Introduction: Drug Action/dosage Regimen (Cram)

Why might some exotics need less sedative than expected?

Many exotics are nocturnal, they often don't need that much sedative to become sedate during the day

What are the six factors that modify drug action and dosage regimen?

Remember: STRIP Down

1. Speceis variation

2. Timing of administration

3. Route of administration

4. Individual variation

5. Pathological conditions

6. Drug augmentation

What requires a lower dose of medication to have a greater response: IV or SQ route?

IV, because a larger amount of the drug will be in the plasma at one time

Fill in the blank: Lidocaine if administered SQ acts as a ______ anesthetic, while administering it IV it affects the ______ [organ].

local, heart (it can be used to treat ventricular tachycardia)

Fill in the blank: ____ depressant drugs are more potent at night while ______ produce greater effects during the day.

CNS, stimulants

What two factors vary greatly with the season of the year, or with the animal's intrinsic biological clock?

1. Hormone levels
2. Metabolic activity

What are some examples of individual varition?

Weight, age, sex, temperament, and biochemical individuality (inherited), idiosyncrasy, drug hypersensitivity, hyperreactive, hyporeactive, tolerance (resistance)

Fill in the blank: Difference in response to a drug may be ______ (degree of) or ______ (nature of).

quantitative, qualitative

What are the three mechanisms that may result in tolerance

1. Cells may increase biotransformation of drug
2. Cells may adapt
3. Increased excretion or decreased absorption of drug

Why might a cat with kidney disease need a different dose of a drug than a healthy cat?

If the kidney disease is effecting excretion, the drug dosage will need to change to reflect this

Explain this graft

This represents drug augmentation, due to cumulative dosing. In A, the first dose of the medication is not totally cleared from the plasma before the next dose is introduced. If this continues, it can lead to a toxic dose. B is what we want

Name some of the possible methods of drug interactions

Increasing absorption of each other, receptor interference, increase or reduce biotransformation of another, interfere with excretion, chemical reaction in body, and bind with one another (making inactive)

The movement of drugs in the body after they are absorbed into the blood stream

Drug distribution

Fill in the blank: Drugs move across ______ and in and out of tissues and cells in response to a _______ _______.

membranes, concentration gradient

What are the three things that the distibution of a drug from plasma into different tissues depends upon?

1. Lipid solubility (the greater the lipid solubility, the greater the tendency to move into tissues)
2. Non–ionized drugs move into the tissues more readily
3. Affinity of the tissues for the drug

What are the three storage areas for drugs in the body?

1. Plasma proteins (usually albumin)
2. Other (fat, liver, kidney, bone, muscle, etc.)
3. Cell storage (bound to proteins in the cell)

What is the "active drug", the amount bound to plasma proteins, or the amount that is not bound and can enter tissues?

The active drug is the amount that is not bound and can enter tissues

What is the most important factor affecting drug distribution?

Binding of the drug to plasma proteins

Fill in the blank: There is usually a _______ _______ between bound and free drug in the plasma. This means that when free drug leaves the plasma, some bound drug is released to restore the balance in the blood.

dynamic equilibrium

A patient has hypoproteinemia, should it be given a larger or smaller dose of a drug (especially a drug that tends to bind to plasma well)?

Smaller dose. The binding of all the protein availible in their blood will mean dynamic equilibrium is impossible to maintain. An overdose is very possible

Give two example of specialized barriers in the body

1. Blood–brain barrier
2. Placental barrier

What type of cells form the blood–brain barrier? They surround the capillaries of the brain

Glial cells

Fill in the blank: The glial cells typically only allow _____- soluble, very small non-______ molecules. And very small ______, _______-soluble molecules to pass through.

lipid, ionized, ionized, water

Which dog breed is known to have a more permeable blood brain barrier?

Border collie

True or false: Drugs tend to pass more readily into the brain of neonates

True. The barrier is more permeable in neonates, making the toxic effects greater

Do highly ionized or non–ionized compounds generally penetrate the blood brain barrier more readily?

Non–ionized compounds penetrate more readily

True or false: Traumatic injury, inflammation, and allergic reactions all increase the permeability of the CNS membranes

True

A patient under anesthesia is experiencing respiratory depression, some hypoxia, and a severe drop in blood pressure. How will this affect the blood brain barrier?

