300 Pharm Exam 1

Therapeutic Approach

Max benefit, minimum harm

Drug

Changes way the body works

The Big Three: Most Important Characteristics for Drugs

Efficacy - gives wanted response

Safety - potential to cause harm, especially in high doses

Selectivity - Elicits only the response for which it is given (limits side effects)

Prescriptions

Requires an order by a licensed health care provider

Black Box Warning

Serious Harmful Effect (Kind of like HA)

National Institute for Occupational Safety and Health (NIOSH)

Identifies which drugs are hazardous for handling

Chemotherapeutic agents

Can cause birth defects for nurses, Pregnancy and Lactation Labeling Rule (PLLR)

Classifications for drugs

Therapeutic Class - What is the drug used for

Pharmacologic Cues - How does this drug produce its effect

Prototype Drug - Model drug

Drug name

Chemical - Chemist, Generic - lowercase, first (FDA) Trade/Brand

Schedule I-V

I - Most potential harm, least potential medical use

V - Cough Syrup, Most potential medical use, least harm

Pharmacokinetics

What the body does to the drug

Half Life

Time to get 50% efficiency, 4-5 half-lives before the drug is out of the system

Cmax, Tmax, Duration of action, MTC, MEC

Cmax - Maximum concentration

Tmax - Time it took to reach the peak

Duration of action - Minimum effective concentration (MEC)

MTC - Minimum toxic concentration

Loading Dose

Take 2, and then one, takes it to the therapeutic range

Pharmacokinetics

Absorption, Distribution, Metabolism, Excretion

More likely to have adverse effects

Very young (not mature organs), very old, disease/illness, immunocompromised, chronic kidney or liver disease

IV push meds typically given

1-5 minutes *Minimum time for IV 60 seconds

Drug patient education

Name, Dose, Schedule, Route, Drug Interactions, Length, Storage, Expected therapeutic response 7 right

Absorption - Bioavailability & Prodrugs

Bioavailability reduction in oral meds

Prodrugs are inactive and then are metabolized by liver enzymes (metabolism)

Distribution - BBB

Blood-brain barrier, keeps toxic things out (lipid-soluble drugs can pass through)

Distribution - Proteins

Drugs need protein, uber, detach once reach target/produced effect

Ligand - medication that attaches

Metabolism 50% of meds are metabolized by the

CYP3A4 enzyme (drug-drug interactions)

Metabolism - CYP System Inducers

Increase the rate of drug metabolism; therefore, increase the dose

CRAP GPS

Carbamazepine

Rifampin

Alcohol (chronic)

Phenytoin

Griseofulvin

Phenobarbital

Sulphonylureas

Metabolism - CYP System Inhibitors

Decrease rate of drug metabolism

CRACK AMIGOS

Cimetidine

Ritonavir (protease inhibitor)

Amiodarone

Ciprofloxacin

Ketoconazole (and other azoles)

Acute alcohol use

Macrolides

Isoniazid

Grapfruit Juice

Omeprazole

Sulfonamides

Excretion

Kidneys, liver (lipophilic drugs)

Pharmacodynamics

What a drug/ligand/medicaiton does to the body

Ceiling effect

No more benefit if the dose is increased (morphine has no ceiling effect)

Drug (Ligand) interact with receptors (4 ways)

Agonists - binds to receptor to mimic biologic effect

Partial Agonist - binds to the receptor to potentiate biological effect, weak agonist

Inverse Agonist - Binds to same receptor, produces opposite biological response of an agonist

Antagonist - binds to the receptor and blocks the agonist from binding

1 kg = 2.2 pounds

1000 mcg = 1 mg

If a drug is Lipid Soluble that means it is:

Faster

Which one hits the therapeutic effect fastest

Elixier (Liquid) —> Capsule —> Tablet

First Pass Effect

A drug is taken by mouth (PO), absorbed from the GI tract, then goes to the liver first, where the liver metabolizes/breaks down some of the drug before it reaches the bloodstream.

