Quiz 3 Flashcards
Understand the difference between blood pressure and cardiac output
Cardiac output (known as ‘Q’) is a measure of the amount of blood that is pumped out of the heart in one minute.
Blood pressure (BP) is a measure of the force being exerted on the walls of arteries as blood is pumped out of the heart.
Outline briefly the mechanism of control of blood pressure
Increasing sympathetic activity will cause decrease in BP.
How?
-Activation of B1 adrenoreceptors on the heart (cause increase in Cardiac O)
-Activation of A1 adrenoreceptors on smooth muscle (increased Venous return)
-Activation of B1 adrenoreceptors on the kidney (increases peripheral resistance)
- decreased Renal blood flow (increases Renin which increases Angiotensin 2 and aldosterone)
- decreased glomerular filtration rate, thus increased Sodium, water retention thus increased Blood volume.
All increase Blood pressure
Give a detailed account of the compensatory physiological response to CHF
- retaining salt and water to increase fluid in blood stream
- increase HR
- Increase H size
List the classes of vasodilator treatments used for CHF?
What are vasodilators purpose?
reduce load on myocardium.
- Direct smooth muscle relaxants
- ACE inhibitor
List with examples the direct smooth muscle relaxants used as vasodilators in CHF
MOA
adverse effects
Direct acting Vasodilators:
1. Hydralazine: MOA: Smooth muscle hyperpolarization through opening of K+ channels. Stimulates formation of nitric oxide leading to cGMP-mediated vasodilation. Also causes reflex increase in CO and HR, so must use with B blocker and diuretic.
Adverse effects: Headache, nausea, sweating, arrhythmia, angina
- Minoxidil:
MOA: causes direct vasodilation of resistance arterioles. Treatment of sever to malignant hypertension which is refractory to other drugs. Reflex tachycardia can be sever thus must be co-scribed with diuretic + B blocker.
Adverse reactions: water and sodium retention, oedema, hypertrichosis (body + hair growth) - Sodium Nitroprusside:
MOA: its metabolized to NO in smooth muscel cells. Used for hypertensive emergency. Non selective and rapidly metabolized.
Adverse reactions: reflex tachycardia, cyanide toxicity.
Give a detailed account of the mechanisms by which ACE inhibitors act in CHF
ACE Inhibitors:
Anything ending in Pril is an ACE inhibitor
Actions: decrease levels of vasoconstrictors (angiotensin 2, aldosterone), increase levels of vasodilators (bradykinin)
Therapeutics: used as an antihypertensive in patients with concominant disease (diabetes, congestive HF, hyperlipidemia)
Contraindications: (K+ supplements, spironolactone). K+ levels must be monitored
Adverse effects: Dry cough, skin rash, hyperkalemia, hypotension, fever
Example: Captopril, Enalapril, Lisinopril
List the major effects of angiotensin 2 in the body
- increases release of Aldosterone which acts to increase Sodium and water retention
2. It increases peripheral resistance
List with examples ACE inhibitors used as vasodilators in CHF
Captopril. Enalapril, Fosinopril, Lisinopril, Quinapril
List the routes of drug administration, giving advantages and disadvantages of each route
o Enteral
• Oral
• Most common way to administer a drug
• Most variable
• Requires the most complicated pathway to the tissues
• Drug is usually absorbed in the upper GI tract and passes into the portal venous system where it can undergo first-pass metabolism
• Other routes should be considered if:
o The drug is unstable or is rapidly inactivated in the GI tract (eg. Insulin)
o There is a loss of drug absorbance via the GI tract of inability for sufficient drug to reach its target through first-pass metabolism in the liver, vomiting or disease state
o Therapeutic effects demand local administration and systemic absorption would lead to adverse drug effects
• Sublingual
• Placement under tongue allows for drug to diffuse into the capillary network, avoiding first-pass liver metabolism and directly entering the systemic circulation
• Rectal
• Limited portal blood flow means exposure of the drug to first-pass metabolism is than with the oral route
• This route is useful if the drug induces vomiting when given orally or if the patient is already: vomiting
o Parenteral:
• Used mainly:
• For drugs that are poorly absorbed from the GI tract
• For drugs that are unstable in the GI tract
• In treatment of unconscious patients
• In treatment where rapid onset of action is required
• Provides most control over actual dose delivered
• Intravascular (IV)
• Most common parenteral route
• Avoids first-pass and is used for drugs that cannot be administered orally
• Intramuscular (IM)
• Subcutaneous (SC)
• Both require absorption of drug into the tissue
o Doesn’t go into the blood
• Use of carrier vehicles (such as peanut oil) allows for control of delivery
o Other
• Inhalation
• Allows for rapid delivery of drug across a large surface area
• Used for drugs that are gases or aerosols
• Intranasal
• Cocaine is generally taken by sniffing
• Intrathecal / Intraventricular
• Introduction of drugs directly into cerebral spinal fluid
• Topical
• Used when a local effect of the drug is required
• Transdermal
• This administration route achieves systemic effect by application of drugs to skin via a transdermal patch
• Used when sustained delivery is needed
Understand The importance of the enteroheptic circulation and first pass drug metabolism
s
describe the chemical and physiological factors that can influence drug absorption
o Chemical properties: • Chemical nature • Molecular weight • Solubility • Partition Coefficient
o Physiological variables: • Gastric motility • pH at absorption site • Area of absorbing surface • Mesenteric blood flow • Presystemic elimination • Ingestion with/without food o In general, most drugs presently used: • Are small organic molecules • Have molecular weights under 1000 • Diffuse through biological membranes in their uncharged form • Exist as either weak acids or bases
Outline what is meant by bioavailability
- Is the fraction of administered drug that reaches the systemic circulation
- Expressed at the fraction of administered drug that gains access to the systemic circulation in a chemically unaltered form
- Is determined by comparing plasma levels of a drug by a particular route of administration (e.g. oral) with plasma levels achieved by IV administration (which must be 100%)
- Plotting plasma concentrations of drugs given by both routes against time then the area under the curve (AUC) gives an indication of the extent of absorption
- Bioavailability of a drug administered orally is the ratio of the area calculated for oral administration compared with the area calculated for IV injection
- If 100mg of a drug is administered orally and 70 mg is absorbed unchanged, the bioavailability is 70%
o The higher the AUC, the better it has been absorbed
o F = (AUC) oral / (AUC) intravenous
Describe factors that influence bioavailability
s
Describe the determinants of drug distribution within the body
- Vd = total amount of drug in the body / Plasma drug concentration
o If the drug is avidly bound to peripheral tissues, its plasma concentration will drop to very low values though the total amount in the body is very large, thus a Vd might exceed the total volume of the body
Understand the concept of volume of distribution
- Volume of distribution (Vd) is a hypothetical volume of fluid into which the drug can be disseminated
- Vd relates the amount of drug in the body to the concentration in plasma
