Pharmacology Exam 3

Sympathomimetic

Imitates nor epinephrine

sympatholytic / parasympathomimetic

Imitates acetycholine

Hypertension

High blood pressure
Increases risk of
– Stroke
– Angina
– Myocardial infarction
– Heart failure
– Kidney disease
Incidence increases with aging

Prehypertension

Sys: 120 to 139 / Dia: 80 to 89

Stage 1 Hypertension

Sys: 140 to 159 / Dia: 90 to 99

Stage 2 Hypertension

Sys: >160 / Dia: >100

a1 receptors

Sympathetic stimulation causes vasoconstriction through

B₁ receptors

Increases heart rate and contractility through

a₂ receptors

Inhibits sympathetic outflow through

calcium channels

– Allow calcium to enter cells of the heart
muscle, arteries, and arterioles
– Leads to muscle contraction
– Also associated with B₁ receptors in heart

Renin-angiotensin aldosterone system

Diuretics

Medications that increase urine output. Increase excretion of Na and chloride. Leads to increased excretion of water. Used to treat hypertension. Also used for edema. Dilate artery right below the heart

Thiazide diuretics

Preferred for hypertension. Drug of choice for uncomplicated stage 1 hypertension. People allergic to sulfa may not be able to take these drugs. Not good with swelling/fluid decrease. Well-tolerated, with little side effects.

Loop diuretics

More potent as diuretics. Preferred for edema. can be used for hypertension when thiazides are not sufficiently effective

Potassium-sparing diuretics

Weak diuretics. Not good at getting rid of excess fluid. Not as effective, but doesn’t have a sulfa group

Adverse effects of loop and thiazide diuretics

Hypokalemia, increased LDL cholesterol. hyperglycemia, sexual dysfunction.

Adverse effects of potassium-sparing diuretics

Hyperkalemia, spironolactone (gynecomastia and sexual dysfunction in males) (deepening of the voice, hirsutism [hair growth in unusual areas], and menstrual irregularities in females

Beta-Blockers

Block beta-adrenergic receptors. Noselective and cardioselective (B1 receptor)

Beta-Blockers

Decrease heart rate and force of contraction. Slow impulse conduction through AV node, decrease release of renin by kidney, bronchoconstriction through B2-receptor blockade, inhibit glycogenolysis due to B2-receptor, affect metabolism of triglycerides and fatty acids, decrease peripheral vascular resistance

Beta-blockers

hypertension, angina, heart failure, migraine prevention, acute panic symptoms, pheochromocytoma, cardiac dysrhythmias, acute myocardial infarction and preventing recurrent myocardial infarction, glaucoma

Beta blocker adverse effects

Bronchoconstriction (do not use in patients with asthma), mask symptoms of hypoglycemia, delay recovery from hypoglycemia (use caution in patients with diabetes), beta-blockers should not be abruptly discontinued, bradycardia, insomnia, sexual dysfunction, depression, nightmares, increased triglycerides, reduced HDL, fatigue, decreased exercise tolerance

ACE Inhibitors

Inhibit the action of angiotensin converting enzyme
Therapeutic uses
– Hypertension
– Heart failure
– Myocardial infarction

ACE Inhibitors

– Arterial and venous vasodilation
– Decreased systemic vascular resistance
– Increased sodium and water excretion
– Increased potassium retention
– Increased blood flow to kidney

ACE Inhibitors and hypertension

Effective alone or in combination
– All ACE inhibitors have similar efficacy
Mechanism of antihypertensive effect
– Vasodilation through reduced angiotensin II
– Vasodilation through increased bradykinin
– Reduced blood volume
More effective in patients with high renin
blood levels

ACE inhibitors adverse effects

Usually well tolerated, persistent dry cough, angioedema (swelling in the blood vessels), first-dose hypotension, contraindicated in pregnancy

Angiotensin II Receptor Blockers (ARBs)

Block the action of angiotensin II at its receptor. similar to ACE inhibitors, no effect on bradykinin

Calcium channel blockers

Block calcium channels and decrease influx of calcium into vascular smooth muscle and cardiac muscle cells (peripheral vasodilation, decreased heart rate, decreased force of contraction, dilate arterioles of the heart). Two types: non-selective (heart and vascular muscle) and selective (vascular muscle) — for those with heart failure

Calcium channel blockers

Recommended for use post-heart attack for black males instead of beta blockers. Also preferred for those with a lot of side effects while on beta blockers

Calcium channel blockers adverse effects

Gingival hyperplasia (growth of gums)

Uncomplicated stage 1 hypertension

Thiazide diuretic. May consider ACE inhibitor, ARB, calcium channel blocker

Stage 2 hypertension

Two-drug therapy. Thiazide diuretic plus ACE inhibitor, ARB, or calcium channel blocker

