NR 565 Pharmacology Week 1 complete verified solutions with 100% accurate solutions

Pharmacokinetics

The study of drug absorption, distribution, metabolism, and excretion in the body

"What the body does to the drug"

Factors that affect drug absorption (5)

Rate of dissolution

Surface area

Blood flow

Lipid solubility

PH partitioning

Factors that affect drug distribution (4)

Blood flow to tissues

Ability to exit vascular system

Blood-brain barrier

Protein-binding capacity

Pharmacodynamics

The study of biochemical and physiologic effects of drugs on the body and the molecular mechanisms by which those effects are produced

"What the body does to the drug"

Phamacodynamics: 3 mechanisms of action

Receptor

Enzyme

Non-selective interactions (i.e. chemo)

Types of drug therapy (7)

Acute

Maintenance (HTN/bc)

Supplemental (insulin)

Palliative

Supportive (IV fluid)

Prophylactic

Empirical (broad-spectrum abx)

Idiosyncratic Effect

Unexpected response to medication

Tolerance

Declining response to a drug

Dependence

Physiological/psychological need for a drug; needs drug for normal function

Addiction

Compulsive use of a drug despite negative/dangerous effects

Drug interactions: drug-drug

When 2 drugs compete for metabolizing enzymes

Drug interactions: food-drug

Grapefruit juice or leafy greens

Drug interactions: additive

1+1 = 2; both provide intended effect

Drug interactions: antagonistic

1+1 = <2; less than desired effect of one or both drugs

Drug interactions: synergistic

1+1 = >2; sum total effect is greater than if given alone (i.e. lisinopril + HCTZ)

Drug interactions: incompatibility

1+1 does not equal 2; two IV drugs given together causing decomposition of one or both drugs

8 rights of medication administration

Patient

Medication

Dose

Route

Time

Reason

Response

Documentation

Adverse reactions: pharmacologic

Extension of a drug's normal effect

Adverse reactions: Allergic/hypersensitivity

Exaggerated immune response (i.e. mild itching to anaphylaxis)

Adverse reactions: idiosyncratic

Peculiar to the patient

Adverse reactions: drug reaction

Most complex, difficult to determine

Teratogenic effects

Causes birth defects

Mutagenic effects

Able to cause changes in genetic tissue

Carcinogen

Substances that can cause cancer

Toxicology

The study of adverse effects of chemicals and their compounds on living organisms and tissues

4 components of pharmacokinetics

Absorption, distribution, metabolism, excretion

Onset of action

The time it takes for medication to take effect

Time to peak effect

Time before medication is at height of effect

Duration of action

How long therapeutic effect lasts

Half-life

Time required for half of a chemical to be eliminated

Steady state

Amount of drug going in = amount of drug going out

Peak

Highest level of the drug achieved

Trough

The level of a drug concentration immediately before next dose

Duration

Length of time drug remains active; measured from therapeutic level to when elimination decreases level below therapeutic range

Absorption

The movement into the bloodstream for distribution

Bioavailability

The extent to which a medication can be absorbed

Absorption: enteral

GI tract > bloodstream > liver = 1st pass effect

Causes of decreased enteral absorption

Bariatric surgery (decreased surface area)

Vigorous activity (blood shunted away from GI tract)

Age (decreased motility)

Parenteral medications

No 1st pass effect; 100% available as they enter the bloodstream

Topical medication administration sites

Skin, eyes, ears, nose, rectum, vagina

Purpose of topical medication application

Intended for action at the site of application

Transdermal medications: intention

Internal effect

Transdermal medications: absorption

Carried through skin to bloodstream; no 1st pass effect

Transdermal medications: sites

Rotate sites to prevent irritation

Trunk or upper extremities with good circulation

Avoid scar tissue due to decreased absorption

Inhaled medications

Intented for lungs and/or other areas of the body

Distribution: transport

Most rapid in areas with high blood flow (major organs)

Slower to fat, skin, and muscles (increased by physical activity)

Distribution: elimination

Occurs primarily in the liver and kidneys

Watch for renal/liver toxicity

Distribution: decreased albumin

Can increase risk of toxicity in burns, starvation, negative nitrogen balance

Metabolism

When a substance is irreversibly transformed into metabolites

Excretion

Elimination of a substance from the body

Agonist

A drug that binds to and activates a receptor

Agonist: full

High efficacy, full response

Agonist: partial

Lower efficacy, sub-maximal activation when occupying all receptors

Agonist: inverse

Produces opposite effect yet binds to the same receptors as agonist

Silent antagonist

Neutral antagonist

Attenuates/weakens effects of agonists/inverse agonists

Produces functional reduction in signal transduction

No intrinsic activity itself

Antagonist

Attenuates/weakens effects of an agonist

Antagonist: competitive

Binds to same receptors without activation, blocking action of agonist

Antagonist: non-competitive

Binds to allosteric (non-agonist) receptor site to prevent activation

Antagonist: reversible

Binds non-covalently; can be washed out

Antagonist: irreversible

Binds covalently; cannot be displaced by competing ligands or washing

Efficacy

How agonists vary in produced response when occupying the same number of receptors

