Exam 2 HLD through Antidepressants

Hemostasis

the physiological process by which bleeding is stopped

Plaelet aggregation

platelets sticking and clumping together

Thrombosis

formation of an unwanted clot within the vessel or heart

Deep Vein Thrombosis (DVT)

clots in the large veins of the legs

Pulmonary Embolism (PE)

clot that lodges in a vessel in the lungs….life threatening

What is stage one of the response to vascular trauma?

Once activated, the platelets will stick to damaged vessel tissue and aggregate together, forming a platelet plug

Antiplatelet drugs

drugs that inhibit platelet aggregation

What is stage 2 of the vascular response to trauma?

activation of the coagulation cascade, which involves many chemical reactions and coagulation factors.

What is the intrinsic pathway?

Conact activation pathway

what is the extrinsic pathway?

tissue factor pathway

Anticoagulants

drugs that inhibit parts of the coagulation cascade

What happens when there is exposed collagen?

Platelets will stick to any exposed collagen

What is adenosine diphosphate?

a substance that is released by platelets when they are triggered by collagen

Thrombolytics

clot busters, breaks down clots that are already formed

What is the name for aspirin (oral) ASA

acetylsalicylic acid

Mechanism of Action of Aspirin

Irreversibly inhibits the enzyme cyclooxygenase

Is aspirin an antiplatelet or anticoagulant?

antiplatelet

What is the use of antiplatelet therapy for primary prevention of cardiovascular disease?

for patients who have not yet experienced a clotting event, but who are at risk. Appropriate for men aged 45- 79 years old and women aged 55- 79 years old who have cardiac risk factors (DM, HTN, high cholesterol, smoker) and are at a low risk of GI hemorrhage.

What is the use of antiplatelet therapy for secondary prevention of cardiovascular disease?

for patients who have already experienced clotting issues (ischemic stroke, TIA, MI, angina, stent placement, etc)

What are the therapeutic uses of antiplatelet drugs?

The main therapeutic use of antiplatelet medications is to prevent blood platelets from clumping together and forming unwanted blood clots in arteries, which helps reduce the risk of heart attacks and strokes.

What are the therapeutic uses of anticoagulants?

slow down the body's process of making blood clots to treat and prevent dangerous blockages in blood vessels

what is the mechanism of action of Warfarin?

Warfarin blocks the active vitamin K needed for the synthesis of factors VII, IX, X, and prothrombin. Vitamin K is required for the liver to synthesize the four factors of the clotting cascade

Why does warfarin have a lag time between a dose and its therapeutic effect.

Warfarin inhibits synthesis of new clotting factors only. It takes 3-5 days for existing factors to be depleted.

What is the antidote for warfarin?

Vitamin K oral: phytonadione (Mephyton)

Vitamin K injection: phytonadione

These are slow-acting antidotes because it won’t work until the body uses the vitamin K to make more clotting factors

If Immediate reversal is needed, fresh frozen plasma, which contains clotting factors, will need to be administered.

What foods are rich in Vitamin K and can interfere with Warfarin?

Green leafy vegetables (spinach, broccoli, brussel sprouts, kale, collard greens, cabbage)

What lab test monitors the theraputic warfarin levels?

Prothrombin time (PT), which is mathematically converted to the International Normalized Ratio (INR)

What is the INR goal for most patients on Warfarin?

Therapeutic INR is usually 2.0-3.0 depending on what is being treated. Someone not treated with Warfarin is 1.0

What does an elevated INR or APTT indicate?

over anticoagulation

What does a low INR or APTT indicate?

under anticoagulation

Compare Heparin vs Warfarin onset of action and duration of action?

Heparin onset is quick with a fairly short duration of action.

Warfarin onset is 3-5 days and the duration of action is 2-5 days.

Compare Heparin and Warfarin monitoring and reversal agents

Heparin monitoring is activated partial thromboplastin time (APTT) (measures the length of time it takes a clot to form. Normal = 30-40 seconds. Therapeutic = 1.5 -2 times). Reversal agents are protamine sulfate (binds to and inactivates heparin molecules)

Warfarin monitoring is PT and INR. Reversal agents are Vitamin K (phytonadione, and immediate reversal is fresh frozen plasma.

Mechanism of Action of Dabigatron (Pradaxa)

Direct thrombin inhibitor: Binds to thrombin, preventing conversion of fibrinogen to fibrin

Mechanism of Action of Rivarozaban (Xeralto)

Direct Factor Xa Inhibitor: binds to Factor Xa inhibiting production of thrombin

Mechanism of Action of Apixaban (Eliquis)

Direct factor Xa inhibitor: binds to factor Xa, inhibiting the production of thrombin

What is the principal side effect common to all anticoagulants, antiplatelets, and throbmolytics?

major and minor bleeding

Hyperlipidemia

Abnormally elevated levels of lipids (fats) in the blood, most commonly cholesterol and triglycerides

What is LDL?