Normal Saline (0.9%) NaCl & lactated Ringers (LR)

2 most common IV solutions; carrier/vehicle for medications or fluid replacement

Normal Electrolyte Values

Sodium (Na+): 135-145 mEq/L

Potassium (K+): 3.5-5.0 mEq/L Hyper or Hypo Kalemia (Cardiac dysrthythmias)

Calcium (Ca2+): 8-11 mg/dL

Peripheral Nervous System (PNS)

CNS signals to the body

Autonomic Nervous System

Involuntary responses influencing organs, glands, and smooth muscles

Sympathetic Division

“Fight of flight” Adrenergic Receptors, Alpha and Beta 

Parasympathetic Division

“Rest and digest" Cholinergic Receptors, Muscarinic

Parasympathetic vs. Sympathetic

Constricts pupil (Miosis) Stimulates salvation  Slows heart Constricts bronchioles Stimulates digestion  Stimulating gallbladder function Contracts bladder Erection and lubrication  Cranial and Sacral nerves

Dilates pupil (mydriasis) Inhibits salvation  Accelerated heart rate Dilates bronchioles Inhibits digestion  Stimulates release of glucose Secretes epinephrine and norepinephrine (Peripheral vasoconstriction) Relax bladder Stimulates ejaculation and orgasm Thoracic Nerves

Cholinergic Drugs - Parasympathetomimets, Muscarinic Agonists (Increased Parasympathetic)

Prototype: Bethanechole 

Indications: Urinary Retention, Dry Mouth

Method of Action: Binds to muscarinic receptors for Parasympathetic “Rest and Digest” effects

Adverse Effects: (Too much Rest and Digest) Hypotension, Bradycardia, Cramping, Diarrhea, Asthma, Exacerbation 

Muscarinic Excess: Urination, Miosis, Bronchospasms, Emesis, Lacrimation 

Contraindications: Urinary or GI obstruction, BPH, PUD (Peptic ulcers), asthma, Hypotension

Antidote: Atropine 

Cholinergic Drugs - Cholinergic Inhibitors (Block effects) (Increased Parasympathetic)

Protype: Neostigmine, Physostigmine

Indications: Myasthenia Gravis, Alzheimer's Disease, Glaucoma, Postop reversal of neuromuscular blockade, or antidote for anticholinergic excess 

Method of Action: Prevents Cholinesterase from inactivating Acetylcholine which increases its availability for Parasympathetic effects

Adverse Effects: Neuromuscular blockade (Too much Parasympathetic)

Contraindications: Urinary or GI obstruction, BPH, Peptic Ulcer, Hypotension 

Anti-Cholinergic Drugs - Muscarinic Antagonists (Increased Sympathetic) 

Prototypical drugs: Atropine, Glycopyrrolate (pre-anesthesia), Scopolamine (motion sickness) 

Indications: Overactive Bladder, Pre-anesthesia, Bradycardia, eye disorders, Muscarinic Excess Antidote 

Method of Action: Inhibits acetylcholine from binding to muscarinic receptors 

Adverse Effects (ABCDS): Agitation, blurry vision, constipation/confusion, dry mouth, stasis of urine/sweat, too much sympathetic 

Contraindications: Glaucoma, Myasthenia Gravis, GI obstruction/urinary retention, BPH, Tachycardia

Alpha 1 - Blood Vessels and Eyes

Promoting: Vasoconstriction (Tightening a blood vessel), Increase BP, Mydriasis (pupil dilation) (Increase sympathetic)

Indication: Add to local anesthesia, nasal decongestion, hemostasis, hypotensive shock 

Adverse Effects, hypertension, necrosis, bradycardia 

Alpha 2 - Brain/CNS

Promoting: Decrease Sympathetic Outflow, Decrease BP by vasodilation

Prototype: Clonidine

Indications: Hypertension, ADHD, pain relief

Adverse Effects: drowsiness, xerostomia (dry mouth), rebound Hypertension

Beta 1 - Heart

Promoting: Increased Heart Rate, contractility, conductivity

Indication: Heart failure, shock, AV block, cardiac arrest 

Adverse Effects: Tachycardia, angina (chest pain), dysrhythmias 

Beta 2 - Lungs and Uterus 

Promoting: Bronchodilation, Uterus smooth muscle relaxation, Glycogenolysis (increase blood sugar) 

Indication: Bronchospasm and some asthma, delays preterm labor

Adverse effects: Hyperglycemia, tremors

Dopamin - Kidney 

Promoting: Dilates vasculature, increase renal perfusion (during shock, decreases risk of renal failure), Enhances cardia performance, activates B1 receptors