It will make it more permeable, which will further depress the respiratory centre, initiating a life–threatening vicious cycle

Fill in the blank: ____-_______, highly _______-soluble compounds move very rapidly into fetal circulation from the mother's blood. These compounds should NOT be used on a pregnant female without considering fetal harm.

Non, ionized, lipid

True or false: Fetal blood concentrion of a drug will never reach the same concentration as maternal blood concentration

False. Fetal blood concentration can become even HIGHER than maternal blood concentration

The phenomenon of the final distribution of drugs in the body not being the same as the initial distribution

Redistribution

Example: The effects of barbiturates are short acting because they are redistributed from the brain to the fat tissues

Any chemical alteration of the drug molecule by the cells of the animal

Biotransformation

Note: Also called drug metabolism

Drugs must be lipid–soluble and non–ionized in order to move across membranes to reach the sites where they'll be active. Can they be excreted in this form?

No. The kidneys will just reabsorb them back into the bloodstream. They need to be converted into a different form

End products of biotransformation

Metabolites

Note: These are more water–soluble and ionized than the drug, they can be excreted in urine and bile

What are the four qualities of metabolites that make them easier to excrete?

1. More ionized
2. Less able to bind to plasma protein or cellular protein
3. Less likely to store in tissues such as fat, muscle, and kidney
4. Less able to pass through membranes

Are metabolites usually more or less active than the original drug?

Usually they are less active, but sometimes they are more active

Principle site of biotransformation in the body

Liver

Which organelle in heptaocytes is responsible for metabolizing drugs?

Smooth endoplasmic reticulum

Name some other tissues that are biotransformation sites in the body

Nervous system, kidney, small intestine, and plasma

If a drug is administered PO or IP and is absorbed first by the intestine, does it still go to the liver?

Yes, it will travel through the circulation directly to the liver and may be metabolized and/or inactivated before even entering sysmic circulation (ie. first pass metabolism)

What are the four types of reactions involved in drug metabolism? Star which 3 types of reaction may increase OR decrease a drug's activity

1. Oxidation *
2. Reduction *
3. Hydrolysis *
4. Conjugation

Note: Conjugation almost always decreases a drug's activity

Splitting a molecule and adding H2O to each part

Hydrolysis

Addition of O2 and/or loss of H+ ion

Oxidation

Gaining an H+ ion

Reduction

Reaction in which the drug is combined with an already existing substance

Conjugation

True or false: Most drugs undergo 100% biotransformation

False. Very few drugs undergo 100% biotransformation. The small unchanged quantities are what can be detected on drug tests

True or false: Newborns and older animals are generally faster at biotransforming drugs

False. Newborns are deficient in the drug metabolizing liver enzymes, and older animals have a decreased ability to synthesize these enzymes. Biotrasformation will be delayed in these animals

True or false: Different species have different levels of enzymes, including those used to metabolize drugs

True. This means that some drugs that are metabolized rapidly by some species can be toxic in others, for whom it takes too long because of a lack of enzymes

Is estrogen or testosterone known to depress some types of metabolism?

Estrogen. Because of this, some drugs can be more dangerous for female animals

Organ that excretes more drugs than any other organ. Proper function of this organ is very important when considering use of some drugs

Kidney

Fill in the blank: In the kidney most drugs are filtered from the blood in the _______ (structure in the kidneys).

glomerulus

Note: Filtration is slowed by the binding of drug to plasma proteins

Fill in the blank: If the urine is acidic, drugs that are weakly _____ are more readily excreted (and vice versa).

basic

Cells that actively secrete some drugs from the blood into the urine. Involves active transport

Tubule cells

A drug is metabolized by the liver, the resulting metabolites can then go to one of two places, what are they?

1. Be excreted into the bile
2. Returned to the bloodstream and excreted by the kidney

Note: Some drugs (not just metabolites) can be secreted into the bile unchanged

Drugs that are reabsorbed from the intenstine and returned to the liver via the portal vein then returned to systemic circulation have undergone what type of circulation?

Entero–hepatic circulation

Note: Also called recirculation

True or false: Just because a drug appears in the bile, does not mean it is on its way out of the body

True

Name some minor routes of excretion

Lungs, salivary glands, sweat glands, mammary glands, male genital fluid, and eggs

Removal of drug in an unaltered form

Clearance. It is different from excretion in that it does not refer to removal of drugs from the body, only removal from the bloodstream