Bad. Delivers cholesterol to tissues = plaque formation

what is HDL?

good. Removes cholesterol from tissues.

what is triglycerides?

very high levels increase pancreatitis risk

What is the mechanism of Action of Statins?

They inhibit HMG-CoA reductase, the rate-limiting enzyme in cholesterol synthesis. This enzyme is responsible for converting HMG-CoA to mevalonate, an early and essential step in cholesterol production. When the liver makes less cholesterol, less LDL cholesterol circulates in the blood, improving the lipid profile.

What are side effects of statins?

myalgia (muscle pain), increased liver enzymes (AST, ALT), rare but serious: rhabdomyolysis

What is the mechanism of action of Ezetimibe?

Decreases intestinal absorption of dietary cholesterol

What is diabetes?

A disorder of carbohydrate metabolism that causes a sustained elevated plasma level of glucose (hyperglycemia). Elevated blood glucose is caused by a lack of or low levels of insulin, or insulin resistance.

what is insulin?

Hormone synthesized in the pancreas by the beta cells. Secretion is stimulated mainly by glucose. Insulin facilitates glucose uptake into cells and stimulates the liver to store glucose as glycogen.

What is type 1 diabetes?

Immune-mediated destruction of pancreatic B cells. Circulating insulin is absent; plasma glucose is elevated. Treatment: insulin replacement is mandatory along with strict dietary control.

What is type 2 diabetes?

Pancreatic B cells are functioning to some degree. Insulin resistance: exercise and weight reduction will reduce resistance. Associated with middle-aged to older adults, abdominal obesity, sedentary lifestlye, genetics. Treatment: diet, exercise, and usually self monitoring of blood glucose

What is gestational diabetes?

Appears only during pregnancy. often associated with large birth weight babies. placenta produces hormones that block the actions of insulin. Treatment: diet, self-monitoring of bloood glucose, sometimes insulin, sometimes metformin

what are long term complications of diabetes?

cardiovascular disease, retinopathy, nephropathy, neuropathy, amputations, gastroparesis, erectile dysfunction

what are common signs/symptoms of hypoglycemia?

tachycardia, palpitations, sweating, anxiety, shakiness, nervousness, headache, irritability, confusion, weakness, and fatigue.

what is the “15-15” rule?

Consume 15 mgs of fast-acting carbohydrates (glucose tablets or gels, 4 oz juice, 1 tbsp sugar, gummy candies, jellybeans), then wait 15 min and check again.

What is the before meal blood glucose goal?

70-130mg/dL

what is the after a meal blood glucose goal?

< 180 mg/dL

what is the HgbA1c goal?

< 7%

What is the fasting plasma glucose test?

Measures the concentration of glucose in the plasma after fasting for at least 8 hrs. Diagnosis range = greater than 126 mg/dL

what is the casual plasma glucose test?

measures the concentration of glucose in the plasma at any time. Diagnosis range=greater than 200

what is the oral glucose tolerance test?

Measure the level of glucose before and after giving a known amount of oral glucose. diagnosis range = greater than 200

what is HgbA1c test?

Measures the average blood glucose concentration over the past 2-3 months. Diagnosis range=6.5% or higher

What is the mechanism of action of Biguanides (metformin)?

Decreases glucose production in the liver (gluconeogenesis)

what is the side effects of Biguanides (metformin)?

decreased appetite, nausea, diarrhea, weight loss (average 7 to 8 lbs), decreased absorption of vitamin B12 and folic acid. rarely lactic acidosis.

What is the mechanism of action of Sulfonylureas (glipizide)?

Primary: stimulate the pancreatic B cells to release insulin

Secondary: enhances the cellular sensitivity to insulin (makes the insulin work better)

what is the side effects of Sulfonylureas (glipizide)?

Can cause hypoglycemia; weight gain

What is the mechanism of action of Meglitinides (Glinides) (repaglinide)

Primary: stimulate the pancreatic B cells to release insulin

what is the side effects of Meglitinides (Glinides) (repaglinide)

can cause hypoglycemia; weight gain

What is the mechanism of action of Thiazolidinediones (Glitazones) (pioglitazone)

Priamry: decreases insulin resistance. Increases sensitivity to insulin in muscle, liver, and fat cells.

what is the side effects of Thiazolidinediones (Glitazones) (pioglitazone)

fluid retention, edema, resumption of ovulation in pts taking oral contraceptives. Raises HDL and lowers triglycerides, may raise LDL.