Adrenergic Agonists - Sympathonitis (Help Fight or Flight)

Prototype: 

Noncatecholamines: Albuterol, Ephedrine (orally, longer half life, cross BBB)

Catecholamines: Natural Epinephrine, Norepinephrine, Dopamin Synthetic Isoproterenol, Dobutamin (Can’t take orally, short action, can’t cross BBB)

Indications

Epi-pen: Bronchospasms, asthmatic attack, anaphylaxis, local and intraspinal anesthetic, topical bleeding control

Norepi: Restores BP

Dopamine: Shock syndrome, acute renal failure, cirrhosis, barbiturate intoxication, low doses increase blood flow, high doses stimulates beta receptors 

Method of Action: Binds to receptors for Sympathetic effects, Indirectly causes Noeprieprine to stay in synaptic cleft (Restore BP) 

Considerations: protect from light, shake, inject slowly 

Antidote for extravasation: Phentolamine

Adrenergic Antagonists - Alpha 

Prototype: Alpha 1 (selective) blockers - Prazosin

Indication: Hypertension, reverse of alpha 1 agonist overdose, replaces smooth muscles in bladder, neck, and prostate 

Prototype: Nonselective alpha blocker - Phentolamin 

Indication: NE extravasation, tissue death, pheochromocytoma (adrenal gland tumor causing too much catecholamine secretion) 

Method of Action: Directly blocks Alpha receptors (selectively or nonselective)

Adverse Effects: Prazosin Orthostatic hypotension, reflex tachycardia, nasal congestion, inhibits ejaculation

Adrenergic Antagonist - Beta

Prototype:

Non-selective beta blocker (First gen) - Propranolol

Selective Beta Blocker (second gen) - Metoprolol

Method of Action: Directly blocks beta receptors (selective or nonselective) to decrease HR

Adverse Effects 

Beta 1: bradycardia, decreased Cardiac output, heart failure, AV heart block, rebound Excitation 

Beta 2: Bronchoconstriction, inhibitions of glycogenolysis (low Blood glucose/sugar)

Indications: HYT, Angina, MI, Cardiac Dysrhythmias, Migraine, Stage Fright, Pheochromocytoma, Glaucoma

Potassium 

Normal K+: 3.5-5.0 mEq/L (Impact heart)

Hypokalemia - S/S: Nausea, fatigue, leg cramps, weakness, cardiac Dysrhythmias, narrow QRS, flat T waves

Hyperkalemia - S/S: Cardiac dysrhythmias, prolonged PR, wide QRS, tented T wave, depressed ST

Infuse it slowly <10 mEq/hr and it has to be diluted in> 10 mL of fluid

Acid Base 

Normal: 7.35-7.45 

Acidosis <7.35 Hydrogen H+ 

Respiratory: Hypoventilation (too much CO2 in lungs), Metabolic: Diarrhea (out the acidosis), kidney failure (can’t pee off H+), excess alcohol

Treatment: Sodium Bicarbonate

Monitor: Sleepiness, dizziness, headache, seizure, hypoventilation

Alkalosis >7.45 Bicarbonate HCO3- 

Respiratory: Hyperventilation (too much CO2 breathed out), Metabolic: Constipation (hold on to bicarb), vomiting (all the acid out), lower potassium 

Treatment mild: Potassium Chloride and sodium chloride severe: ammonium chloride

Monitor: Pallor, sweating, irregular breathing, bradycardia

Diuretics - Excretion of excess fluid

Indication: Hypertension, Heart failure, kidney failure, liver failure, pulmonary edema

Adverse Effects: Dehydration, hypotension, electrolyte imbalance

Contraindications: Severe renal disease, fluid and electrolyte imbalance

Method of Action: Increase urine flow rate (block Na+ reabsorption in the kidney pephron - water stays with Na+ and gets excreted)

Consider: give med early in the day, decrease dose with BP meds, diet adjustments 

Monitor: Electrolytes, weight, BP, I&O

Loop Diuretics

Prototype: Furosemid (furious) 

Indications: Pulmonary edema from Heart failure, when other diuretics don’t work

Method of Action: Blocks Na+ reabsorption in loop of Henle, water stays with the sodium and gets excreted