High efficacy

Maximum response, occupying low number of receptors

Low efficacy

Cannot produce maximum response, occupies more receptors

Therapeutic window

Amount of medication that gives desired effect vs amount that produces more adverse than desired effects

B Max

Maximum amount of drug/radioligand that can bind specifically to receptors in a membrane preparation

Used to measure density of receptor site

Potency

Concentration of a drug at which it is effective

Mechanism of Action (MOA)

Specific biochemical interaction through which a drug produces a pharmacological effect

Desensitization

Reduction in response to an agonist while continuously present at receptor

Progressive decrease in response to repeated exposure

Xenobiotics

Substances that are foreign to the body

Synthetic chemical compounds

Medications

All can potentially adversely affect the body

*Occasionally can be transformed into toxic metabolite

Cytochrome P450 (CYP450)

Xenobioitic-metabolizing enzymes

Necessary for the production of cholesterol and steroids

Role of CYP450

Detoxification of chemicals

Drug metabolism

CYP450: cyto

Binds to cell membrane

CYP450: chrome + p

Contains heme pigment

CYP450: 450 mm

Absorbs light at 450 mm wavelength when exposed to carbon monoxide (CO)

CYP450 system is thought to be ___

Major system of enzymes responsible for phase 1 metabolism

3 possible outcomes of phase 1 metabolism

Oxidized (most common)

Reduced

Hydrolyzed

Oxidation

Drug becomes completely inactive

Reduction

Drug becomes partially inactive; one or more metabolites remain active

Hydrolization

Original drug is not pharmacologically active; one metabolite remains active

Alteration in CYP450 metabolism causes ___

Medication interactions

Substrate

Xenobiotics that require the metabolic process of the body to activate or de-activate the substance

Understanding substrates, inhibitors, and induces is crucial when prescribing ___

Medications for seizures, depression, and psychosis

Inhibitors

Medications that inhibit metabolic activity of one or more CYP450 enzymes

Slows/blocks enzyme's metabolic activity that other medications are dependent on

Dangers of inhibitors

Can cause increased levels of other meds, prolonged pharmacological effect, and potential toxicity

Inhibitors: VISA CK GQ

Valproate

Isoniazid

Sulfonamides

Amiodarone

Chloramphenicol

Ketoconazole

Grapefruit

Quinidine

Inducers

Xenobiotics (medications and environmental agents) that elevate CYP450 enzyme activity by increasing enzyme synthesis

Additional sites for biotransformation = increased medication metabolism

Rifampin

Inducer with short half-life

Phenobarbital

Inducer with long half-life

Carbamazepine

Potent inducer; metabolized by the same CYP450 enzyme it induces

Start at low dose, increase weekly due to steady decrease in half-life over time

Inducers: CRAP GPS

Carbamazepine

Rifampin

Alcohol

Phenytoin

Griseofulvin

Phenobarbital

Sulfonylureas

Prescribing medications during pregnancy/breastfeeding

Physiological changes to the body can change pharmacodynamic/pharmacokinetic properties of drugs

Changes in pregnancy: kidneys

increased GFR = increased drug excretion

Changes in pregnancy: liver

Increased hepatic metabolism of some drugs

Changes in pregnancy: bowel

Decreased tone and mobility

Increased drug absorption

Teratogenesis (prenatal toxicity)

Structural or functional birth defects

Intrauterine growth retardation

Fetal death

Teratogens

Antiepileptic drugs

Tetracyclines

Fluoroquinolones

Vitamin A in large doses (accutane)

Anticoagulants

Hormones (diesthylstilbestrol)

Alcohol

Cocaine

Infant/pediatric prescribing

Infants/peds don't process medications the same as adults

Dosage is based on weight or body surface area

Infant/pediatric prescribing: IM

Neonates: slow and erratic due to decreased blood flow in muscles

Infancy: increased absorption due to increased blood flow

Infant/pediatric prescribing: Transdermal

Thin skin = increased blood flow

Increased absorption

Increased risk of toxicity from topical drugs

Infant/pediatric prescribing: oral administration

Decreased gastric emptying

Increased absorption for stomach-absorbing drugs

Decreased absorption for intestine-absorbing drugs

Decreased gastric acidity for 24 hours after birth

Increased absorption of acid-labile drugs