dissolve.

Front 30

What is the onset, maximum activity and for how long is this maintained in Glargine insulin?

Back 30

Onset = 1-1.5 hours
Maximum Activity = 4-6 hours
Maintained for = 24 hours

Front 31

What are the details of Detemir?

Back 31

Most recently developed - increased self-aggregation and reversible albumin binding - most reproducible effects of all intermediate and long acting insulins with least hypoglycemia.

Front 32

What is the onset and duration of Detemir?

Back 32

Onset = 1-2 hours
Duration = 24 hours

Front 33

Which insulins give you that initial peak that diabetics are missing?

Back 33

Insulin lispro, aspart, glulisine = very rapid insulins

Front 34

Insulin therapy provides what?

Back 34

Normal basal as well as meal time insulin.

Front 35

What are the different mixtures of insulin?

Back 35

NPH + lispro, aspart or glulisine = mixed before injection

NPL + Lispro (50/50 and 75/25), and NPA+Aspart (70/30) are all premixed combinations.

Front 36

What two insulins can not be mixed with any other insulin formation?

Back 36

Insulin glargine and detemir

Front 37

What are the reasons that you would not use intensive insulin Tx in a patient?

Back 37

Patients with severe renal disease, the elderly, childern <7 years of age due to high risk of hypoglycemia.

Front 38

What are the complications of insulin use?

Back 38

Immune response - Formation of anti insulin antibodies.

Hypoglycemia

Front 39

How is Hypoglycemia treated?

Back 39

Hypoglycemia can be dangerous and cause brain damage or death.

Rx = Simple sugar or glucose in liquid form.

Mild cases = any sugar beverage

Serve cases = 20-50ml of 50% glucose IV over 2-3 mins, 1mg of glucagon sc, small amounts of honey in the buccal pouch, call 911.

Front 40

What are physical reactions of hyperglycemia?

Back 40

Increased thirst and urination

Large amounts of sugar and ketone in urine

Weakness, abdominal pain, generalized aches

Loss of appetite, nausea and vomiting

Front 41

What are the physical signs of hypoglycemia?

Back 41

Excessive sweating, faintness, headache, pouding of heart, trembling, impaired vision, hunger, not able to awaken, irritability, personality change.

Front 42

What are the drugs that are in the insulin secretagogues?

Back 42

Sulfonylureas
Meglitinides
D-Phenylalanine Derivatives

Front 43

What drugs are members of the Sulfonylureas?

Back 43

First Generation - Chlorpropamide
Second Generation - Glyburide, Glipizide, Glimepiride

Front 44

What is the MOA for sulfonylureas?

Back 44

Binds to sulfonylurea receptor to close K channel in the B cell membrane resulting in depolarization and subsequent insulin release.

Decrease in glucagon release, indirect inhibition due to enhanced release of insulin and somatostatin.

Front 45

Chlorpropamide has how long of an effect and in what situations is it contraindicated?

Back 45

Chlorpropamide is a first generation sulfonylurea.

It is long lasting.

Contraindicated in patients who have hepatic or renal disease, it causes prolonged hypoglycemia.

Front 46

Glipizide has what kind of half life and what is its benefit?

Back 46

Glipizide is a second generation sulfonylurea. It has a shorter half life 2-4 hours, and it is less likely to cause severe hypoglycemia.

Front 47

Which of the second generation sulfonylureas has a long half life and only requires a once daily dosing leading to better compliance?

Back 47

Glimepiride

Front 48

What is the drug member of the meglitinide class?

Back 48

Repaglinide

Front 49

What is the MOA for Repaglinide?

Back 49

It modulates insulin release by regulating K channel efflux.

Front 50

What are the details of Repaglinide?

Back 50

Taken just before the meals, short acting drug, hypoglycemia is a risk if meal is skipped, monotherapy or in combination with metformin. Caution in patients with liver disease.

Front 51

What insulin secretagogue is specifically good for patients with a sulfur allergy?

Back 51

Repaglinide - a Meglitinide

Front 52

What drug is a member of the D-Phenylalanine class?

Back 52

Nateglinide

Front 53

What is the MOA of Nateglinide?

Back 53

Very rapid and transient rlease via closure of K channel

Front 54

What are the details of Nateglinide?