Adverse Effects: Hypotension, Ototoxicity (ears), hypokalemia

Consider: High K+ foods, monitor tinnitus (from ototoxicity)

Thiazide Diuretics

Prototype: Hydrochlorothiazide 

Indication: first choice for Hypertension, mild edema 

Method of Action: Blocks Na+ reabsorption 

Adverse Effects: dehydration, hyponatremia, hypochloremia, hypokalemia, hyperglycemia (high sugar) 

Contraindications: Pregnancy and breastfeedings (cross placenta and breastmilk)

Potassium Sparing Diuretics

Prototype: Spironolactone

Indications: Heart failure, acne, combined with other diuretics for K+ sparing effects 

Method of action: blocks aldosterone → K+ is retained, Na+water are excreted

Adverse Effects: Hyperkalemia, endocrine effects 

Contraindications: K+ supplementation, other RAAS meds

Consider: low K+ foods

Osmotic Diuretics 

Prototype: Mannitol

Indications: prevent kidney failure from hypovolemic shock and hypotension, elevated intracranial pressure, and intraocular pressure) 

Method of action: Reduces pressure by raising serum osmolarity (draws fluid back into the vascular space) 

Adverse Effects: Heart failure, pulmonary edema, rebound ICP, metabolic acidosis 

Potassium rich foods

Nuts, avocado, banana, potato, dried fruit, oranges, grapefruit

Bethanechol

Pee (para), take atropine if toxicity

Neostigmine/Physostigmine

Myasthenia gravis / Alzheimer’s / glaucoma (para).

Atropine/Glycopyrrolate/Scopolamine

Overactive bladder / bradycardia / preanesthesia / motion sickness (symp).

Albuterol/Ephedrine

Ephedrine - Longer ½-life, crosses BBB

EpiPen / BP / shock / renal failure (symp).

β-blockers

1st gen: propranolol; 2nd gen: metoprolol; decrease heart rate.

α₁-blocker, α-blocker (nonselective)

α₁-blocker – Prazosin

α-blocker (nonselective) – Phentolamine

Acid base balance and solution

7.35 and 7.45

Acidosis - give sodium bicarbonate

Alkalosis - potassium and sodium chloride

Anti Hypertension Drugs, Lifestyle Modifications, & Equations

Diuretics, beta-blockers, Calcium blockers

Sodium < 1500 mg, DASH diet, Physical activity, healthy weight

BP = CO x SVR

CO = HR x SV - know this formula

Preload vs. Afterload

Preload - Stretch of ventricular muscle fibers (Ventricular filling)

After load - Force the heart must work against to pump blood out of ventricles

Veins dilated = preload will decrease

After load dilation of arterioles = decrease in afterload

High Blood Pressure Compensation

Cardiovascular System (Faster)

Kidneys - Increase urine output

Norepinephrine and Renin cause vasoconstriction → Increase BP

Diuretic Agents

Loop Diuretic: Furosemide used for heart failure

Thiazide diuretics: Hydrochlorothiazide by Blocks electrolytes

Potassium sparing diuretics: Spironolactone, retains potassium

Osmotic: Mannitol, treats swelling of brain

Carbonic anhydrase inhibitors: Altude Sickness

RAAS System

Kidney’s way to rescue low blood pressure

Release Renin → Angiotensin II (vasoconstriction; increases BP), Release Aldosterone Kidneys keep salt and water (increases BP)

ACE inhibitors

“ACE hardware” PRIcked my face and made it swell

Acts on the RAAS System

Prototype: Captopril “-pril”

Converts Angiotensin I to Angiotensin II (Angiotensin-Converting Enzyme [ACE)

Inhibits Angiotensin II, lowers vasoconstriction, lowers BP

& increases bradykinin, more vasodilation, lower BP

↓ Angiotensin II + ↑ Bradykinin = ↓ BP

Face swelling - Angioedema from bradykinin

If ACE inhibitors don’t work → ARBs

ARBs = Angiotensin II REceptor Blockers

Prototype: Losartan “-sartan”

Block the action of Angiotensin II; blood vessels relax, lowering BP

ACE inhibitors (-pril): ↓ production of Angiotensin II

ARBs (-sartan): block the action of Angiotensin II

*No coughing, hyperkalemia, or Renal Failure

“Pirates say “ARB” when they get hooked in the kidneys, can’t get pregnant, and harded to say when face swells.”