Angina

B-blockers or calcium channel blockers

History of myocardial infarction

B-blockers, ACE inhibitors, possibly calcium channel blockers

Heart failure

ACE inhibitors, diuretics, B-blockers, ARBs

Renal insufficiency

ACE or ARB

Diabetes mellitus

ACE inhibitors + ARBs first line. Diuretics second line

Asthma

B-blockers are contraindicated

Pregnancy

Drugs affecting the renin-angiotensin-aldosterone system are contraindicated

Angina Pectoris

Myocardial oxygen demand exceeds oxygen supply (results in occurrence of chest pain)

Angina Pectoris

Sudden pain that originates behind breast bone, pain radiates to left shoulder and arm, pain or discomfort may also be felt in neck and jaw

Angina pectoris treatment

Beta-blockers, calcium channel blockers, and nitrates

Nitroglycerin

Used to treat acute anginal attacks. Long-acting forms can be used regularly to reduce frequency of anginal attacks. Causes vasodilation and primarily affects veins

Myocardial infarction

Occlusion of a coronary artery. Prevents sufficient blood from reaching a portion of heart muscle. Persistent ischemia leads to death of some myocardial cells. Caused by platelet aggregation and clot formation at site of atherosclerotic plaque

Heart failure

Heart cannot pump with enough force to adequately supply blood to the tissues. Progressive disease.

Symptoms
– Water retention and edema
– Fatigue
– Exercise intolerance
– Shortness of breath
– Tachycardia

Class I heart failure

No limitation of ordinary physical activity

Class II heart failure

Slight limitation of physical activity. Normal physical activity causes symptoms

Class III heart failure

Marked limitation of physical activity. Even mild activity causes symptoms

Class IV heart failure

Symptoms at rest. Increased discomfort with any physical activity

Digoxin (lanoxin)

Cardiac glycoside. Therapeutic uses: heart failure and cardiac dysrhythmias. No longer considered first-line therapy. Low therapeutic index drug. Many drug interactions. Does not prolong survival in heart failure. Improves quality of life

Diabetes mellitus

Endocrine disorder characterized by hyperglycemia

Type 1 diabetes (IDDM)

<10% of diabetes cases. Do not make insulin

Type 2 diabetes (NIDDM)

Most common form of diabetes. Insulin resistance and altered secretion. Managed with diet, exercise, oral medications, and insulin

Diabetes symptoms

Polydipsia (excessive thirst), polyuria (urinates often), polyphagia (excessive hunger), weight loss, fatigue, blurred vision, irritability

Type 2 diabetes

Continued production of insulin. Characterized by insulin resistance and altered secretion. Patient may be asymptomatic. Can go undiagnosed for years

Incretins

Hormones released by the GI tract in response to absorption of food. Increase release of insulin, preserve insulin-producing capacity of B-cells, decrease appetite, reduce glucagon release. Diminished response in diabetics.

Amylin

Co-secreted with insulin by B-cells. Decreases GI motility, slow rate of glucose absorption, reduces glucagon release, decreases appetite. Insufficient regulation from ____ in diabetics

Risk factors for type 2 diabetes

Obesity, abdominal obesity, sedentary lifestyle, age, genetic link

Complications of diabetes

Acute hypoglycemic episodes, hypertension, heart disease, stroke, kidney disease, neuropathy, amputations, sexual dysfunction, periodontal disease

Mild hypoglycemia

Sweating, intense hunger, inability to concentrate, palpitations, tachycardia, tremor, and anxiety

Moderate hypoglycemia

Mood changes, headache, irritability, confusion, blurred vision, drowsiness

Severe hypoglycemia

Poor responsiveness, unconscious, coma

Nocturnal hypoglycemia

Morning headache, nightmares, lips/tongue tingling, profuse sweating, restless sleep

Sulfonylureas

Increase release of insulin. 2nd gen are more potent and more predictable. Adverse effects: hypoglycemia, weight gain

Meglitinides

Similar to sulfonylureas. Lowers glucose levels by stimulating release of insulin from the pancreas. Generally well tolerated but can cause hypoglycemia and weight gain

Biguanides

Antihyperglycemic agent: lowers blood glucose by decreasing glucose production in the liver and increasing glucose uptake and utilization. Reduces release of glucose by liver. Does not cause hypoglycemia. Adverse effects: GI effects, lactic acidosis

Thiazolidinediones

Adverse effects: liver dysfunction, fluid retention, heart failure, effects on plasma retention, increased risk of MI and heart-related death. Withdrawn from market. Stimulated more production of insulin

Alpha-Glucosidase Inhibitors

Delays absorption of dietary carbohydrates. Adverse effects: GI

DPP-4 Inhibitors

Inhibit dipeptidyl peptidase IV (prolongs activity of incretins). Stimulate insulin secretion. Inhibit glucagon release. Reduce postprandial glucose. Injectable