Back 54

It restores initial insulin release in response to an IV glucose tolerance test. Diminished effect in the presence of normoglycemia. Given alone or in combination with metformin.

Front 55

What are the details of D-Phenylalanine Derivatives?

Back 55

Lowest incidence of hypoglycemia.

Duration of action less than four hours, completely reabsorbed within 20 minutes.

Safe in patients with reduced renal function.

Dose titration not required

Use to control postprandial hyperglycemia.

Front 56

What drug is a member of the Biguanide class?

Back 56

Metformin

Front 57

What is the proposed MOA of Metformin?

Back 57

Decreased hepatic gluconeogenesis AMPK activation.

Stimulation of peripheral glycolysis.

Reduced GI glucose absorption.

Reduced plasma glucagon.

Front 58

What are the details of Metformin?

Back 58

Reduces postprandial and lasting glucose levels in Type 2 patients via unknown mechanism not dependent on living beta cells.

Front 59

Biguanides have no?

Back 59

Hypoglycemia - euglycemic agents.

Front 60

Metformin can be use as monotherapy or given in combination with what other drugs?

Back 60

Insulin Secretagogues or Thiazolidinediones.

Front 61

What is the toxicity of metformin?

Back 61

GI distress - contraindicated in patients with renal disease, hepatic disease, or conditions predisposing to tissue anoxia (chronic cardiopulmonary dysfunction), Also inhibition of B12 absorption. Also can very rarely cause lactic acidosis because it uses a pyruvate dehydrogenase to start making lactic acidosis.

Front 62

What drugs are members of the Thiazolidinediones class?

Back 62

Rosiglitazone, Pioglitazone

Front 63

What is the MOA for the Rosiglitazone and Pioglitazone?

Back 63

Incompletely Understood - Increase target tissue sensitivity to insulin such reducing insulin resistance. PPABy agonist - Orphan receptor, transcription factor, controls genes of carbohydrate and lipid metabolism.

Front 64

What are the effects of Thiazolidinediones?

Back 64

Major site of action adipose tissue promoting glucose uptake, modulation of processes involved in energy regulation, regulation of adipocyte apoptosis and differentiation. Increase muscle uptake of glucose, inhibit hepatic gluconeogenesis, reduce fasting and post prandial hyperglycemia, effects on vascular endothelium, immune system and tumor cells. Use alone or in combination. Euglycemic and efficacious in about 70% of users.

Front 65

What drug classes are showing a benefit int he prevention of Type 2 diabetes?

Back 65

Metformin and the Thizolidinediones.

Front 66

What is the toxicity of the Thiazolidinediones?

Back 66

Hypoglycemia but rare in monotherapy

Hypoglycemia with sulfonylureas

Edema, mild anemia

Pioglitazone is a CYP3A4 iducer - DDIs

Front 67

What drugs are in the alpha glucosidase inhibitor class?

Back 67

Acarbose and Miglitol

Front 68

What is the MOA for Acarbose and Miglitol?

Back 68

Act in intestine by inhibiting the enzyme that converts di- to mono- saccharides.

Front 69

What are the effects of the alpha glucosidase inhibitors?

Back 69

Slowed absorption - lower postprandial glucose

Use in monotherapy or in combination

Front 70

What is the toxicity of the alpha-glucosidase inhibitors?

Back 70

GI tract - abdominal pain, diarrhea. Hypoglycemia only when combined with sulfonylurea - in case of hypoglycemia oral glucose not sucrose should be given

Front 71

What drug has been used since the 1920's for the treatment of type one diabetes?

Back 71

Pramlintide - synthetic analog of amylin

Front 72

What are the details of pramlintide?

Back 72

Modulates postprandial glucose - Suppresses glucagon release via unknown mechanism. Delays gastric emptying thus slowing the absoprtion of glucose - lowers body weight.

Front 73

What drug is a DPP-4 inhibitor?

Back 73

Sitagliptin

Front 74

Sitagliptin's MOA is what?

Back 74

GIP and GLP-1 are degraded by dipeptidyl-peptidase 4. Sitagliptin prolongs the action of normal GLP and GLP-1. It is given once a day alone or in combination with metformin, TZDs, Glitazone, Sulfonylureas.

Front 75

Exenatide is?