Direct Renin Inhibitors

Prototype: Aliskiren

Renin starts the RAAS

Blocks Renin, lowers BP

• ACE’s and ARBs are safer, with less risk

“Alice and Kiren walk in the “Rainin”; Alice can’t get pregnant

Aldosterone Antagonists or blockers

Prototype: Spironolactone and Eplerenone “-one”

“One” adverse effect is hyperkalemia

Potassium-sparing diuretic; blocks Aldosterone

Aldosterone tells the kidneys to retain Na+ and water and get rid of K+. Aldosterone Antagonists do: lower Na+ and water and lower BP

Used for Hypertension, Heart failure

Adverse effects: hyperkalemia

Beta Blockers

Slow the heart rate

Prototype: Propranolol (1st Gen), metoprolol (2nd Gen) “olol”

Sympathetic and adrenergic blockers, Block B-adrenergic receptors,

B1 = Heart; blocking B1 causes decreased heart rate and BP

Beta blockers can cause hypoglycemia (no diabetes)

B2 = lungs; blocking B2 causes bronchoconstriction (no asthma), breathing more difficult, important with nonselective beta blockers

• Propanolol - 1st gen nonselective

• Metoprolol - 2nd Generations, blocks B1

Beta Fish is ugly LOL

Selectivity

How specifically the drug targets its receptor

Calcium Channel Blockers

Block Calcium entry, decrease muscle contraction, cause vasodilation and decrease BP

Two Types:

1) Dihydropyridines “-dipine”

Target blood vessels, Block Ca²⁺ entry into vascular smooth muscle, Vasodilation, lower BP

2) Non-Dihydropyridines (Verapamil: constipation; Diltiazem)

Targets Heart and Blood vessels, blocking calcium entry in the heart; lowers AV node/force of contraction; vasodilation; decreases BP

Adverse Effects: Gingival Hyperplasia

Warning with Verapamil + Digoxin

Verapamil can increase digoxin levels, increasing the risk of digoxin toxicity, “Dr. Summer’s loves Digoxin” Verapamil increases Digoxin levels by 60% → Increases risk for AV block

Vasodilators

Hydralazine - arterial vasodilator (may cause orthostatic hypotension)

Minoxidil - Arterial vasodilator; can cause hair growth

Sodium Nitroprusside - vasodilator of both arteries and veins (Emergencies only; organ damage and rapid BP reduction is needed)

Use if >180/>120, end-organ damage (Dilates arterioles)

Difference between Primary and Secondary Hypertension

Primary: No single identifiable cause

Secondary: Has an identifiable underlying cause

Alpha-1 Adrenergic Blockers

Prototype: Prazosin “-osin” (Blood vessels)

Relaxes smooth muscle, lowers BP; also relaxes urinary and ureteral, BPH muscles (helps kidney stones pass)

Alpha-2 Agonists

Prototype: Clonidine (Don’t abruptly stop, rebound Hypertension)

This one may be tricky; agonist = stimulates

Alpha-2 (Brain)

Brainstem and CNS, reducing sympathetic activity; lowers HR and BP

Atherosclerosis

Atherosclerosis = buildup of fatty/cholesterol plaque inside artery walls (Coronary arteries = heart)

Lipoproteins:

VLDL - triglycerides

LDL - Bad cholesterol, contributes to atherosclerotic plaque

HDL - good cholesterol, protection against atherosclerosis

TLC - Therapeutic Lifestyle Changes, to lower cardiovascular risk and cholesterol (Heart-healthy diet, physical activity, avoid smoking)

HMG-CoA Reductase Inhibitors

“-statin”

The primary/most effective medication class for lowering LDL cholesterol: blocks HMG-CoA reductase in the liver, increases LDL receptors, more LDL from the blood

Liver damage

Taken at bedtime, with dinner; the liver makes more cholesterol at night

Renin-Angiotensin-Aldosterone System (RAAS)

Kidneys → Renin

Renin converts angiotensinogen (from the liver) to Angiotensin I → Angiotensin II (in the lungs)

Angiotensin II causes vasoconstriction and stimulates Aldosterone release from the adrenal glands

Aldosterone causes Na+ and water reabsorption to increase BP