What is the mechanism of action of a- Glucosidase Inhibitors (acarbose)

Inhibit the enzyme a- Glucosidase in the small intestine. This enzyme normally turns dietary starch and sucrose into an absorbable form. Cause delayed glucose absorption. Decreased post-prandial blood glucose levels.

What is the adverse effects of a- Glucosidase Inhibitors (acarbose)

flatulence, cramps, abdominal distention, borborygmus (rumbling bowel sounds), diarrhea

Which diabetes type requires insulin replacement?

Type 1 diabetes; insulin replacement is mandatory.

Which diabetes type is usually treated first with metformin?

Type 2 diabetes.

Why is metformin contraindicated in renal failure?

Poor renal function increases the risk of complications, including lactic acidosis.

Which insulins are rapid-acting?

Lispro (Humalog), aspart (Novolog), and glulisine (Apidra).

What are the onset and duration of rapid-acting insulin?

Onset: 10–30 minutes; duration: 2–4 hours.

Which insulin is short/fast-acting?

Regular insulin (Humulin R, Novolin R).

What are the onset and duration of regular insulin?

Onset: 30–60 minutes; duration: 6–10 hours.

Which insulin is intermediate-acting?

NPH (isophane) insulin.

What are the onset and duration of NPH insulin?

Onset: 60–120 minutes; duration: 12–18 hours

Which insulins are long/slow-acting?

Insulin detemir (Levemir) and insulin glargine (Lantus).

What are the onset and duration of glargine?

Onset: about 70 minutes; duration: >24 hours.

What is basal insulin?

Long-acting insulin that provides ongoing background insulin coverage.

What is bolus insulin?

Mealtime insulin used to cover increases in blood glucose from meals.

Which insulin is commonly used as mealtime bolus insulin?

Rapid-acting insulin, such as lispro.

In a basal/bolus regimen, when is glargine commonly given?

At bedtime as basal insulin.

In a basal/bolus regimen, when is lispro given?

With meals as bolus insulin.

What are examples of Type 2 oral diabetes drugs?

Metformin, sulfonylureas, meglitinides, TZDs, α-glucosidase inhibitors, SGLT-2 inhibitors, and DPP-4 inhibitors.

What neurotransmitters are involved in the current theories of depression?

Norepinephrine, dopamine, and serotonin.

What is the suicide risk associated with antidepressants?

Antidepressants carry a warning for increased suicidality in children, adolescents, and young adults, especially early in treatment and after dose increases. Patients should be closely monitored during these periods.

What is the general onset of action for antidepressants?

Slow; initial response generally takes 1–3 weeks, with maximal benefits possibly taking up to 12 weeks.

Which antidepressants are considered first-line drugs for depression?

SSRIs, SNRIs, bupropion, and mirtazapine.

What is the mechanism of action of SSRIs?

They inhibit serotonin reuptake into CNS nerve terminals, increasing serotonin concentrations in the CNS.

What are common adverse effects of SSRIs?

Nausea, headache, insomnia, nervousness, akathisia, and sexual dysfunction.

What is the mechanism of action of SNRIs?

They inhibit the reuptake of serotonin and norepinephrine, increasing both neurotransmitters in the CNS.

hat are common adverse effects of SNRIs?

Insomnia, nervousness, dry mouth, anorexia, mild cardiovascular effects, sexual dysfunction, sweating, and hypertension.

What is the mechanism of action of TCAs?

They inhibit the reuptake of norepinephrine and serotonin, increasing their concentrations in the CNS.

What are the major adverse effects of TCAs?

Anticholinergic effects, sedation, orthostatic hypotension, cardiovascular effects, weight gain, sexual dysfunction, and decreased seizure threshold.

What anticholinergic effects can TCAs cause?

Dry mouth, blurred vision, urinary retention, constipation, tachycardia, and confusion.

Why are TCA overdoses dangerous?

TCAs have a narrow therapeutic window, and overdoses can be fatal due to potentially life-threatening cardiovascular effects.

Why do TCAs cause more adverse effects than SSRIs?

TCAs are not selective for CNS receptors, so they affect multiple receptor types throughout the body.

What is the mechanism of action of MAO inhibitors?

They inhibit MAO-A and MAO-B, preventing breakdown of monoamine neurotransmitters and increasing their concentrations in the CNS.

Why are MAO inhibitors generally not drugs of choice for depression?

Because of their significant adverse effects and drug/food interactions.

What foods should be avoided with MAO inhibitors?

Tyramine-containing foods such as aged cheese, liver, aged or smoked meats, soy sauce, figs, bananas, and some imported wines and beers.