Back 75

A synthetic analog of GLP1

Front 76

What are the details of Exenatide?

Back 76

Peak at 2 hours, duration of action is 10 hours. It was the first incretin therapy. Approved as injectable, adjunctive therapy with metformin or sulfonylureas. Shown to potentiate glucose mediated insulin secretion, suppress postprandial glucagon release, slow gastric emptying.

Front 77

Glucagon is synthesized by?

Back 77

A-Cells

Front 78

Glucagon is a ?

Back 78

Peptide with a very short half life, given IV or IM

Front 79

What does glucagon due to gut smooth muscle?

Back 79

Relaxes it

Front 80

What are the clinical uses of Glucagon?

Back 80

Diagnostic - give to relax GI tract so it can be viewed easier.

Rx for severe B-blocker overdose - can stimulate heart without access to cardiac b-receptors

Rx for severe hypoglycemia, especially when patient is unable to swallow, requires intact hepatic glycogen stores.

Front 81

What are the drugs used to treat Alzheimers disease?

Back 81

CNS acting cholinesterase inhibitors

NMDA receptor blocker

NSAIDS

Others for multiple symptoms

Front 82

AchE inhibitors are effective for approximately how long?

Back 82

For about 6 months they can delay institutionalization.

Front 83

What are the problems with using cholinesterase inhibitors?

Back 83

Only modest improvement, lasts only six months.

Only effective in about 30% of patients

Does not stop underlying disease

Effects disappear six weeks after the drug is discontinued

Front 84

What are the CNS acting cholinesterase inhibitors?

Back 84

Tacrine
Donepezil
Galantamine
Rivastigmine

Front 85

This cholinesterase inhibitor is the first of the centrally active AchEIs, rarely used now due to hepatotoxicity. If you use this drug you have to monitor LFTs.

Back 85

Tacrine

Front 86

This drug is a reversible AchEI. It is uses for mild or moderate alzheimer's disease.

Back 86

Donepezil

Front 87

What are the Contraindications for Donepazil?

Back 87

Hypersensitivity to piperidines. Cl in liver disease (OK/Renal Disease). Succinylcholine - Prolonged Action. Bradycardia, GI Sx (N, V, D)

Front 88

How is Donepezil metabolized, and what do you have to monitor?

Back 88

Its metabolism is with 2D6 and 3A4, you have to also monitor LFTs if giving this drug.

Front 89

What are the DDIs for Donepezil?

Back 89

Cholinomimetics - additive effects
NSAIDS - Monitor GI for bleeding
Succinylcholine
Ketoconazole - a 3A4 inhibitor
Quinidine - a 2D6 inhibitor

Front 90

How is rivastigmine administered?

Back 90

PO or Patch

Front 91

What is rivastigmine used for?

Back 91

Mild-Moderate Alzheimer's Disease

It is a slowly reversible AchEI

Front 92

Rivastigmine is contraindicated when?

Back 92

Hypersensitivity to Carbamates
Succinylcholine
Hx of bradycardia

Front 93

What is a benefit of Rivastigmine metabolism?

Back 93

It is a plasma esterase, so it has only a small amount of P450 metabolism. This makes it a good choice because it avoids other drugs using this system. The only drawback is that you have to give it twice daily.

Front 94

What are the ADRs for Rivastigmine?

Back 94

N, V, and D. Headache, and dizziness.

Front 95

What are the DDI's of Rivastigmine?

Back 95

Possibly none, although nicotine will increase the clearance of rivastigmine

Front 96

Galantamine is a ?

Back 96

Reversible AchEI

Front 97

What are the contraindications for Galantamine?

Back 97

Same as others, its metabolism is also CYP2D6 and 3A4.

Front 98

What are the ADRs for galantamine?

Back 98

GI effects, bradycardia

Front 99

What is a dosing notice for all of these drugs?

Back 99

If restarting the drug, start at lowest dose and then re-escalate

Front 100

What is the name of the NMDA receptor blocker?

Back 100

Memantine

Front 101

Memantine is used with what for the treatment of moderate to severe Alzheimer's Disease?

Back 101

AchEI

Front 102

What is a major benefit of Memantine?

Back 102

It appears to make the patients rest easier. Although there is no evidence that it prevents or slows disease progression.

