7 Fundamental concepts in Psychopharmacology Flashcards
- What are fast ways of drugs entering the body?
Intravenous
Inhalation
Intraperitoneal – into the tummy
What are medium-speed ways of drugs entering the body?
Intramuscular (IM)
Subcutaneous (SC)
Oral
What are slow ways of drugs entering the body?
Topical or transdermal (eg. nicotine patches)
Depot injections – long-acting subcutaneous/intramuscular injections
- What are some problems with oral administration?
- Gastric acids destroy many compounds
- Eating can affect absorption
- Certain foods change drug metabolism: Grapefruit juice increases bioavailability of methadone and codeine
- First-pass effect – phenomenon of drug metabolism whereby the concentration of a drug is greatly reduced by the liver before it reaches the systemic circulation
What happens when heroin is taken orally?
Heroin (diacetylmorphine) undergoes extensive first-pass metabolism, but it crosses the blood-brain barrier more easily than morphine, making it more potent when injected.
What three factors affect drugs’ ability to enter the brain and body?
- Speed of onset/offset
- bioavailability
- compliance
What are the major ways that drugs can affect neural activity?
- Directly stimulating: by either a) stimulating activity by imitating an NT at a receptor site (agonist) or b) by blocking the receptor (antagonist).
- Affecting synthesis of drug
- Acting as a precursor: L-Dopa is a precursor for dopamine. L-Dopa crosses the blood-brain barrier, which dopamine cannot. Thus is used to increase dopamine concentrations in brain.
- Affecting release of NT: amphetamines pumps more noradrenaline into the synapse
- Affects rate at which NT is degraded: MAO inhibitors
- Affecting reuptake of NT: Eg. Cocaine blocks dopamine transporter, preventing reuptake.
How do MAO inhibitors work?
Monoamine oxidase metabolises the monoamines.
MAO-A – 5-HT, NE, Epinephrine;
MAO-B – DA.
Blocking MAO increases their availability.
Used as anti-depressant in those who don’t respond to SSRIs. Interacts with cheese, vegemite, can cause hypertension, stroke.
How does cocaine interfere with DA transporter activity?
Cocaine blocks dopamine transporter, preventing reuptake. In the normal communication process, dopamine is released by a neuron into the synapse, where it can bind to dopamine receptors on neighboring neurons. Normally, dopamine is then recycled back into the transmitting neuron by a specialized protein called the dopamine transporter. If cocaine is present, it attaches to the dopamine transporter and blocks the normal recycling process, resulting in a buildup of dopamine in the synapse, which contributes to the pleasurable effects of cocaine.
- What are the effects of repeated drug administration?
1, Tolerance – effect of drug is reduced with repeated treatment. More drug is needed. Can change number of, or sensitivity of, receptors.
2. Withdrawal – generally opposite of effect of drug itself.
Eg. Opiates – effects = reward, analgesia, sedation… ; withdrawal = craving, dysphoria, pain, anxiety; heart rate
Do all effects of a drug show similar tolerance over time?
No, not all effects of a drug show similar tolerance, and so overdose risks increase with repeated use, as desired effect may have tolerance, but dangerous side effect not.
How can the context in which a drug is taken affect potency?
Context in which drug is taken can function as CS. The CRs for heroin, for instance, elicits are compensatory – body preparing for onset of drug by weakening physiological responses. Also, café eg.
Dogs were given morphine either in test environment or in home cages. Then tested for withdrawals in test environment. Dogs given morphine in test environment had greater withdrawals.
Conversely, there are more heroin overdoses by those taking the drug in unusual circumstances.
How can cocaine use lead to sensitization?
If animals are given low doses of cocaine, however, no obvious responses occur to the first dose. If the animal is given this same low dose intermittently, for example once every week, it develops an increased sensitivity to the drug, as seen by increased locomotion and the emergence of head bobs. Because these behaviors emerge only after repeated drug administration, something in the brain must be changing to produce the sensitization. This has been shown to correspond to increasing spines on dendrites in nucleus accumbens. Also, Ferrario et al. reported linear increase in distance travelled by rats in a daily trial of cocaine over 7 days.
- What produces differences in the efficacy of different drugs?
- Site of action eg. many different types of pain, and individual differences in response. Also, for Prozac vs Paxil – different 5-HT receptors around the brain in different parts – almost everywhere, so different results in different parts. A drug can be developed that affects only one subtype of receptor.
- Repeated drug use can change efficacy of treatment. As tolerance to drug increases, higher doses are needed to produce desired effect. This can lead to greater side effects – as these do not necessarily have same tolerance profile.
What is the therapeutic index?
Ratio between desired effect and side effect.