Incretin mimetics

Reduce postprandial glucose. Reduce A1c. May cause weight loss. May preserve B-cell function. Adverse effect: pancreatitis, nausea, vomiting, diarrhea

Pramlintide

Amylin-like drug. Used for type 1 and type 2. injectable

Insulin

Can be used alone. Often in combination with oral antidiabetic drug therapy in type 2

Primary neurotransmitters

Norepinephrine, serotonin, dopamine

Norepinephrine

Alertness, concentration, energy, attention, anxiety, impulse, irritability, mood, cognitive function

Dopamine

Pleasure, reward, motivation/drive, attention, appetite, sex, aggression, mood, cognitive function

Serotonin

Obsessions & compulsions, memory, appetite, sex, aggression, anxiety, impulse, irritability, mood, cognitive function

Major depression

Cause not completely understood. Decreased serotonin (5-HT) and NE. Diminished ability to function. Twice as frequent in women. Not age-dependent. Onset can be due to meds or medical conditions

Major depression

Depressed mood, loss of interest or pleasure in activities, change in appetite, change in sleep patterns, loss of energy, feelings of worthlessness or guilt, diminished ability to concentrate, thoughts of suicide

Selective serotonin reuptake inhibitors (SSRI’s)

Most commonly used antidepressents

SSRI’s

Usually well-tolerated. adverse effects: sexual dysfunction, nausea, vomiting, CNS stimulation, headache, potential “serotonin syndrome”

SSRI

Slow onset of effect (4-6 weeks for maximum effect). Can’t quite cold turkey

Serotonin/Norepinephrine reuptake inhibitors (SNRI’s)

Similar in mechanism to TCAs, better side effect profile, newest products

Tricyclic antidepressants (TCA’s)

Block reuptake of serotonin and NE. Also block cholinergic receptors

Tricyclic antidepressants

Adverse effects: orthostatic hypotension, anticholinergic effects, sedation, cardiac toxicity, seizures, weight gain, sexual dysfunction, increased sweating

Bupropion

Approved for major depression and smoking cessation. Mild NE/DA reuptake inhibitor. Well tolerated and could be used in combo. Can cause seizures at higher doses

Tetracyclics

Affects multiple receptors (increase in 5HT and NE). Adverse effects: somnolence, dizziness, weight gain, increased cholesterol, mild anticholinergic effects

Trazadone (Desyrel)

Less effective than other agents. Causes significant sedation. Used to treat insomnia. Other adverse effects: dizziness + orthostatic hypotension

Antidepressants and Bipolar

Treat acute depressive episodes.Use lower doses and shorter duration of therapy than for major depressive disorder

Lithium (Li+)

Treats acute manic episodes. Prevents recurrent episodes of mania and depression. Mechanism of action is unclear.

Lithium adverse effects

Nausea, diarrhea, confusion, muscle weakness, headache, polydipsia, polyuria, fine hand tremor. Long term use: renal toxicity, goiter, hypothyroidism

Lithium

Dosed multiple times per day. low therapeutic index; can be toxic. Advise patient to avoid dehydration (drink 2 to 3 L water daily)

Valproic Acid (VPA)

Mood stabilizer. Mechanism unknown. Used for acute manic episodes and for maintenance therapy. Higher therapeutic index than lithium. Faster onset than litium

Valproic acid adverse effects

Nausea, vomiting, diarrhea, indegestion, sedation, weight gain, headache, prolonged bleeding time, alopecia, hepatitis, thrombocytopenia

Carbamazepine

Mood stabilizer. Used for treatment in acute mania and maintenance therapy. Mechanism of action unknown

Carbamazepine adverse effects

Nausea, vomiting, diarrhea, anorexia, constipation, drowsiness, confusion, headache, dizziness, vertigo, blurred vision, slurred speech, vertigo, blood dyscrasias

Carbamazepine drug interactions

Induces P450 enzymes. Increases metabolism of other drugs. Increases its own metabolism. Interacts with drugs that inhibit P450 (increase concentration of carbamazepine. Grapefruit juice increases absorption

Antipsychotics and Bipolar

Used alone or in combination with mood stabilizer. Effective in treatment of acute manic episode and for maintenance therapy. Atypical preferred

Anxiety disorders

Norepinephrine, serotonin, dopamine, GABA

Generalized anxiety disorder (GAD)

Excessive/uncrontrollable worry. Symptoms persist for 6 months or more. Most patients develop another psychiatric disorder

Panic disorder

Recurrent, spontaneous panic attacks. Persistent concern about another panic attack, worry about consequences of another attack, or significant behavior change after panic attack

Social anxiety disorder (SAD)

Most common anxiety disorder. Intense but irrational fear of being negatively evaluated or scrutinized in a social interaction. Interferes with daily routine, work performance, or social interaction. Interferes with daily routine, work performance, or social life. Patients tend to avoid situations that will cause anxiety