Front 103

What drug is used to treat ALS?

Back 103

Riluzole

Front 104

What are the functions of Riluzole?

Back 104

Decreases glutamate release
Neuroprotective
Interferes with glutaminergic signaling events.

Front 105

What is the metabolism for Riluzole?

Back 105

CYP1A2, then glucoronidation. Watch for DDIs.

Front 106

What is the toxicity of Riluzole?

Back 106

Muscle weakness, N, V, and D, anorexia. Decreased lung function, Neutropenia (rare but caution), elevated liver enzymes. YOU MUST monitor LFTs.

Front 107

How do you treat the acute attacks of MS?

Back 107

Glucocorticoids and Plasmapheresis

Front 108

What are the disease modifying therapies that are used for the treatment of MS?

Back 108

IFNB-1b
IFNB-1a
Glatiramer acetate
Natalizumab

Front 109

What interferon will make MS worse?

Back 109

IFNy

Front 110

What is an effective treatment for RR-MS

Back 110

IFNB

Front 111

What will IFNa do if you try to use it for Tx of RR-MS

Back 111

It is ineffective, or it will cause exacerbations.

Front 112

What is the supposed MOA of IFNb?

Back 112

Enters CNS secondary BBB disruption. Reduces levels of TNFa and IFNy, Increases the number of suppressor T cells - Fewer autoreactive T cells.

Front 113

What are the ARs for IFNb-1b?

Back 113

Injection site reactions (SC only)

Flu-Like Symptoms - Chills, headache, myalgias, nausea, vomiting, diarrhea, fatigue.

Mildly elevated liver enzymes

Leukopenia, anemia

Photosensitivity

Spontaneous Abortion

Front 114

What are the Contraindications for IFNb-1b?

Back 114

Hypersensitivity to IFNB or human albumin.

Depression - Suicide precautions
Seizure History
Cardiac, Hepatic Disease
Monitor CBC, LFTs

Front 115

What are the DDIs for IFNb-1b?

Back 115

Suppression of CYP450?
Zidovudine = 2/3 decrease clearance possible decreased glucorinidation.

Front 116

IFNB-1a is doses how?

Back 116

Avonex = IM weekly
Ribef = SC 3X week

There are fewer injection site reactions for the IM form

Front 117

What drug is an amino acid copolymer?

Back 117

Glatiramer Acetate

Front 118

Glatiramer acetate is a copolymer of what four things?

Back 118

L-ala, L-glu, L-lys, L-tyr

Front 119

What is the MOA for glatiramer acetate?

Back 119

Unknown, but it is an MBP mimic, it stimulates suppressor T cells, and inhibits MBP specific effector T cells leading to a decrease in T cell proliferation, and a decrease in secretion of IL-2 and IFNy

Front 120

What is the efficacy of Glatiramer acetate?

Back 120

32% decrease in relapse rate.

Front 121

What are the ADRs for Glatiramer Acetate?

Back 121

It is given SC daily, so injection site RXNs are common. Transient systemic effects following injection include chest tightening, flushing and anxiety.

Front 122

What drug for MS is a monoclonal antibody?

Back 122

Natalizumab

Front 123

When was Natalizumab first used?

Back 123

Crohn's disease

Front 124

How is Natalizumab useful in RR-MS?

Back 124

It helps to decrease new CNS lesions, and it decreases cerebral inflammation.

Front 125

What is the MOA for Natalizumab?

Back 125

It is an anti-glycoprotein a4-integrin. It is approved for Crohn's disease and MS. The A4-integrin is on surface of lymphocytes, and monocytes. The drug prevents transmigration of leukocytes across endothelium.

Front 126

How does Natalizumab work in comparison to the IFN's?

Back 126

It is at least as effective, or more effective than IFNs, there are fewer relapses BUT there are some rare serious ADRs.

Front 127

What drug is approved to treat CP-MS?

Back 127

Mitoxantrone and Cyclophosphamide

Front 128

What are the details of Mitoxantrone?

Back 128

It is FDA approved, immunosuppressant, anticancer drug

Front 129

What are the ADRs of Mitoxantrone?

Back 129

Cardiotoxic, so monitor LV function before starting

Front 130

Cyclophosphamide is what kind of drug?

Back 130

Anticancer drug for off label use.